항정신병약물 사용 중인 정신분열병 환자에서 올란자판으로의 교체 방법에 관한 연구(II) : Comparison of Safety 안전성 비교

안용민,권용실,권준수,민성호,박두병,양문정,소형석,송종호,신윤식,우행원,유범희,이홍석,정한용,한창환,김용식 大韓神經精神醫學會 2002 신경정신의학 Vol.41 No.5

연구목적: 이 다기관 공동임상연구는 사용 중인 항정신병약물을 ’직접 교체 방법’또는 ’시작-감량 교체 방법’중 한 가지 방법으로 올란자핀으로 교체한 후, 안정성 측면에서 두 교체 방법 간의 비교와 교체후의 변화를 관찰하기 위한 것이다. 방법: 국내 13개 병원의 입원 및 외래에 내원한 환자들 중 ICD-10 지단기준으로 정신분열병에 해당되며, 임상적으로 항정신병약물 교체가 필요한 환자를 대상으로 하였다. 두 가지 교체 방법 중 한 가지를 무작위로 피험자에 적용하였으며, ’직접 교체 방법’에 배정된 경우에는 사용중인 항정신병약물을 일시에 중단하고 10㎎의 올란자핀을 바로 투여하였고, ’시작-감량 교체 방법’에 배정된 경우는 10㎎의 올란자핀 투여하고 2주에 걸쳐서 기존 약물을 감량하여 중단하였다. 올란자핀 사용기간은 총 6주이며, 용량은 5∼20㎎ 범위로 제한하였다. 한정성 평가를 위해서 체중, 생명징후, 자발적인 이상반응 복, 실험실 검사 그리고 Simpson-Angus Scale(SAS), Barnes akathisia rating scale(BARS), Abnormal involuntary movement scale(AIMS). Liverpool University neuroleptic side effect rating scale(LUNSERS)등을 이용하였다. 결과: 총 103명의 정신분열병 환자를 대상으로 하였다. 사용한 올란자핀의 용량, 벤조디아제핀의 병용률, 탈락률과 탈락 사유, 자발적인 이상반응 보고, 생명징후, 실험실 검사 그리고 대부분의 부작용 척도 상에서 임상적으로 의미 있는 차이를 두 교체 방법간에 발견하지 못하였다. 다만 AIMS의 감소는 ’직접 교체 방법’군에서 보다 적었고, 항콜린제의 병용률은 ’시작-감량 교체 방법’군에서 보다 많았다. 기저 상태에서 전체 피험자의 SAS와 BARS 점수는 각각 3.5점과 1.8점이었으며 70% 이상의 피험자가 고프로락틴 혈증을 보였다. 올란자핀으로 교체한 후, SAS, BARS, AIMS 점수의 유의한 감소가 있었으며 고프로락틴 혈증을 보인 피험자 분율도 약 30%이하로 감소하였다. 그러나 교체 방법과 상관없이 올란자핀 교체 후 유의한 체중 증가가 있었다. 결론: 이 연구를 통해 교체 방법에 관계없이 비교적 안전하고 용이하게 올란자핀으로 교체 할 수 있음을 알 수 있었다. 그리고 기존 항정신병약물을 올란자핀으로 교체함으로써 일부 부작용들을 줄일 수 있음을 간접적으로 관찰할 수 있었다. 하지만 이 연구는 여러 제한점과 문제점을 지니고 있기 때문에 보다 체계적인 연구를 통해 검정이 필요하리라 생각된다. Objectives: This multicenter clinical trial involving 13 hospital sites compared the safely of switching to olanzapine between ’direct switching method’ and ’start-tapering switching method’. Method: This study included both inpatients and outpatients who fulfilled the criteria for schizophrenia as defined in the ICD-10, and were in need to be appropriate for switching antipsychotics. Subjects were randomly assigned to one of the two switching methods. For ’direct switching method’group, previous antipsychotics were abruptly discontinued and 10㎎ of olanzapine was administered, and previous antipsychotics was gradually tapered for 2 weeks. Olanzapine was used for 6 weeks and the dose was adjusted within the range of 5-20㎎. The safety of switching to olanzapine was measured with vital sings including body weight, adverse events reported spontaneously, laboratory tests, and various scales such as Simpson-Angus Scale(SAS), Barnes Akathisia Rating Scale(BARS). Abnormal Involuntary Movement Scale(AIMS), and Liverpool University Neuroleptic Side Effect Rating Scale(LUNSERS). Results: 103 patients were switched to olanzapine in this study. The comparison between two switching methods did not show any significant difference in the dosage of olanzapine used, the concomitant use of benzodiazepine, the rate and reasons of drop-out, the adverse events, vital signs, laboratory tests, and most scales for measuring side-effects. However, the decrease in AIMS scores was significantly lower in ’direct switching method’ group, and the concomitant use of anticholinergics was comparatively greater in ’start-tapering switching method’ group. At baseline, SAS and BARS scores were 3.5 and 1.8 points respectively, and more than 70% of the subjects showed hyperprolactinemia. After switching to olanzapine, SAS, BARS, and AIMS scores were significantly decreased and the proportion of the patients with hyperprolactinemia was also decreased to less than 30%. However significant weight gain after the treatment of olanzapine was observed regardless of switching method. Conclusion: This study may suggest that switching to olanzapine can be done with relatively high safety regardless of switching methods and olanzapine can significantly decrease some side-effects induced by other antipsychotics.

^27Al(p,α pn)핵반응에 의한 무담체 ^22Na 제법 연구

유국현,서용섭,양승대 東國大學校 1998 東國論叢 Vol.37 No.-

A method for the production of no-carrier added(NCA) ^22Na was developed via ^27Al(p, ㄷαpn) nuclear reaction with 50.5MeV protons. the half life of ^22Na is 2.6 years and main γ-energy is 1274.5keV and it is used standard source and sodium catabolism study. The cross-section and thick target yield for the reaction was measured in detail in the energy range of 50.5→20.2MeV in order to determine the optimum conditions for the production of ^22Na. the maximum cross-section for the production of ^22Na was 40.8 mbarn at 43.85MeV. the calculated production yield of ^22Na by 50.5MeV protons on aluminium was 60.9μCi/μAh. The seperation of ^22Na was carried out by ion exchange, precipitation and diffusion. It was found that ion exchange column operation using AG50W-X4 resin was the most efficient method among them.

폴록사머를 이용한 디클로페낙 고형 좌제의 개발

용철순,오유경,김정애,김용일,박상만,양준호,이종달,최한곤 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.2

To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting points of various formulations composed of P 124 and P 188 were investigated. To investigate the effect of poloxamer to the dissolution and dissolution mechanism of diclofenac sodium from the suppository the dissolution of diclofenac sodium delivered by the poloxamer-based suppository was performed. Furthermore, to investigate the mucoadhesive property of the poloxamer-based solid suppository, the identification test in the rectum was carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous. Very small amounts of P 188 affected the melting points of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about 32℃ was a solid form at room temperature and instantly melted at physiological temperature. Furthermore, very small amounts of P 188 in the poloxamer-based suppository hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. At 4 h after administration, the blue color of poloxamer-based suppository [diclofenac sodium/poloxamer mixture (2.5/97.5%)] with the P 124/P 188 ratio of (97/3%) and blue lake in the rectum was faded. However, the position of suppository in the rectum did not significantly change with time. Thus, it retained in the rectum for at least 4 h. Our results indicated that the poloxamer-based solid suppository with P 124 and P 188 would be a candidate of rectal dosage from for diclofenac sodium.

관상동맥 누공에 의한 급성 심근 경색 1예

서유승,최재웅,송창섭,조용범,양진수,박준섭,정인수 대한내과학회 2003 대한내과학회지 Vol.65 No.2

관상동맥 동정맥루 기형은 매우 드문 질환으로 치료가 불필요한 경우가 대부분이나 coronary steal 현상으로 인해 증상이 발생하거나 합병증이 발생한 환자에 대해선 치료를 요한다. 최근에는 시술에 적합한 누공을 가진 선택된 환자군을 대상으로 카테터를 이용한 중재적 시술이 시행되어 수술적 치료와 유사한 결과를 얻고 있다. 저자들은 젊은 남자에서 관상동맥 동정맥루 기형과 동반된 급성 심근 경색증을 진단하여 비 수술적 방법인 카테타 코일 색전술로 성공적 치료 후 증상 및 심근 재관류에 호전을 보인 증례를 경험하였기에 문헌고찰과 함께 보고하는 바이다. We report a case of coronary fistula between the left anterior descending and main pulmonary artery complicating acute non-Q wave myocardial infarction. A 27-year-old man visited emergency department because of severe chest pain lasting two hours. The electrocardiogram showed ST segment elevation in precordial leads V3~6. Cardiac enzymes were as follows;CK-MB:36.44 IU/L T-T:0.489 ng/mL, CPK:542 IU/L, and LDH:475 IU/L. The thallium-201 dipyridamole stress perfusion scan showed perfusion defect and reversed redistribution in the anteroseptal wall. The coronary angiogram revealed coronary artery fistula between the proximal left anterior descending artery and main pulmonary artery without significant stenoses of coronary arteries. The result of ergonovine test was negative. After micro-coil embolization to the coronary fistula, symptoms were improved. Follow-up thallium-201 scan showed normalized blood flow in the left anteroseptal wall.

쿠싱 증후군을 동반한 부신피질 흑색선종 2예

유소연,김윤화,박용구,이주희,양문호 대한병리학회 1991 Journal of Pathology and Translational Medicine Vol.25 No.3

사후분해 시체에 대한 법의학적 접근

최영식,이상용,김유훈,조갑래,이봉우,양경무,정낙은,서중석,이한영,이원태,강현욱 大韓法醫學會 2000 대한법의학회지 Vol.24 No.2

Disposal of a homicide victim by dismemberment is rare, but individual cases are on record in most major medicolegal departments. Recognition of postmortem mutilation may be of importance in the interpretation of certain murders committed by sexual perverts and other mentally deranged individuals and sometimes performed for the sole reason of easier disposal of the body. Postmortem dismemberment is usually readily recognizable as such; The edges of the injuries are dry and lack evidence of bleeding. The joints may be disarticulated without fracture, or the use of an axe or saw may be evident from examination of bones. Parallel horizontal or oblique furrows in the bone surface are caused by skipping of the saw prior to establishing depth. Such patterns on the bone may assist in identifying the particular saw involved. So we report 25 dismembered corpses that autopsied in National Institute of Scientific Investigation. This paper can help in attempting to establish not only the first criminal investigation steps but also the medicolegal approach methods in unidentified and dismembered deaths.

폴록사머 및 프로필렌글리콜을 이용한 클로트리마졸 고형 좌제의 물리화학적 특성

현경희,오유경,김정애,공경환,김지현,양준호,배명수,김호동,이종달,장현욱,용철순,최한곤 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.2

To develop a clotrimazole-loaded solid suppository with poloxamer and propylene glycol, the melting points of various formulations composed of poloxamer 188 (P 188) and propylene glycol were investigated. The dissolution study of clotrimazole delivered by the suppository composed of P 188 and propylene glycol was performed. The mixtures composed of P 188 and propylene glycol were homogeneous. Propylene glycol affected the melting points of poloxamer mixtures. In particular, the mixture [P 188/propylene glycol (70/30%)] with the melting point of about 32°C was a solid form at room temperature and instantly melted at physiological temperature. Furthermore, propylene glycol affected greatly the dissolution rates of clotrimazole from the suppository. Dissolution mechanism analysis showed the dissolution of clotrimazole was proportional to the time. Our results indicated that the solid suppository with P 188 and propylene glycol would be a candidate of rectal dosage form for clotrimazole.

중증 만성정신질환자 수의 추산 : Through Two Community Surveys 두 지역사회 조사를 중심으로

홍진표,김윤,배재남,정유진,강영호,양병국,김용익,김병후,이철,조맹제 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.2

국내 중증 만성정신질환자 수를 추정하기 위하여 일 농촌 및 대도시 지역의 지역의료보험 및 의료보호 대상자 중 1993년 1년간 의료기관에서 정신증 상병(ICD-9 code 상 290-299) 및 알콜 남용/중독, 성격장애 및 정신박약 진단하에 치료를 받은 적이 있는 사람에 대해 설문조사를 실시하였다. 연구자들이 개발한 진단도구를 이용하여 진단을 평가하고, Strauss-Carpenter scale 등을 이용하여 기능 장애를 평가하고 유병기간 등을 조사하였다. 결과를 요약하면 다음과 같다. 1) 진단평가상 정신분열병군(61.1%)이 가장 많았으며, 정동장애군(23.7%), 알콜장애군(11.2%), 기질성 정신장애군(4.0%)의 순서이었다. 2) 직업활동정도는 진단군별로 차이가 많았다. 지난 1년간 직업활동이 6개월 미만이거나 전혀 없는 환자 비율이 정신분열병군은 67.2%, 알콜장애군 52.0%, 정동장애20.8%의 순으로 정신분열병군이 가장 불량하였다. 3) 사회활동도 진단군별로 차이가 많아서 지난 1년간 의도적, 사회활동이 없는 비율이 정신분열병군이 가장 높았고(72.3%), 알콜장애군(32.0%), 정동장애군(20.7%)의 순이었다. 4) 국내 의료보험 및 사회복지시설 이용 자료 등을 토대로 본 조사 결과를 적용한 결과 국내중증 만성 정신질환자의 수는 약 8만 7천명으로 추산되었다. Objectives: The purpose of this study was to estimate the number of serious and persistent mentally ill patients in Korea. Methods : Study populations were recruited from medical insurance data of two district areas ; one rural and the other urban areas. Subject were all mentally ill who had ever visited any hospital in 1993 and were diagnosed as having psychosis, personality disorder and drug abuse. We conducted a home visiting survey applying semi-structured diagnostic interview, assessing the level of social adjustment with Strauss-Carpenter Scale, and past psychiatric history by the trained researchers, in October and November,1994. Results : According to diagnostic assessment schizophrenic patients constituted the major portion(61.1%) of study subjects. The distribution of occupational functions and social contacts was variable according to diagnosis. Most schizophrenic patients were unemployed or worked less than 6 months in the previous year(67.2%), and showed poor social contact(72.3%). But affective disorder patients were relatively independent in job maintenance and social relationship. Alcoholic patients lay between those of schizophrenic and affective disorder groups. It was estimated that about 87,000 adult Koreans were suffering from chronic mental disorders which seriously interfere with their daily life. Conclusions : Serious and persistent mentally ill patients were common in Korea. Community support program should be provided for them.

낭성 수막종 -1증례 보고-

박재훈,유소연,김윤화,박용구,양문호 대한병리학회 1991 Journal of Pathology and Translational Medicine Vol.25 No.2

Mitochondrial citrate accumulation drives alveolar epithelial cell necroptosis in lipopolysaccharide-induced acute lung injury

Yang Hui-Hui,Jiang Hui-Ling,Tao Jia-Hao,Zhang Chen-Yu,Xiong Jian-Bing,Yang Jin-Tong,Liu Yu-Biao,Zhong Wen-Jing,Guan Xin-Xin,Duan Jia-Xi,Zhang Yan-Feng,Liu Shao-Kun,Jiang Jian-Xin,Zhou Yong,Guan Cha-Xi 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Necroptosis is the major cause of death in alveolar epithelial cells (AECs) during acute lung injury (ALI). Here, we report a previously unrecognized mechanism for necroptosis. We found an accumulation of mitochondrial citrate (citratemt) in lipopolysaccharide (LPS)-treated AECs because of the downregulation of Idh3α and citrate carrier (CIC, also known as Slc25a1). shRNA- or inhibitor–mediated inhibition of Idh3α and Slc25a1 induced citratemt accumulation and necroptosis in vitro. Mice with AEC-specific Idh3α and Slc25a1 deficiency exhibited exacerbated lung injury and AEC necroptosis. Interestingly, the overexpression of Idh3α and Slc25a1 decreased citratemt levels and rescued AECs from necroptosis. Mechanistically, citratemt accumulation induced mitochondrial fission and excessive mitophagy in AECs. Furthermore, citratemt directly interacted with FUN14 domain-containing protein 1 (FUNDC1) and promoted the interaction of FUNDC1 with dynamin-related protein 1 (DRP1), leading to excessive mitophagy-mediated necroptosis and thereby initiating and promoting ALI. Importantly, necroptosis induced by citratemt accumulation was inhibited in FUNDC1-knockout AECs. We show that citratemt accumulation is a novel target for protection against ALI involving necroptosis.