정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

Comparison of controlled ovarian stimulation outcomes for fertility preservation in women with breast cancer according to KI-67, histologic grade, pathologic type, and cancer stage

( Eun Ji Oh ),( Yeon Hee Hong ),( Seul Ki Kim ),( Jung Ryeol Lee ),( Byung Chul Jee ),( Chang Suk Suh ),( Seok Hyun Kim ) 대한산부인과학회 2020 대한산부인과학회 학술대회 Vol.106 No.-

Objective: This study aims to analyze that specific prognostic factors such as Ki-67 value, histologic grade, pathology type, and cancer stage can affect controlled ovarian stimulation outcomes(COS) for fertility preservation in women with breast cancer. Methods: This retrospective cohort study included 92 patients with breast cancer aged 21-44 who underwent COS from August 2012 to April 2020, excluding patients with previous gonadotoxic therapy history. All COS cycles were conducted letrozole-combined random start GnRH antagonist protocol. COS outcomes were compared according to prognostic factors;Ki-67 (< 30% vs. ≥ 30%), histologic grade (low vs. high), and pathologic type (intraductal carcinoma(IDC) vs. triple-negative breast cancer(TNBC)), and cancer stage (early (I, II) vs. advanced (III, IV)). Multivariate analysis was also conducted to find any parameter that can impact over 10 mature oocytes acquisition. Results: Among the 92 patients, 42 were Ki-67≥30% compared to 49 of Ki-67<30%. The number of oocytes, and initial mature oocytes were comparable between Ki-67<30% and ≥30 group. The maturation rate was significantly higher in Ki-67≥30% group than Ki-67<30% group (57.4±36.8% vs. 44.8±28.3%, p=0.041). The same results were drawn when divided according to IDC or TNBC. The maturation rate was significantly higher in TNBC than the IDC group (73.0±17.6% vs. 47.0±28.1% p=0.001). However, the histologic grade or stage did not show any difference in COS outcomes between high and low grade or early and advanced stages. With multivariate analysis, age and AMH are parameters associated with the acquisition of over 10 mature oocytes (OR 0.863, 95% CI [0.755-0.987], OR 1.408, 95% CI [1.145-1.732], respectively). Conclusion: Either Ki-67 or pathologic type can be a potential reliable marker for predicting COS outcome, especially maturation rate. Further study with larger sample size with specific conditions is necessary to clarify the correlation between breast cancer prognostic factors and COS outcomes.

새로운 연노출의 효과지표로서의 혈장 δ-aminolevulinic acid 측정의 유용성

이금원,황보영,김용배,리갑수,이성수,장봉기,함정오,안규동,이병국 순천향대학교 산업의학연구소 2001 순천향산업의학 Vol.7 No.1

To evaluate the usefulness of the measurement of plasma δ - aminolevulinic acid (ALAP) as a new effect indicator of lead exposure, the association of ALAP with blood lead, DMSA chelatable lead and bone lead with a special emphasis of genetic interaction of ALAD polymorphism was studied with 419 lead exposed workers and 85 non-lead exposed workers. Lead workers were recruited from storage battery industries, secondary smelting industries and other lead using industries and non-lead workers selected from electronic refrigerator manufacturing industry. Blood lead, DMSA chelatable lead and bone lead were chosen for parameters of lead exposure. Plasma and urinary ALA were selected for the effect parameter of lead intoxication. Information for age, smoking, drinking habit and body mass index were also obtained. Job duration for lead workers was also collected. The overall prevalence of the variant allele, ALAD type 1-2 or 2-2(ALAD2) in lead exposed workers was 10.0% (42 out of 419 lead workers) which was not differed from control workers (9.4% : 8 out of 85). The means blood lead and DMSA chelatable lead of lead workers with ALAD 1(ALAD type 1-1) were lower than those of lead workers with ALAD2, but the differences were not statistically significant. On the other hand, the mean of tibia lead of lead workers with ALADI was higher than that of lead workers with ALAD2, but the difference was not statistically significant. DMSA chelatable lead showed highest correlation with log transformed plasma ALA(LALAP)(r=0.682) and blood lead and tibia lead had r=0.650, r=0,402 correlation coefficient with LALAP respectively On the other hand. log transformed urinary ALA(LALAU) had lower correlation coefficient with all three parameters of lead exposure than LALAP. The equation of robustic simple linear regression of blood lead on LALAP was LALAP=2.0439+0.0165PbB in ALADI lead workers and LALAP=2.031+0.0121PbB in ALAD2 lead workers. ALAD genotype in the multiple regression analysis of blood lead with LALAP after adjusting for possible confounders(sex, ago, BMI, smoking and drinking status and job duration) showed significant main effect on LALAP resulting lower LALAP in ALAD2 lead workers than ALADI lead workers. On the other hand, effect modification of ALAD genotype was observed in the multiple regression analysis of tibia lead with LALAP after adjusting for possible confounders, but there was no significant effect of ALAD genotype in the multiple regression analysis of DMSA chelatable lead with LALAP after covariate adjustment. With above results, plasma ALA was found to be a useful effect parameter of lead exposure compared with urinary ALA. It was also observed that ALAD polymorphism made significant effect on the association of blood and tibia lead with ALAP. Thc lower plasma ALA in ALAD2 lead workers suggested supportive effect of ALAD2 in lead exposure.

들잔디 성숙종자로부터 캘러스배양 및 식물체 재분화에 미치는 몇 가지 요인의 영향

이상훈,김범수,원성혜,조진기,김기용,박근제,성병렬,이효신,이병현 Plant molecular biology and biotechnology research 2004 Plant molecular biology and biotechnology research Vol.2004 No.-

In an effort to optimize tissue culture responses of zoysiagrass (Zoysia japonica Steud.) for genetic transformation, factors affecting callus induction and plant regeneration were investigated. MS medium containing 3 ㎎/L 2,4-D was optimal for embryogenic callus induction from mature seed. The plant regeneration frequency of 73.3% was observed when embryogenic calli induced in this medium were transferred to N6 medium supplemented with 0.1 ㎎/L 2,4-D and 5 ㎎/L BA. Among several basic media, MS and N6 medium were optimal for callus induction and plant regeneration, respectively. Regenerated plants were grown normally when shoots transplanted to the soil. A rapid and efficient plant regeneration system established in this study will be useful for molecular breeding of turfgrass through genetic transformation.

도장작업시 유해인자들의 노출수준과 작업환경관리실태

이세기,문덕환,이채관,황용식,선병관,손병철,김대환,이창희,김휘동,이채언 인제대학교 백병원 2002 仁濟醫學 Vol.23 No.5

Objectives: For the purpose of preparing the fundamental data and assessing the status of exposure level of chemical substances in painting process. Methods and Materials: The author determined the concentration of organic solvents, lead(Pb), Chromium(Cr), and Toluene-2, 4-diisocyanate(TDI) in air of painting process to 90 industries classified by 15 types of manufacturing industry during a period from Jan. 1st 2001 to Dec. 31st 2001. Results: The results were as follows: 1. The geometric mean level of each chemical substance was 0.1706 ppm for exposure index in organic solvents, 0.0019㎎/㎥ for Pb, 0.0024 ㎎/㎥ for Cr, and 0.0004ppm for TDI, respectively. 2. The exposure level of each chemical substances by type of painting was the highest in dipping and brush painting for organic solvent, in spray-painting for TDI, and in spray gun-painting for Pb and Cr, respectively. 3. The exposure level of each chemical substances by type of local ventilation equipment was higher in enclosed and booth type for organic solvents. Cr, and TDI, and in exterior type for Pb, respectively than those of other types. 4. The exposure level of each chemical substances by type of hazardous material arresting media was higher in using water for organic substances, in using bag filter for Pb, TDI, respectively than those of other types. Conclusion: According to above results, this study suggests that the exposure level by type of industry exceeded the exposure level in wooden furniture and metal furniture manufacturing industry for organic solvents and Pb, respectively.

Gilbert 증후군에서 열량 제한 시험과 Phenobarbital 자극 시험의 의의(14예)

이헌영,채경훈,정재훈,강윤세,김연수,문희석,박기오,이엄석,김선문,김석현,성재규,이병석,이강욱 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

Gilbert 증후군은 인구의 7%에서까지 나타날 수 있는 매우 흔한 증후군으로서 비진행성인 양성의 만성적 경과를 치하며, 간질환의 증상과 징후가 없는 경한 비포합형 고빌리루빈혈증이 특징인 일종의 체질적인 증상으로서 혈장 빌리루빈 농도에 대한 사춘기의 영향 때문에 10대와 20대에 자주 진단이 된다. 따라서 임상적인 중요성은 미약하지만 높은 빈도가 예상되는 점에 그 중요성이 부여되어야 할 것이다. 따라서 적정한 임상적 진단법으로 기왕에 소개된 열량제한 시험과 phenobarbital 유도 시험을 시행하고 이들의 진단적 가치를 알아보기 위하여 본 연구를 시행하였다. 1990년 7월부터 1999년 4월까지 충남대학교병원에 내원하여 HBsAg, IgG anti-HBc 및 anti-HCV가 음성이고, 간 초음파 스캔에서 이상이 없으며, 혈청 AST, ALT 및 AP가 정상인 비음주자에서 경한 비포합형 고빌리루빈혈증이 있는 14예의 환자들을 대상으로 ^(99m)Tc-DISID 스캔을 시행하였으며, 기저 치 총빌리루빈 및 포합형 빌리루빈 치를 측정한 다음에 하루에 400Kcal로 48시간동안 제한한 열량 제한 시험을 시행하였고, phenobarbital을 하루 60mg씩 5일간 투여한 후에도 각각 총빌리루빈과 포합형 빌리루빈 치를 검사하여 비포합형을 구하였다. 대상 환자들은 모두 14예로서 남자가 11예(78.6%)였고 여자가 3예(21.4%)여서 3.7:1로 남자에서 많았으며, 20대가 6예(42.9%), 30대가 역시 6예(42.9%) 및 40대가 2예(14.2%)로서 2,30대가 대부분(85.8%)이었다. 열량 제한 시험 후의 총빌리루빈 치, 비포합형 및 포합형 빌리루빈 치들은 평균 각각 5.5±2.7, 4.2±2.3 및 1.3±10mg/dL 로서, 시험 전 치들인 3.0±0.8, 2.2±0.8 및 0.7±0.4mg/dL 보다 유의하게(p=0.001, p=0.001, p=0.023) 상승하였다. 포합형 빌리루빈 치도 유의하게 상승하였으나 비포합형의 상승보다는 훨씬 낮아서 주로 비포합형이 증가하였다. phenobarbital 투여 중 설사가 발생하여 중단한 1예를 제외한 13예에서 열량 제한 시험 후에 상승하였던 총, 비포합형 및 포합형 빌리루빈 치가 phenobarbital 유도 시험후에는 2.0±1.1, 1.5±0.8 및 0.5±0.4mg/dL로서 열량 제한 시험 결과보다 유의하게 낮아졌고(p=0.00, p=0.000, p=0.001), 열량 제한 시험 전의 기초치들인 3.0±0.8, 2.2±0.8 및 0.7±0.4mg.dL 보다도 더욱 낮아졌으며 유의한 차이(p=0.001, p=0.02, p=0.005)를 나타내었다. 14예에서 시행한 ^(99m)-Tc DISIDA 스캔에서 9예(64.3%)가 정상이었고, 5예(35.7%)에서는 심장 및 신장으로의 간외 섭취가 3예였고, 60분까지 소장 배출이 없는 배설 지연 예와 담낭 수축 불량 예가 각각 1예 씩 발견되었다. Phenobarbital 투여시험에서 민감도가 열량제한시험에 비해 더 높았다(92.3%와 50.0%). Gilbert 증후군에서 1일 400 Kcal로 48시간의 열량제한 시험과 1일 60mg의 phenobarbital을 5일간 투여하는 유도 시험은 편리하고 유용한 임상적인 진단법으로 이용할 수 있다고 생각된다. 그러나 열량 제한 시험에서는 증가 기준의 통일이 필요하다고 유추되며 phenobarbital 유도 시험이 민감도가 더 높은 것으로 생각된다. Gilbert's syndrome is very frequent and benign chronic process characterized by mild, intermittent, unconjugated hyperbilirubinemia without any symptom and sign of liver disease. Previously intoduced caloric restriction test and phenobarbital stimulation test as two appropriate clinical tests had been examined and their diagnostic values were reevaluated. Fourteen patients with mild, persistent, unconjugated hyperbilirubinemia were included. Subsequently caloric restriction has been applicated by 400 Kcal/day for 48 hours and phenobarbital has been prescribed by 60 mg/day for 5 days. Therafter serum levels of total and direct bilirubin were measured. Most of the patients were third and fourth decade(85.8%) and male predominant. Each basal serum levels of total, indirect and direct bilirubin were 3.0±0.8, 2.2±0.8 and 0.7±0.4 mg/dL. After caloric restriction test, each levels were increased significantly to 5.5±2.7, 4.2±2.3 and 1.3±1.0 mg/dL(p=0.001, p=0.001, p=0.023). After phenobarbital stimulation test for 13 patients had been practiced, increased levels of each bilirubin after caloric restriction test were decreased significantly to 2.0±1.0, 1.5±0.8 and 0.5±0.4 mg/dL(p=0.000, p=0.000, p=0.001) and these levels were significantly lower than basal levels(p=0.001, p=0.02, p=0.005). The sensitivities of caloric restriction test were 85.7%, 50.0%, and 71.4%, 35.7%(1.0, 1.5 mg increase of total bilirubin and 1.0, 1.5 mg/dL increase of indirect bilirubin). The sensitivities of phenobarbital stimulation test were 93.2% and 92.3% at criteria of 1.5 mg/dL increase of total bilirubin and indirect bilirubin. On the diagnosis of Gilbert syndrome, caloric restriction test and phenobarbital stimulation test are convenient and useful diagnostic tools in clinical face. And also phenobarbital stimulation test has higher sensitivity than caloric restriction test. Furthermore, standardization of bilirubin increment would be necessary in caloric restriction test.

업종에 따른 연 취급 사업장의 기중 연 농도 및 연 노출 수준 평가

이병국,김용배,리갑수,안현철,김화성,이용진,황규윤,장봉기,이성수,안규동 순천향대학교 산업의학연구소 1999 순천향산업의학 Vol.5 No.1

In order to obtain an useful information for health management and biological monitoring of lead exposed workers, Authors tried to investigate air lead level and the lead exposed level of workers in lead industry according to occupational category. The subjects in our study were 2074 workers in 7 lead-using industries, and study subjects were divided into 4 occupational categories such as storage battery industry (type 1), primary smelting industry (type 2), secondary smelting industry (type 3) and litharge making industry (type 4). Blood zincprotoporphyrin concentration (ZPP), blood lead concentration (PbB) and urinary δ -aminolevulinic acid (ALAU), hemoglobin (Hb), hematocrit (Hct) were selected as the indices of lead exposure. Personal variables such as age, work duration were also collected. The results were as follows. 1. The geometric mean air lead in 9 lead-using industry was 0.1133±4.3120 ㎎/㎥, and that in type 1, 2, 3 and 4 was 0.1038±3.4952 ㎎/㎥, 0.0429±3.4329 ㎎/㎥, 0.1877±2.5123 ㎎/㎥ and 0.9961±5.2910 ㎎/㎥, respectively. 2. The mean ZPP in 9 lead-using industry was 53.1±28.0 ㎍/㎗, and that in type 1, 2, 3 and 4 was 52.0±24.8 ㎍/㎗, 48.0±16.4 ㎍/㎗, 109.8±85.6 ㎍/㎗ and 74.3±37.8 ㎍/㎗, respectively. There was significant difference in ZPP according to occupational category (P<0.01). The percents of lead workers whose ZPP were above 100 ㎍/㎗ in type 1, 2, 3 and 4 were 4.0%, 1.7%, 34.3% and 21.6%, respectively. 3. The mean PbB in lead-using industry was 26.0±11.2 ㎍/㎗, and that in type 1, 2, 3 and 4 was 25.3±11.1 ㎍/㎗, 26.7±8.8 ㎍/㎗, 50.3±15.2 ㎍/㎗ and 36.4±11.0 ㎍/㎗, respectively. There was significant difference in PbB according to occupational category (P<0.01). The percents of lead workers whose PbB were above 40 ㎍/㎗ in type 1, 2, 3 and 4 were 10.4%, 7.7% 71.9% and 43.2%, respectively. 4. While the correlation of Hb corrected PbB with ZPP was higher than non corrected PbB, the correlation of log-transformed ZPP with PbB was higher than non corrected ZPP. 5. Simple linear regressions of PbB and corrected PbB as independent variable with ZPP, log-transformed ZPP and ALAU as dependent variable were statistically significant (P0.01). Coefficient of determination of corrected PbB with other variables was higher than non corrected PbB. As the result of this study, it was suggested that reconsideration of environmental and biological monitoring program was highly recommended for secondary smelting and litharge making industry.

Ascorbate Peroxidase 유전자의 도입에 의한 식물의 형질전환

이인애,이효신,배은경,김기용,이병헌,손대영,조진기 Plant molecular biology and biotechnology research 2002 Plant molecular biology and biotechnology research Vol.2002 No.-

This study was conducted to obtain the transformed tobacco (Nicotiana tubacum) plants with cytosolic ascorbate peroxidase gene(ApxSC7) using Agrobacterium tumefaciens LBA4404. A cDNA encoding the cytosolic ascorbate peroxidase of strawberry, ApxSC7, was introduced into tobacco plants via Agrobacterium-mediated gene transfer system. The expression vector, pIG-AP8, harboring ApxSC7 gene was used for production of transgenic tobacco plants. A large number of transgenic plants were regenerated on a medium containing hygromycin. Integration of ApxSC7 gene was confirmed by PCR and Southern blot analyses with genomic DNA. Northern blot analyses revealed that the pIGap8 gene was constitutively expressed.

FET형 포도당 센서를 위한 PVP/DAST/GOD 고정화막 형성기술

조병욱,이수근,박이순,이종덕,손병기 경북대학교 센서기술연구소 1992 센서技術學術大會論文集 Vol.3 No.1

Special Issue of Professor Kiehwa Lee`s Retirement: Geophysical Environments of the Korean Peninsula : Articles ; Geoelectrical Structure of the Kyongsang Basin from Magnetotelluric Sounding

( Choon Ki Lee ),( Heui Soon Lee ),( Byung Doo Kwon ),( In Ky Cho ),( Seok Hoon Oh ),( Yoon Ho Song ),( Tae Jong Lee ) 대한지구물리학회 2006 지구물리 Vol.9 No.3