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1.
Strahlenther Onkol ; 196(3): 262-269, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31309264

ABSTRACT

BACKGROUND: Humeral epicondylitis is a common elbow disease. The prevalence is about 1.7%. One of the most effective treatment options is radiotherapy. Some authors mention that they apply a second or third course of radiation for recurrent pain or partial or no response to the initial course. As the results of a re-irradiation have not been systematically analyzed, the aim of this study was to document the results of repeated radiation treatment and to identify those patients who will benefit. MATERIAL AND METHODS: The analysis was performed on patients from three German radiotherapy institutions and included 99 re-irradiated elbows. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy as well as for the follow-up of 24 months. The median age of the patients was 51 years with 48.8% male and 51.2% female patients. Repeated radiation was indicated because the initial radiotherapy resulted in 39.7% of no response, in 41.0% of partial response and in 19.3% of recurrent pain. RESULTS: A significant response to re-irradiation was found. For the whole sample the median pain score was 6 before re-irradiation, 3 after 6 weeks, 2 after 12 months and 1 after 24 months. The percentage of patients being free of pain or with very little pain was 50.9% 24 months after re-irradiation. All subgroups, notably those with no response, partial response and recurrent pain had a significant reduction of pain. CONCLUSION: Re-irradiation of humeral epicondylitis is an effective and safe treatment. All subgroups showed a good response to re-irradiation for at least 24 months.


Subject(s)
Elbow/radiation effects , Tennis Elbow/radiotherapy , Female , Follow-Up Studies , Humans , Humerus/radiation effects , Male , Middle Aged , Pain Measurement , Re-Irradiation , Retrospective Studies , Treatment Outcome
2.
Orthopade ; 46(8): 681-687, 2017 Aug.
Article in German | MEDLINE | ID: mdl-28718006

ABSTRACT

BACKGROUND: Malignant bone tumors themselves and the wide resection required because of them may cause huge bone defects in the bone segment involved. Autologous bone grafts are a reliable option to cover these defects in many cases but their availability is limited. Besides common alternative reconstruction methods, including the use of allografts and/or prostheses, especially extracoroporeal irradiation (ECI) and reimplantation of the bone segment involved is attracting increasingly more attention nowadays. DISCUSSION: In the following, we report on indications/contraindications, details of the operative technique, as well as the recommended rehabilitation regime of ECI. Furthermore, we compare our own results with those published in the recent literature. Especially the advantages and disadvantages of this method, the risks and the complications are illustrated and critically discussed. CONCLUSION: Extracorporeal irradiation of a tumor bearing bone segment is a valuable alternative reconstruction technique following tumor resections of the pelvis, femur and tibia, with encouraging results with respect to local control, complication risks and functional outcome.


Subject(s)
Bone Neoplasms/radiotherapy , Bone Neoplasms/surgery , Orthopedic Procedures/methods , Replantation/methods , Adult , Chondrosarcoma/radiotherapy , Chondrosarcoma/surgery , Combined Modality Therapy , Femoral Neoplasms/radiotherapy , Femoral Neoplasms/surgery , Follow-Up Studies , Humans , Humerus/radiation effects , Humerus/surgery , Osteosarcoma/radiotherapy , Osteosarcoma/surgery , Pelvic Bones/radiation effects , Pelvic Bones/surgery , Sarcoma, Ewing/radiotherapy , Sarcoma, Ewing/surgery , Tibia/radiation effects , Tibia/surgery
3.
J Biomech ; 46(10): 1670-5, 2013 Jun 21.
Article in English | MEDLINE | ID: mdl-23664240

ABSTRACT

The optimal sterilization method for load bearing allografts remains a clinical concern. Recently, supercritical carbon dioxide (SCCO2) treatments have been shown to be capable of terminally sterilizing a range of bacteria and viruses, while preserving the static mechanical properties of cortical bone. This study evaluated the effect of SCCO2 treatment compared with two doses of gamma irradiation, on clinically relevant dynamic mechanical properties of cortical bone. Quasi-static testing was also performed to compare the impairment of treatment. Whole paired adult rabbit humeri were dissected and randomly assigned into either SCCO2 Control, SCCO2 Additive or gamma irradiation at 10 or 25kGy treatment groups. The bones were treated and mechanically tested in three-point bending, with the lefts acting as controls for the treated rights. Maximum load, energy to failure and stiffness were evaluated from static tests. The number of cycles to failure was determined for fatigue at 6-60% of the ultimate load. This study found that SCCO2 treatment with or without additive did not alter static or dynamic mechanical properties. Gamma irradiation had a deleterious dose dependent effect, with statistically significant (p<0.05) reductions in all static mechanical parameters at 25kGy. This effect was increased in fatigue with statistically significant decreases in both the 10 and 25kGy dose groups. This study highlights the expediency of SCCO2 treatment for load bearing bone allograft processing as terminal sterilization can be achieved while maintaining both the quasi-static and dynamic mechanical properties of the graft.


Subject(s)
Humerus/physiology , Sterilization , Animals , Biomechanical Phenomena , Bone Transplantation , Carbon Dioxide/pharmacology , Gamma Rays , Humerus/drug effects , Humerus/radiation effects , Male , Rabbits , Weight-Bearing/physiology
4.
Cell Tissue Bank ; 14(2): 231-42, 2013 Jun.
Article in English | MEDLINE | ID: mdl-22644703

ABSTRACT

Load bearing bone allografts are used to replace the mechanical function of bone that has been removed or to augment bone that has been damaged in trauma. In order to minimize the risk of infection and immune response, the bone is delipidated and terminally sterilized prior to implantation. The optimal method for bone graft sterilization has been the topic of considerable research. Recently, supercritical carbon dioxide (SCCO(2)) treatments have been shown to terminally sterilize bone against a range of bacteria and viruses. This study aimed to evaluate the effect of SCCO(2) treatment compared with two doses of gamma irradiation, on the mechanical properties of whole bone. Paired rabbit humeri were dissected and randomly assigned into either SCCO(2) control, SCCO(2) additive or gamma irradiation at 10 or 25 kGy treatment groups. The bones were mechanically tested in three-point and four-point bending and torsion, with the lefts acting as controls for the treated rights. Maximum load, energy to failure and stiffness were evaluated. This study found that SCCO(2) treatment with or without additive did not alter maximum load, energy to failure or stiffness significantly under any loading modality. Gamma irradiation had a deleterious dose dependant effect, with statistically significant decreases in all mechanical tests at 25 kGy; while at 10 kGy there were reductions in all loading profiles, though only reaching statistical significance in torsion. This study highlights the expediency of SCCO(2) treatment for bone allograft processing as terminal sterilization can be achieved while maintaining the intrinsic mechanical properties of the graft.


Subject(s)
Carbon Dioxide/pharmacology , Gamma Rays , Humerus/drug effects , Humerus/radiation effects , Sterilization/methods , Torsion, Mechanical , Animals , Biomechanical Phenomena , Bone Transplantation/methods , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Humerus/microbiology , In Vitro Techniques , Rabbits , Weight-Bearing/physiology
5.
Am J Hematol ; 87(6): 641-2, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22488443

ABSTRACT

POEMS syndrome is a rare paraneoplastic condition associated to an underlying plasmacellular dyscrasia. The pathogenesis of POEMS is poorly understood, but overproduction of VEGF, probably secreted by clonal plasma cells, is thought to be responsible for the signs and symptoms of the syndrome, and it seems to be useful for the monitoring of the response to therapy. At present, an effective therapeutic option for the patients is represented by autologous peripheral blood stem-cell transplantation (aPBSCT), although relapses have been described, and there is an important morbidity associated with this procedure. Before the implementation of aPBSCT, the clinical course of POEMS syndrome was characterized by progressive polyneuropathy potentially leading to death for respiratory failure. Given the high serum and plasma levels of VEGF observed in POEMS patients, the use of anti-angiogenetic drugs such as thalidomide and lenalidomide and other drugs with anti-VEGF and anti-TNF effect such as bortezomib have been considered to treat this syndrome. There are evidences of lenalidomide benefit in both front-line and previously treated patients, but scanty data are available about its use for relapse after aPBSCT. Here, we report the successful use of lenalidomide in a patient who relapsed after aPBSCT.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Multiple Myeloma/drug therapy , POEMS Syndrome/drug therapy , Peripheral Blood Stem Cell Transplantation , Salvage Therapy , Angiogenesis Inhibitors/administration & dosage , Biomarkers, Tumor/blood , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Humans , Humerus/pathology , Humerus/radiation effects , Immunologic Factors/administration & dosage , Lenalidomide , Male , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/radiotherapy , Multiple Myeloma/surgery , Osteosclerosis/etiology , Osteosclerosis/radiotherapy , POEMS Syndrome/etiology , POEMS Syndrome/surgery , Prednisolone/administration & dosage , Recurrence , Thalidomide/administration & dosage , Thalidomide/analogs & derivatives , Transplantation, Autologous
6.
Radiat Res ; 172(1): 21-9, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19580504

ABSTRACT

On a mission to Mars, astronauts will be exposed to a complex mix of radiation from galactic cosmic rays. We have demonstrated a loss of bone mass from exposure to types of radiation relevant to space flight at doses of 1 and 2 Gy. The effects of space radiation on skeletal muscle, however, have not been investigated. To evaluate the effect of simulated galactic cosmic radiation on muscle fiber area and bone volume, we examined mice from a study in which brains were exposed to collimated iron-ion radiation. The collimator transmitted a complex mix of charged secondary particles to bone and muscle tissue that represented a low-fidelity simulation of the space radiation environment. Measured radiation doses of uncollimated secondary particles were 0.47 Gy at the proximal humerus, 0.24-0.31 Gy at the midbelly of the triceps brachii, and 0.18 Gy at the proximal tibia. Compared to nonirradiated controls, the proximal humerus of irradiated mice had a lower trabecular bone volume fraction, lower trabecular thickness, greater cortical porosity, and lower polar moment of inertia. The tibia showed no differences in any bone parameter. The triceps brachii of irradiated mice had fewer small-diameter fibers and more fibers containing central nuclei. These results demonstrate a negative effect on the skeletal muscle and bone systems of simulated galactic cosmic rays at a dose and LET range relevant to a Mars exploration mission. The presence of evidence of muscle remodeling highlights the need for further study.


Subject(s)
Bone Density/radiation effects , Cosmic Radiation/adverse effects , Humerus/radiation effects , Muscle Fibers, Skeletal/radiation effects , Tibia/radiation effects , Animals , Body Weight/radiation effects , Humerus/diagnostic imaging , Humerus/pathology , Male , Mice , Mice, Inbred C57BL , Organ Size , Radiation Dosage , Tibia/diagnostic imaging , Tibia/pathology , X-Ray Microtomography
8.
Magn Reson Med Sci ; 6(4): 199-209, 2007.
Article in English | MEDLINE | ID: mdl-18239357

ABSTRACT

PURPOSE: We evaluated radiofrequency (RF) heating of a humerus implant embedded in a gel phantom during magnetic resonance (MR) imaging for the specific absorption rate (SAR), angle between the implant and static magnetic field (B(0)), and position of the implant in the irradiation coil. METHODS: We embedded a stainless steel humerus implant 2 cm deep in tissue-equivalent loop and mass phantoms, placed it parallel to the static magnetic field of a 1.5T MR scanner, and recorded the temperatures of the implant surface with RF-transparent fiberoptic sensors. We measured rises in temperature at the tips of the implant by varying the SAR from 0.2 to 4.0 W/kg and evaluated RF heating of the implant for its angle to B(0) and its displacement along B(0) from the center of the RF irradiation coil. RESULTS: RF heating was similar for the loop and mass phantoms because the eddy current flows through the periphery of both. As the SAR increased, the temperature at the implant tip increased, and there was a linear relationship between the SAR and temperature rise. The values were 6.4 degrees C at 2.0 W/kg and 12.7 degrees C at 4.0 W/kg. Rise in temperature decreased steeply as the angle between the implant and B(0) surpassed 45 degrees . In addition, as the implant was displaced from the center of the RF coil to both ends, the rise in temperature decreased. CONCLUSION: The rise in temperature in deep tissue was estimated to be higher than 1.0 degrees C for SAR above 0.4 W/kg. RF heating was greatest when the implant was set parallel to B(0). In MR imaging of patients with implants, there is a risk of RF heating when the loop of the eddy current is formed inside the body.


Subject(s)
Bone Nails , Hot Temperature , Humerus/radiation effects , Magnetic Resonance Imaging/instrumentation , Phantoms, Imaging , Electric Conductivity , Permeability , Radio Waves , Stainless Steel , Thermal Conductivity
9.
Tumori ; 92(4): 366-9, 2006.
Article in English | MEDLINE | ID: mdl-17036535

ABSTRACT

We report the case of a 63-year-old man with a clearly established diagnosis of hairy cell leukemia, treated with multiple lines of chemotherapy, who complained of localized pain in the left humerus. Radiological findings showed a dystrophic-blastic area within the humeral head. Fine-needle biopsy confirmed the hypothesis of bone involvement of hairy cell leukemia. The patient underwent radiotherapy at a dose of 25 Gy, obtaining a complete clinical response with resolution of pain and a partial recovery of the normal radiological structure of the humerus after 2 months. In addition to the case report, we present a short review of the literature focusing on the role of radiotherapy in this subset of patients.


Subject(s)
Bone Neoplasms/radiotherapy , Bone Neoplasms/secondary , Humerus , Leukemia, Hairy Cell/pathology , Biopsy , Humans , Humerus/pathology , Humerus/radiation effects , Male , Middle Aged , Radiotherapy Dosage , Treatment Outcome
10.
Magn Reson Med Sci ; 5(2): 79-88, 2006 Jul.
Article in English | MEDLINE | ID: mdl-17008764

ABSTRACT

PURPOSE: To evaluate the effect of radiofrequency (RF) heating on a metallic implant during magnetic resonance imaging (MRI), temperatures at several positions of an implant were measured, and results are compared with electromagnetic simulations using a finite element method. METHODS: A humerus nail implant made of stainless steel was embedded at various depths of tissue-equivalent gel-phantoms with loop (loop phantom) and partially cut loop (loop-cut phantom), and the phantoms were placed parallel to the static magnetic field of a 1.5T MRI device. Scans were conducted at maximum RF for 15 min, and temperatures were recorded with 2 RF-transparent fiberoptic sensors. Finally, electromagnetic-field analysis was performed. RESULTS: Temperatures increased at both ends of the implants at various depths, and temperature increase was suppressed with increasing depth. The maximum temperature rise was 12.3 degrees C at the tip of the implant and decreased for the loop-cut phantom. These tendencies resembled the results of electromagnetic simulations. CONCLUSION: RF heating was verified even in a nonmagnetizing metal implant in a case of excessive RF irradiation. Particularly, rapid temperature rise was observed at both ends of the implant having large curvatures. The difference in temperature increase by depth was found to reflect the skin-depth effect of RF intensity. Electromagnetic simulation was extremely useful for visualizing the eddy currents within the loop and loop-cut phantoms and for evaluating RF heating of a metallic implant for MRI safety.


Subject(s)
Bone Nails , Electromagnetic Fields , Heating , Humerus/radiation effects , Magnetic Resonance Imaging/instrumentation , Phantoms, Imaging , Radio Waves , Bone Density , Electric Conductivity , Electric Stimulation , Humans , Humerus/chemistry , Models, Theoretical , Permeability , Steel , Temperature , Thermal Conductivity
11.
J Nucl Med ; 43(1): 97-108, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11801712

ABSTRACT

UNLABELLED: Dose assessment to active bone marrow is a critical feature of radionuclide therapy treatment planning. Skeletal dosimetry models currently used to assign radionuclide S values for clinical marrow dose assessment are based on bone and marrow cavity chord-length distributions. Accordingly, these models cannot explicitly consider energy loss to inactive marrow (adipose tissue) during particle transport across the trabecular marrow space (TMS). One method to account for this energy loss is to uniformly scale the resulting TMS absorbed fractions by reference values of site-specific marrow cellularity. In doing so, however, the resulting absorbed fractions for self-irradiation of the trabecular active marrow (TAM) do not converge to unity at low electron source energies. This study attempts to address this issue by using nuclear magnetic resonance microscopy images of trabecular bone to define 3-dimensional (3D) dosimetric models in which explicit spatial distributions of adipose tissue are introduced. METHODS: Cadaveric sources of trabecular bone were taken from both the femoral heads and humeral epiphyses of a 51-y-old male subject. The bone sites were sectioned and subsequently imaged at a proton resonance frequency of 200 MHz (4.7 T) using a 3D spin-echo pulse sequence. After image segmentation, voxel clusters of adipocytes were inserted interior to the marrow cavities of the binary images, which were then coupled to the EGS4 radiation transport code for simulation of active marrow electron sources. RESULTS: Absorbed fractions for self-irradiation of the TAM were tabulated for both skeletal sites. Substantial variations in the absorbed fraction to active marrow are seen with changes in marrow cellularity, particularly in the energy range of 100-500 keV. These variations are seen to be more dramatic in the humeral epiphysis (larger marrow volume fraction) than in the femoral head. CONCLUSION: Results from electron transport in 3D models of the trabecular skeleton indicate that current methods to account for marrow cellularity in chord-based models are incomplete. At 10 keV, for example, the Eckerman and Stabin model underestimates the self-absorbed fraction to active marrow by 75%. At 1 MeV, the model of Bouchet et al. overestimates this same value by 40%. In the energy range of 20-200 keV, neither model accurately predicts energy loss to the active bone marrow. Thus, it is proposed that future extensions of skeletal dosimetry models use 3D transport techniques in which explicit delineation of active and inactive marrow is feasible.


Subject(s)
Bone Marrow/pathology , Bone and Bones/radiation effects , Radiation Dosage , Adipocytes/radiation effects , Bone Marrow/radiation effects , Cadaver , Femur Head/radiation effects , Humans , Humerus/radiation effects , Imaging, Three-Dimensional , Magnetic Resonance Spectroscopy , Male , Middle Aged , Radiometry , Tomography, X-Ray Computed
13.
Int J Radiat Oncol Biol Phys ; 46(1): 119-22, 2000 Jan 01.
Article in English | MEDLINE | ID: mdl-10656382

ABSTRACT

PURPOSE: To evaluate the best position of the arms in mantle field for Hodgkin's disease. METHODS AND MATERIALS: In 12 patients, with surgical clips placed at the time of an axillary dissection for breast cancer, the radiological projection of the clips according to three arm positions was prospectively evaluated: akimbo (A), extended (E), and up over the head (U). The surgical clips were arbitrarily separated into two groups: lower and upper. In each patient, the distance between the surgical clips and chest wall was measured, and the possibility of shielding the lungs and humeral heads was evaluated. RESULTS: The mean displacement of the lower clips away from the chest wall when the patients were in A, E, and U positions was 2.5, 3.0, and 4.6 cm, respectively. The upper group clips showed a lower difference in distance from chest wall. In the U position, there was always a clip of the lower group that projected over the humeral head, making it impossible to block this structure. CONCLUSION: In the A position, there is the possibility of blocking the humeral head, but it is necessary to irradiate more lung parenchyma. Type E treatment setup allows the shielding of both lung and humeral head, while maintaining adequate margins around the axillary nodes. In the U position, there is a greater possibility of shielding the lung parenchyma, but it is impossible to block the humeral heads.


Subject(s)
Arm , Hodgkin Disease/radiotherapy , Lymphatic Irradiation/methods , Radiation Protection/methods , Radiotherapy Planning, Computer-Assisted , Axilla , Breast Neoplasms/surgery , Humans , Humerus/radiation effects , Lung/radiation effects , Lymph Node Excision , Lymph Nodes/radiation effects , Phantoms, Imaging , Prospective Studies
14.
Radiologe ; 38(9): 774-8, 1998 Sep.
Article in German | MEDLINE | ID: mdl-9793136

ABSTRACT

PURPOSE: Evaluation of MRI in radiotherapy of humeroscapular periarthritis. PATIENTS AND METHODS: Seventy-seven patients with humeroscapular periarthritis prospectively underwent MRI before radiotherapy. RESULTS: Six months after radiotherapy, 34% of the patients had achieved complete pain relief, 35% major pain relief. Twenty percent had only slight improvement and 12% no improvement. Positive correlation of radiotherapy outcome and MRI findings could be shown for acute tendinitis, erosions, and complete and incomplete ruptures of the supraspinatus tendon. CONCLUSIONS: Radiotherapy is highly effective in the treatment of humeroscapular periarthritis. The indication can be improved using MRI.


Subject(s)
Periarthritis/radiotherapy , Photons/therapeutic use , Shoulder Joint/radiation effects , Aged , Electromagnetic Fields , Female , Follow-Up Studies , Humans , Humerus/radiation effects , Magnetic Resonance Imaging , Male , Middle Aged , Scapula/radiation effects , Treatment Outcome
15.
Health Phys ; 75(3): 251-8, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9721833

ABSTRACT

The microdistribution of 239Pu was analyzed in the humerus, lumbar vertebra, and proximal ulna of young adult beagles using neutron induced autoradiography. The animals were sacrificed serially in groups of three at 4, 8, 16, 32, and 64 wk after a single injection of 3.5 kBq kg(-1) body weight. The kinetic behavior of surface concentrations was modeled using a simple concept of deposition and clearance in skeletal regions. Bones with high turnover showed a larger initial uptake and a faster clearance than bones with low turnover rates. Using a regression procedure, the surface deposition and clearance of plutonium was calculated as a function of the turnover rate. With time after injection the initial nonuniformity of trabecular surface labels tends to become more uniform. The trabecular:cortical affinity ratio is about 10. Trabecular activity is gradually translocated to cortical sites. The affinity ratio of forming to resting surfaces is about three. In some bones a continuous increase of marrow stars was observed, whereas in other bones no clear-cut tendency could be seen. The highest level of marrow labeling occurred in the lumbar vertebra and the humerus shaft.


Subject(s)
Bone and Bones/metabolism , Bone and Bones/radiation effects , Plutonium/pharmacokinetics , Animals , Autoradiography , Dogs , Humerus/metabolism , Humerus/radiation effects , Lumbar Vertebrae/metabolism , Lumbar Vertebrae/radiation effects , Models, Biological , Plutonium/administration & dosage , Tissue Distribution , Ulna/metabolism , Ulna/radiation effects
16.
Appl Human Sci ; 16(4): 143-8, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9343862

ABSTRACT

Based on the hypothesis that bone calcification is promoted by loading physical pressure, changes in the microstructure of the bone under hyperbaric conditions were analyzed by imaging technology. Hyperbaric exposure was carried out for two weeks at 2 atm (equal to the pressure at a depth of water of 10 m) which was achieved using a mixed gas of helium and oxygen (He:O2 88%:12%) in which the oxygen partial pressure was maintained at constant (PO2: 0.21 bar). In image technological analysis, the growth and development of the bone were evaluated at different stages using Digital Magnification Radiography (DMR) images and based on changes in the X-ray absorption ratio. DMR images after hyperbaric exposure showed calcification in the heads of long bones (humeri, femora, and tibiae) in mice. There were also significant changes in the X-ray absorption ratio in the heads. The accumulation of 99mTc-MDP was higher in all long-bone heads after hyperbaric exposure than before exposure. These results suggest that the hyperbaric environment promotes bone calcification.


Subject(s)
Calcification, Physiologic/physiology , Femur/physiology , Humerus/physiology , Hyperbaric Oxygenation , Tibia/physiology , Animals , Atmospheric Pressure , Body Weight/physiology , Femur/chemistry , Femur/radiation effects , Helium , Humerus/chemistry , Humerus/radiation effects , Male , Mice , Mice, Inbred Strains , Oxygen , Technetium Tc 99m Medronate/analysis , Tibia/chemistry , Tibia/radiation effects , Weight-Bearing/physiology
17.
Blood ; 85(5): 1195-201, 1995 Mar 01.
Article in English | MEDLINE | ID: mdl-7532034

ABSTRACT

We have studied the role of different conditioning regimens for engraftment of genetically marked hematopoietic repopulating cells in dogs. Peripheral blood (PB) and/or marrow cells collected after treatment with recombinant canine stem cell factor (rcSCF) or cyclophosphamide were transduced in a vector-containing long-term culture system. Three different vector-producing cell lines with similar viral titers were used. In two of them, the neo-containing LN vector was packaged either in the PA317 cell line with an amphotropic murine retrovirus envelope or the PG13 cell line with the gibbon ape leukemia virus (GALV) envelope. The MFG/GC vector produced in PA317 cells contained the human glucocerebrosidase gene. Nineteen dogs received either no conditioning (group A, n = 5), irradiation to both humeri with 1,000 cGy (group B, n = 5), a sublethal dose of cyclophosphamide 40 mg/kg (group C, n = 4), a sublethal dose of 200 or 300 cGy total body irradiation (TBI) (group D, n = 3), or an otherwise lethal dose of 920 cGy TBI (group E, n = 3) before intravenous (groups A, C, D, E) or intramedullary (group B) infusion of the transduced autologous hematopoietic cells. Transduction efficiency of hematopoietic cells at the time of infusion into the animals was similar among the different conditioning groups. Dogs were observed for at least 6 months. PB granulocytes were obtained at least every 3 weeks after transplant and analyzed by polymerase chain reaction for the presence of the transduced genes. The percentages of positive results in dogs more than 4 weeks after transplantation were 0% without conditioning, 5% with local irradiation, 18% with sublethal cyclophosphamide, 33% with sublethal TBI, and 17% with otherwise lethal TBI. Analyzing the influence of conditioning regimens by a generalized estimating equation (GEE) technique, which considered the use of different retrovirus vectors and the number of mononuclear cells infused as potential confounding variables, we found that engraftment of genetically marked repopulating cells was significantly improved (P < .001) in dogs receiving systemic conditioning with either otherwise lethal TBI, sublethal TBI, or sublethal cyclophosphamide compared to dogs with local irradiation only or no conditioning. Within the limitation of the experimental design, these data suggest that myeloablative or myelosuppressive conditioning improves engraftment of genetically marked hematopoietic repopulating cells.


Subject(s)
Bone Marrow/drug effects , Bone Marrow/radiation effects , Cyclophosphamide/pharmacology , Graft Enhancement, Immunologic , Hematopoietic Cell Growth Factors/pharmacology , Hematopoietic Stem Cell Transplantation , Animals , Base Sequence , Cells, Cultured/transplantation , Dogs , Dose-Response Relationship, Radiation , Genes, Reporter , Genetic Vectors , Graft Survival , Granulocytes/chemistry , Humerus/radiation effects , Kanamycin Kinase , Molecular Sequence Data , Phosphotransferases (Alcohol Group Acceptor)/genetics , Polymerase Chain Reaction , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/pharmacology , Retroviridae/genetics , Stem Cell Factor , Whole-Body Irradiation
18.
Bioelectromagnetics ; 16(3): 152-9, 1995.
Article in English | MEDLINE | ID: mdl-7677791

ABSTRACT

Whole-body fields were tested for their efficacy in preventing the osteopenia caused by tail suspension in mice. The fields had fundamental frequencies corresponding to the upper range of predicted endogenous impact-generated frequencies (0.25-2.0 kHz) in the long bones. Three distinct whole-body EMFs were applied for 2 weeks on growing mice. Structural, geometric, and material properties of the femora, tibiae, and humeri of suspended mice were altered compared to controls. Comparison of suspended mice and mice subjected to caloric restriction indicates that the changes in caloric intake do not explain either the suspension or the field-induced effects. In agreement with past studies, rather, unloading appears to cause the suspension effects and to be addressed by the EMFs. The EMF effects on bone properties were apparently frequency dependent, with the lower two fundamental frequencies (260 and 910 Hz) altering, albeit slightly, the suspension-induced bone effects. The fields are not apparently optimized for frequency, etc., with respect to therapeutic potential; however, suspension provides a model system for further study of the in vivo effects of EMFs.


Subject(s)
Bone Diseases, Metabolic/prevention & control , Electromagnetic Fields , Animals , Biomechanical Phenomena , Bone Diseases, Metabolic/etiology , Femur/radiation effects , Humerus/radiation effects , Male , Mice , Posture , Reference Values , Tibia/radiation effects
19.
J Fla Med Assoc ; 79(12): 828-32, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1474368

ABSTRACT

Radiation therapy to control heterotopic bone formation does not appear to be commonly used in sites other than hips where effective control is evident following arthroplasty. Reported are the results in 12 sites in 10 patients including three with treatment to the elbow, humerus, and ulna. Ten sites received a radiation dose of 10.00 Gy, one 16.00 Gy, and one was treated to 20.00 Gy, all delivered in 2.00 Gy fractions. Preoperative and follow-up x-rays were reviewed and graded. There was no clinically significant regrowth of heterotopic bone. Five sites (42%) demonstrated mild regrowth or persistence following surgery with the other seven (58%) showing no evidence of heterotopic bone. No complications were seen. Radiation therapy is effective for the prevention of heterotopic bone after total hip arthroplasties as well as surgery for fractures to other areas.


Subject(s)
Bone and Bones/radiation effects , Ossification, Heterotopic/radiotherapy , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Fracture Fixation, Internal , Hip Prosthesis , Humans , Humerus/radiation effects , Male , Middle Aged , Ossification, Heterotopic/prevention & control , Radiotherapy Dosage , Reoperation , Shoulder Fractures/surgery , Ulna/radiation effects , Elbow Injuries
20.
J Bone Joint Surg Am ; 72(10): 1527-33, 1990 Dec.
Article in English | MEDLINE | ID: mdl-2123879

ABSTRACT

A non-weight-bearing porous-coated rod was implanted bilaterally in the proximal part of the humerus in thirty-five adult male mongrel dogs. In all of the animals, one limb was treated with radiation and the opposite limb served as the control. In twenty-one animals, the dose was 1000 centigrays (rads) and in fourteen, it was 500 centigrays. The strength of fixation and the volume fraction of ingrowth of bone were determined two, four, and eight weeks after the operation in the group that received 1000 centigrays and two and four weeks after the operation in the group that received 500 centigrays. Treatment with 500 centigrays had no significant effect on the strength of fixation or the amount of ingrowth of bone. In contrast, at two weeks, treatment with 1000 centigrays had reduced the strength of fixation to 50 per cent of the control value (p less than 0.01), although, at four and eight weeks, the strength of fixation was not significantly different than that in the control limb. The amount of ingrowth of bone in the irradiated limb was significantly reduced at two weeks (30 per cent of the control value) (p less than 0.01), four weeks (70 per cent of the control value) (p less than 0.05), and eight weeks (56 per cent of the control value) (p less than 0.05).


Subject(s)
Humerus/radiation effects , Prostheses and Implants , Animals , Cementation , Dogs , Humerus/surgery , Male , Microscopy, Electron, Scanning , Osseointegration , Ossification, Heterotopic/prevention & control , Porosity , Radiation Dosage , Stress, Mechanical
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