Biomedical subjects

A W Baltzer

Publications and source records attributed to A W Baltzer.

At least 19 recordsLinked to original sources

PubMed2006

Effect of BMP-2 gene transfer on bone healing in sheep.

Critical size defects of bone and delayed fracture healing due to metabolic disorders are still problems in orthopaedic surgery. Adenoviral vectors encoding bone morphogenetic protein-2 (Ad.BMP-2) have been used to stimulate bone formation in small animals. The present study evaluated the use of direct adenoviral gene transfer for inducing bone formation in a large animal. Standardized iliac crest defects were created surgically on both sides of the pelvic bone of white mountain sheep. The efficiency of gene transfer was evaluated using recombinant adenoviruses carrying the cDNA for luciferase. High levels of transgene expression, restricted to the site of injection, were found for the 1st week. Transgene expression then fell considerably, but could still be detected for up to 5 weeks. To investigate the effect on bone healing, Ad.BMP-2 (10(11) particles in 200 mul saline) was unilaterally injected into iliac crest defects and into tibial osteotomies. The contralateral defects remained untreated to evaluate possible systemic effects. The controls were treated with saline solution. Bone formation within the defect, assessed by micro-computed tomography (CT) measurement at 8 weeks, and callus formation after osteotomy were significantly reduced following direct application of Ad.BMP-2. The retardation compared to untreated control animals was additionally found at the contralateral iliac crest indicating a systemic inhibitory effect. Histological analysis confirmed the CT measurement and showed an increased number of inflammatory cells within both defects. Antibodies against the adenovirus and the transgene product were detected in all treated animals. These data show a systemic retardation of bone formation following a single local injection of Ad.BMP-2 in sheep. This finding stands in contrast to the data obtained from small animal models. Further studies are needed to determine the contribution of the immune response to these results, and whether a lower dose of Ad.BMP-2 would be advantageous.

Adenoviridae↗

PubMed2006

Direct adenoviral transfer of bone morphogenetic protein-2 cDNA enhances fracture healing in osteoporotic sheep.

Osteoporosis, a major public health burden, is associated with increased fracture risk. Fracture healing in osteoporosis is delayed, with reduced callus formation and impaired biomechanical properties of newly formed bone leading to high risk of fixation failure. Adenoviral gene transfer of bone morphogenetic protein-2 (BMP-2) has been shown to enhance fracture healing. This study evaluated the ability of gene transfer to enhance bone healing in osteoporosis. An established sheep model of osteoporosis with well-characterized alterations in fracture healing was used. Osteotomies were created surgically in the tibias of adult female sheep and monitored for 8 weeks, using radiographic, biomechanical, and histological methods. For pilot experiments, primary ovine osteoblasts and mesenchymal stem cells were transduced with a recombinant adenovirus carrying BMP-2 cDNA (Ad.BMP-2). Large increases in alkaline phosphatase production and mineralization confirmed the ability of human BMP-2 to stimulate osteoblastic differentiation in sheep. In vivo bending stiffness measurements during fracture healing as well as ex vivo torsional stiffness measurements demonstrated stiffer callus tissue after treatment with Ad.BMP-2. The differences were found mainly in the early fracture-healing period. Computed tomography demonstrated that animals receiving the BMP-2 cDNA had larger cross-sectional callus area and higher callus density. Histological examination of the tibias confirmed enhanced callus formation. Direct, local adenoviral delivery of an osteogenic gene thus led to enhanced healing of fractures in an ovine model of osteoporosis. These promising data encourage the further development of genetic approaches to enhance bone healing in patients suffering osteoporosis-associated fractures.

Adenoviridae↗

PubMed2005

The potential of gene therapy for fracture healing in osteoporosis.

Osteoporosis-associated fractures impair a patient's function and quality of life and represent one of the major public health burdens. Demographic changes predict a dramatic increase in osteoporotic fractures. Experimental data have shown that osteoporosis impairs fracture healing. Clinical observations demonstrate high failure rates of implant fixation in osteoporosis. The reduced healing capacity, including impaired bone formation, in osteoporotic humans might be due to defects in mesenchymal stem cells that lead to reduced proliferation and osteoblastic differentiation. Growth factors show remarkable promise as agents that can improve the healing of bone or increase the proliferation and differentiation capacities of mesenchymal stem cells. Their clinical utility is limited by delivery problems. The attraction of gene-transfer approaches is the unique ability to deliver authentically processed gene products to precise anatomical locations at therapeutic levels for sustained periods of time. Unlike the treatment of chronic diseases, it is neither necessary nor desirable for transgene expression to persist beyond the few weeks or months needed to achieve healing. This review presents different approaches of gene therapy to enhance fracture healing and summarizes the promising results of preclinical studies. It focuses on applications of this new technique to fracture healing in osteoporosis. In our opinion, these applications represent some of the few examples in which gene therapy has a good chance of early clinical success.

Adenoviridae↗

PubMed2003

[Experiences after 150 cartilage-bone-transplantations of the knee: a prospective analysis of the results].

INTRODUCTION: To evaluate the clinical outcome of cartilage-bone-transplantations of the knee in patients with different indications, we studied the clinical results of 45 patients with a follow-up of 24 months after operation. PATIENTS AND METHODS: 29 male and 16 female patients with a mean age of 37.7 yrs (16-58 yrs) were included. Indications for operation were osteochondritis dissecans (OD) (n=13), limited arthritis (n=20), traumatic lesions (n=5) and retropatellar lesions (n=7). The results were evaluated by clinical score (McDermott Score; preoperatively, and 3, 6, 12, 24 months postoperatively), magnetic resonance imaging, and re-arthroscopy for most patients. RESULTS: 42 of 45 patients judged the operation as successful. The mean score value of all patients raised from 66.3 pts (out of 100 pts) preoperatively to 92.7 pts 24 months postoperatively. The results of the patients with circumscript arthritic lesions (62.9 pts. preoperatively vs. 91.5 pts. postoperatively) were comparable to those of the other patients. CONCLUSION: We conclude that cartilage-bone-transplantation of the knee is a valuable procedure to improve joint function not only after OD or trauma, but also in joints with local arthritic lesions on condition that there is an adequate quality of the donor site.

Adolescent↗

PubMed2001

Gene therapy for osteoporosis: evaluation in a murine ovariectomy model.

Various cytokines and cytokine antagonists hold promise as new therapeutic agents for osteoporosis, but their application is hindered by delivery problems. Gene transfer offers an attractive technology with which to obviate these restrictions. Its utility was evaluated in an animal model of osteoporosis. Disease was induced by surgical ovariectomy and monitored by measuring bone weight after 12 days, and by histomorphometry after 5 weeks. Genes were transferred to the mice by intramedullary injection of adenoviral vectors. LacZ and luciferase marker genes were used to identify the bone marrow cells transduced by this procedure, and to track the possible spread of transgenes to other organs. The effect on bone loss of transferring a cDNA encoding the human interleukin-1 receptor antagonist (IL-1Ra) was then evaluated. The intramedullary injection of adenoviral vectors transduced lining osteoblasts, osteocytes and cells within the bone marrow. Luciferase activity persisted within the injected femora and adjacent musculature for at least 3 weeks, and in the draining lymph nodes for 2 weeks. Transient, low level expression was present in the liver, but no luciferase was detected at any time in the lung or spleen. Intramedullary introduction of the IL-1Ra gene resulted in circulation of the corresponding protein at concentrations that peaked on day 3, and returned to baseline by day 12. Transfer of the IL-1Ra gene strongly reduced the early loss of bone mass occurring in response to ovariectomy. Furthermore, it completely inhibited the loss of matrix detected by histomorphometry at 5 weeks. The protective effect of this gene was not restricted to bones receiving intramedullary injection of the vector, but occurred in all bones that were evaluated. This proof of concept encourages further development of gene therapy approaches to the treatment of osteoporosis.

Adenoviridae↗

PubMed2001

[Osteochondral shear fractures in children. A case report and critical review of the literature].

Only few articles on osteochondral flake fractures in children have been published. Diagnostic tools have been improved over the past decades, but still, diagnosis of severe osteochondral defects may be delayed. The presented case report describes the different techniques currently being available for the diagnosis of osteochondral flake fractures. The different therapeutic options for the treatment of osteochondral flake fractures in children are discussed based on the current literature. This article demonstrates the necessity to consider severe injuries, even if impressive clinical symptoms are lacking.

Arthroscopy↗

PubMed2001

[Experimental validation of DXA and MRI-based bone density measurement by ash-method].

Different methods have been established for bone density measurements such as dual energy X-ray absorptiometry (DXA), quantitative computertomography (QCT), and scintigraphy (VQ-Scan). There are hints that magnetic resonance imaging (MRI) might become a new option for the evaluation of bone density. The aim of this study was to investigate correlations between MRI vs. DXA and MRI vs. mineral content of lumbar vertebrae. Data were obtained from ten lumbar vertebral bodies of cattles. The T-1 MRI-sequences SE, PS, and the T-2 Sequence STIR were used for analysis. Total pixel numbers and a pixel per area ratio were determined. Values were compared to DXA-measurements, to the wet weight, and to separated measurements of the spongious, trabecular, and total mineral content of the vertebral body after ashing. We found correlations between DXA (g/vertebral body) vs. mineral content by ash-method (0.918; p < 0.01), DXA vs. MRI (SE-sequence) (-0.872; p < 0.01), and MRI (SE-sequence) vs. mineral content (0.775; p < 0.01). No correlations were found between PS- or STIR-sequences and the ash-method. This study shows that the determination of the bone mineral content of vertebrae is possible applying MRI in the T1-weighted SE-sequence. Without radiation, the MRI provides additionally early detection of trabecular lesions, fractures, and deformities at the spine, without other diagnostic procedures becoming necessary.

Absorptiometry, Photon↗

PubMed2000

[Increasing expression of growth factors by adenovirus gene transfer. A new method of fracture treatment?].

Gene therapy in orthopedic surgery is a new technic based on the idea of biological tissue healing. External gene segments are transferred to cells that overexpress growth factors locally to achieve this effect. The influence of growth factors on fracture healing is very well documented in the literature. Experimental data demonstrate that defect healing in bone can be accelerated by the application of different cytokines in vivo. Gene transfer is a promising, new technic of in situ tissue engineering that will enter clinics within the next decade.

Adenoviridae↗

PubMed2000

Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene.

This study evaluated the ability of gene transfer to enhance bone healing. Segmental defects were created surgically in the femora of New Zealand white rabbits. First generation adenoviruses were used as vectors to introduce into the defects genes encoding either human bone morphogenetic protein-2 (BMP-2) or, as a negative control, firefly luciferase. Representative specimens were evaluated histologically after 8 weeks. Healing of the defects was monitored radiographically for 12 weeks, after which time the repair tissue was evaluated biomechanically. By radiological criteria, animals receiving the BMP-2 gene had healed their osseous lesions after 7 weeks, whereas those receiving the luciferase gene had not. Histologic examination of representative rabbits at 8 weeks confirmed ossification across the entire defect in response to the BMP-2 gene, whereas the control defect was predominantly fibrotic and sparsely ossified. At the end of the 12-week experiment, the control femora still showed no radiological signs of stable healing. The difference in radiologically defined healing between the experimental and control groups was statistically significant (P < 0. 002). Biomechanical testing of the femora at 12 weeks demonstrated statistically significant increases in the mean bending strength (P < 0.005) and bending stiffness (P < 0.05) of the animals treated with the BMP-2 gene. Direct, local adenoviral delivery of an osteogenic gene thus led to the healing of an osseous lesion that otherwise would not do so. These promising data encourage the further development of genetic approaches to enhancing bone healing. Gene Therapy (2000) 7, 734-739.

Adenoviridae↗

PubMed2000

Potential role of direct adenoviral gene transfer in enhancing fracture repair.

Gene therapy has much to offer in the treatment of conditions in which it is necessary to increase the formation of bone. Nonunions, segmental defects, and aseptic loosening are examples of conditions where the local expression of genes that inhibit osteolysis and promote osteogenesis might be helpful. Studies in which one such possibility has been evaluated experimentally are described. These investigations used a surgically produced segmental defect in the femurs of New Zealand White rabbits as the model system. Adjacent muscle was fashioned around the defect to form a chamber into which adenoviral vectors were injected. High levels of transgene expression were found in the muscle surrounding the defect after injection of vectors carrying marker genes. Transgene expression also was seen in the cut ends of the bone and the scar tissue within the gap. No transgene expression was seen in the contralateral limb, spleen, or lung; transient, low levels of expression were found in the liver. Transgene expression declined with time, disappearing from all tissue but bone by Day 26; expression persisted in bone for at least 6 weeks. The control defects did not heal spontaneously. Injection of adenovirus carrying a human bone morphogenetic protein-2 complementary deoxyribonucleic acid led to healing of the segmental defect within 12 weeks, as judged by radiographic, histologic, and biomechanical criteria. Adenovirus carrying a human transforming growth factor-beta 1 complementary deoxyribonucleic acid showed signs of improved healing, but not to the extent seen with the bone morphogenetic protein-2 complementary deoxyribonucleic acid. This approach to therapy holds much promise as a novel means of promoting osteogenesis.

Adenoviridae↗

PubMed1999

[Microsurgical lumbar intervertebral disk operation. Technique and complications].

Lumbar Microdiscetomy requires special instruments and provides a good view with a narrow approach. The microscope is the best surgical aid. Alternatives are a retractorintigrated light or headlamp. A specific complication of lumbar microdiscectomy--the wrong level--can be minimized by an exact preoperative planning. Other complications like dural lesions and exessive bleeding are less frequent with the microscope because of the better view. The most severe complications that can occur with any lumbar disc operation, major vessel or visceral injury, can be avoided by lusing the new rongeur with a depth guard.

Diskectomy↗

PubMed1999

A gene therapy approach to accelerating bone healing. Evaluation of gene expression in a New Zealand white rabbit model.

It has been demonstrated that BMPs, IGFs, and TGFbetas improve the process of bone healing in vivo. We have suggested the use of gene therapy as a possible way to deliver growth factors to fracture sites in order to improve repair. The aim of this study was to develop a minimally invasive gene therapy approach to treat bone injuries locally without damaging the local blood circulation. A segmental defect of 1.3 cm was created in the diaphysis of the femur in mature NZW rabbits. Internal fixation with 7-hole DCP plates and 2.7 mm screws was used to stabilize the bone. After building a chamber by tightly closing the muscles around the segmental defect, 0.5 ml of either saline solution or a collagen gel containing 1 x 10(10) particles of adenovirus carrying cDNA encoding either the bacterial beta-galactosidase gene (LacZ), or the firefly luciferase gene were injected into the gap. The control side received 0.5 ml of saline solution without virus particles. Bone marrow, cortical and trabecular bone and surrounding muscle were harvested from the injected femur and were analyzed for local gene expression through X-gal staining or measurement of local luciferase activity. To determine whether distant sites were transduced, tissue from the spleen, liver, and lung were harvested as well as bone, bone marrow and muscle from the contralateral diaphysis of the femur. The delivery of the adenoviral vector suspended in saline solution led to local transduction of the bone, bone marrow and the muscle surrounding the gap. No luciferase activity was found in the contralateral femur, lung, or spleen, and only transient luciferase activity was seen in the liver. While marker gene expression persisted within the surrounding soft tissues for at least 2 weeks, the expression in bone lasted up to 6 weeks. This study has shown that it is possible to use adenoviral vectors to transfer and express genes locally within a segmental defect. Gene expression persisted for several weeks, which may be already sufficient to accelerate repair.

Adenoviruses, Human↗

PubMed1999

[In vitro transduction of human osteoblast cell populations with retroviral vectors].

OBJECTIVES: The involvement of cytokines in degeneration and inflammation of human tissue is well established. Interleukin-1 (IL-1) is a major agent in the pathophysiology of periarticular bone resorption in rheumatoid arthritis and in osteoporosis. Because the use of recombinant cytokines and growth factors is limited due to their short half lives, techniques are needed to get a permanent release of these therapeutic proteins. The rational of this study was to show that retroviral transduction of human osteoblastic cells is possible in vitro using the marker gene LacZ and the potentially therapeutic gene encoding for human interleukin-1 receptor antagonist protein (IL-1Ra). Different transduction techniques were combined to improve the rate of transduction in vitro. METHODS: Osteoblastic cells were isolated from human spongious bone and cultured in vitro. The beta-galactosidase (LacZ) gene and the cDNA of IL-1Ra were introduced into the isolated cells by retrovirus mediated gene transfer. LacZ activity was determined by Xgal staining, IL-1Ra was measured quantitatively by ELISA. RESULTS: The transfer of retroviral IL-1Ra led to IL-1Ra expression of 8614 to 10,089 pg IRAP/50,000 cells/48 h. By combining different techniques to improve transduction, the X-gal staining established a rate of transduction of 60%. CONCLUSION: Our results demonstrate that retroviral transduction of human osteobalstic cells is possible in vitro, and leads to high levels of the synthesized transgene product. The rate of retroviral transduction can be accelerated in vitro.

Cell Line↗

PubMed1999

Adenoviral transduction of human osteoblastic cell cultures: a new perspective for gene therapy of bone diseases.

This article confirms the susceptibility of osteoblastic cells to adenoviral transduction. Osteoblasts were harvested from human cancellous bone. Cells were transduced, using various amounts of adenoviral vectors carrying the cDNA encoding interleukin-1 receptor antagonist (IL-1 Ra), or the marker genes beta-galactosidase and luciferase. Expression of the transgenes and the biological activity of IL-1 Ra produced by gene transfer were measured quantitatively in a time-course by ELISA. The rate of transduction was 100% after exposure to 1 x 10(7) infective particles of adeno-LacZ. No expression of IL-1Ra was seen after transduction with adeno-IL-1Ra at titers of 1 x 10(4) and less. However, after transduction at titers of 1 x 10(7), infective particles cells expressed IL-1 Ra consistently for 72 days, with levels up to 1 microg IL-1 Ra/1 x 10(6) cells/ 48 hours. None of the control samples expressed detectable levels of IL-1 Ra. The biological activity of the transgenic IL-1 Ra was demonstrated by its ability to suppress successfully IL-1-induced nitric oxide synthesis by rabbit articular chondrocytes. After transduction with 1 x 10(7) infective particles of the adenoluciferase vector, up to 81,000 Units transgenic luciferase/x 10(6) osteoblastic cells were measured 2 days after gene transfer. Our results show that adenovirus transduces osteoblastic cells at a high rate in vitro.

Adenoviruses, Human↗

PubMed1999

[Postoperative, appositional ossifications after lumbar laminectomy].

QUESTION: Post-laminectomy segmental hypermobility as well as appositional ossification were suggested by many authors to contribute to the unsatisfactory long-term results of laminectomy. The aim of this study was to find out whether segmental instability, among other factors, influences the degree of appositional ossification following laminectomy. METHODS: 55 out of 72 patients operated upon by laminectomy or hemilaminectomy for degenerative lumbar spinal stenosis were examined by radiography after an average follow-up period of 5.2 years. Appositional ossification at the site of surgery was evaluated in relation to lumbar instability, the number of segments undergoing laminectomy, and whether simultaneous fusion was done. Instability was determined by measuring angulation and translation using lateral flexion and extension views of the lumbar spine, whereas new-bone formation was best evaluated on antero-posterior radiographs. RESULTS: 94% of the patients had appositional ossification at the site of laminectomy. Patients undergoing simultaneous fusion with laminectomy had a significantly lower amount of appositional ossification compared to patients undergoing laminectomy without segmental fusion. Radiographically measured segmental instability, the number of segments undergoing laminectomy, age, and sex of the patients did not influence the extent of ossification. CONCLUSIONS: Postoperative appositional ossification at the posterior site of resection are seen regularly following laminectomy. The extent of appositional ossification does correlate with lumbar fusions, but does not correlate with the extent of radiographically measured lumbar instability, the number of segments undergoing laminectomy, or the age and sex of the patients. CLINICAL RELEVANCE: Simultaneous lumbar fusion with laminectomy is proved to be associated with less appositional ossification. Therefore lumbar fusion should be considered when planning surgery for spinal stenosis.

Adult↗

PubMed1998

[American football injuries in the German Federal League: risk of injuries and pattern of injuries].

This prospective study investigated the incidence of injuries in German Bundesliga football based on an evaluation of 2 American football teams in the season and pre-season 1995 to 1997. Certified team physicians and team physiotherapists were the initial medical professionals providing on-site diagnosis, injury documentation and first treatment of all injuries. An injury was defined as minor injury (group I) causing a missing of practice or game up to 1 week, as severe injury (group II) causing a missing of practice or game for more than 1 week or hospitalisation and as fatal injury (group III) if the incident lead to treatment in an intensive care unit or remaining neurological or orthopaedical disability or death. Data were collected so that it was possible to calculate the risk of injury per time of exposition per athlete. The function of the athlete, influences of the weather and the mechanisms of the injuries were registered. Overall 713 injuries were documented. The rate of injury was calculated as 15.7 per 1000 hours of practice and game per athlete. Severe injuries with a loss of practice participation of more than 1 week were found in 94 cases. Fatal injuries were not seen in the period of the study. The knee was found to be the most common site of injury, the ankle ranked second. Our study showed that the risk of injury in American football in German Bundesliga is comparable with soccer or handball.

Adolescent↗

PubMed1998

[Injuries specific to ice skating--documentation of the injuries of competitive athletes during a pre-season training camp].

A Prospective Study. Competitive figure skaters absolve a comprehensive training schedule. The musculoskeletal system of pair and single skaters have to tolerate enormous impacts, especially throughout landings after repetitive jumps. Intense training leads therefore to specific sports injuries and chromic overuse injuries of the ice skaters. Twenty-five skaters were studied. We concentrated on the different types and localisations of injuries and on the individual loss of training sessions resulting from these injuries. The results are based on questionnaires and a clinical examination of the athletes. Typical acute and chronic injuries in figure skating mainly manifest at the lower extremity. It is striking that the first symptoms often occur during the preseason and persist the complete season or even for several years. The significance of sport specific and not ice skating related influences with regard to injury susceptibility is explained. Methodical "off-ice-training" seems to be useful to prevent injuries resulting from physical dysbalances. Improvements of the skating boots might protect from typical high impact during the landings after repetitive jumps.

Adolescent↗

PubMed1997

American football injuries in Germany. First results from Bundesliga football.

This study investigated the incidence of injury in German Bundesliga football based on the evaluation of two American football teams before and during the season 1995. Certified team physicians and team physiotherapists were the initial medical professionals providing on-site diagnosis, injury documentation and first aid for all injuries. An injury was defined as minor (group I) causing the player to miss practice or game sessions up to 1 week without requiring surgery; as severe (group II) causing the player to miss practice or game sessions for more than 1 week up to 3 months or requiring surgery; and as catastrophic (group III) if the incident led to treatment for more than 3 months, treatment in an intensive care unit or persistent neurological or orthopaedic disability or death. From the data collected it was possible to calculate the risk of injury per time of exposure per athlete. The athlete's function, influence of the weather and mechanisms of the injuries were registered. In total, 242 injuries were documented. The rate of injury was calculated as 16 per 1000 hours of practice and game per athlete. Severe injuries (group II) were found in 94 cases. Catastrophic injuries were not seen during the study. The knee was found to be the most common site of injury, while the ankle ranked second. Our study showed that the risk of injury in American football in German Bundesliga is comparable with soccer or handball.

Adolescent↗