Proof of concept: hip joint damage occurs at the zone of femoroacetabular impingement (FAI) in an experimental FAI sheep model.

OBJECTIVE: In ovine hips chondrolabral damage as seen in cam-type femoroacetabular impingement (FAI) can be induced via an intertrochanteric varus osteotomy. However, it is yet to proven whether the observed cartilage damage is caused by a dynamic cam type impingement. Thus we asked, (1) whether actual cartilage damage observed after FAI induction in ovine hips occurs at the predicted, computed zone of FAI; (2) whether the extent of cartilage damage increases with ambulation time in this animal model? DESIGN: In this experimental, controlled, comparative study 20 sheep underwent unilateral FAI induction through an intertrochanteric varus osteotomy. Preoperatively sheep underwent computed tomography to generate three-dimensional models of the osseous pelvis and femur. The models were used to predict impingement zones before and after simulated varus osteotomy using range of motion (ROM) analysis. Sheep were sacrificed after 14-40 weeks of ambulation. At sacrifice cartilage was inspected and (1) location of actual damage and computed impingement zones were compared; (2) Cartilage damage was compared between short- and long ambulation groups. RESULTS: (1) The average location and the extent of peripheral and central cartilage lesions did not differ with the computed impingement zones (all P > 0.05). (2) Grades of central, posterior cartilage damage were more severe in the long-compared to the short ambulation group (2.2 ± 1.8 vs 0.4 ± 0.5; P = 0.030). CONCLUSIONS: In this experimental ovine FAI model the surgical induction of an osseous impingement conflict between the femur and acetabulum causes cartilage damage at the zone of simulated FAI.

Femoral osteochondroplasty can be performed effectively without the risk of avascular necrosis or femoral neck fractures in an experimental ovine FAI model.

OBJECTIVE: The experimental induction of cam-type femoroacetabular impingement (FAI) in sheep is established. To tap the full potential of this ovine model, one should be able to perform a femoral osteochondroplasty safely. This study was based on previous cadaver experiments on the blood supply to the ovine femoral head and on the biomechanical strength of the proximal femur following offset creation. We hypothesized that offset creation in this ovine FAI model does not lead to (1) avascular necrosis (AVN) of the ovine femoral head or (2) iatrogenic femoral neck fractures and (3) can be performed effectively. DESIGN: In this experimental, controlled, prospective study nine sheep underwent unilateral FAI induction through an intertrochanteric, varus osteotomy. Seventy days following FAI induction, femoral osteochondroplasty was performed. Sheep were sacrificed after another 140 days. Radiographs, computed tomography (CT) scans and MRI were acquired. Histologic samples were stained with hematoxylin-eosin. (1) The multimodal Association Research Circulation Osseous (ARCO) classification was used for assessment of AVN. (2) Femoral neck fractures were assessed with the multimodal imaging approach. (3) Pre- and postoperative (=after sacrifice) alpha angles and femoral neck diameters were compared. RESULTS: (1) No signs for AVN according to the ARCO classification or (2) for femoral neck fractures were detected. (3) Mean alpha angles and femoral neck diameters decreased significantly (p < 0.001) superiorly by at least 30° respectively 4 mm after the offset creation. CONCLUSIONS: Femoral osteochondroplasty can be performed effectively and without the risk of AVN or femoral neck fractures in this ovine FAI model.

Osteoanabolic effect of alendronate and zoledronate on bone marrow stromal cells (BMSCs) isolated from aged female osteoporotic patients and its implications for their mode of action in the treatment of age-related bone loss.

SUMMARY: In the present study, we evaluated the potential for aminobisphosphonates to enhance the development of bone-forming osteoblasts from progenitor cells isolated from aged female osteoporotic patients. The aminobisphosphonates tested significantly enhanced osteoblast formation and thus lend further insights into their possible mode of action in the treatment of osteoporosis. INTRODUCTION: The primary aim of this study was to evaluate the influence of aminobisphosphonates on the osteogenesis of human bone marrow stromal cells (hBMSCs) and mineralization of differentiating bone-forming cells isolated from osteoporotic patients. METHODS: The influence of aminobisphosphonate treatment on hBMSC osteogenesis was assessed by the quantitative measurement of alkaline phosphatase (ALP) activity, in addition to quantitative reverse transcription polymerase chain reaction and Western blot analysis of known osteogenic markers. Mineralized matrix formation by hBMSC-derived osteoblasts was visualized and quantified using Alizarin red staining. RESULTS: hBMSC cultures treated with osteogenic medium supplemented with zoledronate demonstrated a significant increase in Alizarin red staining after 3 weeks as compared to cells cultured in osteogenic medium alone. Similarly, cultures of differentiating hBMSCs isolated from patients receiving alendronate treatment also demonstrated an increased propensity for mineralization, even in the absence of further in vitro stimulation by zoledronate. The stimulatory effects of aminobisphosphonate treatment on hBMSC-derived osteoblast-mediated mineralization were independent of any alterations in ALP activity, although significant decreases in the expression levels of osteopontin (SPP1) were evident in hBMSCs following exposure to aminobisphosphonates. Further analysis including Western blotting and loss-of-function studies revealed osteopontin as having a negative influence on the mineralization of differentiating osteoporotic bone-forming cells. CONCLUSIONS: The results presented here demonstrate for the first time that aminobisphosphonate treatment of osteoporotic hBMSCs enhances their capacity for osteoblast formation and subsequent mineral deposition, thus supporting the concept of aminobisphosphonates as having an osteoanabolic effect in osteoporosis.

Effect of grain size and microporosity on the in vivo behaviour of ß-tricalcium phosphate scaffolds.

Defining the most adequate architecture of a bone substitute scaffold is a topic that has received much attention over the last 40 years. However, contradictory results exist on the effect of grain size and microporosity. Therefore, the aim of this study was to determine the effect of these two factors on the in vivo behaviour of ß-tricalcium phosphate (ß-TCP) scaffolds. For that purpose, ß-TCP scaffolds were produced with roughly the same macropore size (≈ 150 µm), and porosity (≈ 80 %), but two levels of microporosity (low: 10 % / high: ≈ 25 %) and grain size (small: 1.3 µm /large: ≈ 3.3 µm). The sample architecture was characterised extensively using materialography, Hg porosimetry, micro-computed tomography (µCT), and nitrogen adsorption. The scaffolds were implanted for 2, 4 and 8 weeks in a cylindrical 5-wall cancellous bone defect in sheep. The histological, histomorphometrical and µCT analysis of the samples revealed that all four scaffold types were almost completely resorbed within 8 weeks and replaced by new bone. Despite the three-fold difference in microporosity and grain size, very few biological differences were observed. The only significant effect at p < 0.01 was a slightly faster resorption rate and soft tissue formation between 4 and 8 weeks of implantation when microporosity was increased. Past and present results suggest that the biological response of this particular defect is not very sensitive towards physico-chemical differences of resorbable bone graft substitutes. As bone formed not only in the macropores but also in the micropores, a closer study at the microscopic and localised effects is necessary.

Comparison of chemically and pharmaceutically modified titanium and zirconia implant surfaces in dentistry: a study in sheep.

Advanced surface modifications and materials were tested on the same implant geometry. Six types of dental implants were tested for osseointegration after 2, 4 and 8 weeks in a sheep pelvis model. Four titanium implant types were treated with newly developed surface modifications, of which two were chemically and two were pharmacologically modified. One implant was made of zirconia. A sandblasted and acid-etched titanium surface was used as reference. The chemically modified implants were plasma-anodized or coated with calcium phosphate. The pharmacological coatings contained either bisphosphonate or collagen type I with chondroitin sulphate. The implants were evaluated using macroscopic, radiographic and histomorphometric methods. All implants were well osseointegrated at the time of death. All titanium implants had similar bone implant contact (BIC) at 2 weeks (57-61%); only zirconia was better (77%). The main BIC increase was between 2 and 4 weeks. The pharmacologically coated implants (78-79%) and the calcium phosphate coating (83%) showed similar results compared with the reference implant (80%) at 8 weeks. There were no significant differences in BIC. Compared with previous studies the results of all implants were comparatively good.

Does surface anodisation of titanium implants change osseointegration and make their extraction from bone any easier?

OBJECTIVES: Titanium implants have a tendency for high bone-implant bonding, and, in comparison to stainless steel implants are more difficult to remove. The current study was carried out to evaluate, i) the release strength of three selected anodized titanium surfaces with increased nanohardness and low roughness, and ii) bone-implant bonding in vivo. These modified surfaces were intended to give improved anchorage while facilitating easier removal of temporary implants. MATERIAL AND METHODS: The new surfaces were referenced to a stainless steel implant and a standard titanium implant surface (TiMAX). In a sheep limb model, healing period was 3 months. Bone-implant bonding was evaluated either biomechanically or histologically. RESULTS: The new surface anodized screws demonstrated similar or slightly higher bone-implant-contact (BIC) and torque release forces than the titanium reference. The BIC of the stainless steel implants was significant lower than two of the anodized surfaces (p = 0.04), but differences between stainless steel and all titanium implants in torque release forces were not significant (p = 0.06). CONCLUSION: The new anodized titanium surfaces showed good bone-implant bonding despite a smooth surface and increased nanohardness. However, they failed to facilitate implant removal at 3 months.

Recovery of low volumes of wear debris from rat stifle joint tissues using a novel particle isolation method.

Less than optimal particle isolation techniques have impeded analysis of orthopaedic wear debris in vivo. The purpose of this research was to develop and test an improved method for particle isolation from tissue. A volume of 0.018 mm3 of clinically relevant CoCrMo, Ti-6Al-4V or Si3N4 particles was injected into rat stifle joints for seven days of in vivo exposure. Following sacrifice, particles were located within tissues using histology. The particles were recovered by enzymatic digestion of periarticular tissue with papain and proteinase K, followed by ultracentrifugation using a sodium polytungstate density gradient. Particles were recovered from all samples, observed using SEM and the particle composition was verified using EDX, which demonstrated that all isolated particles were free from contamination. Particle size, aspect ratio and circularity were measured using image analysis software. There were no significant changes to the measured parameters of CoCrMo or Si3N4 particles before and after the recovery process (KS tests, p > 0.05). Titanium particles were too few before and after isolation to analyse statistically, though size and morphologies were similar. Overall the method demonstrated a significant improvement to current particle isolation methods from tissue in terms of sensitivity and efficacy at removal of protein, and has the potential to be used for the isolation of ultra-low wearing total joint replacement materials from periprosthetic tissues. STATEMENT OF SIGNIFICANCE: This research presents a novel method for the isolation of wear particles from tissue. Methodology outlined in this work would be a valuable resource for future researchers wishing to isolate particles from tissues, either as part of preclinical testing, or from explants from patients for diagnostic purposes. It is increasingly recognised that analysis of wear particles is critical to evaluating the safety of an orthopaedic device.

BMP-silk composite matrices heal critically sized femoral defects.

Clinical drawbacks of bone grafting prompt the search for alternative bone augmentation technologies such as use of growth and differentiation factors, gene therapy, and cell therapy. Osteopromotive matrices are frequently employed for the local delivery and controlled release of these augmentation agents. Some matrices also provide an osteoconductive scaffold to support new bone growth. In this study, silkworm-derived silk fibroin was evaluated as an osteoconductive matrix for healing critical sized mid-femoral segmental defects in nude rats. Four treatment groups were assessed over eight weeks: silk scaffolds (SS) with recombinant human BMP-2 (rhBMP-2) and human mesenchymal stem cells (HMSC) that had been pre-differentiated along an osteoblastic lineage ex vivo (Group I; pdHMSC/rhBMP-2/SS); SS with rhBMP-2 and undifferentiated HMSCs (Group II; udHMSC/rhBMP-2/SS); SS and rhBMP-2 alone (Group III; rhBMP-2/SS); and empty defects (Group IV). Bi-weekly radiographs revealed a progressive and similar increase in Group I-III mean defect mineralization through post-operative week (POW) 8. Radiographs, dual energy x-ray absorptiometry, and micro-computed tomography confirmed that Groups I-III exhibited similar substantial and significantly (p<0.05) greater defect mineralization at POW 8 than the unfilled Group IV defects which remained void of bone. No significant differences in Groups I-III defect healing at POW 8 were apparent using these same assays or mechanical testing. Histology at POW 8 revealed moderately good bridging of the parent diaphyseal cortices with woven and lamellar bone bridging islands of silk matrix in Groups I and III. Group II defects possessed comparatively less new bone which was most abundant adjacent to the parent bone margins. Elsewhere the silk matrix was more often enveloped by poorly differentiated loose fibrous connective tissue. Group IV defects showed minimal new bone formation. None of the treatment groups attained the mean mineralization or the mean biomechanical strength of identical defects implanted with SS and pdHMSCs alone in a previous study. However, addition of rhBMP-2 to SS prompted more bone than was previously generated using udHMSC/SS or SS alone. These data imply the clinical potential of silk scaffolds and rhBMP-2 as composite osteopromotive implants when used alone or with select stem cell populations. Additional studies in larger species are now warranted.

An analysis of the in vivo deterioration of Co-Cr-Mo implants through wear and corrosion.

The degradation of Co-Cr-Mo ASTM F75-92 hip implants after a harvesting period of 81 months in sheep was investigated. Hip prostheses and tissue samples were obtained from a medical study involving total hip arthroplasty of the cemented type in 12 sheep. Upon euthanasia, the explants were retrieved for analyses of the surfaces and evidence of degradation, while tissue samples from the interface regions were harvested for chemical analysis and evidence of Co, Cr, and Mo contents. Clear evidence of wear and corrosion was detected. Results also indicated that the modes of metal transport through the poly(methyl methacrylate) bone cement play an important role as the surface degradation mechanisms of the metal. The results are being discussed in terms of electrochemical and triboelectrochemical behaviour of the Co-Cr-Mo alloy.

Tendon retracts more than muscle in experimental chronic tears of the rotator cuff.

We released the infraspinatus tendons of six sheep, allowed retraction of the musculotendinous unit over a period of 40 weeks and then performed a repair. We studied retraction of the musculotendinous unit 35 weeks later using CT, MRI and macroscopic dissection. The tendon was retracted by a mean of 4.7 cm (3.8 to 5.1) 40 weeks after release and remained at a mean of 4.2 cm (3.3 to 4.7) 35 weeks after the repair. Retraction of the muscle was only a mean of 2.7 cm (2.0 to 3.3) and 1.7 cm (1.1 to 2.2) respectively at these two points. Thus, the musculotendinous junction had shifted distally by a mean of 2.5 cm (2.0 to 2.8) relative to the tendon. Sheep muscle showed an ability to compensate for approximately 60% of the tendon retraction in a hitherto unknown fashion. Such retraction may not be a quantitatively reliable indicator of retraction of the muscle and may overestimate the need for elongation of the musculotendinous unit during repair.

Mosaicplasty with photooxidized, mushroom shaped, bovine, osteochondral xenografts in experimental sheep.

The goal was to study the performance of mushroom shaped, photooxidized, osteochondral grafts in mosaicplasty focusing on graft stability and survival. Mushroom shaped, photooxidized grafts (6 mm for the cartilaginous head of the mushroom, 3 mm for the stem) were implanted in the medial femoral condyle of 10 sheep. Four transplants were inserted per condyle in an overlapping fashion using the pressfit technique (n=40 grafts in 10 condyles). The grafts were followed for 6 and 12 months. Semi-quantitative evaluation of graft performance was performed using a validated score system. All grafts were mechanically stable at 6 and 12 months with one exception, where the mushroom head broke off. The formation of cystic lesions in the subchondral bone area was minimal. Repopulation of the old photooxidized cartilage was noticed with cells invading the matrix from the subchondral bone area and also from the pannus on the surface. Fusion between host and graft cartilage was observed in some of the grafts at 12 months, while remodeling of the calcified cartilage zone and tidemark was noticed in all grafts. Results scored significantly better for the 6 months compared to the 12 months group if cartilage surface integrity was compared (p<0.05). In all other variables no significant differences were found between groups. Despite moderate graft recession in the 12 months group partial fusion of grafts and functional results were satisfactory. The photooxidized mushroom shaped osteochondral transplants may be a suitable type of graft for functional results in cartilage resurfacing if stable anchorage of the grafts can be achieved.

[Investigation about the clinical use of brushite- and hydroxylapatite-cement in sheep]. / Untersuchungen uber den klinischen Einsatz von Brushite- und Hydroxylapatit-Zement beim Schaf.

For future clinical use as synthetic bone replacement, an injectable brushite-(chronOS-Inject) and hydroxylapatite-(Biobon) cement were compared in a drill hole model in 10 sheep over time at 2, 4, 6, 8, 16 and 24 weeks. Results were compared regarding their practical use, biocompatibiliy, resorption mechanism and subsequent new bone formation. The cements were filled into drill holes (psi 8 x 13mm) of the proximal and distal humerus, and femur and the samples evaluated macroscopically, radiologically and microscopically including histomorphometrical quantification of percentages of new bone, fibrous tissue and remnants of cements. The cement area decreased continuously from 2 to 24 weeks with chronOS-Inject, as well as the area of granules. Inversely, the subsequent new bone formation increased from 2-24 weeks accordingly. With Biobon the cement area decreased slower between 2 and 24 weeks, and the new bone formation was less. Both cements were well integrated into the bone in long bones. chronOS-Inject demonstrated good biocompatibility and was almost completely replaced through bone within 24 weeks. Biobon was resorbed considerably slower and initially a slight inflammatory reaction including bone resorption was observed within the adjacent host bone.

Compositional changes of a dicalcium phosphate dihydrate cement after implantation in sheep.

A hydraulic calcium phosphate cement having dicalcium phosphate dihydrate (DCPD) as end-product of the setting reaction was implanted in a cylindrical defect in the diaphysis of sheep for up to 6 months. The composition of the cement was investigated as a function of time. After setting, the cement composition consisted essentially of a mixture of DCPD and beta-tricalcium phosphate (beta-TCP). In the first few weeks of implantation, the edges of the cement samples became depleted in DCPD, suggesting a selective dissolution of DCPD, possibly due to low pH conditions. The cement resorption at this stage was high. After 8 weeks, the resorption rate slowed down. Simultaneously, a change of the color and density of the cement center was observed. These changes were due to the conversion of DCPD into a poorly crystalline apatite. Precipitation started after 6-8 weeks and progressed rapidly. At 9 weeks, the colored central zone reached its maximal size. The fraction of beta-TCP in the cement was constant at all time. Therefore, this study demonstrates that the resorption rate of DCPD cement is more pronounced as long as DCPD is not transformed in vivo.

In vivo behavior of three different injectable hydraulic calcium phosphate cements.

Two dicalcium phosphate dihydrate (DCPD) hydraulic cements and one apatite hydraulic cement were implanted in epiphyseal and metaphyseal, cylindrical bone defects of sheep. The in vivo study was performed to assess the biocompatibility of the DCPD cements, using the apatite cement as control. After time periods of 2, 4 and 6 months the cement samples were clinically and histologically evaluated. Histomorphometrically the amount of new bone formation, fibrous tissue and the area of remaining cement were measured over time. In all specimens, no signs of inflammation were detectable either macroscopically or microscopically. All cements were replaced by different amounts of new bone. The two DCPD-cements showed the highest new bone formation and least cement remnants at 6 months, whereas the apatite was almost unchanged over all time periods.

Effect of tendon release and delayed repair on the structure of the muscles of the rotator cuff: an experimental study in sheep.

BACKGROUND: Ruptures of the tendons of the rotator cuff lead to profound and possibly irreversible changes in the structure and physiological properties of the rotator cuff muscles. Muscle atrophy and fatty infiltration are important prognostic factors that affect the natural history and outcome of treatment. The purpose of this study was to examine the amount of muscle atrophy and fatty infiltration in an animal model and to determine whether the repair of a long-standing tendon tear can reverse these changes. METHODS: The infraspinatus tendon in six sheep was released and encased in a silicone tube to prevent spontaneous healing. The musculotendinous unit was allowed to retract for forty weeks. Throughout this period, the muscular changes were studied with use of computed tomography, histological analysis, and electron microscopy. At forty weeks, the elasticity, intramuscular pressure, and perfusion were measured intraoperatively and a tendon repair was carried out. The structural changes of the muscle were studied for thirty-five weeks after the repair. The animals were then killed, and the musculotendinous units were examined macroscopically and by computed tomography, histological analysis, and electron microscopy. RESULTS: At the time of the tendon release, the infraspinatus showed no fatty changes. The force needed to cause a tendon excursion of 1 cm was a mean (and standard deviation) of 6.8 +/- 1 N. The application of tension on the tendon did not alter the perfusion and decreased the intramuscular pressure. After the tendon release, muscular atrophy developed and there was a significant increase (p < 0.001) in interfascicular and intrafascicular fat, representing fatty infiltration rather than fatty degeneration. Furthermore, there was an increase of interstitial connective tissue. At the time of the tendon repair, between forty and forty-two weeks after the release, there was a sevenfold poorer elasticity of the musculotendinous unit but preserved muscle perfusion. The structural changes increased six weeks after the repair and then recovered partially at twelve and thirty-five weeks thereafter but only to the amount demonstrated before the repair. CONCLUSIONS: Musculotendinous retraction induced by tendon release is associated with profound changes in the structure and function of the affected muscle. Vascularization, intramuscular pressure, and individual fiber composition are not markedly affected, and muscle fibers do not appear to degenerate. However, muscle atrophy, infiltration by fat cells, and an increase of interstitial connective tissue lead to impairment of the physiological properties of the muscle. These changes were irreversible under the conditions of this experiment with the repair technique used.

Long term in-vivo studies of a photo-oxidized bovine osteochondral transplant in sheep.

BACKGROUND: Articular cartilage has limited capacity to repair. Defects greater than 3 mm heal with formation of inferior fibrous cartilage. Therefore, many attempts have been made to find the ideal graft for larger cartilage lesions. Different grafts, such as untreated or cryopreserved osteochondral transplants, have been used with variable success. METHODS: Photo-oxidized osteochondral grafts were implanted in both femoral condyles of one ovine knee. Untreated xenogeneic and autogeneic grafts served as controls. Three groups of 8 sheep each were formed and they were sacrificed 6, 12 or 18 months after surgery. RESULTS: The macroscopic evaluation of the condyle and graft showed a well-maintained cartilage surface in most grafts at all time points. However, the host cartilage matrix deteriorated considerably in all xenogeneic, most autogeneic and fewer of the photo-oxidized grafts at 12 and 18 months, respectively. The blue colour of the photo-oxidized grafts resulting from the process of photo-oxidation was visible in all grafts at 6 months, had diminished at 12 months and had completely disappeared at 18 months after surgery. Histologically a loss of matrix staining was almost never noticed in untreated xenografts, transiently at 6 months in photo-oxidized grafts and increased at 12 and 18 months. Fusion between graft and host cartilage could be seen in photo-oxidized grafts at 12 and 18 months, but was never seen in autografts and xenografts. CONCLUSIONS: The photo-oxidation of osteochondral grafts and its use as transplant appears to have a beneficial effect on cartilage and bone remodelling. Osteochondral grafts pre-treated with photo-oxidation may be considered for articular cartilage replacement and therefore may delay artificial joint replacements in human patients.

Upregulation of mRNA of interleukin-1 and -6 in subchondral cystic lesions of four horses.

This study investigated the potential association of interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in subchondral cystic lesions (SCL) in horses. With the technique of in situ hybridisation in paraffin sections of fibrous tissue of SCL and quantitative real-time PCR in fresh frozen fibrous tissue and undecalcified bone sections of SCL embedded in acrylic resin, upregulation of mRNA of both cytokines could be demonstrated. mRNA of IL-1beta was upregulated at the periphery of the cystic lesion adjacent to normal bone, whereas IL-6 mRNA was upregulated within the fibrous tissue found within the centre of the SCL. It was concluded that both cytokines are associated in pathological bone resorption observed in SCL and, in combination with increased production of prostaglandin E2, may be responsible for the slow healing, maintenance or further expansion of the cystic lesions.

Spontaneous production of nitric oxide (NO), prostaglandin (PGE2) and neutral metalloproteinases (NMPs) in media of explant cultures of equine synovial membrane and articular cartilage from normal and osteoarthritic joints.

Nitric oxide (NO), prostaglandin E2 (PGE2), and the activity of neutral metalloproteinases (NMPs) were measured in conditioned media of equine synovial membrane and articular cartilage explant cultures from horses with normal joints (n = 7) and from horses affected with moderate (n = 7) or severe osteoarthritis (n = 14) as judged by macroscopic appearance. Normal articular cartilage appeared glossy and bluish-white, was of normal thickness and showed no evidence of discolouration, fibrillation or other cartilage discontinuity. Slight discolouration and fibrillation or minor clefts of the cartilage were considered as moderate OA, whereas erosions of articular cartilage down to the subchondral bone were considered as cases of severe OA. Explant cultures of equine synovial membrane and articular cartilage released the local mediators, NO and PGE2, as well as detectable levels of NMP activity into culture media. Concentrations of NO were higher in articular cartilage explants compared to synovial membrane explants, whereas concentrations of PGE2 were higher in synovial membrane explants. The NMPs with collagenolytic activities were similar in both explant cultures, whereas gelatinolytic activities were higher in synovial membrane explant cultures and caseinolytic activities were generally higher in articular cartilage explant cultures. Furthermore it was shown that concentrations or enzyme activities increased according to the severity of disease of the joints. Concentrations for NO, collagenolytic and gelatinolytic NMPs were relatively stable, whereas PGE2 and caseinolytic NMP concentrations increased over time in culture.

Decalcified bone grafts in the horse.

The need for early postoperative weight bearing following fracture repair in the horse has led to investigation of various means of expediting the healing process. Bone grafting represents one means of accomplishing this, and the transplantation of autologous tissues has proven to be most useful in equine orthopedics. Acid-decalcified, frozen, allogeneic bone for grafting is easy to prepare, readily contoured, osteogenic, and elicits no obvious immune or rejection response. The most compelling reason for the use of the substance is the elimination of the need of a harvesting operation on a patient already undergoing extensive surgery for the restitution of skeletal integrity.

[Women in veterinary medicine--thoughts on the possibility of integration in the professional world]. / Frauen in der Veterinärmedizin--Gedanken zur Möglichkeit der Integration in die Berufswelt.

In this article an attempt was made to analyze the professional situation of women in Switzerland. Although over 70% female students are registered in both Colleges of Veterinary Medicine in Switzerland, there are still very few women working full time in their later career. Furthermore, only very few female veterinarians are represented in higher positions, either in academia, industry or as head of private hospitals. Even though the professional environment would welcome those female students, it seems that other than professional reasons may be involved in this discrepancy. Family traditions, unrecognized patriarchal structures in education, but also in philosophical and psychological traditions may be responsible for the deep conflict between the external modern environment and the inner values of women, creating an unsurmountable obstacle for women to combine a successful professional and private life. Ideas of how this could be arranged are presented.