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.

젊은 성인 남자의 흡연과 혈청 지질과의 관련성

조선,류소연,박종,강명근,김은숙,김형철,박광희,윤혜은,노희송 朝鮮大學校 附設 醫學硏究所 2007 The Medical Journal of Chosun University Vol.32 No.2

Objectives: This study was performed to find the association of cigarette smoking and blood lipid profiles in healthy young adults. Methods: The data was collected by a self-administered questionnaire and health examination in 489 professional soldiers from 6 to 12 May, 2004. The status of cigarette smoking was classified by non-smoking, ex-smoked, ≤4.9, 5-9.9, and ≥10 pack-years. The statistical analysis were used by chi-square test, analysis of variance and analysis of covariates. Results: In status of subjects cigarette smoking, current smoking, ex-smoked, and non-smoking were 71.8%, 11.2%, and 17.0%, respectively, In distribution by amount of smoking, non-smoking, ex-smoked, ≤4.9 pack-years, 5-9.9 pack-years, and ≥10 pack-years were 17.0%, 11.2%, 37.4%, 21.3%, and 13.1%, respectively. At other confounding variables were controlled, total cholesterol and LDL-cholesterol were increased significantly when amount of smoking was increased. However, triglyceride and HDL-cholesterol did not showed statistically significant differences, Conclusion: Smoking has relevant to total cholesterol and LDL-cholesterol and it is need to perform the further study for finding how blood lipid profiles are affected its level by cigarette smoking and to find an influence of cigarette smoking on cardiovascular disease.

Quinlolone 유도체 국소도포에 의한 좌창치료의 임상적 연구

권철욱,노영석,김재홍,조소연,강형철,함정희 大韓臨床藥理學會 1994 臨床藥理學會誌 Vol.2 No.2

비대칭 Stilbene 유도체의 고체상 합성

조철희,류태용,박광용 한국공업화학회 2004 응용화학 Vol.8 No.2

Stilbene derivatives, which are of great interests due to their potent biological and optical activities (e.g. using emitting materials in OELD's and non-linear optical (NLO) materials), were produced via the nickel-catalyzed cross-coupling reactions of polymer-bound stilbenesulfonates with aryl Grignard reagents employing solid-phase organic synthesis (SPOS). This traceless method would be useful for preparing unfunctionalized arene library in solid-phase parallel synthesis.

정신재활 치료가 정신분열병 환자의 재발율, 입원횟수, 입원일수 그리고 치료 경비에 미치는 효과 : 2년 추적조사 연구

조진석,공지현,김진원,심경순,하준선,김철권,강동호,장정희,변원탄 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.5

목 적 : 사회기술훈련, 환자교육, 가족교육, 집단치료, 예술치료, 작업치료와 같은 포괄적인 정신재활 치료를 약물치료와 병행할 경우 약물치료만 시행할 때에 비해 정신분열병 환자의 재발율, 입원횟수, 입원일수, 직접 치료경비 등에 어떤 효과가 있는 지를 알아보기 위함이다. 연구방법 : 1993년 9월부터 1995년 2월까지 양산 신경정신병원의 폐쇄병동에서 퇴원한 20∼35세 사이의 정신분열병 환자 173명을 대상으로 46명에게는 6개월동안 정신재활 치료를 시행하였고 127명에게는 통상적인 외래치료만 시행한 후 연구시작 시점을 포함하여 2년동안 양군에 속한 환자들을 대상으로 재발율, 입원횟수, 입원일수, 직접 치료경비 등을 1년 단위로 추적 조사하였으며, 연구시작 시점을 기준으로 전과 후의 매년 평균 입원횟수, 입원일수, 직접 치료경비도 서로 비교하였다. 결 과 : 정신재활 치료를 약물치료와 병행할 경우 약물치료만 시행할 때에 비해 재발율, 입원횟수, 입원일수, 직접 치료비용이 현저히 감소되었다. 그리고 정신재활 치료를 받은 군에서는 치료 전에 비해 치료 후에 재발율, 입원횟수, 입원일수, 직접 치료비용이 유의하게 감소하였지만 통상적인 외래치료만 받은 군에서는 치료 전과 후간에 유의한 변화를 보이지 않았다. 결 론 : 정신분열병 환자들에게 정신재활 치료를 약물치료와 병행할 경우 약물치료만 시행할 때에 비해 환자의 임상적 경과를 호전시킬 뿐 아니라 가족의 경제적 부담도 줄일 수 있다. Objective : We evaluated the clinical efficacy of a comprehensive psychiatric rehabilitation of schizophrenia, including family psychoeducation, patient education, social skills training, group psychotherapy, art therapy, and occupational therapy. Method : From September 1993 to February 1995, 173 chronic schizophrenics who met DSM-IV criteria and were discharged from a locked ward were assigned into the psychiatric rehabilitation service group(psychiatric rehabilitation group, n=46) or the customary out-patient service group(out-patient group, n=127) prospectively, but not randomly. Assignment was based on preferences of patients and their relatives, Each subject included in the psychiatric rehabilitation group received twice weekly patient education, social skills training, family psychoeducation, group psychotherapy, art therapy, occupational therapy and maintenance chemotherapy during a 6-month period. Those in the out-patient group received individual supportive psychotherapy and maintenance chemotherapy according to their clinical needs for 10-20 minutes once per week. After entry into the study, all subjects were assessed for the number of readmission, days of hospitalization, and the direct treatment costs through the first and second year of follow-ups. These outcome variables were also compared pre-and post-2 years at the time point of entry into the study. Aftercare chemotherapy on a weekly to monthly basis continued for the remainder of the two year follow-up period. Results : With regard to the mean number of hospital admissions per year, the mean days of hospitalization per year, and the direct treatment costs per year, the psychiatric rehabilitation group had significantly decreased all clinical outcomes 2 years after compared with before receiving psychiatric rehabilitation. But there were no significant differences in the all clinical outcomes between before and after study intake in the out-patient group. For the number of relapse regardless of drug compliance, 4 patients(9%) during first year and 14 patients(30%) during second year were relapsed in the 46 subjects of the psychiatric rehabilitation group. In contrast, 75 patients(59%) during first year and 90 patients (71%) during second year relapsed in the out-patient group. When considering the effect of drug noncompliance to relapse, 4(9%) and 14 patients(30%) were relapsed while on medication respectively during the first and second year in the 46 of the psychiatric rehabilitation group, vs. 27(34%) of 79 patients on medication during the first year and 31(46%) of 68 patients on medication during the second year were relapsed in the out-patient group. Conclusions : These results indicate that the comprehensive psychiatric rehabilitation can be useful therapeutic intervention both to improve the clinical outcomes of schizophrenic patients and to reduce the economical burden of their relatives.

불임여성에서 스트레스 지각, 대처방식, 우울 및 불안

조행신,정상근,류철희,황익근 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.3

목 적 : 불임여성에서 불임에 의한 스트레스 때문에 심리적 후유증이 발생할 수 있다. 이러한 심리적 영향을 평가하여 정신과적 중재의 필요성을 파악하고자 하였다. 방 법 : 환자군은 전북대학병원 산부인과 불임클리닉에 내원한 불임으로 확직된 34명을 대상으로 하였다. 대조군은 환자군과 연령 및 학력수준이 대등한 1명 이상의 자녀를 둔 34명의 건강한 기혼여성으로 선정하였다. 양군모두 인구통계학적 특성 및 불임관련사항에 관한 반구조화된 설문지, 스트레스 지각검사, 대처방식 체크 리스트, Beck Depression Inventory, Hamilton Anxiety Scale, Hamilton Rating Scale for Depression, SCL-90-R 그리고 상태-특성불안 검사를 이용하여 평가하였다. 결 과 : 불임여성은 대조군에 비해 다음과 같은 결과를 보였다. 1) 스트레스 지각검사 중 금전적인 문제에 스트레스를 더 많이 지각하고 있었으며 (p=0.026), 최근 1년간의 부정적 사건 및 중성적 사건의 빈도가 유의하게 더 높았다.(p〈0.05). 2) 스트레스 대처방식중 정서완화적 대처가 주가되는 소극적 대처의 빈도가 유의하게 높았다(p〈0.05). 3) Hamilton 우울척도수준, Hamilton 불안척도수준 그리고 특성불안수준이 유의하게 더 높았다(p〈0.05). 4) Beck 우울수준, SCL-90-R의 우울수준 그리고 상태-특성 불안수준이 높을수록 일주일간의 스트레스 지각점수가 더 높았으며(p〈0.05), Beck 우울수준, Hamilton 불안수준 그리고 상태-특성 불안 수준이 높을수록 소극적 대처의 빈도가 더 높았다(p〈0.05). 결 론 : 상기 결과로 미루어 불임여성들이 소극적 대처방식과 높은 수준의 우울, 불안을 보이는 바, 이에 대한 정신과적 중재가 필요할 것으로 생각한다. Objective : The purpose of this study was to investigate psychological impacts of infertility related stress in Korean infertile women. Methods : Both the 34 infertile women group and the control group(34 married women) were evaluated by using Semistructured Questionnaire, Stress Perception Scale, Coping Behavior checklist, Beck Depression Inventory(BDI), Hamilton Anxiety Scale(HAS), Hamilton Rating Scale for Depression(HRSD), SCL-90-R and State Trait Anxiety Inventory(STAT). Results : Perceived financial stress of negative and neutral life events and frequency of passive coping(especially, emotion-focused coping) were significantly higher in infertile women than control group. In infertile women, totally perceived stress was positively correlated with BDI, SCL-90-R(depression) and STAI. Passive coping behavior was positively correlated with EDI, HAS and STAI. Conclusion : Above results suggest that infertile women would have a tendency to passive coping and high level of depression and anxiety, and should be considered for psychiatric intervention.

비대칭 Terphenyl 유도체 합성

조철희,박광용 중앙대학교 미래신기술연구소 2003 미래신기술연구소 논문집 Vol.12 No.2

Terphenyl 유도체들은 다양한 생물학적·광학적 활성을 갖고 있으며, 천연물 및 의약품에서 광범위하게 발견되는 화합물이다. Neopentyl bromobenzenesulfonates 와 arylboronic acids를 palladium 촉매를 사용하여 반응하여 형성된 biphenylsulfonates를 arylmagnesium bromides 와 nickel 촉매 하에서 반응시킴으로써, 다양한 비대칭 terphenyl 유도체들을 우수한 수율로 합성하였다. Terphenyl derivatives possess various biological and optical activities. They have been extensively found in natural products and pharmaceuticals. A variety of asymmetric terphenyls were synthesized in high yields via the coupling reactions of biphenylsulfonates, which were prepared by the palladium-catalyzed reactions of neopentyl brombenzenesulfonates with arylboronic acids, with arylmagnesium bromides in the presence of a nickel catalyst.

위삼차신경핵에서 일차구심성 신경섬유 종말부의 미세구조 및 연접양상

배용철,박국필,정경원,박매자,조희중 대한해부학회 1995 Anatomy & Cell Biology Vol.28 No.5

구강에 발생한 편평상피암종의 MMP-2, MMP-9, TIMP-1, TIMP-2 발현과 EGFR 및 E-cadherin 발현의 상호연관성

조성재,권창석,김용환,윤혜경,김우형,이희철 인제대학교 백병원 2002 仁濟醫學 Vol.23 No.4

Objective : Matrix metalloproteinases(MMPs) are involved in the degradation of extracellular matrix, which is related to infiltrative growth and metastasis of tumor. Positive correlation between MMPs expression and clinico-pathologic parameters were reported, and MMPs expressions were regulated by tissue inhibitor of metalloproteinases(TIMPs) or cell adhesion molecules such as E-cadherin and epidermal growth factor receptor EGFR). The aim of this study is to evaluate the relationship between MMP-2, MMP-9 expressions and clinico-pathologic factors such as clinical stage. recurrence. histologic grade and invasion pattern, and between MMP-2 and MMP-9 Expressions and TIMP-1, TIMP-2, and E-cadherin expressions. Methods and Material : The materials were 55 cases of squamous cell carcinoma of the oral cavity, and immunohisdtochemical studies for MMP-2, MMP-9, TIMP-1, TIMP-2, E-cadherin and EGFR were performed. Clinico-pathologic factors such as clinical stage, recurrence, histologic grade and invasion pattern were recorded through microscopic examination and clinical record review. Statistical analyses between MMP-2, MMP-9 expressions and clinico-pathologic factors, TIMP-1, TIMP-2 expressions and EGFR and E-cadherin expressions were done. Results : 1. MMP-2 and MMP-9 expressions were noted in 30(54.5%) and 22(40.0%) of 55 cases, respectively. TIMP-1 and TIMP-2 expressions were observed in 21(38.2%) and 33(60.0%), and E-cadherin and EGFR expressions were found in 35(63.6%) and 26(47.3%) of 55 cases, respectively. 2. MMP-2 expression rate was slightly higher in cases without recurrence, and TIMP-2 expression rate was slightly higher in cases showing more infiltrative growth pattern. However, there were no significant differences of MMP-2, MMP-9, TIMP-1, and TIMP-2 expression rates according to other clinico-pathologic parameters were noted. 3. The expression rate of EGFR was higher in cases with well differentiation (p=0.0047), but no positive relationship between the expression rate of E-cadherin and histologic grade was found. There were no significant differences of the expression rates of E-cadherin and EGFR according to other clinico-pathologic parameters. 4. Cases with positive reaction for MMP-9 showed an increasing tendency of negative reaction for TIMP-1. However, signigicant relationships between MMP-2, MMP-9 expressions and TIMP-1, TIMP-2 expressions were not noted. 5. The expression rate of MMP-2 was higher in cases with positive reaction for Ecadherin and EGFR with no statistical significance. The expression rate of MMP-9 was significantly higher in cases with positive reaction for E-cadherin(p=0.0221), but there was no significant relationship between MMP-9 and EGFR expression. Conclusion : These results suggest that MMP-2, MMP-9, TIMP-1 and TIMP-2 expressions are involved in the development of oral squamos cell carcinomas, but MMP-2, MMP-9, TIMP-1, and TIMP-2 expressions might not seem to be a sueful prognostic factors because there were no significant relationship between clinicopathologic parameters, EGFR expression showed positive correlation with low histologic grace, so EGFR expression could be regarded as a good prognostic factor. In the progression of squamous cell carcinoma of oral cavity, MMP-9 and E-cadherin might be involved with positive correlation, but there were no significant correlations between MMP-2, MMP-9 and TIMP-1, TIMP-2 and EGFR expressions rate. Further study for other factors such as cytokines or growth factors except TIMP-1, TIMP-2 and EGFR will be needed.

정신분열병 환자 자녀에서의 주의력 장애

김철권,조현기,장정희,강동호,조진석,김명정,변원탄 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

본 연구의 목적은 정신분열병 환자의 자녀들과 알코올 의존증 환자의 자녀, 그리고 정신과학적으로 건강한 부모의 자녀들을 대상으로 연속 작업수행력 검사를 이용한 정보처리 과정에서의 지속적 주의력에 관한 사항과 정보 감지능력 검사를 이용한 정보 처리과정에서의 감각등록에 관한 사항을 측정하고 세 군간에 그 결과를 서로 비교하여 차이 유무를 검증하기 위함이다. 연구 대상은 정신분열병 환자의 자녀 28명을 대상군으로 그리고 알코올 의존증 환자의 자녀 18명과 정신과학적으로 건강한 부모를 둔 중고등학생 41명을 대조군으로 하였다. 연구 방법은 대상군 및 두 대조군 모두에게 연속 작업수행력 검사와 정보 감지능력 검사를 순차적으로 시행한 후 그 결과를 서로 비교하였다. 그 결과는 다음과 같다. 1) 연속 작업수행력 검사에서는 대상군이 두 대조군에 비해 맞춘 횟수와 비율이 유의하게 낮았고 놓친 횟수는 반대로 유의하게 높았다. 가장 중요한 변인인 민감도는 대상군이 두 대조군에 비해 유의하게 낮았다. 2) 연속 작업수행력 검사에서 시간 경과에 따른 각 변인의 변화를 보면 맞춘 횟수와 비율에서 대상군이 두 대조군에 비해 시간이 경과할수록 유의하게 감소하였다. 민감도 역시 시간이 경과할수록 대상군이 두 대조군에 비해 유의하게 감소하였다. 3) 연속 작업수행력 검사의 민감도, 정보 감지능력 검사에서의 정답반응 횟수에서 정상 대조군의 분포 곡선중 하위 10% 수치를 절단점으로 잡아 그 수치 이하를 보이는 대상 숫자를 비교해 보면 연속 작업수행력 검사에서만 정신분열병 환자의 자녀군과 정상 대조군 사이에 유의한 차이를 보였다. 4) 대상군, 정상 대조군, 대상군중 연속 작업수행력 검사의 민감도가 하위 10% 이하에 속하는 군의 MMPI를 서로 비교한 결과 세 군간에 MMPI의 모든 변인에서 유의한 차이를 발견할 수 없었다. 5) 정보 감지능력 검사에서는 대상군이 두 대조군에 비해 정답반응과 오답반응을 보이기까지 걸린 평균 시간이 유의하게 길었다. 이상의 연구결과를 통해 저자들은 정신분열병의 발병 위험성이 높은 정신분열병 환자의 자녀군이 알코올 의존증 환자의 자녀군이나 정신과학적으로 건강한 부모를 둔 대조군보다 지속적 주의력에서 결손이 있음을 발견하였고 나아가 이와 같은 지속적 주의력에서의 결손이 정신분열병의 한 가능한 취약지표가 될 수 있을 것으로 사료된다. In order to study the possible vulnerability in the markers of schizophrenia, offsprings of the schizophrenic parents(n=28), offsprings of the alcohol dependent parents(n=18), and offsprings of the psychiatrically normal persons(n=41) were examined for their sustained attention and sensory register by means of Continuous performance test(CPT) and Span apprehension task(SPAN) respectively. The results were as follows : 1) The offsprings of the schizophrenic parents showed a significant deficit in the sustained attention as manifested in the data of CPT by significantly lower hit rate and sensitivity, compared with the offsprings of the alcohol dependent parents and those of the psychiatrically normal persons. No difference was evident in the false alarm rate and response bias among three groups. There was no difference in all variables of the CPT between the offsprings of the alcohol dependent parents and those of the psychiatrically normal persons. 2) The deficit in the sustained attention as revealed by lower hit rate and sensitivity was not apparent in the first part of the CPT. However it emerged and aggravated itself as the test continued in the offsprings of the schizophrenic parents only. 3) Proportion of subjects falling in the extreme low sensitivity of lower 10% of the normal controls was significantly higher in the offsprings of the schizophrenic parent group as compared with the offsprings of the alcohol dependent parents and those of the psychiatrically normal persons with a rate of 29%, 17%, and 10% respectively. 4) No significant difference was noted in all variables of MMPI among normal controls, index group, and the extreme low CPT sensitivity subgroup of index group. 5) The offsprings of the schizophrenic parents showed a significantly delayed response in the time to correct and incorrect response in SPAN compared to the offsprings of the alcohol dependent parents and those of the psychiatrically normal persons. No difference was evident in the number of correct response, number of incorrect response, and number of no response among three groups. There was no difference in all variables of the SPAN between the offsprings of the alcohol dependent parents and those of the psychiatrically normal persons. These results suggest that a subgroup of the offsprings of schizophrenic parents may suffer from the deficit in the sustained attention which may be a vulnerability marker of schizophrenia.