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Biomedical subjects

G E Friedlaender

Publications and source records attributed to G E Friedlaender.

At least 19 recordsLinked to original sources

A curriculum for the ideal orthopaedic residency. Academic Orthopaedic Society.

The Academic Orthopaedic Society met in April 1994 to discuss manpower issues in orthopaedics. The members developed an approach using the Delphi system to define and obtain consensus on the characteristics of the ideal residency. Six categories of educational attributes were included: General; Clinical Management; Skills and Technical Aspects; Rehabilitation; Basic Science and Research; and Educational Environment. The following year a questionnaire was sent to more than 125 programs in an attempt to have residents and staff anonymously self score their residencies according to the standards defined by the Delphi panels. The results obtained from the 745 responders from 73 programs validate effectively the characteristics of the ideal program and also show the variation among the programs.

Clinical Competence

The Nicolas Andry Award-1995. Fracture healing. Radiation induced alterations.

This study investigated the effects of radiation on fractures in a rat femur model. Two different radiation dosage fractionation schemes (1100 rads given in one dose and 2500 rads given in 10 divided doses over 12 days) and three different times of initiation of radiation (1 day before fracture, 3 or 10 days after fracture) were studied. Fractures exposed to these levels of radiation all appeared to heal during the course of this experiment, although with varying degrees of delay, with the exception of those exposed to a single dose of 1100 rads 3 days after fracture. These animals remained at a more immature level of repair histologically compared with the control group, throughout the entire time evaluated. The strength of the final repair remained less than the control for all the groups receiving treatment. These results may offer some explanation for the clinical observations of an increased incidence of delayed union and nonunion of fractures, an increased incidence of fracture and refracture in irradiated bone, and an increased incidence of fracture and nonunion in constructs using radiation in conjunction with allogeneic bone. Furthermore, the observed effects were generally no different in the animals treated with the two clinically relevant dose fractionation schemes chosen for this study.

Animals

The immune response: the efferent arm.

Once naive T cells encounter antigen, they become primed effector cells. The scope of effector functions mediated by these cells defines the efferent arm of the immune response. The change from naive to primed effector cell is known as adaptive immunity and takes 2 forms: cell mediated, in which T cells mediate effector function, and humoral, in which antibodies are the effector molecules. There are 3 types of effector T cells: inflammatory CD4 T cells, which activate macrophages; helper CD4 T cells, which help B lymphocytes produce antibody; and cytotoxic CD8 T cells, which kill their target cells. The interaction of primed effector cells with their targets results in phenotypic changes in the cells and the secretion of cytokines. These cytokines may be secreted by the primed effector T cell, the target cell, or both. Cytokines function in either autocrine (secreted and used by the same cell) or paracrine (secreted by 1 cell and used by a different cell) circuits and have marked regulatory effects on cells in both the immune and skeletal systems. Many of these cytokines, which were once thought to be products exclusively of immune cells, are now known to be produced by cells of the skeletal system. Both the specific and nonspecific components of the immune response have profound effects on remodeling of the musculoskeletal system during normal and pathologic states.

Antigens, CD

Immunologic responses in human recipients of osseous and osteochondral allografts.

A multiinstitutional study was carried out to evaluate immunologic responses for human recipients of massive frozen (-80 degrees C) osseous and osteochondral allografts. Allografts were used to reconstruct skeletal defects associated with a variety of traumatic degenerative and neoplastic disorders. Serum samples were obtained before surgery and from 1 month to 4 years after surgery. Sera were tested by microcytotoxicity against T cells from 60 donors for human leukocyte antigen Class I antibodies and against beta 2-microglobulin treated B cells from 40 donors for human leukocyte antigen Class II antibodies. Panels were selected to represent the majority of known human leukocyte antigen specificities. Of the 84 cases evaluated, 62 (74%) received blood transfusions and 28 of 44 (64%) female recipients had been previously pregnant. Sensitization before transplant was shown in 33 of 84 (39%) patients. After grafting, 49 of 84 (58%) recipients showed evidence of sensitization to Class I antigens and 46 of 84 (55%) recipients showed evidence to sensitization to Class II antigens. Overall sensitization was 67%.

Adolescent

Effects of prefracture irradiation on the biomechanical parameters of fracture healing.

This study examined the effects on the biomechanical parameters of fracture healing of a single dose of 900 rad (the approximate single-dose equivalent of 2,500 rad in 10 divided doses), given 1 day prior to closed fracture of the femur. The femurs were recovered at 2, 3, 4, 8, and 16 weeks after fracture and were mounted and tested to failure in torsion; the results were compared with those in nonirradiated controls from a previously published study. Prefracture irradiation delayed the progressive increase in biomechanical parameters of fracture healing. The delay was statistically significant up to 8 weeks after fracture. At 4 weeks, the normalized torque was 44% that of intact bone in the treated group compared with 75% for the control group. Sixteen weeks after fracture, the biomechanical and histological parameters of fracture healing of the irradiated femurs were no different from those of the nonirradiated controls. Within the treated group, the irradiated fractures remained significantly weaker than their contralateral intact bone at all time intervals, with a torque of only 79% that of intact bone at 16 weeks. Thus, femoral fractures in rats healed (or regained substantial strength) following palliative doses of radiation delivered 1 day prior to injury, but the repair process was delayed compared with that of nonirradiated controls.

Animals

Bone graft and total hip arthroplasty. A review.

The success of total hip arthroplasty has been well documented. Aseptic loosening remains the major long-term problem that can lead to significant bone loss and structural deficits. Bone graft has been used with increasing frequency to reconstruct these difficult cases. In this review, the authors detail the biology, biomechanics, and banking of bone grafts. A summary of currently available data on the clinical result of autograft and allograft in reconstructive hip surgery is presented.

Acetabulum

Immune responses to osteochondral allografts: nature and significance.

Osteochondral allografts evoke immune responses. The nature of these immune responses and their biologic significance are still only partially understood. It is clear, however, that cell surface antigens of the major histocompatibility complex represented on the cellular elements of bone grafts cause T-cell activation, specifically those of the suppressor/cytotoxic phenotype. In numerous animal models, the most immunogenic bone allografts (mismatched, fresh) have demonstrated the poorest clinical and biologic outcomes, while more closely matched and/or grafts treated to reduce immunogenicity (frozen, freeze-dried) have more successfully incorporated. These observations support the hypothesis that immune responses against bone-graft related antigens have biologic significance and that reducing these responses may improve clinical results.

Antibody Formation

The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats.

Ibuprofen is a widely used cyclo-oxygenase inhibitor in clinical practice. It has been demonstrated by others to have an inhibitory effect on fracture repair in animals. In the present study, we were unable to demonstrate any significant alterations in fracture biomechanics as measured by torsion testing and fracture stage in mature Sprague-Dawley rats treated with 30 mg/kg/day oral dose of ibuprofen, starting 3 days following fracture, over a 12-week time interval. Fracture histology and serum osteocalcin levels were no different in treated animals than control animals. Furthermore, histomorphometric parameters of bone remodeling, including bone volume and bone formation rate in the intact tail vertebrae of these animals with unilateral femur fractures, were no different between treated and control animals.

Animals

Postfracture irradiation effects on the biomechanical and histologic parameters of fracture healing.

The effects of single-dose local irradiation on the biomechanical properties of closed femoral fractures were studied in 75 mature Sprague-Dawley rats. Ten days after fracture, the rats were irradiated with 900 rads at 250 kV to the entire fractured femur. At 2, 3, 4, 8, and 16 weeks after fracture, both fractured and contralateral intact femurs were recovered and evaluated biomechanically by testing to failure in torsion. Results were compared with those from a similar study involving fractures irradiated 3 days after fracture as well as nonirradiated control fractures. Fracture healing progressed faster when irradiation was delayed 10 days than when delayed 3 days, and control fractures healed more rapidly than after either delay. In the 10-day delay group, fractures showed greater strength than did those in the 3-day delay group at 8 weeks, but the strength of irradiated fractures in both groups was similarly depressed at 16 weeks, with a maximum torque well below that of control fractures. These results suggest that delaying radiation exposure of a fracture may mitigate short-term deleterious effects on fracture repair, but that long-term results may be similar to those associated with expeditious irradiation.

Animals

Induction of specific T-cell responsiveness to allogeneic bone.

The capacity of fresh murine allogeneic bone to induce a specific immune response in vitro was studied. T-cells stimulated by allogeneic bone in vitro were collected and were characterized for state of activation, cell-surface phenotype, and antigen specificity. The stimulating antigens were determined by genetic mapping with use of recombinant inbred strains of mice and by blocking of mixed lymphocyte cultures with use of neutralizing antibodies. Purified T-cells were cultured alone or with allogeneic or syngeneic bone. In some experiments, the bone marrow was removed before in vitro culture. Responding cells were recovered after a secondary exposure to the stimulating bone. Primed cells were used immediately or cell-lines were developed. The data demonstrated that (1) allogeneic bone activated T-cells and induced their proliferation; (2) bone-induced proliferation of T-cells was specific for antigens that map to the major histocompatibility complex of the bone donor; (3) within the major histocompatibility complex, the antigens responsible for proliferation of T-cells were apparently class-I and class-II determinants; (4) removal of bone-marrow cells had no effect on the ability of that bone to stimulate alloreactivity; and (5) all of the alloreactive T-cells had the cell-surface phenotype Thy-+ CD8+ CD4-.

Animals

The effect of radiation on the fracture repair process. A biomechanical evaluation of a closed fracture in a rat model.

The effects of a single dose of irradiation on the biomechanical parameters of the fracture healing process were studied in a rat model. Intramedullary pinning was performed before production of a closed femoral midshaft fracture. The experimental group was exposed to 900 rad 3 days after fracture and was compared with a control group with a similar fracture that received no irradiation. Animals were killed at intervals ranging from 2-16 weeks after surgery and the bones were tested until failure in torsion. In the irradiated groups, a delay of 4 weeks was noted in the biomechanical parameters associated with fracture healing (torque to failure, torsional stiffness, angle to failure, and biomechanical stage). Despite this delay in the normal temporal progression, the staging and stiffness approached normal controls within an 8-week period. However, the torque to failure remained below normal levels at the conclusion of this study. These results differ from a previous study using an open fracture model.

Animals

Allograft incorporation: a biomechanical evaluation in a rat model.

Allogeneic bone from Sprague-Dawley rat femurs was subjected to levels of freezing and/or irradiation that are known to have produced changes in the associated immune responses to these grafts. This bone was transplanted into an experimentally created gap in the femur of Lewis rats. The subsequent healing of the transplants in the Lewis rats was studied at 2, 4, 8, and 16 weeks after transplantation using torsion testing to failure. There was no clear advantageous biologic response in the union of the grafted material accompanying the alterations in immunologic response as measured by biomechanical testing of the proximal osteosynthesis site in torsion. The torsional strength of all of these groups remained lower than that of intact bone. Furthermore, none of the frozen and/or irradiated allografts exceeded the strength of the fresh allograft at a statistically significant level.

Animals

Angiosarcoma associated with foreign body material. A report of three cases.

The production of tumors through solid-state mechanisms has been demonstrated in experimental animals, but foreign body tumorigenesis has not been proven definitively in man. The authors report three patients with angiosarcoma that occurred in intimate association with foreign material retained for prolonged periods. Although several etiologic factors have been defined in angiosarcoma, foreign bodies generally are not appreciated to have this potential. Review of the literature disclosed six cases of angiosarcoma and 40 cases of sarcomas of other histologic types associated with foreign material, with latency periods of from 4 months to 63 years. Implanted foreign material thus should be considered capable of inducing virtually any form of sarcoma in humans.

Abdominal Neoplasms