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Biomedical subjects

S J Warden

Publications and source records attributed to S J Warden.

12 recordsLinked to original sources

Animal models for the study of tendinopathy.

Tendinopathy is a common and significant clinical problem characterised by activity-related pain, focal tendon tenderness and intratendinous imaging changes. Recent histopathological studies have indicated the underlying pathology to be one of tendinosis (degeneration) as opposed to tendinitis (inflammation). Relatively little is known about tendinosis and its pathogenesis. Contributing to this is an absence of validated animal models of the pathology. Animal models of tendinosis represent potential efficient and effective means of furthering our understanding of human tendinopathy and its underlying pathology. By selecting an appropriate species and introducing known risk factors for tendinopathy in humans, it is possible to develop tendon changes in animal models that are consistent with the human condition. This paper overviews the role of animal models in tendinopathy research by discussing the benefits and development of animal models of tendinosis, highlighting potential outcome measures that may be used in animal tendon research, and reviewing current animal models of tendinosis. It is hoped that with further development of animal models of tendinosis, new strategies for the prevention and treatment of tendinopathy in humans will be generated.

Achilles Tendon↗

Mechanotransduction in the cortical bone is most efficient at loading frequencies of 5-10 Hz.

A dose-response relationship has been shown between loading frequency and cortical bone adaptation for frequencies of up to 10 Hz, and is presumed to persist with further increases in frequency. Studies herein aimed to investigate cortical bone adaptation to loading frequencies of 1, 5, 10, 20 and 30 Hz. Two studies were performed in adult C57BL/6 mice using the ulna axial compression-loading model. In the first study, the histomorphometric response of the ulna was studied when loaded for 120 cycles day(-1) for 3 days at one of the five frequencies and one of two load magnitudes (1.5 or 2.0 N). In the second study, the changes in ulna geometry and mechanical properties were studied following loading for 5 min day(-1), 3 days week(-1) for 4 weeks at one of the five frequencies and one of two load magnitudes (1.0 or 1.6 N). Preliminary strain gauge measurements showed that frequency had no effect on mechanical strain per unit load. In study 1, loading frequency significantly influenced bone adaptation when loading at 2.0 N, with loading at 10 Hz resulting in significantly greater adaptation than with loading at other frequencies. In study 2, loading frequency significantly influenced the change in geometry when loading at 1.6 N, with loading at 5, 10 or 30 Hz resulting in significantly greater change than with loading at 1 Hz. Loading at 5 Hz also resulted in significantly greater change than with loading at 20 Hz. No frequency effect was found on any of the mechanical properties at either load. Overall, we found cortical bone adaptation to mechanical loading to increase with increasing loading frequency up to 5-10 Hz and to plateau with frequencies beyond 10 Hz. The mechanism for this nonlinear frequency response is not known; however, based on strain gauge measurements, we do not believe it resulted from dampening associated with high frequency loading through the flexed carpal joint. The obtained findings may relate to the mechanism of mechanotransduction within the bone. This requires further investigation.

Animals↗

Steps for targeting exercise towards the skeleton to increase bone strength.

Osteoporosis is a disease of bone fragility resulting mostly from low bone mass and a concomitant increase in the risk for fracture. Exercise is a commonly prescribed intervention for osteoporosis because bone tissue is mechanosensitive. The ability of mechanical stimuli to influence bone biology has been known for over a century, but it has been only in the past several decades that great gains have been made in terms of understanding factors that influence this response. By understanding these factors, steps can be developed to maximize the osteogenic effects of exercise on the skeleton and potentially reduce the incidence of bone fractures. This paper outlines these steps. They include: 1) starting exercise when young while the skeleton is most responsive to mechanical stimuli; 2) selecting exercises that are dynamic and high-impact to maximize osteogenic responses, such as jumping for the lower extremity and racquet sports for the upper extremity; 3) exercising the specific skeletal regions you want to strengthen as the bone response to mechanical loading is highly site-specific; 4) exercising briefly, yet often to offset the desensitization of skeletal mechanotransduction pathways; and 5) continuing to exercise as you age to prevent bone loss and reduce the risk of falls. Following these steps will help to promote skeletal health at all ages and may reduce an individuals risk for fracture by augmenting bone mass and size during youth, while reducing age-related bone loss and the risk for falls in adulthood.

Journal Article↗

Quantitative ultrasound assessment of acute bone loss following spinal cord injury: a longitudinal pilot study.

Spinal cord injury (SCI) results in substantial and rapid osteoporosis. Given its rapid onset, assessment of bone changes in the early stages (first 6 months) following SCI is important. This is particularly pertinent if intervention is to be implemented. Quantitative ultrasound (QUS) represents a potential assessment tool for the evaluation of skeletal changes in the early stages following SCI. This longitudinal pilot study assessed changes in QUS measures of calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) in 15 male subjects (age 23.9+/-7.3 years) over a 6-week period. Their mean time since SCI was 110.3+/-34.5 days. Also assessed were bone mineral density of the calcaneus (BMDc) and proximal tibia (BMDt) using dual-energy X-ray absorptiometry (DXA). Confirming the rapid onset of bone loss following SCI, BMDc and BMDt decreased by 7.5+/-3.0% ( p<0.001) and 5.3+/-4.2% ( p<0.001), respectively. QUS was sensitive to these changes. BUA decreased by 8.5+/-6.9% ( p<0.001), whilst SOS decreased by 1.5+/- 1.3% ( p<0.001). Suggesting an influence of the material properties of bone on BUA, BUA was correlated with BMDc at both the initial ( r = 0.68, p<0.01) and final ( r = 0.62, p<0.01) assessments. There were no significant correlations in the magnitude of change over the 6-week assessment period between any of the skeletal measures (all p>0.05). This suggests that skeletal qualities other than material properties also influence QUS measures. Overall, this study confirmed the rapid onset of bone loss following SCI and showed QUS to be a useful portable measure of acute bone changes. This may allow assessment of bone loss and the efficacy of intervention on this loss in the early stages following injury, a period where traditional axial DXA assessment is limited by practical constraints.

Absorptiometry, Photon↗

Low-intensity pulsed ultrasound stimulates a bone-forming response in UMR-106 cells.

Low-intensity (<100 mW/cm(2)) pulsed ultrasound (US) is an established therapy for fracture repair. In both animal and human trials, such US has been shown to facilitate fresh fracture repair and initiate healing in fractures with repair defects. However, the mechanism by which US achieves these outcomes is not clear. One possible mechanism is the direct stimulation of bone formation. To investigate this hypothesis, the current study investigated the mRNA response of isolated bone-forming cells (UMR-106 cells) to a single 20-min dose of low-intensity pulsed US. Using a novel US-cell coupling method, US was found to stimulate expression of the immediate-early response genes c-fos and COX-2 and elevate mRNA levels for the bone matrix proteins ALP and OC. These findings suggest that low-intensity pulsed US has a direct effect on bone formation. This may contribute to the beneficial effect of low-intensity pulsed US on fracture repair.

Alkaline Phosphatase↗

Skeletal effects of low-intensity pulsed ultrasound on the ovariectomized rodent.

Growing evidence supports low-intensity pulsed ultrasound (US) as an osteogenic mechanical stimulus. Its effects on isolated bone cells and on fractured bone are established. However, its effects on osteoporosis are not clear. This study examined US effects on ovariectomy (OVX) induced bone changes within the rodent hindlimb (distal femur and proximal tibia), and on normal bone in animals following sham-OVX. Animals were exposed to daily unilateral active-US and contralateral inactive-US for 12 weeks. Bone status was assessed using dual energy X-ray absorptiometry and histomorphometry. Ovariectomy resulted in significant bone changes. Low-intensity pulsed US did not influence these changes. These results suggest that the US dose introduced may not be a beneficial treatment for osteoporosis, and that intact bone may be less sensitive to US than fractured bone and isolated bone cells. This may relate to the biophysical mechanisms of action of US, US-bone interactions and tissue level processes taking place.

Absorptiometry, Photon↗

Efficacy of low-intensity pulsed ultrasound in the prevention of osteoporosis following spinal cord injury.

Ultrasound (US), a high-frequency acoustic energy traveling in the form of a mechanical wave, represents a potential site-specific intervention for osteoporosis. Bone is a dynamic tissue that remodels in response to applied mechanical stimuli. As a form of mechanical stimulation, US is anticipated to produce a similar remodeling response. This theory is supported by growing in vitro and in vivo evidence demonstrating an osteogenic effect of pulsed-wave US at low spatial-averaged temporal-averaged intensities. The aim of this study was to investigate whether low-intensity pulsed US could prevent calcaneal osteoporosis in individuals following spinal cord injury (SCI). Fifteen patients with a 1-6 month history of SCI were recruited. Active US was introduced to one heel for 20 min/day, 5 days/week, over 6 weeks. The contralateral heel was simultaneously treated with inactive US. Patients were blind to which heel was being actively treated. Active US pulsed with a 10 microsec burst of 1.0 MHz sine waves repeating at 3.3 kHz. The spatial-averaged temporal-averaged intensity was set at 30 mW/cm(2). Bone status was assessed at baseline and following the intervention period by dual-energy X-ray absorptiometry and quantitative US. SCI resulted in significant bone loss. Bone mineral content decreased by 7.5 +/- 3.0% in inactive US-treated calcanei (p < 0.001). Broadband US attenuation and speed of sound decreased by 8.5 +/- 6.9% (p < 0.001) and 1.5 +/- 1.3% (p < 0.001), respectively. There were no differences between active and inactive US-treated calcanei for any skeletal measure (p > 0.05). These findings confirm the negative skeletal impact of SCI, and demonstrate that US at the dose and mode administered was not a beneficial intervention for SCI-induced osteoporosis. This latter finding may primarily relate to the inability of US to effectively penetrate the outer cortex of bone due to its acoustic properties.

Absorptiometry, Photon↗

Acceleration of fresh fracture repair using the sonic accelerated fracture healing system (SAFHS): a review.

The Sonic Accelerated Fracture Healing System (SAFHS) is a relatively new fracture management tool which incorporates the application of a specifically modified diagnostic ultrasound unit to healing fractures with the intention of accelerating repair. In an animal fracture model, this device has been shown to accelerate the rate of biomechanical healing by a factor of 1.4-1.6. In two randomized, controlled trials in humans, the same unit has been shown to reduce the time frame of clinical and radiographic healing by 38%. In the two fracture regions investigated, tibial diaphysis and distal radius, this represented a 58 day and 37 day reduction in healing time, respectively. Despite its effect on the entire process of fresh fracture repair, the effect of the SAFHS on the individual stages and processes involved has not been established. This paper reviews these stages and processes, and discusses the clinical and practical implications of the effect of the SAFHS on fracture repair and the need for further research into this modality.

Animals↗

A technique for restraining rodents during hindlimb interventions.

Recently interest has grown in the skeletal effects of external electrophysical modalities. To introduce these modalities into the rodent hindlimb, restraining the animals is often necessary. This report describes a novel restraint device that was highly successful when used on 10 Sprague-Dawley rats for 20 min daily for 6 days each week over a period of 12 weeks. The restrained animals gained less weight than did 10 cage control animals, suggesting that animals experienced stress. However, this weight loss was significant (p < 0.05) only during the first six weeks, suggesting a degree of acclimatization. Restraint had no observable effect on measures of bone mineral content of the hindlimb. The restraint device we developed restrained animals without the need for anesthetics, enabling our device to be used in future studies investigating the skeletal effect of external electrophysical modalities on the rodent hindlimb.

Animal Husbandry↗

Comparison of Abshaper and conventionally performed abdominal exercises using surface electromyography.

PURPOSE: Many commercially available pieces of abdominal exercise equipment have been introduced to facilitate endurance training of the abdominal musculature. One of the latest devices is the Abshaper. The aim of this study was to investigate whether there is any difference between abdominal exercises performed while using the Abshaper compared with those performed conventionally. METHODS: Using surface electromyography (EMG), the upper and lower regions of rectus abdominis (RA), the external oblique (EO), and sternocleidomastoid (SCM) muscles of 22 first-year physical therapy students were assessed. Each participant performed five straight trunk curls and five side trunk curls both with the Abshaper and conventionally. To test for differences in relative peak and mean EMG activity between the two modes of exercise execution, paired t-tests (alpha = 0.05) were performed. Differences in the average time percentile at which peak EMG activity occurred were assessed by repeated measures ANOVA (alpha = 0.05). RESULTS: Exercises performed while using the Abshaper resulted in significantly greater relative peak and mean EMG activity within the upper portion of RA. For both the lower portion of RA and the EO muscles, no differences were found between the two modes of exercise execution. For SCM, Abshaper exercises resulted in significantly lower relative peak and mean EMG activity. In respect to the timing of peak EMG activity, no difference was found between the two modes of exercise execution for either the upper portion of RA, the EO, or SCM muscles. For lower RA, peak EMG activity occurred significantly earlier during conventional abdominal exercises in comparison with those performed while using the Abshaper. CONCLUSIONS: The Abshaper has a role in exercising the abdominal musculature.

Abdominal Muscles↗

Hospital days in clozapine-treated patients.

OBJECTIVE: To examine inpatient hospital days used by a group of patients with treatment-resistant schizophrenia for 3 years before and 3 years after clozapine initiation. METHOD: A retrospective chart review of 26 consecutive admissions to an outpatient clozapine clinic was conducted for a 6-year period. The total number of hospital days was recorded. RESULTS: Patients separated into 3 groups: those who used clozapine for 3 uninterrupted years (N = 11, 42.3%), those who interrupted but resumed clozapine and continued on to 3 years (N = 4, 15.4%), and those who abandoned clozapine treatment (N = 11, 42.3%). Only the group that was continuously on clozapine showed a decline in percentage of inpatient days during the 3-year follow-up period. Three of the 11 patients who discontinued clozapine died during the posttreatment period: 2 suicides and 1 "death by misadventure." CONCLUSIONS: Continuous clozapine treatment significantly reduces days in hospital; this reduction was sustained throughout 3 years' follow-up. While the sample size is small, all patients were tracked over a 6-year period, and both drug continuers and dropouts were followed. The reduction in inpatient days may be lost if patients stop and then restart clozapine. For patients who do not respond to or abandon trials of clozapine, there is an urgent need to develop more effective treatment strategies.

Adult↗