Supramacroparticulate PE in 6 different joint endoprostheses localisations: An indicator for PE damage?

In the histopathological particle algorithm polyethylene (PE) particles with maximum lengths of more than 100µm - called PE supramacroparticles - are identified exclusively for knee joint and hip prostheses. However, a definitive characterisation, detection in all joint localisations and a causal clarification of the pathogenesis are lacking. In this study a total of 175 SLIM (synovial-like interface membrane) cases with PE supramacroparticles of knee joint prostheses (n=89), hip joint prostheses (n=44), ankle joint prostheses (n=36) and prostheses in three localisations of the upper extremities (n=6) were systematically investigated. The arithmetic mean of the particle length varied greatly within the prosthesis types. This had a significant positive correlation with the prosthesis lifetime and negative correlation with the date of implantation. It can be concluded that both the lifetime and the time of implantation have an influence on the particle length. The prostheses with supramacroparticulate damage moreover showed a clearly reduced survival rate compared with other data published on the prosthesis lifetime. The material wear therefore could not be attributed solely to the usual fatigue factors. Since loosening of the prostheses, decentring of the PE components or damage to the PE inlay existed in all cases, mechanical dysloading seems to be the most probable cause of PE supramacroparticle genesis. Due to the striking length and for demarcation from PE macroparticles, the term supramacroparticulate PE is proposed for a length of more than 100µm. In the extended histopathological particle algorithm supramacroparticulate PE has been included in the macroparticles category and should be taken into account and interpreted causally in histopathological diagnostics of joint prosthesis failure.

Magnetic drug targeting in a rhabdomyosarcoma rat model using magnetite-dextran composite nanoparticle-bound mitoxantrone and 0.6 tesla extracorporeal magnets - sarcoma treatment in progress.

BACKGROUND: Magnetic drug targeting (MDT) is a new treatment principle for tumors. Passive MDT (pMDT) uses cytostatics coupled to ferromagnetic nanoparticles, whereas in active MDT (aMDT), extracorporeal magnets are additionally placed over the tumor area. PURPOSE: Mitoxantrone-magnetite-dextran composite particles were used to assess the distribution and effect of MDT. METHODS: We conducted two trials with n = 60 rats transfected with R(1)H rhabdomyosarcoma cells. In the biodistribution trial (n = 36) mitoxantrone concentrations in tumor tissue versus plasma were measured after one or two dose administration for aMDT, pMDT, and uncoupled mitoxantrone. The dose/effect trial (n = 24) assessed change in tumor volume at day 1 and 7 days after administration of 4, 6, or 8 doses of mitoxantrone using aMDT. RESULTS: Mitoxantrone-magnetite-dextran concentration in blood was significantly (p < 0.05) lower when using aMDT and as low as uncoupled mitoxantrone. Concentrations in tumor tissue were always significantly higher using MDT when compared to uncoupled mitoxantrone. Two doses resulted in drug accumulation inside the tumor. Tumor growth was significantly decreased with four doses using aMDT versus no treatment. Tumor size on day 8 versus day 1 was significantly (p < 0.05) reduced after administration of six doses of mitoxantrone-magnetite-dextran. No allergies/toxic reactions were observed. CONCLUSIONS: The MDT achieves higher levels of cytostatics in tumor tissue without increased systemic concentrations and succeeds in reducing tumor volume.