한국인의 유전성 혈전증

김인호(In Ho Kim),박선양(Seon Yang Park),이종태(Jong Tai Lee),방수미(Soo Mee Bang),김효수(Hyo Su Kim),김병국(Byoung Kook Kim),김노경(Noe Kyeong Kim),박성섭(Seong Sub Park),조한익(Han Ik Cho),정해영(Hae Young Jeong),유욱준(Ook Joon Yo 대한내과학회 1996 대한내과학회지 Vol.51 No.6

N/A Objectives: Thromboembolism is a serious medical problem causing considerable morbidity and mortality. Major clinical risk factors for thrombosis included surgery, fracture, malignancy, old age, immobilization and the use of oral contraceptives. In the last several decades, substantial progress has been made in identifying hereditary factors predisposing to thrombosis. The genetic defects known to be associated with thrombophilia are deficiencies of antithrombin 3, protein C, protein S, dysfibrinogenemia and resistance to the anticoagulant action of activated protein C. We have elucidated the characteristics of heriditary thrombophilia of the Korean patients. Methods: The clinical profiles of 48 patients with heriditary thrombophilia (12 cases of our hospital and 36 cases reported previously in Korea) were analyzed. The underlying hemostatic abnormalities about antithrombin 3, Protein C, Protein S, activated protein C, fibriongen were investigated. Family studies of 6 patients of our 12 patients were done. Nucleotide sequences of antithrombin 3 genes of 2 patients were studied. Results: 1) Seven patients (58%) among our 12 patients had thrombotic onset before fifth decades, and 5 patients developed thromboses at their third decades. 2) Pulmonary embolisms were diagnosed in 10 cases (83%) among our 12 cases. Deep vein thromboses of lower extremities were 8 cases (67%) and usually rare site thromboses like a portal vein thrombosis occurred frequently (8 cases, 67%). Arterial thromboses occurred in two cases (17%). Hereditability of 5 families were confirmed by family study. 3) Analysis of 48 cases showed that protein C deficiency (12 cases, 25%) and protein S deficiency (19 cases, 40%) occurred relatively frequently. 4) Neither Resistance to activated protein C nor mutation in the factor V gene was demonstrated in Korean patients with deep vein thrombosis and normal persons. This result suggests that activated protein C resistance may be extremely rare in Korean population. 5) Two new mutations of antithrombin 3 genes were identified in two patients via nucleotide sequencing, and they were named 'AT 3 Seoul' and 'AT 3 Kosung' respectively. Conclusion: We elucidated clinical and laboratory characteristics of hereditary thrombophilia in Korea. Hereditary thrombophilia were not uncommon in Korean patients with deep vein thrombosis, with/without pulmonary embolism. Strong suspicion for hereditary thrombophilia may lead to correct diagnosis and appropriate treatment in these patients.

증례 : Kimura 병 경과관찰 중 발생한 NK/T 세포 림프종 1예

양기영 ( Ki Young Yang ),고성준 ( Seong Joon Koh ),김철우 ( Chul Woo Kim ),김인호 ( In Ho Kim ),윤성수 ( Sung Soo Yoon ),박선양 ( Seon Yang Park ),김병국 ( Byoung Kook Kim ) 대한내과학회 2007 대한내과학회지 Vol.73 No.6

본 증례는 Kimura 병으로 진단받은 후 경과관찰 중폐에 악성 림프종이 발생하였으며, 두 질환의 조직 모두에서 Epstein-Barr virus가 발견되었던 예로 이를 통해 두 질환 사이의 발병 기전의 연관 가능성을 시사하는 증례로서 국내외에 유사보고가 없는 것으로 생각되어 보고하는 바이다. Kimura`s disease is a rare chronic inflammatory disease of the lymphoid organs and this presents as painless nodules in the head and neck area. It occurs endemically in the Far East Asia and sporadically in the West. Its exact etiology is unknown and it has no potential to transform into malignant disease. However, it is often confused with malignant disease such as malignant lymphoma. We report a case of NK/T cell lymphoma patient who had Kimura`s disease in the right thigh 3 years ago. She then suffered from sudden dyspnea. Radiological studies revealed multiple small nodules scattered in both lung fields. NK/T cell lymphoma was diagnosed by open lung biopsy. In addition, Epstein-Barr virus (EBV) was detected in the previous site of Kimura`s disease and lung nodule by molecular pathologic examination. To the best of our knowledge, this is the first case of NK/T cell lymphoma complicating Kimura`s disease with coexisting chronic EBV infection.(Korean J Med 73:656-660, 2007)

심부정맥혈전증의 병인 분석

이제환 ( Lee Je Hwan ),박선양 ( Park Seon Yang ),계경채 ( Gye Gyeong Chae ),정철원 ( Jeong Cheol Won ),신현춘 ( Sin Hyeon Chun ),이진학 ( Lee Jin Hag ),양성현 ( Yang Seong Hyeon ),김병국 ( Kim Byeong Gug ),김노경 ( Kim No Gyeon 대한내과학회 1993 대한내과학회지 Vol.44 No.3

연구배경 : 심부정맥혈전증은 체내 지혈혈전계의 불균형에 의해 발생하며 최근 혈전증 연구의 발달로 심부정맥혈전증의 여러 가지 선행 인자들이 알려져 있다. 국내에서도 상당수의 심부정맥혈전증이 발생하고 있으나 그임상상 및 발생요인 등의 병인론에 관해서는 잘 알려져 있지 않다. 이에 저자들은 서울대학교병원 내과에서 심부정맥혈전증(종양색전은 제외)으로 진단받은 85예의 환자를 대상으로 임상적 선행 인자를 조사하였으며 동시에 혈액응고학적 선행 인자에 대한 검사를 실시하였다. 방법 : 혈전증의 임상상 및 혈전증의 임상적 선행 인자를 알기 위하여 대상 환자들의 병록지와 심부정맥혈전증의 진단시 시행된 방사선학적 검사를 검토하였으며, 혈전증을 유발할 수 있는 혈액응고학적 선행인자의 분석을 위하여는 항 cardiolipin 항체, C 단백, S 단백, antithtombin Ⅲ, tissue-type plasminogen activator 및 plasminogen activator inhibitor type 1, 혈장 섬유소 용해능을 검사하였다. 결과 : 1) 대상 환자 85예중 남자 40예, 여자 45예로 남녀비는 1 : 1.13 이었고, 나이는 15세에서 77세로 중앙치는 47세였다. 대상 환자의 연령별 분포는 40대가 21예 (24.7%)로 가장 많았고, 50대가 19예(22.4%), 30대가 16예 (18.8%), 20대가 10예(11.7%), 60대가 9예 (10.6%), 70세 이상이 6예(7.1%)였고, 20세 미만도 4예 (4.7%) 있었다. 2) 심부정맥 혈전증의 발생 부위로는 장단지(calf)의 정맥에 국한된 경우가 7예(8.2%), 근위부쪽으로 슬와정맥(popliteal vein)까지 관여된 경우가 7예(8.2%), 장골 정맥(femoral vein)까지 관여된 경우가 12예 (14.1%), 대퇴 정맥(iliac vein)까지 관여된 경우가 37예(43.5%)로 하지가 전체 대상 환자의 74.1%인 63예였으며, 하대 정맥과 신 정맥이 관여된 경우가 8예(9.4%), 문 맥(portal vein)이 관여된 경우가 8예(9.4%)로 복강내 정맥 혈전증이 16예(18.8%) 있었다. 그외 상지의 정맥이 관여된 경우가 4예(4.7%), 상대 정맥 혈전증이 1예(1.2%)있었으며, 심부정맥혈전증의 증거가 없는 폐동맥 색전증이 1예(1.2%)있었다. 전체 대상 환자중 29예(34.1%)에서 폐동맥 색전증이 합병하였다. 3) 심부정맥혈전증의 임상적 선행 인자로는 고령(60세 이상)이 15예(17.0%), 악성종양 13예(15.3%), 혈전증의 과거력이 있는 경우가 11예(12.9%), 수술후 상태가 9예(10.6%), immobilization이 7예(8.2%), 고지질혈증 5예(5.9%), 비만증 4예(4.7%), 혈류의 정체 4예(4.7%), 신증후군 3예(3.5%), 당뇨병 3예(3.5%), Behcet씨 병 2예(2.4%), 여성호르몬제 복용 2예(2.4%) 등이었으며, 특별한 임상적 위험인자가 발견되지 않은 경우가 25예(29.4%)였다. 4) 심부정맥혈전증의 혈액응고학적 선행 인자로는 항 cardiolipin 항체가 양성인 경우, C 단백의 기능적 활성도나 유리형 S 단백의 항원량이 정상의 60% 미만인 경우, antithrombin Ⅲ의 기능적 활성도가 정상의 70%미만인 경우, t-PA값이 정상치보다 낮거나 PAI-1 값이 정상치보다 높은 경우, 그리고 섬유소 용해능이 정상치 보다 낮은 경우 등을 생각하였는데, 항 cardiolipin 항체양성이 7예(19.4%), C 단백의 기능적 활성도가 정상의 60% 미만인 경우가 3예(16.7%), S단백(free form)의 항원량이 정상의 60% 미만인 경우가 3예(10.7%), antithtombin Ⅲ의 기능적 활성도가 정상의 70% 미만인 경우가 2예(5.9%), t-PA가 정상치보다 낮은 경우가 5예(22.7%), PAI-1이 정상치보다 높은 경우가 10예(29.4%), 섬유소 용해능 검사가 정상치보다 낮게 나온 경우가 14예(42.4%) 있었다. 결론 : 한국인에서의 심부정맥혈전증의 중요한 임상적 선행원인으로는 고령, 악성종양, 혈전증의 과거력, 수술후 상태, 기동장애였고, 혈전증과 관련된 혈액응고학적 검사의 이상소견으로는 PAI-1의 증가와 t-PA의 감소, 항 cardiolipin 항체 양성이 흔히 관찰되었다. Background : The formation of deep vein thrombosis reflects a balance between the effects of thrombogenic stimuli and a series of protective mechanisms. Substantial progress has been made in the last several decades in identifying hereditary and acquired risk factors predisposing to deep vein trombosis. Even so, a large number of patients still have no identifiable underlying cause for recurrent venous thrombosis. Elucidation of specific predisposing factor (s) is required for proper management of thrombosis. For the Korean patients, these factors have not been well characterized. Methods : We analyzed clinical profiles of the patients with venous thromboembolism and investigated the laboratory abnormalities known to be associated with increased risk of thrombosis. Results : 1) The male-female ratio was 1 : 1. 13 and age distribution showed 24.7% in fifth decade, 22.4% in sixth, 18.8% in fourth, 11.7% in third, 10.6% in seventh, 7.1% over 70 years old, and 4.7% under 20 years. 2) The thromboses were most commonly located in lower extremities (74.1%), and intraabdominal thromboses were 16 cases (18.8%), thromboses of upper extremities 4 cases (4.7%), superior vena cave thrombosis 1 case (1.2%) and pulmonary embolism without evidence of deep vein thrombosis 1 case (1.2%). Thirty-four percent of the cases were diagnosed as having pulmonary embolism. 3) The clinical risk factors for venous thromboembolism were old age(17.0%), malignancy (15.3%), prior history of venous thromboembolism (12.9%), postoperative state (10.6%), immobilization (8.2%), hyperlipidemia (5.9%), systemic lupus erythemato년 (4.7%), obesity (4.7%), stasis (4.7%), nephrotic syndrome (3.5%), diabetes mellitus (3.5%), Behcet`s disease (2.4%), estrogen (2.4%). Twenty-nine percent of the cases had no indentifiable clinical risk factors. 4) The laboratory abnormalities associated with venous thromboembolism were increase of anticardiolipin antibody (19.4%), decrese of protein C activity (16.7%), decrease of protein S (free form) antigenicity (10.7%), decrease of antithrombin Ⅲ activity (5.9%), decrease of tissue-type plasminogen activator (t-PA) (22.7%), increase of plasminogen activator inhibitor type 1 (PAI-1) (29.4%) and decrease of fibrinolytic activity (42.4%). Conclusion : Clinical and laboratory risk factors have been determined in 85 patients with deep vein thrombosis and/or pulmonary embolism in Korea. Major clinical risk factors for venous thromboembolism included old age, malignancy, prior history, postoperative state and immobilization. Among the laboratory abnormalities associated with venous thromboembolism, increase of PAI-1 and/of decrease of t-PA, and increase of anticardiolipin antibody were most frequently observed.

조혈모세포 이식 후 발생한 급성 신부전의 원인과 급성 신부전이 예후에 미치는 영향

김세중(Se Joong Kim),김성균(Seong Gyun Kim),오윤규(Yoon Kyu Oh),김현리(Hyun Lee Kim),김연수(Yon Su Kim),안규리(Cu Rie Ahn),한진석(Jin Suk Han),박선양(Seon Yang Park),김성권(Shung Gwon Kim),김병국(Byoung Kook Kim),이정상(Jung Sang Lee 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.3

배 경 : 조혈모세포 이식(hematopoietic stem cell transplantation; HCT) 후 합병증으로 패혈증(sepsis), 이식편대숙주반응(graft versus host disease; GVHD), 정맥폐색성 질환(venoocclusive disease; VOD), 약물에 의한 부작용(drug induced nephrotoxicity; DT), 급성 신부전(acute renal failure; ARF) 등이 있다. HCT 후 발생하는 ARF는 환자의 생존율에 영향을 미치는 것으로 알려져 있으나 우리나라에서의 연구는 미흡한 실정이다. 저자들은 HCT 후 ARF의 발생빈도, 위험인자를 살펴보고, ARF의 발생이 HCT 후 환자의 예후에 미치는 영향을 알아보고자 본 연구를 시행하였다. 방 법 : 1985년부터 2000년까지 서울대학교병원에서 HCT를 받은 환자 163명 중 분석이 가능하였던 107명을 대상으로 하였다. 결 과: HCT 후 ARF는 총 107명의 환자 중 52명(48.6%)에서 발생하였다. VOD, sepsis, GVHD 중 VOD가 ARF의 위험도를 4.4(1.13-17.2)배 증가시켰다(p<0.05). ARF의 원인은 시기에 따라 차이가 있었으나, cyclosporin 신독성이 전 기간에 걸쳐 ARF의 주된 원인이었다. ARF 발생군에서 전체 생존율은 60%였으며, ARF 비발생군(NARF)에서는 73%로, ARF 발생군에서 생존율이 낮았다(p<0.05). ARF 발생군을 최고 혈청 크레아티닌 3.0 ㎎/dL을 기준으로 경증과 중증 ARF로 나누어, NARF 군, 경증 ARF 발생군, 중증 ARF 발생군을 비교하였을 때, 중증 ARF 발생군에서 생존율이 낮았다(p<0.01). 결 론 : HCT 후 VOD, sepsis, GVHD 등이 ARF의 위험도를 증가시켰으나, ARF의 주된 원인은 cyclosporin 신독성이었다. ARF는 중증인 경우 HCT를 받은 환자의 예후를 결정하는 인자였다. Background : Common complications after hematopoietic stem cell transplantation(HCT) include sepsis, graft versus host disease(GVHD), veno-occlusive disease(VOD), drug-induced nephrotoxicity, and acute renal failure(ARF). Prior studies report that the presence of ARF affects prognosis. However, we are unaware of such reports on the incidence of ARF after HCT in Koreans, and whether or not the development of ARF is related to prognosis. The purpose of our study was to investigate the cause of ARF after HCT and its relation to prognosis. Methods : 163 patients received HCT at Seoul National University Hospital since 1985, of which, 107 were available for review. Results : ARF after HCT developed in 52 patients (48.6%). In the three clinical causes, VOD, sepsis, and GVHD, risk factor related to the development of ARF was preexisting VOD. Logistic regression confirmed this association(odds ratio 4.4). The causes of ARF were different according to the periods it developed, and cyclosporin nephrotoxicity was the main cause through the whole period after HCT. The overall survival was worse in the ARF group(60 vs 73 %; p<0.05). ARF group was split into two groups : patients whose peak serum creatinine levels were below 3.0 ㎎/dL(mild ARF group) and those who were above 3.0 ㎎/dL(severe ARF group). Severe ARF group had worse survival than mild ARF group and patients without ARF(p<0.01). Conclusion : VOD, sepsis, GVHD after HCT increase the risk of the deveolopment of ARF, but cyclosprin nephrotoxicity is the main cause of ARF. Severe ARF is a factor influencing the prognosis of patients who received HCT.

골수이형성증후군 ( Myelodysplastic syndrome ) 의 임상상에 대한 연구

김노경 ( Noe Kyung Kim ),조한익 ( Han Ik Cho ),이문호 ( Mun Ho Lee ),김병국 ( Byoung Kook Kim ),박석건 ( Seok Gun Park ),이재훈 ( Jae Hoon Lee ),이혁엽 ( Hyok Yop Lee ),박선양 ( Seong Yang Park ),박찬정 ( Chan Jung Park ) 대한내과학회 1985 대한내과학회지 Vol.28 No.6

한국인에서 발생한 Sweet 증후군에 대한분석

이근석(Keun Seok Lee),이윤종(Yun Jong Lee),이원섭(Won Sup Lee),안진석(Jin Seok Ahn),이종태(Jong Tae Lee),김원석(Wen Seong Kim),허대석(Dae Seog Heo),방영주(Yung Jue Bang),박선양(Seon Yang Park),조광현(kwang Hyun Cho),김병국(Byoung Koo 대한내과학회 1996 대한내과학회지 Vol.51 No.3

N/A Objectives: Sweet`s syndrome(acute febrile neutrophilic dermetosis) is characterized by fever, neutrophilia, erythematous painful cutaneous plaques, a dense dermal infiltrate onsisting of mature neutrophils, and a rapid response to steroid therapy, This condition is clinically important because it is associated with malignancy and it should be one of the differential diagnosis in the febrile immunocompromized patients with skin lesion, In spite of its clinical importance, there was no report on the epidemiologic characteristics of Sweets syndrome in Korean patients so far because of the rarity of Sweet`s syndrome, This study was performed to investigate characteristics and clinical significance of Sweet`s syndrome in Korean patients. Methods : The authors report a case of Sweet`s syndrome associated with acute myelogenous leukemia, and review the other 23 Korean patients with Sweet's syndrome that have been published in the literature. The characteristics of malignancy-associa- ted Sweet`s syndrome are compared with those of Sweet`s syndrome without malignancy association. Results: 1) Twenty-four cases of Sweet`s syndrome were analysed. Male to female ratio was 8:16 and the mean age was 44.8± 11.7 years. In 79% of patients, fever was noticed during the episodes of Sweet's syndrome. The most frequent sites of skin lesions were the upper extremities(83%), followed by face and head(75%), the lower extremities(75%), neck(46%), and trunk (13%). 2) Associated underlying systemic disorders were present in 15(62%) of the patients. The most frequent associations were chronic inflammatory bowel disease in seven patients, hematologic neoplasia in five, and solid neoplasia in one patients. 3) Leukocyte counts(mean 13,400±8,000/mm3) were higher than 10,000/mm3 in 16(67%) of patients. Erythrocyte sedimentation rates(mean 66.8±44.4mm/ hour) were elevated in 18(82%) of patients. 4) Skin lesion improvements were observed within 2 to 5 days from the initiation of steroid therapy. 5) Malignancies were associated in 6 patients. The initial appearance of Sweet`s syndrome lesions preceded or occurred concurrently with the detection of previously unsuspected malignancy in 67%(4 of 6 patients), In malignancy associated Sweet's syndrome, relative male preponderance, older age, and higher leukocyte counts were observed compared with Sweet's syndrome which is not associated with malignancy. There were no statistical significances, however. The erythrocyte sedimentation rate was the only statistically significant parameter. Conclusion: The characteristics of Sweet`s syndrome in Korean patients were similar to the characteristics of their western counterparts. Workup for malignancy seems appropriate far newly diagnosed Sweet`s syndrome patients in case of elevated erythrocyte sedimentation rate, leukocytosis, old age, and male sex

급성 백혈병 환자에서 발생한 감염 양상의 분석(1986~1992)

박선양,오명돈,김양수,백경란,김병국,최강원,김성민 대한감염학회 1993 감염 Vol.25 No.3

Infection is a major complication and potentially life-threatening in patients with acute leukemia. The patients require prompt broad-spectrum antibiotics therapy when fever develops. One of the keys to successful patient management is the recognition of institutional trends of the spectrum of infections and infecting microorganisms. So we evaluated 138 patients with acute leukemia and blastic crisis of chronic myelogenous leukemia admitted to Seoul National University Hospital from July 1986 to June 1992. The results are following: 1) Total number of febrile episodes was 224 and 60% of them occurred after chemotherapy. 2) Microbiologically-defined infection, clinically-defined infection, and unexplained fever accounted for 28%, 45%, 27% of the febrile episodes respectively. 3) Fifty-eight percent of microbiologically-defined infections were caused by gram-negative bactria, and 36% were gram-positive bacteria. There was a tendency to a greater proportion of gram (+) organisms than that of the last study (p>0.1). Escherichia coli was the most common organism, and coagulase-negative staphylococci, Pseudomonas aeruginosa, Klebsiella pneumoniae were common in decreasing order. 4) Pneumonia was the most common type of infection, followed by skin and soft tissue infection, perianal infection, gingivitis and primary septicemia. 5) Seventy-two percent of total infections improved with therapy and this success rate was higher than that of the last study(p<0.001).

동종 골수이식 후 재발한 백혈병에서 공여자 백혈구 주입 : 이식편대백혈병효과에 관한 다기관 임상연구

이석,박선양,김병국,이홍기,박찬형,남동기,김효철,이경희,현명수,오도연,김영철,이순남,성주명 大韓血液學會 1999 大韓血液學會誌 Vol.34 No.2

급성백혈병의 항암화학요법시 Ciprofloxacin의 감염예방효과에 관한 비교연구

김성민,신형식,오명돈,최강원,박선양,김병국 대한화학요법학회 1995 대한화학요법학회지 Vol.13 No.1

We evaluated the effect of ciprofloxacin, 500mg given orally every 12hours, on the prevention of bacterial infections in 40 patients receiving anticancer chemotherapy for acute leukemia. Nineteen patients were randomly assigned to receive ciprofloxacin, twenty-one patients assigned as control group did not receive any prophylactic antibioties. The rate of febrile episodes, microbiologically documented infection, clinically documented infection, possible infection, and mortality were similar in the two groups. There were no significant difference in the duration of granulocytopenia, use of parenteral antibiotics. Although streptococcal bacteremia occurred in only ciprofloxacin group(2cases), and gram-negative bacteremia occurred in only control group(4 cases), no difference was seen statistically.

위혈소판감소증의 기전에 관한 연구

김병국,양성현,이재훈,박선양,김노경,김승택,이홍복,서철원,이문호 대한내과학회 1990 대한내과학회지 Vol.38 No.4

We found 4 pseudothrombocytopenia patients and studied the mechanism of platelet agglutination. 1) Platelets were aggregated only in the presence of EDTA. 2) There were one case of cold agglutinin and two cases of warm agglutinins. 3) Three cases were persistent and one case was transient during the period of observation. 4) Normal platelets suspended in the patient's sera were also aggregated in the presence of EDTA. 5) Among 4 cases of pseudothrombocytopenia, 2 cases were IgM agglutinins and the other 2 cases were IgG agglutinins, which reaction occurred in the presence of EDTA. If platelet counts are very low in the absence of bleeding tendency and normal appearance on the peripheral blood smear, pseudothrombocytopenia should be suspected.