| 1. |
- Di Gennaro, Antonio, et al.
(författare)
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Increased expression of leukotriene C-4 synthase and predominant formation of cysteinyl-leukotrienes in human abdominal aortic aneurysm
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:49, s. 21093-21097
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Tidskriftsartikel (refereegranskat)abstract
- Leukotrienes (LTs) are arachidonic acid-derived lipid mediators involved in the pathogenesis and progression of diverse inflammatory disorders. The cysteinyl-leukotrienes LTC4, LTD4, and LTE4 are important mediators of asthma, and LTB4 has recently been implicated in atherosclerosis. Here we report that mRNA levels for the three key enzymes/proteins in the biosynthesis of cysteinyl-leukotrienes, 5-lipoxygenase (5-LO), 5-LO-activating protein (FLAP), and LTC4 synthase (LTC4S), are significantly increased in the wall of human abdominal aortic aneurysms (AAAs). In contrast, mRNA levels of LTA(4) hydrolase, the enzyme responsible for the biosynthesis of LTB4, are not increased. Immunohistochemical staining of AAA wall revealed focal expression of 5-LO, FLAP, and LTC4S proteins in the media and adventitia, localized in areas rich in inflammatory cells, including macrophages, neutrophils, and mast cells. Human AAA wall tissue converts arachidonic acid and the unstable epoxide LTA(4) into significant amounts of cysteinyl-leukotrienes and to a lesser extent LTB4. Furthermore, challenge of AAA wall tissue with exogenous LTD4 increases the release of matrix metalloproteinase (MMP) 2 and 9, and selective inhibition of the CysLT1 receptor by montelukast blocks this effect. The increased expression of LTC4S, together with the predominant formation of cysteinyl-leukotrienes and effects on MMPs production, suggests a mechanism by which LTs may promote matrix degradation in the AAA wall and identify the components of the cysteinyl-leukotriene pathway as potential targets for prevention and treatment of AAA.
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| 2. |
- Bergqvist, David, et al.
(författare)
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Klinisk värdering av kritisk ischemi skall alltid göras före amputation
- 1999
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 96:7, s. 727-729
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Patients with critical limb ischemia (rest pain and/or ulcer/gangrene, together with low ankle pressure) are at risk of amputation, and should therefore undergo arterial reconstruction if that is at all technically possible. Thorough clinical investigation will usually distinguish patients in need of further evaluation by a vascular surgeon. No amputation should be undertaken without such evaluation. Diabetic patients belong to a special category, in that neuropathy makes it difficult to evaluate pain, and ankle pressure is often falsely high due to medial arterios sclerosis.
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| 3. |
- Biasetti, Jacopo, et al.
(författare)
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An Integrated Fluid-Chemical Model Toward Modeling the Formation of Intra-Luminal Thrombus in Abdominal Aortic Aneurysms
- 2012
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 3:266
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Tidskriftsartikel (refereegranskat)abstract
- Abdominal Aortic Aneurysms (AAAs) are frequently characterized by the presence of an Intra-Luminal Thrombus (ILT) known to influence their evolution biochemically and biomechanically. The ILT progression mechanism is still unclear and little is known regarding the impact of the chemical species transported by blood flow on this mechanism. Chemical agonists and antagonists of platelets activation, aggregation, and adhesion and the proteins involved in the coagulation cascade (CC) may play an important role in ILT development. Starting from this assumption, the evolution of chemical species involved in the CC, their relation to coherent vortical structures (VSs) and their possible effect on ILT evolution have been studied. To this end a fluid-chemical model that simulates the CC through a series of convection-diffusion-reaction (CDR) equations has been developed. The model involves plasma-phase and surface-bound enzymes and zymogens, and includes both plasma-phase and membrane-phase reactions. Blood is modeled as a non-Newtonian incompressible fluid. VSs convect thrombin in the domain and lead to the high concentration observed in the distal portion of the AAA. This finding is in line with the clinical observations showing that the thickest ILT is usually seen in the distal AAA region. The proposed model, due to its ability to couple the fluid and chemical domains, provides an integrated mechanochemical picture that potentially could help unveil mechanisms of ILT formation and development.
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| 4. |
- Folkesson, Maggie, et al.
(författare)
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Proteolytically active ADAM10 and ADAM17 carried on membrane microvesicles in human abdominal aortic aneurysms
- 2015
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Ingår i: Thrombosis and Haemostasis. - : SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN. - 0340-6245 .- 2567-689X. ; 114:6, s. 1165-1174
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Tidskriftsartikel (refereegranskat)abstract
- The intraluminal thrombus (ILT) of human abdominal aortic aneurysm (AAA) has been suggested to damage the underlying aortic wall, but previous work found scant activity of soluble proteases in the abluminal layer of the ILT, adjacent to the aneurysm. We hypothesised that transmembrane proteases carried by membrane microvesicles (MV) from dying cells remain active in the abluminal ILT. ILTs and AAA segments collected from 21 patients during surgical repair were assayed for two major transmembrane proteases, ADAM10 (a disintegrin and metalloprotease-10) and ADAM17. We also exposed cultured cells to tobacco smoke and assessed ADAM10 and ADAM17 expression and release on MVs. Immunohistochemistry showed abundant ADAM10 and ADAM17 protein in the ILT and underlying aneurysmal aorta. Domain-specific antibodies indicated both transmembrane and shed ADAM17. Importantly, ADAM10 and ADAM 17 in the abluminal ILT were enzymatically active. Electron microscopy of abluminal ILT and aortic wall showed MVs with ADAM10 and ADAM17. By flow cytometry, ADAM-positive microvesicles from abluminal ILT carried the neutrophil marker CD66, but not the platelet marker CD61. Cultured HL60 neutrophils exposed to tobacco smoke extract showed increased ADAM10 and ADAM17 content, cleavage of these molecules into active forms, and release of MVs carrying mature ADAM10 and detectable ADAM17. In conclusion, our results implicate persistent, enzymatically active ADAMs on MVs in the abluminal ILT, adjacent to the aneurysmal wall. The production of ADAM10- and ADAM17-positive MVs from smoke-exposed neutrophils provides a novel molecular mechanism for the vastly accelerated risk of AAA in smokers.
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| 5. |
- Forsell, Caroline, et al.
(författare)
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The Quasi-Static Failure Properties of the Abdominal Aortic Aneurysm Wall Estimated by a Mixed Experimental-Numerical Approach
- 2012
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Ingår i: Annals of Biomedical Engineering. - : Springer-Verlag New York. - 0090-6964 .- 1573-9686. ; 41:7, s. 1554-1566
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Tidskriftsartikel (refereegranskat)abstract
- Assessing the risk for abdominal aortic aneurysm (AAA) rupture is critical in the management of aneurysm patients and an individual assessment is possible with the biomechanical rupture risk assessment. Such an assessment could potentially be improved by a constitutive AAA wall model that accounts for irreversible damage-related deformations. Because of that the present study estimated the elastic and inelastic properties of the AAA wall through a mixed experimental-numerical approach. Specifically, finite element (FE) models of bone-shaped tensile specimens were used to merge data from failure testing of the AAA wall with their measured collagen orientation distribution. A histo-mechanical constitutive model for collagen fibers was employed, where plastic fibril sliding determined not only remaining deformations but also weakening of the fiber. The developed FE models were able to replicate the experimentally recorded load-displacement property of all 16 AAA wall specimens that were investigated in the study. Tensile testing in longitudinal direction of the AAA defined a Cauchy strength of 569(SD 411) kPa that was reached at a stretch of 1.436(SD 0.118). The stiffness and strength of specimens decreased with the wall thickness and were elevated (p = 0.018; p = 0.030) in patients with chronic obstructive pulmonary disease (COPD). Smoking affected the tissue parameters that were related to the irreversible deformation response, and no correlation with gender and age was found. The observed effects on the biomechanical properties of the AAA wall could have long-term consequences for the management of aneurysm patients, i.e., specifically they might influence future AAA rupture risk assessments. However, in order to design appropriate clinical validation studies our findings should firstly be verified in a larger patient cohort.
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| 6. |
- Gasser, T. Christian, et al.
(författare)
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Collagen fiber orientation in Abdominal Aortic Aneurysms wall
- 2010
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Konferensbidrag (refereegranskat)abstract
- Introduction Collagen is the most abundant protein in mammals and gives mechanical strength, stiffness and toughness to biological tissues like skin, tendon, bone, and vasculature [1]. Collagen fibrils of about 0.1 micrometers in diameters are the basic building blocks of fibrous collagenous tissues and their organization into suprafibrilar structures determines the tissue’s macroscopic mechanical properties. For example, detailed data regarding the organization of strong bundles of collagen might be critical to predict the onset of tissue failure, as it is clinically motivated by a rupture risk assessment of Abdominal Aortic Aneurysm (AAA). Previously proposed structural constitutive models for soft biological tissues [2, 3] integrated information regarding the collagen orientation, and regardless of their popularity, the requested microstructural information is not yet available in the open literature. Method and Materials The present study investigated the collagen formation in 12 AAA wall specimens stemming from 9 patients and harvested during elective aneurysm repair at Karolinska University Hospital, Stockholm, Sweden. Specimens of about 1.0 x 1.0 centimeter were squeezed between Plexiglas plates and fixated in formaldehyde for 24 hours. Fixated specimens were dehydrated and embedded in paraffin (Tissue Tek VIP 3000, Sakura)and sliced at a thickness of 7.0 micrometers (HM 360, Microm). To reinforce the birefringend properties of collagen the slices were stained with Picrus Sirius red before three-dimensional collagen fiber orientations were identified in a polarized light microscope (BX 50, Olympus) equipped with an Universal Rotary Stage (Zeiss). Specifically, the collagen orientations were measured at 36 points at each slice, where three slices across the thickness of the AAA wall were considered. The derived structural information was included in two different structural constitutive models and reported macroscopic mechanical data [4] was used to estimate mechanical parameters of the constitutive formulations. Results and Conclusions Collagen fiber orientation in the AAA wall is considerably spread out and no difference amongst medial and adventitial layers could be identified; a result in line with the layered structure of, e.g., cerebral aneurysms [5] but in clear contrast to the structural differences amongst the layers of normal arteries [6]. Collagen fibers in the AAA wall are predominantly aligned in circumferential direction, which might explain its higher stiffness along that direction [4]. Naturally, the complex collagen formation cannot be captured by a single (or two) families of collagen fibers and associated constitutive models are not applicable. Collagen turnover is thought to be mediated by the local stress or strain state [7] and the supra-physiological stresses in the AAA wall might cause the identified pathological collagen orientation. References [1] P. Fratzl, editor. Springer-Verlag, New York, 2008. [2] T. C. Gasser, et. al. J. R. Soc. Interface, 3:15–35, 2006. [3] S. Federico and T. C. Gasser. J. R.Soc. Interface, 2009. [4] J. P. Vande Geest et al.. J Biomech. 39, 1324--1334, 2006. [5] P. B. Canham, et al.. Neurological Res., 21, 618--626, 1999. [6] P. B. Canham, et al. Cardiovasc. Res. 23, 973-982, 1989. [7] J. D. Humphrey, Springer-Verlag, New York, 2002.
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| 7. |
- Gasser, T. Christian, et al.
(författare)
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Spatial orientation of collagen fibers in the abdominal aortic aneurysm's wall and its relation to wall mechanics
- 2012
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 8:8, s. 3091-3103
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Tidskriftsartikel (refereegranskat)abstract
- Collagen is the most abundant protein in mammals and provides the abdominal aortic aneurysm (AAA) wall with mechanical strength, stiffness and toughness. Specifically, the spatial orientation of collagen fibers in the wall has a major impact on its mechanical properties. Apart from valuable microhistological information, this data can be integrated by histomechanical constitutive models thought to improve biomechanical simulations, i.e. to improve the biomechanical rupture risk assessment of AAAs. Tissue samples (n = 24) from the AAA wall were harvested during elective AAA repair, fixated, embedded, sectioned and investigated by polarized light microscopy. The birefringent properties of collagen were reinforced by picrosirius red staining and the three-dimensional collagen fiber orientations were identified with a universal rotary stage. Two constitutive models for collagen fibers were used to integrate the identified structural information in a macroscopic AAA wall model. The collagen fiber orientation in the AM wall was widely dispersed and could be captured by a Bingham distribution function (kappa(1) = 11.6, kappa(2) = 9.7). The dispersion was much larger in the tangential plane than in the cross-sectional plane, and no significant difference between the medial and adventitial layers could be identified. The layered directional organization of collagen in normal aortas was not evident in the AAA. The collagen organization identified, combined with constitutive descriptions of collagen fibers that depend on its orientation, explain the anisotropic (orthotropic) mechanical properties of the AAA wall. The mechanical properties of collagen fibers depend largely on their undulation, which is an important structural parameter that requires further experimental investigation.
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| 8. |
- Giampaolo, Martufi, et al.
(författare)
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Abdominal Aortic Aneurysm development over time : Experimental evidence and constitutive modeling
- 2010
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Ingår i: Proceedings of the 6th World Congress of Biomechanics. - : Springer. - 9783642145148
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Konferensbidrag (refereegranskat)abstract
- Abdominal Aortic Aneurysms (AAAs) are defined as a localized permanent dilatation of the infrarenal aorta at least 50 % of its normal diameter. AAAs are frequently diagnosed in the elderly male population and evaluating rupture risk is critically important as aneurysm rupture carries high mortality rates. Growth predictors might be helpful to assess AAA rupture risk and could therefore give a better graded indication for elective repair in order to reduce related mortality without unnecessarily increasing the rate of interventions. Factors associated with AAA growth are still limited but there are some evidence that higher initial AAA diameter is related to faster AAA expansion [1]. The initial dilatation is dependent on elastin degradation, but strength of the AAA is maintained by increased production of collagen. It has been suggested that rupture occurs when collagen production is insufficient to counteract load-bearing at high pressure [2]. AAA growth quantification 30 patients with infrarenal AAAs were included in this study. Criteria for inclusion were 1-year follow-up and availability of at least two high-resolution Computer Tomography-Angiography (CTA) scans. Consequently, 60 CT-A scans were systematically segmented, reconstructed and analyzed (A4research, VASCOPS GmbH), in order to investigate geometrical and mechanical factors likely to be correlated with AAA growth. Derived results were analyzed with an especially developed (automatic) analyzing schema (MatLab, The MathWorks), and the derived information aims at guiding the development of an analytical growth model for AAAs. Constitutive Modeling Collagen is a structural protein responsible for the mechanical strength, stiffness and toughness of biological tissues like skin, tendon, bone, cornea, lung and vasculature. In the present study we considered the enlargement of the aneurysm as a consequence of a pathological degradation and synthesis of collagen, i.e. malfunction of collagen turn-over. Consequently, the vascular wall is modeled by an (inert) matrix material representing the elastin, which is reinforced by a dynamic structure of bundles of collagen. Specifically, collagen is formed by a continuous stress-mediated process and deposited in the current configuration [3] and removed by a constant degradation rate. Finally the micro-plane concept [4] is used for the Finite Element implementation [5] of the constitutive model. Results and conclusions The quantitative description of AAA growth by examining patient follow-up data revealed novel insights into the natural history of this disease. Most interestingly not all portions of the AAA seem to enlarge, some might be stable or even shrink over time; a feature that has not yet been considered by models reported in the literature. The model proposed within this study has a strong biological motivation and captures saline feature of AAA growth. Besides that, the micro-plane approach allows a straight forward FE implementation and preliminary results indicate its numerical robustness. References [1] F.J.V. Schlösser, et al., J Vasc Surg, 47:1127–1133 2008. [2] E. Choke, et al., Eur.j.Vasc.endovasc.surg, 30(3):227-44 2005. [3] J.D.Humphrey, J Biomech Eng, 121:591–597 1999. [4] Z.P. Bazant and P.C. Prat, J Eng Mech, 113(7) 1050-1064 1987. [5] S. Federico and T.C Gasser, J R Soc Interface (in press)
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| 9. |
- Hirschberg, Daniel, et al.
(författare)
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Identification of endothelial proteins by MALDI-MS using a compact disc microfluidic system.
- 2004
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Ingår i: The Protein Journal. - 1572-3887 .- 1875-8355. ; 23:4
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial proteins have been analyzed using two-dimensional (2D) gel electrophoresis and subsequent mass spectrometry, with separate methods for the intervening sample preparations. Compact disc (CD) technology was found to be rapid, giving high overall yield both with ordinary Coomassie staining and with Sypro Ruby staining. Combined with automatic in-gel digestion, the CD technology has great capacity for large numbers of protein analysis, although for limited sample numbers, manual methods can give similar sequence coverage. In a test set of 48 samples, 45 proteins were identified using the CD preparation technique, 32 identified with higher sequence coverage using the CD technique, 7 with higher using ZipTips in a robotic workstation, and 5 with higher coverage using dried droplets of unpurified samples. In the process of these methodological comparisons, basic patterns for 116 endothelial proteins were defined, representing 297 separate protein spots on the 2D gels.
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| 10. |
- Johnell, Matilda, 1961-
(författare)
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Monocytes, Tissue Factor and Heparin-coated Surfaces : Clinical and Experimental Studies
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiopulmonary bypass (CPB) is associated with inflammatory response and activation of coagulation. Heparin coating of the CPB circuit is shown to improve the biocompatibility of the surface. The biological effects of a new heparin surface, the Corline Heparin Surface (CHS), prepared according to a new principle, have been studied. The CHS used during coronary artery bypass grafting with CPB in sixty patients prevented adhesion of cells to the extracorporeal device. The activation of inflammation, coagulation, and fibrinolysis was significantly reduced by the use of CHS. Both a reduced and an increased dose of systemic heparin in combination with the heparin-coated surface resulted in more activation of inflammation and coagulation. Photoelectron spectroscopy studies of the molecular structure of the CHS demonstrated that a single layer of the heparin surface, equivalent to what was used in the in vivo studies, did not completely cover the substrate surface. Additional layer of immobilized heparin has resulted in a complete coverage. We examined the biological effects, i.e. activation of inflammation and coagulation, by CHS in one and two layers in an in vitro-study. The data from this study clearly demonstrated that a uniform surface coating of the CHS results in only minor activation of coagulation, inflammation and cell activation. Monocytes do not normally express tissue factor (TF), initiator of the coagulation in vivo, but can be induced upon adhesion to artificial surfaces. TF is receptor for coagulation factor VIIa (FVIIa) and binding subsequently leads to formation of thrombin. Other biological effects beyond coagulation, as inflammation and angiogenesis, has recently been associated with the formation of TF·FVIIa. The TF∙FVIIa signal transduction induced an increased sensitivity to PDGF-BB-stimulated migration and an increased production of IL-8 and TNF-α in monocytes. These could be important mechanisms for continued recruitment of cells to sites of inflammation.
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| 11. |
- Larsson, Emma, et al.
(författare)
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Analysis of aortic wall stress and rupture risk in patients with abdominal aortic aneurysm with a gender perspective
- 2011
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Ingår i: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 54:2, s. 295-299
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The most commonly used predictor of rupture of an abdominal aortic aneurysm (AAA) is the diameter; however, this does not estimate the true risk for each patient. Why women with AAAs have an increased growth rate, weaker aortic wall, and increased risk for rupture is yet unclear. It is likely that geometrical and biomechanical properties contribute to found gender differences. Several studies have shown that peak wall stress (PWS) and peak wall rupture risk (PWRR), predicted by a finite element (FE) analysis of AAAs derived from computed tomography (CT), is a better predictor of rupture than maximum diameter. The purpose of this study was to investigate if women with AAAs have an increased PWS and PWRR using an FE model compared to men. Method: Fifteen men and 15 women (AAAs 4-6 cm) were included. AAA geometry was derived from CT scans, and PWS and PWRR were estimated using the FE method. Comparisons were made by t test and Mann-Whitney test. Results: Mean age (women 73 years old vs men 71 years old) and mean AAA diameter was similar (49.7 mm vs 50.1 mm) for women and men. PWS did not differ for women 184 and men 198 kPa. PWRR was 0.54 (0.28-0.85) for women and 0.43 (0.24-0.66) for men, P = .06. Conclusion: This is the first analysis of stress and strength of the aneurysm wall with a gender perspective. The reported higher rupture risk for women has previously not been tested with geometrical and biomechanical properties. PWS did not differ, but the PWRR was slightly higher in women. However, the difference did not reach statistical significance, probably due to the small sample size. In summary, the results in the present study suggest that differences in biomechanical properties could be a contributing explanation for the higher rupture risk reported for female patients with AAAs. (J Vase Surg 2011;54:295-9.)
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| 12. |
- Malmstedt, Jonas, et al.
(författare)
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Outcome after leg bypass surgery for critical limb ischemia is poor in patients with diabetes
- 2008
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Ingår i: Diabetes Care. - Alexandria, VA, United States : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 31:5, s. 887-892
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—Our aim was to assess the risk of major amputation or death after leg bypass surgery for critical limb ischemia in patients with diabetes versus those without.RESEARCH DESIGN AND METHODS—We did a population-based cohort study by linking nationwide databases in Sweden. We identified 1,840 patients in the Swedish Vascular Registry who had their first leg bypass procedure for critical lower-limb ischemia between 1 January 2001 and 31 December 2003—742 with and 1,098 without diabetes. Our primary end point was first major amputation of the limb on which bypass was done or death. Individuals were followed up until 31 December 2005 through the National Hospital Patient Registry and the Cause-of-Death Registry.RESULTS—Incidence of ipsilateral amputation or death was higher in patients with diabetes than in patients without (30.2 vs. 22 events/100 person-years; crude hazard ratio [HR] 1.32 [95% CI 1.17–1.50]). Similarly, individuals with diabetes had a shorter amputation-free survival period than individuals without (2.3 years, range 1.9–2.8 vs. 3.4 years, range 3.1–3.7). Adjustment for demographic characteristics, comorbidities, and risk factors for amputation or death did not substantially affect the risk (HR 1.46 [95% CI 1.26–1.69]). The effect was more pronounced in male (1.75 [1.47–2.08]) than in female (1.35 [1.11–1.64]) patients after adjustment for age.CONCLUSIONS—Diabetes is associated with lower amputation–free survival after leg bypass for critical limb ischemia. Patients with diabetes and limb ischemia need intensified treatment of diabetes-related risk factors to improve outcome.
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| 13. |
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| 14. |
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| 15. |
- Martufi, Giampaolo, 1980-, et al.
(författare)
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Multidimensional growth measurements of abdominal aortic aneurysms
- 2013
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Ingår i: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 58:3, s. 748-755
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Tidskriftsartikel (refereegranskat)abstract
- Background: Monitoring the expansion of abdominal aortic aneurysms (AAAs) is critical to avoid aneurysm rupture in surveillance programs, for instance. However, measuring the change of the maximum diameter over time can only provide limited information about AAA expansion. Specifically, regions of fast diameter growth may be missed, axial growth cannot be quantified, and shape changes of potential interest for decisions related to endovascular aneurysm repair cannot be captured. Methods: This study used multiple centerline-based diameter measurements between the renal arteries and the aortic bifurcation to quantify AAA growth in 51 patients from computed tomography angiography (CTA) data. Criteria for inclusion were at least 1 year of patient follow-up and the availability of at least two sufficiently high-resolution CTA scans that allowed an accurate three-dimensional reconstruction. Consequently, 124 CTA scans were systematically analyzed by using A4clinics diagnostic software (VASCOPS GmbH, Graz, Austria), and aneurysm growth was monitored at 100 cross-sections perpendicular to the centerline. Results: Monitoring diameter development over the entire aneurysm revealed the sites of the fastest diameter growth, quantified the axial growth, and showed the evolution of the neck morphology over time. Monitoring the development of an aneurysm's maximum diameter or its volume over time can assess the mean diameter growth (r = 0.69, r = 0.77) but not the maximum diameter growth (r = 0.43, r = 0.34). The diameter growth measured at the site of maximum expansion was similar to 16%/y, almost four times larger than the mean diameter expansion of 4.4%/y. The sites at which the maximum diameter growth was recorded did not coincide with the position of the maximum baseline diameter (rho = 0.12; P = .31). The overall aneurysm sac length increased from 84 to 89 mm during the follow-up (P < .001), which relates to the median longitudinal growth of 3.5%/y. The neck length shortened, on average, by 6.2% per year and was accompanied by a slight increase in neck angulation. Conclusions: Neither maximum diameter nor volume measurements over time are able to measure the fastest diameter growth of the aneurysm sac. Consequently, expansion-related wall weakening might be inappropriately reflected by this type of surveillance data. In contrast, localized spots of fast diameter growth can be detected through multiple centerline-based diameter measurements over the entire aneurysm sac. This information might further reinforce the quality of aneurysm surveillance programs.
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| 16. |
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| 17. |
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| 18. |
- Swedenborg, Jesper, et al.
(författare)
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Symtomgivande karotisstenos bör opereras, inte behandlas med stent : Stent ger för stora risker, enligt studier
- 2007
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 104:6, s. 412-414
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Tidskriftsartikel (refereegranskat)abstract
- [Symptomatic carotid stenosis should be treated surgically, not with stenting. Great risks with stents, according to studies] The benefit of addition carotid endarterectomy to best medical treatment for stroke prevention has been proven for both symptomatic and asymptomatic severe carotid stenosis. During recent years endovascular treatment of carotid stenosis has grown. A meta analysis of five trials published 2005 concluded that carotid artery stenting should only be done within the framework of ongoing studies and that the evidence base was lacking to change routine treatment from carotid endarterectomy to carotid artery stenting. Recently two large studies, stent supported percutaneous angioplasty of the carotid artery versus endarterectomy (SPACE) and endarterectomy versus angioplasty in patients with symptomatic severe carotid stenosis (EVA-3S) have been published. Both studies tested the hypothesis of non-inferiority of carotid artery stenting compared to carotid endarterectomy. EVA-3S was terminated prematurely because of significantly inferior results for carotid stenting, both at 30 days and 6 months. The combined incidence of stroke or death was 9.6 % in the stented group and 3.9 in the operated group and 6.1 % and 11.7 % respectively at 6 months. All differences were highly significant. In the SPACE trial non-inferiority could not be shown. Based on intention to treat no significant difference in outcome for the primary end point, ipsilateral ischaemic stroke or death within 30 days could be shown. Analyses per protocol, however, revealed a significant difference for ipsilateral stroke at 30 days, 6.95 % versus 5.64 % in the stented and the operated group respectively. SPACE did not report any long term results. Based on available evidence it is concluded that carotid artery stenting should not be performed outside ongoing randomised trials.
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| 19. |
- Villard, Christina, et al.
(författare)
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Biomarkers for Abdominal Aortic Aneurysms From a Sex Perspective
- 2012
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Ingår i: Gender Medicine. - : Elsevier. - 1550-8579 .- 1878-7398. ; 9:4, s. 259-266
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Abdominal aortic aneurysms (AAAs) differ in men and women. Women are older at diagnosis, have a higher risk of rupture, and worse outcome after surgery compared with men. The higher occurrence of AAAs in men accounts for the dominance of men in biomarker analyses.OBJECTIVE:The primary aim of this study was to investigate levels of established biomarkers for AAA in men and women, and the secondary aim was to compare biomarker levels in women with and without AAAs.METHODS:In this prospective case-control study, blood samples were collected from 16 women and 18 men with AAAs ≥5.5 cm, from 20 women with AAAs <5.5 cm, and from 18 women with peripheral artery disease (PAD). Plasma concentrations of matrix metalloproteinase (MMP) -2, -9, and -13; tissue inhibitor of MMP-1 (TIMP-1); plasminogen activator inhibitor 1 (PAI-1); high-sensitivity C-reactive protein (hsCRP); and estradiol levels were analyzed by ELISA. An ultrasound examination was performed in women with PAD to exclude an AAA.RESULTS:Age and other comorbid conditions were similar between men and women with AAAs. Women with AAAs had higher levels of MMP-9 compared with men with equally large AAAs (42.8 ng/mL vs 36.2 ng/mL, P = 0.036) and lower levels of estradiol (30.0 pmoL vs 86.5 pmol/L, P < 0.001). Women with AAAs had lower levels of MMP-9 compared with women without (59.5 ng/mL vs 132.6 ng/mL, P = 0.010). There was no significant difference in the plasma levels of MMP-2, MMP-13, hsCRP, PAI-1, TIMP-1, and estradiol between women with and without AAAs.CONCLUSION:The higher levels of MMP-9 in women compared with men with equally large AAAs could suggest that MMP-9 is a biomarker related to the sex differences in aneurysm development. The lower levels of estradiol in women with AAAs compared with men suggest that the possible protective effect of endogenous estrogen cannot be explained by a difference in circulating levels of estradiol.
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| 20. |
- Wanhainen, Anders, 1966-
(författare)
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Abdominal Aortic Aneurysm : Experience from a Screening Study in Northern Sweden
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abdominal aortic aneurysm (AAA) is a common problem with life-threatening consequences and was suspected to be a serious health problem in Norsjö, a municipality in northern Sweden. A screening study was undertaken to investigate the prevalence, risk factors associated with AAA and the effect of screening on quality of life (QoL). All men and women, aged 65-75 years, were invited to an ultrasonography (US) examination, 91% attended and 92 subjects were also evaluated with computed tomography (CT).Depending on diagnostic criteria, the AAA prevalence was 3.6-16.9% in men and 0.8-9.4% in women. Seventy-five percent of the differences between US- and CT anteroposterior measurements were less than 5 mm. A decrease in mental health was observed among AAA patients with low baseline SF-36 scale scores. Elevated cholesterol at age 60 years were associated with screening detected AAA after 12 years of follow-up. Smoking, atherosclerosis and having a first degree relative with AAA were associated with AAA at screening. Compared to blood samples obtained 12 years prior to screening an elevation of hsCRP over time was observed among AAA patients. Based on a systematic review of the literature, different screening strategies were analysed in a Markov cohort model. The cost per life year gained ranged from $8 309 to $14 084 and was estimated to $10 474 when 65 year old men were screened once.Conclusions: The highest prevalence of AAA ever reported, in a population-based screening program, was found in Norsjö. The risk of having an AAA at screening showed a strong but complex association with atherosclerosis and its risk factors, genetic and inflammatory mechanisms may also be important. Screening 65-year-old men for AAA may be cost-effective, but QoL aspects on the cost-effectiveness of AAA screening merits further investigation.
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