Biocompatibility of cardiovascular gene delivery catheters with adenovirus vectors: an important determinant of the efficiency of cardiovascular gene transfer.
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Gene therapy approaches hold promise for the treatment of a wide variety of cardiovascular diseases. Many strategies for cardiovascular gene therapy involve catheter-mediated vector delivery via intramyocardial injection, intracoronary infusion, or direct gene transfer into the vessel wall. Several different gene delivery catheters have been developed and utilized in preclinical and clinical studies of cardiovascular gene therapy. However, rigorous studies of the biocompatibility of these catheters with gene therapy vectors have not yet been reported. In this report, we have examined the compatibility of cardiovascular gene therapy catheters and catheter constituents with first-generation E1/E3-deleted adenovirus vectors. We show that (i) currently available catheters rapidly and efficiently inactivate adenovirus vector infectivity; (ii) this inactivation is mediated by a variety of commonly used catheter constituents including stainless steel, nitinol, and polycarbonate; (iii) catheter-mediated inactivation of adenovirus vectors can be prevented by preflushing catheters with solutions of serum albumin; and (iv) it is possible to identify a set of catheter materials that are compatible with current adenovirus vectors. These results underscore the importance of catheter/vector compatibility and suggest methods for increasing the efficiency of catheter-mediated cardiovascular gene therapy. (+info)
Surface analysis of a femoral stem after failed total hip replacement.
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We analysed the surface of a Ti alloy femoral stem in a cementless total hip replacement with early failure. A specific protocol consisting of non destructive and destructive tests was used in the evaluation of the retrieved stem. The tests confirmed that implant fretting due to bone abrasion constitutes an early phase of loosening. (+info)
Neoplastic transformation of human osteoblast cells to the tumorigenic phenotype by heavy metal-tungsten alloy particles: induction of genotoxic effects.
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Heavy metal-tungsten alloys (HMTAs) are dense heavy metal composite materials used primarily in military applications. HMTAs are composed of a mixture of tungsten (91-93%), nickel (3-5%) and either cobalt (2-4%) or iron (2-4%) particles. Like the heavy metal depleted uranium (DU), the use of HMTAs in military munitions could result in their internalization in humans. Limited data exist, however, regarding the long-term health effects of internalized HMTAs in humans. We used an immortalized, non-tumorigenic, human osteoblast-like cell line (HOS) to study the tumorigenic transforming potential of reconstituted mixtures of tungsten, nickel and cobalt (rWNiCo) and tungsten, nickel and iron (rWNiFe). We report the ability of rWNiCo and rWNiFe to transform immortalized HOS cells to the tumorigenic phenotype. These HMTA transformants are characterized by anchorage-independent growth, tumor formation in nude mice and high level expression of the K-ras oncogene. Cellular exposure to rWNiCo and rWNiFe resulted in 8.90 +/- 0.93- and 9.50 +/- 0.91-fold increases in transformation frequency, respectively, compared with the frequency in untreated cells. In comparison, an equivalent dose of crystalline NiS resulted in a 7.7 +/- 0.73-fold increase in transformation frequency. The inert metal tantalum oxide did not enhance HOS transformation frequency above untreated levels. The mechanism by which rWNiCo and rWNiFe induce cell transformation in vitro appears to involve, at least partially, direct damage to the genetic material, manifested as increased DNA breakage or chromosomal aberrations (i.e. micronuclei). This is the first report showing that HMTA mixtures of W, Ni and Co or Fe cause human cell transformation to the neoplastic phenotype. While additional studies are needed to determine if protracted HMTA exposure produces tumors in vivo, the implication from these in vitro results is that the risk of cancer induction from internalized HMTAs exposure may be comparable with the risk from other biologically reactive and insoluble carcinogenic heavy metal compounds (e.g. nickel subsulfide and nickel oxide). (+info)
Sealing effect of hydroxyapatite coating on peri-implant migration of particles. An experimental study in dogs.
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We have studied the beneficial effects of a hydroxyapatite (HA) coating on the prevention of the migration of wear debris along the implant-bone interface. We implanted a loaded HA-coated implant and a non-coated grit-blasted titanium alloy (Ti) implant in each distal femoral condyle of eight Labrador dogs. The test implant was surrounded by a gap communicating with the joint space and allowing access of joint fluid to the implant-bone interface. We injected polyethylene (PE) particles into the right knee three weeks after surgery and repeated this weekly for the following five weeks. The left knee received sham injections. The animals were killed eight weeks after surgery. Specimens from the implant-bone interface were examined under plain and polarised light. Only a few particles were found around HA-coated implants, but around Ti implants there was a large amount of particles. HA-coated implants had approximately 35% bone ingrowth, whereas Ti implants had virtually no bone ingrowth and were surrounded by a fibrous membrane. Our findings suggest that HA coating of implants is able to inhibit peri-implant migration of PE particles by creating a seal of tightly-bonded bone on the surface of the implant. (+info)
HLA-association in patients with intolerance to mercury and other metals in dental materials.
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A group of selected 25 patients with serious intolerance to heavy metals used for dental restoration were examined for HLA antigens. A significant increase for HLA -- B37, B47 and DR4 was found. The value of the relative risk is not significant after correction for the number of antigens tested and therefore further studies of more patients are needed. (+info)
Increased loosening of cemented straight stem prostheses made from titanium alloys. An analysis and comparison with prostheses made of cobalt-chromium-nickel alloy.
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We studied the rate of aseptic loosening of three different types of femoral stems in primary total hip replacement. After a median follow-up of 10.2 years 4/147 CoCrNi (SS77) straight stems (type M.E. Muller) were revised. After a median follow-up of 7.7 years 32/239 Ti-6A1-7Nb (SS77) were revised and after a median follow-up of 5.2 years 52/203 SLS Titanium alloy stems were revised. Whereas the first two stems are of identical design (smooth-blasted, anterior and posterior collar), the SLS stem design is different. Surgical procedure and cementing technique have remained unchanged. There is a significantly higher risk of failure for smaller titanium stem sizes and in males and patients who are physically active. This indicates that the greater elasticity of the Titanium alloy is one of the factors responsible for loosening. (+info)
Results of a cemented titanium alloy straight femoral shaft prosthesis after 10 years of follow-up.
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Two-hundred fifty implantations of a cemented femoral stem made of titanium alloy in 239 patients were followed for 9.7 years (range 8.7-10.3 years). Eighty-nine patients with 93 hips have died and two could not be located. Five hips have been revised, two for infection, one for aseptic loosening and two during revision of the cup. Three stems showed radiological loosening but have not been revised. The average hip score was 85. The results are encouraging and comparable to other cemented femoral stems. (+info)
Periprosthetic bone mineral density changes with femoral components of differing design philosophy.
(16/452)
We measured the bone mineral density in 22 patients with the cylindrical stemmed cobalt-chrome AML prosthesis (collared) and in 22 patients with the tapered stem titanium CLS prosthesis (collarless). DEXA scanning was undertaken at a mean of 40 months in the AML and 52 months in the CLS group from the time of implant insertion. In both groups the greatest mean loss of BMD was found in Gruen zone 7 and the least change in Gruen zone 5. In all zones the BMD loss was greater in the AML group but only statistically significant in zones 6 (P<0.05) and 7 (P<0.01). Although numerous factors affect BMD changes around cementless implants, this study suggests that less bone loss can be associated with the titanium CLS stem. (+info)