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At least 649 records · Page 36Linked to original sources
PubMed2003

Adenoviral VEGF-A gene transfer induces angiogenesis and promotes bone formation in healing osseous tissues.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. VEGF has been safely and efficiently applied to stimulate neovascularization in ischemic tissues in atherosclerotic patients. VEGF has an important role in bone repair by promoting angiogenesis and by stimulating major skeletal cell populations, chondrocytes, osteoblasts and osteoclasts. METHODS: We studied the effect of VEGF-A on the recovery of bone drilling defects in rat femur delivered with first-generation adenoviral vector. The virus was injected into the muscle layer surrounding the bone defect made by drilling and the healing was followed for 1, 2, and 4 weeks. RESULTS: The VEGF effect was first demonstrated with an increased number of FVIII-related antigen-positive blood vessels in the defect area 1 week after the procedure. The proportional area of remaining reparative tissue was significantly reduced in the VEGF-treated animals 2 weeks after the injury suggesting favorable effect on bone healing. Increased periosteal cartilage was seen at the early phases of healing suggesting endochondral ossification. VEGF overexpression, however, completed the endochondral phase earlier compared with the control condition. Bone mineral content was enhanced in the VEGF-treated femurs measured with peripheral quantitative computed tomography at a 2-week time point. CONCLUSIONS: Our data confirm the important role of VEGF in bone healing. We show for the first time that adenoviral VEGF-A gene transfer may modify bone defect healing in a rodent model.

Adenoviridae↗
PubMed2004

Local ex vivo gene therapy with bone marrow stromal cells expressing human BMP4 promotes endosteal bone formation in mice.

BACKGROUND: Bone loss in osteoporosis is caused by an imbalance between resorption and formation on endosteal surfaces of trabecular and cortical bone. We investigated the feasibility of increasing endosteal bone formation in mice by ex vivo gene therapy with bone marrow stromal cells (MSCs) transduced with a MLV-based retroviral vector to express human bone morphogenetic protein 4 (BMP4). METHODS: We assessed two approaches for administering transduced MSCs. beta-Galactosidase (beta-Gal) transduced C57BL/6J mouse MSCs were injected intravenously via tail vein or directly injected into the femoral bone marrow cavity of non-marrow-ablated syngenic recipient mice and bone marrow cavity engraftment was assessed. BMP4- or beta-Gal-transduced cells were injected into the femoral bone marrow cavity and effects on bone were evaluated by X-ray, peripheral quantitative computed tomography (pQCT), and histology. RESULTS: After tail-vein injection less than 20% of recipient mice contained beta-Gal-positive donor cells in femur, humerus or vertebra marrow cavities combined, and in these mice only 0.02-0.29% of injected cells were present in the bone marrow. In contrast, direct intramedullary injection was always successful and an average of 2% of injected cells were present in the injected femur marrow cavity 24 hours after injection. Numbers of donor cells decreased over the next 14 days. Intramedullary injection of BMP4-transduced MSCs induced bone formation. Trabecular bone mineral density (BMD) determined by pQCT increased 20.5% at 14 days and total BMD increased 6.5% at 14 days and 10.4% at 56 days. CONCLUSIONS: The present findings support the feasibility of using ex vivo MSC-based retroviral gene therapy to induce relatively sustained new bone formation, with normal histological appearance, at endosteal bone sites.

Animals↗
PubMed2006

Low intensity pulsed ultrasound accelerated bone remodeling during consolidation stage of distraction osteogenesis.

Bone regeneration in distraction osteogenesis occurs under tensile stress with axial rhythmic distraction after osteotomy. In this study, we evaluated if the low intensity pulsed ultrasound (LIPUS) was also effective on enhancement of bone remodeling during consolidation stage of distraction osteogenesis. Open osteotomy of seventeen 18-week-old female New Zealand rabbit tibiae were performed. The distraction was applied with the rate of 1 mm per day. LIPUS (30 mW/cm(2), 1.5 MHz) was delivered for 20 min per day during 4-week consolidation stage (n=10). The animals without treatment served as sham group (n=7). Plain X-ray, peripheral quantitative computational tomography (pQCT), and torsional test were performed. Results showed that smaller radiolucent interzone of LIPUS treatment group was gradually occupied by calcified tissue in plain X-ray at week 2. The bone mineral density (BMD) measured on radiographs increased by 9.18% in the LIPUS group. Bone mineral content (BMC), hard callus volume, and bone strength index (BSI) measured by pQCT were 83%, 116%, and 94%, respectively, in LIPUS group that were significantly greater than those of the controls. At the 4th week, LIPUS-treated callus showed the development of neocorticalization in the proximal and distal region. The BMC, hard callus volume, and BSI of LIPUS group decreased and was not significantly different from control. This was also confirmed by the maximum torque of LIPUS-treated callus (1424.2+/-457.3 N . mm) obtained at week 4, which did not differ from that of the sham group (1968.8+/-895.1 N . mm). In conclusion, the effective period of LIPUS treatment was at the initial stage of consolidation, with accelerated bone formation and remodeling.

Animals↗
PubMed2006

Allogenic peripheral blood derived mesenchymal stem cells (MSCs) enhance bone regeneration in rabbit ulna critical-sized bone defect model.

Mesenchymal stem cells (MSCs) were demonstrated to exist within peripheral blood (PB) of several mammalian species including human, guinea pig, mice, rat, and rabbit. Whether or not the PB derived MSCs (PBMSCs) could enhance the regeneration of large bone defects have not been reported. In this study, rabbit MSCs were obtained from mononuclear cells (MNCs) cultures of both the PB and bone marrow (BM) origin. The number of PBMSCs was relatively lower, with the colony forming efficiency (CFE) ranging from 1.2 to 13 per million MNCs. Under specific inductive conditions, PBMSCs differentiated into osteoblasts, chondrocytes, and adipocytes, showing multidifferentiation ability similar to BMMSCs. Bilateral 20 mm critical-sized bone defects were created in the ulnae of 12 6-month-old New Zealand white rabbits. The defects were treated with allogenic PBMSCs/Skelite (porous calcium phosphate resorbable substitute), BMMSCs/Skelite, PBMNCs/Skelite, Skelite alone, and left empty for 12 weeks. Bone regeneration was evaluated by serial radiography, peripheral quantitative computed tomography (pQCT), and histological examinations. The X-ray scores and the pQCT total bone mineral density in the PBMSCs/Skelite and BMMSCs/Skelite treated groups were significantly greater than those of the PBMNCs/Skelite and Skelite alone groups ( p < 0.05), respectively. Histologically, newly formed bone was evident in the PBMSCs/Skelite and BMMSCs/Skelite treated groups. The findings demonstrated that the rabbit PBMSCs possessed multidifferentiation potential comparable with BMMSCs, allogenic PBMSCs seeded onto porous calcium phosphate resorbable substitutes enhanced bone regeneration in the rabbit ulna critical-sized bone defect model, suggesting allogenic PBMSCs may be a new source of circulating osteogenic stem cells for bone regeneration and tissue engineering.

Animals↗
PubMed2006

Density and structural changes in the bone of growing rats after weekly alendronate administration with and without a methotrexate challenge.

Alendronate (ALN) and other bisphosphonates have been used successfully in pediatric patients with osteopenia secondary to connective tissue diseases. Loss of growth in height has not been reported, but concerns remain regarding the effect of these potent antiresorptive agents when used in children and adolescents. High-dose methotrexate (MTX) and other chemotherapy drugs have been implicated in osteoporosis and a high fracture incidence in survivors of childhood cancers and are also associated with osteopenia in adult animals. The effect of high dose MTX on bone density during rapid skeletal growth, however, has not been widely studied, nor has the potentially therapeutic effect of bisphosphonates in this setting. We examined the effects of ALN and MTX administration, alone and in combination, on bone density, morphology, mechanical strength, and longitudinal growth in normal growing rats. Sprague-Dawley rats were given ALN once weekly (0.3 mg/kg) from 5 to 11 weeks of age, with and without a course of methotrexate (MTX) given daily in weeks 1 and 3 (0.75 mg/kg/day). Twenty-four animals were randomly divided into four groups: Control (vehicle), ALN alone, ALN + MTX, and MTX alone. After 6 weeks, the femora, tibiae, and lumbar spine were studied by dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, mechanical strength testing, microradiography, light microscopy, and by determination of ash weights and bone lengths. ALN treatment increased bone mineral density (BMD) by 23% to 68%. The largest increases in the femur occurred in the distal third where endochondral bone growth was greatest and included large increases in trabecular bone and total cross-sectional area. ALN + MTX produced similar effects to ALN alone. MTX only reduced BMD by 8% in the vertebrae, but not significantly at other sites. MTX also led to femoral length reductions of 2.9%. The small reductions in BMD due to MTX were overwhelmed by the increases due to ALN, whereas the length loss was unaffected. Transverse density banding corresponding to weekly ALN administrations were clearly evident radiographically throughout the growing skeleton, likely due to decreased resorption and possibly increased mineralization in the bands. ALN or ALN + MTX treatment also led to increases in mechanical strength in the femora. Although MTX administration during growth leads to some BMD reduction, ALN given with MTX eliminates this reduction and in fact bone density and strength increase above control levels.

Alendronate↗
PubMed2006

Dose-dependent effect of low-intensity pulsed ultrasound on callus formation during rapid distraction osteogenesis.

Distraction osteogenesis of bone or callotasis causes poor bone formation when the distraction rate is beyond the optimal rate. Low-intensity pulsed ultrasound was reported to enhance fracture healing, treatment of nonunion, and accelerate bone maturation and remodeling during consolidation stage of distraction osteogenesis. In this study, we evaluated the efficacy of different durations of LIPUS treatments during rapid bone lengthening. After 7-day latent period, osteotomized New Zealand white rabbit tibiae were lengthened at the rate of 2 mm per day for 1 week. Two different LIPUS treatment durations of 20 min and 40 min were selected for treatment groups. Rabbits without treatment served as the control group. Plain X-ray, peripheral quantitative computed tomography (pQCT) and histology were performed to assess bone acquisition in the distraction callus. The results showed that LIPUS increased bone mineral content and volume of the mineralized tissue of distraction callus in a dose-dependent manner. The different regions of distraction callus exhibited various spatial response to LIPUS treatment. Moreover, LIPUS enhanced dose-dependant endochondral formation. Compared with 20-min treatment, the 40-min LIPUS treatment was a more favorable treatment duration for bone regeneration in the distraction callus. In conclusion, LIPUS was able to enhance bone regeneration under rapid distraction, and its effect was dose-dependent.

Animals↗
PubMed2006

Influence of bone quality on the strength of internal and external fixation of tibial plateau fractures.

We studied the influence of different parameters of bone quality on the fixation strength of bicondylar tibial plateau fractures and examined the relationship between these parameters. Bone quality was measured in the plateau of 16 cadaveric tibias using three modalities: dual-energy X-ray absorptiometry (DXA), peripheral quantitative computer tomography (pQCT), and spectral analysis of digitized radiographs (SADR). The tibias were divided into two groups by the median bone mineral density (BMD) and randomized to receive either dual plating or external fixator for the stabilization of a standardized bicondylar tibial fracture. The fixed fractures were subjected to axial compression until failure. DXA BMD correlated most significantly with the failure load (r>or=0.79, p<0.001), followed by the pQCT parameters of cancellous bone (0.52>or=r>or=0.73, p<0.01). Similar strong correlations were also evident in both fixation methods. For parameters derived from SADR, only those including both longitudinal and transverse trabecular orientations had modest correlation with the fixation strength (0.53>or=r>or=0.71, p<0.01). The failure loads of the two fixation techniques were not significantly different (mean+/-SD=3522+/-1386 N and 3710+/-1356 N, respectively, p=0.78). However, BMD in the dual-plating group influenced the failure load significantly (p=0.03), whereas in the external fixation group this was less evident (p=0.100). The majority of bone quality parameters that correlated with fixation strength were also strongly correlated with each other, particularly the BMDs measured by DXA and pQCT. This is the first study that relates fixation strength of bicondylar tibial plateau fractures to bone quality assessed at the same anatomical site. BMD around the fracture site had the best correlation with the failure load regardless of the fixation technique. The two fixation methods tested performed equally well, and the choice between them depends on the soft tissue condition and surgeon preference.

Biomechanical Phenomena↗
PubMed2007

Bone formation after damaging in vivo fatigue loading results in recovery of whole-bone monotonic strength and increased fatigue life.

Bone has a remarkable capacity for self-repair. We previously reported a woven bone response after damaging in vivo fatigue loading of the rat ulna that led to a rapid recovery of whole-bone strength. In the current study we asked: does the bone response in the 12 days after damaging fatigue loading result in a bone that has normal fatigue properties? The right forelimbs of 52 adult rats were subjected to a single bout of in vivo fatigue loading. Nonloaded left forelimbs were used as controls. Ulnar geometric properties were assessed by peripheral quantitative computed tomography (pQCT) and ex vivo mechanical properties were assessed by three-point bending. On day 0, ulnae from loaded forelimbs had a 15-20% reduction in stiffness and ultimate force versus controls (p < 0.10), indicative of structural damage. On day 12, bone area at the midshaft was increased by 27% (p < 0.001) and microCT scans revealed periosteal woven bone at this site. This bone response led to a recovery of the monotonic properties of loaded ulnae at day 12 versus control (stiffness, p = 0.73; ultimate force, p = 0.96). Importantly, fatigue testing ex vivo at day 12 demonstrated significantly greater fatigue life in in vivo loaded ulnae versus controls (p < 0.001). Additionally, the slope of the fatigue-life curve was significantly less in loaded versus control ulnae (p < 0.002). We conclude that woven bone "repair" of a bone damaged by fatigue loading restores whole-bone strength and enhances resistance to further damage by repetitive loading.

Animals↗
PubMed1994

Influence of steroid medication on bone mineral density in children with nephrotic syndrome.

Bone mineral density (BMD) was studied in 26 children with idiopathic nephrotic syndrome and in age- and sex-matched healthy controls. BMD was selectively measured in trabecular (TBD), cortical (CBD) and total bone (BD) using peripheral quantitative computed tomography. Patients showed a decrease in BD, CBD and TBD. BD and CBD were inversely correlated with the cumulative dose of steroid treatment. Of the 26 patients with high cumulative doses of steroid, 16 were also treated with cyclophosphamide. In this group BD and CBD were decreased significantly compared with the children with a low cumulative steroid dose only. Compared with controls for each subgroup, significant decreases in BD, CBD and TBD were found in the group with high cumulative doses of steroids only. The higher cumulative steroid dose and the initial steroid toxicity which made cytotoxic therapy necessary, rather than cyclophosphamide itself, may be responsible for these findings.

Adolescent↗
PubMed1995

Countinuous Laser-Doppler free-flap monitoring via the telephone line. Preliminary experiences.

It is possible to link a Laser-Doppler to a DOS-compatible personal computer in order to monitor microcirculation of the free flap after plastic surgery. We connected such a system to a second computer by telephone modems, in order to control the Laser-Doppler via the telephone line from a distant location using only commercially available hardware and software. The aim was to develop a low-cost system which would not require the purchase or construction of any specialised equipment. Using this system, it was possible to show the Laser-Doppler waveforms to colleagues who were not at the patient site, for their (more experienced) opinions without any further delays. Preliminary tests on five cases showed that it was indeed possible to transfer recorded information about the blood flow rate of free skin flaps from one computer to a remote one, without any loss of information. In these cases, the measured blood flow and clinical surveillance of the blood supply were adequate, thus making revision of the tissues not necessary. This preliminary study suggests that standard 'off-the-shelf' personal computer tools may be useful in improving the monitoring of microcirculation after plastic surgery.

Computer Peripherals↗
PubMed1991

Comparative accuracies of a finger blood pressure monitor and an oscillometric blood pressure monitor.

A noninvasive blood pressure monitor (Finapres) that uses the methodology of Penaz to continuously display the arterial waveform from the finger has been introduced recently. The Finapres monitor overestimated systolic pressure by 5.8 +/- 11.9 mm Hg, while the Dinamap monitor underestimated systolic pressure by -6.9 +/- 9.2 mm Hg (P = 0.003). Dinamap mean and diastolic pressure biases were less than 2 mm Hg, while the Finapres biases for these variables were significantly greater (7.7 +/- 10.0 and 8.2 +/- 9.8 mm Hg, respectively). There was no difference in systolic or mean pressure precision between the two devices (approximately 10 mm Hg), but the diastolic precision of the Dinamap unit was superior to that of the Finapres. While in most patients the Finapres monitor provided continuous blood pressure data equivalent to the data from the radial artery, marked bias (greater than 15 mm Hg) was exhibited in 2 patients for all three pressure variables. Despite this bias, blood pressure changes were tracked closely in these 2 patients. We conclude that, in its current form, the Finapres monitor cannot be relied upon independently to accurately measure blood pressure in patients undergoing general anesthesia. Since the Dinamap monitor measures mean pressure reliably and accurately, we suggest that mean blood pressure values between the Finapres and Dinamap monitors be compared to guide one in interpreting Finapres data.

Adolescent↗
PubMed1994

Monitoring of right ventricular function using a conventional slow response thermistor catheter.

OBJECTIVE: To investigate whether determination of right ventricular end-diastolic volume (RVEDV) and right ventricular ejection fraction (RVEF) can be performed with reasonable accuracy and reproducibility using a conventional slow response thermistor pulmonary artery catheter (CPAC) applying an adaptive algorithm. DESIGN: To study RVEDV and RVEF simultaneously with pulmonary artery catheters equipped with slow and fast response thermistors (FRPAC) under a broad range of cardiac output. SETTING: Laboratory of Institute of Experimental Surgery, Technical University. ANIMALS: 11 anaesthetised piglets. INTERVENTIONS: Hypovolemia (V-) was induced by withdrawal of blood up to 50 ml/kg, hypervolemia (V+) was produced by retransfusing blood and adding up to 30 mg/kg hydroxyethyl starch. In 5 animals in phases V- and V+ beta-adrenergic stimulation was achieved with dobutamine. Finally pulmonary artery hypertension was induced by infusion of small air bubbles. MEASUREMENTS AND RESULTS: Cardiac output (CO), RVEDV and RVEF were determined simultaneously with FRPAC and CPAC placed in the same pulmonary artery branch. Measurements were repeated 8 times sequentially in steady state normovolemia. A total of 130 measurements could be analysed. The coefficient of variation was 6.7 +/- 4.2% for CO(FRPAC) and 4.6 +/- 1.7% for CO(CPAC); for RVEF it was 9.7 +/- 6.2% (FRPAC) and 9.9 +/- 3.9% (CPAC); for RVEDV it was 11.6 +/- 4.8% (FRPAC) and 8.54 +/- 3.2 (CPAC). Mean difference (bias) was 0.06 +/- 0.39 l/min for CO measured with both methods, 19 +/- 35 ml for RVEDV and -3.3 +/- 6.5% for RVEF. CO(CPAC) displayed a strong correlation to CO(FRPAC) (R = 0.97, p = 0.001) as well as RVEF (R for RVEF(CPAC) versus RVEF(FRPAC) = 0.90, p = 0.001). R for RVEDV(CPAC) versus RVEDV(FRPAC) was 0.67, p = 0.001. We conclude that this animal study demonstrates good agreement between RVEF and RVEDV obtained with catheters equipped with a fast response thermistor or with a conventional slow response thermistor allowing accurate monitoring of right ventricular function with a conventional pulmonary artery catheter.

Algorithms↗
PubMed1994

[Electronic picture and data storage and processing with PC in trauma surgery--an anachronism?].

Acquisition, storage and processing of any images relevant in trauma surgery together or in combination with (alpha) numeric data nowadays are possible employing a personal computer. The computing speed that is achieved with 486 cpu's "inside" is sufficient to process images in motion as well as single images to be filtered. The display and process-resolutions required for processing of X-ray-images can be achieved with the PC's hardware as well as with the software available. That is why there is no need any longer for special configurations for X-ray-departments. Calculating the price of the process-environment proposed, about 25,000 DM should be enough including the video tape recorders and the CD-ROM-recorder that are required.

Computer Peripherals↗
PubMed1998

Lifelong administration of high doses of ibandronate increases bone mass and maintains bone quality of lumbar vertebrae in rats.

As part of a long-term safety study the bisphosphonate ibandronate was investigated for its effects on bone quality in lumbar vertebrae in rats. Bone area, bone density and mechanical properties were assessed by peripheral quantitative computed tomography (pQCT), dual-energy X-ray absorptiometry (DXA) and compression tests. Female and male groups of Wistar rats received either vehicle or 3, 7 or 15 mg/kg per day of ibandronate over 104 weeks orally by gavage. Compared with the control group, bone mineral density, compressive strength and stiffness were significantly higher in ibandronate-treated animals, whereas no changes occurred in strain or modulus of elasticity. The increase in vertebral body stress was significant in some of the ibandronate-treated groups. The changes in mechanical properties appear to be due mainly to an increase in bone mass. A highly significant correlation was found between bone mineral density measured either by DXA (r = 0.86) or pQCT (r = 0.85) and maximal strength in vertebral bodies (p < 0.0001 each). In conclusion, we demonstrated that lifelong administration of doses of ibandronate far in excess of any therapeutically intended dose not only increases bone mass and apparent density, but also maintains or even slightly improves bone quality. Bone mineral density measured either by pQCT or DXA can be used as a predictor for ultimate strength in rat lumbar vertebral bodies after treatment with ibandronate.

Animals↗
PubMed2000

Computed radiography printing problems: a quantitative, observer-independent solution.

Even though facilities using computed radiography (CR) operate in an electronic environment, the production of hard-copy films is still necessary during the transition period, as well as for particular needs following complete implementation. We have implemented a quantitative technique to match the response of printed CR film with that of previous screen/film combinations. A stepwedge is radiographed using the conventional system. The same stepwedge is then radiographed (same geometry and technique) using the CR system. Following processing and printing, the plot of optical density versus step for the CR system is compared with that of the screen/film system. Adjustments are made to the printing parameters until the response curves are identical. All other translation tables in the system are set to be linear. This has proven to be a valuable technique for us and provides CR printed image quality that is equivalent to that of our previous screen/film combinations.

Computer Peripherals↗
PubMed1992

Quality monitoring of soft-copy displays for medical radiography.

As presentation of medical radiographic images on soft-copy displays (cathode ray tubes) becomes increasingly prevalent in electronic radiography, methods of quality assurance must be developed to ensure that radiologists can effectively transfer film-based reading skills. Luminance measurements provide the basis for evaluating the state of soft-copy displays. An integrated approach has been implemented at Mallinckrodt Institute of Radiology (MIR, Washington University, St Louis, MO) that facilitates measurement of geographically distributed soft-copy displays with centralized data logging, performance tracking, and calibration. MIR's central radiology image manager exercises the display station that drives the monitor, harvests the measurement data, stores the results, and submits the resulting data for additional processing. The luminance measurements are collected by a small, portable, photometric instrument designed at MIR that includes a serial port that is accessed via local area terminal service supported by the radiology image manager. The design details of the photometric instrument and example luminance characteristics of several soft-copy displays used at MIR are presented in this report.

Computer Peripherals↗