한국인 원발성 고콜레스테롤혈증 환자에서 Ezetimibe와 Simvastatin 병용투여의 유효성과 안전성에 관한 연구

배장환 ( Jang Whan Bae ),김효수 ( Hyo Soo Kim ),이상철 ( Sang Chol Lee ),한기훈 ( Ki Hoon Han ),전은석 ( Eun Seok Jeon ) 대한내과학회 2005 대한내과학회지 Vol.68 No.5

목적 : Ezetimibe는 소장내에서 콜레스테롤 흡수를 막아 스타틴제제의 저밀도 콜레스테롤 감소에 추가적인 효과를 나타내는 것으로 알려져 있다. 한국인 성인 원발성 고콜레스테롤혈증 환자를 대상으로 ezetimibe 10mg과 simvastatin 10mg 병용투여의 저밀도 지단백 콜레스테롤 저하효과와 안전성의 평가를 위하여 본 임상연구를 시행하였다. 방법 : 연구약의 무작위 배정 전 4주간 식이요법을 실시하고 공복시 중성지방이 350mg/dL 이하이며 Background : The prevalence of hypercholesterolemia in Korea is growing. In spite of the wide use of HMG-CoA reductase inhibitors (statins), some patients don`t reach optimal cholesterol reduction and suffer hepatotoxicity or myopathy. Combination therapy

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.

GSTM1과 GSTT1, 그리고 CYP1A1, CYP2E1 다형성이 폐암발생에 미치는 영향에 대한 환자-대조군연구

남홍매,강종원,배장환,최강현,이기형,김승택,원중희,김용민,김헌,Nan, Hong-Mei,Kang, Jong-Won,Bae, Jang-Whan,Choe, Kang-Hyeon,Lee, Ki-Hyeong,Kim, Seung-Taik,Won, Choong-Hee,Kim, Yong-Min,Kim, Heon 대한예방의학회 1999 예방의학회지 Vol.32 No.2

1997년 3월부터 1998년 6월까지 충북대학교병원 내과에 입원하여 치료를 받은 폐암환자 98명과 암 아닌 다른 질환을 가진 대조군 98명을 대상으로 흡연, 음주, 여러 가지 질병과거력 등을 포함한 생활습관과, GSTM1과 GSTT1, 그리고 CYP1A1, CYP1E1 유전자 다형성 양상을 조사하여 다음과 같은 결론을 얻었다. 1. GSTM1의 결손은 환자군이 67.01%, 대조군이 58.16%로 확인되었으며, OR(95% CI)이 1.46(0.82-2.62)으로 폐암 발생에 대해 유의한 영향을 미치지 않는 것으로 나타났다. 2. GSTT1의 결손은 환자군이 58.76%, 대조군이 50.00%로 확인되었으며, OR (95% CD가 1.43(0.81-2.51)으로 폐암 발생과 관련이 없는 것으로 나타났다. 3. CYP1A1 유전자 다형성은 Ile/Ile, Ile/Val, Val/Val 환자군이 각각 59.18%, 35.71%, 5.10%, 대조군이 각각 52.04%, 45.92%, 2.04%로 CYP1A1 유전자 다형성과 폐암 위험도 사이의 관련성은 유의하지 않은 것으로 나타났다$(x^2trend=0.253,\;p-value>0.05)$. 4. CYP1E1 유전자 다형성은 c1/c1, c1/c2, c2/c2 형 이 환자군에서 각각 50.00%, 42.86%, 7.14%, 대조군에서 각각 66.33%, 30.61%, 3.06%로 CYP1E1 활성이 폐암 발생에 유의한 영향을 미치는 것으로 나타났다$(x^2trend=5.783,\;p-value<0.05)$. 특히 환자군이 대조군에 비하여 아주 드문 대립유전자인 c2형이 더 많은 것으로 나타났다. 5. 폐암과 밀접한 연관이 있는 흡연습관의 OR(95% CI)이 3.03(1.58-5.81)으로 확인되어, 폐암의 위험인자로 재확인 되었다. 6. GSTM1, GSTT1, CYP1A1, CYP2-E1과 흡연습관을 포함한 다변량 분석에서 흡연습관만이 유의한 폐암의 위험인자로 나타났다. 이 결과로부터 위의 4가지 유전자의 다형성이 폐암발생에 미치는 영향은, 흡연을 포함한 환경적 요인에 비하여 크지 않을 것으로 판단된다. Objectives: This study was performed to investigate sweets of genetic polymorphisms of glutathione S-transferase M1 (GSTM1), glutathione S-transferase M1 (GSTT1), cytochrome P450 1A1 (CYP1A1) and cytoehrome P450 2E1 (CYP2E1) on lung cancer development. Methods: Ninety-eight lung cancer patients and 98 age-sex matched non-cancer patients hospitalized in Chungbuk National University Hospital form March 1997 to August 1998, were the subjects of this case-control study. Direct interview was done and genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1 were investigated using multiplex PCR or PCR-RFLP methods with DNA extracted from venous blood. Effects of the polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1, lifestyle factors including smoking, and their interactions on lung rancor were statistically analyzed. Results: GSTM1 was deleted in 67.01% of the cases and 58.16% of the controls, and the odds ratio(95% CI) was 1.46(0.82-2.62). GSTT1 deletion was 58.76% for the lung cancer patients and 50.00% for the controls[OR:1.43(0.81-2.51)]. The frequencies of lle/lle, lle/Val and Val/Val of the CYP1A1 polymorphisms were 59.18-18%, 35.71%, and 5.10% for the cases, and 52.04%, 45.92%, 2.04% for the controls, respectively. Risk of lung cancer was not associated with polymorphism of CYP1A1 ($x^2trend=0.253$, p-value>0.05). The respective frequency of c1/c1 c1/c2, c2/c2 genotypes for CYP2E1 were 50.00%, 42.86%, 7.14% for the lung cancer patients, and 66.33%, 30.61%, 3.06% for the controls $(x^2trend=5.783,\;p<0.05)$. c2 allele was a significant risk factor for lung cancer. We also observed a significant association of cigarette smoking history with lung cancer risk. The odds ratio(95% Cl) of cigarette smoking was 3.03(1.58-5.81). In multiple logistic analysis including genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1, and smoking habit, only snaking habit came out to be a significant risk factor for lung cancer. Conclusion: Genetic polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1 are not so strongly associated with lung cancer as lifestyle factors including cigarette smoking.

고지혈증이 있는 급성 심근경색환자에서 statin/ezetimibe 병합요법의 효과

이미연 ( Mi Yeoun Yi ),배장환 ( Jang Whan Bae ),황경국 ( Kyung Kuk Hwang ),김동운 ( Dong Woon Kim ),조명찬 ( Myeong Chan Cho ) 대한내과학회 2008 대한내과학회지 Vol.74 No.1

목적: 원발성 고콜레스테롤혈증 환자에서 상용량의 스타틴/에제티미브 병합요법은 고용량의 스타틴 단독요법에 비해 이상반응의 증가 없이 저밀도 지단백 콜레스테롤을 효과적으로 감소시켰다. 그러나 급성 심근경색 환자에 대한 스타틴/에제티미브 병합요법의 효과에 안전성에 대한 연구는 없는 상태이다. 방법: 본 연구는 급성 심근경색으로 본원에 내원한 82명의 환자를 대상으로 임상특성과 지질의 변화양상을 후향적으로 분석하였다. 대상 환자군은 흉통 발생 후 12시간 내에 응급 관상동맥 중재술을 성공적으로 시행 받았고, 이 중 저밀도 지단백 콜레스테롤이 100 mg/dL 이상인 고지혈증 환자이며, 입원 후 72시간 이내에 스타틴 단독요법 혹은 스타틴/에제티마이브 병합요법을 시행 받은 환자로 하였다. 그리고 두 군 간의 입원 당시 및 1개월, 6개월 후의 지질 수치, 안정성 등을 비교하였다. 결과: 초기의 총 콜레스테롤 및 저밀도 지단백 콜레스테롤은 병합요법군이 단독요법군에 비하여 유의하게 높았으나 치료 1개월 후의 총콜레스테롤은 병합요법군이 27.9±13.1%, 단독요법군이 17.0±15.0%였고(p=0.004), 저밀도 지단백 콜레스테롤은 병합요법군이 38.5±12.5%, 단독요법군이 25.1±18.9%로 병합요법군이 우수하였다(p=0.001). 안전성면에서는 CPK가 정상의 정상상한치의 3배 이상으로 상승한 경우가 병합요법군에서 1명, ALT가 정상상한치의 2배 이상으로 상승한 경우는 단독요법군에서 1예가 있었다. 결론: 응급 관동맥 중재술을 통하여 성공적으로 재관류가 이루어진 급성 심근경색환자의 경우 지질저하를 위한 병합요법이 단독 스타틴 요법에 비해 지질 저하 면에서 우수하며 안전한 치료법이라 판단된다. Background/Aims: A moderate dose of statin/ezetimbe combination therapy reduced the LDL-C (low density lipoprotein-cholesterol) in a fashion comparable to high dose statin without increasing the adverse events in patients with primary hypercholesterolemia. Yet there is no data on the effectiveness and safety of statin/ezetimbe combination therapy in patients suffering with acute myocardial infarction (AMI). Methods: We retrospectively compared the lipid profiles and clinical variables of 82 patients who were admitted to our institution with AMI. These patients were successfully treated with emergent coronary intervention within 12 hours after the chest pain onset and they were prescribed a single statin (statin group) or statin/ezetimibe combination therapy (dual inhibition group) for treating their hyperlipidemia within 72 hours after the admission. We compared the initial lipid profiles, the % reduction of total cholesterol (TC), the LDL-C at 1 and 6 months and the safety profiles between the two therapeutic groups. Results: Although the initial TC and LDL-C levels were significantly higher in the dual inhibition group than the statin group, one month later, the % reduction of the TC was 27.9±13.1% and 17.0±15.0% (p=0.004) and the % reduction of the LDL-C was 38.5±12.5% and 25.1±18.9% (p=0.001) in each group, respectively. One patient in the dual inhibition group showed CPK elevation more than 3 times the upper normal limit and ALT elevation more than 2 times of upper normal limit was observed in one patient in the statin group. Conclusions: Cholesterol dual inhibition therapy is superior to single statin therapy for the aspect of cholesterol reduction and safety in successfully reperfused AMI patients. (Korean J Med 74:59-67, 2008)

한국인 성인 천식 환자에서의 증상의 중등증에 따른 안지오텐신 Ⅰ전환요소 ( ACE )

김미경(Mi Kyeong Kim),배장환(Jang Whan Bae) 대한천식알레르기학회 2000 천식 및 알레르기 Vol.20 No.3

N/A Background: and objective Many chemical mediators such as histamine, prostaglandins, leukotrienes, bradykinin, angiotensisn II(A II), and even angiotensin converting enzyme (ACE) affect the pathophysiology of asthma. ACE exists in the epithelium, endothelium, neuroepithelium, plasma, and especially in high concentrations in human lung tissue. ACE converts A I to A II, which is highly vasoconstrictive, bronchoconstrictive, inflammatory substance and can also inactivate bradykinin. ACE polymorphism determines the level of ACE such as DD, higher concentration of ACE, but II, lowest concentration of that, so in DD type, the level of A II increase, but that of bradykinin decrease. From that point we can speculate polymorphism of ACE gene anyhow affects asthma, so we carried out this study for evaluating relationships between the ACE genotype distribution and genesis and severity of asthma in Korean adult asthmatics. Materials and Methods: The study population consisted of 150 asthmatics, 57 patients of non asthmatic lung diseases including lung cancer (n=l0), pulmonary tuberculosis (n=27), empyema(n=3), pneumonia (n=11), bronchiectasis (n=5) and lung abscess (n=1) and 100 normal healthy subjects without hypertension, cardiovascular disease, diabetes mellitus and nephropathy which may bias the result. Bronchial asthmatics were classified into 3 groups according to the criteria of the NAPE. PCR (polymerase chain reaction) for ACE genotypes was performed. PCR products were electrophoresed in 1% agarose gels, and then DNA pattern was directly visualized under ethidium bromide staining. Results The frequency for II, ID, and DD genotypes were 46 (46%), 38 (38%), 16 (16%) in control group, 59 (39.6%). 74 (49.5%), 17 (10.9%) in asthma group and 28 (49.1%), 24 (42.1%), 5 (8.8%) in non-bronchial lung disease group, respectively. There was no significant difference in frequency of ACE genotype distribution among the 3 groups (p > 0.05). The frequency for II, ID, and DD genotypes in the 3 groups of asthmatics were 17 (34%), 27 (54%), 6 (12%) in mild subset, 13 (26%), 30 (60%), 7 (14%) in moderate subset, and 11 (22%), 33 (66%), 6 (12%) in severe subset. Even though there was also no significant difference among the 3 severity subsets in the asthma group, the frequency of non-DD subsets such as II and ID was higher in moderate and severe asthmatics. Conclusion #' The results suggest that ACE gene polymorphism dose not affect the genesis but can progress asthma in Korean adult asthmatics. However, further mass studies on asthmatics will be needed to clarify the effect of ACE polymorphism on the severity of Korean adult asthmatics.

소모성 응고 장애가 병발된 대동맥류의 중재시술 및 연속된 수술로 성공적으로 치료한 증례

김지현 ( Jee Hyun Kim ),양범희 ( Bum-hee Yang ),이주희 ( Ju-hee Lee ),이상엽 ( Sang Yeub Lee ),배장환 ( Jang-whan Bae ),황경국 ( Kyung-kuk Hwang ),김상민 ( Sang Min Kim ) 대한내과학회 2016 대한내과학회지 Vol.90 No.6

Aortic aneurysm-induced chronic consumptive coagulopathy is a very rare complication but can be a source of critical complications and mortality. A 72-year-old man presented with a rapidly expanding descending thoracic aortic aneurysm with a penetrating ulcer and an infrarenal abdominal aortic aneurysm complicated by chronic coagulopathy. We were aware of the bleeding risk during surgical replacement based on the patient’s chronic coagulopathy status and successfully performed endovascular repair of the thoracic aortic aneurysm with a penetrating ulcer. Platelet transfusion, antiplatelet agents, and proteinase inhibitors improved the coagulopathy. A delayed type Ib endoleak developed, and the coagulopathy recurred 2 months later when the patient presented with purpura of both lower legs. We successfully managed the condition by elective surgical replacement of the entire aorta after improving the coagulopathy with platelet replacement and administration of proteinase inhibitors. (Korean J Med 2016;90:537-541)

자발성 비장 파열이 발생한 혈액투석 환자에서 보존요법 치험

유숙희 ( Suk Hee Yoo ),박재근 ( Jae Geun Park ),김성무 ( Sung Moo Kim ),김정은 ( Jeong Eun Kim ),권순길 ( Soon Kil Kwon ),배장환 ( Jang Whan Bae ),김혜영 ( Hye Young Kim ),정진욱 ( Jin Uk Jeong ) 대한신장학회 2010 Kidney Research and Clinical Practice Vol.29 No.3

Spontaneous splenic rupture is a rare disease but can cause a life threatening situation. It can occur under a pathological spleen such as infection, neoplastic, infiltrative and inflammatory disease. Although splenectomy is the treatment of choice for splenic rupture, it is uncertain that the effectiveness of non- surgical treatment in the hemodynamically stable patient. We report a case of a 66-year-old male undergoing hemodialysis for 4 years who presented to the emergency department with abdominal pain and distention. Blood pressure was 130/80 mmHg, heart rate was 108 bpm. White blood cell count was 7,130/mm3, hemoglobin was 6.7 g/dL, platelet was 156,000/mm3. PT INR was elevated up to 2.01 because he had taken warfarin due to splenic infarction. Abdominal CT scan revealed hemoperitoneum due to splenic rupture. We performed angiography but there was no active bleeding. We decided conservative management without embolization because of stable condition and increased bleeding risk in operation. He received 6 pints of packed red blood cell transfusion during continuous renal replacement therapy for 24 hours on ICU. He was discharged with complete recovery on the 21st hospital day. We suggest that non-surgical treatment in splenic rupture also could be considered in hemodynamically stable patients with a high risk of postoperative complication.

심전도의 디지털 기록화 모듈과 개인용컴퓨터 저장/분석시스템의 개발

조명찬,김기석,배장환,연태진,김동운,이태수,전은석,김유진 충북대학교 의학연구소 2001 忠北醫大學術誌 Vol.11 No.2

연구목적: 현재 우리나라의 의료분야에서는 정보기술의 발전으로 처방 전달 시스템과 전자차트의 활용이 상용화 되고 있으나 병원내에서 가장 많이 처방되고 검사되는 12-유도 심전도의 디지털화와 이에 연계된 심전도 결과의 개인용 컴퓨터로의 저장, 인터넷을 이용한 병원으로의 전송이나 타 기관에서의 심전도 결과의 동시 관찰 등에 관한 기술 등은 개발되지 못한 상태이다. 이에 본 연구에서는 심전도를 디지털화하며 저장이 가능한 PC 모듈을 개발하고 심전도 결과를 병원 전산 시스템에 포함시켜 병원내외에서 편리하게 조회, 검색할 수 있는 디지털 인터페이스를 개발하려 하였다. 재료 및 방법 : 낮은 전력에서 잡음특성이 우수한 대역여파기와 증폭기를 설계하였으며 각종기능이 내장된 고신뢰성 프로세서를 채택하였으며 전원 잡음이 고려된 필터와 전원 회로 설계로 하드웨어를 개발하였다. MSC 6.0과 Visual Basic 6.0을 바탕으로 하여 active X 모듈화를 유도하고 조회용 PC에서의 복원과 PACS로의 연동을 통해 순환기내과용 PACS 개발이 가능하도록 소프트웨어를 준비하였다. 결과: 심전도 검사자가 쉽게 장착, 검사가 가능한 소형화된 측정 모듈을 개발하였고 극저전류에서 동작이 가능하였으며 우수한 데이터의 압축 및 복원률을 구현하였다. 결론: 이번 심전도 디지털 모듈의 개발로 기존의 감광지에 의존하던 심전도 결과의 보존과 보관공간에 의한 경제적인 손실을 상당 부분 해결할 수 있으며 OCS에 연계된 결과로 인해 원내에서의 다면적 진료가 가능하다. 이번 연구에서 개발된 기술은 향후 디지털화된 심전도 기록장치와 같은 고부가 의료장치의 국산화와 광파일 의무기록 시스템이나 검사물의 무선 전송에 채용되어 의료 전달 체계나 응급체계의 발전에 기여하리라 사료된다. Purpose : The progressed communication technology commercialized the order communication system ( OCS) and the electric medical records( EMR) in the field of medicine in Korea. However, technologies of digitalization such as recording to personal computer, transfer to internet and simultaneous observation of electrocardiogram ( ECG) recorded at the different center were not realized yet. This study tried to invent personal computer module that can digitalize and record of the ECG and design the digital interface that can approach and search digitalized ECG in various part of hospital simultaneously. Materials and Methods : We had designed high-fidelity digital filter and amplifier which can work in very low voltage, had selected multifunctioned microprocessor. Activation X modulation was conducted by MSC 6.0 and Visual Basic 6.0. Softwares were prepared for the transfer of ECG informations from terminal PC to PACS and cardiologic PACS was designed for future application. Results : We have developed the small, portable, very low voltage managed ECG module and high quality digitalized information compression software in OCS and PACS. Conclusion : This invented ECG digital archive module can save hospital cost by substitution of ECG papers for digital storage or on-line storage, therefore ECG data can be handled in multisector of the hospital and through telemedicine. This technology can be applied to domestic ECG digitalizing device development and effective medical transfer system by adoption cordless medical information delivery.

혈압이 떨어질 정도의 심한 장출혈을 보인 크론병 1예

박선미,배장환,고병성,전현정,이상전,김도형,윤세진 대한소화기내시경학회 1998 Clinical Endoscopy Vol.18 No.2

Life-threatening gastrointestinal hemorrhage is a rare complication in Crohn's disease. The authors experienced a case of Crohn's disease manifested with massive lower intestinal bleeding. A 22-year-old woman, who had underwent small bowel resection for bowel perforation and intestinal fistula, was admitted with lower abdominal pain and massive hernatochezia. A radioisotope bleeding scan and mesenteric angiography revealed suspi- cious intestinal bleeding in the small bowel area. The colonoscopy showed multiple shallow ulcers at the terminal ileum and scars on the cecum. In spite of medical management with the diagnosis of Crohn's disease, she continuecl to rebleed and required fistuloplasty and ileal resection. In the surgical specimen was discovered multiple exposed small vessels and diffuse blood oozing at terminal ileum. After surgery, there were no more bleeding episodes and she recovered with the aid treatment of sulfasalazine and prednisolone.

우측 신 탈장을 동반한 성인형 Bochdalek 탈장 1례

김도형,최강현,배장환,고병성,전현정 대한내과학회 1998 대한내과학회지 Vol.54 No.4

Bochdalek hernia through Bochdalek foramen, defect at the posterolateral side of the diaphragm is one of the congenital diaphragmatic hernias. It usually occurs in infants, but very rare in old age and also on the right side. We experienced the right-side Bochdalek hemia including kidney herniation in 68 years old man manifested by hernoptysis. CT scan revealed diaphragmatic defect and herniated liver, colon and kidney. Thoracotomy was performed and the 10 cm-sized large defect was closed with patch. After then, the patient has been well without symptom. Bochdalek hernia through Bochdalek foramen, defect at the posterolateral side of the diaphragm is one of the congenital diaphragmatic hernias. It usually occurs in infants, but very rare in old age and also on the right side. We experienced the right-side Bochdalek hemia including kidney herniation in 68 years old man manifested by hernoptysis. CT scan revealed diaphragmatic defect and herniated liver, colon and kidney. Thoracotomy was performed and the 10 cm-sized large defect was closed with patch. After then, the patient has been well without symptom.