Identification of Molecular Defects in Korean Patients with Marfan Syndrome

BACKGROUND AND OBJECTIVES: Marfan syndrome is an autosomal dominant heritable disease of connective tissue which is characterized by cardinal features mainly in the cardiovascular, ocular and skeletal systems. Aneurysms or dissections of the aorta are the major cardiovascular complications of the disorder causing early mortality. Mutations in the fibrillin-1 (FBN1) gene on chromosome 15q21.1 have been found to be major causes of Marfan syndrome. The purpose of this study was to characterize the molecular defect in Korean Marfan patients, thus contributing to the effort of correlating the genotype with the phenotype. SUBJECTS AND METHODS: We screened all 65 exons of the FBN1 gene in 14 subjects diagnosed as Marfan syndrome by the method of single strand conformation polymorphism-heteroduplex analysis. RESULTS: We found mutations in only 10 among 14 patients. This study identified 8 novel mutations and 2 previously reported mutations in 14 Korean Marfan patients. Two cases were nonsense mutations and 8 were missense mutations, including 3 frameshift. Seven cases of the mutations occurred in one of the 43 calcium binding epidermal growth factor-like domains within an FBN1 gene. Mutations in Marfan patients occurred variably over the whole field of this FBN1 gene. CONCLUSION: Our results will contribute to the establishment of a database of Korean Marfan patients. Extending this study and using the database will help early detection of the disease and prevention of complications.

Coexpression of cyclooxygenase-2 and matrix metalloproteinases in human aortic atherosclerotic lesions

Inflammation appears to have a major role in the development of atherosclerosis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the production of matrix metalloproteinases (MMPs). This study aimed to investigate atherosclerosis in human aortas for in situ tissue distribution of COX-2, MMPs including MMP-9 and membrane type 1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinase-2 (TIMP-2). Immunohistochemical studies were performed on atherosclerotic lesions of aortas from patients with aortic aneurysms (n = 4) and dissections (n = 3) by using antibodies to COX-2, MMP-9, MT1-MMP, and TIMP-2. Control tissues were obtained from traumatically dissected aortas (n = 2). All specimens from diseased aortas had atherosclerotic lesions ranging from fatty streak to atheromatous plaques. In control, there was no expression of COX-2, MMP-9, and MT1-MMP in all aortic layers. Immunoreactivity for COX-2 was predominantly noted in macrophages and smooth muscle cells (SMCs) of the intima including atherosclerotic plaque itself and the medial layer of the plaque base, as well as in SMCs and endothelial lining of the vasa vasorum in the adventitia. Immunoreactivity for MMP-9 and MT1-MMP was found in the same distribution as that of COX-2. Additionally, the expression of TIMP-2 increased in relation to MMP-9 expression. This study demonstrates that COX-2 is coexpressed with MMP-9 and MT1-MMP, not only by macrophages and SMCs in atherosclerotic lesions, but also in endothelial lining of the vasa vasorum of human aortas. Thus, vascular inflammatory reactions may influence extracellular matrix remodeling by coactivation of MMPs in the development of atherosclerosis and, in turn, the progression of disease.

Arterry Bypas Graft with the Right Gastroepiploic Artery: Clinical and Angiographic Short-Term Results / 대한흉부외과학회지

BACKGROUND: The right gastroepiploic artery(RGEA) has been use in coronary artery bypass grafting from 1987. The RGEA is the most useful arterial conduit in coronary artery bypass grafting(CABG) followed by the internal mammary artery, MATERIALS AND METHOD: From Septermber 1998 to February 1999 the RGEA was used for coronary artery bypass grafting in 11 patients 10 males and 1 female. Postoperative angiography was performed in all of the patients before discharge RESULT: Early patent rate of the RGEA was 100%. The flow competition of the REGA graft was seen in 4 patients(36.4%) The flow pattern war RGEA dependent type in the inner diameter of the recipient coronary artery 1.5 mm the inner diameter of the RGEA 2.5 mm and the rtio of inner diameter of the RGEA and the recipient coronary artery 1(p<0.05) CONCLUSION: Early results of CABG with RGEA was satisfactory. However the RGEA graft has a tendency of flow competition in relation to the inner diameter of graft. Preoperative angiographic evaluation for RGEA and meticulous operative technique are required for a good surgical results.

Prosthetic Mitral Valve Thrombosis

No abstract available.

Pregnancy in Patients with Prosthetic Heart Valve / 대한흉부외과학회지

BACKGROUND: This is a retrospective study of 42 pregnancies from 33 women with prosthetic heart valves who were on anticoagulation regimen prior to or during their pregnancy. MATERIAL AND METHOD: Of the 17 women with bioprosthesis, 15 had 21 pregnancies following cessation of the anticoagulation therapy which resulted in the delivery of 20 healthy babies and 1 abortion. Remaining 2 had 3 pregnancies maintained with heparin, resulting in 2 healthy babies and 1 spontaneous abortion. RESULT: Among 16 women with mechanical heart valves, there were 7 pregnancies during which warfarin was used and this was associated with 4 fetal wastages(2 therapeutic abortion, 1 spontaneous abortion and 1 stillbirth with cerebral hemorrhage). However, in pregnancies where heparin was used, there was no fetal wastage. A patient who did not take anticoagulant for the first trimester and took warfarin for the remaining period and a patient who did not take anticoagulant during pregnancy delivered normal babies. There was an other fetal wastage in a patient on anti-platelet therapy for the first trimester and warfarin therapy for the remaining periods. There was 1 minor petechial complication in a heparin administered group. CONCLUSION: The study indicates that woman with bioprosthetic heart valves can go through pregnancy without undue risks or complications. On the other hand, the use of warfarin during pregnancy in women with mechanical heart valves, was shown to be associated with unacceptable high risk for the fetus. However, in the same group of women, judicious use of heparin during pregnancy was accompanied by a much reduced risk. The safety and adequate therapeutic range of heparin usage under such circumstances are subject to further studies.

Endovascular Treatment of Abdominal Aortic Aneurysm by Bifurcated Stent Graft

PURPOSE: To evaluate the effectiveness and safety of endoluminal bifurcated stent graft for the treatment of AAA. MATERIALS AND METHODS: Between August 1997 and August 1998, 20 patients with AAA underwent treatment involving the use of a bifurcated stent graft. Fourteen in whom the aneurysm involved only bifurcation and six patients in whom the common iliac arteries were involved. For one patient, a stent with a short proximal neck measuring 12 mm was used. The stent graft was inserted by means of a unilateral surgical femoral arteriotomy. After the procedure, follow up involving CT and aortography was performed between month 3 and month 12. RESULTS: The primary success rate with the first trial was 79 percent (15 of 19 patients), and the overall success rate was 84 percent; one perigraft leak was successfully corrected. In one case, technical failure occurred due to a tortuous iliac vessel and spasm. Procedure-related complications occurred in 16% of patients (3 of 19), one of whom died due to acute renal failure following a contrast overdose. CONCLUSION: Endovascular treatment of infrarenal AAA by means of a bifurcated stent graft was effective and safe. In particular, if the proximal neck measured more than 1cm, any AAA could be treated using bifurcated stent graft. Further investigation of the outcome and complications arising during long-term follow-up are needed, however.

Bifurcated Stent-Graft(Vanguard) for the Endovascular Treatment of Abdominal Aortic Aneurysm

PURPOSE: The purpose of this study was to evaluate the safety, feasibility and effectiveness of an endoluminally-placed bifurcated stent-graft (Vanguard) for the treatment of infrarenal abdominal aortic aneurysm (AAA). METHODS: Transluminal endovascular stent-graft placements were attempted in 29 patients (28 male, mean age 69+/-7 years) with AAAs involving the common iliac arteries from Aug. 1997 to Jan. 1999. Endovascular therapy was performed in the cardiac catheterization laboratory with epidural anesthesia. One side of the femoral artery was opened by surgical cutdown for the bifurcated stent-graft entry and the other side was punctured percutaneously for the straight stent-graft. Computed tomography and/or intraarterial angiography were performed during an average follow-up of 10 months (2-18 months). RESULTS: Primary success rate was 75.9% (22 of 29 patients) and the overall success rate was 79.3% with successful correction of one perigraft leak. Twenty patients (69.0%) had significant coronary artery disease. There were two technical failure cases, the one was tortuous iliac vessel with spasm, the other was disconnection of the stent-graft connecting portion. Complications related to procedure occurred in 13.8% of patients (4 of 29 patients) and two of these four patients had procedure-related mortality because of acute renal failure following contrast overdose and sepsis after operation. CONCLUSIONS: Endovascular treatment of infrarenal AAA with bifurcated stent-graft (Vanguard) is effective, feasible and relatively safe. However, further investigation for the outcome, complication and long-term follow-up are needed.

Interventional Treatment of Total Occlusion of Abdominal Aorta

BACKGROUND: Total occlusion of the infrarenal abdominal aorta is a very rare disease in clinical practice. The clinical outcome may be poor unless management is attempted promptly. Surgical bypass has been recommended as the treatment of choice for these lesions. However, there was relatively high surgical mortality and morbidity associad with aorto-bifemoral bypass graft in patients with other systemic disease, especially coronary artery disease. As a result, the use of, thrombolysis with percutaneous transluminal angioplasty (PTA) has recently been extended to this disease as an alternative method to surgery. PTA is technically simpler with less morbidity and mortality than surgery.We report our experience with thrombolysis and balloon angioplasty of total aortic occlusion in 14 patients between March 1991 and December 1996. METHODS: Fourteen patients, whose mean age was 59+/-13 years (11 male, 3 female), serve as the study's patients. Aortography was introduced via transbrachial artery. The end hole multipurpose catheter with guidewire was introduced into the thrombotic portion of the total occlusion. Urokinase was infused into the thrombus through the catheter if there were no contraindications. in sysremic thrombolysis. Thrombolytic therapy was continued until the thrombi was resolved and flow was restored. Balloon dilatation was followed in residual stenotic lesions. Stents were implanted in case of suboptimal results after ballooning. RESULTS: Clinical findings were resting leg pain in 6 patients, gangrene in 5 patients, and claudication in 3 patients. The causes of aortic occlusion were thromboembolism in 4 patients and thrombosis of an atherosclerotic aorta in 10 patients. Location of obstruction was below the renal artery in all cases. The clinical outcome of interventional therapy was successful in all cases except one patients. Operative treatment was undertaken in 2 cases because they could not received thrombolytic therapy due to contraindication and complication of thrombolytic therapy (gastrointestinal bleeding). Near normal revascularization was achieved in 3 patients by thrombolytic therapy only. PTA was performed at the stenotic after thrombolytic therapy in 4 patients. Stenting were performed at the stenotic sites after balloon dilatation in another 4 patients. There was bleeding complication in one case. CONCLUSIONS: Interventional therapy such as thrombolytic therapy with PTA is an effective and safe treatment modality for abdominal aortic total occlusion in selected cases. These techniques were very useful in some high risk patients who received surgical bypass procedures.

Primary Intracardiac Hemangioma: 1 case / 대한흉부외과학회지

Intracardiac hemangiomas are very rare primary cardiac tumor and there have been at least 37 reports of surgically resected cardiac hemangiomas. Most cardiac hemangiomas are asymptomatic. In symptomatic patients, symptoms are related to the location of tumor and outflow tract obstruction or obstruction of inferior and/or superior vena cava. Sudden death may occur due to conduction disturbances. The principle of treatment is surgical resection, and the prognosis is dependent upon the size, location and multiplicity of the tumor. A 40 year old man was admitted due to chest contusion and was found to have an intracardiac mass during echocardiographic examination. The mass was successfully removed and pathologic examination showed benign hemangioma. The patient was recovered uneventfully in postoperative period and was followed up for 1 year without evidence of recurrence.

Aortic Root Replacement with Valve Preservation in a Patient with Annuloaortic Ectasia / 대한흉부외과학회지

Patients with aortic root disease, frequently seen in Marfan syndrome have progressive dilatation of the aortic sinuses and dilatation and distortion of the aortic annulus, leading to aortic incompetence. They are currently treated with composite graft replacement of the ascending aorta and aortic valve and reimplantation of the coronary arteries. Recently, we experienced an aortic root replacement with aortic valve preservation in a patient with annuloaortic ectasia. The ascending aorta and sinus was excised except the aortic annulus and aortic valve. The aortic valve was reimplanted inside of a collagen-impregnated tubular Dacron graft. The coronary arteries were also reimplanted. The patient was followed up for six months and reevaluated with the echocardiography. Postoperative Doppler echocardiography revealed normal aortic valve function. With this technique, it is possible to preserve the native aortic valve if the aortic leaflets are anatomically normal.

Animal Experiment and Blood Biocompatibility Study of Polymer Valve / 대한흉부외과학회지

In vivo testings of the monoleaflet polymer valve were performed in seven dogs to prove its blood biocompatibility. The monoleaflet polymer valve used in this study was developed for short-term usage n the ventricular assist device. The frame and leaflet of the polymer valve were made of polyurethane. The inter-aortic valved conduit were implanted in four dogs and the ventriculo-atrial valved conduit was implanted in one dog. The ventricular assist devices with polymer valve were implanted in two dogs. The longest survival was 20 days. Main causes of death were bleeding and infection. To examine the blood compatibility, each blood sample was collected and RBC, WBC, hematocrit, hemoglobin, platelet and lactic acid dehydrogenase were analyzed. These studies thus far demonstrated that, with further development, a reliable and inexpensive polymer valve will be used in the ventricular assist device as short term usage.