Bacterial colonization and infection of electrophysiological cardiac devices detected with sonication and swab culture.

BACKGROUND: Electrophysiological cardiac devices are increasingly used. The frequency of subclinical infection is unknown. We investigated all explanted devices using sonication, a method for detection of microbial biofilms on foreign bodies. METHODS AND RESULTS: Consecutive patients in whom cardiac pacemakers and implantable cardioverter/defibrillators were removed at our institution between October 2007 and December 2008 were prospectively included. Devices (generator and/or leads) were aseptically removed and sonicated, and the resulting sonication fluid was cultured. In parallel, conventional swabs of the generator pouch were performed. A total of 121 removed devices (68 pacemakers, 53 implantable cardioverter/defibrillators) were included. The reasons for removal were insufficient battery charge (n=102), device upgrading (n=9), device dysfunction (n=4), or infection (n=6). In 115 episodes (95%) without clinical evidence of infection, 44 (38%) grew bacteria in sonication fluid, including Propionibacterium acnes (n=27), coagulase-negative staphylococci (n=11), Gram-positive anaerobe cocci (n=3), Gram-positive anaerobe rods (n=1), Gram-negative rods (n=1), and mixed bacteria (n=1). In 21 of 44 sonication-positive episodes, bacterial counts were significant (>or=10 colony-forming units/mL of sonication fluid). In 26 sterilized controls, sonication cultures remained negative in 25 cases (96%). In 112 cases without clinical infection, conventional swab cultures were performed: 30 cultures (27%) were positive, and 18 (60%) were concordant with sonication fluid cultures. Six devices and leads were removed because of infection, growing Staphylococcus aureus, Streptococcus mitis, and coagulase-negative staphylococci in 6 sonication fluid cultures and 4 conventional swab cultures. CONCLUSIONS: Bacteria can colonize cardiac electrophysiological devices without clinical signs of infection.

Geostatistical determination of heavy-metal distribution in a contaminated site - A case study

A two stage sampling strategy is necessary in order to optimize the study of distribution of pollution in soils and groundwater. First, detailed sampling from a limited area coupled with statistical analysis of the data are used to determine the microvariability of the parameter(s). The results from this detailed analysis are then used to calculate the optimal spacing between samples for the larger scale study. This two stage sampling strategy can result in significant financial savings during subsequent soil or groundwater remediation. This combined sampling and statistical analysis approach is illustrated with an example from a heavy metal contaminated site.

Assessment of the occurrence of nanoparticles in Swiss industry and evaluation of the appropriatenesss of the measurement devices to determine the workforce exposure

Abstract : The occupational health risk involved with handling nanoparticles is the probability that a worker will experience an adverse health effect: this is calculated as a function of the worker's exposure relative to the potential biological hazard of the material. Addressing the risks of nanoparticles requires therefore knowledge on occupational exposure and the release of nanoparticles into the environment as well as toxicological data. However, information on exposure is currently not systematically collected; therefore this risk assessment lacks quantitative data. This thesis aimed at, first creating the fundamental data necessary for a quantitative assessment and, second, evaluating methods to measure the occupational nanoparticle exposure. The first goal was to determine what is being used where in Swiss industries. This was followed by an evaluation of the adequacy of existing measurement methods to assess workplace nanopaiticle exposure to complex size distributions and concentration gradients. The study was conceived as a series of methodological evaluations aimed at better understanding nanoparticle measurement devices and methods. lt focused on inhalation exposure to airborne particles, as respiration is considered to be the most important entrance pathway for nanoparticles in the body in terms of risk. The targeted survey (pilot study) was conducted as a feasibility study for a later nationwide survey on the handling of nanoparticles and the applications of specific protection means in industry. The study consisted of targeted phone interviews with health and safety officers of Swiss companies that were believed to use or produce nanoparticles. This was followed by a representative survey on the level of nanoparticle usage in Switzerland. lt was designed based on the results of the pilot study. The study was conducted among a representative selection of clients of the Swiss National Accident Insurance Fund (SUVA), covering about 85% of Swiss production companies. The third part of this thesis focused on the methods to measure nanoparticles. Several pre- studies were conducted studying the limits of commonly used measurement devices in the presence of nanoparticle agglomerates, This focus was chosen, because several discussions with users and producers of the measurement devices raised questions about their accuracy measuring nanoparticle agglomerates and because, at the same time, the two survey studies revealed that such powders are frequently used in industry. The first preparatory experiment focused on the accuracy of the scanning mobility particle sizer (SMPS), which showed an improbable size distribution when measuring powders of nanoparticle agglomerates. Furthermore, the thesis includes a series of smaller experiments that took a closer look at problems encountered with other measurement devices in the presence of nanoparticle agglomerates: condensation particle counters (CPC), portable aerosol spectrometer (PAS) a device to estimate the aerodynamic diameter, as well as diffusion size classifiers. Some initial feasibility tests for the efficiency of filter based sampling and subsequent counting of carbon nanotubes (CNT) were conducted last. The pilot study provided a detailed picture of the types and amounts of nanoparticles used and the knowledge of the health and safety experts in the companies. Considerable maximal quantities (> l'000 kg/year per company) of Ag, Al-Ox, Fe-Ox, SiO2, TiO2, and ZnO (mainly first generation particles) were declared by the contacted Swiss companies, The median quantity of handled nanoparticles, however, was 100 kg/year. The representative survey was conducted by contacting by post mail a representative selection of l '626 SUVA-clients (Swiss Accident Insurance Fund). It allowed estimation of the number of companies and workers dealing with nanoparticles in Switzerland. The extrapolation from the surveyed companies to all companies of the Swiss production sector suggested that l'309 workers (95%-confidence interval l'073 to l'545) of the Swiss production sector are potentially exposed to nanoparticles in 586 companies (145 to l'027). These numbers correspond to 0.08% (0.06% to 0.09%) of all workers and to 0.6% (0.2% to 1.1%) of companies in the Swiss production sector. To measure airborne concentrations of sub micrometre-sized particles, a few well known methods exist. However, it was unclear how well the different instruments perform in the presence of the often quite large agglomerates of nanostructured materials. The evaluation of devices and methods focused on nanoparticle agglomerate powders. lt allowed the identification of the following potential sources of inaccurate measurements at workplaces with considerable high concentrations of airborne agglomerates: - A standard SMPS showed bi-modal particle size distributions when measuring large nanoparticle agglomerates. - Differences in the range of a factor of a thousand were shown between diffusion size classifiers and CPC/SMPS. - The comparison between CPC/SMPS and portable aerosol Spectrometer (PAS) was much better, but depending on the concentration, size or type of the powders measured, the differences were still of a high order of magnitude - Specific difficulties and uncertainties in the assessment of workplaces were identified: the background particles can interact with particles created by a process, which make the handling of background concentration difficult. - Electric motors produce high numbers of nanoparticles and confound the measurement of the process-related exposure. Conclusion: The surveys showed that nanoparticles applications exist in many industrial sectors in Switzerland and that some companies already use high quantities of them. The representative survey demonstrated a low prevalence of nanoparticle usage in most branches of the Swiss industry and led to the conclusion that the introduction of applications using nanoparticles (especially outside industrial chemistry) is only beginning. Even though the number of potentially exposed workers was reportedly rather small, it nevertheless underscores the need for exposure assessments. Understanding exposure and how to measure it correctly is very important because the potential health effects of nanornaterials are not yet fully understood. The evaluation showed that many devices and methods of measuring nanoparticles need to be validated for nanoparticles agglomerates before large exposure assessment studies can begin. Zusammenfassung : Das Gesundheitsrisiko von Nanopartikel am Arbeitsplatz ist die Wahrscheinlichkeit dass ein Arbeitnehmer einen möglichen Gesundheitsschaden erleidet wenn er diesem Stoff ausgesetzt ist: sie wird gewöhnlich als Produkt von Schaden mal Exposition gerechnet. Für eine gründliche Abklärung möglicher Risiken von Nanomaterialien müssen also auf der einen Seite Informationen über die Freisetzung von solchen Materialien in die Umwelt vorhanden sein und auf der anderen Seite solche über die Exposition von Arbeitnehmenden. Viele dieser Informationen werden heute noch nicht systematisch gesarnmelt und felilen daher für Risikoanalysen, Die Doktorarbeit hatte als Ziel, die Grundlagen zu schaffen für eine quantitative Schatzung der Exposition gegenüber Nanopartikel am Arbeitsplatz und die Methoden zu evaluieren die zur Messung einer solchen Exposition nötig sind. Die Studie sollte untersuchen, in welchem Ausmass Nanopartikel bereits in der Schweizer Industrie eingesetzt werden, wie viele Arbeitnehrner damit potentiel] in Kontakt komrrien ob die Messtechnologie für die nötigen Arbeitsplatzbelastungsmessungen bereits genügt, Die Studie folcussierte dabei auf Exposition gegenüber luftgetragenen Partikel, weil die Atmung als Haupteintrittspforte iïlr Partikel in den Körper angesehen wird. Die Doktorarbeit besteht baut auf drei Phasen auf eine qualitative Umfrage (Pilotstudie), eine repräsentative, schweizerische Umfrage und mehrere technische Stndien welche dem spezitischen Verständnis der Mëglichkeiten und Grenzen einzelner Messgeräte und - teclmikeri dienen. Die qualitative Telephonumfrage wurde durchgeführt als Vorstudie zu einer nationalen und repräsentativen Umfrage in der Schweizer Industrie. Sie zielte auf Informationen ab zum Vorkommen von Nanopartikeln, und den angewendeten Schutzmassnahmen. Die Studie bestand aus gezielten Telefoninterviews mit Arbeit- und Gesundheitsfachpersonen von Schweizer Unternehmen. Die Untemehmen wurden aufgrund von offentlich zugànglichen lnformationen ausgewählt die darauf hinwiesen, dass sie mit Nanopartikeln umgehen. Der zweite Teil der Dolctorarbeit war die repräsentative Studie zur Evalniernng der Verbreitnng von Nanopaitikelanwendungen in der Schweizer lndustrie. Die Studie baute auf lnformationen der Pilotstudie auf und wurde mit einer repräsentativen Selektion von Firmen der Schweizerischen Unfall Versicherungsanstalt (SUVA) durchgeüihxt. Die Mehrheit der Schweizerischen Unternehmen im lndustrieselctor wurde damit abgedeckt. Der dritte Teil der Doktorarbeit fokussierte auf die Methodik zur Messung von Nanopartikeln. Mehrere Vorstudien wurden dnrchgefîihrt, um die Grenzen von oft eingesetzten Nanopartikelmessgeräten auszuloten, wenn sie grösseren Mengen von Nanopartikel Agglomeraten ausgesetzt messen sollen. Dieser F okns wurde ans zwei Gründen gewählt: weil mehrere Dislcussionen rnit Anwendem und auch dem Produzent der Messgeràte dort eine Schwachstelle vermuten liessen, welche Zweifel an der Genauigkeit der Messgeräte aufkommen liessen und weil in den zwei Umfragestudien ein häufiges Vorkommen von solchen Nanopartikel-Agglomeraten aufgezeigt wurde. i Als erstes widmete sich eine Vorstndie der Genauigkeit des Scanning Mobility Particle Sizer (SMPS). Dieses Messgerät zeigte in Präsenz von Nanopartikel Agglorneraten unsinnige bimodale Partikelgrössenverteilung an. Eine Serie von kurzen Experimenten folgte, welche sich auf andere Messgeräte und deren Probleme beim Messen von Nanopartikel-Agglomeraten konzentrierten. Der Condensation Particle Counter (CPC), der portable aerosol spectrometer (PAS), ein Gerät zur Schàtzung des aerodynamischen Durchniessers von Teilchen, sowie der Diffusion Size Classifier wurden getestet. Einige erste Machbarkeitstests zur Ermittlnng der Effizienz von tilterbasierter Messung von luftgetragenen Carbon Nanotubes (CNT) wnrden als letztes durchgeiührt. Die Pilotstudie hat ein detailliiertes Bild der Typen und Mengen von genutzten Nanopartikel in Schweizer Unternehmen geliefert, und hat den Stand des Wissens der interviewten Gesundheitsschntz und Sicherheitsfachleute aufgezeigt. Folgende Typen von Nanopaitikeln wurden von den kontaktierten Firmen als Maximalmengen angegeben (> 1'000 kg pro Jahr / Unternehrnen): Ag, Al-Ox, Fe-Ox, SiO2, TiO2, und ZnO (hauptsächlich Nanopartikel der ersten Generation). Die Quantitäten von eingesetzten Nanopartikeln waren stark verschieden mit einem ein Median von 100 kg pro Jahr. ln der quantitativen Fragebogenstudie wurden l'626 Unternehmen brieflich kontaktiert; allesamt Klienten der Schweizerischen Unfallversicherringsanstalt (SUVA). Die Resultate der Umfrage erlaubten eine Abschätzung der Anzahl von Unternehmen und Arbeiter, welche Nanopartikel in der Schweiz anwenden. Die Hochrechnung auf den Schweizer lndnstriesektor hat folgendes Bild ergeben: ln 586 Unternehmen (95% Vertrauensintervallz 145 bis 1'027 Unternehmen) sind 1'309 Arbeiter potentiell gegenüber Nanopartikel exponiert (95%-Vl: l'073 bis l'545). Diese Zahlen stehen für 0.6% der Schweizer Unternehmen (95%-Vl: 0.2% bis 1.1%) und 0.08% der Arbeiternehmerschaft (95%-V1: 0.06% bis 0.09%). Es gibt einige gut etablierte Technologien um die Luftkonzentration von Submikrometerpartikel zu messen. Es besteht jedoch Zweifel daran, inwiefern sich diese Technologien auch für die Messurrg von künstlich hergestellten Nanopartikeln verwenden lassen. Aus diesem Grund folcussierten die vorbereitenden Studien für die Arbeitsplatzbeurteilnngen auf die Messung von Pulverri, welche Nan0partike1-Agg10merate enthalten. Sie erlaubten die ldentifikation folgender rnöglicher Quellen von fehlerhaften Messungen an Arbeitsplätzen mit erhöhter Luft-K0nzentrati0n von Nanopartikel Agglomeratenz - Ein Standard SMPS zeigte eine unglaubwürdige bimodale Partikelgrössenverteilung wenn er grössere Nan0par'til<e1Agg10merate gemessen hat. - Grosse Unterschiede im Bereich von Faktor tausend wurden festgestellt zwischen einem Diffusion Size Classiîier und einigen CPC (beziehungsweise dem SMPS). - Die Unterschiede zwischen CPC/SMPS und dem PAS waren geringer, aber abhängig von Grosse oder Typ des gemessenen Pulvers waren sie dennoch in der Grössenordnung von einer guten Grössenordnung. - Spezifische Schwierigkeiten und Unsicherheiten im Bereich von Arbeitsplatzmessungen wurden identitiziert: Hintergrundpartikel können mit Partikeln interagieren die während einem Arbeitsprozess freigesetzt werden. Solche Interaktionen erschweren eine korrekte Einbettung der Hintergrunds-Partikel-Konzentration in die Messdaten. - Elektromotoren produzieren grosse Mengen von Nanopartikeln und können so die Messung der prozessbezogenen Exposition stören. Fazit: Die Umfragen zeigten, dass Nanopartikel bereits Realitàt sind in der Schweizer Industrie und dass einige Unternehmen bereits grosse Mengen davon einsetzen. Die repräsentative Umfrage hat diese explosive Nachricht jedoch etwas moderiert, indem sie aufgezeigt hat, dass die Zahl der Unternehmen in der gesamtschweizerischen Industrie relativ gering ist. In den meisten Branchen (vor allem ausserhalb der Chemischen Industrie) wurden wenig oder keine Anwendungen gefunden, was schliessen last, dass die Einführung dieser neuen Technologie erst am Anfang einer Entwicklung steht. Auch wenn die Zahl der potentiell exponierten Arbeiter immer noch relativ gering ist, so unterstreicht die Studie dennoch die Notwendigkeit von Expositionsmessungen an diesen Arbeitsplätzen. Kenntnisse um die Exposition und das Wissen, wie solche Exposition korrekt zu messen, sind sehr wichtig, vor allem weil die möglichen Auswirkungen auf die Gesundheit noch nicht völlig verstanden sind. Die Evaluation einiger Geräte und Methoden zeigte jedoch, dass hier noch Nachholbedarf herrscht. Bevor grössere Mess-Studien durgefîihrt werden können, müssen die Geräte und Methodem für den Einsatz mit Nanopartikel-Agglomeraten validiert werden.

Two-step chromatographic purification of human plasma alpha(1)-acid glycoprotein: its application to the purification of rare phenotype samples of the protein and their study by chromatography on immobilized metal chelate affinity adsorbent.

Alpha1-Acid glycoprotein (AAG) or orosomucoid was purified to homogeneity from human plasma by a separate two-step method using chromatography on immobilized Cibacron Blue F3G-A to cross-linked agarose and chromatography on hydroxyapatite. The conditions for the pre-purification of AAG by chromatography on immobilized Cibacron Blue F3G-A were first optimized using different buffer systems with different pH values. The overall yield of the combined techniques was 80% and ca. 12 mg of AAG were purified from an initial total amount of ca. 15 mg in a ca. 40 ml sample of human plasma. This method was applied to the purification of AAG samples corresponding to the three main phenotypes of the protein (FI*S/A, F1/A and S/A), from individual human plasma previously phenotyped for AAG. A study by isoelectric focusing with carrier ampholytes showed that the microheterogeneity of the purified F1*S/A, F1/A and S/A AAG samples was similar to that of AAG in the corresponding plasma, thus suggesting that no apparent desialylation of the glycoprotein occurred during the purification steps. This method was also applied to the purification of AAG samples corresponding to rare phenotypes of the protein (F1/A*AD, S/A*X0 and F1/A*C1) and the interactions of these variants with immobilized copper(II) ions were then studied at pH 7, by chromatography on an iminodiacetate Sepharose-Cu(II) gel. It was found that the different variants encoded by the first of the two genes coding for AAG in humans (i.e. the F1 and S variants) interacted non-specifically with the immobilized ligand, whereas those encoded by the second gene of AAG (i.e. the A, AD, X0 and C1 variants) strongly bound to immobilized Cu(II) ions. These results suggested that chromatography on an immobilized affinity Cu(II) adsorbent could be helpful to distinguish between the respective products of the two highly polymorphic genes which code for human AAG.

Foam pore size is a critical interface parameter of suction-based wound healing devices.

BACKGROUND: Suction-based wound healing devices with open-pore foam interfaces are widely used to treat complex tissue defects. The impact of changes in physicochemical parameters of the wound interfaces has not been investigated. METHODS: Full-thickness wounds in diabetic mice were treated with occlusive dressing or a suction device with a polyurethane foam interface varying in mean pore size diameter. Wound surface deformation on day 2 was measured on fixed tissues. Histologic cross-sections were analyzed for granulation tissue thickness (hematoxylin and eosin), myofibroblast density (α-smooth muscle actin), blood vessel density (platelet endothelial cell adhesion molecule-1), and cell proliferation (Ki67) on day 7. RESULTS: Polyurethane foam-induced wound surface deformation increased with polyurethane foam pore diameter: 15 percent (small pore size), 60 percent (medium pore size), and 150 percent (large pore size). The extent of wound strain correlated with granulation tissue thickness that increased 1.7-fold in small pore size foam-treated wounds, 2.5-fold in medium pore size foam-treated wounds, and 4.9-fold in large pore size foam-treated wounds (p < 0.05) compared with wounds treated with an occlusive dressing. All polyurethane foams increased the number of myofibroblasts over occlusive dressing, with maximal presence in large pore size foam-treated wounds compared with all other groups (p < 0.05). CONCLUSIONS: The pore size of the interface material of suction devices has a significant impact on the wound healing response. Larger pores increased wound surface strain, tissue growth, and transformation of contractile cells. Modification of the pore size is a powerful approach for meeting biological needs of specific wounds.

Polymorphisms in fibronectin binding protein A of Staphylococcus aureus are associated with infection of cardiovascular devices.

Medical implants, like cardiovascular devices, improve the quality of life for countless individuals but may become infected with bacteria like Staphylococcus aureus. Such infections take the form of a biofilm, a structured community of bacterial cells adherent to the surface of a solid substrate. Every biofilm begins with an attractive force or bond between bacterium and substratum. We used atomic force microscopy to probe experimentally forces between a fibronectin-coated surface (i.e., proxy for an implanted cardiac device) and fibronectin-binding receptors on the surface of individual living bacteria from each of 80 clinical isolates of S. aureus. These isolates originated from humans with infected cardiac devices (CDI; n = 26), uninfected cardiac devices (n = 20), and the anterior nares of asymptomatic subjects (n = 34). CDI isolates exhibited a distinct binding-force signature and had specific single amino acid polymorphisms in fibronectin-binding protein A corresponding to E652D, H782Q, and K786N. In silico molecular dynamics simulations demonstrate that residues D652, Q782, and N786 in fibronectin-binding protein A form extra hydrogen bonds with fibronectin, complementing the higher binding force and energy measured by atomic force microscopy for the CDI isolates. This study is significant, because it links pathogenic bacteria biofilms from the length scale of bonds acting across a nanometer-scale space to the clinical presentation of disease at the human dimension.

Metal concentrations in soils around the copper smelter and surrounding industrial complex of Port Kembla, NSW, Australia

Anthropogenic emissions of metals from sources such as smelters are an international problem, but there is limited published information on emissions from Australian smelters. The objective of this study was to investigate the regional distribution of heavy metals in soils in the vicinity of the industrial complex of Port Kembla, NSW, Australia, which comprises a copper smelter, steelworks and associated industries. Soil samples (n=25) were collected at the depths of 0-5 and 5-20 cm, air dried and sieved to < 2 mm. Aqua regia extractable amounts of As, Cr, Cu, Ph and Zn were analysed by inductively coupled plasma mass spectrometry (lCP-MS) and inductively coupled plasma atomic emission spectrometry (ICP-AES). Outliers were identified from background levels by statistical methods. Mean background levels at a depth of 0-5 cm were estimated at 3.2 mg/kg As, 12 mg/kg Cr, 49 mg/kg Cu, 20 mg/kg Ph and 42 mg/kg Zn. Outliers for elevated As and Cu values were mainly present within 4 km from the Port Kembla industrial complex, but high Ph at two sites and high Zn concentrations were found at six sites up to 23 km from Port Kembla. Chromium concentrations were not anomalous close to the industrial complex. There was no significant difference of metal concentrations at depths of 0-5 and 5-20 cm, except for Ph and Zn. Copper and As concentrations in the soils are probably related to the concentrations in the parent rock. From this investigation, the extent of the contamination emanating from the Port Kembla industrial complex is limited to 1-13 km, but most likely <4 km, depending on the element; the contamination at the greater distance may not originate from the industrial complex. (C) 2003 Elsevier B.V. All rights reserved.

The PEDRO (Pocketable Electronic Devices in Radiation Oncology) project: how clinical practice is changing among young radiation oncologists.

Purpose. To evaluate the impact of mobile devices and apps on the daily clinical activity of young radiation oncologists. Methods. A web-based questionnaire was sent to 382 young (≤40 years) members of the Italian Association of Radiation Oncology (AIRO). The 14 items investigated the diffusion of mobile devices (smartphones and/or tablets), their impact on daily clinical activity, and possible differences perceived by the participants over time. Results. A total of 158 questionnaires were available for statistical evaluation (response rate 41%). Up to 75% of respondents declared they used an electronic device during their clinical activity. Conversely, 82% considered the impact of smartphones/tables on daily practice low to moderate. Daily device use increased significantly from 2009 to 2012, with high daily use rates rising from 5% to 39.9%. Fulfillment of professional needs was declared by less than 42% of respondents and compliance with app indications by 32%. Almost all physicians desired in 2012 a comprehensive website concerning a variety of apps covering radiation oncologists' needs. Conclusions. Mobile devices are widely used by young Italian radiation oncologists in their daily clinical practice, while the indications so obtained are not always followed. Nevertheless, it would be important to verify the consistency of information found within apps, in order to avoid potential errors that might be detrimental to patients.

Evaluation of the toxicity of different metal compounds in the developing brain using aggregating cell cultures as a model.

To evaluate their toxicity in the developing brain, eight metal compounds, [bismuth sodium tartrate (BiNA-tartrate), CdCl(2), CoCl(2), HgCl(2), dimethyl mercury, NiCl(2), TlCl and triethyltin chloride (TET)] were tested in aggregating cell cultures of foetal rat telencephalon. The compounds were applied to the cultures continuously, either during an early developmental stage (between days 5 and 14) or during and advanced stage of maturation (between days 24 and 34). Changes in the activities of cell type-specific enzymes were used as a criterion for toxicity. A general cytotoxic effect was observed after treatment with either CdCl(2), HgCl(2) or TET at 10(-6)m, and with TlCl at 10(-5)m. Selective effects were found with BiNa-tartrate and dimethylmercury. CoCl(2) did not modify the parameters tested, whereas a stimulant effect was found with NiCl(2). The effects of several compounds were development dependent: HgCl(2), TET and TlCl were more toxic in immature cultures, whereas BiNa-tartrate, dimethylmercury and NiCl(2) were more effective in differentiated cultures.

A multimodality vascular imaging phantom with fiducial markers visible in DSA, CTA, MRA, and ultrasound.

The objective was to design a vascular phantom compatible with digital subtraction angiography, computerized tomography angiography, ultrasound and magnetic resonance angiography (MRA). Fiducial markers were implanted at precise known locations in the phantom to facilitate identification and orientation of plane views from three-dimensional (3-D) reconstructed images. A vascular conduit connected to tubing at the extremities of the phantom ran through an agar-based gel filling it. A vessel wall in latex was included around the conduit to avoid diffusion of contrast agents. Using a lost-material casting technique based on a low melting point metal, geometries of pathological vessels were modeled. During the experimental testing, fiducial markers were detectable in all modalities without distortion. No leak of gadolinium through the vascular wall was observed on MRA after 5 hours. Moreover, no significant deformation of the vascular conduit was noted during the fabrication process (confirmed by microtome slicing along the vessel). The potential use of the phantom for calibration, rescaling, and fusion of 3-D images obtained from the different modalities as well as its use for the evaluation of intra- and inter-modality comparative studies of imaging systems are discussed. In conclusion, the vascular phantom can allow accurate calibration of radiological imaging devices based on x-ray, magnetic resonance and ultrasound and quantitative comparisons of the geometric accuracy of the vessel lumen obtained with each of these methods on a given well defined 3-D geometry.

The VAD connection : connecting ventricular assist devices to the aorta in silico

Les systèmes d'assistance ventriculaire sont apparus durant la dernière décade comme une approche thérapeutique efficace du traitement de l'insuffisance cardiaque terminale, en particulier dans le contexte de manque de donneurs d'organes. Néanmoins, et ceci malgré les progrès techniques majeurs, les taux de complications restent élevés et sont en partie liés à la configuration géométrique, en particulier le site d'implantation de la cannule de sortie à l'aorte thoracique. Bien que l'anastomose à l'aorte descendante permette une chirurgie moins invasive, les bénéfices de cette technique sont toujours controversés, comparée à la méthode standard de l'aorte ascendante, en raison du risque thrombo-embolique possiblement augmenté et des modifications hémodynamiques induites au niveau de l'arc aortique. Dans ce travail, nous comparons in silico en terme de débit et pression les deux possibilités anastomotiques. Nous développons un réseau de modèles mathématiques unidimensionnels, et l'appliquons à diverses situations cliniques, pour différents stades d'insuffisance cardiaque et de vitesses de rotation de la machine. Les données initiales sont obtenues grâce à un modèle OD (c'est-à-dire qui dépend uniquement du temps mais pas de l'espace) du système cardiovasculaire comprenant une assistance circulatoire, validé avec des données cliniques. Les simulations réalisées montrent que les deux méthodes sont similaires, en terme de débit et courbes de pression, ceci pour tous les cas cliniques étudiés. Ces résultats numériques soutiennent la possibilité d'utiliser la technique d'anastomose à l'aorte thoracique descendante, permettant une chirurgie moins invasive. Sur un plan plus fondamental, le système cardiovasculaire peut être simulé par le biais de multiples modèles de niveau de complexité différents, au prix d'un coût computationnel toujours plus élevé. Nous évaluons les avantages de modèles géométriques à plusieurs échelles (uni- et tridimensionnelle) avec données provenant de patients, comparés à des modèles simplifiés. Les résultats montrent que ces modèles de dimensions hétérogènes apportent un bénéfice important en terme de ressources de calcul, tout en conservant une précision acceptable. En conclusion, ces résultats encourageant montrent la relevance des études numériques dans le domaine médical, tant sur le plan fondamental et la compréhension des mécanismes physiopathologiques, que sur le plan applicatif et le développement de nouvelles thérapeutiques.

FM127: Systemic metal ion levels in patients with modular neck total hip arthroplasties: a prospective cohort study

There is increasing evidence that modular neck stems are prone to corrosion-related complications. Recent studies showed elevated metal ions levels and occasional pseudotumor formation in patients with such implants. The purpose of this study was to compare systemic metal-ion levels in patients after primary THA with modular neck stems to those of patients after non-modular implants. To our knowledge, this is the first cohort study including a control group, THA without CoCr heads and dry-assembled neck-stem connections. Methods: 50 patients after THA at a minimum follow-up of 1 year have been selected for the study. Patients with multiple prosthesis or other implants have been deselected. All received a cementless SPS stem from Symbios (Ti6Al4V). 40 patients have the modular neck (CoCr) version and 10 a monobloc version. All bearings were either ceramic-ceramic or ceramic-polyethylene to minimize other sources of CoCr ion release. In the modular group, the neck was chosen pre-operatively based on a 3D planning, allowing for a dry assembly of the stem and neck on the back table before implantation. A plasma system coupled to mass spectrometry was used for a complete elementary quantification in blood and serum separately. Clinical outcome was measured using the Oxford Hip Score. Results : Complete data sets of 29 patients (24 in the modular neck-group (10male, mean age 63y, 35-84y) and 5 in the monobloc-group (3 male, 69 y, 51-83y) are available to date. Mean Co blood levels were .95 ug/L (.14-12.4) in the modular group vs .27 ug/L (.10-.73) in the monobloc group (p=.2). Respective values for Cr were significantly higher in the modular group (.99 g/L; range .75-1.21) compared to those in the monobloc group (.74 g/L ;.62-.86; p=.001). No significant difference was found when comparing serum levels. 5/24 patients had Co levels above 1 g/L (12/24 for Cr), which is by some considered as a relevant elevation. The maximum Co level was measured in an asymptomatic patient. The Oxford Hip Scores were similar in both groups. Conclusion: Cr levels were significantly elevated in the modular neck group compared to those in the monobloc group. 1/24 patients with a modular prosthesis exhibited Co levels, which are beyond the threshold accepted even for metal-on-metal bearing couples. These results have contributed to our decision to abandon the use of modular neck stems. Routine follow-up including annual measurements of systemic CoCr concentrations should be considered.

The role of embolic protection devices during carotid stenting prior to cardiac surgery in asymptomatic patients: Empty filters?

Objectives: The purpose of this study was to analyze the debris captured in the distal protection filters used during carotid artery stenting (CAS). Background: CAS is an option available to high-risk patients requiring revascularization. Filters are suggested for optimal stroke prevention during CAS. Methods: From May 2005 to June 2007, filters from 59 asymptomatic patients who underwent CAS were collected and sent to a specialized laboratory for light-microscope and histological analysis. Peri- and postprocedural outcomes were assessed during 1-year follow-up. Results: On the basis of biomedical imaging of the filter debris, the captured material could not be identified as embolized particles from the carotid plaque. On histological analysis the debris consisted mainly of red blood cell aggregates and/ or platelets, occasionally accompanied by granulocytes. We found no consistent histological evidence of embolized particles originating from atherosclerotic plaques. Post-procedure, three neurological events were reported: two (3.4%) transient ischemic attacks (TIA) and one (1.7%) ipsilateral minor stroke. Conclusion: The filters used during CAS in asymptomatic patients planned for cardiac surgery often remained empty. These findings may be explained by assuming that asymptomatic patients feature a different atherosclerotic plaque composition or stabilization through antiplatelet medication. Larger, randomized trials are clearly warranted, especially in the asymptomatic population. © 2012 Wiley Periodicals, Inc.