한국여성에서 자궁내막증의 발생위험도와 Estrogen Receptor-α 유전자 다형성과의 관련성에 관한 연구

이사라,허성은,문혜성,김형래,정혜원 이화여자대학교 의과대학 2003 EMJ (Ewha medical journal) Vol.26 No.2

Objectives: To investigate whether polymorphism of gene encoding estrogen receptor-a is asso-ciated with the risk of endometriosis in Korean women. Material and Methods :We investigated 136 patients with histopathologically confirmed endo-metriosis rAFS stage III/IV and 251 control group women who were surgically proven to have no endometriosis. Polymerase chain reaction(PCR) and restriction fragment length polymorphism (RFLP) of PCR products were done to determine each participant's estrogen receptor-a genotype. Results : The distridution according to PvuII genetic polymorphism of estrogen receptor-a were as follows. PP, Pp and pp were 14.7%(20 women), 39.0%(53 women) and 46.3%(63 women) in the study group and 13.9%(35 women), 38.6%(98 women) and 47.4%(119 women) in the con-trol group, respectively. There was no significant difference between the study group and the control group. Conclusion : The results suggest that estrogen receptor-a genetic polymorphism may not be associated with the development of endometriosis in Korean women. 목적: 자궁내막증은 에스트로겐에 의존적인 질환이므로 에스트로겐의 합성, 대사 및 작용에 관여하는 유전자의 다형성이 자궁내막증의 발생기전에 중요한 역할을 할 수 있다. 이에 본 연구에서는 한국인 여성에서 에스트로겐 수용체-a의 유전자 다형성이 자궁내막증의 발생 위험도를 증가시키는 지에 대해 연구하고자 하였다. 방법: 1996년 9월부터 2003년 8월가지 본원 산부인과에서 수술을 통해 병리조직학적으로 자궁내막증 III기와 IV기를 확인한 한국인 여성 136명을 대상으로 하였다. 대조군은 자궁내막증 환자군과 연령이 비슷한 만삭 산모에서 제왕절개술을 시행하거나 양성 난소낭종으로 수술을 시행 하였을 때, 자궁내막증이 없음을 확인한 여성 251명 으로 하였다. 결과: ER-a 유전자의 PvuII 다형성의 분포는 자궁내막증 환자군에서 PP군이 20명(14.7%), Pp군이 53명(39.0%), pp군이 63명(46.3%) 이었고 대조군에서의 분포는 각각 35명(13.9%), 97명(38.7%), 119명(47.4%)으로 나타났으며 자궁내막증 환자군과 대조군 사이의 유의한 차이는 없었다. Pp, pp형을 가지는 경우가 자궁 내막증 환자의 85.3%(116명), 대조군의 86.1%(216명)로 나타났으며, 이 경우 자궁내막증이 발생할 odds ratio가 0.904(95% CI, 0.519~1.702)로 통계적으로 유의한 차이가 없었다. 결론: 이상의 결과로 볼 때, 한국인 여성에서 자궁내막증의 발생위험과 에스트로겐 수용체 a 유전자 다형성간에 연관성은 없는 것으로 나타났다.

2005년 약국에서 판매된 코감기약

하기철,정문현,이진수,조래정,이혜경,김은실 대한감염학회 2007 감염과 화학요법 Vol.39 No.1

Background:Upper respiratory infections (URIs) are the most common infections in developed countries and are the major reasons for the consumption of medicines including antibiotics. In Korea, antibiotics and glucocorticoids were dispensed by pharmacies without prescriptions before July 2000, when the dispensation of antibiotics without doctor's prescriptions was prohibited. The objective of this study is to investigate the rate of antibiotic dispensation by pharmacies for the treatment of common cold and to identify the dispensing pattern for URI management in 2005, i.e., 5 years after the establishment of the prohibition policy. Materials and Methods:In August 2005, medical students visited 90 drugstores in three cities (Seoul, Chonan, and Chunchun) and received medications for the treatment of illnesses that simulate the common cold, i.e., rhinorrhea and nasal stuffiness that had lasted for one day and were not accompanied by fever. The components of the dispensed medicines were identified by pharmacists at a university hospital. Results:All the components of the dispensed medicines were identifiable in 85 cases (94.4%), and the mean number of medicines was 1.36 (S.D.±0.724); no difference was observed among the three cities. The antibiotics ampicillin and chloramphenicol were identified in two pharmacies in Seoul and Chunchun, respectively. Glucocorticoids were not dispensed in any case, and a nonsteroidal antiinflammatory drug was dispensed in only one case. Compound medicines are increasingly used as cold remedies; the components of the most frequently dispensed medicine were acetaminophen, chlorpheniramine, and pseudoephedrine. Herbal medicines were also frequently included in cold remedies (38.9%); licorice (30%) and ginger (26%) were the two most frequently used medicinal herbs. Conclusion:There was a marked decrease in the dispensation of antimicrobials, glucocorticoids, and nonsteroidal antiinflammatory drugs without doctor's prescriptions. Chloramphenicol continued to be dispensed as a URI medication. Increased use of compound and herbal medicines as cold remedies suggests a need for the evaluation of the additional benefits of herbal medicines, their adverse effects, and the drug interactions between herbal and conventional medicines. 배경 : 상기도 감염은 선진국에서 발생하는 가장 흔한 감염증이어서 이를 치료하기 위해 투여되는 약제는 전체약제 소모의 중요한 원인이며, 약제 부작용, 경제적 손실, 항균제 내성 유발에 큰 영향을 미칠 수 있다. 한국에서는 의약분업이 시행된 2000년 이전에는 항균제나 부신피질호르몬의 처방이 약국에서 자유롭게 되었지만, 의약분업이 시행되면서 감소하였을 것으로 추정되나 이에 대한 연구는 없었다. 이에 약국에서 판매되는 감기약에 항균제가 얼마나 포함되는지를 조사하고 판매되는 감기약의 실정을 알기 위해 이번 조사를 하였다. 재료 및 방법 : 2005년 8월 11일과 12일에 걸쳐 서울, 춘천, 천안의 개원 약국을 대상으로 의과대학 학생이 직접 방문하여 조사하였다. 비염(발열이 동반되지 않은 1일간의 콧물과 코막힘)을 주소로 하여 감기약을 받았으며, 이를 대학병원의 약품정보실 근무 전문 약사가 동정하였다. 결과 : 판매한 모든 약을 확인할 수 있는 경우가 85건(94.4%)이었다. 약의 종류는 1.36(S.D.±0.724)종이였으며, 지역별 차이는 없었다. 2개(2.2%) 약국에서 판매한 감기약에 항균제가 포함되었고, 서울과 천안에서 각각 1개 약국이었다. 서울 약국에서는 ampicillin이, 춘천에서는 chloramphenicol이 포함되었다. 부신피질호르몬이 포함된 경우는 없었으며, 비스테로이성 항염증제로는 이부프로펜 1건(1.1%)만이 있었다. 복합 감기약의 사용이 늘었으며, 3가지 성분을 포함한 경우가 제일 흔해 acetaminophen, chlorpheniramine, pseudoephedrine의 조합이었다. 한약제가 감기약에 포함된 경우는 35건(38.9%)이었고, 흔한 성분은 감초와 생강 또는 건강(ginger)이었다. 결론 : 의약분업 이후 약국에서 처방된 감기약에는 항균제, 부신피질호르몬, 비스테로이드 항염제의 판매는 급격히 감소하였다. Chloramphenicol이 아직도 감기 치료제로 판매되고 있으며, 복합 감기약의 사용이 늘었고, 생약이 흔히 포함되어 이의 효과 판정, 부작용, 약물 상호작용에 대한 조사가 필요하다.

여름에 비정형 폐렴으로 발현한 쯔쯔가무시병 1예

박상돈,정문현,이혜명,김미경,강재승 대한감염학회 2008 감염과 화학요법 Vol.40 No.4

Scrub typhus usually occurs in October and November in Korea. Its typical clinical manifestations are fever, rash, eschar, and lymphadenopathies. Pneumonitis may occur, however it occurs as a complication at the late phase of scrub typhus, when it is inappropriately treated. We encountered a case of pneumonitis that was an initial manifestation of scrub typhus which was confirmed by rickettsial culture, Positive seroconversion, and polymerase chain reaction. The case was a 16-year-old high school adolescent who presented with fever and headache that lasted for 1 day in July, 2007, He denied of any outdoor activities. A chest radiograph showed patchy infiltrates in the left lower lung, which improved with the administration of cefotaxime and azithromycin for empirical treatment of community-acquired pneumonia. Blood taken on the second febrile day showed a positive culture for Orientia tsutsugamushi and was also positive for O. tsutsugamushi DNA polymerase chain reaction. Immunofluorescent antibody (IFA) test for O. tsutsugamushi showed that the initial antibody was negative, but convalescent serum tested positive with an antibody titer of 1:80. IFA for Coxiella burnetii showed false positive results; the initial IgM and IgG liters were 1:128 and 1:256, respectively, and the IgM and IgG titers in convalescent serum were 1:128 and 1:128, respectively.

일개대학병원에서 수막알균 백신 사용의 경험

손동욱,이찬우,정영국,조래정,이혜경,김은실,이진수,정문현 대한감염학회 2007 감염과 화학요법 Vol.39 No.6

Meningococcal infection is a life threatening disease that leaves serious sequelae in spite of appropriate treatment, thus vaccination for high risk groups are Important for the prevention of meningococcal diseases. However, the vaccine for Neisseria meningitidis has not been available in Korea until we introduced bivalent (serogroup A and C) polysaccharide vaccine for the first time for relief works in our university hospital. The vaccine was administered from January 2005 to March 2007 to 317 persons. of the groups administered, the largest group among them were 133 (133/317, 42%) students who planned to study abroad and needed the vaccination for secure entrance to school dormitories. This group was followed by health care workers, travellers to the regions of the world with high risks of meningococcal diseases, and splenectomised patients. To ratioalize the domestic use of meningococcal vaccine, the availability of vaccines first needs to be simplified by introducing them to the domestic market; for this to be possible, the approval system for vaccines should be reformed and epidemiogical studies need to be carried out.

Orientia tsutsugamushi 감염에서 doxycycline 용량과 투여기간에 대한 실험

김은실,김미경,이혜명,정문현,이진수,박재은,강재승 대한감염학회 2008 감염과 화학요법 Vol.40 No.5

Background : Doxycycline, azithromycin, and chloramphenicol have been used for the treatment of scrub typhus; however, the duration of treatment for this disease is still controversial. Most clinical studies on the treatment of scrub typhus focus on the effectiveness of antibiotics; few studies have focused on the duration of the treatment. There has been no in vitro evaluation of the optimal duration of treatment of scrub typhus. We performed an experiment to evaluate the regrowth of Orientia tsutsugamushi after exposure to doxycycline of various concentration and exposure time. Materials and Methods : O. tsutsugamushi strain Boryong was inoculated into the ECV304 cell line. The infected cells were stained with FS15, a monoclonal antibody reacting against a linear epitope on the 56-kDa major outer membrane protein of O. tsutsugamushi; thereafter, the antimicrobial susceptibilities were measured by flow cytometry and expressed as a growth index (total mass of Orientia). Incubation in media containing 0.1 (the minimal inhibitory concentration of doxycycline against O. tsutsugamushi strain Boryong), 0.2, and 2 ug/mL doxycycline for 1, 3, 5, and 7 day was followed by incubation in antibiotic-free media for 5 day. Two inocula sizes were employed; low inoculum (45.18% of cells were infected) and high inoculum (87.21% of cells). Results : The incubation with 0.1 ug/mL doxycycline resulted in O. tsutsugamushi regrowth irrespective of doxycycline treatment duration. When the concentration of doxycycline was increased to 0.2 or 2 ug/mL, regrowth was observed in short duration treatments (1-5 day at 0.2 ug/mL; 1 day at 2 ug/mL). Higher inoculum size of O. tsutsugamushi increased regrowth (1 day at the low inoculum; 1-5 day at the high inoculum). Conclusions : The regrowth of O. tsutsugamushi after doxycycline treatment depends on the doxycycline dose; the higher the dose, the lower the relapse rate. If this result is extrapolated to humans, higher dose of doxycycline might be preferred to lower the relapse rate. The inoculum effect in O. tsutsugamushi infection needs further investigations.

유세포분석법으로 조사한 Orientia tsutsugamushi Boryong주의 항균제 감수성

김은실,김미경,이혜명,정문현,이진수,박재은,강재승 대한감염학회 2008 감염과 화학요법 Vol.40 No.4

Background : Scrub typhus, an infectious disease caused by Orientia tsutsugamushi, is endemic in Korea. With the introduction of tetracycline and chloramphenicol in clinical practice, the mortality due to scrub typhus has markedly decreased, In 1995, scrub typhus poorly responsive to doxycycline was reported in Thailand; the need for safe antibiotics for the treatment of scrub typhus acquired during pregnancy or for children is emerging; also, broader spectrum antibiotics having anti-Orientia activity may be preferred for empirical therapy of enteric fever syndrome and for complicated scrub typhus. The anti-Orientia activities of various antibiotics, including recently licensed antibiotics, were investigated by flow cytometry. Materials and Methods : O. tsutsugamushi strain Boryong was inoculated into the ECV304 cell line. The infected cells were stained with FS15, a monoclonal antibody reacting against a linear epitope on 56-kDa major outer membrane protein of 0. tsutsugamushi. Then the antimicrobial susceptibilities were measured by flow cytometry and expressed as a growth index (total mass of Orientia). A concentration at which no further decrease in growth index occurred was defined as the minimal inhibitory concentration (MIC). Microbial susceptibilities to the following antibiotics were measured: quinupristin-dalfopristin (Synercid), levofloxacin, ciprofloxacin, moxifloxacin, metronidazole, linezolid, clindamycin, chloramphenicol, doxycycline, azithromycin, and rifampin. Results : Considering the usual serum concentrations of rifampin (M1C=0.025-0.05 ug/mL), azithromycin (M1C=0.05-0.5 ug/mL) and doxycycline (MIC=0.05-0.1 ug/mL), these antibiotics exhibited very low MICs. Synercid (MIC=0.2-1.0 ug/mL), clindamycin (MIC=1.0 ug/mL) and chloramphenicol (MIC=1-2 ug/mL) exhibited moderately low MICs; moxifloxacin (MIC=8 ug/mL), ciprofloxacin (M1C=25.6 ug/mL or more) and levofloxacin (M1C=30 ug/mL) exhibited relatively high MICs; and cefotaxime (MIC>50 ug/mL), metronidazole (MIC>30 ug/mL) and linezolid (>30 ug/mL) exhibited high MICs. Conclusions : Among the new antibiotics, none was superior to doxycycline, azithromycin or rifampin with respect to anti-Orientia activity. Synercid, clindamycin, and moxifloxacin may show moderate therapeutic efficacies in human.

Orientia tsutsugamoshi에 대한 항균제 병용의 실험실 효과

김은실,김미경,이혜명,정문현,이진수,강재승 대한감염학회 2008 감염과 화학요법 Vol.40 No.6

Background : Occasionally, combinations of antibiotics are used for the treatment of scrub typhus. However, the effectiveness of such combined therapies has rarely been evaluated. To date, no experimental studies have been performed; only 1 clinical study has assessed the efficacy of combined doxycycline and rifampin therapy. To elucidate the efficacies of other antibiotic combinations, we performed an experiment to evaluate the in vitro efficacy of antibiotic combinations against Orientia tsutsugamushi. Materials and Methods : O. tsutsugamushi strain Boryong was inoculated into the ECV304 cell line. The infected cells were cultured in antibiotic-containing media for 3-5 days and stained with FS15, a monoclonal antibody reacting against the linear epitope on the 56-kDa major outer membrane protein of O. tsutsugamushi. Thereafter, antimicrobial susceptibility was measured by flow cytometry and expressed as a growth index (total mass of Orientia). The growth indices of doxycycline (0.1 ug/mL), azithromycin (0.1 ug/mL), rifampin (0.0125 ug/mL), cefotaxime (2 and 20 ug/mL), and their various combinations (doxycycline+cefotaxime, doxycycline+rifampin, azithromycin+cefotaxime, and rifampin+cefotaxime) were measured. The above mentioned antibiotic concentrations, except for that of cefotaxime, represent the minimal inhibitory concentrations of each antibiotic. Results : The growth indices of doxycycline (4.67% and 0.52%), rifampin (2.35% and 0.26%), and azithromycin (7.54%) were within the range of full suppression of O. tsutsugamushi', in contrast, cefotaxime (87.60%) was in effective. The growth indices of doxycycline + rifampin were 0.10% and 0.10% which were similar to those obtained with doxycycline or rifampin alone. The growth indices of doxycycline+cefotaxime were 3.99% and 3.65% in low-dose cefotaxime (2 ug/mL), and 3.69% and 4.40% in high-dose cefotaxime (20 ug/mL). The growth indices of rifampin +cefotaxime (2.19% and 2.19% at 2 ug/mL; 1.84% and 2.04% at 20 ug/mL cefotaxime) were similar to those obtained with rifampin alone (2.35% and 0.26%). Azithromycin+cefotaxime (11.06-14.63%) showed higher growth indices than azithromycin alone; this suggests that this combination may be antagonistic. Conclusions : The anti-Orientia efficacies of doxycycline+rifampin, doxycycline+cefotaxime, and rifampin+cefotaxime were not antagonistic. The efficacy of the azithromycin+cefotaxime combination needs to be confirmed by more sensitive methods to exclude the possibility of antagonistic interactions between the antibiotics.

국내 환자에서 분리된 Orientia tsutsugamushi에서 doxycycline 내성

김은실,김미경,이혜명,길세희,정문현,이진수,강재승 대한감염학회 2008 감염과 화학요법 Vol.40 No.5

Background : Doxycycline has been the drug of choice for the treatment of scrub typhus. However, scrub typhus with poor response to doxycycline was first reported in Thailand in 1996. To date, it is not known whether doxycycline resistant scrub typhus is present in Korea. To investigate the doxycycline resistance of scrub typhus in Korea, we performed an experiment to evaluate the degree of growth inhibition of Orientia tsutsugamushi at the minimal inhibitory concentration (MIC) of doxycycline. Materials and Methods : 37 isolates of Orientia tsutsugamushi were collected from Korean patients with scrub typhus during 10 year period (from 1997 to 2007). 34 isolates consisted of Boryong serotype or related serotypes. These strains were stained with FS15, a monoclonal antibody against the linear epitope on the protein located at the outer membrane of O. tsutsugamushi. Three isolates were confirmed as serotype Gilliam, which was stained by anti-Gilliam antibody. The antibody-stainable 35 isolates were incubated in media containing 0.1 and 0.2 ug/mL of doxycycline for 3 days. Then the growth indices of Orient/a were measured by flow cytometry. If the growth index was greater than 10%, the isolate was tentatively classified as an isolate resistant to doxycycline and its MIC was measured. Results : Demographic and treatment data were similar to the results of previous reports. Infection was mainly observed in Inchon and the Chungcheongnam province. No patient showed delayed response to antibiotics. Of 35 hospitalized patients, 4 (11.4%) were managed at the intensive care unit and 1 (2.9%) died of nosocomial pneumonia. All the 2 patients whose isolates were serotype Gilliam Yonchon/Ikeda-like strain were managed at the intensive care unit. Six of the 34 isolates from Korean patients exhibited growth indices greater than 10% at the MIC of doxycycline; however, the MICs of these isolates did not exceed 0.2 ug/mL. One isolate of serotype Gilliam showed an MIC of 0.0125 ug/mL, which seemed to be underestimated due to weak fluorescence of the anti-GiIIiam antibody. Conclusions : Although the number of tested isolates is small, insensitivity of scrub typhus to doxy-cycline is not a major reason for treatment failure in Korea. Serotype Gilliam, especially Yochon/Ikeda-like strain may be associated with severe form of scrub typhus. More studies concerning the antibiotic susceptibility for serotype Gilliam are warranted.

보건간호활동으로 추진한 노인건강증진 프로그램

유인영(In-Young Yoo),조정민(Chung0Min Cho),최영숙(Young-Sook Choi),정문희(Moon-Hee Jung),김미혜(Mi-Hye Kim),유광수(Kwang-Soo You),윤숙례(Suk-Rye Yoon),한명화(Myung-Hwa Han),최선하(Sun-Ha Choi),하영(Young Ha),김규성(Kyu-Sung Kim),이현주 한국보건간호학회 1997 韓國保健看護學會誌 Vol.11 No.1

6-(3,4-디클로로페닐)아미노-7-클로로-5,8-퀴놀린디온의 항진균작용 및 안전성 평가

윤여표,김동현,이병무,허문영,정해문,강혜영,최정아,김도희,유충규 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1

6-(3.4-Dichlorophenyl)amino-7-chloro-5.8-quinolinedione (RCK50) was tested for antifungal activities in mice systemically infected with Candida albicans. The therapeutic potential of RCK50 was also assessed in comparison with ketoconazole. RCK50 had ED_50 0.22±0.01 ㎎/㎏. Ketoconazole as a positive control had ED_50 6.00±1.70 ㎎/㎏. Intraperitoneally administered RCK50 at the ED_50 for 7 days and 14 days reduced Candida albicans colony count in the kidneys and liver. And administered RCK50 at the ED_50 for 14 days improved survival rates. The genotoxicities of RCK50 had been evaluated. RCK50 was negative in Ames test with Salmonella typhimurium and chromosomal aberration test in CHL cells. RCK50 did not show any clastogenic effect in mouse peripheral blood and was negative in mouse micronucleus assay. These results indicate that RCK50 has no genotoxic potential under these experimental conditions. Acute oral toxicity studies of RCK50 were carried out in ICR mice of both sexes. RCK50 did not show acute oral toxicities and LD_50 values were over 2.850 ㎎/㎏ in ICR mice.