Propionibacterium acnes and Staphylococcus lugdunensis Cause Pyogenic Osteomyelitis in an Intramedullary Nail Model in Rabbits

Propionibacterium acnes and coagulase-negative staphylococci (CoNS) are opportunistic pathogens implicated in prosthetic joint and fracture fixation device-related infections. The purpose of this study was to determine whether P. acnes and the CoNS species Staphylococcus lugdunensis, isolated from an "aseptically failed" prosthetic hip joint and a united intramedullary nail-fixed tibial fracture, respectively, could cause osteomyelitis in an established implant-related osteomyelitis model in rabbits in the absence of wear debris from the implant material. The histological features of P. acnes infection in the in vivo rabbit model were consistent with localized pyogenic osteomyelitis, and a biofilm was present on all explanted intramedullary (IM) nails. The animals displayed no outward signs of infection, such as swelling, lameness, weight loss, or elevated white blood cell count. In contrast, infection with S. lugdunensis resulted in histological features consistent with both pyogenic osteomyelitis and septic arthritis, and all S. lugdunensis-infected animals displayed weight loss and an elevated white blood cell count despite biofilm detection in only two out of six rabbits. The differences in the histological and bacteriological profiles of the two species in this rabbit model of infection are reflective of their different clinical presentations: low-grade infection in the case of P. acnes and acute infection for S. lugdunensis. These results are especially important in light of the growing recognition of chronic P. acnes biofilm infections in prosthetic joint failure and nonunion of fracture fixations, which may be currently reported as "aseptic" failure. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Computer simulating a trial of a load-bearing implant: example of an intramedullary prosthesis

Computational modelling is becoming ever more important for obtaining regulatory approval for new medical devices. An accepted approach is to infer performance in a population from an analysis conducted for an idealised or ‘average’ patient; we present here a method for predicting the performance of an orthopaedic implant when released into a population—effectively simulating a clinical trial. Specifically we hypothesise that an analysis based on a method for predicting the performance in a population will lead to different conclusions than an analysis based on an idealised or ‘average’ patient. To test this hypothesis we use a finite element model of an intramedullary implant in a bone whose size and remodelling activity is different for each individual in the population. We compare the performance of a low Young’s modulus implant (View the MathML source) to one with a higher Young’s modulus (200 GPa). Cyclic loading is applied and failure is assumed when the migration of the implant relative to the bone exceeds a threshold magnitude. The analysis for an idealised of ‘average’ patient predicts that the lower modulus device survives longer whereas the analysis simulating a clinical trial predicts no statistically-significant tendency (p=0.77) for the low modulus device to perform better. It is concluded that population-based simulations of implant performance–simulating a clinical trial–present a very valuable opportunity for more realistic computational pre-clinical testing of medical devices.

Spontaneous intramedullary apoptosis is present in disorders other than myelodysplasia

Myelodysplastic syndrome (MDS) is a group of hematopoietic disorders characterized by peripheral cytopenias in the presence of normo- or hypercellular dysplastic marrow. It has been suggested that premature intramedullary apoptosis may contribute to this phenomenon. We used terminal dUTP nick-end labeling (TUNEL) of bone marrow biopsy specimens and cytocentrifuge preparations from patients with MDS and a variety of other hematopoietic disorders to determine whether there is increased intramedullary apoptosis in MDS and whether any such effect is specific to MDS. TUNEL labeling of bone marrow from 24 patients with MDS revealed significant positivity in 10 of 11 patients with refractory anemia (RA), five of seven with RA and excess of blasts (RAEB), all three patients with RAEB in transformation (RAEB-t), and all three patients with RA with ring sideroblasts (RARS). The percent of positive cells ranged from 5 to 50% but showed no apparent correlation with morphological subtype. In a series of 29 patients with acute leukemia, 17 showed significant positivity (13 of 13 with myeloid disease: three M1, seven M2, one M3, two M4; four of 16 patients with lymphoid disease: one Burkitt-type lymphoma, two null acute leukemia, and one common acute lymphoid leukemia). Intramedullary apoptosis was associated with myeloid or early committed progenitor cells and was highest in secondary acute myeloid leukemia (AML). Normal bone marrow samples from 12 individuals showed no evidence of apoptosis. Our results suggest that an increased level of intramedullary apoptosis is apparent in both patients with MDS and those with AML; those with secondary AML have the highest levels. The relative absence of such findings in lymphoid malignancy suggests that the apoptotic pathways are different in this lineage.

Short comment: To Nail a Jellyfish? Finding a progressive agenda for EU anti-discrimination law

The title of this short (about 4500 words) intervention translates to "To Nail a Jellyfish? Finding a progressive agenda for EU anti-discrimination law". I engage with those criticising EU anti-discrimination law as yet another emanation of the EU's "neo-liberal" nature which fails to establish a viable social policy regime. I criticise this in two directions. First, I take issue with the theory that anti-discrimination law and policy has to be part of social policy. Actually, the field has a mission which differs from social policy, in that it addresses disadvantage resulting from othering, combating stereotypes as well as promoting accomodation of difference. Second, I show how the critique of judicialisation of policy is not unique to anti-discrimination law and policy. The so called turn to rights based employment law has been criticised under this mantra by those who fear that collective labour law mechanisms will become less prevalent. Further, those who have engaged with anti-discrimination law for a much longer time than those criticising it have also devised means to overcome the individualistic tendencies of rights adjudication. They have (partly successfully) argued in favour of establishing equality bodies and creating positive obligations. Thus, the critique neglects the field it takes on, and does not accept the fact that anti-discrimination law and policy must be considered a field in its own right instead of the servant of social law and policy.
Now, this is more a summary than an abstract - since I realise that not everyone reads German.

Long-term bone marrow culture profiles in patients with myelodysplastic syndromes are not explicable by defective apoptosis

It has been suggested that increased intramedullary apoptosis may explain the paradox between peripheral blood cytopenias and the hyper- or normo-cellular bone marrow observed in the myelodysplastic syndromes (MDS). We wished to see if culture performance could be related to the presence of apoptotic cells in a group of patients with MDS (12 patients) and other patients with peripheral blood cytopenias (six patients) which caused diagnostic difficulty. There was no correlation between LTBMC or adherent cell growth and the presence of apoptotic cells in the original marrow sample. A variable degree of apoptosis was observed in both groups of patients. LTBMC profiles correlated well with diagnosis but were unrelated to the extent of intramedullary apoptosis. This suggests that apoptosis is a much more ubiquitous process in disease than previously thought. (C) 1998 Elsevier Science Ltd. All rights reserved.