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Jay R Lieberman

Publications and source records attributed to Jay R Lieberman.

At least 55 records · Page 3Linked to original sources
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↗
PubMed2003

Gene therapy in orthopaedic surgery.

Gene therapy has the potential to revolutionize the treatment of a variety of musculoskeletal disorders. In the past decade, more than 4,000 patients have been enrolled in clinical trials involving gene therapy. Gene therapy is becoming increasingly important in modern orthopaedic clinical practice. It is important to discuss the issues that physicians and scientists face when designing an experiment or clinical trial involving gene therapy, along with the potential clinical applications for gene therapy in the treatment of patients with musculoskeletal problems.

Bone Development↗
PubMed2002

Ximelagatran versus warfarin for the prevention of venous thromboembolism after total knee arthroplasty. A randomized, double-blind trial.

BACKGROUND: Warfarin is used for prophylaxis of venous thromboembolism in patients undergoing total knee arthroplasty. However, it is associated with rates of deep venous thrombosis (DVT) of approximately 38% to 55% and requires routine coagulation monitoring and frequent dose adjustment. Ximelagatran, an oral direct thrombin inhibitor, has shown promising efficacy and tolerability in patients undergoing total hip or knee arthroplasty. OBJECTIVE: To compare the efficacy and safety of ximelagatran and warfarin for prophylaxis of venous thromboembolism after total knee arthroplasty. DESIGN: Randomized, double-blind, parallel-group trial. SETTING: 74 North American hospitals. PATIENTS: 680 patients who had undergone total knee arthroplasty. INTERVENTION: 7 to 12 days of treatment with oral ximelagatran, 24 mg twice daily, starting on the morning after surgery, or warfarin (target international normalized ratio, 2.5 [range, 1.8 to 3.0]), starting on the evening of the day of surgery. MEASUREMENTS: Principal end points were asymptomatic DVT on mandatory venography; symptomatic DVT confirmed by ultrasonography or venography; symptomatic, objectively proven pulmonary embolism; and bleeding. All were assessed by blinded adjudication locally and at a central study laboratory. RESULTS: On central adjudication, incidence of venous thromboembolism was 19.2% (53 of 276 patients) in the ximelagatran group and 25.7% (67 of 261 patients) in the warfarin group (difference, -6.5 percentage points [95% CI, -13.5 to 0.6 percentage points]; P = 0.070). On local assessment, incidence was 25.4% in the ximelagatran group and 33.5% in the warfarin group (P = 0.043). In the ximelagatran and warfarin groups, respectively, major bleeding occurred in 1.7% and 0.9% of patients and minor bleeding occurred in 7.8% and 6.4% of patients. No variables related to bleeding differed significantly between the two groups. CONCLUSIONS: For prophylaxis of venous thromboembolism, fixed-dose ximelagatran started the morning after total knee arthroplasty is well tolerated and at least as effective as warfarin, but it does not require coagulation monitoring or dose adjustment.

Administration, Oral↗
PubMed2002

Use of zoledronate to treat osteoblastic versus osteolytic lesions in a severe-combined-immunodeficient mouse model.

Prostate adenocarcinoma is associated with the formation of osteoblastic metastases in bone. It has been hypothesized that osteoclastic bone resorption is a critical component before the development of these osteoblastic lesions in bone. This observation has led researchers to test agents that inhibit osteoclastic activity to prevent or halt the formation of metastatic prostate cancer lesions in bone. Bisphosphonates inhibit osteoclast activity, and previous studies showed that they have the ability to reduce the osteolytic bone resorption associated with multiple myeloma and breast cancer. The objective of this study was to evaluate the efficacy of zoledronate in limiting the formation and/or progression of osteoblastic lesions produced by the injection of known prostate cancer cells (LAPC-9 and PC-3 cells) into the tibia of SCID mice. The mice were treated with either 30- micro g or 150- micro g doses of zoledronate before tumor implantation (pretreatment group), or at weekly intervals after tumor implantation (weekly treatment group), or weekly starting one month after tumor implantation (delayed-treatment group). The zoledronate was very effective in limiting the formation of osteolytic lesions in PC-3 implanted tibias by inhibiting osteoclast activity. Radiographic and histological analysis at weekly intervals revealed that osteolytic lesions developed in the control tibias by 2 weeks, and there was complete destruction of the cortical bone in much of the proximal tibias by 4 weeks. In the treatment groups, there was minimal cortical destruction noted in the weekly treatment groups at both doses, whereas mild cortical erosion was evident in the pretreatment groups, with more cortical destruction noted in the 30- micro g group compared with the 150- micro g group. Tartrate-resistant acid phosphatase (TRAP) staining showed that zoledronate decreased osteoclastic numbers and that there was a dose-dependent response. In tibias implanted with the LAPC-9 cells, the zoledronate was not effective in halting the formation of the osteoblastic lesions. Radiographic and histological analysis revealed that osteoblastic lesions either had formed or were developing in 18 of 18 of the control tibias and 36 of 36 of the treated tibias at 8 weeks regardless of dose or treatment schedule. Furthermore, TRAP staining demonstrated that osteoblastic lesions had formed in the LAPC-9 tibias under conditions in which osteoclast numbers were significantly reduced. These results suggest that osteoclast activity may not be critical for the development of osteoblastic lesions associated with prostate tumor cells. Hence, bisphosphonates may not be ideal agents to prevent the formation of osteoblastic lesions associated with prostate cancer metastases to bone.

Adenocarcinoma↗
PubMed2002

Enhancement of bone repair with a helper-dependent adenoviral transfer of bone morphogenetic protein-2.

Regional gene therapy, which involves the delivery of growth factors to a specific anatomic site, has the potential to enhance bone formation in clinical application. Helper-dependent adenoviral vectors, which have deleted all of the viral coding regions, have been shown to be safe and highly efficient with long-lasting transgene expression. In this study, we constructed a helper-dependent adenoviral vector producing bone morphogenetic protein-2 (AdHDBMP-2). The AdHDBMP-2 increased the alkaline phosphatase activity of W-20-17 cells in vitro. In addition, when AdHDBMP-2 infected rat bone marrow cells were implanted into the hindlimbs of SCID mice, orthotopic bone formation was shown at 2 weeks. To our knowledge, this is the first study to demonstrate bone formation with the helper-dependent adenoviral vector with the BMP-2 expression cassette. This type of gene therapy vector could prove to be highly useful for bone augmentation in patients with bone loss associated with trauma, revision total joint arthroplasty, or cancer.

Adenoviridae↗
PubMed2002

Whole-body skeletal imaging in mice utilizing microPET: optimization of reproducibility and applications in animal models of bone disease.

The aims were to optimize reproducibility and establish [(18)F]fluoride ion bone scanning in mice, using a dedicated small animal positron emission tomography (PET) scanner (microPET) and to correlate functional findings with anatomical imaging using computed tomography (microCAT). Optimal tracer uptake time for [(18)F]fluoride ion was determined by performing dynamic microPET scans. Quantitative reproducibility was measured using region of interest (ROI)-based counts normalized to (a) the injected dose, (b) integral of the heart time-activity curve, or (c) ROI over the whole skeleton. Bone lesions were repetitively imaged. Functional images were correlated with X-ray and microCAT. The plateau of [(18)F]fluoride uptake occurs 60 min after injection. The highest reproducibility was achieved by normalizing to an ROI over the whole skeleton, with a mean percent coefficient of variation [(SD/mean) x 100] of <15%-20%. Benign and malignant bone lesions were successfully repetitively imaged. Preliminary correlation of microPET with microCAT demonstrated the high sensitivity of microPET and the ability of microCAT to detect small osteolytic lesions. Whole-body [(18)F]fluoride ion bone imaging using microPET is reproducible and can be used to serially monitor normal and pathological changes to the mouse skeleton. Morphological imaging with microCAT is useful to display correlative changes in anatomy. Detailed in vivo studies of the murine skeleton in various small animal models of bone diseases should now be possible.

Animals↗
PubMed2002

Effect of repeated irrigation and debridement on fracture healing in an animal model.

The initial management of open fractures often requires repeated irrigation and debridement of the open wound and stabilization of the fracture. However, washing out the fracture hematoma could delay the early healing process of stable fractures. Because delayed union and non-union are serious complications, the effect of repeated irrigation and debridement on the fracture healing process was investigated. Twenty-four rabbits received unilateral, transverse. mid-tibial open osteotomies with a 3 mm gap. The osteotomy site was thoroughly irrigated and stabilized with double-bar external fixators. The osteotomy sites in the study groups underwent repeat irrigation and debridement on either the third day (Group II), the fourth day (Group III), or consecutively on the first and second days (Group IV) after the index procedure. The bone healing was assessed with weekly radiographs and peripheral quantitative computerized tomographs. In Group I (control), all osteotomies healed radiographically before the tenth week. In Group II, five out of six osteotomies healed radiographically before the tenth week. In Group III, only two of five osteotomies healed before the tenth week. In Group IV, none of the osteotomies had healed by week fifteen. All of the non-healed osteotomies exhibited atrophic non-unions at fifteen weeks. Compared to the control group at the tenth week, the average bone mineral content at the osteotomy site and the area of high mineral density callus (> or = 890 mg/cm3) were significantly lower in Groups III (63%, p = 0.002 and 95%, p = 0.05, respectively) and IV (99%, p < 0.001 and 100%, p = 0.05, respectively). The results of this study suggest that repeated irrigation and debridement, associated with persistent rigid immobilization, may contribute to the development of delayed unions or atrophic non-unions.

Animals↗
PubMed2002

Extended-duration low-molecular-weight heparin prophylaxis following total joint arthroplasty.

Patients undergoing total joint arthroplasty are predisposed to the development of venous thromboembolic disease, including deep venous thrombosis and pulmonary embolism. Despite a standard course of postoperative prophylaxis, orthopedic patients remain at significant risk for late venous thromboembolic complications, resulting in considerable morbidity and mortality. Since routine screening for asymptomatic deep venous thrombosis with duplex ultrasound has not been found to be effective, the practice of extended out-of-hospital prophylaxis with low-molecular-weight heparin after total joint arthroplasty has been proposed in order to better protect these patients from delayed venous thromboembolic events. Multiple controlled, randomized clinical trials have shown that extended-duration low-molecular-weight heparin therapy significantly reduces the incidence of asymptomatic venous thromboembolic events following total hip arthroplasty, although no similar benefit has been observed in patients undergoing total knee arthroplasty. There are currently no comparative studies assessing the efficacy of long-term venous thromboembolic prophylaxis with oral anti-coagulant agents. Extending low-molecular-weight heparin therapy is not associated with any increase in major bleeding complications, but it may result in more frequent minor bleeding episodes. In addition, the cost-effectiveness of prolonging low-molecular-weight heparin treatment has not yet been firmly established. Although there is evidence supporting the use of extended out-of-hospital low-molecular-weight heparin prophylaxis after total hip arthroplasty, this strategy has not gained widespread acceptance in North America because of concerns regarding its adverse effects, cost-effectiveness, and uncertain patient compliance. There is general agreement that prophylaxis is needed after hospital discharge, and a minimum of 10 to 14 days of prophylaxis has been shown to be both safe and effective. However, further studies are necessary to determine the optimal duration of treatment.

Anticoagulants↗
PubMedDate not supplied

Healing of critically sized femoral defects, using genetically modified mesenchymal stem cells from human adipose tissue.

The FDA has approved the clinical use of recombinant bone morphogenetic proteins (BMPs). However, the use of recombinant BMPs in humans has required large doses of the proteins to be effective, which suggests that the delivery method of bone morphogenetic proteins needs to be optimized. Gene therapy is an alternative method to deliver such recombinant proteins, and gene transfer techniques have been tested on a variety of cell types including bone marrow cells, skin fibroblasts, peripheral blood monocytes, and muscle-derived cells. In this study, we sought to determine the ability of BMP-2-producing human adipose-derived mesenchymal stem cells to heal a critically sized femoral defect in a nude rat model. After approval by the human subjects protection committee, human adipose tissue was obtained from healthy donors. The lipoaspirate was processed as previously described (De Ugarte, D.A., et al. Cells Tissues Organs 174, 101, 2003). Cells were grown in culture and infected with a BMP-2-carrying adenovirus. Five million cells were applied to a collagen- ceramic carrier and implanted into femoral defects as previously described (Zuk, P.A., et al. Mol. Biol. 13, 4279, 2002). All animals were killed at 8 weeks. Femora were dissected out and underwent radiographic, histologic, and biomechanical analysis. Eleven of the 12 femora in the group treated with human processed lipoaspirate (HPLA) cells genetically modified to overexpress BMP-2 had healed at 8 weeks. This was assessed by radiographs, by mechanical testing, and by histology. The one femur that did not heal had a subacute infection. All eight of the femora treated with the rhBMP-2-impregnated collagen-ceramic carrier healed. No statistically significant difference was detected between these two groups. Evaluation of the control groups: group II (collagen- ceramic carrier with HPLA cells) and group III (collagen-ceramic carrier alone) showed that none of the femora had healed by 8 weeks. Our results indicate that HPLA cells genetically modified by adenoviral gene transfer to overexpress BMP-2 can induce bone formation in vivo and heal a critically sized femoral defect in an athymic rat. The HPLA cells alone did not induce significant bone formation. However, when combined with an osteoinductive factor these cells may be an effective method for enhancing bone healing and the tissue engineering of bone.

Adenoviridae↗