			Home About us Contact

Segmental Defects (segmental + defect)

Distribution by Scientific Domains

Life Sciences	55%
Medical Sciences	33%

Selected Abstracts

Shock Wave Application Enhances Pertussis Toxin Protein-Sensitive Bone Formation of Segmental Femoral Defect in Rats,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2003
Yeung-Jen Chen
Abstract Extracorporeal shock waves (ESWs) elicit a dose-dependent effect on the healing of segmental femoral defects in rats. After ESW treatment, the segmental defect underwent progressive mesenchymal aggregation, endochondral ossification, and hard callus formation. Along with the intensive bone formation, there was a persistent increase in TGF-,1 and BMP-2 expression. Pretreatment with pertussis toxin reduced ESW-promoted callus formation and gap healing, which presumably suggests that Gi proteins mediate osteogenic signaling. Introduction: Extracorporeal shock waves (ESWs) have previously been used to promote bone repair. In our previous report, we found that ESWs promoted osteogenic differentiation of mesenchymal cells through membrane perturbation and activation of Ras protein. In this report, we show that ESWs elicit a dose-dependent effect on the healing of segmental defects and that Gi proteins play an important role in mediating ESW stimulation. Materials and Methods: Rats with segmental femoral defects were subjected to ESW treatment at different energy flux densities (EFD) and impulses. Bone mass (mineral density and calcium content), osteogenic activities (bone alkaline phosphatase activity and osteocalcin content), and immunohistochemistry were assessed. Results: An optimal ESW energy (500 impulses at 0.16 mJ/mm2 EFD) stimulated complete bone healing without complications. ESW-augmented healing was characterized by significant increases (p < 0.01) in callus size, bone mineral density, and bone tissue formation. With exposure to ESW, alkaline phosphatase activity and osteocalcin production in calluses were found to be significantly enhanced (p < 0.05). After ESW treatment, the histological changes we noted included progressive mesenchymal aggregation, endochondral ossification, and hard callus formation. Intensive bone formation was associated with a persistent increase in transforming growth factor-beta 1 (TGF-,1) and bone morphogenetic protein-2 (BMP-2) expression, suggesting both growth factors were active in ESW-promoted bone formation. We also found that pertussis toxin, an inhibitor of membrane-bound Gi proteins, significantly reduced (p < 0.01) ESW promotion of callus formation and fracture healing. Conclusion: ESW treatments enhanced bone formation and the healing of segmental femoral defects in rats. It also seems likely that TGF-,1 and BMP-2 are important osteogenic factors for ESW promotion of fracture healing, presumably through Gi protein-mediated osteogenic signaling. [source]

Effect of cell-based VEGF gene therapy on healing of a segmental bone defect

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2009
Ru Li
Fracture healing requires coordinated coupling between osteogenesis and angiogenesis in which vascular endothelial growth factor (VEGF) plays a key role. We hypothesized that targeted over-expression of angiogenic and osteogenic factors within the fracture would promote bone healing by inducing development of new blood vessels and stimulating/affecting proliferation, survival, and activity of skeletal cells. Using a cell-based method of gene transfer, without viral vector, 5.0,×,106 fibroblasts transfected with VEGF were delivered to a 10-mm bone defect in rabbit tibiae (Group 1) (n,=,9); control groups were treated with fibroblasts (Group 2) (n,=,7), or saline (Group 3) (n,=,7) only. After 12 weeks, eight tibial fractures healed in Group 1, compared to four each in Groups 2 and 3. In Group 1, ossification was seen across the entire defect; in Groups 2 and 3, the defects were fibrous and sparsely ossified. Group 1 had more positively stained (CD31) vessels than Groups 2 and 3. MicroCT 3-D showed complete bridging of the new bone for Group 1, but incomplete healing for Groups 2 and 3. MicroCT bone structural parameters showed significant differences between VEGF treatment and control groups (p,<,0.05). These results indicate that the cell-based VEGF gene therapy has significant angiogenic and osteogenic effects to enhance healing of a segmental defect in the long bone of rabbits. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:8,14, 2009 [source]

The efficacy of cylindrical titanium mesh cage for the reconstruction of a critical-size canine segmental femoral diaphyseal defect

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 7 2006
Ronald W. Lindsey
Abstract The authors developed a novel technique for the reconstruction of large segmental long bone defects using a cylindrical titanium mesh cage (CTMC). Although the initial clinical reports have been favorable, the CTMC technique has yet to be validated in a clinically relevant large animal model, which is the purpose of this study. Under general anesthesia, a unilateral, 3-cm mid-diaphyseal segmental defect was created in the femur of an adult canine. The defect reconstruction technique consisted of a CTMC that was packed and surrounded with a standard volume of morselized canine cancellous allograft and canine demineralized bone matrix. The limb was stabilized with a reamed titanium intramedullary nail. Animals were distributed into four experimental groups: in Groups A, B, and C (six dogs each), defects were CTMC reconstructed, and the animals euthanized at 6, 12, and 18 weeks, respectively; in Group D (three dogs), the same defect reconstruction was performed but without a CTMC, and the animals were euthanized at 18 weeks. The femurs were harvested and analyzed by gross inspection, plain radiography, computed tomography (CT), and single photon emission computed tomography (SPECT). The femurs were mechanically tested in axial torsion to failure; two randomly selected defect femurs from each group were analyzed histologically. Groups A, B, and C specimens gross inspection, plain radiography, and CT, demonstrated bony restoration of the defect, and SPECT confirmed sustained biological activity throughout the CTMC. Compared to the contralateral femur, the 6-, 12-, and 18-week mean defect torsional stiffness was 44.4, 45.7, and 72.5%, respectively; the mean torsional strength was 51.0, 73.6, and 83.4%, respectively. Histology documented new bone formation spanning the defect. Conversely, Group D specimens (without CTMC) demonstrated no meaningful bone formation, biologic activity, or mechanical integrity at 18 weeks. The CTMC technique facilitated healing of a canine femur segmental defect model, while the same technique without a cage did not. The CTMC technique may be a viable alternative for the treatment of segmental long bone defects. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1438,1453, 2006 [source]

One gene, two phenotypes: ROR2 mutations in autosomal recessive Robinow syndrome and autosomal dominant brachydactyly type B,

HUMAN MUTATION, Issue 1 2003
Ali R. Afzal
Abstract Autosomal recessive Robinow syndrome (RRS) is a severe skeletal dysplasia with short stature, generalized limb shortening, segmental defects of the spine, brachydactyly, and a dysmorphic facial appearance. The gene encoding receptor orphan receptor tyrosine kinase 2 (ROR2) is located on chromosome 9q22 and homozygous loss-of-function mutations in this gene are responsible for RRS. Moreover, knocking out the mouse Ror2 gene causes mesomelic dwarfism in the homozygous state, with almost identical features to recessive Robinow syndrome. The protein product of this gene is a cell membrane receptor, containing distinct motifs including an immunoglobulin-like (Ig) domain, a Frizzled-like cysteine-rich domain (FRZ or CRD), and a kringle domain (KD) in the extracellular region; and an intracellular region with tyrosine kinase (TK), serine/threonine-rich, and proline-rich structures. The extracellular motifs of the ROR2 protein are known to be involved in protein,protein interactions. The tyrosine kinase domain is involved in an as yet uncharacterized signaling pathway. Interestingly, heterozygous mutations in ROR2 have recently been shown to give rise to autosomal dominant brachydactyly type B1 (BDB1). This condition is characterized by terminal deficiency of fingers and toes. A variety of mutations have been reported in ROR2. Here, these genetic defects are compiled and possible genotype,phenotype correlations are discussed. Hum Mutat 22:1,11, 2003. © 2003 Wiley-Liss, Inc. [source]

Repair of segmental defects in rabbit humeri with titanium fiber mesh cylinders containing recombinant human bone morphogenetic protein-2 (rhBMP-2) and a synthetic polymer

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2002
Narumichi Murakami
Abstract To develop a new technology that enhances the regeneration potential of bone and the repair of large intercalated defects in long bone, recombinant human bone morphogenetic protein-2 (BMP-2; 20 ,g or 40 ,g) was mixed in a polymer gel (poly-lactic acid-polyethyleneglycol block copolymer; PLA-PEG; 200 mg) and incorporated into titanium fiber-mesh cylinders. Three 5-mm cylinders were placed end-to-end to fill a 15-mm defect created in the humeri of adult rabbits and were stabilized by an intramedullary rod. In controls, the titanium fiber-mesh cylinders were combined with PLA-PEG in the absence of BMP. Six weeks after implantation, new bone had formed on the surface of the implant and had bridged the defect. All of the defects (5/5) treated by cylinders containing 120 ,g (40 ,g × 3) of BMP were repaired completely. New bone formation was also found inside the pores of the cylinders. The defect was not repaired in the control animals. These results demonstrate that these new composite implants fabricated by combining rhBMP, synthetic degradable polymers and compatible biomaterials enhance the regeneration potential of bone. Thus, it is possible that large skeletal defects can be repaired using this prosthesis in lieu of autogenous bone graft. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 169,174, 2002 [source]

Shock Wave Application Enhances Pertussis Toxin Protein-Sensitive Bone Formation of Segmental Femoral Defect in Rats,

Repair of rabbit segmental defects with the thrombin peptide, TP508

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2004
Michael R. Sheller
Abstract The synthetic peptide, TP508 (Chrysalin®), was delivered to rabbit segmental bone defects in biodegradable controlled-release PLGA microspheres to determine its potential efficacy for enhancing healing of non-critically and critically sized segmental defects. Non-critically sized radial defects were created in the forelimbs of New Zealand White rabbits, which were randomized into three treatment groups receiving 10, 50 and 100 ,g doses of TP508 in the right radius and control microspheres (without TP508) in the left radius. Torsional testing of the radii at six weeks showed a significant increase in ultimate torque, failure torque, ultimate energy, failure energy, and stiffness when treated with TP508 compared to controls (p < 0.01 for all measures). Thus, TP508 appeared to enhance or accelerate bone growth in these defects. In a second set of experiments, critically sized ulnar defects were created in the forelimbs of New Zealand White rabbits, which were randomized into two groups with each rabbit receiving microspheres with 100 or 200 ,g of TP508 into the right ulnar defect and control microspheres (without TP508) alone into the left ulnar defect. Bone healing was evaluated with plain radiographs, synchrotron-based microtomography, and mechanical testing. Radiographs of the rabbit limbs scored by three blinded, independent reviewers demonstrated a significantly higher degree of healing when treated with TP508 than their untreated control limbs (p < 0.05). Three-dimensional synchrotron tomography of a limited number of samples showed that the new bone in TP508-treated samples had a less porous surface appearance and open marrow spaces, suggesting progression of bone remodeling. Torsional testing of the ulnae at nine weeks showed a significant increase in maximum torque and failure energy when treated with TP508 compared to controls (p < 0.01 for both measures). These results suggest that TP508 in a controlled release delivery vehicle has the potential to enhance healing of segmental defects in both critically and non-critically sized defects. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source]

Isolated congenital spleen agenesis: A rare cause of chronic thromboembolic pulmonary hypertension in an adult

RESPIROLOGY, Issue 6 2008
Fumiyuki TAKAHASHI
Abstract: This report describes a case of isolated congenital spleen agenesis complicated by chronic thromboembolic pulmonary hypertension (CTPH) in a 44-year-old female patient. The patient had increasing exertional dyspnoea and thrombocytosis. An echocardiogram showed severe pulmonary hypertension and right ventricular hypertrophy, and contrast-enhanced chest CT revealed multiple thromboemboli within both pulmonary arteries. A perfusion lung scan demonstrated multiple segmental defects and no spleen was detected by abdominal CT, ultrasonography or scintigraphy. Comprehensive clinical examinations disclosed no evidence of a thrombus elsewhere or of an associated malformation such as a cardiac anomaly. Anticoagulation therapy was started, and a perfusion lung scan revealed partial improvement of the hypoperfusion in the right lower lobe. However, repeat echocardiography showed the pulmonary hypertension persisting for 1 year. The multiple segmental defects in the perfusion lung scans were also persistent. Collectively, a diagnosis of CTPH with isolated congenital spleen agenesis was established. This is the first documented case of CTPH in an adult with isolated congenital asplenia. Although congenital spleen agenesis is a rare condition, this case report suggests that this possibility should be considered when a diagnosis of CTPH and thrombocytosis is made. [source]