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1.
J Mol Med (Berl) ; 91(1): 37-47, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22772377

ABSTRACT

Excessive activation of the transforming growth factor beta signaling pathway and disorganized cellular skeleton caused by genetic mutations are known to be responsible for the inherited thoracic aortic aneurysms and dissections (TAAD), a life-threatening vascular disease. To investigate the genotype-phenotype correlation, we screened genetic mutations of fibrillin-1 (FBN1), transforming growth factor-ß receptor-1 (TGFBR1) and transforming growth factor-ß receptor-2 (TGFBR2) for TAAD in 7 affected families and 22 sporadic patients. Of 19 potential mutations identified in FBN1, 11 appeared novel while the others were recurrent. Two mutations were detected in TGFBR2. Eight patients carried no mutation in either of these genes. Characterization of FBN1 c.5917+6T>C in transfected HEK293 cells demonstrated that it caused skipping of exon 47, leading to the loss of the 33th calcium binding epidermal growth factor-like domain associated with Marfan syndrome. Compared with exon 46, skipping of 47 did not cause patients ectopia lentis in all carriers. To correlate genotypes with phenotypes in different human ancestries, we reviewed the published mutational studies on FBN1 and found that the probability of cardiovascular defects were significantly increased in Chinese patients with premature termination codon or splicing mutations than those with missense mutations (91.7 % vs 54.2 %, P = 0.0307) or with noncysteine-involved point mutations than those with cysteine-involved mutations (88.9 % vs 33.3 %, P = 0.0131). Thus, we conclude that exon 47 skipping of FBN1 leads preferentially to cardiovascular defects and human ancestries influence genotype-phenotype correlation in TAAD.


Subject(s)
Aorta, Thoracic/metabolism , Aortic Aneurysm, Thoracic/genetics , Aortic Dissection/genetics , Microfilament Proteins/genetics , Adolescent , Adult , Aortic Dissection/ethnology , Aortic Dissection/pathology , Aorta, Thoracic/pathology , Aortic Aneurysm, Thoracic/ethnology , Aortic Aneurysm, Thoracic/pathology , Asian People , Child , Exons , Female , Fibrillin-1 , Fibrillins , Gene Expression , Genetic Association Studies , HEK293 Cells , Humans , Male , Middle Aged , Mutation , Pedigree , Protein Serine-Threonine Kinases/genetics , Protein Structure, Tertiary , Receptor, Transforming Growth Factor-beta Type I , Receptor, Transforming Growth Factor-beta Type II , Receptors, Transforming Growth Factor beta/genetics , Transfection
2.
Beijing Da Xue Xue Bao Yi Xue Ban ; 40(2): 223-4, 2008 Apr.
Article in Chinese | MEDLINE | ID: mdl-18458703

ABSTRACT

Acute massive pulmonary thromboembolism after pneumonectomy usually results in death if not diagnosed early and treated aggressively. It was a case of acute embolism in the main pulmonary artery with thrombus following right pulmonary wedge resection. Diagnosis was made clinically and with computerized tomography before emergency surgery. Thromboembolectomy was successfully performed on cardiopulmonary bypass and the patient was subsequently discharged home after uneventful recovery. Although the patient had no previous history of thrombosis, he took high dose of warfarin for anticoagulating postoperatively, which suggested that the patient with pulmonary embolism attack may be associated with the hypercoagulable state of his own.


Subject(s)
Embolectomy , Lung/surgery , Postoperative Complications/surgery , Pulmonary Embolism/surgery , Humans , Lung Diseases/surgery , Male , Middle Aged
3.
J Biomed Mater Res A ; 82(1): 139-44, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17269141

ABSTRACT

The clinical benefits of coronary artery bypass graft operations can be compromised by postoperative vasospasm. Traditionally, local papaverine (PPV) has been employed during the procedure to prevent and counteract vasospasm. But the relatively short action period limited its application. Fibrin glue (FG) might be a potential carrier of PPV for counteracting vasospasm in a longer action period than PPV solution. After FG incorporated with PPV (PPV-FG) was locally administrated in axillary and femoral arteries of dogs, PPV concentrations in artery vessels surrounding the administration sites were compared with the concentrations at the same sites in dogs given PPV solution. The properties of PPV's release in vitro and maintenance in vessel as well as the influence on the mean peripheral blood pressure and drug concentration in peripheral vein after the introduction PPV-FG on the surface of artery in dogs were evaluated. FG was considered to provide a sustained release of PPV and could maintain a high PPV concentration in artery vessel around the administration site. The results suggested that FG was an effective substrate for reserving PPV in the administrated site in a defined period.


Subject(s)
Biocompatible Materials , Drug Delivery Systems , Fibrin Tissue Adhesive , Vasodilator Agents/administration & dosage , Animals , Blood Vessel Prosthesis , Coronary Artery Bypass/adverse effects , Coronary Vasospasm/prevention & control , Delayed-Action Preparations , Dogs , Female , Femoral Artery/transplantation , Humans , In Vitro Techniques , Male , Materials Testing , Papaverine/administration & dosage
4.
Zhonghua Wai Ke Za Zhi ; 44(22): 1532-4, 2006 Nov 15.
Article in Chinese | MEDLINE | ID: mdl-17359656

ABSTRACT

OBJECTIVE: To study the risk factors of acute renal insufficiency (ARI) following coronary artery bypass grafting (CABG). METHODS: The clinic data of 2242 patients undertaking CABG between July 1997 and July 2006 were retrospectively analyzed, and ARI following CABG was included. RESULTS: ARI occurred in 219 patients, with an incidence of 9.8%. Univariate analysis revealed that advanced age, diabetes mellitus, preoperative chronic renal dysfunction, left main disease, low left ventricular erection faction, emergency operation, on-pump CABG, ascending aortic atherosclerosis, postoperative respiratory function insufficiency and low cardiac output syndrome were significantly related to ARI following CABG, and logistic multivariate regression analysis showed that presence of advanced age (P = 0.031), preoperatively chronic renal dysfunction (CrCl or= 150 micromol/L, P = 0.041), on-pump CABG (P < 0.001), postoperative respiratory function insufficiency (P = 0.013) and low cardiac output syndrome (P = 0.004) were independent risk factors of ARI. CONCLUSIONS: Advanced age, preoperatively chronic renal dysfunction, on-pump CABG, postoperative respiratory function insufficiency and low cardiac output syndrome are the risk factors of ARI following CABG.


Subject(s)
Acute Kidney Injury/etiology , Coronary Artery Bypass/adverse effects , Acute Kidney Injury/epidemiology , China/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Risk Factors
5.
Zhonghua Wai Ke Za Zhi ; 41(8): 597-9, 2003 Aug.
Article in Chinese | MEDLINE | ID: mdl-14505534

ABSTRACT

OBJECTIVE: The increasing number of aged patients with severe ascending aorta atherosclerosis who are undergoing coronary artery bypass graft (CABG) present high risk for ascending aortic cannulation, cross-clamping or partial occluding and proximal anastomosis. We reviewed the surgical experience in 22 patients of CABG with ascending aorta atherosclerosis and tried to find the way to minimize the complications. METHODS: Twenty-two patients with severe atherosclerotic and calcified ascending aorta underwent CABG in our hospital. Thirteen of them received CABG on beating heart. Nine patients had their CABG with extracorporeal circulation. With deep hypothermia, we reduced the flow rate and intermittently arrested the circulation for the proximal anastomosis on ascending aorta in 5 patients with neither cross-clamping nor partial occluding. The sequential grafts and "Y" type anastomosis between reversed saphenous venous grafts were employed. RESULTS: Twenty of the patients survived after surgery. One died of inhalation pneumonia in two weeks after surgery. Another died of right hemothorax in ten days after surgery. The complications include: pneumonia 4 patients (18%), angina 2 patients (9%), ventricular fibrillation 1 patients (5%), post-CABG myocardium infarction 1 case (5%) and hemothorax 1 case (5%). There is no neurologic complications or aortic dissection after CABG. CONCLUSION: CABG on beating heart with pedicel arterial grafts is the best approach to performing the surgery without touching the diseased ascending aorta. Ventricular fibrillation under mild hypothermia cardiopulmonary bypass and left ventricular suction were employed for quiet and bloodless field while distal anastomosis had no cross-clamping the ascending aorta. Also deep hypothermia and intermittently circulatory arrest offer quiet and bloodless field for the proximal anastomosis on ascending aorta without cross-clamping or partial-occluding. Distal sequential anastomosis and proximal "Y" type anastomosis are the effective approach to minimizing the proximal anastomosis on the ascending aorta.


Subject(s)
Aortic Diseases/surgery , Atherosclerosis/surgery , Coronary Artery Bypass/methods , Aged , Aged, 80 and over , Aortic Diseases/complications , Atherosclerosis/complications , Coronary Artery Disease/complications , Coronary Artery Disease/surgery , Female , Humans , Male , Retrospective Studies , Treatment Outcome
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