Biomedical subjects

D S Musgrave

Publications and source records attributed to D S Musgrave.

15 recordsLinked to original sources

PubMed2002

Human skeletal muscle cells in ex vivo gene therapy to deliver bone morphogenetic protein-2.

We have examined whether primary human muscle-derived cells can be used in ex vivo gene therapy to deliver BMP-2 and to produce bone in vivo. Two in vitro experiments and one in vivo experiment were used to determine the osteocompetence and BMP-2 secretion capacity of cells isolated from human skeletal muscle. We isolated five different populations of primary muscle cells from human skeletal muscle in three patients. In the first in vitro experiment, production of alkaline phosphatase by the cells in response to stimulation by rhBMP-2 was measured and used as an indicator of cellular osteocompetence. In the second, secretion of BMP-2 was measured after the cell populations had been transduced by an adenovirus encoding for BMP-2. In the in vivo experiment, the cells were cotransduced with a retrovirus encoding for a nuclear localised beta-galactosidase gene and an adenovirus encoding for BMP-2. The cotransduced cells were then injected into the hind limbs of severe combined immune-deficient (SCID) mice and analysed radiographically and histologically. The nuclear localised beta-galactosidase gene allowed identification of the injected cells in histological specimens. In the first in vitro experiment, the five different cell populations all responded to in vitro stimulation of rhBMP-2 by producing higher levels of alkaline phosphatase when compared with non-stimulated cells. In the second, the five different cell populations were all successfully transduced by an adenovirus to express and secrete BMP-2. The cells secreted between 444 and 2551 ng of BMP-2 over three days. In the in vivo experiment, injection of the transduced cells into the hind-limb musculature of SCID mice resulted in the formation of ectopic bone at 1, 2, 3 and 4 weeks after injection. Retroviral labelling of the cell nuclei showed labelled human muscle-derived cells occupying locations of osteoblasts in the ectopic bone, further supporting their osteocompetence. Cells from human skeletal muscle, because of their availability to orthopaedic surgeons, their osteocompetence, and their ability to express BMP-2 after genetic engineering, are an attractive cell population for use in BMP-2 gene therapy approaches.

Adenoviridae↗

PubMed2001

Back problems among postmenopausal women taking estrogen replacement therapy: the study of osteoporotic fractures.

STUDY DESIGN: Cross-sectional and prospective. OBJECTIVES: To investigate the association between estrogen replacement therapy use, back pain, and back function in a large cohort of elderly women. BACKGROUND: Several studies have suggested that women who use estrogen replacement therapy may be more likely to experience back pain than those who do not. However, the relationships between estrogen replacement therapy, back pain, and impaired back function have not been clearly delineated. METHODS: At baseline information on estrogen replacement therapy use, functional status, back pain and function, and general lifestyle variables was obtained from 7209 elderly white women (mean age 71 years)enrolled in the Study of Osteoporotic Fractures. Lateral radiographs of the lumbar and thoracic spine were taken at baseline and at the third clinic visit, an average of 3.7 years after the baseline visit. Bone mineral density at the hip and spine was measured approximately 2 years after baseline. Follow-up information on back pain and function was also obtained at the third clinic visit. RESULTS: A total of 1039 (14.4%) women were using estrogen replacement therapy at baseline, 2016(28.0%) reported former use, and 4154 (57.6%) had never used estrogen replacement therapy. Compared with never-users, a statistically significant higher percentage of current estrogen users reported clinical back pain (52.7% vs. 43.4%) and back impairment (12.3% vs. 9.2%) at baseline and at the follow-up visit (pain 50.8% vs. 41%; impairment 16.0% vs. 12.1%). This occurred despite a higher prevalence of vertebral fractures in never-users of estrogen at the baseline visit. Current and former estrogen users without vertebral fractures had statistically significant higher likelihoods of having back pain and back dysfunction at both the baseline and third follow-up visit. The increased likelihood of back pain and back impairment in current and former estrogen users remained despite statistical adjustment for age, vertebral fracture, body mass index,smoking history, parity, exercise, arthritis, and diabetes in multivariate models. The relative risk (95%confidence interval) for impaired back function in former and current users at follow-up was 1.1 (0.9, 1.3) and 1.6 (1.3, 2.0), respectively. CONCLUSIONS: Our results indicate that postmenopausal estrogen use is associated with an increased likelihood of back pain and impaired back function in elderly white women.

Aged↗

PubMed2001

Diagnosis and management of acute fracture-dislocation of the carpus.

Acute fracture-dislocations of the carpus are uncommon. If treated inadequately, however, these injuries can lead to wrist pain and dysfunction as a result of progressive traumatic arthritis. Accurate diagnosis and early intervention are essential for optimal recovery. This article presents the anatomy, epidemiology, and mechanisms of injury of the carpus and the diagnosis, treatment, and treatment results of dislocation of the carpus.

Carpal Bones↗

PubMed2001

The effect of bone morphogenetic protein-2 expression on the early fate of skeletal muscle-derived cells.

The identification of bone morphogenetic proteins (BMPs) has stimulated intense interest in BMP delivery approaches. Ex vivo BMP-2 gene delivery has recently been described using skeletal muscle-derived cells. Skeletal muscle-derived cells, because of proven efficient transgene delivery and osteocompetence, represent an attractive cell population on which to base ex vivo BMP-2 gene delivery. However, the early in vivo fate of BMP-2-expressing muscle-derived cells is unknown. This study investigates the in vivo effects of BMP-2 secretion on skeletal muscle-derived cells in terms of cell survival and cell differentiation. The first experiment compared survival of BMP-2-expressing cells with control cells during the first 48 h after in vivo implantation. The results demonstrate that BMP-2 secretion did not adversely affect cell survival 8, 24, or 48 h after intramuscular implantation. The second experiment histologically compared the fate of BMP-2-expressing muscle-derived cells to the same cells not expressing BMP-2. The results show that BMP-2 expression prevented in vivo myogenic differentiation and promoted osteogenic differentiation of the transduced cells. This study further supports the existence of osteoprogenitor cells residing within skeletal muscle. Moreover, it is demonstrated that BMP-2 secretion does not adversely affect early cell survival of muscle-derived cells. These data are important for future investigations into BMP-2 gene delivery approaches to the musculoskeletal system.

Animals↗

PubMed2001

Minimal medial epicondylectomy and decompression for cubital tunnel syndrome.

Sixty-four patients (66 elbows) treated for refractory cubital tunnel syndrome had minimal medial epicondylectomy and in situ decompression to minimize the potential disadvantages of classic medial epicondylectomy. After a mean followup of 27 months results were excellent in 27 patients (44%), good in 23 patients (35%), fair in 10 patients (15%), and poor in four patients (6%). No ulnar nerve palsy, ulnar nerve subluxation, or medial elbow instability were seen. The main complaint of patients regarding the procedure was tenderness at the osteotomy site. The results show that minimal medial epicondylectomy and in situ decompression of the ulnar nerve is a safe and effective method to treat patients with cubital tunnel syndrome. This procedure minimizes the disadvantage of medial instability and recurrent symptoms attributable to nerve trauma after a classic medial epicondylectomy.

Adolescent↗

PubMed2001

SLAP lesions: current concepts.

The presence and significance of superior glenoid labral tears have received increasing attention in the 1990s. The symptoms associated with labral tears can be quite disabling to competitive and recreational athletes alike. Recent basic science and clinical studies have contributed much to the understanding of these injuries, including their association with suprascapular nerve entrapment. This article reviews the current basic science and clinical understanding of SLAP (superior labrum anterior and posterior) lesions in order to guide clinicians and promote further investigation.

Biomechanical Phenomena↗

PubMed2000

Osteoprogenitor cells within skeletal muscle.

The formation of ectopic bone within skeletal muscle is a widely observed phenomenon. However, the source of the osteoprogenitor cells responsible for ectopic bone formation remains unknown. This study was designed to test for osteogenic differentiation among cells isolated from skeletal muscle tissue. Different subpopulations of cells derived from an adult mouse skeletal muscle were tested for induction of alkaline phosphatase activity after exposure to bone morphogenetic protein-2 in vitro. A responsive subpopulation was identified, transduced with a retrovirus encoding for beta-galactosidase (Rv-lacZ) and an adenoviral construct encoding for one bone morphogenetic protein-2, and injected into the hindlimb of immune compromised (severe combined immunodeficient, or SCID) mice. The injected cells appeared to actively participate in the ectopic bone formation. The existence of lacZ-positive muscle-derived cells colocalized with osteocalcin-producing cells within lacunae of newly formed bone matrix suggests osteoblast and osteocyte differentiation. Although a specific cell was not isolated, these data support the contentions that osteoprogenitor cells reside within skeletal muscle and that muscle may represent a source other than bone marrow for the harvest of these cells.

Alkaline Phosphatase↗

PubMed2000

Ex vivo gene therapy to produce bone using different cell types.

Gene therapy and tissue engineering promise to revolutionize orthopaedic surgery. This study comprehensively compares five different cell types in ex vivo gene therapy to produce bone. The cell types include a bone marrow stromal cell line, primary muscle derived cells, primary bone marrow stromal cells, primary articular chondrocytes, and primary fibroblasts. After transduction by an adenovirus encoding for bone morphogenetic protein-2, all of the cell types were capable of secreting bone morphogenetic protein-2. However, the bone marrow stromal cell line and muscle derived cells showed more responsiveness to recombinant human bone morphogenetic protein-2 than did the other cell types. In vivo injection of each of the cell populations transduced to secrete bone morphogenetic protein-2 resulted in bone formation. Radiographic and histologic analyses corroborated the in vitro data regarding bone morphogenetic protein-2 secretion and cellular osteocompetence. This study showed the feasibility of using primary bone marrow stromal cells, primary muscle derived cells, primary articular chondrocytes, primary fibroblasts, and an osteogenesis imperfecta stromal cell line in ex vivo gene therapy to produce bone. The study also showed the advantages and disadvantages inherent in using each cell type.

Adenoviridae↗

PubMed2000

Validity of photoelastic strain measurement on cadaveric proximal femora.

Rosette strain gages indicate shear and principal strains at specific points, whereas photoelastic coatings provide shear strain information over a broad area. Information regarding bone loading and load transfer from a prosthetic implant to adjacent bone can be obtained using either strain-measuring technique on loaded femora. This study compared proximal femoral strains derived from photoelastic coatings to those obtained from rosette strain gages applied directly to the bone in order to determine the relationships between photoelastic shear strains and rosette shear and principal strains. Photoelastic shear strains underestimated rosette shear strains and exceeded the larger of the rosette principal strains. Principal strains derived from photoelastic coatings augmented with strain separator gages underestimated their rosette counterparts in most instances. Correlation was strong and nearly linear for all measures, indicating that photoelastic coatings can accurately express proportional strain changes despite imperfect agreement in absolute strain magnitudes. The best agreement between absolute strain magnitudes occurred in the proximal medial, or calcar, region. Understanding the relationships between the various measures obtained using the two strain measurement methods will allow more accurate estimates of actual strains to be made from photoelastic coatings.

Adult↗

PubMed2000

Monoarticular acromioclavicular joint gout: a case report.

Acromioclavicular joint gout is extremely rare. The case presented represents the first case of monoarticular acromioclavicular joint gout reported. It is also the first reported case of acromioclavicular joint gout in an immunosuppressed patient. The diagnostic pitfalls inherent in the evaluation of acute monoarticular arthritis in an immunosuppressed patient are illustrated. Furthermore, the case demonstrates one of the atypical presentations of gout that may occur in renal transplant patients taking cyclosporin A.

Acromioclavicular Joint↗

PubMed1999

Adenovirus-mediated direct gene therapy with bone morphogenetic protein-2 produces bone.

The need to improve bone healing permeates the discipline of orthopedic surgery. Bone morphogenetic proteins (BMPs) are capable of inducing ectopic and orthotopic bone formation. However, the ideal approach with which to deliver BMPs remains unknown. Gene therapy to deliver BMPs offers several theoretical advantages over implantation of a recombinant BMP protein, including persistent BMP delivery and eliminating the need for a foreign body carrier. A replication defective adenoviral vector was constructed to carry the rhBMP-2 gene (AdBMP-2). The direct in vivo gene therapy approach was applied in both immunodeficient and immunocompetent animals to produce intramuscular bone as early as 2 weeks following injection. Radiographic and histologic analysis revealed radiodense bone containing mature bone marrow elements. Adenovirus-mediated delivery of a marker gene (beta-galactosidase) into control animals produced no bone but indicated the cells transduced with the AdBMP-2 vector. Furthermore, comparisons between immunodeficient and immunocompetent animals illustrated the magnitude and significance of the immune response. Gene therapy to deliver BMP-2 has innumerable potential clinical applications from bone defect healing to joint replacement prosthesis stabilization. This study is the first to establish the feasibility of in vivo gene therapy to deliver active BMP-2 and produce bone.

Adenoviridae↗

PubMed1997

Effects of coronally slotted femoral prostheses on cortical bone strain.

The photoelastic method was used to assess the effects on femoral cortical strain of total hip arthroplasty cementless femoral prostheses containing distal coronal slots. Eight cadaveric femurs were tested, although three were eliminated secondary to fractures. Loaded and unloaded cortical strains were determined at 72 points on the implanted femoral cortex and compared with the values obtained in the intact femur. Three different prostheses were sequentially implanted, in a random order, into each femur. The prostheses consisted of a standard solid stem, an identical stem with a coronal slot in its distal one fourth, and an identical stem with a coronal slot in its distal one half. The slotted stems did not enhance axial load transfer to the proximal medial femur but did result in increased proximal medial assembly strains and statistically significant (P < .05) decreased anterior and posterior assembly strains. The increased proximal medial assembly strains are hypothesized to enhance proximal medial femoral loading, while the decreased anterior and posterior assembly strains may minimize operative implantation fractures.

Aged↗

PubMed1984

IgG aggregates of different sizes stimulate or suppress Ig secretion by human lymphocytes in vitro.

The regulatory effects of IgG aggregates on Ig production in vitro by human peripheral blood lymphocytes were shown to be highly dependent on the aggregate size and the degree of mitogenic stimulation. Covalently linked oligometers of IgG were prepared with dimethylsuberimidate cross-linking and chromatographic separation; larger aggregates were prepared by heating (63 degrees C) and preparative zonal ultracentrifugation. The storage and culture conditions used were shown to preserve the stability of aggregate sizes. Although both positive and negative regulatory effects were seen with cells isolated directly from blood, more predictable dose-related effects were seen if cells were vigorously washed, possibly due to the removal of IgG or natural immune complexes bound by the cells in vivo. Some preparations of small IgG oligomers produced marked stimulation of Ig production, especially in cells cultured without mitogen or with suboptimal pokeweed mitogen doses. Aggregates containing six or more IgGs suppressed Ig production, especially when cells were stimulated by mitogen at optimal concentrations.

Antigen-Antibody Complex↗

PubMed1977

Phytomitogen-induced, lymphokine-mediated cartilage proteoglycan degradation.

The significance of T-cell activation in the immunopathogenesis of articular disease has been studied in an in vitro model to assess the capacity of phytomitogen-induced lymphokines to degrade cartilage matrix proteoglycans. Supernatants derived from T-cell activation of normal human peripheral blood lymphocytes were shown to contain a monocyte-dependent, serum-inhibitable, dialyzable factor or factors capable of inducing significant proteoglycan degradation, as assessed by release of macroprecipitable 35S-labeled proteoglycan from heterologous cartilage substrates.

Animals↗

PubMedDate not supplied

Partial rupture of the distal biceps tendon.

We report on 7 cases of partial rupture of the distal biceps tendon. The mean patient age was 52 years (range, 38-58 years). There were 5 men and 2 women. The dominant arm was affected in all 7 patients. Pain was the chief complaint in all patients. Immobilization and physiotherapy were attempted in all patients, and 4 had at least 1 local steroid injection. No patient improved from the conservative treatment. All patients eventually underwent surgical debridement and reattachment of the biceps tendon with use of a 1-incision technique with suture anchors. After a mean follow-up of 31 months (range, 25-44 months), all patients reported a significant decrease in their pain. No complications were noted.

Adult↗