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Biomedical subjects

S L Gordon

Publications and source records attributed to S L Gordon.

At least 19 recordsLinked to original sources

Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair.

This investigation tested the hypothesis that delivering mesenchymal stem cell-seeded implants to a tendon gap model results in significantly improved repair biomechanics. Cultured, autologous, marrow-derived mesenchymal stem cells were suspended in a collagen gel delivery vehicle; the cell-gel composite was subsequently contracted onto a pretensioned suture. The resulting tissue prosthesis was then implanted into a 1-cm-long gap defect in the rabbit Achilles tendon. Identical procedures were performed on the contralateral tendon, but only the suture material was implanted. The tendon-implant constructs were evaluated 4, 8, and 12 weeks later by biomechanical and histological criteria. Significantly greater load-related structural and material properties were seen at all time intervals in the mesenchymal stem cell-treated tendons than in the contralateral, treated control repairs (p < 0.05), which contained suture alone with natural cell recruitment. The values were typically twice those for the control tissues at each time interval. Load-related material properties for the treated tissues also increased significantly over time (p < 0.05). The treated tissues had a significantly larger cross-sectional area (p < 0.05), and their collagen fibers appeared to be better aligned than those in the matched controls. The results indicate that delivering mesenchymal stem cell-contracted, organized collagen implants to large tendon defects can significantly improve the biomechanics, structure, and probably the function of the tendon after injury.

Achilles Tendon

A review of basic science issues in low back pain.

This review article is based on a workshop, "New Horizons in Low Back Pain" that was held in November 1995 in San Diego, California. The current article follows the 1995 workshop format of a series of three case study models. Three classical clinical profiles were presented for consideration: lumbar radiculopathy, idiopathic (degenerative disk) low back pain, and degenerative stenosis. This article summarizes the basic science perspectives that were presented and discussed on each topic.

Animals

Effects of spaceflight on the musculoskeletal system: NIH and NASA future directions.

Prolonged bed rest, undertaken by volunteers or resulting from injury and disease, can impair bone and muscle function and structure; extended travel in space also induces these effects. Fluid shifts and disrupted fluid balance may also contribute to observed musculoskeletal aberrations in the weightless environment. Some molecular and cellular events involved in the loading and unloading of the musculoskeletal system are under neural and endocrine influence or control, whereas other events are influenced by local growth factors. Studies are in progress to develop interventions that preserve or improve musculoskeletal integrity in 1g. The NIAMS and NASA are interested in basic and clinical studies of the influence of microgravity on the musculoskeletal system. The interagency workshop results form the basis for new collaborative and cooperative research emphases for the biomedical community under a broad agreement between the National Institutes of Health and NASA.

Bone and Bones

Use and importance of the NIH noncompeting continuation application.

Each year National Institutes of Health (NIH) grant recipients must submit a noncompeting continuation application before receiving continued federal funding. This paper describes the use and value of the application. Investigators benefit by a yearly self-assessment of the research progress and future plans. The noncompeting continuation application is part of the important communication and interaction that should exist between the investigator and NIH staff. NIH staff members use the application to determine important scientific advances that have resulted from supported grants. Many planning activities and required reports are based on information contained in these applications. NIH staff performs scientific and budgetary review to ensure that research progress is satisfactory and that all budgetary and certification issues are in order. Detailed guidance is provided to help the grantee prepare the application. A separate significance section is suggested as a means to document key findings and their importance.

Financing, Government

Ingredients of a successful grant application to the National Institutes of Health.

Many factors determine the scientific merit of an NIH research grant application. This paper is intended to help optimize the organization and logical development of investigators' research ideas so that grant applications will be evaluated by the reviewers in as favorable a light as possible. The ingredients of a successful grant application are good ideas, good science, and a good application. The research should be based on a significant hypothesis and, if possible, oriented towards uncovering an important biological mechanism. Specific methods should be directly related to each aim of the project. Likewise, the specific aims should be related to each hypothesis. All aspects of the application should be clear and focused. It is best to define all assumptions, limitations, and alternative approaches. In general, the best philosophy is for the applicant to address all possible problems before the reviewers.

National Institutes of Health (U.S.)

Total hip arthroplasty after renal transplantation. Long-term follow-up study and assessment of metabolic bone status.

Twenty-two patients had 36 total hip arthroplasties for painful osteonecrosis of the femoral head. At a mean of 86 months after operation, a complete follow-up evaluation, including physical examination, was obtained in 24 hips in 15 patients. An additional 12 hips in seven patients were followed by telephone interview and radiographic evaluation. Although most patients experienced improved hip function and symptomatic relief from pain as a result of the operation, 10 hips developed heterotopic bone, 5 hips dislocated after operation, 6 hips failed due to aseptic loosening, and 1 hip developed a deep infection, and one patient died due to pulmonary embolism. Neither sex, preoperative steroid dose, nor postoperative mean alternate-day steroid dose could be related to aseptic loosening. However, histologic examination of transilial bone biopsy specimens (7 patients, 13 hips) revealed steroid-induced osteoporosis, by the presence of hyperosteoidosis (increased unmineralized osteoid) and increased bone resorption. Bilateral hip involvement, osteoporosis, and high turnover skeletal remodelling at the cement-bone interface potentially contributed to a failure rate that was higher in this group than that reported for primary hip arthroplasty for other diagnoses. The existence of steroid-induced metabolic bone disease and preexisting renal osteodystrophy may pose a significant threat to the long-term survival of a total hip implant.

Adolescent

Management of skeletal giant cell tumors of the phalanges of the hand.

Five cases of unicentric benign giant cell tumors of the phalanges of the hand are reported. Three patients were initially treated with curettage and bone grafting; two had recurrences that necessitated ray resection as the definitive treatment, and one was free of disease at 16 years' follow-up. The two patients who were primarily treated with ray resection were free of disease at follow-up of 2 and 1 years, respectively. Enneking's surgical staging system and Lodwick's x-ray grading of bone tumors were used to evaluate management methods.

Adolescent

Scapulothoracic dissociation (closed avulsion of the scapula, subclavian artery, and brachial plexus): a newly recognized variant, a new classification, and a review of the literature and treatment options.

Scapulothoracic (ST) dissociation is a closed complete traumatic forequarter amputation manifested by a flail pulseless arm and well-defined roentgenographic findings. These roentgenographic findings were previously reported to be lateral displacement of the scapula and either acromioclavicular separation (17) or displaced clavicular fracture (20). In this paper we present four patients with ST dissociation who had a previously unreported combination of roentgenographic findings: lateral displacement of the scapula and sternoclavicular separation. Polytrauma was present in all previously reported cases of patients with ST dissociation. We present one patient, however, in whom ST dissociation is an isolated finding. A review of the literature, and a review of treatment options that includes some combination of amputation, shoulder arthrodesis, prosthetic fitting, and reconstructive tendon transfers, are presented.

Adult

Unicameral bone cyst of the talus.

Unicameral bone cysts are rarely observed in the foot. A histologically proven unicameral bone cyst occurred in the talus of a three-year-old boy. Six additional cases in the world literature are cited to illustrate the therapeutic and diagnostic problems encountered with this lesion.

Bone Cysts

Functional limb salvage with multimodality treatment in epithelioid sarcoma of the hand: a report of two cases.

Two cases of epithelioid sarcoma in the hand are reported. The first presented as a space-occupying lesion causing carpal tunnel syndrome, which has not been previously reported. The second case presented with a tumor in the palm that was initially misdiagnosed as a benign tumor and was treated inadequately and recurred. With treatment consisting of surgical excision, adjuvant local radiotherapy, and pulsed systemic chemotherapy combined with early detection and aggressive treatment of distant metastases, both patients have functional hands without local recurrence. They are presently free of obvious disease and remain under close observation at short follow-up of 6 and 4 years, respectively.

Adult

Matrix vesicle enzymes in human osteoarthritis.

The enzymatic activities and in vitro calcification properties of matrix vesicle fractions isolated from normal and osteoarthritic (OA) human articular cartilage were compared to determine the essential conditions for calcification in these tissues. Four groups of human cartilage were examined, I, normal articular cartilage from aged, nonOA joints; II, discolored or fibrillated cartilage from OA joints; III, osteophytic cartilage from OA joints; IV, loose body cartilage from OA joints. Fetal bovine growth plate cartilage was also studied. Both ATP- and 5'-AMP-dependent in vitro matrix vesicle calcification occurs in all cartilage groups examined and, for human articular cartilage, these activities increase progressively from Groups I to II to III. Calcification does not occur in the absence of either phosphate or pyrophosphate. Alkaline phosphatase, 5'-AMPase, and ATP:pyrophosphohydrolase activities are increased in Groups III and IV cartilage compared with Group I and are detected at high levels in fetal bovine growth plate cartilage. Pyrophosphatase activity occurs in only those cartilage groups juxtaposed to areas of new bone formation (osteophytic, loose body, and bovine growth plate). These results suggest that OA, growth plate, and even normal articular cartilage all have the potential to undergo calcification as long as both phosphate and pyrophosphate ions can be generated at sufficiently high levels. However, the capacity for cartilage to deposit hydroxyapatite, as it does during bone formation, may depend on the presence of pyrophosphatase activity.

Adenosine Triphosphatases

Assessment of bone grafts used for acetabular augmentation in total hip arthroplasty. A study using roentgenograms and bone scintigraphy.

Total hip arthroplasty was performed in 13 hips with acetabular bone grafts for secure component fixation. The incorporation and healing of acetabular bone grafts were investigated with the aid of roentgenograms, planar bone scans, and a newer scintigraphic technique, three-dimensional single photon emission computed tomography (SPECT). Conventional roentgenograms proved unreliable in evaluating bone graft reconstitution because of overlapping trabecular bone patterns of the graft and iliac wing. There was no evidence of graft failure or acetabular loosening. Bone grafts in the late follow-up group (four to seven years postoperation) exhibited normal radionuclide activity, whereas grafts less than one year postsurgery demonstrated patterns of increased activity. SPECT was helpful in producing an anatomic reconstruction of the acetabulum. The observation that bone grafts exhibited normal biological viability is crucial for ensuring secure acetabular component fixation on a long-term basis.

Acetabulum

Solvent proton magnetic resonance dispersion in protocatechuate 3,4-dioxygenase and complexes with 3-halo-4-hydroxybenzoate inhibitors.

Solvent proton nuclear magnetic dispersion studies at 25, 100, and 300 MHz have been performed on protocatechuate 3,4-dioxygenase (PCD) and its complexes with 3-chloro-4-hydroxybenzoate and 3-fluoro-4-hydroxybenzoate. Longitudinal and transverse relaxation rates were measured for these compounds and for the apoenzyme. The paramagnetic enhancement of solvent T1 is interpreted in terms of dominant dipole-dipole relaxation of fast-exchanging solvent protons with a negligible contribution from outer sphere relaxation and an electronic spin relaxation time of 0.5 ns for the high-spin ferric ion. A discrepancy between the observed T2 at 300 MHz and that calculated by assuming the usual dipolar relaxation provides evidence for an additional Curie-spin dipolar or hyperfine interaction between the proton and iron. Quantitation of the additional relaxivity provides an estimated chemical exchange lifetime of 0.1-0.14 microseconds, which suggests proton exchange by a hydroxide ligand. Proton-to-iron distances are 2.7-3.1 A in PCD and lengthen to 3.6-4.1 A in the halohydroxybenzoate complexes.

Apoenzymes