Correct alignment is important for success in total knee replacement. Currently this is achieved by a combination of intramedullary and extramedullary alignment using jigs and cutting blocks. This multicentre study evaluates the use of computer assisted planning and the interactive guidance of instruments for total knee replacement. Prior to surgery computer scans of the hip, knee and ankle were performed of patients enrolled in the study. Pre operative planning of the position and size of the knee components was performed by the surgeon using a CT based Vector Vision Navigation System (Brain LAB AG, Heimstetten, Germany). P.F.C.x (De Puy Leeds UK) knee replacements were then implanted in 38 patients. Surgery was carried out according to the standard surgical technique using traditional instruments. Information of the planned and intraoperatively recorded position of the cutting blocks were analysed to check varus/valgus alignment, flexion/extension alignment, the amount of planned resection from both the femoral and tibial bones and the size of the components. Information from all the separate centres was sent to a central data processing base for analysis. Results were calculated comparing the differences between the planned and performed cuts for each of the different variables studied. Graphs demonstrate the differences in the alignment between that planned by the surgical navigation system and what was actually carried out by the instrumented cuts. Based on the data obtained from the multicentre study we have concluded that the planned position of the implants using the standard instruments was similar to that using the Vector Vision Navigation System. We believe that it is safe to proceed with surgical navigation total knee arthroplasty using the P.F.C.x total knee prosthesis with Image Guided Surgery and a further multicentre study is currently underway evaluating this.
In rheumatoid arthritis, the forefoot is frequently affected. A variety of surgical procedures have been established in the treatment of rheumatic forefoot disorders. Postoperatively, patients are mobilized in specially designed footwear to reduce forefoot stress. Our study was conducted to investigate peak and mean plantar pressure occurring in two differently designed forefoot relief shoes by using the novel pedar ® system.
Ten symptom-free volunteers were asked to walk on a treatmill, performing two trials at self-selected speed. The ”Barouk” (sole and heel supporting proximal fifty percent of the foot) and “Hannover” (Sole under whole foot, heel supporting proximal fifty percent of the foot) forefoot relief shoe (fior and gentz, Lueneburg, Germany) were compared. In a first trial, the shoe had to be used adequately, while in a second trial, the volunteers tried to put pressure on the forefoot, mimicking non-compliance. Peak and mean plantar pressure were obtained using the pedar® cable system (novel, Munich) and compared to the contralateral foot. Statistical t-test analysis was performed using SPSS 10. 0 for windows™.
When wearing the “Barouk” shoe with short sole, the forefoot was completely relieved in all trials. Non-compliant use of the shoe did not result in any forefoot stress. At the edge of the sole, peak pressure values were not higher than in conventional footwear. The shoework with complete sole reduced forefoot peak and mean pressure in contrast to normal gait by a mean of 34 percent. However, all volunteers were able to put stress on the forefoot when mimicking non-compliance, reaching peak values similar to normal gait.
With regard to reconstructive forefoot surgery, the design of forefoot relief shoework affects the safety to non-compliance.
Matrilin-3 is a member of the recently described matrilin family of extracellular matrix proteins containing von Willebrand factor A-like domains. The matrilin-3 subunit can form homotetramers as well as hetero-oligomers together with subunits of matrilin-1 (cartilage matrix protein). It has a restricted tissue distribution and is strongly expressed in growing skeletal tissues. Detailed information on expression and distribution of extracellular matrix proteins is important to understand cartilage function in health and in disease like osteoarthritis.
Matrilin-3 expression was analysed on decalcified normal cartilage/bone sections (N = 5) and decalcified cartilage/ bone sections with minor (N= 10), moderate (N = 10), and severe osteoarthritic lesions (N = 10). Osteoarthritic changes were classified histomorphologically, using the grading system of Mankin. Matrilin-3 expression was investigated by immunohistochemistry, in situ hybridization, Western blot analysis, and quantitative PCR. For immunohistochemistry, a polyclonal antibody against matrilin-3 was used. For Western blot analysis, cartilage extracts were obtained from normal and osteoarthritic samples, partially purified, and separated in SDS poly-acrylamide gelelectrophoreses. After blotting onto nitro-cellulose, matrilin-3 was visualized by incubation with the polyclonal anti-matrilin-3 antibody and chemiluminescence detection. Matrilin-3 -mRNA expression was determined by in situ hybridization using a digoxigenin-labeled anti-sense probe.
Our results indicate that matrilin-3 is a mandatory component of mature articular cartilage with its expression being restricted to chondrocytes from the tangential zone and the upper middle cartilage zone. Osteoarthritic cartilage samples with only moderate morphological osteoarthritic destructions have elevated levels of matrilin-3 mRNA. In parallel, we found an increased deposition of matrilin-3 protein in the cartilage matrix. Matrilin-3 staining was diffusely distributed in the cartilage matrix, with no cellular staining being detectable. In cartilage samples with minor osteoarthritic lesions, matrilin-3 deposition was restricted to the middle zone and to the upper deep zone. A strong correlation was found between enhanced matrilin-3 gene and protein expression and the extent of tissue damage. Sections with severe osteoarthritic destruction showed the highest amount of matrilin-3 mRNA, strong signals in in situ hybridization, and prominent protein deposition in the middle and deep cartilage zone.
We conclude that matrilin-3 is an integral component of human articular cartilage matrix and that the enhanced expression of matrilin-3 in osteoarthritis may be a cellular response to the modified microenvironment in the disease.
Thrombospondin-1 (TSP-1) a trimeric heigh-molecular weight glycoprotein is a multifunctional extra-cellular matrix protein. TSP-1 is involved in cell-matrix interactions of a various tissues. TSP-1 can bind to cells via different TSP-1 domains, its main receptors are CD 36 and CD51 (avb3-integrin). Nothern and western analysis showed the expression of TSP-1 in human cartilage, but its cellular source as well as the presence of its receptors CD36 and CD51 in normal and osteoarthritic cartilage are totally unknown.
We investigated 7 normal and 23 osteoarthritic cartilage samples on the expression patterns of TSP-1, CD36 and CD51, by immunohistochemistry and in situ hybridization.
In normal cartilage we found TSP-1 to be present in the middle and upper deep zone. Predominantly chondrocytes of the middle zone showed RNA-expression. Also, its receptor CD36 was found mainely in the chondrocytes of the superficial and middle zone. In moderate osteoarthritic cartilage we found an increased number of TSP-1 expressing chondrocytes, as well as an increased pericellular immunostainig quite near to the surface. However, a small number of CD36 positive cells were observed across the whole OA cartilage. In severe osteo-arthritic cartilage were observed a strong decrease in TSP-1 synthesizing chondrocytes by in situ hybridization as well as a strong reduction in the immunohistochemically matrix staining. In contrast to the decrease in TSP-1 we observed in 5 out of 8 these samples a overall enhanced number in CD 36 stained chondrocytes. Further, osteophytes with strong TSP-1 expression showed a large number of CD36 positive cells. However, CD51 positive chondrocytes could not be detected.
TSP-1 and its receptor are expressed in normal and osteoarthritic cartilage. The source of TSP-1 in normal cartilage are the middle zone chondrocytes, which also express the CD36-receptor. In early osteoarthritic cartilage an increase of TSP-1 was observed, whereas in later osteoarthritic cartilage TSP-1-synthesis is strongly decreased. It can be hypothesized that the strong enhanced number of CD36-stained chondrocytes in severe OA cartilage is a sign of chondrocytes frustrate efforts to contact the ECM, by binding to TSP-1.
Mechanical loading has been hypothesized to play an important role in the development, remodeling and in diseases of many skeletal tissues, including cartilage. In order to study the metabolic response of cartilage to physical forces, in vitro systems have often been used because of the precise control with which mechanical loads can be applied. We developed a new mechanical loading system, in which we were able to load the intact femoral condyle in order to preserve the native cartilage/subchondral bone structure. This system represents a more ‚in vivo‘ situation than cartilage explants or chondrocyte cell culture systems. Our approach focused on changes in mRNA expression of type II collagen, type VI collagen, and aggrecan in loaded versus adjacent unloaded cartilage in order to analyse the early response of chondrocytes to well-defined mechanical stresses.
Femoral condyles were obtained from two-year-old cows. The integrity of the cartilage surface was controlled by staining with safranin O. The femoral condyles were compressed in an Instron 8501 material testing machine. Cyclic compression pressure was applied for 2000 cycles in a sinusoidal waveform of 0. 5 Hz-frequency with a peak stress of 0. 2 to12. 5 MPa. Following loading, full depth cartilage sections were cut out and one half immediately frozen in liquid nitrogen for RNA isolation and the other half soaked in 4% paraformaldehyde for paraffin embedding. As control, the adjacent unloaded cartilage was collected and treated in the same way. Total RNA was isolated and changes in mRNA expression were quantitated by competitive quantitative PCR, using an internal standard of a C-terminal truncated version of the corresponding genes. The PCR-reactions were separated by agarose gel electrophoresis and amplified fragments quantified using video-densitometry analysis. The results were expressed as the ratio of mRNA from loaded to unloaded cartilage
Cyclic compression with peak stresses of 12. 5, 6. 3, 2. 5 and 0. 6 MPa lead to a two-fold decrease in the mRNA expression of type II collagen and aggrecan and a threefold decrease of type VI collagen, in consideration of the intra-assay variability of about 30%. Compression with peak stresses of 0. 3 and 0. 2 MPa lead to a three-fold increase of the mRNA expression of type II collagen, a four-fold increase of aggrecan and a slight decrease of type VI collagen. Low compression strength leads to an increase of the mRNA expression of the major components of cartilage, type II collagen and aggrecan, whereas high loading leads to a decrease of the mRNA expression.
The results show that our system can be used to analyze early responses of chondrocytes to well-defined mechanical stresses in an intact cartilage/bone-system and therefore will enable us to investigate the role of physiological and non-physiological high loading on the induction of cartilage degradation and regeneration in joint trauma and osteoarthritis. Since the cartilage/bone samples are incubated in medium during the experiment, this system will also offer us the opportunity to investigate additives to the medium as potential pharmacological therapeutics in osteoarthritis.
