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Biomedical subjects

S Stevenson

Publications and source records attributed to S Stevenson.

At least 73 records · Page 4Linked to original sources

The biology of bone grafts.

The clinical outcome of bone grafting procedures depends on many factors, including type and fixation of the bone graft as well as the site and status of the host bed. Bone grafts serve one or both of two main functions, as a source of osteogenesis and as a mechanical support. Autografts, both cancellous and cortical, are implanted fresh, provide a source of osteoprogenitor cells, and are osteoinductive. The latter is a process whereby the transplanted tissue induces mesenchymal cells of the recipient to differentiate into osteoblastic cells. Cortical grafts, whether autogeneic or allogeneic, at least initially act as weight-bearing space fillers. All bone grafts are initially resorbed; cancellous grafts are completely replaced in time by creeping substitution, whereas cortical grafts remain an admixture of necrotic and viable bone for a prolonged period of time. The three-dimensional framework that supports invasion of the bone grafts by capillaries and osteoprogenitor cells, termed "osteoconduction", is another important function of both autografts and allografts. Because fresh allographs evoke both local and systemic immune responses that diminish or destroy the osteoinductive and conductive processes, freezing or freeze-drying of allografts is used clinically to improve incorporation. Graft incorporation is also influenced by the vascularity and composition of the host bed. Thus, the interaction of the host and the bone graft determines the success of these procedures, which ultimately is to provide a mechanically efficient support structure.

Bone Transplantation↗

Evaluation of biocompatible osteoconductive polymer as an orthopedic implant in dogs.

The biocompatibility and osteoconductive properties of biocompatible osteoconductive polymer (BOP), a synthetic implant, were evaluated. Bilateral oval cortical defects (1 x 2 cm) were made in the lateral subtrochanteric area of the proximal portion of the femur in 16 dogs that later were treated with BOP fiber (n = 16) or autogenous cancellous bone (n = 11), or were not treated (n = 5). The BOP block was attached extraperiosteally to the proximal portion of the humerus in 6 dogs. Radiographic assessment of surgery sites was performed at 4-week intervals, and histologic evaluation was performed at 4, 8, 16, and 24 weeks after surgery. Radiographic signs of bone healing were not observed in defects treated with BOP fiber. Defects treated with cancellous bone or not treated had radiographic signs of progressive bone ingrowth. Radiographic evidence of periosteal new bone formation near control and BOP-treated defects was observed 4 weeks after surgery; increased periosteal reaction was associated with BOP fiber. This new bone had resorbed by week 24, except bone adjacent to BOP fiber, where continued periosteal reaction was apparent. Histologic evidence of bone formation was observed extending to, but not incorporating, BOP fibers. The BOP fibers became surrounded by a fibrous capsule, and fibrovascular connective tissue infiltrated between and into BOP fibers, but minimal bone formation incorporated the BOP material during the follow-up period. During that time, active periosteal new bone formation was evident adjacent to the BOP fibers. Defects treated with cancellous bone or not treated healed by ingrowth of cancellous bone during the first 12 weeks after surgery and by reformation of the lateral cortical wall by week 24. The BOP blocks became surrounded by a fibrous capsule, but connective tissue or bone ingrowth into BOP blocks was not observed. Results indicate that BOP is not osteoconductive within a 6-month time frame when used in subtrochanteric femoral defects or when placed extraperiosteally on the proximal portion of the humerus of clinically normal dogs.

Animals↗

Alternative splicing of the mRNA encoding the human cholesteryl ester transfer protein.

The plasma cholesteryl ester transfer protein (CETP) is known to facilitate the transfer of lipids between plasma lipoproteins. The human CETP gene is a complex locus encompassing 16 exons. The CETP mRNA is found in liver and small intestine as well as in a variety of peripheral tissues. While the CETP cDNA from human adipose tissue was being cloned, a variant CETP cDNA was discovered which excluded the complete sequence encoded by exon 9, but which was otherwise identical to the full-length CETP cDNA, suggesting modification of the CETP gene transcript by an alternative RNA splicing mechanism. RNase protection analysis of tissue RNA confirmed the presence of exon 9 deleted transcripts and showed that they represented a variable proportion of the total CETP mRNA in various human tissues including adipose tissue (25%), liver (33%), and spleen (46%). Transient expression of the exon 9 deleted cDNA in COS cells or stable expression in CHO cells showed that the protein encoded by the alternatively spliced transcript was inactive in neutral lipid transfer, smaller, and poorly secreted compared to the protein derived from the full-length cDNA. Endo H digestion suggested that the inactive, cell-associated protein was present within the endoplasmic reticulum. The experiments show that the expression of the human CETP gene is modified by alternative splicing of the ninth exon, in a tissue-specific fashion. The function of alternative splicing is unknown but could serve to produce a protein with a function other than plasma neutral lipid transfer, or as an on-off switch to regulate the local concentration of biologically active protein.

Adipose Tissue↗

S-100 protein immunostaining identifies cells expressing a chondrocytic phenotype during articular cartilage repair.

The healing of articular surface defects has been studied with conventional histology, which relies on the staining of the extracellular matrix to identify the phenotype of the cells present. A chondrospecific cellular marker would be useful. S-100 protein has been found in all chondroid tissues studied, and we evaluated its usefulness in the study of articular cartilage repair. Full-thickness rabbit femoral condylar defects were made, and the specimens were studied at serial time intervals. S-100 protein staining positively showed chondroid cells in the 7- and 14-day specimens, which were not identifiable by conventional techniques. At 30 and 60 days, an S-100 positive band of cells separated a deep safranin-O positive hypertrophic layer from a fibrocellular surface layer. At 120 days, the presence of S-100 protein identified cells with chondrogenic potential, and the lack of S-100 protein in other cells embedded in conventionally stained matrix suggested that these cells were no longer of a chondroid phenotype. The presence of S-100 protein-identified chondroid cells early in the repair process when the cells had not begun to synthesize conventionally stainable matrix and the lack of S-100 protein in cells late in the repair positively identified a phenotypic change earlier than conventional histology.

Animals↗

The effects of vascularity and cyclosporin A on the mechanical properties of canine fibular autografts.

We studied the biomechanical behavior of orthotopic canine autografts as influenced by vascularized supply and the administration of cyclosporin A at three months and six months post-surgery. The model was the proximal 8 cm of the fibula in young adult dogs. In vascularized grafts, blood supply was re-established by microvascular re-anastomosis. Experimental controls were sham-operated and unoperated bones. Mid-graft test sections were subjected to loading-to-failure in torsion to determine the strength and stiffness. In both three- and six-month groups, vascularized grafts were significantly stronger and stiffer than contralateral nonvascularized grafts. Vascularized grafts were not significantly different from sham-operated bones. A 30-day regimen of cyclosporin A was found to have no measurable effect on mechanical properties for any individual treatment group. The results indicate that re-established blood supply can be a major factor in maintaining the mechanical integrity in large-segment cortical autografts.

Animals↗

A semiquantitative scale for histologic grading of articular cartilage repair.

This laboratory has developed a semiquantitative scale for grading the natural healing process of defects drilled into articular cartilage. The scale is composed of four parameters: percent filling of the defect, reconstitution of the osteochondral junction, matrix staining and cell morphology; it has a score range from 0 (best) to 14 (worst). The scale was used to evaluate the healing of defects drilled into rabbit knee articular cartilage at 2, 14, 30, 60 and 120 days after surgery. No statistically significant difference in the graded score was found between the two different defect sizes (2.7 and 1.5 mm). However, the differences in score observed between specimens from different sacrifice times were significant (p less than 0.01). Currently many investigators are manipulating cartilaginous lesions in an attempt to improve healing, and this scale will provide a means for quantitatively comparing results from control and experimental groups.

Animals↗

Evaluation of the proximal portion of the femur as an autogenous cancellous bone donor site in dogs.

The proximal portion of the femur was evaluated as a source of autogenous cancellous bone in dogs. Bilateral oval cortical defects were created in the lateral subtrochanteric area of the femur in 16 dogs. Cancellous bone was removed and the weight recorded. Cancellous bone was similarly harvested from the proximal portion of the humerus in 7 of these dogs. Subtrochanteric femoral defects in 11 dogs were randomly assigned to receive cancellous bone graft obtained from the femur (n = 4) or the humerus (n = 7). Subtrochanteric defects in 5 dogs were not grafted. Radiographic assessment of subtrochanteric defects was performed at 4-week intervals, and histologic assessment at 4, 8, 16, and 24 weeks after surgery. Nongrafted donor sites healed by ingrowth of trabecular bone during the first 12 weeks after surgery. By week 24, the lateral cortical wall had reformed, but remodeling was incomplete. Donor sites grafted with cancellous bone healed similarly, but with more rapid healing and more complete remodeling evident by week 24. Although the mean weight of cancellous bone harvested from the proximal portion of the femur (0.82 +/- 0.22 g) was significantly (P less than 0.05) less than that harvested from the proximal portion of the humerus (1.38 +/- 0.29 g), there was no qualitative histologic or radiographic difference in bony healing of grafted defects. We determined that the proximal portion of the femur can be safely used to provide moderate amounts of cancellous bone, and that a second bone graft can be collected from the same subtrochanteric donor site after 12 weeks.

Animals↗

Negative feedback control model of proximal convergence and accommodation.

A comprehensive model has been developed to illustrate the interactions between the observer and the surrounding environment in the control of oculomotor responses to distance or 3-D space. Accommodation and vergence respond to both spatiotopic (body reference) proximal percepts and retinotopic (eye referenced) physical stimuli of blur and disparity. Both spatiotopic and retinotopic stimuli are derived respectively from perceptual and physical correlates of negative feedback for eye position. The spatiotopic and retinotopic stimulus errors are combined in the feedforward path and drive a common oculomotor controller which has a phasic-tonic organization. Spatiotopic and retinotopic stimuli are shown to be effective over complementary operating ranges. Perceptual spatiotopic errors of gaze provide optimal stimuli for near responses to large depth intervals whereas physical-retinotopic cues of blur and disparity provide quantitative information about small binocular fixation errors. Small dynamic variations of target distance are sensed both spatiotopically and retinotopically. Coarse and fine spatiotopic errors of gaze are processed differently. Large spatiotopic errors are sampled intermittently at the beginning of the near response, whereas small retinotopic position errors and spatiotopic velocity errors are sampled continuously throughout the near response. Former reports of empirically observed higher velocity of vergence responses to very large depth intervals is explained in terms of stimulus sampling modes rather than in terms of separate oculomotor control mechanisms. The model demonstrates a complementary function of top-down spatiotopic cues, which are used to initiate the near response, and bottom-up retinotopic cues, which are used to refine and complete the near response. Cross-couplings by vergence-accommodation and accommodative-vergence serve to coordinate the components of the near response when feedback from sensed response of one motor system (i.e. vergence) is more accurate than that of the other motor system (i.e. accommodation). The model presented here is concerned primarily with the near response mediated by accommodation and disjunctive eye movements and not by the independent vergence mediated by non-conjugate or yoked saccades of unequal amplitude.

Accommodation, Ocular↗

Bone mass and comparative rates of bone resorption and formation of fibular autografts: comparison of vascular and nonvascular grafts in dogs.

The metabolic fate of whole grafts that were either vascularized or nonvascularized were compared. This study was designed to quantify and correlate changes in bone resorption, formation, and mass in orthotopic, stably fixed, weight-bearing autografts. The grafts were 8-cm segments of the fibula that were internally fixed. Fibula segments subjected to sham operations, nonvascularized autografts, and vascularized autografts were studied in 16 dogs at three months after surgery. Three months prior to surgery the dogs were labeled repeatedly over two months with 3H-tetracycline and 3H-proline. Metabolic turnover of whole grafts was evaluated by quantifying loss of 3H-tetracycline for measuring postoperative resorption of bone mineral and loss of 3H-collagen for resorption of bone collagen. Net changes in bone dry weight, calcium, and collagen per whole grafts were obtained to determine differential changes in the mineral and matrix mass. The difference in change between bone resorption and bone mass was used to determine the amount of new bone formation that had replaced the resorbed bone. Vascularized autografts lost more mass (12%), and had more bone resorption (40%) and more bone formation (28%) than sham operated and unoperated fibulas. Nonvascularized grafts lost much more bone mass (48%) because resorption was large (61%) and formation was relatively small (13%). More new bone was formed in vascularized autografts than in nonvascularized autografts. During the incorporation of bone grafts, resorption is an early and rapid process, whereas formation is a late and slow process.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fracture-associated sarcomas.

Fracture-associated sarcomas occur at the site of a fracture that usually occurred 5 or more years ago. This article reviews hypotheses regarding the casualty of these sarcomas. Diagnosis and treatment are described, and ways to avoid development of fracture-associated sarcomas are discussed. At present, the best treatment is prevention, and the best mode of prevention is to achieve uncomplicated fracture healing.

Animals↗

Differential patterns of incorporation and remodeling among various types of bone grafts.

The early (3 months) and later (6 months) patterns of incorporation and bone formation have been evaluated histomorphometrically for different types of bone grafts; that is, vascularized and nonvascularized autografts with and without ciclosporin, and vascularized and nonvascularized dog leukocyte antigen (DLA)-mismatched allografts with and without ciclosporin. The vascularized bones were superior to the nonvascularized ones in healing and remodeling their grafted segments. In the autograft bones, ciclosporin did not alter the incorporation process 3 months after transplantation but delayed and increased the remodeling activities in the long run (6 months). Nonvascularized allografts underwent vigorous resorption, and were markedly porotic. Ciclosporin administration significantly reduced resorption and enhanced remodeling in nonvascularized allografts. The remodeling of allografts was similar to that of autografts in the presence of ciclosporin, but stopped soon after the administration of ciclosporin ceased.

Animals↗

Heading off violence with verbal de-escalation.

Respect for the rights and dignity of patients is the underlying principle of therapeutic communication. Its effective practice requires the nurse to identify personal issues, stressors, and one's own anxiety and effectiveness levels. It is important that the caregiver maintain self-control to help others control themselves. By constantly observing patient behavior, the nurse should be able to detect agitation and intervene in a timely fashion, avoiding physical confrontation and the physical restraints that are its usual consequence. To make this outcome possible, the nurse should learn to recognize signs of agitation and escalation; should practice presenting himself or herself as a calm, caring professional; and should maintain poise even when facing a potentially violent patient. The nurse should remain open-minded, knowing that patients frequently react to assumptions made about them, and use the information acquired to find acceptable alternatives to aggression. These alternatives should be presented to the patient, making the choices clear, yet allowing the dignity of choice. Every effort should be made to provide opportunity for patients to be in control of their own behavior. Physical confrontation should always be a last resort, and one used only when there is a clear danger of immediate physical harm to a patient or staff member. Keep in mind that the use of force is an encouragement to aggressive behavior and a hindrance to treatment. Effective use of therapeutic communication encourages patients to express their feelings and become cooperative partners in their treatment.

Communication↗

Anterior cruciate ligament allograft transplantation in dogs.

The biomechanical and clinical performance of bone-ligament-bone anterior cruciate ligament (ACL) allografts was studied in eight dogs. Allografts were collected from skeletally mature, healthy dogs using aseptic technique, and stored at -70 degrees for three to five weeks before implantation. The allografts were size-matched to the recipient dogs using ACL length and then rigidly fixed in position with interference screws and Kirschner wires. Three dogs regained a normal gait, and their grafts sustained breaking loads that were 25%, 41%, and 59% of controls. Partial or complete graft failure occurred in the other five dogs at some point in the study. Four had intraligamentous rupture and one had an avulsion fracture of the femoral attachment site. Joint-fluid cytology was normal in all eight dogs. Histologic examination showed persistent lymphoplasmacytic infiltrate. Eventually the allograft cores were incorporated in the host bed. Hyperplasia and fibrosis of the synovial membrane were diffuse and persisted as focal accumulations of mononuclear inflammatory cells.

Animals↗

The fate of cancellous and cortical bone after transplantation of fresh and frozen tissue-antigen-matched and mismatched osteochondral allografts in dogs.

After implantation, a massive osteochondral allograft cannot be completely protected from the stresses that are produced by weight-bearing, and it is susceptible to collapse during incorporation, revascularization, and substitution. How these processes are affected by disparities between the tissue antigens of the host and the graft remain unclear. To clarify the role of histocompatibility antigen-matching in the incorporation of cancellous and cortical bone, we orthotopically implanted both fresh and cryopreserved dog leukocyte-antigen-matched and mismatched proximal osteochondral radial allografts in beagles. Four groups of beagle dogs were used; they received (1) a dog leukocyte-antigen-mismatched frozen allograft, (2) a dog leukocyte-antigen-mismatched fresh allograft, (3) a dog leukocyte-antigen-matched fresh allograft, or (4) a dog leukocyte-antigen-matched frozen allograft. In twelve dogs, a sham operation was done in the contralateral limb (the first living donor had a sham operation), and in the remaining ten dogs, the proximal part of the contralateral radius was removed and then replaced as an autogenous (control) graft. The animals were given fluorochromes periodically, and they were killed eleven months after the operation. The osseous portion of the grafts was evaluated radiographically, biomechanically, and histomorphometrically. No dog had grossly obvious clinical abnormalities, all host-graft interfaces healed, and no joints dislocated. Radiographic examination of the allografts frequently showed deformation of the radial head and variable peripheral resorption. No significant difference in the modulus of elasticity at the host-graft interface was found among the groups. The repair process of the cortical bone was similar for all grafted segments. New periosteal and endosteal bone formed, and the cortical bone became porotic as vessels penetrated it. The uptake of fluorochrome was the most active in the autogenous grafts and the least active in the fresh antigen-mismatched grafts. The volume of cancellous bone was significantly greater and the trabeculae were thicker in all allografts compared with the bones on which a sham operation had been done and compared with the autogenous grafts. The volume of intertrabecular fibrous connective tissue was directly proportional to the immunogenicity of the allografts, and the percentage of the surface on which bone was forming tended to be inversely proportional to the immunogenicity of the allografts. The grafts were revascularized by the ingrowth of vessels into the intertrabecular spaces; necrotic trabeculae were not penetrated by vessels. This pattern was particularly pronounced in the antigen-mismatched grafts, regardless of whether they were fresh or frozen.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Is longitudinal bone growth influenced by diurnal variation in the mitotic activity of chondrocytes of the growth plate?

The diurnal variations in the mitotic index, height, and rate of linear bone growth were determined and correlations between these parameters examined. Young, unweaned, female Wistar rats were housed under standardized conditions, labeled with a fluorochrome 60 h before sacrifice, and killed at intervals throughout a 24-h period, specifically 0600, 1200, 1800, and 2400. The proximal tibial epiphyseal growth plates were collected and processed, and the mitotic index, growth plate height, and the rate of linear bone growth were measured. The mitotic index measured at 0600 was significantly higher than that measured at 1800 and 2400. Growth plates of rats sacrificed at 1200 were taller than those of rats sacrificed at 1800, but there was no difference between heights of growth plates from rats sacrificed at other times. Daily growth rate for all rats averaged 283.9 microns/day and there were no statistically significant differences between daily growth rates measured at any time period. Our findings imply that in comparative, quantitative structural studies of animal groups, sacrifice should be carried out at identical times of the day, since, given a constant speed of vascular ingrowth and diurnal variation in width, relative diurnal accumulation and depletions of cells may take place. We also suggest that the daily growth rate and mitotic index be measured directly and not be considered a function of the height of the growth plate.

Animals↗

Volumetric three-dimensional computed tomography for acute calcaneus fractures: preliminary report.

Volumetric three-dimensional (3-D) computed tomographic reconstructions were performed on three cadaver specimens before and after fracture for 16 acute calcaneal fractures. This "second-generation" 3-D reconstruction technique produced accurate, detailed images of the extra-articular fracture anatomy. Use of this method provided visualization of specific fracture component displacement otherwise unappreciated prior to surgery. In two cases, vertical splits in the superomedial fragment were demonstrated to best advantage by this 3-D technique.

Calcaneus↗