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Jay R Lieberman

Publications and source records attributed to Jay R Lieberman.

At least 19 recordsLinked to original sources
PubMed2004

Combined bone morphogenetic protein-2 and -7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model.

UNLABELLED: To enhance the osteogenic activity of BMP, combination BMP2 and BMP7 gene transfer was performed. This approach led to a significant increase in osteoblastic differentiation of mesenchymal precursors compared with single BMP gene transfer in vitro. When tested in 78 rats, combination gene transfer enhanced mechanically stable spine fusion and bone formation rate versus single BMP gene transfer. INTRODUCTION: Although clinical bone morphogenetic protein (BMP) therapy is effective, required doses are very high. Previous studies have suggested that the co-expression of two different BMP genes can result in the production of heterodimeric BMPs that may be more potent than homodimers. In this study, combined BMP2 and BMP7 gene transfer was performed to test whether this approach improves osteoblastic differentiation and bone formation compared with single BMP gene transfer. MATERIALS AND METHODS: A producer cell (A549) was co-transfected with adenovirus vectors encoding BMP2 (AdBMP2) and BMP7 (AdBMP7) or, as controls, each vector alone, AdNull (with no transgene) or no virus. Supernatants were compared for their ability to stimulate osteoblastic differentiation of C2C12 myoblasts and MC3T3-E1 pre-osteoblasts. In a rat posterolateral spine fusion model, co-administration of AdBMP2 and AdBMP7 was compared with treatment with each vector alone, AdNull or no virus in 78 rats. The spines were assessed 8 weeks after surgery for radiographic and mechanical fusion, bone formation, and mineralization. RESULTS: BMP2 and BMP7 were co-precipitated from supernatants of cells co-transfected with AdBMP2 and AdBMP7, indicating the presence of BMP2/7 heterodimer. Supernatants of co-transfected cells containing relatively low doses (7-140 ng/ml) of BMPs induced osteocalcin expression and alkaline phosphatase activity in both C2C12 and MC3T3-E1 cells, that were up to 6- and 40-fold higher, respectively, than levels induced by maximal doses (200-1000 ng/ml) of either BMP2 or BMP7 alone. In the spine fusion model, co-administration of AdBMP2 and AdBMP7 resulted in a significantly greater number of mechanically stable fusions and also 2-fold higher mineralization rate and bone volume in the fusion mass versus single BMP gene transfer (p < 0.02, all comparisons). CONCLUSION: Combined BMP2 and BMP7 gene transfer is significantly more effective in inducing osteoblastic differentiation and spine fusion than individual BMP gene transfer.

3T3 Cells↗
PubMed2004

Genetic modification of stem cells to enhance bone repair.

Orthopaedic surgeons are often faced with difficult bone loss problems. Conventional bone grafting is usually accomplished with autogenous iliac crest bone graft that provides osteogenic cells, osteoinductive growth factors, and an osteoconductive matrix. Cadaveric bone allograft and bone graft substitutes are inferior to autogenous bone graft because they fail to supply osteogenic cells or a significant amount of osteoinductive growth factors. Recombinant growth factors such as bone morphogenetic protein-2 and osteogenic protein-1 are currently in clinical use but these proteins require supraphysiologic dosing and considerable expense while failing to provide a sustained osteoinductive signal at the implantation site. Mesenchymal stem cells capable of differentiating into mesodermal tissues have been isolated and expanded in culture from several different sources including bone marrow, adipose tissue, and muscle. In the presence of appropriate growth factors these cells can differentiate into osteoblast lineage cells that will form bone in vitro and in vivo. Recent attention has focused on genetic modification of mesenchymal stem cells to both produce and respond to osteogenic growth factors with the goal of developing a tissue engineering strategy for bone repair. This review examines the current potential and limitations of these cellular systems for bone repair.

Animals↗
PubMed2004

Core decompression for osteonecrosis of the hip.

The ultimate goal of treatment of patients with osteonecrosis of the hip is preservation of the femoral head. However, the development of a successful strategy to treat this disease has been difficult because neither the etiology nor the natural history of osteonecrosis of the hip has been defined clearly. Core decompression of the hip is one of the most commonly done surgical procedures to treat the early stages of osteonecrosis of the femoral head. However, there is no general consensus among investigators regarding either the specific indications for this procedure, or the specific technique of core decompression that would optimize results. The data available suggest that core decompression is more effective than nonoperative treatment particularly for patients with limited involvement of the femoral head and with an area of sclerosis surrounding the necrotic bone. The combination of core decompression with the use of osteoinductive or angiogenic agents to enhance bone formation and repair may enhance the results of this surgical procedure in the future.

Decompression, Surgical↗
PubMed2004

New technology and the orthopaedic surgeon: are you protecting your patients?

The treatment of patients with musculoskeletal disease will be revolutionized during the next two decades by advances in technology. Orthopaedic surgeons are eager to incorporate new technology into their practices to improve patient outcomes and practice efficiency. However, as the orthopaedic community embraces new technology and innovative surgical procedures, there is an increased need to consider issues of patient safety and to determine the best way to incorporate technology into our practices.

Conflict of Interest↗
PubMed2004

Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein.

A retrospective evaluation was done of 15 patients (17 hips) with symptomatic osteonecrosis of the hip treated with core decompression combined with an allogeneic, antigen-extracted, autolyzed fibula allograft and 50 mg of partially purified human bone morphogenetic protein and noncollagenous proteins. The average duration of clinical followup of the patients was 53 months (range, 26-94 months). The osteonecrotic involvement of the hip was classified by plain radiographs using a modification of the Ficat staging system and MRI evaluations. Fifteen hips were classified as Ficat Stage IIA, one hip (one patient) was classified as Ficat Stage IIB, and one hip (one patient) was classified as Ficat Stage III. Fourteen hips had involvement of 50% or less of the femoral head and 2/3 or less involvement of the weight-bearing surface of the femoral head, based on a magnetic resonance imaging evaluation. The procedures were a clinical success in 14 of 15 hips (93%; 13 patients) with Stage IIA disease. Three of 17 hips (three patients) had radiographic progression (Ficat Stages IIA, IIB, and III) of the femoral head and were converted to total hip replacements. Only one of seven hips (six patients) with 50% or less involvement of the femoral head and between 1/3 and 2/3 of the weightbearing surface of the femoral head developed radiographic progression of the femoral head. There was no radiographic progression in the 3 hips with less than 1/3 involvement of the weightbearing surface of the femoral head. Further evaluation of the potential efficacy of bone morphogenetic protein is required in randomized trials.

Adult↗
PubMed2004

Osteoinductivity of commercially available demineralized bone matrix. Preparations in a spine fusion model.

BACKGROUND: Although autogenous bone is the most widely used graft material for spinal fusion, demineralized bone matrix preparations are available as alternatives or supplements to autograft. They are prepared by acid extraction of most of the mineralized component, with retention of the collagen and noncollagenous proteins, including growth factors. Differences in allograft processing methods among suppliers might yield products with different osteoinductive activities. The purpose of this study was to compare the efficacy of three different commercially available demineralized bone matrix products for inducing spinal fusion in an athymic rat model. METHODS: Sixty male athymic rats underwent spinal fusion and were divided into three groups of eighteen animals each. Group I received Grafton Putty; Group II, DBX Putty; and Group III, AlloMatrix Injectable Putty. A control group of six animals (Group IV) underwent decortication alone. Six animals from each of the three experimental groups were killed at each of three intervals (two, four, and eight weeks), and the six animals from the control group were killed at eight weeks. At each of the time-points, radiographic and histologic analysis and manual testing of the explanted spines were performed. RESULTS: The spines in Group I demonstrated higher rates of radiographically evident fusion at eight weeks than did the spines in Group III or Group IV (p < 0.05). Manual testing of the spines at four weeks revealed variable fusion rates (five of six in Group I, two of six in Group II, and none of six in Group III). At eight weeks, all six spines in Group I, three of the six in Group II, and no spine in Group III or IV had fused. Histologic analysis of the spines in Groups I, II, and III demonstrated varying amounts of residual demineralized bone matrix and new bone formation. Group-I spines demonstrated the most new bone formation. CONCLUSIONS: This study demonstrated differences in the osteoinductive potentials of commercially available demineralized bone matrices in this animal model.

Animals↗
PubMed2004

Hyaluronan therapy: looking toward the future.

Hyaluronan therapy has numerous medical applications, including the treatment of joint arthropathies, wound healing, prevention of postsurgical adhesions, treatment of urinary incontinence, ophthalmic surgery, and tissue augmentation and engineering. Studies have been conducted and are ongoing to evaluate the efficacy of intra-articular hyaluronans in disease modification in osteoarthritis of the knee; efficacy in disease states other than osteoarthritis; as adjunct therapy after joint surgery; and in joints other than the knee--namely the shoulder, hand, hip, temporomandibular joint, spine, foot, and ankle. Preliminary results have been promising and parallel what has been found in treatment of osteoarthritis of the knee. Research also continues into the development of chemically modified derivatized hyaluronan to optimize responses and enhance duration of action, as well as to expand the uses of this therapeutic modality.

Animals↗
PubMed2004

Restoring articular cartilage in the knee.

Following damage or injury, as well as normal wear and tear, articular cartilage in adults has limited healing potential. Repair of cartilage is dependent on the extent and depth of the injury, its location, and the surviving chondrocytes and extracellular matrix. The ultimate goal of cartilage repair is to restore the normal composition and matrix of the cartilage, but for most patients this is not feasible. In these cases, filling the defect using interventions that provide adequate, albeit not optimal, functionality and pain relief is desirable. Therefore, a more realistic goal in these patients may be restoration of their respective activity levels and the delay or avoidance of prosthetic replacement. Depending on the age, activity level, and degree of cartilage damage, several methods to decrease pain and attempt cartilage repair are available; these include lavage and debridement, abrasion arthroplasty, and tissue and cell transplantation. Future strategies for cartilage repair may involve tissue engineering techniques, possibly coupled with specific growth factors. Randomized clinical trials must be established.

Cartilage, Articular↗
PubMed2003

Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement.

BACKGROUND: In a previous study of the prevention of venous thromboembolism after total knee replacement, the efficacy of ximelagatran, an oral direct thrombin inhibitor that does not require monitoring of coagulation or dose adjustment, was found to be similar to that of warfarin at a dose of 24 mg of ximelagatran twice daily. The purpose of the present study was to determine whether a higher dose of ximelagatran is superior to warfarin. METHODS: This randomized, double-blind trial compared a regimen of 7 to 12 days of oral ximelagatran, at a dose of 24 or 36 mg twice daily, starting the morning after surgery, with warfarin therapy started the evening of the day of surgery. The composite end point of venous thromboembolism and death from all causes and the incidence of bleeding were the primary outcome measures. RESULTS: Among the 1851 patients in the efficacy analysis, oral ximelagatran at a dose of 36 mg twice daily was superior to warfarin with respect to the primary composite end point of venous thromboembolism and death from all causes (20.3 percent vs. 27.6 percent; P=0.003). There were no significant differences between these two groups with respect to major bleeding (incidence, 0.8 percent and 0.7 percent, respectively), perioperative indicators of bleeding, wound characteristics, or the composite secondary end point of proximal deep-vein thrombosis, pulmonary embolism, and death (2.7 percent vs. 4.1 percent; P=0.17). CONCLUSIONS: The efficacy of oral ximelagatran, administered starting the morning after total knee replacement, was superior to that of warfarin for prevention of venous thromboembolism. Rates of hemorrhagic complications with the two drugs were similar.

Administration, Oral↗
PubMed2003

Bone induction by BMP-2 transduced stem cells derived from human fat.

PURPOSE: We have isolated pluripotent mesenchymal progenitor cells in large numbers from liposuction aspirates (processed lipoaspirate cells or PLAs). This study examines the osteogenic potential of PLAs and bone marrow aspirate cells (BMAs), when exposed to either recombinant human bone morphogenetic protein (BMP)-2 (rh-BMP-2) or adenovirus containing BMP-2 cDNA (Ad-BMP-2). METHODS: Liposuction aspirates underwent proteolytic digestion to obtain PLAs. After exposure to exogenous rh-BMP-2 or Ad-BMP-2 for four or seven days, PLAs and BMAs were assessed by histochemistry, spectrophotometry and RT-PCR. Western blotting and ELISA confirmed BMP gene transduction. Results were compared to osteoblasts and cells in osteogenic media only. PLA-Ad-BMP-2 cells were seeded on matrices and implanted in the hind limbs of SCID mice. RESULTS: Analysis of quantified bone precursor assays including extracellular ALP histomorphometry, intracellular ALP spectrophotometry, and calcified extracellular matrix (von Kossa) histomorphometry revealed that PLAs treated with exogenous rh-BMP-2 or transduced with a BMP-2 containing adenovirus (PLA-Ad-BMP-2) produced more bone precursors than osteoblasts (p=0.001). PLAs treated with exogenous rh-BMP-2 or PLA-Ad-BMP-2 also produced more bone precursors than BMAs (p=0.001), except for day 7 ALP histomorphometry (p=0.343). ELISA confirmed successful BMP-2 production by both progenitor cell groups transduced with Ad-BMP-2. H&E sections from collagen I matrices seeded with PLA-Ad-BMP-2 cells confirmed bone formation at six weeks. CONCLUSIONS: Liposuction aspirates contain PLAs that can be transfected with the BMP-2 gene, with rapid induction into the osteoblast phenotype at a rate comparable to rh-BMP-2 and osteoblast groups. Transduced PLAs produce more bone precursors with faster onset of calcified extracellular matrix than transduced BMAs. PLAs may be an ideal source of mesenchyme-lineage stem cells for gene therapy and tissue engineering.

Adenoviridae↗
PubMed2003

Patients' reasons for undergoing total hip arthroplasty can change over time.

The purpose of this study was to determine if a patient's reasons for undergoing a primary total hip arthroplasty (THA) changed at 1 year follow-up and, if the reasons did change, how does this change influence patient satisfaction with the procedure. Patients undergoing THA (101 patients) were evaluated with the McMaster Toronto Arthritis Patient Preference Disability (MACTAR) questionnaire and questions related to their expectations regarding the procedure. With the exception of pain and walking, most patients did not select the same preoperative and postoperative reasons for undergoing the procedure. In fact, 60% chose 2 new postoperative items. Patients whose expectations were not met were less likely to choose the same reasons for undergoing THA. Surgeons need to clarify patients' reasons for wanting a THA and attempt to identify new factors at follow-up that may influence patient satisfaction with the procedure.

Adult↗
PubMed2003

The impact of the garden classification on proposed operative treatment.

The current study evaluates the interobserver reliability and intraobserver reproducibility of the Garden classification of femoral neck fractures, assesses the influence of a lateral radiograph on a fracture's classification, and determines the classification's impact on the surgeon's choice of operative treatment. Forty radiographs of femoral neck fractures were evaluated independently by five orthopaedic surgeons. Kappa values were calculated for interobserver reliability and intraobserver variability with respect to the readers' ability to assess the fractures using the Garden classification and to determine fracture displacement with and without access to a lateral radiograph. In 69% of the instances in which a reader changed the classification of a fracture, the proposed treatment of the fracture did not change. The Garden classification has poor interobserver reliability but good intraobserver reproducibility. The addition of a lateral radiograph does not seem to improve the reliability of the current Garden classification system but may improve the reader's ability to determine fracture displacement. To improve the reliability and usefulness of the Garden classification, the authors suggest that the classification should be modified to have only two stages (Garden A-nondisplaced or valgus impacted and Garden B-displaced) and to include the use of a lateral radiograph.

Adult↗
PubMed2003

An evaluation of human demineralized bone matrices in a rat femoral defect model.

The osteoconductive and osteoinductive potential of two human allogeneic demineralized bone matrix putties were compared in a critical-sized athymic rat femoral defect model. Defects were treated with (1) a demineralized bone matrix in a hyaluronic acid carrier, (2) a demineralized bone matrix in a glycerol carrier, (3) a hyaluronic acid carrier alone, or (4) with no implant. Radiographic examinations and histologic analyses were done at 4, 8, and 16 weeks postoperatively. Eight of the 48 defects treated with a demineralized bone matrix and none of the 36 surgical controls showed complete radiographic healing by 16 weeks and no statistically significant difference between the radiographic scores for the two demineralized bone matrix preparations was found. On histologic review, both preparations of demineralized bone matrix had passive remineralization. The largest foci of endochondral ossification were seen in limbs treated with a demineralized bone matrix in a hyaluronic acid carrier. The 8-mm rat femoral defect allows for stringent assessment of the osteoinductive potential of bone graft substitutes. Hyaluronic acid and glycerol are viable carriers for demineralized bone matrices. As both de-mineralized bone matrices tested provided an adequate osteoconductive matrix and showed some, although limited, osteoinductive capacity, these materials should be used in clinical practice only as bone graft extenders or enhancers.

Aged↗
PubMed2003

Bone graft for revision hip arthroplasty: biology and future applications.

Revision total hip arthroplasty often presents surgeons with difficult bone loss problems. The selection of an appropriate bone graft is influenced by the size of the bone defect, the location, the biology of the bone graft site, and whether the graft is required for structural support. Autogenous bone graft remains the gold standard bone graft material but there only is a limited amount available and there is morbidity associated with the harvesting of these grafts. The most frequently used bone graft materials include autogenous iliac crest bone graft, cancellous allograft chips, demineralized bone matrix, and bulk structural allografts (femoral head, distal or proximal femoral allograft, whole acetabuli, and femoral strut grafts). It often is difficult to determine on plain radiographs whether nonstructural grafts actually incorporate into the host bone. Recently, attention has focused on the use of new materials for bone grafting including: new demineralized bone matrices, ceramics, autologous platelet concentrates, recombinant proteins, and stem cells. The purpose of this review was to assess the biologic potential of these nonstructural grafts in revision hip arthroplasty and their limitations. Are these agents actually incorporating into host bone? Future bone graft options, including tissue engineering and gene therapy will be discussed briefly.

Arthroplasty, Replacement, Hip↗
PubMed2003

Effect of regional gene therapy with bone morphogenetic protein-2-producing bone marrow cells on spinal fusion in rats.

BACKGROUND: Bone morphogenetic proteins (BMPs) are now being used as bone-graft substitutes to enhance spinal fusion. However, the large doses of BMP required to induce a spinal fusion in humans suggests that the delivery of these proteins should be improved. We used ex vivo adenoviral gene transfer to create BMP-2-producing bone marrow cells, and these autologous cells were found to induce a posterolateral fusion of the spine in syngeneic rats. METHODS: Intertransverse spinal arthrodesis (L4 and L5) was attempted in ten groups of Lewis rats with 5 x 10 (6) BMP-2-producing rat bone marrow cells (Ad-BMP-2 cells), created through adenoviral gene transfer with guanidine hydrochloride-extracted demineralized bone matrix as a carrier (Group I); 5 x 10 (6) Ad-BMP-2 cells on a collagen sponge carrier (Group II); 10 micro g of recombinant BMP-2 (rhBMP-2) in a guanidine hydrochloride-extracted demineralized bone matrix carrier (Group III); 10 micro g of rhBMP-2 in a collagen sponge carrier (Group IV); autogenous iliac crest bone-grafting (Group V); 5 x 10 (6) beta-galactosidase-producing rat bone marrow cells, created through adenoviral gene transfer with guanidine hydrochloride-extracted demineralized bone matrix as a carrier (Group VI); decortication of the transverse processes alone (Group VII); 5 x 10 (6) uninfected rat bone marrow cells with a guanidine hydrochloride-extracted demineralized bone matrix carrier (Group VIII); guanidine hydrochloride-extracted demineralized bone matrix only (Group IX); or a collagen sponge alone (Group X). Each specimen underwent plain radiography, manual palpation, and histological analysis. RESULTS: All spines in Groups I and II (BMP-2-producing bone marrow cells) and all spines in Groups III and IV were fused at four weeks postoperatively. In contrast, none of the spines in the other groups had fused at a minimum of eight weeks after implantation. Histological analysis of the specimens revealed that the spines that had received BMP-2-producing bone marrow cells (Groups I and II) were filled with coarse trabecular bone postoperatively, whereas those that had received rhBMP-2 (Groups III and IV) were filled with thin, lace-like trabecular bone. All of the other spines, including those that had been treated with autogenous iliac crest bone-grafting (Group V), produced little or no new bone. CONCLUSION: BMP-2-producing bone marrow cells, created by adenoviral gene transfer, produce sufficient BMP to induce an intertransverse fusion in the rat spine model.

Animals↗
PubMed2003

Osteonecrosis of the hip: management in the 21st century.

Osteonecrosis of the femoral head is a progressive condition that often leads to collapse of the femoral head. The ultimate goal in the treatment for osteonecrosis of the hip is preservation of the femoral head. However, the condition is difficult to treat because it is associated with a number of different diseases, and the etiology and natural history of the condition have not been definitively determined. The delineation of new information regarding the etiology, pathogenesis, and natural history of osteonecrosis is ongoing. Core decompression, vascularized and nonvascularized bone grafting procedures, and arthroplasty procedures play an important role in treatment.

Algorithms↗