나린진의 콜레스테롤 강하효과에 대한 제2상 임상시험의 중간보고

최진호 ( Choe Jin Ho ),오세일 ( O Se Il ),채인호 ( Chae In Ho ),김효수 ( Kim Hyo Su ),김철호 ( Kim Cheol Ho ),손대원 ( Son Dae Won ),오병희 ( O Byeong Hui ),이명묵 ( Lee Myeong Mug ),최윤식 ( Choe Yun Sig ),박영배 ( Park Yeong Bae 한국지질동맥경화학회 ( 구 한국지질학회 ) 2002 韓國脂質學會誌 Vol.12 No.1

목적 : 동물실험결과 현저한 혈중 지질치 개선효과와 항동맥 경화 효과를 보이고 본 연구자들이 시행한 제1상 임상 시험 결과 안전성이 증명된 바이오플라보노이드인 나린진의 임상적인 효능을 검증하고자 제2상 임상시험을 시행하였다. 방법 : 지질 강하제를 복용하고 있지 않은 20명의 경한 고콜레스테롤 남성환자 (평균연령 57±7세, 혈중 콜레스테롤 = 200~250mg/dL)를 대상으로 나린진 350mg을 8주동안 매일 투여하면서 혈중지질수치를 측정하고 추적관

가족성 고콜레스테롤 혈증 한국인 환자에서의 저비중 지단백 수용체 유전자의 돌연변이 분석

김효수(Hyo Soo Kim),채인호(In Ho Chae),박영배(Young Bae Park),최성준(Sung Choon Choe),한기훈(Ki Hoon Han),채재진(Jae Jin Chae),김성한(Sung Han Kim) 대한내과학회 1999 대한내과학회지 Vol.57 No.5

N/A Familial hypercholesterolemia (FH) is a common autosomal dominant disorder caused by a defect in the low-density-lipoprotein (LDL) receptor, disrupting the normal control of cholesterol metabolism. We have collected 86 FH families for over 5 years who met following Dx criteria 1) hypercholesterolemia over 280 mg/dl 2) Achilles tendon xanthoma thicker than 9 mm, and 3) familial tendency, and characterized the pattern of mutations in Korea FH patients. Method : Mutation was screened with linkage analysis into two ways; large structural rearrangements were screened by genomic Southern blotting or long-PCR technique, and small structural rearrangements were screened by PCR of each exon followed by SSCP analysis. The exact mutation sites were confirmed by sequencing. Result : 1) Large mutation : Three different large deletions(FH110, FH29, FH32) were found in 7(11.5%) among 61 families screened. FH110 was a deletion of 5.7kb from intron 8 to 12, which was found in 5 unrelated families. FH29 was a deletion of 3.8kb from intron 6 to 8, and FH32 was a deletion of 2kb from intron 6 to 7. These three deletions have not been reported previously. The mechanism of deletion was unequal crossover from mispairing Alu-sequences. 2) Small or point mutations : Nineteen different small mutations were found in 19(31.4%) among 86 families screened . These mutations comprised 9 missense, 3 nonsense, 2 splicing mutations, 3 small deletions, and 2 small insertions. One missense mutation (Pro664Leu) was found in 6 unrelated families. Among these mutations, 12 have not been reported previously.Conclusions : LDL receptor gene mutations are heterogeneous in Korean FH patients. We could not observe founder mutation but detect common mutations.(Korean. J. Med 57:881-895, 1999)

심폐바이패스없이 심박동상태에서 시행한 관상동맥우회술후 중기 개통율

이철,장우익,임청,김기봉,채인호,오병희,이명묵,박영배,Lee, Cheul,Chang, Woo-Ik,Lim, Cheong,Kim, Ki-Bong,Chae, In-Ho,Oh, Byung-Hee,Lee, Myoung-Mook,Park, Young-Bae 대한흉부심장혈관외과학회 2001 Journal of Chest Surgery (J Chest Surg) Vol.34 No.8

배경: 심폐바이패스없이 심박동상태에서 시행하는 관상동맥우회술 후의 각종 도관들의 1년째 개통율을 심패바이패스하의 심정지상태에서 시행하는 통상적 관상동맥우회술 및 심폐바이패스하의 심박동상태에서 시행한 관상동맥우회술 후의 1년재 개통율과 각각 비교하고 그 차이를 알아보고자 하였다. 대상 및 방법: 심폐바이패스없이 심박동상태에서 시행한 관상동맥우회술(I군; n=122)의 결과를 심폐바이패스하의 심정지상태에서 시행하는 통상적 관상동맥우회술(II군; n=65) 및 심폐바이패스하의 심박동상태에서 시행하는 관상동맥우회술(III군; n=19)의 결과와 비교, 분석하였다. I 군에서는 수술 직후와 수술후 1년째에 관상동맥조영술이 시행되었고, II군 및 III군에서는 수술후 1년째에서 시행되었다. 도관의 개통정도는 A(excellent), B(fair), 혹은 O(occluded)의 3등급으로 평가하였다. 결과: I, II, III군에서의 평균 원위 문합수는 각각 3.1$\pm$1.1, 3.7$\pm$0.9, 3.6$\pm$0.9개 이었다. I 군에서는 92%(112/122)의 환자들에서 퇴원 전 관상동맥조영술이 시행되었는데 개통율 (A+B)은 동맥 도관이 96.4%(162/168), 복재정맥이 85.6%(160/187) 이었다. 74%(90/122)의 환자들에서 술후 1년째 관상동맥조영술이 시행되었으며, 개통율은 동맥 도관이 97.89%(132/135), 복재정맥이 67.9%(106/156) 이었다. II군에서는 65%(42/65)의 환자들에서 술후 1년째 관상동맥조영술이 시행되었다. 개통율은 동맥 도관이 93.5%(43/46), 복재정맥이 88.3%(98/111) 이었다. III군에서는 89%(17/19)DML 환자들에서 술후 1년째 관상동맥조영술이 시행되었다. TRO통율은 동맥 도관이 100%(19/19), 복재정맥이 86.8%(33/38) 이었다. 결론: 세 군간에 동맥 도관들의 1년째 개통율은 유의한 차이를 보이지 않았다. 심폐바이패스 없이 심박동상태에서 시행하는 관상동맥우회술후 복재정맥의 개통율은 수술 직후에도 동맥 도관에 비하여 유의하게 낮았으며(p<0.001), 술후 1년째 복재정맥 개통율 또한 II군(p<0.001) 및 III(p<0.01)의 수술후 1년째 복재정맥 개통율에 비하여 유의하게 낮았다. 이러한 결과는 복재정맥을 이용하여 심폐바이패스없이 시행하는 관상동맥우회술의 경우, 수술전후 항응고 요법에 특별한 주의가 필요할 것이라는 사실을 시사한다. The aim of this study was to compare one-year graft patency after coronary artery bypass grafting without cardiopulmonary bypass(OPCAB) with that of conventional CABG and that of on-pump beating CABG, and to demonstrate any differences in patency of various conduits among the three groups. Material and Method: We analyzed the results of OPCAB cases(group I; n=122) compared with those of conventional CABG cases(group II; n=65) and those of on-pump beating CABG cases(group III; n=19). In group I, coronary angiography(CAG) was performed immediately postoperatively and 1 year after surgery. In group II and III, CAG was performed 1 year after surgery. Graft patency was graded as grade A(excellent), grade B(fair), or grade O(occluded). Result: The average number of distal anastomoses in groups I, II, and II were 3.1$\pm$1.1, 3.7$\pm$0.9, and 3.6$\pm$0.9, respectively. In group I, postoperative CAG was performed in 92%(112/122) of patients before discharge. The patency rate(grade A+B) was 96.4$(162/168) for arterial grafts, and 85.6%(160/187) for saphenous vein grafts(SVG). One-year follow-up CAG was performed in 74%(90/122) of patients. The patency rate was 97.8%(132/135) for arterial grafts, and 67.9%(106/156) for SVG. In group II, one-year follow-up CAG was performed in 65%(42/65) of patients. The patency rate(grade A+B) was 93.5%(43/46) for arterial grafts, and 86.8%(33/38) for SVG. Conclusion: Our results demonstrated that the patency rate of SVG after OPCAB was significantly lower than that of arterial grafts in the early postoperative CAG(p<0.001), and was also significantly lower than those of SVG of group II(p<0.001) and group III(p<0.01) in the postoperative one-year CAG, although there was no significant difference is one-year patency of arterial grafts among the three groups. Our data suggest that a specific perioperative anticoagulant therapy may be advisable in patients undergoing OPCAB with SVG.

Poster Presentation : Role of Akt in Modulating Vascualr Response to Injury

양한모 ( Yang Han Mo ),채인호 ( Chae In Ho ),김효수 ( Kim Hyo Su ),오병희 ( O Byeong Hui ),이명묵 ( Lee Myeong Mug ),박영배 ( Park Yeong Bae ),최윤식 ( Choe Yun Sig ) 한국지질동맥경화학회 ( 구 한국지질학회 ) 2003 춘계학술대회 Vol.- No.-

고혈압 환자에 대한 이베사탄의 혈압강하효과 및 안전성을 평가하기 위한 양측 눈가림, 무작위 배정, 에날라프릴과의 비열등성 4상 임상시험

김광일,배장환,강현재,서선예,김상현,오세일,채인호,조주희,김명아,김효수,손대원,오병희,박영배,최윤식,박병주,이명묵,Kim, Kwang-Il,Bae, Jang-Whan,Kang, Hyun-Jae,Suh, Sun-Ye,Kim, Sang-Hyun,Oh, Se-Il,Chae, In-Ho,Zo, Joo-Hee,Kim, Myoung-A,Kim, Hyo-Soo,Sohn 대한임상약리학회 2003 Translational and Clinical Pharmacology Vol.11 No.2

Background: Irbersartan, an orally active antihypertensive agent, effectively reduces blood pressure by blocking angiotensin II receptors without any significant adverse effects. The purpose of this study is to compare the antihypertensive efficacy, safety and tolerability of irbesartan and enalapril in hypertensive patients. Methods: In this two centers, double-blind, randomized, non-inferiority study, the efficacy, safety and tolerability of once-daily irbesartan(150mg) versus once-daily enalapril(10mg) were evaluated over 8 weeks in 67 patients who had diastolic pressure between 95mmHg and 114mmHg on two measurements. If trough sitting diastolic blood pressure was equal to or greater than 90mmHg after a 4-week treatment period, the dosage for both study drugs was doubled until the end of the study. Baseline pressures, antihypertensive effect, side effects, laboratory findings were compared before and after treatment. Results: Data from 57 of 67 patients were eligible for intention to treat analysis. After the 8 weeks treatment with dose titration, mean reductions in peak sitting diastolic blood pressure were 11.9mmHg(95% confidence interval 7.61 -16.13) with irbesartan and 10.9mmHg$(95%\;confidence\;interval\;7.05{\sim}14.70)$ with enalapril. There was no significant difference between the two treatments in the percentage of patients achieving an effective blood pressure reduction or in the degree of change in mean systolic and/or diastolic blood pressure. Safety profiles were also similar between treatments. Conclusions: The antihypertensive efficacy of once-daily administration of irbesartan is non-inferior to that of enalapril in hypertensive patients. Both irbesartan and enalapril are well tolerated with similar safety profiles.

Poster Presentation : Association between lipids and coronary artery disease -focused on HDL-cholesterol-

조영석 ( Jo Yeong Seog ),김철호 ( Kim Cheol Ho ),오세일 ( O Se Il ),채인호 ( Chae In Ho ),김효수 ( Kim Hyo Su ),오병희 ( O Byeong Hui ),이명묵 ( Lee Myeong Mug ),최윤식 ( Choe Yun Sig ),박영배 ( Park Yeong Bae ) 한국지질동맥경화학회 ( 구 한국지질학회 ) 2002 韓國脂質學會誌 Vol.12 No.1

Background : Dyslipidemia is a known risk factor for coronary artery disease, and several epidemiologic studies suggest that HDL cholesterol is independently associated with the risk of coronary artery disease. Methods and Results : To determine the risk

고혈압 환자에서 내피의존성 혈관반응에 대한 칼슘길항제와 비타민 C 의 효과에 대한 요구

온영근(Young Yeun On),최진호(Jin Ho Choi),채인호(In Ho Chae),김철호(Cheol Ho Kim),손대원(Dae Won Sohn),오병희(Byung Hee Oh),이명묵(Myoung Mook Lee),박영배(Young Bae Park),최윤식(Yun Shik Choi) 대한내과학회 2001 대한내과학회지 Vol.61 No.5

N/A Background: The effect s of antihypertensive agents on endothelial function have not been fully evaluated in human hypertension and data on the forearm circulation of humans are controversial. The aim of this study was 1) to evaluate the endothelial function in hypertensive patients 2) to investigate whether vitamin C administration has any benefit on the endothelial function and 3) to determine whether treatment with calcium ant agonist improves endothelial dysfunction in hypertensive patients. Methods: The endothelial function was estimated using venous occlusion plethysmography (VOP) in 8 hyper tensive patients and 8 healthy volunteer s. The patients in the hypertension group were treated with amlodipine, then examined again. The change of forearm blood flow (FBF) was measured wit hacetylcholine infusion through brachial artery and also with intra-ar terial vitamin C. Results: Forearm blood flow response to acetylcholine was significantly enhanced with intra- arterial infusion of vitamin C in hypertensive group before antihypertensive treatment. Co- infusion of L- NMMA, an inhibit or of nitric oxide synthase, blunted forearm blood flow response toacetylcholine. After treatment with amlodipine for 2 months in hypertensive group, endothelium-dependent vasorelaxation to acetylcholine was significantly improved comparedt opretreatment, and vitamin C did not affect the improved endothelial function by amlodipine treatment. Conclusion: Vitamin C (acutely) and amlodipine (chronically) improved endothelial function inhypertensive patients. These results suggest that increased oxidative stress, at least in part , maybe involved in the decreased endothelial function in hypertension.(Korean J Med 61:518- 526, 2001)

원발성 폐 고혈압 환자의 생존율과 예후에 영향을 미치는 인자

송종민(Jong Min Song),최윤식(Yun Shik Choi),채인호(In Ho Chae),김효수(Hyo Soo Kim),손대원(Dae Won Sohn),오병희(Byung Hee Oh),이명묵(Myoung Mook Lee),박영배(Young Bae Park),이영우(Young Woo Lee),전국진(Kook Jin Chun),홍택종(Taek Jong 대한내과학회 2000 대한내과학회지 Vol.59 No.3

Background : Mucosa-associated lymphoid tissue(MALT) lymphoma has an indolent natural course. However, extra-gastric MALT lymphoma has been reported to have more frequent relapses and shorter time to progress than gastric MALT lymphoma. We performed this study to analyze clinical features of extra-gastric MALT lymphoma. Methods : We retrospectively reviewed the medical records of the patients who were diagnosed as extra-gastric MALT lymphoma at the Samsung Medical Center from March 1995 to January 1999. The survival was analyzed by Kaplan-Meier method. Results : During the study period, extra-gastric MALT lymphoma was diagnosed in 50 patients. The median age was 51(28-87)yaers. The male to female ratio was 22:28. Commonly involved sites were conjunctiva (25/50, 50%), lung (6/50, 12%) and intestine(6/50, 12%). Histopathologically, low to high grade ratio of extra-gastric MALT lymphoma was 47:3. Among 41 patients who were staged, 32 patients(78%) had stage I or II and 9 patients(22%)had stage IV. B symptoms were seen in only 3 patients. Bone marrow involvement was observed in 4 patients. The duration of median follow up was 22 months. The 1-year and 2-year survival rates were 95.1% and 91.4% retrospectively. Conclusion : Majoity of our cases with extra-gastric MALT lymphoma had low grade, early stage, good treatement reponse and good prognosis.(Korean J Med 59:261-267, 2000)

심장 점액종의 임상적 고찰

황의석(Eui Seock Hwang),김용석(Yong Seok Kim),최진오(Jin Oh Choi),채인호(In Ho Chae),손대원(Dae Won Sohn),김철호(Cheol Ho Kim),오병희(Byung Heui Oh),이명묵(Myoung Mook Lee),박영배(Young Bae Park),최윤식(Yun Shik Choi),이영우(Young Wo 대한내과학회 2002 대한내과학회지 Vol.62 No.1

N/A Background: Cardiac myxoma is uncommon, even though accounts for 50% of primary cardiac tumor, histologically benign disease but may be lethal because of its strategic position. It has diverse clinical manifestations mimicking various diseases, which can be described under the three headings: constitutional, obstructive and embolic and the diagnosis can be easily missed unless clinician has high index of suspicion. A correct diagnosis is made before operation with the development of echocardiography. We reviewed our clinical experience in diagnosis and management of 21 cases of myxomas from 1985 to 2000. Methods: There were 4 males (19%) and 17 females (81%). Their ages ranged from 17 to 66 years (mean 42.2 years). All the patient`s medical records on their clinical features, laboratory findings, chest X-rays, electrocardiograms, echocardiographic findings, operative findings and post operative follow-up were reviewed. Results: Seventeen cases (81%) of the myxomas originated in left atrium and four (19%) in right atrium. Most common symptom was that of intracardiac obstruction such as dyspnea or dyspnea on exertion (62%). Fatigue which accounted for most of the constitutional symptom found in 38% of the 21 patients while embolism accounted for 38%. In all patients, echocardiography was used for diagnosis and the diagnostic accuracy of echocardiography was 100%. All patient s received surgical treatment and immediate postoperative complications occurred in seven patients (33%). Among them, serious complications were found in two cases and one expired due to congestive heart failure. Follow-up duration ranged from 2 months to 15 year s. There was no recurrence or other problem in all patient s during the follow-up period. Conclusion: Although clinical suspicion is difficult due to the nonspecific presentation of myxoma, the diagnosis can be made easily with echocardiographic examination in all cases and surgical excision of myxoma may be curative with good long-term result.(Korean J Med 62:49-57, 2002)

산화질소-합성효소 유전자의 다형성이 급성 관동맥 증후군과 이형 협심증 환자에 미치는 영향의 차이

최수연(Soo Yeon Choi),유경훈(Kyung Hoon Yoo),박진식(Jin Sik Park),채인호(In Ho Chae),김효수(Hyo Soo Kim),손대원(Dae Won Son),오병희(Byung Hee Oh),이명묵(Myoung Mook Lee),박영배(Young Bae Park),최윤식(Yun Shick Choi),이영우(Young Woo 대한내과학회 2000 대한내과학회지 Vol.58 No.1

N/A Background : Nitric oxide, also known as endothelial derived relaxing factor(EDRF), regulates the vascular tone and inhibits the proliferation of vascular smooth muscle cells and platelet adhesions and endothelium-leukocyte interactions. Thus, nitric oxide may be involved in the pathogenesis of atherosclerosis and vasospasm. We analyzed the genotype distributions of two eNOS gene polymorphisms in normal healthy Koreans and compared it with those in the patients with acute coronary syndrome and variant angina. Methods : We analyzed the two eNOS polymorphisms (eNOS A/B polymorphism is the variable numbers of tandem repeat in intron 4 and eNOS T/G polymorphism is a mis-sense mutation in exon 7) using PCR and clinical characteristics of the risk factors for coronary artery disease in 142 normal healthy Koreans and 164 patients with acute coronary syndrome and 104 patients with variant angina. Results : The genotype distribution of A/B polymorphism of eNOS gene, A/A, A/B, B/B was 4.9%, 21.1%, 74% in control group and 2.4%, 12.8%, 84.8% in the patients with acute coronary syndrome(p=0.02) and 2.9%, 16.3%, 80.8% in the patients with variant angina(p=NS), respectively. The genotype distribution of T/G polymorphism of eNOS gene, T/T, T/G, G/G was 1.4%, 15.5%, 83.1% in control group and 0.6%, 21.3%, 78.1% in the patients with acute coronary syndrome(p=NS) and 0%, 18.3%,81.7% in the patients with variant angina(p=NS), respectively. The odds ratio for acute coronary syndrome of non B/B(A/A & A/B) to B/B was 0.489 (95% CI : 0.257∼0.928). We found that age, sex (male), diabetes mellitus, hyperlipidemia, smoking, B/B genotype were independent risk factors for acute coronary syndrome. But, in variant angina, smoking was the only significant independent risk factor(odds ratio=5.934, 95% CI 2.843-12.388, p<0.05). Conclusion : The B/B genotype frequency of eNOS gene was significantly higher in patients with acute coronary syndrome than in normal controls. But neither A/B nor T/G polymorphism of eNOS gene was associated with variant angina. These results suggest that eNOS gene may play some roles in the pathogenesis of ACS rather than vasospasm.(Korean J Med 58:19-27, 2000)