Joint replacement surgery is one of the success stories of modern medicine, restoring mobility, diminishing pain and improving the overall quality of life for millions of people. Unfortunately, wear of these prostheses over time generates debris, which activates an innate immune response that can ultimately lead to periprosthetic resorption of bone (osteolysis) and failure of the implant. Over the past decade, the biological interactions between the particulate debris from various implant materials and the immune system have begun to be better understood. The wear debris induces a multifaceted immune response encompassing the generation of reactive oxygen species and damage-associated molecular patterns, Toll-like receptor signaling and NALP3 inflammasome activation. Acting alone or in concert, these events generate chronic inflammation, periprosthetic bone loss and decreased osteointegration that ultimately leads to implant failure.

Ultra high molecular weight polyethylene is widely used as a bearing surface in prosthetic arthroplasty. Over time the generation of implant-derived wear particles can initiate an inflammatory reaction characterized by periprosthetic inflammation and ultimately bone resorption at the prosthetic bone interface. Herein we present evidence that the different sized particles as well as the different length alkane polymers generated by implant wear leads to a two component inflammatory response. Polymeric alkane structures, with side chain oxidations, directly bind and activate the TLR-1/2 signaling pathway. Whereas micron and nanometer sized particulate debris are extensively phagocyted and induce enlargement, fusion and disruption of endosomal compartments. The resulting lysosomal damage and subsequent enzymatic leakage induces the NALP3 inflammasome activation as determined by cathepsins S and B cytosolic release, Caspase 1 activation and processing of pro-IL-1β, and pro-IL-18. These two processes synergistically results in the initiation of a strong inflammatory response with consequent cellular necrosis and extra-cellular matrix degradation.

Complex cystic breast masses demonstrate both anechoic (cystic) and echogenic (solid) components at ultrasonography (US). US is used to identify and characterize such masses and to guide percutaneous biopsy. Numerous pathologic entities may produce complex cystic breast lesions or may be associated with them, and biopsy is usually indicated. Common benign findings include fibrocystic changes, intraductal or intracystic papilloma without atypia, and fibroadenoma. Common atypical findings include atypical ductal hyperplasia, atypical papilloma, atypical lobular hyperplasia, and lobular carcinoma in situ. Malignant findings include ductal carcinoma in situ, infiltrating ductal carcinoma, and infiltrating lobular carcinoma. If the biopsy approach is tailored to the individual patient and if the imaging features are closely correlated with findings at pathologic analysis, US-guided percutaneous biopsy may be used effectively to diagnose and to guide management of complex cystic masses.

SUMMARY Eight consecutive patients with CT scan evidence of a bilateral infarct in the territory of the paramedian thalamic artery are reported. In seven cases the infarct also extended to the territory of the polar artery. The main symptoms were: (1) disorder of vigilance which cleared in a few days, and hypersomnolence which lasted longer and in two patients was still present a year later; (2) amnesia, detectable clinically in four patients and only with tests in two patients, which persisted in one patient for three years; (3) changes of mood and bulimia present in five and four patients respectively; and (4) vertical gaze paresis in five patients. Only one patient died, and in the remainder the symptoms tended to subside, but none of the patients who could be followed-up for a year returned to normal behaviour. Clinical and CT scan correlations pointed to the mammillo-thalamic tract as the structure whose damage was responsible for the memory disorders.Before computed tomography (CT) infarct of the thalamus was a diagnosis that the clinician could at most suspect, when confronted with a clinical picture resembling the classical Dejerine-Roussy's syndrome,1 but not substantiate in the absence of verification by necropsy. Even more difficult and tentative was the recognition of the other topographical thalamic syndromes that had been reported.2 CT scan has greatly improved our ability to identify in vivo discrete syndromes corresponding to the involvement of the territories supplied by the thalamic arteries. Based on the anatomical description provided by Percheron3 -5 the following types have been identified:6 (1) antero-lateral infarct, associated with polar artery occlusion; (2) postero-lateral infarct, associated with geniculo-thalamic artery occlusion; (3) infero-median infarct, associated with paramedian artery occlusion; and (4) infarct involving the globus pallidus, the posterior limb of the internal capsule and the lateral thalamic nuclei, associated with anterior choroidal artery occlusion.

BackgroundWith the advancement of biomedical technology, artificial materials have been developed to replace diseased, damaged or nonfunctional body parts. Among such materials, ultra high molecular weight alkane or modified alkyl polymers have been extensively used in heart valves, stents, pacemakers, ear implants, as well as total joint replacement devices. Although much research has been undertaken to design the most non-reactive biologically inert polyethylene derivatives, strong inflammatory responses followed by rejection and failure of the implant have been noted.Methodology/Principal FindingsPurification of the alkane polymers from the site of inflammation revealed extensive “in vivo” oxidation as detected by fourier transformed infra-red spectroscopy. Herein, we report the novel observation that oxidized alkane polymers induced activation of TLR1/2 pathway as determined by ligand dependent changes in intrinsic tyrosine fluorescence intensity and NF-κΒ luciferase gene assays. Oxidized polymers were very effective in activating dendritic cells and inducing secretion of pro-inflammatory cytokines. Molecular docking of the oxidized alkanes designated ligand specificity and polymeric conformations fitting into the TLR1/2 binding grooves.Conclusion/SignificanceThis is the first report of a synthetic polymer activating immune responses through TLR binding.