기억력 저하를 호소하는 노인들을 대상으로 INM176를 3개월간 임상시험한 후의 치료성적 및 부작용 평가 보고

김지혜,고선규,고효정,권영아,김성환,김재경,김태은,박재우,서민영,송영란,이인수,김도관 大韓神經精神醫學會 2003 신경정신의학 Vol.42 No.2

Objectives : We examined the effects of INM 176 (K-l107) compared with placebo on the cognitive functions of 92 old aged subjects with cognitive impairment. Methods : This was a prospective, 12 week, double-blind, Placebo-controlled clinical trial. The elderly who achieved a score of less than 25 points on the K-MMSE or showed a high risk of Alzheimer's disease from the 7-Minute Neurocognitive Screening Battery were considered to have objective impairment and were selected as subjects for this study. The subjects were randomized to placebo or INM 176 group. The outcome measures were from the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog), the Instrumental Activities ofDaily Living (IADL) and the Korean Geriatric Depression Scale (KGDS) and two kinds of computerized priming tests. After setting the total error score in the Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-cog) as the repeated measurement factor, an analysis of variance of the combined factor design was done between the placebo and INM 176 group. Results : The interaction effect of time (pre- and post-trial) and group (placebo and INM 176 group) was significant in the analysis of the ADAS-cog's total error score. The INM 176 group's total error score in the ADAS-cog decreased significantly (p<0.01), whereas the placebo group showed a slight increase. The mean changes in IADL and GDS from baseline scores favored in the INM 176 group than in the placebo group. Outcome changes ofADAS-cog, IADL, KGDS scores during the 12 week clinical trail ofINM 176 and placebo demonstrated favorable responses in the INM176 administered group. Conclusions : This is a preliminary clinical trial result of INM176 as a memory pill. Based on these results, INM176 may be a candidate molecule for the improvement of cognitive functions, including memory, Further clinical trial should demonstrate its efficacy.

Rat의 복강내에 투여한 5-fluorouracil-polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구

강대영,송규상,최정목,노승무,정경수,오정연,김진향,양준묵,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

For more effective intraperitoneal chemotherapy, the authers made 5-fluorouracil-polyglycolic acid composite disks(FU-PGA disks) with 5-fluorouracil and polyglycolic acid, a biodegradable polymer. We inserted the FU-PGA disk into the peritoneal cavites of Sprague-Dawley male rats, the control and three experimental groups; one FU-PGA disk insert group(300mg/kg), two FU-PGA disk insert group(600mg/kg), and three FU-PGA disk insert group(900mg/kg). The control group received a similar number of PGA disk inserts. A pharmacokinetic study was performed to measure the 5-fluorouracil concentration in the peritoneal fluid, blood, and tissues(liver, kidney and heart) at 24 hours, 72hours and 168 hours after insertion of the FU-PGA disk. Light and electron microscopic studies were done. The results were as follows: 1) The number of white blood cells and platelets decreased after FU-PGA insertion. The degree was proportional to the duration and amounts inserted. The change in the number of red blood cells varied slightly. 2) Light microscopically, slight changes were noted at 168 hours in the 3 disk insert group (900mg/kg). Mild fatty change and hepatocyte degeneration around the central veins of the liver were noted, with vacuolar degeneration in the proximal convoluted tubules of the kidney. 3) Electron microscopically,the liver showed focal increases of lipid droplets in the hepatocytes, and irregular nuclear membrane with focal nucleolar segregation of the fibrillar and granular elements. Also the double membranous structure of the hepatocytes and Kupffer cells was widened with bleb formation. The kidney showed wide separation of the nuclear double membrane in the proximal convoluted tubular cells and mesangial cells, with vacuolation and myelin figure formation in the mitochondria of the proximal convoluted tubular cells, at 72 hours and 168 hours in the 2 to 3 FU-PGA insert groups. The heart showed focal loss of cristae,vacuolation and myelin figure formation in the mitochondria of the 2 to 3 FU-PGA insert groups. In conclusion, despite the large amont of FU-PGA inserted, the histopathological changes in the liver, kidney and heart were slight, and consonant with the very low amount of 5-fluorouracil concentrations detected in the liver, kidney and heart. The above results suggest that the FU-PGA composite can serve as a new device for releasing drugs in a controlled manner and easily targeted to intraperitoneal organs. This device can improve the efficacy of intraperitoneal chemotherapy for gastric cancer.

Risk of Traumatic Intracranial Hemorrhage From Low-Energy Falls in the Oldest-Old Patients

Sung Kyu Kim,Ki Young Jeong,이종석,Han Sung Choi,홍훈표,고영관 대한노인병학회 2016 Annals of geriatric medicine and research Vol.20 No.4

Background: The population of individuals classified as oldest-old (aged ≥85 years) has increased rapidly in recent years. The rates of morbidity from chronic diseases and physical dependence tend to be higher in the oldest-old compared with individuals classified as young-to-middle-old (aged 65-84 years). Therefore, the classification and evaluation of traumatic injuries in the oldest-old group are necessary. Herein we focused on the risk of traumatic intracranial hemorrhage from low-energy falls in older patients. Methods: Patient medical records from the Emergency Department after low-energy falls that occurred between November 2014 and April 2016 were retrospectively analyzed. Patients were divided into an older group (aged ≥65 years) and an adult group (aged 18-64 years); the older group was subdivided into the oldest-old group (aged ≥85 years) and a young-to-middle-old group (aged 65-84 years). The rate of intracranial hemorrhage and related factors were also investigated. Results: The older group had a greater risk of traumatic intracranial hemorrhage than the adult group (20% vs. 12.6%, p=0.019). Furthermore, more cases of traumatic intracranial hemorrhage were found in the oldest-old group than in the young-to-middle-old group (37.5% vs. 18.0%, p=0.024). Similarly, the risk of traumatic intracranial hemorrhage in the oldest-old was higher than in the young-to-middle-old group (p=0.032). Conclusion: The risk of traumatic intracranial hemorrhage from low-energy falls in the oldest-old patients was higher than in the young-to-middleold patients. Therefore, physicians need to pay particular attention to oldest-old patients, even to those with mental integrity and without neurological deficits.

65세 이상의 노령층에서 고지혈증의 위험요인

김용배,장원기,황보영,김화성,안규동,이병국,이용진,김세훈,김승수,김승훈,김영록,김웅빈,이성수 순천향의학연구소 2006 Journal of Soonchunhyang Medical Science Vol.12 No.1

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백서의 복강내에 투여한 Mitomycin-C-Polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구

송규상,강대영,최정목,노승무,정경수,오정연,김진향,양준목,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

To evaluate the in-vivo effects of mitomycin-C-polyglycolic acid composite(MMC-PGA) the disk: shaped composite were implanted into the peritoneal cavity of the Sprague-Dawley rats. The pathologic changes were examined at various time points up to 12 weeks. Initially the soft tissue around the inserted disks showed capillary congestion at 3 days. Inflammatory infiltrates with foreign body giant cells appeared from the 2nd week and reached peak response at 6-8 weeks. These reaction diminished prominently at 12 weeks. No specific pathologic change was found in the liver, the kidneys, and the heart. The above results suggest that the MMC-PGA composite can serve as a new device for intraperitoneal chemotherapy of various types of cancers.

고령자 남녀와 20대 남녀에 있어서 다양한 등속수축중 최대 모멘트의 비교

金智源(Ji-Won Kim),金相佑(Sang-Woo Kim),文基旭(Ki-Wook Moon),嚴光文(Gwang-Moon Eom),李泳揆(Young-Gyu Lee),南貞淑(Jung-Sook Nam),朴寬龍(Kwan-Yong Park),金耀翰(Yo-Han Kim),洪廷和(Jeong-Hwa Hong),朴炳奎(Bung-Kyu Park) 대한전기학회 2008 전기학회논문지 Vol.57 No.10

In this paper, we investigated the maximum ankle joint plantarflexion moment (MPM) of young and elderly subjects during various modes of isokinetic contractions with special interest in the elderly females who were reported to have higher fall rate than the elderly males. Subjects include the young subjects (14 males: 22.7±2.5yrs, 13 females: 20.5±1.3yrs) and the elderly subjects (17 males: 65.8±10.5yrs, 26 females: 71.4±5.2yrs). The MPM was normalized by each subject's body weight. The MPM of elderly females was the weakest among the groups, particularly, at the eccentric contractions. The male-to-female ratio of MPM was greater in the elderly than in the young and the young-to-elderly ratio of MPM was greater in female than in male, both during the eccentric contractions. The result suggests that the decreased muscle force per body weight, especially at the eccentric contraction, may be one reason for the more frequent fall of the elderly female than the elderly male.

전경대원에서 발생한 결핵의 임상 양상

문창기,박상준,조민구,김영중,김소연,김윤권,정준오,안석진,김은실,서승오,김지훈,최원제,이윤영,박형기,최규영,김현근 대한감염학회 2006 감염과 화학요법 Vol.38 No.6

Background: The purpose of this study was to document the incidence and clinical characteristics of patients with tuberculosis (TB) in combat and auxiliary police, living in a group, in Korea where the incidence rate of active TB in a general population is higher than in Western countries. Materials and Methods:We retrospectively reviewed the medical records of all tuberculosis patients diagnosed at National Police Hospital from January 2002 through December 2004. Results:In 2002-2004, a total of 156 cases of tuberculosis were identified with the mean (Standard deviation) age of 20.6 (±1.0) years. Of these, 134 (85.9%) patients were registered as new cases, 11 (7.1%) as relapse, 2 (1.3%) as failure, 5 (3.1%) as treatment-after-default cases whereas 4 (2.6 %) patients were not included in any categories. Average annual new TB rate and smear-positive TB rate were 86.5/10^(5) and 17.4/10^(5) person-years, respectively. In 12 of 31 smear-positive cases, time from onset of symptoms to diagnosis was more than 30 days. Two multidrug-resistance TB cases were identified and two suspected outbreak episodes of TB had occurred during 3 years. Conclusion:There was no statistically significant difference in the incidence rate of new cases of TB between the general population aged 20 to 29 years and combat and auxiliary police in Korea. 배경 : 국내 결핵의 발생은 감소 추세에 있으나 여전히 후진국형 발생양상을 보이고 있다. 특히 집단생활을 하는 젊은이들에서 발생하는 결핵의 유행이 간헐적으로 알려지고 있어 우려를 낳고 있다. 이에 저자들은 최근 전경대원의 결핵 발병 양상에 대해 알아보고자 본 연구를 시행하였다. 재료 및 방법 : 2002년 1월부터 2004년 12월까지 3년간 경찰병원에서 결핵 진료를 받은 전경대원의 의무기록을 후향적으로 분석하여 연도별 결핵 신환발생률, 도말양성결핵 신환율, 진단 지연, 집단발병, 다제내성결핵을 조사하였다. 결과 : 연도별 결핵 신환자 수(10만명당 발생추정치)는 2002년 50명(83.6명), 2003년 42명(83.7명), 2004년 42명(93.5명)이었고 도말양성 폐결핵 신환자 수는 2002년 10명(16.7명), 2003년 11명(21.9명), 2004년 6명(13.4명)이었다. 3년간 도말양성 폐결핵 환자는 31명이 있었고 그 중 12명은 호흡기 증상 발생 30일이 지나서 진단을 받았다. 다제내성 결핵은 2명이 있었으며 결핵의 집단발병이 의심되는 사례는 2차례 있었다. 결론 : 전경대원과 20-29세 연령군 일반인의 결핵 신환발생률, 도말양성 폐결핵 발생률의 통계적으로 유의한 차이는 없었다.

하안면부에서 입술의 돌출 정도와 안면 비대칭의 인지도에 관한 연구

김규선,김영진,이근혜,김영호,국윤아 대한치과교정학회 2006 대한치과교정학회지 Vol.36 No.6

교정 치료를 하고자 하는 가장 큰 동기 중의 하나는 좋은 안면을 얻고자 하는 것이므로 교정 치료 후 안면부에 나타나는 변화에 대한 환자들의 인지도를 이해하는 것은 교정 치료의 진단과 치료 계획 수립에 매우 중요한 일이다. 이에 본 연구는 정면 및 측모에서 하 안면부위의 입술의 위치와 안면 비대칭의 변화에 관하여 인지할 수 있는 최소한의 변화량을 알아보고자 균형 잡힌 비율을 지닌 가상의 정모와 측모 사진을 컴퓨터 영상으로 제작한 후 입술의 위치는 Ricketts의 E-line을 기준으로, 안면의 비대칭은 턱 끝의 중앙 지점을 기준으로 각각 1, 2, 3, 4 mm 변화시킨 디지털 영상을 이용하여 40명의 미술학도를 관찰자로 인지도 조사를 하였다. 연구 결과 환자가 입술의 위치와 비대칭의 변화를 인지하기 위해서는 측모에서 최소한 2 mm 이상, 정모에서 3 mm 이상의 변화가 필요하였으며 하 안면부 변화에 대한 인지도는 정모에서보다 측모 변화에 대한 인지도가 높았다. 또한 변화에 대한 사전 정보는 변화에 대한 인지율을 현저하게 높여 주었다. Objective: While one of the most prevailing motivations for seeking orthodontic treatment is to achieve good facial esthetics, understanding the level of a person's perception to the changes that have occurred on the face after orthodontic treatment is critical to the process of orthodontic diagnosis and treatment planing. Methods: 40 students attending art school participated in determining the level of their perception of changed lip position and facial asymmetry. Computer-graphic frontal face and facial profile photographs with balanced proportions were used to evaluate the level of a participant's perception of the changes in facial asymmetry and in lip position. Results: Change of lip position over 2 mm and over a 3 mm change of facial asymmetry was perceived significantly. Conclusion: The results indicated that at least a 2 mm change of lip position was needed to be perceived after orthodontic treatment. The level of perception of the change in facial asymmetry was lower than that of the change in lip position. Information about facial changes given prior to the evaluation enhanced the level of perception.

물리학 선량법을 이용한 갑상선암의 개인별 최대안전용량 I-131 치료법 개발과 유용성 평가

김정철,윤정한,범희승,제갈영종,송호천,민정준,정환정,김성민,허영준,이명호,박영규,정준기 대한핵의학회 2003 핵의학 분자영상 Vol.37 No.2

목적 : 분화갑상선암 환자에 대한 방사성옥소(I-131) 치료는 재발율과 사망률을 감소시키는 효과적인 치료법이지만, 치료용량을 증가시킴으로써 치료율을 향상시킬 수 있는지에 대해서는 아직 논란이 있다. 본 연구에서는 최대허용선량 치료법의 효용성을 검증하고자 하였다. 대상 및 방법 : 임상적 병기가 제3, 4병기이고, 6개월 이후에 I-131 전신스캔(이하 IWBS)과 혈중 thyroglobulin (이하 Tg), anti-thyroglobulin antibody (이하 ATA), 초음파검사 (이하 US) 및 F-18 FDG PET 등을 통해 치료여부를 확인할 수 있었던 58명(남:여=9:49, 평균연령 50±11세)의 유두상갑상선암 환자를 대상으로 하였다. 이중 11명은 제4병기, 47명은 제3병기였으며, 43명(남:여=4:39), 평균연령 50±11세)은 7.4 GBq 이하의 고식적인 저용량치료법으로 치료하였고, 9.25 GBq 이상의 고용량 치료를 받은 환자는 15명(남:여=5:10, 평균연령 50±12세)으로 고용량군에서 남자가 더 많았으나 연령의 차이는 없었다. 고용량군 환자 모두에서 추적용량의 방사성옥소(평균 77±3 MBq)를 경구 투여한 후 혈중 방사능소실곡선을 통해 최대허용선량(maximum permissible dose, 이하 MPD)을 계산하였으며, 7명에서는 말초혈액림프구의 중기염색체분석법에 의해 생물학적으로 MPD를 계산하였다. 14명에서는 치료용량의 방사성옥소를 투여한 후 혈중 방사능소실곡선을 통해 MPD를 계사하였다. 완전치유(complete response, 이하 CR)는 IWBS에서 병소가 없어지고, 혈중 Tg치가 1 ng/mL 이하로 감소한 경우로 정의하였으며, 부분치유(partial response, 이하 PR)는 IWBS에서 병소가 없어졌더라도 혈중 Tg, ATA치가 높거나, US 또는 PET 검사에서 병소가 남아있는 경우로 정의하였다. 치료후 IWBS에서 병소가 오히려 증가하거나 변함없는 경우는 없었다. 방사성옥소 치료에 의한 부작용은 입원기간 중 타액선이 현저하게 붓고 통증이 있거나, 구토를 심하게 하는 경우, 그리고 퇴원후 1개월째 백혈구수가 20% 이상 감소한 경우로 정의하였다. 결과 : 양 군간에 연속적인 수치변화를 비교하는 경우는 paired t-test를 이용하였으며, 대상군간 치료효과와 부작용의 비교는 chi-square test를 이용하였다. p값 0.05 미만을 통계적으로 유의한 차이로 인정하였다. 고용량군 환자 모두에서 추적용량과 치료용량의 방사성옥소 투여 후 혈액의 피폭선량은 각각 0.012±0.3 Gy, 1.66±25 Gy였으며, 방사성옥소 투여 후 혈액에 전달되는 피폭선량은 추적용량보다 치료용량에서 더 많았고 (1.21: 166 rad, p<0.001), 방사성옥소 1 mCi당 혈액에 전달되는 피폭선량은 차이가 없었다(0.58±0.1 vs. 0.56±0.1 rad/37 MBq, p=0.34). 추적용량 방사성옥소 투여 후 구한 MPD는 평균 13.3±1.9 GBq (9.7 ~ 16 GBq) 이였고, 치료용량 방사성옥소 투여 후 구한 MPD는 평균 13.8±2.1 GBq (10.4 ~ 16.3 GBq)로 유의한 차이가 없었으며 (p=0.20), 두 수치간에는 유의한 상관 관계가 있었다(r=0.8, p<0.0001). 7명의 환자에서 말초혈액림프구 중기염색체 분석법으로 MPD를 측정하였는데 혈액의 피폭선량은 1.78±0.03 G였으며, 같은 환자에서 혈중 방사능소실곡선으로부터 구한 피폭선량은 1.54±0.03 G로 유의하게 낮았으나 (p=0.01), 두 측정치 간에는 유의한 상관관계(r=0.86, p=0.01)가 있었다. 저용량 치료군 43명 중 22명(51.2%)에서 완전치유를 보였고 21명(48.8%)에서는 부분치유를 보인 반면 고용량 치료군 15명 중 12명(80%)에서 완전치유를 보였고 3명(20%)에서만 부분치유를 보여 고용량 치료군에서 유의하게 높은 완전치유를 얻을 수 있었다(p=0.05). 한편 부작용 발생빈도는 저용량 치료군 43명 중 13(30.2%), 고용량 치료군 15명 중 6명(40%)로 양군간에 유의한 차이가 없었다(p=0.46). 임상적인 병기, 연령 및 성별에 따라서는 치유의 차이가 없었다(p>0.05). 결론 : 혈중소실곡선으로부터 MPD를 결정하고 이를 토대로 환자 개개인별로 적절한 선량을 선택하여 치료하는 방법은 부작용을 최소화하면서도 치료효과를 높일 수 있는 매우 유용한 치료법이며, 고위험군 분화갑상선 암 환자에게 가장 적절한 치료법이라고 사료되었다. Purpose: Radioiodine (1-131) therapy is an effective modality to reduce both recurrence and mortality rates in differentiated thyroid cancer. Whether higher doses shows higher therapeutic responses was still debatable. The purpose of this study was to validate curve-fitting (CF) method measuring maximum permissible dose (MPD) by a biological dosimetry using metaphase analysis of peripheral blood lymphocytes. Materials and Methods: Therapeutic effects of MPD was evaluated in 58 patients (49 females and 9 males, mean age 50±11 years) of papillary thyroid cancer. Among them 43 patients were treated with ≤7.4 GBq, while 15 patients with ≥9.25 GBq. The former was defined as low-dose group, and the latter high-dose group. Therapeutic response was defined as complete response when complete disappearance of lesions on follow-up 1-131 scan and undetectable serum thyroglobulin levels were found. Statistical comparison between groups were done using chi-square test. P value less than 0.05 was regarded as statistically significant. Results: MPD measured by CF method using tracer and therapeutic doses were 13.3±1.9 and 13.8±2.1 GBq, respectively (p=0.20). They showed a significant correlation (r=0.8, p<0.0001). Exposed doses to blood measured by CF and biological methods were 1.54±0.03 and 1.78±0.03 Gy (p=0.01). They also showed a significant correlation (r=0.86, p=0.01). High-does group showed a significantly higher rate of complete response (12/15, 80%) as compared to the low-dose group (22/43, 51.2%) (p=0.05). While occurrence of side effects was not different between two groups (40% vs. 30.2%, p=0.46). Conclusion: Measurement of MPD using CF method is reliable, and the high-dose 1-131 therapy using MPD gains significantly higher therapeutic effects as compared with low-dose therapy.

HMG-CoA 환원효소 억제제에 의한 ICAM-1 유전자의 발현조절

김현진,정효균,홍우정,김군순,조영석,김도희,채수흥,구본정,송민호,노흥규,김영건 충남대학교 의과대학 지역사회의학연구소 2001 충남의대잡지 Vol.28 No.1

Background : ICAM-1 act as one of major adhesion molecules in the atherosclerotic lesion. ICAM-1 expression is mainly regulated at the level of transcription and depend on IFN-γ signal transduction pathway in which the STAT1 transcrption factor is a critical intermediate. IFN-γreceptor not only initiates tyrosine 701 phosphorylation of STAT1 by Jak1 and Jak2, but also phosphorylates serine 727 through the activation of Raf-1/MAP kinases. HMG-CoA reductase inhibitors have anti-atherosclertic effects, beyond normalization of hypercholesterolemia, by directly acting on endothelial cells, macrophages and vascular smooth muscle cells. HMG-CoA reductase inhibitors suppress the synthesis of isoprenoid intermediates such as geranylgeranyl-pyrophosphate or farnesylpyrophosphate. These effects results inhibitors suppress the synthesis of isoprenoid intermediates such as geranylgeranyl-pyrophosphate or farnesylpyrophosphate. These effects results inhibition posttranslational farnesylation and geranyl-geranylation processing of small GTP-binding preoteins and inhibition of normal signaling activities. Method : We made several 5'-deletion constructs of rat ICAM-1 promoter and analyzed the promoter activities by measuring the luciferase activity after transfection into ECV304 cells and smooth muscle cells. We checked the level of total and phosphorylated STAT1 protein by immunoblot analysis using specific antibodies. Results : Lovastatin inhibits IFN-γ-induced ICAM-1 gene expression in the ECV304cell. The cells pretreated with PD98059, MEKK inhibitor showed significantly low ICAM-1 RNA induction with IFN-γ stimulatio. IFN-γ induced phosphorylation of tyrosine 701 was not significantly changed by the pretreatment of lovastatin. But lovastatin suppresses IFN-γ-induced phosphorylation of ERK1/ERK2 which are responsible for the seine 727 phosphorylation in STAT1. Conclusion : We showed that HMG-CoA reductase inhibitors, lovastatin, suppresses IFN-γ mediated ICAM-1 gene expression through the inhibition of transcription. HMG-CoA reductase inhibitor suppresses IFN-γ-induced phosphorylation of serine 727 in STAT1 through the modulation of MAP kinases.