18 research outputs found

    Herbestemming Scheepsbouwloods

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    Transformatie van een scheepsbouwloods in Rotterdam, Heijplaat, tot een natuureducatiecentrumArchitectureArchitecture and The Built Environmen

    Perspectives of Patients and Professionals on Patient Education in Complex Endovascular Aortic Repair

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    Background: Misinterpretation of patient preferences in perioperative education can lead to an undesired treatment decision. This explorative interview study presents differences in perspectives of patients and professionals on patient education in complex endovascular aortic aneurysm management. Methods: Using convenience sampling, a cross-sectional interview study was performed among patients who were in various stages of the decision-making process for complex endovascular aortic repair. Five physicians were interviewed, representing the main providers of clinical information. Interviews were transcribed verbatim and analyzed inductively. Results: Twelve patients (mean age 76.6 [standard deviation: 6.4], 83% male) were interviewed. Ten (83%) felt like they had no other realistic option besides undergoing surgery, whereas all professionals (5/5) stressed the importance of delicate patient selection. Five patients out of 10 (50%) who commented on their preferred decisional role considered the professional's advice as decisive. All but 1 patient (11/12) reported that the information was easy to understand, whereas 4 out of 5 professionals (80%) doubted whether patients could fully comprehend everything. Patients experienced a lack of information on the recovery process, although professionals stated that this was addressed during consultation. Conclusions: Several differences were found in the perspectives of patients and professionals on education in complex aortic aneurysm management. In order to optimize patient involvement in decision-making, professionals should be aware of these possible discrepancies and address them during consultation. Future research could focus on these differences in more detail by including more patients depending on their treatment and decision stages.Industrial Design EngineeringApplied Ergonomics and Desig

    In vivo suppression of vein graft disease by nonviral, electroporation-mediated, gene transfer of tissue inhibitor of metalloproteinase-1 linked to the amino terminal fragment of urokinase (TIMP-1.ATF), a cell-surface directed matrix metalloproteinase inhibitor

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    BackgroundSmooth muscle cell (SMC) migration and proliferation are important in the development of intimal hyperplasia, the major cause of vein graft failure. Proteases of the plasminogen activator (PA) system and of the matrix metalloproteinase (MMP) system are pivotal in extracellular matrix degradation and, by that, SMC migration. Previously, we demonstrated that inhibition of both protease systems simultaneously with viral gene delivery of the hybrid protein TIMP-1.ATF, consisting of the tissue inhibitor of metalloproteinase-1 (TIMP-1) and the receptor-binding amino terminal fragment (ATF) of urokinase, reduces SMC migration and neointima formation in an in vitro restenosis model using human saphenous vein cultures more efficiently than both protease systems separately. Because use of viral gene delivery is difficult in clinical application, this study used nonviral delivery of TIMP-1.ATF plasmid to reduce vein graft disease in a murine bypass model. Nonviral gene transfer by electroporation was used to avert major disadvantages of viral gene delivery, such as immune responses and short-term expression.MethodsPlasmids encoding ATF, TIMP-1, TIMP-1.ATF, or luciferase, as a control, were injected and electroporated in both calf muscles of hypercholesterolemic apolipoprotein E3-Leiden (APOE*3Leiden) mice (n = 8). One day after electroporation, a venous interposition of a donor mouse was placed into the carotid artery of a recipient mouse. In this model, vein graft thickening develops with features of accelerated atherosclerosis. Vein grafts were harvested 4 weeks after electroporation and surgery, and histologic analysis of the vessel wall was performed.ResultsElectroporation-mediated overexpression of the plasmid vectors resulted in a prolonged expression of the transgenes and resulted in a significant reduction of vein graft thickening (ATF: 36% ± 9%, TIMP-1: 49% ± 5%, TIMP-1.ATF: 58% ± 5%; P < .025). Although all constructs reduced vein graft thickening compared with the controls, the luminal area was best preserved in the TIMP-1.ATF-treated mice.ConclusionIntramuscular electroporation of TIMP-1.ATF inhibits vein graft thickening in vein grafts in carotid arteries of hypercholesterolemic mice. Binding of TIMP-1.ATF hybrid protein to the u-PA receptor at the cell surface enhances the inhibitory effect of TIMP-1 on vein graft remodeling in vitro as well as in vivo and may be an effective strategy to prevent vein graft disease.Clinical RelevanceVenous bypass graft failure is a serious clinical problem that occurs in up to 40% to 60% of patients after bypass surgery, and reinterventions are often required both in cardiac and peripheral vascular disease. Smooth muscle cell migration and proliferation in the vessel wall, mediated by proteases of the plasminogen activator system and matrix metalloproteinase system, are important in the development of vein graft disease. Nonviral gene transfer by intramuscular electroporation of the hybrid protein TIMP-1.ATF, consisting of the tissue inhibitor of metalloproteinase-1 (TIMP-1) and the receptor-binding amino terminal fragment (ATF) of urokinase, to inhibit these proteases directly at the cell surface, suppresses the development of vein graft thickening, without the major disadvantages of viral gene delivery such as immune responses and short-term expression, and therefore may be a potential therapeutic tool to improve vein graft disease

    Short-term dexamethasone treatment inhibits vein graft thickening in hypercholesterolemic ApoE3Leiden transgenic mice

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    ObjectiveThe aim of this study was to assess whether the anti-inflammatory agent dexamethasone can inhibit vein graft thickening without the occurrence of serious side effects.MethodsVenous interposition grafting was performed in the common carotid artery of hypercholesterolemic ApoE3Leiden transgenic mice. Mice were treated with dexamethasone (0.15 mg · kg−1 · d−1 orally), and after 28 days, vein graft thickening was quantified.ResultsTreatment with dexamethasone resulted in a significant 43% reduction in lesion area without changes in lesion composition when compared with nontreated controls. However, dexamethasone, when administered for a prolonged period of time, is known for its potentially serious side effects. To overcome these potential side effects of prolonged dexamethasone treatment, the effect of a short-term 7-day dexamethasone treatment was studied. This short dexamethasone treatment resulted in a 49% decrease of vein graft thickening at 28 days. Furthermore, it was demonstrated that dexamethasone treatment led to reduced local expression of several proinflammatory cytokines and factors in the vein grafts 24 hours after surgery. Finally, observations in mice were verified in human saphenous organ cultures. Exposure to dexamethasone for either 7 or 28 days significantly reduced intimal hyperplasia formation on cultured saphenous vein segments.ConclusionsShort-term anti-inflammatory treatment with dexamethasone leads to a significant reduction in vein graft thickening over an extended period, possibly by the reduction of early expression of proinflammatory cytokines. This 7-day treatment minimizes the risk of unwanted side effects of long-term dexamethasone treatment and may be a new approach to prevent graft failure.Clinical RelevanceAortocoronary and peripheral vein grafts are known to have high failure rates (10%-40% after 1 year and 50%-60% after 10 years). As a consequence, relapse of ischemic symptoms may occur and may necessitate redo bypass surgery or (more severely) amputation. Late vein graft failure occurs as a result of the development of intimal hyperplasia and accelerated atherosclerosis, which lead to vein graft stenosis. In this study, the authors investigated the effect of short-term dexamethasone treatment on intimal hyperplasia and accelerated atherosclerosis to prevent vein graft failure

    A novel urokinase receptor-targeted inhibitor for plasmin and matrix metalloproteinases suppresses vein graft disease

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    Aims Matrix metalloproteinases (MMP) and plasminogen activator (PA)/plasmin-mediated proteolysis, especially at the cell surface, play important roles in matrix degeneration and smooth muscle cell migration, which largely contributes to vein graft failure. In this study, a novel hybrid protein was designed to inhibit both protease systems simultaneously. MMP and plasmin activity were inhibited at the cell surface by this hybrid protein, consisting of the receptor-binding amino-terminal fragment (ATF) of urokinase-type PA, linked to both the tissue inhibitor of metalloproteinases (TIMP-1) and bovine pancreas trypsin inhibitor (BPTI), a potent protease inhibitor. The effect of overexpression of this protein on vein graft disease was studied. Methods and resultsA non-viral expression vector encoding the hybrid protein TIMP-1.ATF.BPTI was constructed and validated. Next, cultured segments of human veins were transfected with this vector. Expressing TIMP-1.ATF.BPTI in vein segments resulted in a mean 36 ± 14 reduction in neointima formation after 4 weeks. In vivo inhibition of vein graft disease by TIMP-1.ATF.BPTI is demonstrated in venous interpositions placed into carotid arteries of hypercholesterolaemic APOE*3Leiden mice. After 4 weeks, vein graft thickening was significantly inhibited in mice treated with the domains TIMP-1, ATF, or BPTI (36-49 reduction). In the TIMP-1.ATF.BPTI-treated mice, vein graft thickening was reduced by 67±4, which was also significantly stronger when compared with the individual components.Conclusion These data provide evidence that cell surface-bound inhibition of the PA and MMP system by the hybrid protein TIMP-1.ATF.BPTI, overexpressed in distant tissues after electroporation-mediated non-viral gene transfer, is a powerful approach to prevent vein graft disease. © 2010 The Author

    Increased aortic exclusion in endovascular treatment of complex aortic aneurysms

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    Purpose: Perioperative risk assessments for complex aneurysms are based on the anatomical extent of the aneurysm and do not take the length of the aortic exclusion into account, as it was developed for open repair. Nevertheless, in the endovascular repair (ER) of complex aortic aneurysms, additional segments of healthy aorta are excluded compared with open repair (OR). The aim of this study was to assess differences in aortic exclusion between the ER and OR of complex aortic aneurysms, to subsequently assess the current classification for complex aneurysm repair. Methods: This retrospective observational study included patients that underwent complex endovascular aortic aneurysm repair by means of fenestrated endovascular aneurysm repair (FEVAR), fenestrated and branched EVAR (FBEVAR), or branched EVAR (BEVAR). The length of aortic exclusion and the number of patent segmental arteries were determined and compared per case in ER and hypothetical OR, using a Wilcoxon signed-rank test. Results: A total of 71 patients were included, who were treated with FEVAR (n = 44), FBEVAR (n = 8), or BEVAR (n = 19) for Crawford types I (n = 5), II (n = 7), III (n = 6), IV (n = 7), and V (n = 2) thoracoabdominal or juxtarenal (n = 44) aneurysms. There was a significant increase in the median exclusion of types I, II, III, IV, and juxtarenal aneurysms (p < 0.05) in ER, compared with hypothetical OR. The number of patent segmental arteries in the ER of type I-IV and juxtarenal aneurysms was significantly lower than in hypothetical OR (p < 0.05). Conclusion: There are significant differences in the length of aortic exclusion between ER and hypothetical OR, with the increased exclusion in ER resulting in a lower number of patent segmental arteries. The ER and OR of complex aortic aneurysms should be regarded as distinct modalities, and as each approach deserves a particular risk assessment, future efforts should focus on reporting on the extent of exclusion per treatment modality, to allow for appropriate comparison.Vascular Surger

    Experience with the GORE EXCLUDER iliac branch endoprosthesis for common iliac artery aneurysms

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    Objective: In this study, we analyzed the procedural success and early outcome of endovascular treatment of a multicenter cohort of patients with common iliac artery (CIA) aneurysms treated with the new GORE EXCLUDER (W. L. Gore & Associates, Flagstaff, Ariz) iliac branch endoprosthesis (IBE). Methods: A retrospective cohort analysis was performed in 13 sites in The Netherlands. Anatomic, demographic, procedural, and follow-up data were assessed from hospital records. Results: From November 2013 to December 2014, 51 CIA aneurysms were treated with an IBE in 46 patients. The median diameter of the treated aneurysm was 40.5 (range, 25.0-90.0) mm. The mean procedural time was 198 +/- 56 minutes. All but one implantation were successful; two type Ib endoleaks were noticed, resulting in a procedural success rate of 93.5%. The two type Ib endoleaks spontaneously disappeared at 30 days. There was no 30-day mortality. Ipsilateral buttock claudication was present in only two cases at 30 days and disappeared during follow-up. The incidence of reported erectile dysfunction was low and severe ischemic complications were absent. After a mean follow-up of 6 months, data on 17 treated aneurysms were available. Two showed a stable diameter, whereas 15 showed a mean decrease of 3.9 +/- 2.2 mm (P <.001). Reinterventions were performed in two patients (7.1%). The 6-month primary patency of the internal component of the IBE device was 94%. Conclusions: The use of the GORE EXCLUDER IBE device for CIA aneurysms is related to high procedural success, high patency rates, and low reintervention rates at short-term follow-up. Prospective data with longer follow-up are awaited to establish the role of the device in the treatment algorithm of CIA aneurysms

    Auditory and speech processing in specific language impairment (SLI) and dyslexia

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    This thesis investigates auditory and speech processing in Specific Language Impairment (SLI) and dyslexia. One influential theory of SLI and dyslexia postulates that both SLI and dyslexia stem from similar underlying sensory deficit that impacts speech perception and phonological development leading to oral language and literacy deficits. Previous studies, however, have shown that these underlying sensory deficits exist in only a subgroup of language impaired individuals, and the exact nature of these deficits is still largely unknown. The present thesis investigates three aspects of auditory-phonetic interface: 1) The weighting of acoustic cues to phonetic voicing contrast 2) the preattentive and attentive discrimination of speech and non-linguistic stimuli and 3) the formation of auditory memory traces for speech and non-linguistic stimuli in young adults with SLI and dyslexia. This thesis focuses on looking at both individial and group-level data of auditory and speech processing and their relationship with higher-level language measures. The groups of people with SLI and dyslexia who participated were aged between 14 and 25 and their performance was compared to a group of controls matched on chronological age, IQ, gender and handedness. Investigations revealed a complex pattern of behaviour. The results showed that individuals with SLI or dyslexia are not poor at discriminating sounds (whether speech or non-speech). However, in all experiments, there was more variation and more outliers in the SLI group indicating that auditory deficits may occur in a small subgroup of the SLI population. Moreover, investigations of the exact nature of the input-processing deficit revealed that some individuals with SLI have less categorical representations for speech sounds and that they weight the acoustic cues to phonemic identity differently from controls and dyslexics
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