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.

Reconstruction of Rabbit Corneal Epithelium on Lyophilized Amniotic Membrane Using the Tilting Dynamic Culture Method

Ahn, Jae-Il,Lee, Doo-Hoon,Ryu, Yang-Hwan,Jang, In-Keun,Yoon, Mun-Young,Shin, Youn Ho,Seo, Young-Kwon,Yoon, Hee-Hoon,Kim, Jae-Chan,Song, Kye-Yong,Yang, Eun-Kyung,Kim, Ki-Ho,Park, Jung-Keug Blackwell Publishing Inc 2007 Artificial Organs Vol.31 No.9

<P>Abstract: </P><P>Rabbit corneal epithelium was reconstructed using tilting dynamic culture with a self-manufactured, amniotic membrane (AM) supporter and a lyophilized amniotic membrane (LAM). Rabbit corneal epithelial (RCE) cells were cultured and cryopreserved after isolation from the limbus. The second- and third-passage RCE cells were plated onto the epithelial side of the LAM of Ahn's AM supporter. Two days later, the air–liquid interface culture was maintained with third-passage RCE cells for 6 days and second-passage corneal epithelial cells for 9 days. The average viability of thawed RCE cells, assessed using trypan blue dye exclusion, was 77.42%. The reconstructed corneal epithelium was characterized by histological (hematoxylin and eosin) and immunohistochemical staining (proliferating cell nuclear antigen) for light microscopy, and by reverse transcriptase-polymerase chain reaction, glucose assay, and transmission electron microscopy. The basal layer of the reconstructed corneal epithelium was well formed, and the epithelium was tightly constructed due to the increase in cell proliferation and differentiation caused by the tilting dynamic culture, as opposed to static culture. Tilting dynamic culture was useful for the reconstruction of the epithelium using easily damaged epithelial cells and resulted in more stratum cell layers. Moreover, cytokeratin (CK3) mRNA expression in tilting dynamic cultured third-passage RCE cells seeded onto AM was greater than in static cultured third-passage RCE cells. The morphology of the reconstructed corneal epithelium on LAM by tilting dynamic culture for 9 days resembled that of the skin epidermis. This was thought to be because the tilting dynamic culture not only accelerated the proliferation and differentiation of cells by physical or mechanical stimulation, but also ensured that the supply of medium was delivered to the basal cells more efficiently. Thus, the reconstruction of the corneal epithelium using LAM and tilting dynamic culture was considered to be a good in vitro model for autologous or allogeneic transplantation of corneal epithelium and skin epidermis in patients with damaged epithelia. </P>

A Comparison of Lyophilized Amniotic Membrane with Cryopreserved Amniotic Membrane for the Reconstruction of Rabbit Corneal Epithelium

Ahn Jae-Il,Jang In-Keun,Lee Doo-Hoon,Seo Young-Kwon,Yoon Hee-Hoon,Shin Youn-Ho,Kim Jae-Chan,Song Kye-Yong,Lee Hee-Gu,Yang Eun-Kyung,Kim Ki-Ho,Park Jung-Keung The Korean Society for Biotechnology and Bioengine 2005 Biotechnology and Bioprocess Engineering Vol.10 No.3

Many researchers have employed cryopreserved amniotic membrane (CAM) in the treatment of a severely damaged cornea, using corneal epithelial cells cultured on an amniotic membrane (AM). In this study, two Teflon rings were made for culturing the cells on the LAM and CAM, and were then used to support the AM, which is referred to in this paper as an Ahn's AM supporter. The primary corneal epithelial cells were obtained from the limbus, using an ex-plantation method. The corneal epithelium could be reconstructed by culturing the third­passage corneal epithelial cells on the AM. A lyophilized amniotic membrane (LAM) has a higher rate of graft take, a longer shelf life, is easier to store, and safer, due to gamma irradiation, than a (AM. The corneal epithelium reconstructed on the LAM and (AM, supported by the two­Teflon rings, was similar to normal corneal epithelium. However, the advantages of the LAM over that of the (AM make the former more useful. The reconstruction model of the corneal epithelium, using AM, is considered as a good in vitro model for transplantation of cornel epithelium into patients with a severely damaged cornea.

한국인에서 DXS7132 유전좌와 GATA31D10 유전좌의 다형성에 관한 연구

안종성,장영길,이숭덕,신창호,이윤성,이정빈 大韓法醫學會 2000 대한법의학회지 Vol.24 No.1

The validation study for two STR loci on X-chromosome, DXS7132 and GATA31D10, was done including allelic distribution and frequency of each allele to use these results for individual identification and paternity testing. For 496 unrelated Koreans, above two STR loci were amplified simultaneously using duplex PCR amplification method. The amplified products were analyzed by polyarylamide gel electrophoresis followed by silver staining. In male DXS7132 locus revealed 7 different alleles ranging from 276bp to 300bp. The largest allele was consisted of 14 repetition of [TCTA] unit and took 0.3417. The allele 15 followed next as 0.3165 and allele 13 as 0.1726. In female general distribution was same except one allele, allele 18 was found additionally. The heterozygosity was 0.7706 and 23 different genotypes were found. Polymorphism information content(PIC) was 0.727. Two cases of mutation were noted in DXS7132 locus In both male and femal 7 different alleles were noted in GATA31D10 locus and the alleles ranged from 195bp to 231bp. The allele 15(199bp) took the majority of all as 0.825. The other alleles showed rather relatively low frequency. The heterozygosity was 0.2385 and 11 different genotypes were found. PIC was 0.2521, and no mutation was noted in GATA31D10 locus. Considering these two loci together, 22 different halpotype were noted.

면역방사계수법을 이용한 Thyroglobulin 측정시 항 Thyroglobulin 항체의 존재가 미치는 영향

안병철,배진호,정신영,박호용,김정국,하승우,이재태,김보완,이규보 대한내분비학회 2004 Endocrinology and metabolism Vol.19 No.1

연구배경: 혈청 thyroglobulin (Tg)은 옥소전신스캔과 함께 분화갑상선암환자에서 갑상선암 재발에 대한 추적관찰에 매우 예민하고, 중요한 표지자로 임상에서 널리 이용된다. 그러나 많은 수의 분화갑상선암환자는 Tg 항체인 항 Tg 항체를 가지고 있고, 이는 방사면역검사법 (radioimmunoassay) 및 면역방사계수 검사법(immunoradiometric assay)으로 Tg 측정시 영향을 미칠 수 있다. 이에 연자들은 면역방사계수법으로 Tg를 측정할 경우, 항 Tg항체에 의하여 어떤 영향이 생길수 있는지를 알아보고자 하였다. 방법: 이중위치 고상법 (solid phase two-site)법을 이용하는 ELSA-hTg in vivo test (CIS international, Schering, France) 시약을 이용하여 Tg를 측정하였다. Tg과 항 Tg 항체는 검사시약에 포함된 표준용액을 사용하였으며, Tg는 두 가지 농도 (23.5 ng/mL, 62.5 ng/mL)로, 항 thyroglobulin 항체는 세 가지 농도(25U/mL, 50U/mL, 100U/mL)로 이용하였다. Tg가 높게 나타나는 환자의 혈청에 항 Tg 항체가 높게 나타나는 환자의 혈청을 혼합하여 동일한 방법으로 Tg 검사를 시행하였다. 통계학적 분석은 ANOVA와 Scheffe test 및 Quadratic regression modeling을 시행하였다. 결과: 면역방사계수법을 이용한 Tg 측정시 항 thyroglobulin 항체가 존재하는 경우 그 값이 낮게 측정되었다. Tg 농도가 23.5 ng/mL인 표준용액이 항 Tg 항체의 농도가 0, 25, 50 및 100U/mL 경우, 각각 24.5±1.1, 11.8±0.4, 7.7±0.1 및 4.5±0.4ng/mL로 측정되었으며, Tg 농도가 62.5 ng/mL인 표준용액은 각각 65.9±5.7, 36.3±2.2, 23.7±0.7, 및 14.0±1.0 ng/mL로 측정되었다(ANOVA test, p=0.000). 항 Tg 항체에 의한 Tg 측정값의 저하 정도는 항 Tg 항체의 농도에 비례하는 것으로 나타났다 (Quadratic model regression, SigT=0.000). 결론: 분화갑상선암환자에서 항 Tg 항체의 존재는 면역방사계수법을 이용한 혈청 Tg 측정으로 갑상선암 재발을 파악하는데 방해하는 인자로 작용될 수 있으며, Tg 측정시 항 Tg 항체의 측정이 꼭 필요하며, 항 Tg 항체를 가진 분화갑상선암환자에서 Tg 수치를 해석할 경우 세심한 주의가 요구된다. Background: Serum thyroglobulin (Tg) is a valuable and sensitive tool needed in the follow-up of patients with differentiated thyroid cancer (DTC), but antithyroglobulin antibody (Anti-Tg), common in patients with DTC, can interfere with the assay for Tg. In this study, we evaluated the influence of Anti-Tg on the measurement of Tg using the immunoradiometric assay (IRMA). Methods: In using ELSA-hTg in vivo test (CIS international, Schering, France), a solid phase two-site IRMA was used to measure Tg (23.5 ng/mL, 62.5 ng/mL) under the absence or presence of three concentrations of Anti-Tg (25U/mL, 50U/mL, 100U/mL). We also performed Tg measurement using patients serum that was mixed with patients serum containing high Anti-Tg. ANOVA and Scheffe tests were performed to evaluate the effect of Anti-Tg on Tg IRMA, and an inverse regression was made to calculate the level of Tg from measured Tg and used Anti-Tg levels and also to assess the degree of effect of anti-Tg on Tg IRMA. Results: In measuring Tg using the standard solution, the presence of Anti-Tg resulted in a falsely suppressed Tg value. The IRMAs for 23.5ng/mL of the standard Tg solution resulted in 24.5±1.1 ng/mL under no Anti-Tg, 11.8±0.4 ng/mL under 25U/mL of Anti-Tg, 7.7±0.1 ng/mL under 50U/mL of Anti-Tg, and 4.5±0.4 ng/mL under 100U/mL of Anti-Tg. IRMAs 62.5 ng/mL of the standard Tg solution resulted in 65.9±5.7 ng/mL under no Anti-Tg, 36.3±2.2 ng/mL under 25U/mL of Anti-Tg, 23.7±0.7 ng/mL under 50U/mL of Anti-Tg, and 14.0±1.0 ng/mL under 100U/mL of Anti-Tg. (ANOVA test, p=0.000). The degree of suppression of the measured Tg value was positively correlated with the Anti-Tg level (Quadratic model regression, Sig T=0.000). The presence of Anti-Tg also resulted in a falsely suppressed Tg value for the Tg measurement using patient's serum. 2004). Conclusion: The presence of Anti-Tg could consist of the use of Tg as a tumor, therefore Anti-Tg should be measured in all patients diagnosed with DTC. The interpretation of the Tg level must be performed with extreme caution in patients with Anti-Tg (J Kor Soc Endocrinol 19:42∼47, 2004)

장거리 달리기 선수에서 횡문근융해와 생화학적 지표의 변화에 대한 연구

안선호,최석채,김태현,나용호,송주흥,이영진,조지현,최석준 대한신장학회 2000 대한신장학회잡지 Vol.19 No.5

上向流式 好氣性 生物膜에 의한 農藥含有廢水의 處理에 관한 硏究

안용희,장성호,안종수,박출재,김수생 동아대학교 공과대학 부설 한국자원개발연구소 1994 硏究報告 Vol.18 No.2

This study has been carried out to determine the toxicity of agricultural chemical (TPN) as to wastewater treatment. This system used Aerated Submerged Up-Flow Biofilm Reactor. This reactor can withstand the variation of concentration, flow rate and presence of certain toxic materials in the wastewater to be treated. An acclimation experiment was variated influent COD from 250㎎/ℓ~70㎎/ℓ. The agricultural chemical was added to obtained optimum condition at influent COD 400㎎/ℓ by the acclimation experiment. The conclusions from the experimental results are as follows ; 1. Influent COD concentration was variated 250㎎/ℓ~600㎎/ℓ. The treatment efficiency was stability(86% to 93.3%). When influent COD was 400㎎/ℓ, the treatment efficiency was at best-93.2%. Accordingly, this system was proved to be suitable in treating the wastewater with wide range of concentration. 2. The influent TPN concentration below 1ppm at Up-Flow Aerated Biofillm Reactor, raised no harmful result to treatment efficiency. 3. The treatment efficiency was decreased to 29.8% when the lapse of time. 4. When the experimental TPN toxicity was compared with the DDT toxicity in the reference, it was proved that both of the toxicity had the similer trend.

Ethephon 및 Aminoethoxyvinylglycine 처리가 ‘원황’ 배 모의 수출 환경에서의 품질 및 생리장해 발생에 미치는 영향

최진호,이욱용,안영직,황용수,천종필 충남대학교 농업과학연구소 2013 농업과학연구 Vol.40 No.2

We investigate the effect of preharvest spray of aminoethoxyvinylglycine (AVG), an inhibitor of ACC synthase activity, on fruit quality of ‘Wonhwang’ pear (Pyrus pyrifolia Nakai). And the effects were compared with ethephon which releasing ethylene to elucidate treatment efficacy of ethylene biosynthesis inhibitor on Asian pears. Chemicals were sprayed on 30 days before harvest with AVG (75 and 150 mg/L) and ethephon (100 mg/L), respectively. Highest flesh firmness during 21 days of shelf-life at 25℃ after 30 days of cold storage was attained in the fruit treated with 150 mg/L AVG (26.5N) when compared with untreated control (16.7N), while the fruits treated with 100 mg/L ethephon completely lost their marketability within 14 days of shelf-life by mass drop of firmness down to 11.6N. Low incidence of physiological disorders including pithiness and core browning were attained at the fruits treated with 150 mg/L AVG when we compared with untreated control. No occurrence of mealiness found in the fruits treated with AVG but ethephon treated fruits showed 36.4% during 14 days of shelf-life. Consequently, AVG spray at the concentration of 150mg/L on Asian pear ‘Wonhwang’ fruit regarded as useful preharvest management approach for keeping quality during marketing period after simulated exportation.

자발성 기흉을 동반한 폐림프관평활근종증 1예

안용환,정종훈,김소영,김휘정,김학렬,양세훈,최순호,문형배,조향정,정은택 圓光大學校 醫科學硏究所 2005 圓光醫科學 Vol.20 No.1

정신분열병 및 정신분열형 장애에 대한 올란자핀의 효과와 안전성

안용민,강대엽,권준수,김창윤,김철응,반건호,신영민,이기철,이동우,이중서,조현상,채정호,김용식 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.4

연구목적 : 본 다기관 공동임상연구는 국내 환자를 대상으로 새로운 항정신병약물인 올라자핀의 치료 효과와 안전성을 확인하고자 시행되었다. 방 법 : 1999년 7월부터 2000년 3월까지 국내 10개 병원에 방문한 정신분열병 및 정신분열형 장애 105명을 대상으로 비대조 개방 임상연구를 시행하였다. 중등도 이상의 정신병 증상을 지니거나, 부작용으로 약물교체가 필요한 경우 또는 기분장애 증상의 치료가 필요한 환자를 대상으로 하였다. 2∼7일간의 약물 배설기간 후에 1일 10mg의 올란자핀을 투여하였고, 이후로 3∼7일 간격으로 용량을 조절하여 총 8주간 투여하였다. 치료 효과는 PANSS(Positive and Negative Syndrome Scale), BPRS(Brief Psychiatric Rating Scale), CGI(Clinical Global Impression-Severity), MADRS(Montgomery-Asberg Depression Rating Scale), HAM-A(Hamilton Rating Scale for Anxiety)로 판정하였다. 안전성 평가는 자발적인 이상반응 보고, 활력징후와 혈액 검사 및 SAS(Simpson-Angus Scale), BARS(Barnes Akathisia Rating Scale), AIMS(Abnormal Involuntary Movement Scale)척도를 이용하였다. 결 과 : 105명중에서 85.7%인 90명이 8주간의 치료를 완료하였다. 평균 최빈 용량은 일일 16.1(±4.7)mg이었고, 종료시점에서의 BPRS전체 점수가 기저 상태에 비해 40%이상 감소된 반응군은 69.5%이었다. PANSS의 양성 증후군과 일반정신병리 뿐만 아니라 음성 증후군 소척도에서도 유의한 감소를 보였으며, 이 감소들은 치료 초기부터 나타나서 8주간 지속되었다. 43.8%의 피험자가 중등도 이상의 우울증상을 같이 지니고 있었으며, 올란자핀에 의해 MADRS와 HAM-A가 유의하게 감소하였다. 치료 기간 동안에 활력징후에는 뚜렷한 변화가 없었으나 체중은 8주간 지속적으로 증가하였다. SAS와 AIMS는 감소하였으며, 정좌불능증을 제외한 나머지 추체외로 증상의 발생비율도 낮았다. 임상적인 증상이나 징후를 동반하지 않는 ALT/SGPT의 상승을 보였지만 프로락틴을 포함하는 대부분의 혈액 검사상 뚜렷한 이상 변화는 없었다. 결 론 ; 비록 본 임상연구가 비대조 개방 임상연구로서 많은 제한점을 가지고 있지만, 올란자핀이 기존 약물에 내약성을 보이거나 기분증상을 동반하는 정신병에 치료 효과가 있었다. 그리고 기존 항정신병약물 치료시에 문제가 되었던 추체외로 증상과 고프르로락틴 혈증을 포함하는 대부분의 부작용면에서 안전성을 보여 주었다. Objective : This multicenter clinical trial was carried out to investigate the efficacy and the safety of olanzpine for the treatment of Korean patients. Mothod : 105 patients with schizophrenia and schizophreniform disorder, visited at 10 mental or university hospitals, had received an open and non-comparative treatment with olanzapine for 8 weeks. Patients had psychotic or depressive symptoms with the severity above moderate degree or intolerable side effects to previous antipsychotics. After a wash-out period of 2-7 days, 10mg olanzapine was prescribed initially to all the patients, and then the dosage could be adjusted within the range of 5-20mg/day of olanzapine by 3-7 days. Results : 90(85.7%) of 105 patients completed the 8-weeks trial and the mean modal dose of olanzapine was 16.1(±4.7%)mg/day. At the end of the trial, 73 patients(69.5%) were classified as responder, which was defined as 40% or more improvement in BPRS(Brief Psychiatric Rating Scale) score comparing to baseline. There was a significant reduction in the scores of PANSS(Positive and Negative Syndrome Scale)and subscales including negative symptom scores and CGI. Also weekly analysis showed that the reductions in scores were kept on for the whole period of the trial. 43.8% of all the patients had depressive symptoms at the baseline and total scores of MADRS(Montgomery-Asberg Depression Rating Scale) and HAM-A(Hamilton Rating Scale for Anxiety) were also reduced after the trials. Vital signs revealed no clinically significant changes but continuous weight gain was observed during the treatment with olanzapine. The scores of SAS(Simpson-Angus Scale) and AIMS(Abnormal Involuntary Movement Scale) for assessing the EPS(extrapyramidal symptoms)and tardive dyskinesia respectively were significantly decreased and only a few patients reported EPS as adverse events. Although mild and clinically non-significant of ALT/SGPT was observed, most laboratory parameters including plasma prolactin level showed to significant changes during the trial. Conclusions : Although this trial had many limitations because it was a non-comparative and open study, olanzapine showed high efficacy on the positive, negative and depressive symptoms in schizophrenia and schizophreniform disorder.In addition to that, olanzapine showed a substantially favorable safety profile, such as low incidence of EPS and hyperprolactinemia.