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Biomedical subjects

S Stevenson

Publications and source records attributed to S Stevenson.

At least 91 records · Page 5Linked to original sources

Cyclosporin A and tissue antigen matching in bone transplantation. Fibular allografts studied in the dog.

We studied the mechanical, metabolic, and histologic properties of short-term nonvascularized cortical bone grafts in a canine fibular graft model. Sham operated nonvascularized autotransplanted and allotransplanted bones were compared. The allografts were performed between dog leukocyte antigen (DLA) class I and II matched; DLA class I and II mismatched; and cyclosporin A (CsA) treated, DLA class I and II mismatched animals. Cyclosporin was given for 1 month, and all the animals were followed for 3 months after surgery. Mechanical properties were investigated using standard torsional tests, metabolic kinetics were assessed using isotopic prelabeling techniques, and histomorphometric analysis of cross-sectional area properties and sequential fluorochrome labels were performed. Autografts were mechanically stronger and stiffer than all the types of allograft. CsA-treated, DLA-mismatched allografts performed better than matched allografts. These in turn were stronger than non-CsA-treated, mismatched allografts, which underwent nearly complete resorption. These relationships were preserved in the metabolic and histologic analyses. In this short-term animal study, although DLA matching resulted in a slight improvement in graft outcome, mismatched grafts in dogs receiving a short course of cyclosporin A fared even better.

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Biological and physical properties of autogenous vascularized fibular grafts in dogs.

The biological and biomechanical properties of normal fibulae, fibulae that had had a sham operation, and both vascularized and non-vascularized autogenous grafts were studied in dogs at three months after the operation. The study was designed to quantify and correlate changes in these properties in orthotopic, stably fixed, weight-bearing grafts and to provide a baseline for additional studies of allografts. The grafts were eight centimeters long and internally fixed. The mechanical properties of the grafts were studied by torsional testing. Metabolic turnover of the grafts was evaluated by preoperative labeling of the dogs with 3H-tetracycline for resorption of bone mineral and with 3H-proline for turnover of collagen. Cortical bone area and porosity were measured. Postoperative formation of bone was evaluated by sequential labeling with fluorochrome. The vascularized grafts resembled the fibulae that had had a sham operation and those that had not had an operation with regard to the total number of osteons and the remodeling process, as measured both morphometrically and metabolically. The vascularized grafts were stronger and stiffer than the non-vascularized grafts and were not different from the bones that had had a sham operation. In contrast, the non-vascularized grafts were smaller, weaker, less stiff, and more porotic, had fewer osteons, and demonstrated increased turnover and resorption compared with the vascularized grafts, the bones that had had a sham operation, and the bones that had not been operated on.

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Mode of inheritance of Perthes' disease in Manchester terriers.

A test mating between two Manchester Terriers affected by Perthes' disease (PD) resulted in the birth of three affected males and two unaffected females. In the three puppies with PD, roentgenographically detectable changes in the affected femurs were observed two to three weeks before the onset of lameness and muscle atrophy in the corresponding limb. Analysis of the related pedigrees and of the results of the test mating indicated that PD is an inherited condition with high heritability.

Animals↗

The fate of articular cartilage after transplantation of fresh and cryopreserved tissue-antigen-matched and mismatched osteochondral allografts in dogs.

The long-term success of massive osteochondral allografts depends not only on the incorporation of the transplanted articular cartilage. Osteochondral allografts are immunogenic, and, once an immune response is stimulated by exposure to donor cellular antigens, the cartilage becomes vulnerable to direct injury by cytotoxic antibodies or by lymphocytes, or to indirect injury by inflammatory mediators and enzymes induced by the immune response. To clarify the role of histocompatibility antigen-matching on the health of transplanted articular cartilage, we orthotopically implanted canine leukocyte antigen-matched and mismatched proximal osteochondral allografts of the radius, both fresh and cryopreserved, in beagles. Four groups of dogs received: (1) canine leukocyte antigen-mismatched frozen allografts, (2) canine leukocyte antigen-mismatched fresh allografts, (3) canine leukocyte antigen-matched fresh allografts, or (4) canine leukocyte antigen-matched frozen allografts. In twelve of the dogs, the contralateral leg was subjected to a sham operation, and in ten of the dogs, the proximal part of the radius was removed and replaced as an autogenous graft control. All animals were followed for eleven months after the operation and then were killed. The cartilage of the grafts was evaluated grossly, histologically, and biochemically. The biochemical analysis consisted of measurement of dry weight, content of glycosaminoglycan and hydroxyproline, and galactosamine-to-glucosamine ratios. Analyses of variance were used to study the effect of tissue antigen-matching and freezing on degradation of cartilage. During the study, no dog had grossly obvious clinical abnormalities, all host-graft interfaces healed, and no joints dislocated. The gross appearance of the cartilage was normal for both the joints that had an autogenous graft and those that were subjected to the sham operation. The cartilage of all allografts was thinned, dull, and roughened. The synovial membrane of all of the joints that had been operated on was mildly fibrotic and hyperplastic, but only that of the dogs that had an allograft was severely fibrotic and hyperplastic and demonstrated an inflammatory response. The inflammatory response was most severe in joints that had received a fresh canine leukocyte antigen-mismatched allograft. Invasive pannus was more frequent in joints that had received a fresh graft, particularly those that had received a canine leukocyte antigen-mismatched allograft, and cartilage was sometimes eroded to subchondral bone. Freezing was harmful to the cartilage. Very few cells survived the freezing procedure, and frozen grafts received s significantly worse histological scores had significantly less glycosaminoglycans and had a lower ratio of galactosamine to glucosamine than fresh grafts.

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Natural history of autografts and allografts.

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 osteogenetic cells and as a mechanical support. Autografts, both cancellous and cortical, are usually implanted fresh and are often osteogenetic, whether by providing a source of osteoprogenitor cells or by being 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 or struts. All bone grafts are initially resorbed, but cancellous grafts are completely replaced in time by creeping substitution, while cortical grafts remain an admixture of necrotic and viable bone for a prolonged period of time. The three-dimensional framework, which supports invasion of the bone grafts by capillaries and osteoprogenitor cells, termed "osteoconduction", is another important function of both autografts and allografts. Fresh allografts are more slowly and less completely replaced by host bones because they invoke both local and systemic immune responses that diminish or destroy the osteoinductive and conductive processes. Although freezing or freeze-drying of allografts improves acceptance, their failure rate is still too high. These processes are 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.

Animals↗

The immune response to osteochondral allografts in dogs.

Dog leukocyte antigen (DLA)-matched and mismatched, fresh and frozen (cryopreserved) osteochondral allografts of the proximal part of the radius were implanted orthotopically in beagles. The systemic and local (intra-articular) immune responses were monitored for eleven months using a 51chromium release assay with donor peripheral-blood lymphocytes as target cells. DLA-mismatched fresh grafts markedly and persistently stimulated the formation of antibody directed against donor cell-surface antigens, while DLA-matched grafts did not elicit systemically detectable antibody. The same general pattern was noted when antibody-dependent cell-mediated cytotoxicity was assayed. There was measurable cell-mediated immunity to donor cells from six weeks after surgery onward, although no distinct pattern or differences between experimental groups were noted. Higher titers of anti-DLA antibody were found in synovial fluid than in serum; in fact, synovial antibody was detectable when systemic antibody was not. Joints that received DLA-mismatched grafts had the highest titer of antibody and the intra-articular response was significantly reduced when the graft had been frozen.

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Replacement of the anterior cruciate ligament with a bone-ligament-bone anterior cruciate ligament allograft in dogs.

Acute replacement of the canine anterior cruciate ligament (ACL) with a frozen, bone-ligament-bone anterior cruciate ligament preparation was studied using biochemical, immunologic, and biomechanical testing methods. Nine dogs were used for the study, six dogs received allografts and three received autografts. No tissue antigen matching was performed. All nine dogs were killed nine months after surgery. Necropsy examination revealed that the ACL was not present in three joints (one autograft, two allografts). The two autograft and four allograft ligaments available for mechanical testing sustained mean maximum loads that were 10% and 14%, respectively, of the mean maximum loads sustained by the contralateral ACL. Autoradiography indicated that cellular activity was more pronounced in the autograft specimens. Hydroxyproline uptake was 200% and 45% of normal in the autograft and allograft ligaments, respectively. Both autograft and allograft specimens were producing Type I collagen at the time of killing. Antidonor dog leukocyte antigen (DLA) antibody was detected in the synovial fluid taken at the time of killing from six of six dogs that received allografts and in zero of three dogs that received autografts.

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Spontaneous lower motor neuron disease with neurofibrillary accumulation in young pigs.

A spontaneous neurologic disease occurred in six 5 weeks old Yorkshire pigs of both sexes from four litters sired by one boar. Clinically, the disease was characterized initially by bilateral posterior ataxia and weakness which rapidly progressed to tetraplegia by 10 weeks of age. By light microscopy, there was bilateral neuronal chromatolysis, degeneration and loss restricted to motor nuclei in the ventral horns of the spinal cord, in the medulla oblongata and midbrain. In addition to diffuse Wallerian-type degeneration in the spinal cord white matter and ventral peripheral nerve roots, there was prominent neurogenic atrophy of skeletal muscle. Ultrastructurally, the perikaryon and processes of affected neurons contained massive accumulations of single 10 nm diameter neurofilaments. Copper concentrations of both the commercially prepared ration and the livers were within normal limits.

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Effects of tissue antigen matching on the healing of fresh cancellous bone allografts in dogs.

The radiographic and histologic healing patterns of fresh cancellous bone allografts were compared with those of fresh cancellous autografts in dogs. Two groups of allografts were studied: 1 group of littermate pairs with minor histocompatibility mismatches, and 1 group of unrelated pairs with major histocompatibility mismatches. Pairs were chosen on the basis of preoperative serologic typing and mixed lymphocyte cultural assay of lymphocyte-defined compatibility. Generally, grafts with minor mismatches and autografts achieved bony union in 6 weeks with grafted bone serving as a scaffold for new bone formation. Grafts with major mismatches were resorbed and replaced by fibrocartilage. Healing of osteotomy sites grafted with mismatched bone occurred by ingrowth of host periosteal and endosteal new bone.

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Validation and application of nutrition education objectives.

Nutrition education is more likely to be effective when nutrition and education professionals set goals in working with individuals. In an effort to assist such professionals with these goals, 24 objectives for nutrition education were identified and validated. Teachers, dietitians, and nutritionists can use these objectives in analyzing and targeting their nutrition efforts to influence behavior change in students, patients, employees, and clients. Ways to use the objectives and a process for behavior change to use with students are suggested.

Curriculum↗

Fracture-associated sarcoma in the dog.

Seven fracture-associated sarcomas developed in large-breed dogs after stabilization of comminuted long bone fractures with stainless steel plates and screws. In most cases, the healing pattern of the fractures was disturbed. The mean interval between fracture occurrence and tumor diagnosis was 5.5 years. Radiographically, the sarcomas were typified by smooth-bordered subperiosteal proliferation and soft tissue mineralization. Cortical destruction was variable. Several histologic subtypes of osteosarcoma were seen. Four sarcomas had a marked inflammatory cell component and 5 of the dogs had clinical evidence of chronic infection. These findings were similar to those in 35 previously reported fracture-associated sarcomas, even though many types of fixation devices in addition to plates, as well as no fixation at all, were represented in these cases. Fracture-associated sarcomas most frequently were found to be diaphyseal, and the femur accounted for almost half of the sarcomas reported.

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Osteosarcoma at the site of a cortical bone allograft in a dog.

An osteosarcoma developed in the proximal femur of a 9-year-old female Great Dane. The femur had been fractured 5 years previously and was stabilized with plate fixation with the incorporation of a frozen cortical bone allograft. The dog recovered without complications after the surgery and had normal use of the leg before the osteosarcoma developed. The tumor had metastasized to the lungs, spleen, and ipsilateral popliteal lymph node.

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