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Biomedical subjects

Joseph A Buckwalter

Publications and source records attributed to Joseph A Buckwalter.

At least 19 recordsLinked to original sources
PubMed2006

Intrinsic radiation resistance in human chondrosarcoma cells.

Human chondrosarcomas rarely respond to radiation treatment, limiting the options for eradication of these tumors. The basis of radiation resistance in chondrosarcomas remains obscure. In normal cells radiation induces DNA damage that leads to growth arrest or death. However, cells that lack cell cycle control mechanisms needed for these responses show intrinsic radiation resistance. In previous work, we identified immortalized human chondrosarcoma cell lines that lacked p16(ink4a), one of the major tumor suppressor proteins that regulate the cell cycle. We hypothesized that the absence of p16(ink4a) contributes to the intrinsic radiation resistance of chondrosarcomas and that restoring p16(ink4a) expression would increase their radiation sensitivity. To test this we determined the effects of ectopic p16(ink4a) expression on chondrosarcoma cell resistance to low-dose gamma-irradiation (1-5 Gy). p16(ink4a) expression significantly increased radiation sensitivity in clonogenic assays. Apoptosis did not increase significantly with radiation and was unaffected by p16(ink4a) transduction of chondrosarcoma cells, indicating that mitotic catastrophe, rather than programmed cell death, was the predominant radiation effect. These results support the hypothesis that p16(ink4a) plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas.

Acridine Orange↗
PubMed2006

Osteoblastomatosis of bone. A benign, multifocal osteoblastic lesion, distinct from osteoid osteoma and osteoblastoma, radiologically simulating a vascular tumor.

Two adult patients are described with multifocal osteolytic lesions radiologically simulating a vascular tumor. One patient had multiple bones involved. Histologically, the individual lesions had the features of the nidus of osteoid osteoma/osteoblastoma. A review of the English language medical literature yielded only one other reported case with similar features. The process is designated as osteoblastomatosis to indicate its bone-forming character, prominent osteoblast proliferation, and multiplicity. The cases are distinguished from multifocal/multicentric osteoid osteoma and osteoblastoma, and from benign and malignant vascular tumors.

Adult↗
PubMed2006

Osteoarthritis.

Osteoarthritis (OA), the syndrome of joint pain and dysfunction caused by joint degeneration, affects more people than any other joint disease. In most instances joint degeneration develops in the absence of an identifiable cause, but increasing age, excessive joint loading, and joint abnormalities and insults increase the risk of OA. Articular surface contact stress that causes tissue damage and compromises that ability of chondrocytes to maintain and restore the tissue has an important role in the development of joint degeneration Current methods of attempting to restore an articular surface in osteoarthritic joints include penetrating subchondral bone, altering joint loading, osteotomies and insertion of soft tissue grafts. Dramatic advances in the prevention and treatment of OA are likely to stem from better understanding of the role of mechanical forces in the initiation and progression of joint degeneration.

Cartilage, Articular↗
PubMed2006

Frequency response of pig intervertebral disc cells subjected to dynamic hydrostatic pressure.

The pathogenesis of vibration-induced disorders of intervertebral disc at the cellular level is largely unknown. Dynamic loads with frequencies close to that of the in vivo human spine resonant frequency (4-6 Hz) have a destructive effect, which may induce extracellular disc matrix (ECM) degradation. To investigate this issue, three-dimensional (3D) alginate cultures of normal pig intervertebral disc nucleus and inner annulus cells were tested under dynamic hydrostatic loading. Alginate cultures of each region were divided into six groups; five groups were exposed to cyclic hydrostatic pressures of frequencies 1, 3, 5, 8, and 10 Hz with the same amplitude (1 MPa), and group 6 was the control group (no loading). Cultures of different groups were loaded for 3 days (30 min daily) in a hydraulic chamber. Effects of loading frequency on disc collagen and protein metabolism were investigated by measuring 3H-proline-labeled proteins associated with the cells in the extracellular matrix and release of 3H-proline-labeled molecules into culture medium. The results indicated a poor synthesis rate and more degradation near the 5 Hz frequency. The repeatability of experiments was verified by performing two experiments with the same protocol. Both experiments indicated that a threshold frequency of around 5 Hz disrupted protein metabolism.

Animals↗
PubMed2006

Other surgical techniques for osteoarthritis.

Prior to the need for arthroplasty, there are numerous surgical options for management of osteoarthritis. This chapter is aimed at addressing the current state of knowledge and practice regarding: (1) arthroscopic lavage and debridement; (2) articular surface stimulation by means of penetration or microfracture; (3) high tibial osteotomies; (4) preventative ligament stabilization and joint distraction; and (5) transplantation of soft tissue, osteochondral, chondrocyte and matrix implantation as well as use of growth factors. Evidence is reviewed regarding the outcomes and indications for each of these operations, and where evidence is lacking, needs for further research are indicated. Future directions building upon promising early results of articular surface regeneration are also described.

Humans↗
PubMed2006

Impact of comorbidities on the measurement of health in patients with ankle osteoarthritis.

BACKGROUND: Investigators seeking to understand the impact of musculoskeletal disorders commonly use validated outcome instruments to assess the effect of diseases on physical function and quality of life. However, the influence of concomitant systemic or musculoskeletal comorbidities on these scores has not been widely considered in orthopaedic research. The purpose of this study was to determine how morbidity unrelated to the ankle influences the perception of physical function and pain by patients with ankle osteoarthritis. METHODS: Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, Ankle Osteoarthritis Scale (AOS) pain scale scores, demographic data, and systemic and musculoskeletal comorbidities were determined prospectively for 195 patients with ankle osteoarthritis and ninety-five age and gender-matched controls. The effect of systemic and musculoskeletal comorbidities on each of the scores was determined. RESULTS: On the average, patients with ankle osteoarthritis had a relatively normal MCS score (47 +/- 13 points) and a markedly diminished PCS score (32 +/- 8 points). Both of these scores averaged 50 +/- 9 points in the control group. The AOS pain score averaged 61 +/- 23 points in the group with ankle osteoarthritis, whereas it averaged 10 +/- 15 points in the control group. We found the perception of ankle pain by patients with ankle osteoarthritis to be significantly and linearly associated with the number of other musculoskeletal problems (not related to the foot or ankle). CONCLUSIONS: The degree of physical impairment associated with ankle osteoarthritis, as measured with the SF-36, is equivalent to that reported to be associated with severely disabling medical problems including end-stage kidney disease and congestive heart failure. The perception of ankle health status as measured with a validated, patient-oriented, anatomically specific instrument is influenced by the patients' perception of their overall musculoskeletal comorbidity status. The authors of clinical studies using these instruments should adjust for concomitant musculoskeletal disease.

Ankle Joint↗
PubMed2006

Ethanol as a local adjuvant for giant cell tumor of bone.

Giant cell tumor is an aggressive benign neoplasm of bone. A number of adjuvant agents have been used to supplement intralesional curettage to reduce the otherwise high local recurrence rate. High concentration ethanol is more readily available and less toxic to use than some common alternatives. No report on its use in a group of patients with giant cell tumor is available. Records were retrospectively reviewed for all giant cell tumors treated by intralesional curettage and high concentration ethanol irrigation as the only chemical adjuvant. Twenty-five primary excisional curettages and 12 repeat curettages for giant cell tumors of bone were performed in 31 patients. Patients were followed for a mean of three years and 10 months. There were five recurrences after primary excision procedures, and three after repeat excisions. Only use of a high-speed burr and lower Campanacci staging correlated with reduced recurrence rate, and these were not statistically significant. Most defects were filled with allograft or calcium sulfate. In the 11 patients treated primarily with curettage using a high-speed burr and adjuvant ethanol with minimum two-year follow-up, only one stage 3 lesion in a distal radius recurred. Multiple washes with high concentration ethanol, when used in conjunction with aggressive curettage including high-speed burring, is an effective and safe adjuvant. The necessity of any chemical adjuvant after appropriately aggressive curettage and burring can only be definitively demonstrated with a prospective, randomized, multi-center trial. Until such evidence becomes available, the use of adjuvant ethanol offers a compromise between higher toxicity adjuvants and no chemical adjuvant at all.

Adult↗
PubMed2006

Randomized surgical trials and "sham" surgery: relevance to modern orthopaedics and minimally invasive surgery.

Surgical techniques are constantly changing and evolving, though research trials supporting the value of a specific surgical intervention are often limited by the lack of a legitimate control group. In surgical trials, the use of a placebo, or a "sham" surgery, is controversial. This article explores the debate regarding the use of sham surgeries and summarizes the few surgical studies that have used them. Arguments for and against their use in research are presented.

Humans↗
PubMed2006

Parosteal osteosarcoma of the thumb metacarpal: a case report.

A 60-year-old man presented with increasing swelling of his right thumb, duration one year. Imaging studies demonstrated a bone-forming lesion extending from the dorsal cortex of the thumb metacarpal and involving the underlying medullary canal. Incisional biopsy yielded the diagnosis of parosteal osteosarcoma. The differential diagnosis for and rarity of parosteal osteosarcoma arising in the tubular bones of the hand are discussed.

Humans↗
PubMed2006

Intraosseous neurilemmoma involving the distal tibia and fibula: a case report.

Schwannoma, or neurilemmoma, is a benign nerve sheath tumor most commonly located in the soft tissue. Occasionally, Schwannomas involve osseous structures. Involvement of two adjacent long bones was not found in a review of the English language medical literature. We present the case of a neurilemmoma affecting both the distal fibula and tibia. Although rare, intraosseous neurilemmoma should be included on the differential diagnosis of painful, radiographically benign-appearing lesions arising in long bones.

Adult↗
PubMed2006

Perspectives on chondrocyte mechanobiology and osteoarthritis.

Osteoarthritis, the clinical syndrome of joint pain and dysfunction due to joint degeneration, is among the most frequent and symptomatic medical problems for middle aged and older people, and it is the most common cause of long term disability in most populations of people over 65. Currently there are no effective methods of preventing or curing osteoarthritis. Post-traumatic OA, the joint degeneration, pain and dysfunction that develop following joint injury, is the form of OA that is most directly related to elevated articular surface contact stress. However, mechanical stress that exceeds the tolerance of the articular surface can cause or accelerate the progression of joint degeneration in all individuals and in all synovial joints. In some patients, decreasing mechanical forces on degenerated joint surfaces stimulates formation of a new biologic articular surface. The advances in understanding of the effects of mechanical forces on chondrocytes and cartilage presented and discussed at the 4th Symposium on Mechanobiology: Cartilage and Chondrocyte will help in the efforts to develop new methods of preventing and treating osteoarthritis.

Aged↗
PubMed2005

Articular cartilage and osteoarthritis.

Articular cartilage, which makes possible the painless, low-friction movement of synovial joints, consists of a sparsely distributed population of highly specialized cells called chondrocytes that are embedded within a matrix and provide articular cartilage with remarkable mechanical properties. Chondrocytes form the tissue matrix macromolecular framework from three classes of molecules: collagens, proteoglycans, and noncollagenous proteins. The matrix protects the cells from injury resulting from normal joint use, determines the types and concentrations of molecules that reach the cells, acts as a mechanical signal transducer for the cells, and helps maintain the chondrocyte phenotype. Throughout life, articular cartilage undergoes internal remodeling as the cells replace matrix macromolecules lost through degradation. Aging decreases the ability of chondrocytes to maintain and restore articular cartilage and thereby increases the risk of degeneration of the articular cartilage surface. Progressive degeneration of articular cartilage leads to joint pain and dysfunction that is clinically identified as osteoarthritis. Investigation regarding the pathogenesis of posttraumatic osteoarthritis, the form of osteoarthritis that develops following joint injury, is helping to explain the development and progression of joint degeneration.

Aged↗
PubMed2005

Epidemiology of ankle arthritis: report of a consecutive series of 639 patients from a tertiary orthopaedic center.

The purpose of our study was to identify the cause of symptomatic ankle arthritis in a consecutive series of patients presenting in a tertiary care setting. Between 1991 and 2004, 639 patients with Kellgren grade 3 or 4 ankle arthritis presented to the University of Iowa Orthopaedic Foot and Ankle Surgery service. The cause of the arthritis was determined based on medical history, physical examination, and imaging studies. To get a sense of the relative prevalence of the etiologies of lower extremity arthritis in our setting, we evaluated the cause of arthritis of all new patients presenting to the University of Iowa Orthopaedic Department from 1999-2004 with arthritis of the ankle, to those with arthritis of the hip or knee during one year. Of the 639 arthritic ankles, 445 (70%) were post-traumatic, 76 (12%) were rheumatoid disease and 46 (7%) were idiopathic (primary osteoarthritis). The post-traumatic ankle arthritis patients were most commonly associated with past rotational ankle fractures. The majority of ankle arthritis is associated with previous trauma, whereas the primary cause of knee or hip arthritis is idiopathic. Unique strategies to prevent or treat post-traumatic ankle arthritis are needed.

Ankle Injuries↗
PubMed2005

Severe periprosthetic cortical atrophy in the skeletally immature: a report of three cases.

We describe three patients who developed cortical bone atrophy around cemented endoprostheses used for partial femur reconstructions after resection of Ewing's sarcoma. We believe this to be related to remodeling secondary to stress-shielding. Rather than increased porosity and decreased mineral density, the stress-shielding in these skeletally immature patients resulted in altered morphology of the cortical bone, with apparent maintenance of density.

Atrophy↗
PubMed2004

Effects of oxidative damage and telomerase activity on human articular cartilage chondrocyte senescence.

Senescence compromises the ability of chondrocytes to maintain and repair articular cartilage. We hypothesized that oxidative stress and telomere loss contribute to chondrocyte senescence. To test this hypothesis, we compared the growth of human articular cartilage chondrocytes incubated in 5% O2 and 21% O2. Cells grown in 5% O2 reached 60 population doublings (PD) before senescing, but growth in 21% O2 induced DNA damage and premature senescence at less than 40 PD. Human telomerase reverse transcriptase (hTERT)-transduction failed to prevent chondrocyte senescence in 21% O2, but allowed 1 of 3 chondrocyte strains to exceed 90 PD in 5% O2. These results show that oxidative stress causes premature chondrocyte senescence. They may help explain the increased risk of osteoarthritis with age and after joint trauma and inflammation, and suggest that minimizing oxidative damage will help produce optimal results for chondrocyte transplantation.

Aging↗
PubMed2004

Telomerase reverse transcriptase subunit expression is associated with chondrosarcoma malignancy.

Expression of the telomerase reverse transcriptase subunit telomerase reverse transcriptase gene is associated with most human malignancies. Because telomerase reverse transcriptase is rarely expressed in normal tissue, its presence in pathologic specimens is considered a marker of transformed cells. Moreover, high levels of expression have been correlated with poor prognosis in many cancers. Although telomerase activity has been found in chondrosarcomas, its prognostic significance in these malignant cartilage tumors is unknown. Malignancy in cartilage-derived tumors is assessed routinely by histomorphologic grading, but even well differentiated, low-grade lesions can metastasize. This unpredictable behavior greatly complicates the clinical treatment of cartilage tumors, making better prognostic indicators desirable. To address this issue we used immunohistochemistry to compare telomerase reverse transcriptase expression in a collection of 61 tumors consisting of malignant chondrosarcomas of varying grade and benign enchondromas. Associated case histories were reviewed to test the hypothesis that telomerase reverse transcriptase expression levels correlated with subsequent tumor recurrence. We found that the relative abundance of telomerase reverse transcriptase-expressing cells correlated significantly with grade and recurrence. These findings indicate that telomerase reverse transcriptase immunostaining may be a useful adjunct to the conventional three-level grading system.

Biomarkers, Tumor↗