In vivo evaluation of edge-loading in metal-on-metal hip resurfacing patients with pseudotumours

Objectives: Pseudotumours (abnormal peri-prosthetic soft-tissue reactions) following metal-on-metal hip resurfacing arthroplasty (MoMHRA) have been associated with elevated metal ion levels, suggesting that excessive wear may occur due to edge-loading of these MoM implants. This study aimed to quantify in vivo edge-loading in MoMHRA patients with and without pseudotumours during functional activities. Methods: The duration and magnitude of edge-loading in vivo was quantified during functional activities by combining the dynamic hip joint segment contact force calculated from the three-dimensional (3D) motion analysis system with the 3D reconstruction of orientation of the acetabular component and each patient’s specific hip joint centre, based on CT scans. Results: Edge-loading in the hips with pseudotumours occurred with a four-fold increase in duration and magnitude of force compared with the hips without pseudotumours (p = 0.02). Conclusions: The study provides the first in vivo evidence to support that edge-loading is an important mechanism that leads to localised excessive wear (edge-wear), with subsequent elevation of metal ion levels in MoMHRA patients with pseudotumours

Lifetime revision risk for medial unicompartmental knee replacement is lower than expected

Purpose: Unicompartmental knee replacement (UKR) is widely considered to be a pre-total knee replacement (TKR) particularly in the young. The implication of this is that it is sensible to do a UKR, even though it will be revised at some stage, as it will delay the need for a TKR. The chance of a UKR being revised during a patient’s life time has not previously been calculated. The aim of this study was to estimate this lifetime revision risks for patients of different ages undergoing UKR. Methods: Calculations were based on data from a designer series of 1000 medial Oxford UKR with mean 10-year follow up. These UKR were implanted for the recommended indications using the recommended surgical technique. Parametric survival models were developed for patients of different ages based on observed data, and were extrapolated using a Markov model to estimate lifetime revision risk. Results: The estimated lifetime revision risk reduced with increasing age at surgery. Lifetime revision risk at age 55 was 15% (95% CI 12–19), at 65 it was 11% (8–13), at 75 it was 7% (5–9), and at 85 it was 4% (3–5). Conclusion: Provided UKR is used appropriately, the lifetime revision risk is markedly lower than expected. UKR should be considered to be a definitive knee replacement rather than a Pre-TKR even in the young. These lifetime estimates, alongside established benefits for UKR in speed of recovery, morbidity, mortality and function, can be discussed with appropriate patients when considering whether to implant a UKR or TKR. Level of Evidence:III.</p

Notices sur les collaborateurs et les collaboratrices

Periprosthetic fracture (PF) after primary total hip replacement (THR) is an uncommon but potentially devastating complication. We analysed data on 257,202 primary THRs with cemented stems and 390 linked first revisions for PF recorded in the National Joint Registry (NJR) of England and Wales to determine if cemented femoral stem brand was associated with the risk of having revision for a PF after primary THR. All cemented femoral stem brands with more than 10,000 primary operations recorded in the NJR were identified. The four most commonly used cemented femoral stems were: Exeter V40 (n=146,409), CPT (n=24,300), C-Stem (n=15,113) and Charnley (n=20,182). We compared the revision risk ratios due to PF amongst the stems using a Poisson regression model adjusting for patient factors. Compared to the Exeter V40, the age, gender and ASA grade adjusted revision rate ratio for the cemented CPT stem was 3.89 (95%CI 3.07,4.93), for the C-Stem 0.89 (95%CI 0.57,1.41) and for the Charnley stem 0.41 (95%CI 0.24,0.70). Limitations of the study include incomplete data capture, analysis of only PF requiring revision and that observation does not imply causality. Nevertheless, this study demonstrates that the choice of a cemented stem is associated with the risk of revision for PF. </p

Introduction to special section on the Phoenix Mission: Landing Site Characterization Experiments, Mission Overviews, and Expected Science

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94752/1/jgre2486.pd

Brain architecture in the terrestrial hermit crab Coenobita clypeatus (Anomura, Coenobitidae), a crustacean with a good aerial sense of smell

<p>Abstract</p> <p>Background</p> <p>During the evolutionary radiation of Crustacea, several lineages in this taxon convergently succeeded in meeting the physiological challenges connected to establishing a fully terrestrial life style. These physiological adaptations include the need for sensory organs of terrestrial species to function in air rather than in water. Previous behavioral and neuroethological studies have provided solid evidence that the land hermit crabs (Coenobitidae, Anomura) are a group of crustaceans that have evolved a good sense of aerial olfaction during the conquest of land. We wanted to study the central olfactory processing areas in the brains of these organisms and to that end analyzed the brain of <it>Coenobita clypeatus </it>(Herbst, 1791; Anomura, Coenobitidae), a fully terrestrial tropical hermit crab, by immunohistochemistry against synaptic proteins, serotonin, FMRFamide-related peptides, and glutamine synthetase.</p> <p>Results</p> <p>The primary olfactory centers in this species dominate the brain and are composed of many elongate olfactory glomeruli. The secondary olfactory centers that receive an input from olfactory projection neurons are almost equally large as the olfactory lobes and are organized into parallel neuropil lamellae. The architecture of the optic neuropils and those areas associated with antenna two suggest that <it>C. clypeatus </it>has visual and mechanosensory skills that are comparable to those of marine Crustacea.</p> <p>Conclusion</p> <p>In parallel to previous behavioral findings of a good sense of aerial olfaction in C. clypeatus, our results indicate that in fact their central olfactory pathway is most prominent, indicating that olfaction is a major sensory modality that these brains process. Interestingly, the secondary olfactory neuropils of insects, the mushroom bodies, also display a layered structure (vertical and medial lobes), superficially similar to the lamellae in the secondary olfactory centers of <it>C. clypeatus</it>. More detailed analyses with additional markers will be necessary to explore the question if these similarities have evolved convergently with the establishment of superb aerial olfactory abilities or if this design goes back to a shared principle in the common ancestor of Crustacea and Hexapoda.</p

Results from the Mars Phoenix Lander Robotic Arm experiment

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95618/1/jgre2693.pd

Pregnane X receptor (PXR) activation: A mechanism for neuroprotection in a mouse model of Niemann-Pick C disease

Niemann–Pick type C1 (NPC1) disease is a fatal neurodegenerative disease characterized by neuronal lipid storage and progressive Purkinje cell loss in the cerebellum. We investigated whether therapeutic approaches to bypass the cholesterol trafficking defect in NPC1 disease might delay disease progression in the npc1−/− mouse model. We show that the neurosteroid allopregnanolone (ALLO) and T0901317, a synthetic oxysterol ligand, act in concert to delay onset of neurological symptoms and prolong the lifespan of npc1−/− mice. ALLO and T0901317 therapy preserved Purkinje cells, suppressed cerebellar expression of microglial-associated genes and inflammatory mediators, and reduced infiltration of activated microglia in the cerebellar tissue. To establish whether the mechanism of neuroprotection in npc1−/− mice involves GABAA receptor activation, we compared treatment of natural ALLO and ent-ALLO, a stereoisomer that has identical physical properties of natural ALLO but is not a GABAA receptor agonist. ent-ALLO provided identical functional and survival benefits as natural ALLO in npc1−/− mice, strongly supporting a GABAA receptor-independent mechanism for ALLO action. On the other hand, the efficacy of ALLO, ent-ALLO, and T0901317 therapy correlated with the ability of these compounds to activate pregnane X receptor-dependent pathways in vivo. These findings suggest that treatment with pregnane X receptor ligands may be useful clinically in delaying the progressive neurodegeneration in human NPC disease