Modular titanium alloy neck adapter failures in hip replacement - failure mode analysis and influence of implant material

<p>Abstract</p> <p>Background</p> <p>Modular neck adapters for hip arthroplasty stems allow the surgeon to modify CCD angle, offset and femoral anteversion intraoperatively. Fretting or crevice corrosion may lead to failure of such a modular device due to high loads or surface contamination inside the modular coupling. Unfortunately we have experienced such a failure of implants and now report our clinical experience with the failures in order to advance orthopaedic material research and joint replacement surgery.</p> <p>The failed neck adapters were implanted between August 2004 and November 2006 a total of about 5000 devices. After this period, the titanium neck adapters were replaced by adapters out of cobalt-chromium. Until the end of 2008 in total 1.4% (n = 68) of the implanted titanium alloy neck adapters failed with an average time of 2.0 years (0.7 to 4.0 years) postoperatively. All, but one, patients were male, their average age being 57.4 years (36 to 75 years) and the average weight 102.3 kg (75 to 130 kg). The failures of neck adapters were divided into 66% with small CCD of 130° and 60% with head lengths of L or larger. Assuming an average time to failure of 2.8 years, the cumulative failure rate was calculated with 2.4%.</p> <p>Methods</p> <p>A series of adapter failures of titanium alloy modular neck adapters in combination with a titanium alloy modular short hip stem was investigated. For patients having received this particular implant combination risk factors were identified which were associated with the occurence of implant failure. A Kaplan-Meier survival-failure-analysis was conducted. The retrieved implants were analysed using microscopic and chemical methods. Modes of failure were simulated in biomechanical tests. Comparative tests included modular neck adapters made of titanium alloy and cobalt chrome alloy material.</p> <p>Results</p> <p>Retrieval examinations and biomechanical simulation revealed that primary micromotions initiated fretting within the modular tapered neck connection. A continuous abrasion and repassivation process with a subsequent cold welding at the titanium alloy modular interface. Surface layers of 10 - 30 μm titanium oxide were observed. Surface cracks caused by fretting or fretting corrosion finally lead to fatigue fracture of the titanium alloy modular neck adapters. Neck adapters made of cobalt chrome alloy show significantly reduced micromotions especially in case of contaminated cone connection. With a cobalt-chromium neck the micromotions can be reduced by a factor of 3 compared to the titanium neck. The incidence of fretting corrosion was also substantially lower with the cobalt-chromium neck configuration.</p> <p>Conclusions</p> <p>Failure of modular titanium alloy neck adapters can be initiated by surface micromotions due to surface contamination or highly loaded implant components. In the present study, the patients at risk were men with an average weight over 100 kg. Modular cobalt chrome neck adapters provide higher safety compared to titanium alloy material.</p

The Functions of Auxilin and Rab11 in Drosophila Suggest That the Fundamental Role of Ligand Endocytosis in Notch Signaling Cells Is Not Recycling

Notch signaling requires ligand internalization by the signal sending cells. Two endocytic proteins, epsin and auxilin, are essential for ligand internalization and signaling. Epsin promotes clathrin-coated vesicle formation, and auxilin uncoats clathrin from newly internalized vesicles. Two hypotheses have been advanced to explain the requirement for ligand endocytosis. One idea is that after ligand/receptor binding, ligand endocytosis leads to receptor activation by pulling on the receptor, which either exposes a cleavage site on the extracellular domain, or dissociates two receptor subunits. Alternatively, ligand internalization prior to receptor binding, followed by trafficking through an endosomal pathway and recycling to the plasma membrane may enable ligand activation. Activation could mean ligand modification or ligand transcytosis to a membrane environment conducive to signaling. A key piece of evidence supporting the recycling model is the requirement in signaling cells for Rab11, which encodes a GTPase critical for endosomal recycling. Here, we use Drosophila Rab11 and auxilin mutants to test the ligand recycling hypothesis. First, we find that Rab11 is dispensable for several Notch signaling events in the eye disc. Second, we find that Drosophila female germline cells, the one cell type known to signal without clathrin, also do not require auxilin to signal. Third, we find that much of the requirement for auxilin in Notch signaling was bypassed by overexpression of both clathrin heavy chain and epsin. Thus, the main role of auxilin in Notch signaling is not to produce uncoated ligand-containing vesicles, but to maintain the pool of free clathrin. Taken together, these results argue strongly that at least in some cell types, the primary function of Notch ligand endocytosis is not for ligand recycling

D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients

The solute carrier SLC9C1 is a Na+/H+-exchanger gated by an S4-type voltage-sensor and cyclic-nucleotide binding

Voltage-sensing (VSD) and cyclic nucleotide-binding domains (CNBD) gate ion channels for rapid electrical signaling. By contrast, solute carriers (SLCs) that passively redistribute substrates are gated by their substrates themselves. Here, we study the orphan sperm-specific solute carriers SLC9C1 that feature a unique tripartite structure: an exchanger domain, a VSD, and a CNBD. Voltage-clamp fluorimetry shows that SLC9C1 is a genuine Na+/H+ exchanger gated by voltage. The cellular messenger cAMP shifts the voltage range of activation. Mutations in the transport domain, the VSD, or the CNBD strongly affect Na+/H+ exchange, voltage gating, or cAMP sensitivity, respectively. Our results establish SLC9C1 as a phylogenetic chimaera that combines the ion-exchange mechanism of solute carriers with the gating mechanism of ion channels. Classic SLCs slowly readjust changes in the intra-and extracellular milieu, whereas voltage gating endows the Na+/H+ exchanger with the ability to produce a rapid pH response that enables downstream signaling events