Proteoglycan 4 downregulation in a sheep meniscectomy model of early osteoarthritis

Osteoarthritis is a disease of multifactorial aetiology characterised by progressive breakdown of articular cartilage. In the early stages of the disease, changes become apparent in the superficial zone of articular cartilage, including fibrillation and fissuring. Normally, a monolayer of lubricating molecules is adsorbed on the surface of cartilage and contributes to the minimal friction and wear properties of synovial joints. Proteoglycan 4 is the lubricating glycoprotein believed to be primarily responsible for this boundary lubrication. Here we have used an established ovine meniscectomy model of osteoarthritis, in which typical degenerative changes are observed in the operated knee joints at three months after surgery, to evaluate alterations in proteoglycan 4 expression and localisation in the early phases of the disease. In normal control joints, proteoglycan 4 was immunolocalised in the superficial zone of cartilage, particularly in those regions of the knee joint covered by a meniscus. After the onset of early osteoarthritis, we demonstrated a loss of cellular proteoglycan 4 immunostaining in degenerative articular cartilage, accompanied by a significant (p < 0.01) decrease in corresponding mRNA levels. Early loss of proteoglycan 4 from the cartilage surface in association with a decrease in its expression by superficial-zone chondrocytes might have a role in the pathogenesis of osteoarthritis

Evaluating qualitative management research: towards a contingent criteriology

The term qualitative management research embraces an array of non-statistical research practices. Here it is argued that this diversity is an outcome of competing philosophical assumptions which produce distinctive research perspectives and legitimate the appropriation of different sets of evaluation criteria. Some confusion can arise when evaluation criteria constituted by particular philosophical conventions are universally applied to this heterogeneous management field. In order to avoid such misappropriation, this paper presents a first step towards a contingent criteriology located in a metatheoretical analysis of three modes of qualitative management research which are compared with the positivist mainstream to elaborate different forms of evaluation. It is argued that once armed with criteria that vary accordingly, evaluation can reflexively focus upon the extent to which any management research consistently embraces the particular methodological principles that are sanctioned by its a priori philosophical commitments

Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: Results from three randomized clinical trials, SAVE-HIP1, SAVE-HIP2 and SAVE-KNEE

Background: Semuloparin is a novel ultra-low-molecular-weight heparin under development for venous thromboembolism (VTE) prevention in patients at increased risk, such as surgical and cancer patients. Objectives: Three Phase III studies compared semuloparin and enoxaparin after major orthopedic surgery: elective knee replacement (SAVE-KNEE), elective hip replacement (SAVE-HIP1) and hip fracture surgery (SAVE-HIP2). Patients/Methods: All studies were multinational, randomized and double-blind. Semuloparin and enoxaparin were administered for 7-10days after surgery. Mandatory bilateral venography was to be performed between days 7 and 11. The primary efficacy endpoint was a composite of any deep vein thrombosis, non-fatal pulmonary embolism or all-cause death. Safety outcomes included major bleeding, clinically relevant non-major (CRNM) bleeding, and any clinically relevant bleeding (major bleeding plus CRNM). Results: In total, 1150, 2326 and 1003 patients were randomized in SAVE-KNEE, SAVE-HIP1 and SAVE-HIP2, respectively. In all studies, the incidences of the primary efficacy endpoint were numerically lower in the semuloparin group vs. the enoxaparin group, but the difference was statistically significant only in SAVE-HIP1. In SAVE-HIP1, clinically relevant bleeding and major bleeding were significantly lower in the semuloparin vs. the enoxaparin group. In SAVE-KNEE and SAVE-HIP2, clinically relevant bleeding tended to be higher in the semuloparin group, but rates of major bleeding were similar in the two groups. Other safety parameters were generally similar between treatment groups. Conclusions: Semuloparin was superior to enoxaparin for VTE prevention after hip replacement surgery, but failed to demonstrate superiority after knee replacement surgery and hip fracture surgery. Semuloparin and enoxaparin exhibited generally similar safety profiles. \ua9 2012 International Society on Thrombosis and Haemostasis