Neoangiogenesis drives the replacement of mineralised cartilage by trabecular bone during bone growth regulated by molecules like e.g. VEGF, OPG and RANKL. The Heparan sulfate proteoglycan Syndecan-1 (Sdc1) plays a role in the interaction of osteoclasts and osteoblasts and the development of blood vessels. We expected Sdc1 to have an influence on bone structure and vessel development. Therefore, bone structure and angiogenesis at the growth plate in mice was compared and the influence of Syndecan-1 deficiency was characterised. Animals: Femura of male and female C57BL/6 WT (5♀, 6♂) and Sdc1-/- (9♀, 5♂) mice were used for native bone analysis at 4 month age. Histology: Bone structure was analysed using microCT scans with a resolution of 9µm. Vascularisation was visualised using an anti-Endomucin antibody in 80µm thick cryosections. In vitro angiogenesis: Bone marrow isolates were used to generate endothelial progenitor cells by sequential cultivation on fibronectin. Microvessel development was analysed 4h after plating on matrigel. Bone structure in male Sdc1 deficient mice was significantly reduced compare to male WT, whereas female mice of both genotypes did not differ. Sdc1 deficient mice at the age of 4 month showed a high decrease in the number of vessel bulbs at the chondro-osseous border (growth plate) compared to WT mice. However, no sex related differences were shown. Quantification of microvessel outgrowth of endothelial cells revealed a decreased amount of sprouting, but increased length of microvessels of Sdc1-/- cells compared to WT. Syndecan-1 has a significant impact on neoangiogenesis at the chondro-osseous border of the native bone, but the impact of Syndecan-1 deficiency on the loss of bone structure was significantly higher in male mice. This emphasises the importance to further characterise the function of Syndecan-1 regulated processes during enchondral ossification in a sex dependent manner.
The purpose of this study is to report our experience with revision of total elbow arthroplasty by exchange cementation. Between 1982 and 2004 at our institution, forty six elbows were treated with exchange cementation of a total elbow arthroplasty into the existing cement mantle or debrided bone interface, without the use of an osteotomy, bone graft or prosthetic augmentation. Indications for the procedure were aseptic loosening (17), second stage after septic loosening (14), instability (7), prosthetic fracture (4), periprosthetic fracture (2), failed hemiarthroplasty (1) and ulnar component wear (1). Both components were exchanged in 18 elbows, the humerus alone in 25 and the ulna in 3. Mean follow up was 90.5 months (10 to 266 months);18 patients had died with the prosthesis in situ. Complications were noted in 22 elbows; periprosthetic fracture of ulna (6) and humerus (2), humeral component fracture (1), aseptic loosening (4), non-union (1), heterotrophic ossification (2), soft tissue contracture (2) and soft tissue failure (2), delayed wound healing (1) and bushing failure (1). Reoperation was required in 10 elbows for revision of both components (2), ulna (3), humerus (1), bushing revision (2), soft tissue debridement (1) and soft tissue repair (1). There were no septic recurrences in previously infected elbows; however the reoperation rate in this group was 29% versus 19% after re-cementation for other causes. Revision of total elbow arthroplasty by exchange cementation is a reasonable treatment for those elbows with adequate bone stock for secure prosthetic fixation; however careful consideration should be given to augmentation of the ulna due to the high rate of periprosthetic fracture in this series. Re-cementation following débridement for infection is effective despite having a higher rate of revision operation compared to re-cementation in the aseptic elbow.
Leucocytes represent a very important host defence against a number of invading pathogens and neoplasia. However, the activity of phagocytic leucocytes has been heavily implicated in the development of ischaemia-reperfusion injury, and as an aetiological factor in the pathology of other clinically important inflammatory conditions. Ischaemia-reperfusion injury occurs in diseases such as stroke and ischaemic heart disease (IHD), and during surgical procedures such as orthopaedic surgery. Investigations presented here employed a model of tourniquet-induced forearm ischaemia-reperfusion injury to investigate the effect on leucocyte adhesion and trapping (n=20). Neutrophil and monocyte leucocyte subpopulations were isolated by density gradient centrifugation techniques. Neutrophil and monocyte cell surface expression of the adhesion molecule CD11b was measured by labelling with fluorescent anti-CD11b monoclonal antibody via flow cytometry. Plasma concentrations of the soluble intercellular adhesion molecule-1 (sICAM-1) and soluble L-selectin (sL-selectin) adhesion molecules were measured using commercially available ELISA kits. Leucocyte trapping was investigated by measuring the concentration of leukocytes in venous blood leaving the arm. During ischaemia-reperfusion there was an increase in CD11b expression on neutrophils (p=0.040) and monocytes (p=0.049), a decrease in sL-selectin (p=0.387) and sICAM-1 (p=0.089) concentrations, and a decrease in peripheral blood leucocyte concentration (p=0.019). Evidence of increased leucocyte adhesion and trapping during ischaemia-reperfusion injury was supported by an increase in CD11b cell surface expression of neutrophils and monocytes. CD11b is expressed on phagocytic leucocytes and binds to ICAM-1 expressed on the surface of vascular endothelium. This increased expression of CD11b on leucocytes may therefore play a central role as the mechanism by which leucocyte trapping in the microcirculation occurs. The measured decrease in plasma concentration of sICAM-1 and sL-selectin suggests that these adhesion molecules retain their functional activity, and may bind to their corresponding cell surface ligands. It is therefore reasonable to believe that ICAM-1 expressed on the endothelium and L-selectin expressed on leucocytes is also binding to their corresponding cell surface ligands. A decrease in the number of leucocytes in the peripheral circulation may be due to increased trapping of leucocytes in the microcirculation. When leucocytes become trapped their concentration in blood leaving the microcirculation decreases, resulting in the measured decrease in leucocyte concentration. In conclusion, this study confirms the important role of leucocytes during ischaemia-reperfusion injury, which could allow for the possibility of future research that may provide therapeutic intervention for inflammatory conditions.