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Contains fulltext : 35791.pdf (publisher's version ) (Closed access), Dendritic cells (DCs) are specialized APCs that can be activated upon pathogen recognition as well as recognition of endogenous ligands, which are released during inflammation and cell stress. The recognition of exogenous and endogenous ligands depends on TLRs, which are abundantly expressed in synovial tissue from rheumatoid arthritis (RA) patients. Furthermore TLR ligands are found to be present in RA serum and synovial fluid and are significantly increased, compared with serum and synovial fluid from healthy volunteers and patients with systemic sclerosis and systemic lupus erythematosus. Identification of novel endogenous TLR ligands might contribute to the elucidation of the role of TLRs in RA and other autoimmune diseases. In this study, we investigated whether five members of the small heat shock protein (HSP) family were involved in TLR4-mediated DC activation and whether these small HSPs were present in RA synovial tissue. In vitro, monocyte-derived DCs were stimulated with recombinant alphaA crystallin, alphaB crystallin, HSP20, HSPB8, and HSP27. Using flow cytometry and multiplex cytokine assays, we showed that both alphaA crystallin and HSPB8 were able to activate DCs and that this activation was TLR4 dependent. Furthermore, Western blot and immunohistochemistry showed that HSPB8 was abundantly expressed in synovial tissue from patients with RA. With these experiments, we identified sHSP alphaA crystallin and HSPB8 as two new endogenous TLR4 ligands from which HSPB8 is abundantly expressed in RA synovial tissue. These findings suggest a role for HSPB8 during the inflammatory process in autoimmune diseases such as RA.

Contains fulltext : 50182.pdf (publisher's version ) (Open Access)

Contains fulltext : 50741.pdf (publisher's version ) (Open Access), BACKGROUND: Bone defects after failed total hip arthroplasty can be reconstructed with impacted morselized bone grafts and a cemented cup. On the acetabular side, the effects on initial cup stability of washing bone grafts prior to impaction and bone graft size remain unclear. Related to these variables, cement penetration and inter-particle shear resistance have been suggested to be critical factors to ensure initial cup stability. METHODS: Using a synthetic acetabular model, we studied the effects of (1) washing bone grafts prior to impaction, and (2) bone graft size on the initial stability of cemented cups. In addition, cement penetration was measured using CT scans. RESULTS: Reconstructions with large, washed bone grafts provided the highest stability during mechanical compression and in a lever-out situation. Washing of the bone grafts had a positive effect on initial cup stability, but the size of the bone grafts appeared to be more important. Cement penetration was affected by bone graft size but not by washing. INTERPRETATION: From a mechanical standpoint, large bone grafts that have been washed prior to impaction may be preferable in order to obtain optimal cup stability using the bone impaction grafting technique.

Contains fulltext : 144018.pdf (publisher's version ) (Open Access), BACKGROUND: The T cell attracting chemokine CCL18 is produced by antigen presenting cells and a role for CCL18 has been suggested in the pathogenesis of a variety of diseases. Rheumatoid arthritis (RA) is one of these conditions, in which abundant CCL18 production is present. Although Th2 cytokines and IL-10 are known to have an effect on CCL18 production, there are several gaps in our knowledge regarding the exact regulation of CCL18 secretion, both in general and in RA. In this study we provide new insights in the regulation of CCL18 secretion by monocytes and dendritic cells. RESULTS: In contrast to a large panel of pro-inflammatory stimuli (IL-1beta, TNF-alpha, IL-10, IL-13, IL-15, IL-17, IL-18, IFN-gamma), T cell mimicking molecules (RANKL, CD40L) or TLR driven maturation, the anti-inflammatory IL-10 strongly stimulated DC to secrete CCL18. On freshly isolated monocytes, CCL18 secretion was induced by IL-4 and IL-13, in strong synergy with IL-10. This synergistic effect could already be observed after only 24 hours, indicating that not only macrophages and dendritic cells, but also monocytes secrete CCL18 under these stimulatory conditions. A high CCL18 expression was detected in RA synovial tissue and incubation of monocytes with synovial fluid from RA patients clearly enhanced the effects of IL-4, IL-13 and IL-10. Surprisingly, the effect of synovial fluid was not driven by IL-10 of IL-13, suggesting the presence of another CCL18 inducing factor in synovial fluid. CONCLUSION: In summary, IL-10 synergistically induces CCL18 secretion in combination with IL-4 of IL-13 on monocytes and monocyte derived cells. The effects of IL-14, IL-13 and IL-10 are strongly enhanced by synovial fluid. This synergy may contribute to the high CCL18 expression in RA.

Contains fulltext : 49802.pdf (publisher's version ) (Closed access), Calcium phosphates such as TCP-HA granules are considered promising bone graft substitutes. In the future, they may completely replace allograft bone for impaction grafting procedures. Mechanically, acetabular reconstructions with TCP-HA granules show high stability, however this is partly caused by excessive cement penetration, which is unfavourable from a biological perspective. It has been hypothesised that mixtures of morselised cancellous bone grafts (MCB) and/or TCP-HA granules with a nano-crystalline hydroxyapatite paste (Ostim) may reduce cement penetration while maintaining adequate implant stability and biocompatibility of the graft mixture. To investigate this hypothesis, destructive lever-out tests and in vivo animal test were performed with various combinations of materials. Mechanically, the addition of 10% Ostim to mixtures of MCB and/or TCP-HA granules reduced cement penetration and resulted in a mechanical stability comparable to pure allograft (the current gold standard). Biologically, the application of Ostim with MCB or TCP-HA granules did not hamper the biocompatibility of the materials. Ostim was mostly osseous-integrated with MCB or TCP-HA granules after 8 weeks. Also, non-osseous-integrated Ostim remnants were observed. In tartrate resistant acid phosphatase stained sections, these few non-osseous integrated Ostim remnants were actively being resorbed by osteoclasts. In conclusion, Ostim HA-paste could be a valuable addition when TCP-HA ceramic granules are being used for acetabular bone impaction grafting procedures.

Contains fulltext : 35791.pdf (publisher's version ) (Closed access)

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1 maart 2005, Promotores : Duysens, J.E.J., Allum, J.H.J., Veth, R.P.H. Co-promotor : Schreurs, B.W., Contains fulltext : 49146.pdf (publisher's version ) (Open Access), Je evenwicht verliezen - het gebeurt iedereen wel eens. Meestal loopt het goed af en val je niet, omdat je nog tijdig je balans weet te corrigeren. Hoe doe je dat? Promovendus Christian Grüneberg heeft met name gekeken naar de motorische reacties waarmee plotselinge externe verstoringen in de balans worden opgevangen. Door proefpersonen met behulp van een korset op verschillende manieren te 'verstijven', blijkt dat controle van de armen en de romp van essentieel belang is voor een stabiele staande houding. Tevens tonen de resultaten aan dat een toename van de rompstijfheid - in het bijzonder in de zijwaartse richting - een verklaring voor rompinstabiliteit bij ouderen zou kunnen zijn.

Item does not contain fulltext, Bone defects after failed total hip arthroplasty can be reconstructed with impacted morselized bone grafts and a cemented cup. In the near future the amount of bone grafts available for surgical purposes will be insufficient. Ceramic calcium phosphates [tricalcium phosphate (TCP) and hydroxyapatite (HA)] have been widely considered as potential bone graft substitutes or bone graft extenders. In the past, mechanical experiments have been performed to determine implant stability of bone grafts and ceramic TCP-HA granules mixes under a compressive load. However, in-vivo migration studies suggest that shear loading may be equally important. This in-vitro study investigated the initial stability of cups reconstructed with various mixes of bone grafts and ceramic TCP-HA granules in a lever-out situation, where shearing is the predominant loading mode. It was found that the cups reconstructed with mixes of bone graft and TCP-HA granules exhibited greater mechanical stability than the cups reconstructed with bone grafts only. It is concluded that from a mechanical standpoint, when considering shear force resistance, 50-50 per cent volume mix and 25-75 per cent volume mix of morselized cancellous bone graft and TCP-HA granules both provide adequate initial cup stability and can be used for acetabular reconstructions with the bone impaction grafting technique.

Item does not contain fulltext, The outcome of total hip arthroplasty after acetabular fracture is compromised. We studied if the bone impaction grafting technique could provide long-term prosthesis survival in deformed and irregular acetabula. We studied 20 hips in 20 patients (mean age, 53.3 years; range, 35-75 years) that were reconstructed with acetabular bone impaction grafting and a cemented total hip prosthesis after acetabular fracture. No patient was lost to followup. At review the mean followup was 9.5 years (range, 3-18 years) and the average Harris hip score was 93 (range, 62-100). During followup there were two cup revisions: one after 14.5 years for septic loosening, and one after 15.3 years for aseptic loosening. The Kaplan-Meier survival rate of the cup with end-point revision for any reason was 100% at 10 years and 80% (95% CI; range, 62-98%) after 15 years. With end-point cup revision for aseptic loosening the survival rate was 100% at 10 years. Acetabular bone impaction grafting with a cemented cup is a biologically attractive technique with good long-term survival used to reconstruct bone stock loss after posttraumatic arthritis. The complication and reoperation rate was low in this relatively young group of patients. LEVEL OF EVIDENCE: Therapeutic study, Level IV (Case series--no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.

Contains fulltext : 48153.pdf (publisher's version ) (Closed access), The transtrochanteric rotational osteotomy described by Sugioka is used to preserve the femoral head and to prevent secondary osteoarthritis in young patients with osteonecrosis of the femoral head. Several Japanese studies have shown favourable results, but European and American studies were disappointing. An explanation for these outcomes may be that the original protocol was not followed exactly. The objective of our study was to investigate this trans-trochanteric rotational osteotomy in Caucasian patients with osteonecrosis in which we followed the original method of Sugioka as closely as possible, including a 6-month period of non-weight bearing. We included 26 hips in 22 consecutive patients who were followed up for 8.7 (range 6.6-10) years. At review, 17 hips had been converted to total hip arthroplasty. The clinical survival rate was 56% after 7 years (95% CI 36-76%). The radiological survival rate was 54% after one year (95% CI 35-73%). Even after excluding the failures due to problems with osteosynthesis and infection, the results were not satisfactory and the osteoarthritic process was not delayed. Based on our results, we cannot recommend this technique as an alternative for total hip arthroplasty in Caucasians.

Contains fulltext : 47703.pdf (publisher's version ) (Open Access)

KUN, 25 maart 2004, Promotor : Veth, R.P.H. Co-promotores : Schreurs, B.W., Verdonschot, N.J.J., Buma, P., Item does not contain fulltext

Contains fulltext : 59080.pdf (publisher's version ) (Closed access), From a needle biopsy of the body of the 12th thoracic vertebra in a 74-year-old man with spinal osteomyelitis a Veillonella parvula was isolated. The significance of this bacterium as lactic acid indicator has been considered and discussed. Since this strictly anaerobic bacterium mainly uses lactic acid for energy generation, lactic acid must continuously and sufficiently have been produced in or near to the vertebrate body to permit outgrowth of this bacterium. Since neither microbial infections nor tumours could be demonstrated, we finally hypothesised that in this patient poor tissue perfusion has been the primary cause of lactic acid production.

Contains fulltext : 57643.pdf (publisher's version ) (Open Access), BACKGROUND: Acetabular bone deficiency can present a challenge during total hip arthroplasty, especially in young patients. The purpose of the present study was to evaluate the long-term clinical and radiographic outcomes of primary and revision acetabular reconstruction with use of an impaction bone-grafting technique and a cemented polyethylene cup in young patients who had preexisting acetabular bone deficiency. METHODS: Forty-two consecutive acetabular reconstructions were performed in thirty-seven patients who were younger than fifty years old (average, 37.2 years old). The impaction bone-grafting technique was used for twenty-three primary and nineteen revision acetabular reconstructions. Twenty-eight patients (thirty-one hips) were available for review after a minimum duration of follow-up of fifteen years. Clinical and radiographic results were assessed, and survivorship analysis was performed with the Kaplan-Meier method. RESULTS: Eight hips were revised at a mean of twelve years (range, three to twenty-one years) after a primary reconstruction (four hips) or revision reconstruction (four hips). The revision was performed because of aseptic loosening of the acetabular component in four hips and because of culture-proven septic loosening in two. Two additional cups (both in hips that had had a revision reconstruction) were revised, during revision of the femoral stem, because of wear (one hip) or because of persistent intraoperative instability (one hip). Twenty-eight hips (in twenty-five patients) had retention of the acetabular component for a minimum of fifteen years. The mean Harris hip score for that group was 89 points. Twenty-six of these twenty-eight hips had no or slight pain. Kaplan-Meier analysis revealed a twenty-year survival rate of 80% (95% confidence interval, 67% to 94%) with acetabular revision for any reason as the end point and of 91% (95% confidence interval, 80% to 100%) with acetabular revision because of aseptic loosening as the end p

Contains fulltext : 59362.pdf (publisher's version ) (Closed access), Bone impaction grafting of the femur is associated with more complications when segmental defects are present. The effect of segmental defect repair on initial stem stability was studied in an in vitro study with fresh-frozen goat femora. A standardized medial segmental defect was reconstructed using a cortical strut or a metal mesh. As controls, we used intact femora and femora with a nonreconstructed defect. In all 4 groups, impacted bone grafting was performed in combination with a cemented Exeter stem. Each group contained 5 femora. Reconstructions were dynamically loaded up to 1,500 N. Migration was measured with Roentgen stereophotogrammetric analysis. All cases with a nonreconstructed segmental defect failed into excessive varus rotation. None of the femora with a reconstructed defect failed. Cortical struts and metal meshes were equally effective in creating a stable stem construction (varus rotation, 2.89 +/- 2.27 and 2.27 +/- 0.57, respectively). Reconstructions with a metal mesh were more reproducible, although the obtained stability was significantly lower (P<.01) when compared with impaction grafting in an intact femur (varus rotation, 0.58 +/- 0.36).

Item does not contain fulltext, In a one-surgeon study the clinical and radiographic results of 30 cementless bipolar hip prostheses in 24 patients younger than 55 years were evaluated. Eleven noncoated prostheses (Noncoated Group) and 19 hydroxyapatite-coated prostheses (Hydroxyapatite Group) were compared after a mean followup of 10.4 years. The Harris hip score increased from a preoperative average of 41 points to 76 points at final followup (Noncoated Group, 70 points; Hydroxyapatite Group, 80 points). Thigh or groin pain was present in 15 patients (16 hips) (Noncoated Group, 55%; Hydroxyapatite Group, 53%). Radiographically, subsidence was the major problem at the noncoated prostheses (Noncoated Group, 91%; Hydroxyapatite Group, 5%), whereas osteolysis mainly was seen at the hydroxyapatite-coated prostheses (Noncoated Group, 18%; Hydroxyapatite Group, 89%). The obtained aseptic revision rate of 27% (Noncoated Group, 27%; Hydroxyapatite Group, 26%) is too high to use this implant in young patients. The large amounts of polyethylene wear debris generated by the bipolar system play an important role in this limited success. In the initially well-fixed hydroxyapatite-coated prostheses the sealing effect of a hydroxyapatite coating creates high concentrations of polyethylene in the limited joint space, resulting in massive proximal femoral osteolysis. Consequently, a hydroxyapatite coating introduces a new failure mechanism. Therefore, hydroxyapatite does not improve the outcome of a cementless bipolar hemiarthroplasty in the long-term.

Item does not contain fulltext, Tricalciumphosphate (TCP) and hydroxyapatite (HA) have been suggested as bone graft substitutes in a wide range of applications. In this study, the initial stability of cemented acetabular cups was determined after reconstructing a combined cavitary and segmental defect in a realistic acetabular revision surgery model. The defects were reconstructed with mixes of TCP/HA particles and human bone grafts using the bone impaction grafting technique. In comparison with defect reconstruction with human bone grafts only, cup translation and tilt decreased by 27% when mixes of bone grafts and porous TCP/HA particles were used and by 55% when mixing the bone grafts with solid TCP/HA particles. Increasing the TCP/HA ratio within the mix significantly decreased cup translation. From a biomechanical perspective, mixes of TCP/HA particles and bone grafts are an attractive alternative for morsellized bone grafts when using the bone impaction grafting technique in the reconstruction of large defects of the acetabulum.

Item does not contain fulltext, Bone defects in revision hip surgery can be reconstructed with impacted morselized bone grafts. Rinsing these trabecular allografts may enhance graft incorporation by washing out immunogenic factors present in blood, marrow, and fat. However, it has been proposed that impaction of the graft releases biologically active factors, which can provide sufficient activity to stimulate new bone formation. Rinsing before impaction could enhance bone allograft incorporation, but rinsing after impaction could diminish the incorporation process of impacted bone graft. To study the effect of rinsing and impaction of morselized bone grafts on bone ingrowth, a bone chamber study was done in goats. Autografts and allografts were divided into three treatment groups: (A) impacted; (B) rinsed and impacted; and (C) rinsed, impacted, rinsed, and impacted again. Ten goats received three bone chambers in each proximal tibia. The chambers were filled with either allograft or autograft, yielding six different implants per goat. After 6 weeks, histologic analyses were done and bone and tissue ingrowth were measured. New bone and total tissue ingrowth were higher in autografts than in allografts, especially in the nonrinsed group. With rinsing, total tissue ingrowth increased in the allograft group to approach that of autografts. Rinsing after impaction did not additionally alter bone ingrowth. The current findings show that incorporation of allografts can be improved by rinsing the grafts before impaction.

Item does not contain fulltext, We determined the effect of bone graft particle size and impaction technique on the initial stability of cemented acetabular cups. First, acetabular reconstructions were performed in human cadaveric pelvic bones in which type 2 AAOS cavitary defects were created. Reconstructions were made with small bone grafts (average 2 mm) produced by a bone mill or large bone grafts (average 9 mm) produced by hand with a rongeur. All chips were made from freshly-frozen femoral heads. Impaction was done using acetabular impactors and a hammer. We did a loading experiment with a gradually increasing dynamic load up to 3000 N. We used radiostereometric analysis (RSA) to determine cup stability. The cups were more stable when large bone grafts were used. Because of limitations of the cadaver model, we developed a synthetic acetabular model. For validation of this model, we repeated the experiments using small and large bone grafts. The results with both models were similar. In the synthetic model, we compared impaction with hammer and impactors with the reversed reaming technique using manual compression on the reamer. The latter method resulted in more migration. We recommend firm impaction with a hammer of large bone grafts for optimal stability of the cup.

KUN, 14 mei 2002, Promotor : Slooff, T.J.J.H. Co-promotores : Buma, P., Schreurs, B.W., Item does not contain fulltext

Item does not contain fulltext, In revision surgery of the acetabulum bone defects can be filled with impacted human morsellized bone grafts. Because of a worldwide limited availability of human bone, alternatives are being considered. In this study we compared the initial stability of acetabular cups after reconstructing a cavitary defect with various compositions of impacted tricalciumphosphate-hydroxyapatite (TCP/HA) particles and mixes of TCP/HA particles and human grafts in a realistic acetabulum model. Primary cemented cups and reconstructions with impacted human cancellous grafts were used as reference. A dynamic load displaced the acetabular cups superomedially. The primary cemented cups showed the highest stability. The cups with impacted human grafts produced the most displacement. All reconstructions with the TCP/HA particles showed a high stability of the cups. However, especially when using large TCP/HA particles this was probably due to a large amount of cement penetration. Mixing TCP/HA particles with human grafts seemed to decrease cement penetration. although still a high stability was obtained. In this perspective, we concluded that TCP/HA particles might be useful as a bone graft extender in the reconstruction of acetabular bone defects.

Item does not contain fulltext, Impacted morsellized bone grafts are clinically successful to restore bony defects after failed total hip arthroplasties. The incorporation process seems to be dependent on the location where the reconstruction is performed, which suggests that load could play a role. In this study, we hypothesised that, as in fracture healing, physiological loading has a stimulatory effect on the process of early bone graft incorporation. To test this hypothesis we created a standardised defect in the distal femur of twelve goats. Allograft bone chips were impacted into the defect and a subcutaneous pressure implant was screwed in. With this implant the graft can be loaded under controlled circumstances. Six goats were subjected to a daily loading regime of 3 MPa, the other six were non-loaded. After five weeks the bone mineral density was measured with peripheral quantitative computer tomography. Thereafter, routine histology and histomorphometry were carried out. Bone mineral density was not affected by load. Histology revealed microscopic evidence of bone graft incorporation, which proceeded in a similar way in both loaded and non-loaded specimens. New bone was formed free in the stroma or on graft remnants after osteoclastic resorption of the graft. Only the area of active incorporating bone graft was higher under load. In conclusion, the formation of a new bony structure was not affected by load after five weeks. However, load resulted in a larger area of active graft incorporation at this early stage. Possibly biological and immunological factors govern the early incorporation process independent of the local loading regime.

Item does not contain fulltext, We evaluated the results of 27 acetabular reconstructions in 21 patients with secondary osteoarthritis resulting from congenital dysplasia of the hip in which the acetabular bone defects were restored with impacted morcellized bone-grafts in combination with a cemented cup. At an average follow-up of 7 years, 7 months (range, 5-15 years), 2 hips were revised. One cup was revised after 27 months for sciatic nerve problems; the other hip was revised for aseptic loosening of the cup at 12 years' follow-up. The cumulative survival of the acetabular reconstruction was 96.3% at 5- and 10-year intervals. Additionally, 2 hips (7.7%) showed stable radiolucent lines in zone III without migration of the cup. None of the cemented stems were revised. The bone impaction grafting technique is a safe and attractive method to restore bone deficiencies in dysplastic hips.

Item does not contain fulltext, We report a long-term review of 41 acetabular reconstructions using impacted morsellized bone grafts and a cemented total hip arthroplasty (THA) in patients younger than 50 (22-49; average 38) years. Reconstruction was performed in 23 primary THA (19 patients) and 18 revision THA (17 patients). 3 patients were lost to follow-up and 3 (4 hips) died within 10 years of surgery; none had a revision. Thus, 34 hips (30 patients) were reviewed with an average follow-up of 13 (10-18) years. In 2 hips, a revision was performed for aseptic loosening of the acetabular component 7 and 11 years after surgery. One additional cup was revised after 12 years during a femoral stem revision due to wear and matching problems, but was well fixed. The survival rate of the acetabular reconstruction technique was 94% (95% CI: 90-98%).

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Item does not contain fulltext, In reconstructive surgery human bone defects are sometimes filled with the use of the impaction bone grafting technique. Currently different types of biomaterial particles are being developed as bone-substitute materials. Before these biomaterials can be applied their mechanical and biological behavior should be characterized. In this study the time-dependent mechanical behavior of biomaterial particles with different tri-calcium-phosphate/hydroxy-apatite (TCP:HA) ratios, particle sizes, and porosities is determined and compared to the behavior of human bone grafts, the latter being the standard material currently used to augment bone defects. The mechanical properties were assessed with the use of dynamic confined compression creep tests with a loading and unloading phase. Different graft material groups were tested, consisting of 100% human bone grafts, 100% biomaterial particles, and 50:50 weight mixtures of human grafts and biomaterial particles. No damage to the particles was observed by the impaction in the test chamber or by the dynamic load. Relative to the human graft material, the biomaterial particles hardly deformed under loading, were much stiffer, and showed almost no viscoelastic behavior. The mixtures showed intermediate results. Particle size and porosity influenced the behavior of the biomaterial particles. TCP:HA ratio did not have a great effect. The conclusion is that the application of these particles should be done with great care, as their mechanical behavior is drastically different than that of the human graft material. Mixing it with human bone grafts gave the material some biphasic, viscoelastic behavior that may be important for its biological response.

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4th Congress of the European Federation of National Associations of Orthopaedics and Traumatology, Brussels, Belgium, 3 juni 1999, Item does not contain fulltext

45th Annuak Meeting Orthopaedic Research Society. Anaheim, CA, USA, 01 februari 1999, Item does not contain fulltext

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