716 research outputs found

    Evaluation of the vascular response of a novel fibrin-based coating for an intracranial stent in a rabbit model

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    Hintergrund Aufgrund der FĂ€higkeit den intra-aneurysmalen Blutfluss zu reduzieren und das TrĂ€gergefĂ€ĂŸ durch Ausbildung einer Neointima zu rekonstruieren besitzen Flow Diverter insbesondere in der Behandlung breitbasiger oder fusiformer intrakranieller Aneurysmen einen großen therapeutischen Stellenwert. Trotz kontinuierlicher Entwicklungen der Materialien ist der Einsatz von Flow Divertern in seltenen FĂ€llen mit schwerwiegenden Komplikationen wie thromboembolischen Ereignissen oder In-Stent-Stenosen verbunden, wodurch der langfristige Einsatz einer dualen PlĂ€ttchenhemmung notwendig ist. In dieser Studie testeten wir eine neuartige OberflĂ€chenbeschichtung auf Fibrinbasis, welche in Voruntersuchungen in vitro eine Reduktion der ThrombogenitĂ€t zeigte. Hierzu wurde im Kaninchenmodell die GefĂ€ĂŸreaktion eines beschichteten Flow Diverter (Derivo HealÂź) mit einem unbeschichteten Flow Diverter (Derivo bare) unter dualer PlĂ€ttchenhemmung verglichen. Methoden Es erfolgte die Implantation von insgesamt 30 Flow-Divertern in 10 Kaninchen. 10 Derivo bare und 10 Derivo HealÂź wurden in die Arteriae carotides communes implantiert. Bei jedem Kaninchen wurde randomisiert und verblindet jeweils ein Derivo HealÂź in die eine Arteria carotis communis und ein Derivo bare in die andere Arteria carotis communis implantiert. ZusĂ€tzlich wurde entweder ein Derivo bare (n = 5) oder ein Derivo HealÂź (n = 5) in die Aorta abdominalis eines jeden Tieres zur ÜberprĂŒfung der DurchgĂ€ngigkeit von SeitenĂ€sten implantiert. Die Explantation der Devices erfolgte nach 28 Tagen zur histologischen Untersuchung. Angiographie erfolgte unmittelbar nach Flow Diverter-Implantation sowie nach 28 Tagen. Ergebnisse Ein Kaninchen verstarb aufgrund einer verlĂ€ngerten Narkose nach Flow Diverter-Implantation und wurde von der histologischen und angiographischen Untersuchung ausgeschlossen. Bei einem weiteren Kaninchen kam es in der Arteria carotis communis rechts zu einem „Fischmaul-Effekt“ am proximalen Derivo bare mit GefĂ€ĂŸverschluss nach 28 Tagen. Die beiden Arteriae carotides communes wurden bei diesem Kaninchen von der histologischen Untersuchung ausgeschlossen. Alle Devices zeigten eine vollstĂ€ndige Endothelialisierung. Es ergab sich kein signifikanter Unterschied in der Neointimadicke zwischen Derivo bare und Derivo HealÂź. FĂŒr Derivo HealÂź wurde eine signifikant niedrigere Anzahl an Makrophagen in der GefĂ€ĂŸwand der Arteria carotis communis (p = 0,02) und eine signifikant niedrigere Anzahl an Fibrin-/Thrombozytenablagerungen auf der Flow Diverter-OberflĂ€che in der Aorta abdominalis (p = 0,03) beobachtet. Schlussfolgerung In diesem Kaninchenmodell zeigte die neuartige Beschichtung auf Fibrinbasis im Vergleich zu dem nicht beschichteten Flow Diverter eine vergleichbare Blut- und GewebevertrĂ€glichkeit unter dualer PlĂ€ttchenhemmung.Background Due to their ability to reduce intra-aneurysmal blood flow and reconstruct the parent vessel by forming a neointima, flow diverters have great therapeutic value, especially in the treatment of broad-based or fusiform intracranial aneurysms. Despite continuous developments in materials, the use of flow diverters is associated with serious complications such as thromboembolic events or in-stent stenosis in rare cases, which necessitates the long-term use of dual antiplatelet therapy. In this study, we tested a novel fibrin-based surface coating that demonstrated a reduction in thrombogenicity in preliminary in vitro studies. For this purpose, the vascular response of a coated flow diverter (Derivo HealÂź) was compared with an uncoated flow diverter (Derivo bare) under dual antiplatelet therapy in a rabbit model. Methods A total of 30 flow-diverters were implanted in 10 rabbits. 10 Derivo bare and 10 Derivo HealÂź were implanted into the common carotid arteries. In each rabbit, a Derivo HealÂź was implanted in one common carotid artery and a Derivo bare in the other common carotid artery in a randomized, blinded fashion. In addition, either a Derivo bare (n = 5) or a Derivo HealÂź (n = 5) was implanted into the abdominal aorta of each animal to check side branches for patency. Devices were explanted after 28 days for histological examination. Angiography was performed immediately after flow diverter implantation and after 28 days. Results One rabbit died due to prolonged narcosis after flow diverter implantation and was excluded from histological and angiographic examination. In another rabbit, fish-mouthing occurred in the right common carotid artery at the proximal Derivo bare with vessel occlusion after 28 days. Both common carotid arteries were excluded from histological examination in this rabbit. All devices showed complete endothelialization. There was no significant difference in neointima thickness between Derivo bare and Derivo HealÂź. For Derivo HealÂź, a significantly lower number of macrophages was observed in the vessel wall of the common carotid artery (p = 0.02) and a significantly lower number of fibrin/platelet deposits on the flow diverter surface in the abdominal aorta (p = 0.03). Conclusion In this rabbit model, the novel fibrin-based coating showed comparable blood and tissue compatibility under dual antiplatelet therapy compared to the uncoated flow diverter

    Safety of Catheter Embolization of Pulmonary Arteriovenous Malformations—Evaluation of Possible Cerebrovascular Embolism after Catheter Embolization of Pulmonary Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia/Osler Disease by Pre- and Post-Interventional DWI

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    Background. This paper aimed to prospectively evaluate the safety of embolization therapy of pulmonary arteriovenous malformations (PAVMs) for the detection of cerebral infarctions by preand post-interventional MRI. Method One hundred and five patients (male/female = 44/61; mean age 48.6+/−15.8; range 5–86) with pre-diagnosed PAVMs on contrast-enhanced MRA underwent embolization therapy. The number of PAVMs treated in each patient ranged from 1–8 PAVMs. Depending on the size and localization of the feeding arteries, either Nester-Coils or Amplatzer vascular plugs were used for embolization therapy. cMRI was performed immediately before, and at the 4 h and 3-month post-embolization therapy. Detection of peri-interventional cerebral emboli was performed via T2w and DWI sequences using three different b-values, with calculation of ADC maps. Results Embolization did not show any post-/peri-interventional, newly developed ischemic lesions in the brain. Only one patient who underwent re-embolization and was previously treated with tungsten coils that corroded over time showed newly developed, small, diffuse emboli in the post-interventional DWI sequence. This patient already had several episodes of brain emboli before re-treatment due to the corroded coils, and during treatment, when passing the corroded coils, experienced additional small, clinically inconspicuous brain emboli. However, this complication was anticipated but accepted, since the vessel had to be occluded distally. Conclusion Catheter-based embolization of PAVMs is a safe method for treatment and does not result in clinically inconspicuous cerebral ischemia, which was not demonstrated previously

    The mutation causing the black-and-tan pigmentation phenotype of Mangalitza pigs maps to the porcine ASIP locus but does not affect its coding sequence

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    The gene for agouti signaling protein (ASIP) is centrally involved in the expression of coat color traits in animals. The Mangalitza pig breed is characterized by a black-and-tan phenotype with black dorsal pigmentation and yellow or white ventral pigmentation. We investigated a Mangalitza × PiĂ©train cross and observed a coat color segregation pattern in the F2 generation that can be explained by virtue of two alleles at the MC1R locus and two alleles at the ASIP locus. Complete linkage of the black-and-tan phenotype to microsatellite alleles at the ASIP locus on SSC 17q21 was observed. Corroborated by the knowledge of similar mouse coat color mutants, it seems therefore conceivable that the black-and-tan pigmentation of Mangalitza pigs is caused by an ASIP allele at, which is recessive to the wild-type allele A. Toward positional cloning of the at mutation, a 200-kb genomic BAC/PAC contig of this chromosomal region has been constructed and subsequently sequenced. Full-length ASIP cDNAs obtained by RACE differed in their 5â€Č untranslated regions, whereas they shared a common open reading frame. Comparative sequencing of all ASIP exons and ASIP cDNAs between Mangalitza and PiĂ©train pigs did not reveal any differences associated with the coat color phenotype. Relative qRT-PCR analyses showed different dorsoventral skin expression intensities of the five ASIP transcripts in black-and-tan Mangalitza. The at mutation is therefore probably a regulatory ASIP mutation that alters its dorsoventral expression patter

    Iatrogenic arterio-biliary fistula and peripheral hepatic artery pseudoaneurysm after transjugular liver biopsy: complication management using a microvascular plug

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    This study aimed to report on complication management in a 58-year-old woman referred for transjugular biopsy for the evaluation of unknown liver disease. After an initial uneventful biopsy procedure, the patient complained of severe upper abdominal pain. Laboratory tests revealed increasing liver enzymes. Imaging studies depicted an iatrogenic pseudoaneurysm associated with an arterio-biliary fistula originating from the right peripheral hepatic artery. Angiography and percutaneous transarterial superselective embolotherapy was performed by means of a microcatheter and microvascular plug. Precise device positioning allowed for successful closure of the bleeding site without compromising the hepatic vasculature

    Diagnostic Performance of a Lower-dose Contrast-Enhanced 4D Dynamic MR Angiography of the Lower Extremities at 3 T Using Multisegmental Time-Resolved Maximum Intensity Projections

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    Background For peripheral artery disease (PAD), MR angiography (MRA) is a well-established diagnostic modality providing morphologic and dynamic information comparable to digital subtraction angiography (DSA). However, relatively large amounts of contrast agents are necessary to achieve this. Purpose To evaluate the diagnostic accuracy of time-resolved 4D MR-angiography with interleaved stochastic trajectories (TWIST-MRA) by using maximum intensity projections (MIPs) of dynamic images acquired with reduced doses of contrast agent. Study Type Retrospective. Population Forty adult PAD patients yielding 1088 artery segments. Field Strength/Sequence A 3.0 T, time-resolved 4D MR-angiography with TWIST-MRA and MIP of dynamic images. Assessment DSA was available in 14 patients (256 artery segments) and used as reference standard. Three-segmental MIP reconstructions of TWIST-images after administration of 3 mL of gadolinium-based contrast agent (Gadoteridol/ProhanceÂź, 0.5 M) per anatomical level (pelvis, thighs, and lower legs) yielded 256 artery segments for correlation between MRA and DSA. Three independent observers rated image quality (scale: 1 [nondiagnostic] to 4 [excellent]) and the degree of venous overlay (scale: 0 [none] to 2 [significant]) for all segments. Diagnostic accuracy for the detection of >50% stenosis and artery occlusion was calculated for all observers. Statistical Tests Binary classification test (sensitivity, specificity, positive/negative predictive values, diagnostic accuracy). Intraclass correlation coefficients (ICCs), logistic regression analysis with comparison of areas under the receiver-operating-characteristics (ROC) curves (AUCs) with the DeLong method. Bland–Altman-comparison. Results High diagnostic performance was achieved for the detection of >50% stenosis (sensitivity 92.9% [84.3–99.9% (95%-CI)] and specificity 98.5% [95.7–99.8% (95%-CI)]) and artery occlusion (sensitivity 93.1% [77.2–99.2% (95%-CI)] and specificity 99.1% [96.9–99.9% (95%-CI)]). Inter-reader agreement was excellent with ICC values ranging from 0.95 to 1.0 for >50% artery stenosis and occlusion. Image quality was good to excellent for both readers (3.41 ± 0.72, 3.33 ± 0.65, and 3.38 ± 0.61 [mean ± SD]) with good correlation between observer ratings (ICC 0.71–0.81). No significant venous overlay was observed (0.06 ± 0.24, 0.23 ± 0.43 and 0.11 ± 0.45 [mean ± SD]). Data Conclusion MIPs of dynamic TWIST-MRA offer a promising diagnostic alternative necessitating only reduced amounts (50%) of gadolinium-based contrast agents for the entire runoff vasculature. Evidence Level 3 Technical Efficacy Stage

    When is Learning “Effortful”? Scrutinizing the Concept of Mental Effort in Cognitively Oriented Research from a Motivational Perspective

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    peer reviewedIn the context of instructional design and self-regulated learning research, the notion of mental effort allocation, monitoring, and control has gained increasing attention. Bringing together a cognitive perspective, focusing on Cognitive Load Theory, and a motivational perspective, merging central accounts from Situated Expectancy Value Theory and Self-Determination Theory, we plea for a three-fold conception of effort that clearly distinguishes the different psychological sources of experiencing and allocating effort in learning environments: effort-by-complexity, effort-by-need frustration, and effort-by-allocation. Such a detailed conception has important implications for how effort should be studied and how it can be influenced by instructional support or by the learning individual itself. A first conclusion we draw is that cognitively oriented research needs to be careful when taking students’ self-reports on the “effortfulness” of a task as an indication of the object-level cognitive requirements of the task, as such appraisals may also reflect the affective-emotional requirements of task execution as well as motivational beliefs regarding the likelihood of success and meaningfulness of a task. A second conclusion is that instructional procedures rooted in cognition-oriented theory ideally are complemented by motivation theory to support student learning optimally

    Alteration of the Route to Menaquinone towards Isochorismate-Derived Metabolites

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    Chorismate and isochorismate constitute branch-point intermediates in the biosynthesis of many aromatic metabolites in microorganisms and plants. To obtain unnatural compounds, we modified the route to menaquinone in Escherichia coli. We propose a model for the binding of isochorismate to the active site of MenD ((1R,2S, 5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC) synthase) that explains the outcome of the native reaction with α-ketoglutarate. We have rationally designed variants of MenD for the conversion of several isochorismate analogues. The double-variant Asn117Arg–Leu478Thr preferentially converts (5S,6S)-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHD), the hydrolysis product of isochorismate, with a >70-fold higher ratio than that for the wild type. The single-variant Arg107Ile uses (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHA) as substrate with >6-fold conversion compared to wild-type MenD. The novel compounds have been made accessible in vivo (up to 5.3 g L−1). Unexpectedly, as the identified residues such as Arg107 are highly conserved (>94 %), some of the designed variations can be found in wild-type SEPHCHC synthases from other bacteria (Arg107Lys, 0.3 %). This raises the question for the possible natural occurrence of as yet unexplored branches of the shikimate pathway.Fil: Fries, Alexander Erich. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina. Albert Ludwigs University of Freiburg; AlemaniaFil: Mazzaferro, Laura. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina. Albert Ludwigs University of Freiburg; AlemaniaFil: GrĂŒning, Björn. Albert Ludwigs University of Freiburg; AlemaniaFil: Bisel, Philippe. Albert Ludwigs University of Freiburg; AlemaniaFil: Stibal, Karin. Albert Ludwigs University of Freiburg; AlemaniaFil: Buchholz, Patrick C. F.. University of Stuttgart; AlemaniaFil: Pleiss, JĂŒrgen. UniversitĂ€t Stuttgart;Fil: Sprenger, Georg A.. UniversitĂ€t Stuttgart;Fil: MĂŒller, Michael. Albert Ludwigs University of Freiburg; Alemani
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