심방세동 환자에서 혈전색전성 합병증의 새로운 위험인자

조천영 ( Cheon Yeong Cho ),정대호 ( Dae Ho Jung ),고점석 ( Jum Suk Ko ),윤남식 ( Nam Sik Yoon ),이상록 ( Sang Rok Lee ),임상엽 ( Sang Yup Lim ),박형욱 ( Hyung Wook Park ),손일석 ( Il Suk Sohn ),김계훈 ( Kye Hun Kim ),홍영준 ( Youn 대한내과학회 2006 대한내과학회지 Vol.71 No.4

목적: 심방세동은 가장 흔한 지속성 부정맥이며 전신 혈전색전증의 가장 흔한 원인이다. 심방세동에서 혈전색전증은 사망률이 높고 심각한 불구를 초래하므로 예방이 무엇보다도 중요하며 이를 위해서는 위험인자의 정확한 규명이 필수적이다. 본 연구는 심혈관 질환 치료에 안지오텐신 전환효소 억제제, 안지오텐신-II 수용체 차단제, 스타틴 등이 활발히 사용된 이후에 심방세동의 혈전색전 위험인자에 새로운 변화가 있는지 조사하고 심방세동에서 혈전색전 위험의 증가 기전을 규명하기 위해 시행되었다. 방법: 혈전색전의 위험인자를 파악하기 위해 심방세동으로 치료받고 있는 환자 192명(61±11세, 남자 137)을 색전성 뇌경색증이 합병한 색전군(n=95명)과 합병하지 않은 비색전군(n=97명)으로 나누어 인구학적 특성, 동반 질환, 심전도 소견, 심초음파도 소견 및 치료 약제 등을 비교하였다. 혈전색전의 위험을 증가시키는 기전을 규명하기 위해서는 심장 율동이 정상인 25명과 심방세동 환자 71명[발작성: 21명(46±18세), 지속성: 19명(59±10세), 영속성: 31명(51±12세)]을 대상으로 내피세포기능을 반영하는 von Willebrand factor (vWF; factor 8 related antigen), 전신 염증 상태를 나타내는 백혈구 수, 적혈구 침강속도, 고예민성 C-reactive protein (hsCRP), 혈액 응고계 상태를 반영하는 fibrinogen, fibrinogen degradation product, fibrin d-dimer 등을 측정하여 비교하였다. 결과: 1. 심방세동에서 혈전색전의 위험인자 심방세동 환자 중 색전군이 비색전군에 비해 의미있게 나이가 많았고(p<0.05), 동반 질환으로 고혈압, 당뇨병, 이상지질혈증, 흡연이 색전군에서 의미있게 더 많았다(각각 p<0.05). 심전도에서는 심방세동파의 크기가 1mm 미만인 경우가 색전군에서 의미있게 많았고(p<0.05), 심초음파도에서는 좌심실기능부전(좌심실 구혈률 <40%), 판막질환, 심근증의 빈도가 색전군에서 의미있게 높았고(각각, p<0.05), 좌심방 직경도 색전군에서 의미있게 컸다(p<0.05). 색전군에서 비색전군에 비해 항응고제(p<0.01), 안지오텐신-II 수용체 차단제(p<0.05), 스타틴(p<0.05)을 복용한 경우가 의미게 적었다. 2. 심방세동에서 혈전색전 위험 증가의 기전 심방세동 환자에서 vWF-factor 8 related antigen의 농도는 좌심실부전(EF<40%), 고혈압, 고령(>65세), 당뇨병, 승모판협착증이 동반된 경우에 의미있게 증가하였다(각각, 165±53% vs. 116±49%, p<0.05; 135±22% vs. 119±24%, p<0.05; 136±55% vs. 113±51%, p<0.05; 138±59% vs. 120±52%, p<0.05; 151±34% vs. 120±33%, p<0.05). 또한 vWF-factor 8 related antigen의 농도는 나이(r=0.392, p<0.001), 좌심방 크기(r=0.375, p<0.01), 좌심실 수축기말 직경(r=0.283, p<0.05), 좌심실 확장기말 직경(r=0.234, p<0.05), 좌심실구혈률(r=0.255, p<0.05), 심방세동의 유병 기간(r=0.341, p<0.01) 등과 의미있는 상관관계가 있었다. 전신 염증 표지자는 혈전색전 위험인자 동반 유무에 따른 차이가 없었다. 혈중 fibrinogen 농도는 나이(r=0.368, p<0.001), NYHA class (r=0.314, p<0.01)와 의미있는 상관관계가 있었고 d-dimer는 NYHA class와 의미있는 상관관계가 있었다(r=0.505, p<0.001). 결론: 본 연구 결과로 기존의 혈전색전 위험인자에 더하여 흡연, 심전도에서 미세 심방세동파(<1 mm), 안지오텐신-II 수용체 차단제나 스타틴의 무복용 등이 심방세동의 새로운 혈전색전 위험인자가 될 수 있음을 알 수 있었다. 심방세동에서 혈전색전의 증가는 주로 심내막과 동맥의 내피세포 기능 저하에 의해 일어남을 알 수 있었다. Background: Atrial fibrillation (AF) is the most common cause of embolic cerebral infarction. This study was performed to determine new risk factors and the mechanism underlying thromboembolism (TE) in patients with AF. Methods: 192 patients (M:F=137:55, 61±11 years) with AF were randomly selected and divided into a TE (n=95) and non-TE group (n=97). Another 71 patients with AF (M:F=38:33, 55±14) were studied for endothelial function by measuring the level of von Willebrand factor (vWF; factor 8 related antigen), inflammation by WBC, ESR, and high sensitive CRP and coagulation system by fibrinogen, fibrinogen degradation product and fibrin d-dimer; the results were compared with 25 patients with normal sinus rhythm. Results: The TE group was older than non-TE group. Hypertension (HTN), diabetes mellitus (DM), hypercholesterolemia, smoking and fine AF (AF wave amplitude <1 mm) were more frequent in the TE group. Mitral valvular disease, an ejection fraction <40% and dilated cardiomyopathy were more frequent in the TE group and the left atrial (LA) dimension was greater in the TE group. The use of anticoagulants, an angiotensin-II receptor blocker and statins were less frequently observed in the TE group. The vWF-factor 8 related antigen was higher in patients with advanced age, LV dysfunction, HTN, DM, mitral stenosis and positively correlated with age, LA dimension, LV end-diastolic and end-systolic dimension, ejection fraction, NYHA class and AF duration. The fibrinogen level was positively correlated with age, NYHA class, LA dimension and d-dimer with NYHA class. Markers for inflammation or coagulation were not significantly different in the atrial fibrillation and the sinus rhythm group. Conclusions: No use of an angiotensin-II receptor blocker or statin and fine AF may be new risk factors for TE in patients with AF. The TE risk factors are thought to increase TE by impairing endothelial function.(Korean J Med 71:371-380, 2006)

호두까기 식도증에서 하부식도와 하부식도괄약근을 통한 유동식의 비정상 통과

오원태,조천영,이완식,박창환,최성규,유종선,윤종만,범희승 大韓消化器病學會 1998 大韓消化器病學會誌 Vol.31 No.5

췌장 외분비에 미치는 Gabexate Megilate의 영향

최성규,김현수,조천영,유종선,김세종,윤종만 大韓消化器病學會 1998 大韓消化器病學會誌 Vol.32 No.3

간세포암 감별진단에 있어서 tens Cuinaris Agglutinin-A에 반응하는 AFP분획의 유용성

김신묵,김현수,조천영,김기태,구철,최성규,유종선,김세종,윤종만 大韓消化器病學會 1997 大韓消化器病學會誌 Vol.30 No.5

호두까기 식도증에서 하부식도와 하부식도괄약근을 통한 유동식의 비정상 통과

최성규,범희승,박창환,이완식,유종선,윤종만,오원태,조천영 대한소화기학회 1998 대한소화기학회지 Vol.31 No.5

Background/Aims: The nutcraeker esophagus is characterized manometrically by peristaltic waves of abnormally high amplitude exceeding 180 mmHg in the distal esophagus. It has been known as one of the most frequent esophageal motor disorder causing noncardiac chest pain and dysphagia. But there is a controversy on the food passage through the esophagus of patients with nutcracker esophagus. We performed this study to evaluate the food passage disturbance through the distal esophagus and lower esophageal sphincter (LES) in patients with nutcracker esophagus. Methods: We examined 26 consecutive patients with nutcracker esophagus and 20 age-sex matched volunteers by means of both esophageal mamometry and radionuclide esophageal transit study on the same day. Esophageal manometry was performed with pneumohydraulically perfused catheters attached to transducer. A station pull-through technique was employed to record peristaltic amplitude and duration. The pressure and relaxation percentage of LES were measured after 3 times wet swallows. Radionuclide esopbageal transit study included distal esophageal transit time, the presence of to and fro movement, and the time-activity curve of LES. Results: Patients with nutcracker esophagus showed significantly higher values in amplitude and duration of peristaltic contractions, and LES pressure as compared with those of the normal volunteers (236.2±47.5 mmHg, 5.5±1.4 sec, 31.2+8.1 mmHg vs 92.0±11.5 mmHg, 3.5±1.2 sec, 22.3±4.7 mmHg, respectiveiy) (p$lt;0.01). Distal esophageal transit time was significantly longer in patients with nutcracker esophagus (12.7±7.0 see) than that of the normal volunteers (5.6±1.0 sec)(p$lt;0.01). To and fro movement was found in 50% (13/26) of nutcracker esophagus group, but not in the nomal volunteers. Broad transit curves of LES were more frequent in patients with nutcracker esophagus (88%, 23/26) than in normal volunteers (45%, 9/20)(p$lt;0.05). Conclusions: These findings suggest that the pathology of nutcracker esophagus might include other disturbances besides elevated distal amplitude. Thus, other parameters should also be studied in the evaluation of new therapeutic modalities.

간세포암 감별진단에 있어서 Lens Culinaris Agglutinin-A에 반응하는 AFP분획의 유용성

김기태,김현수,김세종,유종선,윤종만,김신묵,조천영 대한소화기학회 1998 대한소화기학회지 Vol.30 No.5

Background/Aims: Alpha-fetoprotein(AFP) is the most widely used and effective tumor marker for the diagnosis of hepatocellular carcinoma(HCC), and the high titer of serum AFP is predictive of a high risk for HCC. However, the level of serum AFP has a wider overlapping zone between benign and malignant liver disease. Several studies have indicated that increased levels of several lectin-reactive AFP, including AFP that react with Lens culinaris agglutinin-A(LCA-A), could serve as an alternative index that is more specific than increased ]evels of serum AFP for HCC. The aim of this study was to determine tbe value of AFP L3 by AFP differentiation kit as a differential diagnostic method of HCC and liver cirrhosis. Methods: Sera were collected from 41 patients consisting of 16 patients with liver cirrhosis(LC) and 25 patients with HCC. Lectin-reactive fraction of AFP were determined by lectin affinity eclectrophoresis coupled with antibody-affinity blotting using AFP Differentiation Kit L(Wako Pure Chemical Industries. Ltd., Osaka Japan). Results: The positive rate of AFP L3 in LC and HCC was 75.0% and 96.0% respectively. AFP L3 fraction over 15% was found in 43.8% of LC and 76.0% of HCC(p$lt;0.05). No significant correlations were found between the tumor size or serum AFP levels and AFP L3 fraction in HCC. In 10 HCC patients with serum AFP levels below 20ng/ml, cases of AFP L3 fraction over 15% were 9 patients and AFP L3 fraction of those was 37.2%. Conclusions: These results lead us to conclude that the level of lectin-reactive AFP is a useful rnarker for diagnosis of hepatocellular carcinoma with low AFP levels.

췌장 외분비에 미치는 Gabexate Mesilate의 영향

최성규,김현수,김세종,유종선,윤종만,조천영 대한소화기학회 1998 대한소화기학회지 Vol.32 No.3

Background/Aims: Gabexate mesilate, a serine protease inhibitor, is a synthetic compound which is not antigenic and diffuses easily. We have investigated the effect of gabexate mesilate on exocrine pancreatic secretion in rat at basal and cholecytokinin-stimulated state. Methods: After anesthetized male Sprague-Dwaley rats were incised in the midline of abdomen, PE-10 tube was inserted into the pancreatic duct. The secretion was collected after the ligation of the bile duct between pancreas and liver. The volume, of pancreatic secretion and the amount of bicarbonate and protein in pancreatic secretion were measured in basal and CCK-8 (3.9 pmol/hr) stimulated state with and without the administration of gabexate mesilate (30 mg/kg). Resalts: The volume was 20.1±1.1 μL/30 min in basal state and 58.9±3.9 μL/30 min in CCK-8 stimulated state. The amount of bicarbonate in basal and CCK-8 stimulated state was 30.1±1.3 umol/ 30 min and 193.1±4.3 umol/30 min, respectively. After infusion of gabexate, the volume and the amount of bicarbonate were not changed significantly. The amount of protein was 39.8±1.2 ㎍/30 min in basa1 state and 396.0±6.2 ㎍/30 min in CCK-8 stimulated state. After the infusion of gabexate mesilate, the amount of the protein in basal and CCK-8 stimulated state was significantly decreased to 30.1±l.3 ㎍/30 min and 295.9±5.9 ㎍/30 min, respectively (p$lt;0.05). Conclusions: With the infusion of gabexate mesilate in both basal and CCK stimulated state of rat, only the protein in pancreatic exocrine secretions was significantly decreased.