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  • 1
    ISSN: 1573-4838
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Tissue reactions to rat lead samples, modelling for clinically used leads, were investigated in a late infection model, in which injection of bacteria was performed after a 3-week encapsulation process. At the site of injection, detachment of the original fibrous capsule, wound fluid infiltration, fibrin formation and granulocyte and macrophage infiltrations, occurred. Spreading of infection did not occur via the generally assumed direct bacterial adhesion to materials, but through blood vessels at the outside of capsules and through wound fluid passage at the interface and in the lumen of the lead sample. At day 5, infection had spread all over, but, apart from two small abscesses, seemed to be suppressed at day 10. However, probably due to luminal bacterial growth, at weeks 3 and 6 the reaction intensified showing larger abscesses with accumulations of lymphocytes. The results of this study represent a good basis for further studies aimed at developing infection-resistent lead material. Research efforts are first directed on modification of material surfaces to provide controlled release of antimicrobial agents.
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  • 2
    ISSN: 1573-4838
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: One of the major clinical complications in the biomedical application of synthetic materials is the incidence of implant-associated infections. Such infections are very often induced by Staphylococcus aureus. To obtain information on tissue reactions and minimal bacterial challenge needed to create an infection related to untreated implant surfaces, we injected polyurethane tubing segments with a series of Staphylococcus aureus. The segments were subcutaneously implanted in rats. Implantation periods varied from 2, 5 and 10 days to 3 weeks. Specimen were evaluated using light and transmission electron microscopy. At least 0.25×104 of Staphylococci aureus were needed to clearly recognize that bacteria had been injected in the polyurethane tubing segments. The evidence was indirect, showing high infiltration and activation of neutrophils and macrophages, but not bacteria. Furthermore, 0.25×106 S. aureus were needed to induce a persistent specific inflammatory reaction with high concentrations of lymphocytes, i.e. mainly plasma-cells, at 3 weeks. The results indicate that this model functioned well to obtain the wanted information. Results are discussed with respect to (a-) specific inflammatory reactions occurring with (bacterial-challenged) biomaterials. Ultimately, our goal is to develop infection-resistant materials, for which the in vivo model developed may be used to qualify the processed materials
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  • 3
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: A surface modification technique was developed to achieve controlled release of gentamicin from implanted polyurethane (PU) rat lead samples. PU tubing first was provided with an acrylic acid/acrylamide copolymer surface graft and then loaded with gentamicin. This surface modification technique resulted in release of gentamicin base (GB) and was applied either to the inner luminal surface only (PU-GB-1x) or to both the inner and outer surfaces (PU-GB-2x). First we investigated whether the early tissue response was harmfully compromised when surface-modified rat lead samples were implanted without any infectious challenge. Additionally, the efficacy of this type of local gentamicin therapy was investigated by establishing its effect on tissue response and its ability to prevent lead-related infections after inoculation with Staphylococcus aureus. It was demonstrated that the applied surface modification(s) did not induce adverse effects although an increase in the infiltration of granulocytes and macrophages and an increase in the formation of wound fluid and fibrin were observed. This effect was stronger with PU-GB-2x than with PU-GB-1x. With bacterial inoculation the applied surface modification successfully suppressed the infectious challenge, PU-GB-2x more effectively than PU-GB-1x. PU-GB-2x also was more effective when compared to the gentamicin-delivery methods discussed in the first part of this two-part study, i.e., release through a vicinal gentamicin-containing collagen sponge and preoperative gentamicin solution-dipping of rat lead samples. © 1997 John Wiley & Sons, Inc.
    Additional Material: 7 Ill.
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  • 4
    ISSN: 0021-9304
    Keywords: biomaterials ; polyurethanes ; infection ; infection resistance ; surface modification ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Tissue reactions to implantable pacemaker leads were investigated in an early infection model in rabbits. Both standard leads and surface-modified leads were used. The surface modification technique was applied to achieve controlled release of the antibiotic gentamicin. The insulating polyurethane tubing material of the leads was provided with an acrylic acid/acrylamide copolymer surface graft and then loaded with gentamicin. Implantation periods varied from day 4, to week 3½, to week 10. We investigated tissue reactions in the absence of an infectious challenge and also the efficacy of surface-modified leads in preventing infection after challenge with Staphylococcus aureus was evaluated. It was demonstrated that the applied surface modification did not induce adverse effects although during early postimplantation an increase in infiltration of granulocytes and macrophages and wound fluid and fibrin deposition were observed. After bacterial challenge, standard leads were heavily infected at each explantation period, denoted by abscesses, cellular debris, and bacterial colonies. In contrast, little or no infection was observed, either macroscopically or by bacterial cultures, with the surface-modified leads. Microscopy showed little evidence of the bacterial challenge, and that primarily at day 4. It was concluded that the applied surface modification demonstrated enhanced infection resistance and thus represents a sound approach to the battle against infectious complications with biomaterials. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 41, 142-153, 1998.
    Additional Material: 12 Ill.
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  • 5
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Polyacrylamide-grafted polyetherurethane sheets were modified by end-point and multipoint attachment of heparin. The surface-bound heparin was firmly attached. No release of heparin activity could be detected when the surface was rinsed at a wall shear rate of 2000 s-1. Uptake of antithrombin and thrombin inactivation were investigated under well-defined flow conditions by the use of a spinning device with an attached disk-shaped heparinized surface. It is demonstrated that the rate of thrombin inactivation at the antithrombin-heparin surface equals the maximal rate of transport of thrombin toward the surface when the surface coverage of antithrombin exceeds 10 pmol/cm2. This result indicates that a higher intrinsic catalytic efficiency of a surface does not necessarily result in a higher antithrombin activity. We varied the heparin content of the surfaces between 0 and 35 μg/cm2 by increasing the number of functional groups to which heparin could be covalently attached. The uptake of antithrombin increased with the heparin content of the surface, but the stoichiometry decreased from 2 to 0.5 pmol antithrombin/μg heparin. Apparently, antithrombin could not bind to heparins buried in the poly(acrylamide) layer. The rate of thrombin inactivation at surfaces with low heparin content (2 μg/cm2) fells below the transport limit of thrombin and became proportional with the heparin content of the surface. Although the contribution of surface-bound heparin to the neutralization of fluidphase thrombin was found to be negligible compared with the effect of fluid-phase antithrombin at physiologic relevant concentrations, these heparinized surfaces markedly delayed the onset of thrombin generation in platelet-rich plasma. It is concluded that the inhibition of locally produced thrombin might contribute to the thromboresistance of the heparinized surface. © 1995 John Wiley & Sons, Inc.
    Additional Material: 8 Ill.
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  • 6
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The effect of local gentamicin release through a vicinal collagen sponge or through preoperative solution-dipping of rat lead samples was investigated in an early-infection model. The efficacy of these methods and their effect on tissue response were determined. It was demonstrated that both methods of local gentamicin release suppress lead-related infectious complications as compared to the control lead, which showed a high presence of inflamed/infected tissues and bacterial growth at each explantation time point. The first day the vicinal collagen sponge was more effective in suppressing the infection than was the solution-dipped lead, probably because there is a faster and higher dose release of gentamicin from the sponge. However, continued implantation time revealed that gentamicin release from the solution-dipped lead was more effective than the sponge. This supports our hypothesis that the presence of lumina are decisive for bacterial growth and persistence of implant-related infections. © 1997 John Wiley & Sons, Inc.
    Additional Material: 7 Ill.
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