Long term relative survival after surgery for abdominal aortic aneurysm in Western Australia: population based study

Objective: To determine the long term relative survival of all patients who had surgery for abdominal aortic aneurysm in Western Australia during 1985-94.

Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme.

Certain matrix metalloproteinases (MMP) are expressed within the fibrous areas surrounding acellular lipid cores of atherosclerotic plaques, suggesting that these proteinases degrade matrix proteins within these areas and weaken the structural integrity of the lesion. We report that matrilysin and macrophage metalloelastase, two broad-acting MMPs, were expressed in human atherosclerotic lesions in carotid endarterectomy samples (n = 18) but were not expressed in normal arteries (n = 7). In situ hybridization and immunohistochemistry revealed prominent expression of matrilysin in cells confined to the border between acellular lipid cores and overlying fibrous areas, a distribution distinct from other MMPs found in similar lesions. Metalloelastase was expressed in these same border areas. Matrilysin was present in lipid-laden macrophages, identified by staining with anti-CD-68 antibody. Furthermore, endarterectomy tissue in organ culture released matrilysin. Staining for versican demonstrated that this vascular proteoglycan was present at sites of matrilysin expression. Biochemical studies showed that matrilysin degraded versican much more efficiently than other MMPs present in atherosclerotic lesions. Our findings suggest that matrilysin, specifically expressed in atherosclerotic lesions, could cleave structural proteoglycans and other matrix components, potentially leading to separation of caps and shoulders from lipid cores.

Hypoxia enhances stimulus-dependent induction of E-selectin on aortic endothelial cells.

In many diseases, tissue hypoxia occurs in conjunction with other inflammatory processes. Since previous studies have demonstrated a role for leukocytes in ischemia/reperfusion injury, we hypothesized that endothelial hypoxia may "superinduce" expression of an important leukocyte adhesion molecule, E-selectin (ELAM-1, CD62E). Bovine aortic endothelial monolayers were exposed to hypoxia in the presence or absence of tumor-necrosis factor alpha (TNF-alpha) or lipopolysaccharide (LPS). Cell surface E-selectin was quantitated by whole cell ELISA or by immunoprecipitation using polyclonal anti-E-selectin sera. Endothelial mRNA levels were assessed using ribonuclease protection assays. Hypoxia alone did not induce endothelial E-selectin expression. However, enhanced induction of E-selectin was observed with the combination of hypoxia and TNF-alpha (270% increase over normoxia and TNF-alpha) or hypoxia and LPS (190% increase over normoxia and LPS). These studies revealed that a mechanism for such enhancement may be hypoxia-elicited decrements in endothelial intracellular levels of cAMP (<50% compared with normoxia). Addition of forskolin and isobutyl-methyl-xanthine during hypoxia resulted in reversal of cAMP decreases and a loss of enhanced E-selectin surface expression with the combination of TNF-alpha and hypoxia. We conclude that endothelial hypoxia may provide a novel signal for superinduction of E-selectin during states of inflammation.

Nonuniformity of the constitutive law parameters for shear rupture and quasistatic nucleation to dynamic rupture: a physical model of earthquake generation processes.

Based on the recent high-resolution laboratory experiments on propagating shear rupture, the constitutive law that governs shear rupture processes is discussed in view of the physical principles and constraints, and a specific constitutive law is proposed for shear rupture. It is demonstrated that nonuniform distributions of the constitutive law parameters on the fault are necessary for creating the nucleation process, which consists of two phases: (i) a stable, quasistatic phase, and (ii) the subsequent accelerating phase. Physical models of the breakdown zone and the nucleation zone are presented for shear rupture in the brittle regime. The constitutive law for shear rupture explicitly includes a scaling parameter Dc that enables one to give a common interpretation to both small scale rupture in the laboratory and large scale rupture as earthquake source in the Earth. Both the breakdown zone size Xc and the nucleation zone size L are prescribed and scaled by Dc, which in turn is prescribed by a characteristic length lambda c representing geometrical irregularities of the fault. The models presented here make it possible to understand the earthquake generation process from nucleation to unstable, dynamic rupture propagation in terms of physics. Since the nucleation process itself is an immediate earthquake precursor, deep understanding of the nucleation process in terms of physics is crucial for the short-term (or immediate) earthquake prediction.

cAMP- and rapamycin-sensitive regulation of the association of eukaryotic initiation factor 4E and the translational regulator PHAS-I in aortic smooth muscle cells.

Incubating rat aortic smooth muscle cells with either platelet-derived growth factor BB (PDGF) or insulin-like growth factor I (IGF-I) increased the phosphorylation of PHAS-I, an inhibitor of the mRNA cap binding protein, eukaryotic initiation factor (eIF) 4E. Phosphorylation of PHAS-I promoted dissociation of the PHAS-I-eIF-4E complex, an effect that could partly explain the stimulation of protein synthesis by the two growth factors. Increasing cAMP with forskolin decreased PHAS-I phosphorylation and markedly increased the amount of eIF-4E bound to PHAS-I, effects consistent with an action of cAMP to inhibit protein synthesis. Both PDGF and IGF-I activated p70S6K, but only PDGF increased mitogen-activated protein kinase activity. Forskolin decreased by 50% the effect of PDGF on increasing p70S6K, and forskolin abolished the effect of IGF-I on the kinase. The effects of PDGF and IGF-I on increasing PHAS-I phosphorylation, on dissociating the PHAS-I-eIF-4E complex, and on increasing p70S6K were abolished by rapamycin. The results indicate that IGF-I and PDGF increase PHAS-I phosphorylation in smooth muscle cells by the same rapamycin-sensitive pathway that leads to activation of p70S6K.

Identification of endothelin 1 and big endothelin 1 in secretory vesicles isolated from bovine aortic endothelial cells.

Vesicles containing endothelin 1 (ET-1) were isolated from bovine aortic endothelial cells (BAECs) by fractionation of homogenates on sucrose density gradients by ultracentrifugation. The vesicles were localized at the 1.0/1.2 M sucrose interface using a specific anti-ET-1-(16-21) RIA. Identification of ET-1 and big ET-1 in this fraction was confirmed by HPLC analysis combined with RIA. Morphological examination of the ET-1-enriched fraction by electron microscopy identified clusters of vesicles approximately 100 nm in diameter. Immunostaining of ultrathin cryosections prepared from the vesicle fraction for ET-1 or big ET-1 showed clusters of 15-nm gold particles attached to or within vesicles. Immunofluorescence staining of whole BAECs using a specific ET-1-(16-21) IgG purified by affinity chromatography revealed punctate granulation of the cell cytoplasm viewed under light microscopy. This distinct pattern of staining was shown by confocal light microscopy to be intracellular. Immunofluorescence staining of whole cells with a polyclonal antiserum for big ET-1-(22-39) showed a defined perinuclear localization of precursor molecule. Hence, several different approaches have demonstrated that ET-1 and big ET-1 are localized within intracellular vesicles in BAECs, suggesting that these subcellular compartments are an important site for processing of big ET-1 by endothelin-converting enzyme.

Automatic Abdominal Aortic Aneurysm segmentation in MR images

Abdominal Aortic Aneurism is a disease related to a weakening in the aortic wall that can cause a break in the aorta and the death. The detection of an unusual dilatation of a section of the aorta is an indicative of this disease. However, it is difficult to diagnose because it is necessary image diagnosis using computed tomography or magnetic resonance. An automatic diagnosis system would allow to analyze abdominal magnetic resonance images and to warn doctors if any anomaly is detected. We focus our research in magnetic resonance images because of the absence of ionizing radiation. Although there are proposals to identify this disease in magnetic resonance images, they need an intervention from clinicians to be precise and some of them are computationally hard. In this paper we develop a novel approach to analyze magnetic resonance abdominal images and detect the lumen and the aortic wall. The method combines different algorithms in two stages to improve the detection and the segmentation so it can be applied to similar problems with other type of images or structures. In a first stage, we use a spatial fuzzy C-means algorithm with morphological image analysis to detect and segment the lumen; and subsequently, in a second stage, we apply a graph cut algorithm to segment the aortic wall. The obtained results in the analyzed images are pretty successful obtaining an average of 79% of overlapping between the automatic segmentation provided by our method and the aortic wall identified by a medical specialist. The main impact of the proposed method is that it works in a completely automatic way with a low computational cost, which is of great significance for any expert and intelligent system.

Méthode bayésienne de détection de rupture et/ou de tendance pour des données temporelles

Ce mémoire a pour but de déterminer des nouvelles méthodes de détection de rupture et/ou de tendance. Après une brève introduction théorique sur les splines, plusieurs méthodes de détection de rupture existant déjà dans la littérature seront présentées. Puis, de nouvelles méthodes de détection de rupture qui utilisent les splines et la statistique bayésienne seront présentées. De plus, afin de bien comprendre d’où provient la méthode utilisant la statistique bayésienne, une introduction sur la théorie bayésienne sera présentée. À l’aide de simulations, nous effectuerons une comparaison de la puissance de toutes ces méthodes. Toujours en utilisant des simulations, une analyse plus en profondeur de la nouvelle méthode la plus efficace sera effectuée. Ensuite, celle-ci sera appliquée sur des données réelles. Une brève conclusion fera une récapitulation de ce mémoire.

Type A aortic dissection model to improve endovascular research and technologies.

OBJECTIVE Type A aortic dissection is a life-threatening disease requiring immediate surgical treatment. With emerging catheter-based technologies, endovascular stent-graft implantation to treat aneurysms and dissections has become a standardized procedure. However, endovascular treatment of the ascending aorta remains challenging. Thus we designed an ascending aortic dissection model to allow simulation of endovascular treatment. METHODS Five formalin-fixed human aortas were prepared. The ascending aorta was opened semicircularly in the middle portion and the medial layer was separated from the intima. The intimal tube was readapted using running monofilament sutures. The preparations were assessed by 128-slice computed tomography. A bare-metal stent was implanted for thoracic endovascular aortic repair in 4 of the aortic dissection models. RESULTS Separation of the intimal and medial layer of the aorta was considered to be sufficient because computed tomography showed a clear image of the dissection membrane in each aorta. The dissection was located 3.9 ± 1.4 cm proximally from the aortic annulus, with a length of 4.6 ± 0.9 cm. Before stent implantation, the mean distance from the intimal flap to the aortic wall was measured as 0.63 ± 0.163 cm in the ascending aorta. After stent implantation, this distance decreased to 0.26 ± 0.12 cm. CONCLUSION This model of aortic dissection of the ascending human aorta was reproducible with a comparable pathological and morphological appearance. The technique and model can be used to evaluate new stent-graft technologies to treat type A dissection and facilitate training for surgeons.

The sutureless aortic valve at 1 year: A large multicenter cohort study

OBJECTIVE Sutureless aortic valve replacement (AVR) offers an alternative to standard AVR in aortic stenosis. This prospective, single-arm study aimed to demonstrate safety and effectiveness of a bovine pericardial sutureless aortic valve at 1 year. METHODS From February 2010 to September 2013, 658 patients (mean age 78.3 ± 5.6 years; 40.0% octogenarian; 64.4% female; mean Society of Thoracic Surgeons score 7.2 ± 7.4) underwent sutureless AVR in 25 European centers. Concomitant cardiac procedures were performed in 29.5% and minimally invasive cardiac surgery in 33.3%. RESULTS One-year site-reported event rates were 8.1% for all-cause mortality, 4.5% for cardiac mortality, 3.0% for stroke, 1.9% for valve-related reoperation, 1.4% for endocarditis, and 0.6% for major paravalvular leak. No valve thrombosis, migration, or structural valve deterioration occurred. New York Heart Association class improved at least 1 level in 77.5% and remained stable (70.4% New York Heart Association class I or II at 1 year). Mean effective orifice area was 1.5 ± 0.4 cm(2); pressure gradient was 9.2 ± 5.0 mm Hg. Left ventricular mass decreased from 138.5 g/m(2) before surgery to 115.3 g/m(2) at 1 year (P < .001). Echocardiographic core laboratory findings confirmed that paravalvular leak was rare and remained stable during follow-up. CONCLUSIONS The Perceval sutureless valve resulted in low 1-year event rates in intermediate-risk patients undergoing AVR. New York Heart Association class improved in more than three-quarters of patients and remained stable. These data support the safety and efficacy to 1 year of the Perceval sutureless valve in this intermediate-risk population.

Cerebral Microembolization During Aortic Valve Replacement Using Minimally Invasive or Conventional Extracorporeal Circulation: A Randomized Trial.

To compare intraoperative cerebral microembolic load between minimally invasive extracorporeal circulation (MiECC) and conventional extracorporeal circulation (CECC) during isolated surgical aortic valve replacement (SAVR), we conducted a randomized trial in patients undergoing primary elective SAVR at a tertiary referral hospital. The primary outcome was the procedural phase-related rate of high-intensity transient signals (HITS) on transcranial Doppler ultrasound. HITS rate was used as a surrogate of cerebral microembolism in pre-defined procedural phases in SAVR using MiECC or CECC with (+F) or without (-F) an oxygenator with integrated arterial filter. Forty-eight patients were randomized in a 1:1 ratio to MiECC or CECC. Due to intraprocedural Doppler signal loss (n = 3), 45 patients were included in final analysis. MiECC perfusion regimen showed a significantly increased HITS rate compared to CECC (by a factor of 1.75; 95% confidence interval, 1.19-2.56). This was due to different HITS rates in procedural phases from aortic cross-clamping until declamping [phase 4] (P = 0.01), and from aortic declamping until stop of extracorporeal perfusion [phase 5] (P = 0.05). Post hoc analysis revealed that MiECC-F generated a higher HITS rate than CECC+F (P = 0.005), CECC-F (P = 0.05) in phase 4, and CECC-F (P = 0.03) in phase 5, respectively. In open-heart surgery, MiECC is not superior to CECC with regard to gaseous cerebral microembolism. When using MiECC for SAVR, the use of oxygenators with integrated arterial line filter appears highly advisable. Only with this precaution, MiECC confers a cerebral microembolic load comparable to CECC during this type of open heart surgery.

Méthode bayésienne de détection de rupture et/ou de tendance pour des données temporelles

Ce mémoire a pour but de déterminer des nouvelles méthodes de détection de rupture et/ou de tendance. Après une brève introduction théorique sur les splines, plusieurs méthodes de détection de rupture existant déjà dans la littérature seront présentées. Puis, de nouvelles méthodes de détection de rupture qui utilisent les splines et la statistique bayésienne seront présentées. De plus, afin de bien comprendre d’où provient la méthode utilisant la statistique bayésienne, une introduction sur la théorie bayésienne sera présentée. À l’aide de simulations, nous effectuerons une comparaison de la puissance de toutes ces méthodes. Toujours en utilisant des simulations, une analyse plus en profondeur de la nouvelle méthode la plus efficace sera effectuée. Ensuite, celle-ci sera appliquée sur des données réelles. Une brève conclusion fera une récapitulation de ce mémoire.