Study of the healing process after transplantation of pasteurized bone grafts in rabbits.
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Different bone allografts (pasteurized, autoclaved, and frozen) were compared based on their osteoinductive properties. Our primary purpose was to examine the biologic qualities of pasteurized allografts, as pasteurization inactivates most viruses transmitted by transplantation. Frozen, pasteurized, and autoclaved allografts were packed into a standard defect of rabbit ulna. The animals were sacrificed at 2 and 4 weeks after surgery. The parts of bones with experimental defects were explored en bloc, and a roentgenogram was carried out. Ulna bone samples were then embedded in methyl-methacrylate. Roentgenograms showed that after 2 weeks, calluses were well-formed, but irregular in shape in all 3 types of allografts. After 4 weeks, the calluses were regular in shape in all but the autoclaved grafts. After 2 weeks, the healing processes had begun in the frozen and pasteurized grafts, with the reaching approximately the same stage, while in the autoclaved grafts these processes were not seen and the bone particles were surrounded by connective tissue without any changes. After 4 weeks, osteoinductive processes were very strong, with the first signs of complete bone remodeling at the bone edges of the defect in pasteurized and frozen allografts. The osteoinductive values of these 2 types were very high and similar. Autoclaved allografts, on the other hand, had very low osteoinductive values, as they were still at the very beginning of the healing process. Histomorphometric analysis revealed a significant difference in both newly formed osteoid thickness and osteoblast number per microm of bone surface in all experimental groups (P < 0.005). Values of osteoid thickness and osteoblast number were significantly higher in both frozen and pasteurized grafts when compared with the autoclaved ones (P < 0.005). Osteogenic properties of pasteurized bone allografts were preserved, and the allografts have been gradually replaced with newly formed bone. As such, pasteurized bone grafts from a bone bank have approximately the same biologic validity as frozen grafts, while autoclaved grafts impair bone healing. (+info)
Complication rate and factors affecting outcome of olecranon osteotomies repaired with pin and tension-band fixation in dogs.
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The objective of this study was to determine the complication rate and evaluate factors affecting the outcome of olecranon osteotomy in dogs. Medical records were searched to identify dogs that had undergone olecranon osteotomy (stabilized with 2 Kirschner wires and a figure-of-8 wire) during internal fixation of a supracondylar or condylar humeral fracture. Signalment, description of the fracture, parameters regarding the osteotomy and its repair, and radiographic outcome were recorded. A logistic regression model compared patient and technical parameters with the osteotomy outcome. Of the 19 dogs, 7 (37%) had complications of the osteotomy, including osteomyelitis, loss of reduction, and improper placement and migration of the Kirschner wires. Olecranon osteotomy is associated with a high complication rate in dogs; however, there was no correlation between patient-related or technical parameters and the development of complications. Further clinical and biomechanical investigations are warranted to improve the results of olecranon osteotomy and its repair. (+info)
Inherited thrombocytopenias: from genes to therapy.
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BACKGROUND AND OBJECTIVES: Inherited thrombocytopenias are a heterogeneous group of rare diseases characterized by a reduced number of blood platelets. Some of these diseases are exclusive to megakaryocytes and platelets, while in others the pathology extends to other cell types. Although the defective genes, coding for membrane glyoproteins, cytoskeleton components and intracellular signaling pathways, as well as transcription factors, have been identified in most cases, the pathophysiology of these disorders is often unknown. This review describes recent contributions to clinical and diagnostic aspects, biology and treatments of familial thrombocytopenias. EVIDENCE AND INFORMATION SOURCES: The information presented here derives from literature and the experience of the authors. The most relevant studies are critically analyzed and discussed. STATE OF ART: The clinical and laboratory features of most of the inherited thrombocytopenias have been reviewed. The different forms have been classified into 3 groups depending on platelet volume. Although this criterion is not completely satisfactory, it is one of the most useful in diagnostic algorithms. We report on recent advances in Wiskott-Aldrich and Bernard-Soulier syndromes, as well as in MYH9-related diseases, a new nosological entity that groups old distinct forms known as May-Hegglin anomaly, Sebastian, Fetchner, and Epstein syndromes. Other, less frequent forms are also discussed, including non-syndromic forms of mild thrombocytopenia that are genetically heterogeneous. PERSPECTIVES: In the past, inherited thrombocytopenias were considered exceedingly rare and the number of well-defined forms was very small. In the last few years, the widespread diffusion of electronic cell counters has allowed these conditions to be detected more frequently and several new entities have been identified through the co-ordinated efforts of physicians, biologists and geneticists. The pathogenesis of many new and old forms is being unraveled, thus providing insights on the molecular basis of platelet production and function. This knowledge will be a valuable resource for clinicians in the diagnostic approaches to such disorders. (+info)
Low-magnitude mechanical loading becomes osteogenic when rest is inserted between each load cycle.
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Strategies to counteract bone loss with exercise have had fairly limited success, particularly those regimens subjecting the skeleton to mild activity such as walking. In contrast, here we show that it is possible to induce substantial bone formation with low-magnitude loading. In two distinct in vivo models of bone adaptation, we found that insertion of a 10-s rest interval between each load cycle transformed a locomotion-like loading regime that minimally influenced osteoblast activity into a potent anabolic stimulus. In the avian ulna model, the minimal mean (+SE) periosteal labeled surface (Ps.LS) observed in the intact contralateral bones (1.6 +/- 1.5%) was doubled after 3 consecutive days of low-magnitude loading (3.8 +/- 1.5%; p = 0.03). However, modifying the regimen by inserting 10 s of rest between each load cycle significantly enhanced the periosteal response (21.9 +/- 4.5%; p = 0.03). In the murine tibia model, 5 consecutive days of 100 low-magnitude loading cycles did not significantly alter mean periosteal bone formation rate (BFR) compared with contralateral bones (0.011 +/- 0.005 microm3/microm2 per day vs. 0.021 +/- 0.013 microm3/microm2 per day). In contrast, separating each of 10 of the same loading cycles with 10 s of rest significantly elevated periosteal BFR (0.167 +/- 0.049 microm3/microm2 per day; p = 0.01). Endocortical bone formation parameters were not altered by any loading regimen in either model. We conclude that 10 s of rest between each load cycle of a low-magnitude loading protocol greatly enhances the osteogenic potential of the regimen. (+info)
Hemiarthroplasty of the elbow with a vascularized fibular graft after excision of Ewing's sarcoma of the proximal ulna: a case report.
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We report an 8-year-old girl with a Ewing's sarcoma in the right proximal ulna. The patient presented with pain in her right elbow, and plain radiographs showed destructive changes with a periosteal reaction in the proximal third of the ulna. A biopsy confirmed the diagnosis of Ewing's sarcoma. For preoperative chemotherapy, the patient received two courses of vincristine, doxorubicin and cyclophosphamide alternating with high-dose ifosfamide. MRI and angiography demonstrated that the chemotherapy was effective and therefore the patient underwent wide local excision of the tumor and reconstruction of the elbow joint using a vascularized fibular graft. Pathological examination of the resected specimen showed no evidence of viable tumor cells. After surgery, the patient received three courses of chemotherapy consisting of the same agents as those for the preoperative chemotherapy. Four years after surgery, there is no evidence of local recurrence or distant metastasis. Furthermore, the grafted bone is extending favorably and the patient has excellent function with active movement of the elbow. (+info)
Stochastic resonance in osteogenic response to mechanical loading.
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Stochastic resonance, in which noise enhances the response of a nonlinear system to a weak signal, has been observed in various biological sensory systems. We speculated that bone formation in response to mechanical loading could be enhanced by adding noise (vibration) to a standard exercise regimen. To test this hypothesis, three different loading regimens were applied to the ulnae of mice: (1) high amplitude, low frequency sinusoidal loading at 2 Hz with an amplitude of 3 N to simulate exercise; (2) low amplitude, broad frequency vibration with frequency components 0-50 Hz and 0.3 N of mean amplitude; (3) the sinusoidal wave combined with vibration (S+V) to invoke stochastic resonance. The simulated exercise regimen induced new bone formation on the periosteal surface of the ulna, however the addition of vibration noise with exercise enhanced the osteogenic response by almost 4-fold. Vibration by itself had no effect on bone formation. It was concluded that adding low magnitude vibration greatly enhanced bone formation in response to loading, suggesting a contribution of stochastic resonance in the osteogenic response. (+info)
Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone.
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Bone is removed or replaced in defined locations by targeting osteoclasts and osteoblasts in response to its local history of mechanical loading. There is increasing evidence that osteocytes modulate this targeting by their apoptosis, which is associated with locally increased bone resorption. To investigate the role of osteocytes in the control of loading-related modeling or remodeling, we studied the effects on osteocyte viability of short periods of mechanical loading applied to the ulnae of rats. Loading, which produced peak compressive strains of -0.003 or -0.004, was associated with a 78% reduction in the resorption surface at the midshaft. The same loading regimen resulted in a 40% relative reduction in osteocyte apoptosis at the same site 3 days after loading compared with the contralateral side (P = 0.01). The proportion of osteocytes that were apoptotic was inversely related to the estimated local strain (P < 0.02). In contrast, a single short period of loading resulting in strains of -0.008 engendered both tissue microdamage and subsequent bone remodeling and was associated with an eightfold increase in the proportion of apoptotic osteocytes (P = 0.02) at 7 days. This increase in osteocyte apoptosis was transient and preceded both intracortical remodeling and death of half of the osteocytes (P < 0.01). The data suggest that osteocytes might use their U-shaped survival response to strain as a mechanism to influence bone remodeling. We hypothesize that this relationship reflects a causal mechanism by which osteocyte apoptosis regulates bone's structural architecture. (+info)
Bone adaptation to load: microdamage as a stimulus for bone remodelling.
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Mechanical loading in the proximal radius was increased by ulnar osteotomy (Group O), altered by Steinmann pinning (Group P) or unaltered in sham operated controls (Group C) in skeletally mature female sheep, aged 2-4 years. A series of intravenous fluorochromes were given to label bone formation and fuchsin-stained microdamage assessed at intervals of up to 24 weeks. Microcracks were present in all groups and were found in the original cortex near the periosteal surface. No microcracks were found in the new, fibrolamellar bone laid down at periosteal or endosteal surfaces. Mean microcrack length (49 microm, SD 10 microm) did not differ between groups or overtime. Microcrack numerical and surface densities and resorption cavity density peaked in all groups at 6 weeks, consistent with a regional acceleratory phenomenon (RAP), but the peaks were significantly greater in Group O. The density of refilling or secondary osteons peaked at 10 weeks and the mean time required for the formation of an osteon was 7.51 +/- 0.59 weeks. Fatigue-induced microdamage is normally present in bone and is increased due to repetitive loading of the mechanically overloaded radius. The location and timing of microcracks, resorption cavities and secondary osteons are consistent with the activation-resorption-formation remodelling cycle and suggest that microdamage is a stimulus for bone remodelling. (+info)