Variability of vertical ground reaction forces collected with one and two force plates in healthy dogs.

OBJECTIVE: To compare peak vertical force (PVF) and vertical impulse (VI) data collected with one and two force plates during the same collection time period in healthy dogs at a trot. ANIMALS: Seventeen healthy client-owned adult dogs. METHODS: Vertical ground reaction force (GRF) data were collected in a crossover study design, with four sessions on two consecutive days, and then two weeks apart (days 1, 2, 15, and 16) using both one and two force plates collection methods. A repeated measures model analysis of variance (ANOVA) was used to test for differences in force plate PVF, VI, and average time per trial (ATT) between days, weeks, and systems (1 plate versus 2 plates). Coefficients of variation for PVF and VI were also calculated separately by forelimbs and hindlimbs, plates, day, and week. RESULTS: The time required to obtain a valid trial was significantly longer using a single force plate when compared with two force plates. Comparing GRF data for all dogs, significant differences in PVF data were found between one and two force plates, however, these differences were diminutive in absolute magnitude, and of unknown clinical importance. Examination of the coefficients of variation for PVF and VI during the different collection periods yielded similar results. CONCLUSIONS: Use of two force plates decreased trial repetition and collection time. Vertical GRF data had a similar coefficient of variation with either one or two force plates collection techniques in healthy dogs.

Efficacy of cyclo-oxygenase inhibition by two commercially available firocoxib products in horses.

REASONS FOR PERFORMING STUDY: Two firocoxib preparations for oral use are approved for use in animals in many countries: a chewable canine tablet and an equine paste. In order to reduce costs, many veterinarians use the canine product in horses even though this is an off-label use of the preparation. OBJECTIVE: To determine the relative efficacy of 2 commercially available firocoxib products to inhibit prostaglandin E2 (PGE2) synthesis after oral dosing in horses. STUDY DESIGN: A crossover design using 8 adult horses (n = 4 for each preparation during each treatment period). Body weight range 532-614 kg. METHODS: Horses received 57 mg of the assigned firocoxib preparation orally once daily for 7 days, with a 14 day washout period between drug crossover. Ten healthy adult light breed horses were used as no-treatment controls. During each treatment period, blood was taken before dosing on Days 0 and 7 and on Day 7 1 h after dosing for ex vivo lipopolysaccharide (LPS) stimulation to induce (PGE2 ) synthesis. Heparinised plasma was also collected on Day 7 immediately prior to and 1 h after dosing to determine plasma firocoxib concentrations. RESULTS: In the control group, there was no significant change in LPS-induced PGE2 over time. In contrast, immediately prior to and 1 h after treatment on Day 7, the mean LPS-induced PGE2 concentration decreased significantly compared to Day 0 values in all treated horses. There was no difference in PGE2 or plasma firocoxib concentrations between firocoxib treatment groups. CONCLUSION: In this model, the canine chewable preparation of firocoxib was as effective as the equine paste formulation at reducing LPS-induced PGE2 synthesis. POTENTIAL RELEVANCE: The canine chewable preparation of firocoxib may be a suitable alternative to the paste formulation in horses for situations where extra-label drug use can be legally justified. The Summary is available in Chinese - see Supporting information.

5-Lipoxygenase expression in benign and malignant canine prostate tissues.

5-Lipoxygenase (5-LO) is overexpressed in human prostate carcinomas (PCs), and its inhibition decreases proliferation and induces apoptosis in prostate cancer cell lines. We hypothesized that 5-LO would be overexpressed in canine PC compared with benign prostate tissue and may be important in the pathogenesis of the disease. Immunoblot analysis of canine PC and benign prostatic hyperplasia (BPH) tissues demonstrated 5-LO expression in both. 5-LO immunohistochemical staining was not significantly different within the stromal or epithelial components of canine primary PC, BPH or suppurative prostatitis, suggesting that differential expression of this enzyme does not occur in these conditions. The percentage of tumour cells expressing 5-LO was significantly lower in metastatic PC lesions compared with primary PC (P < 0.0001). This decreased expression may indicate down-regulation or altered expression of the enzyme with progression of canine PC to a metastatic phenotype.

Effects of firocoxib and tepoxalin on healing in a canine gastric mucosal injury model.

BACKGROUND: Little is known about the effect of dual cyclooxygenase (COX) and lipoxygenase inhibition on canine gastric mucosal healing. OBJECTIVE: This study compares the effects of putative dual COX and 5-lipoxygenase inhibition with that of COX-2 selective inhibition on gastric mucosal lesion healing in dogs. ANIMALS: Six normal adult mixed-breed research dogs. METHODS: Gastric body and pyloric lesions were induced by endoscopic biopsy. Dogs were treated with tepoxalin, firocoxib, or placebo for 7 days in a randomized 3-way crossover study design. Healing was evaluated on days 2, 4, and 7 of treatment by endoscopic lesion scoring. Eicosanoid concentrations in plasma and at the lesion margins were determined on days 2, 4, and 7. Repeated measures analyses were performed. All hypothesis tests were 2-sided with P < .05. Multiple comparisons were adjusted using Tukey's test. RESULTS: Significant treatment differences were noted in the pyloric lesion area measurements. Overall, the firocoxib group had larger lesions than the placebo (P= .0469) or tepoxalin (P= .0089) groups. Despite larger pyloric lesions in the firocoxib group, mucosal prostaglandin production did not differ significantly from placebo. In contrast, the tepoxalin group had significantly lower pyloric mucosal prostaglandin production compared with the firocoxib (P < .0001) or the placebo (P < .0001) groups but pyloric lesions were not significantly larger than those of the placebo group (P= .7829). CONCLUSION: COX-2 inhibition by firocoxib slowed wound healing by a mechanism independent of prostaglandin synthesis. Suppression of mucosal prostaglandin production by tepoxalin did not alter mucosal lesion healing compared with placebo.

Leukotriene inhibition in small animal medicine.

Leukotrienes are important mediators of inflammatory and allergic conditions in people and are suspected to play an important role in tumorigenesis and tumor growth of several different tumor types. Based on this, researchers are making great progress in identifying novel pharmacologic targets for several human diseases. Leukotriene inhibition has resulted in therapeutic benefit in clinical trials involving people with osteoarthritis, allergic asthma, and atopic dermatitis. Despite this progress and the possibility that leukotriene inhibition may also play an important therapeutic role in veterinary patients, parallel advances have not yet been made in veterinary medicine. This article summarizes leukotriene function and synthesis. It also reviews the published literature regarding potential therapeutic applications of leukotriene inhibition in both human and veterinary medicine, focusing primarily on osteoarthritis, NSAID induced gastrointestinal mucosal damage, allergic asthma, atopic dermatitis, and cancer.

Measurement of velocity with a kinematic system versus a photocell system in the collection of canine ground reaction forces.

Velocities obtained from a five photocell system were compared to velocities of nine anatomical points on a handler and canine subject as reported by a kinematic system over the same distance. There was not a statistically significant difference between the velocities of the markers on the dogs' occipital protuberance and interscapular region compared with the velocity as reported by the photocell system. The average velocities of the three markers on the forelimb of the dogs and three markers on the handler's leg and one on the sacrum had statistically different values than the photocell system. Given these results, photocell systems with the same configuration in this study can be trusted to report accurate trunk velocities of canine subjects during the collection of ground reaction forces.

Measurement differences between three versus five photocells during collection of ground reaction forces in dogs.

The differences between velocities and accelerations obtained from three and five photocells were examined when obtaining ground reaction force (GRF) data in dogs. Ground reaction force data was collected 259 times from 16 different dogs in two experimental phases. The first phase compared velocities and accelerations reported by the two systems based on trials accepted by the three photocell system. The second phase accepted trials based on data from five photocells. Three photocell data were calculated mathematically in the second phase in order to compare the values of both systems. The velocity and acceleration values obtained from each system were significantly different (at the hundredth of a meter per second). Differences in measured values did not result in acceptance of data by the three photocell system that would not have been acceptable with the five photocell system (false positives), but did result in rejection of acceptable data by the three photocell system (11% false negative rate). Given the small differences between the two systems, GRF data collected should not be significantly different, though the three photocell system is less efficient in gathering data due to the number of trials rejected as false negatives.

Sample size and statistical power in the small-animal analgesia literature.

OBJECTIVE: To document the power and required sample sizes to achieve certain treatment objectives in the veterinary analgesia literature. METHODS: Pubmed's MEDLINE database and selected journals were searched. Only publications produced between 1994 and 2004 that reported 'no difference' between experimental groups in the abstract, results or conclusion sections and those that were randomised, prospective and blinded were reviewed. The data reported in the publications were then subjected to power analyses to determine the power and necessary sample size (to achieve a power of 0.8) to allow detection of 20 per cent, 50 per cent and 80 per cent treatment effects. RESULTS: Twenty-two studies provided sufficient data for analysis. Five out of 22 (23 per cent) had sufficient power to detect a 20 per cent treatment effect, 12 of 22 (54 per cent) had sufficient power to detect a 50 per cent treatment effect and 18 of 22 (82 per cent) had sufficient power to detect an 80 per cent treatment effect. The mean number of animals required per group to document a 20 per cent, 50 per cent and 80 per cent treatment effect were 90, 15 and 7, respectively. CLINICAL SIGNIFICANCE: Publications that report no significant difference between analgesic regimens may have committed a Type II error. The reader may inappropriately conclude that there is no difference between treatments when there may, in fact, be a superior analgesic regimen. Clinical practice based on the principles of evidence-based medicine could therefore result in suboptimal care for patients.

Effect of durotomy on functional outcome of dogs with type I thoracolumbar disc extrusion and absent deep pain perception.

Spinal cord durotomy is performed as a diagnostic aid in determining spinal cord structural integrity, and this may be useful as an indicator of prognosis in cases with loss of deep pain perception (DPP). It has been suggested that a durotomy may relieve intramedullary compression but there is some debate about the therapeutic value. The purpose of this study was to compare ambulatory outcome of dogs that had loss of DPP treated with hemilaminectomy with durotomy versus hemilaminectomy without durotomy. Medical records of 81 dogs diagnosed with type I thoracolumbar IVD were reviewed. Dogs were included in the study if DPP was absent upon initial neurological examination and surgical decompression via hemilaminectomy was performed. Of the 81 cases, 48 were included in this study. The number of dogs that recovered ambulatory function were compared between durotomy and non-durotomy groups with a chi-squared test (p < 0.05). No differences were found. The findings of this study suggest that durotomy is useful as a diagnostic modality and that performing a durotomy does not significantly affect post-operative recovery of voluntary motor function.

Effect of starting distance on vertical ground reaction forces in the normal dog.

The purpose of this study was to evaluate the effect of starting distance on the peak vertical force (PVF) and associated vertical impulses (VI) of normal dogs. Five dogs of similar weight and body type were trotted at a velocity of 1.6-2.2 m/s from each of three starting distances; 2, 4, and 6 m, from the first plate in a two plate test field. A total of ten trials were recorded from each starting distance, five left first contacts and five right first contacts. Each ground reaction force (GRF) of interest was evaluated both within and between the three starting distances using a complete block ANOVA. There was not any significant effect of distance found on peak vertical forces in our study. However, distance did affect VI. Forelimb VI generated at a 2 m trot was significantly less than VI generated at a 6 m trot. Neither extreme distance was found to be significantly different than the 4 m VI. The VI of the hind limb was not significantly affected.

The effect of enrofloxacin on cell proliferation and proteoglycans in horse tendon cells.

Fluoroquinolone antibiotics have been used widely in humans and domestic animals, including horses, because of their broad-spectrum bactericidal activity, and relative safety. The use of fluoroquinolones, however, is not without risk. Tendonitis and spontaneous tendon rupture have been reported in people during or following therapy with fluoroquinolones. We have studied the effects of enrofloxacin, a fluoroquinolone antibiotic used commonly in domestic animals, on tendon cell cultures established from equine superficial digital flexor tendons. Effects on cell proliferation and morphology were studied using cell counting and scanning electron microscopy. Monosaccharide content and composition was determined by gas chromatography-mass spectrometry analysis. Western and Northern blot analyses were utilized to evaluate the synthesis and expression of two proteoglycans, biglycan and decorin. Our data demonstrate that enrofloxacin inhibits cell proliferation, induces morphological changes, decreases total monosacharide content and alters small proteoglycan synthesis at the glycosylation level in equine tendon cell cultures. These effects are more pronounced in juvenile tendon cells than in adult equine tendon cells. We hypothesize that morphological changes and inhibition of cell proliferation are a result of impaired production of biglycan and decorin, proteoglycans involved in fibrillogenesis of collagen, the most important structural component of the tendon of enrofloxacin-treated tendon cells. Our findings suggest that fluoroquinolones should be used with caution in horses, especially in foals.

Long-term temporal evaluation of ground reaction forces during development of experimentally induced osteoarthritis in dogs.

OBJECTIVE: To describe changes in vertical ground reaction forces (GRF) over 48 months in dogs with osteoarthritis (OA) of the stifle joint induced by transection of a cranial cruciate ligament (CCL). ANIMALS: 12 clinically normal adult dogs. PROCEDURE: Vertical GRF (eg, peak force and impulse) were determined prior to and 1, 2, 3, 6, 10, and 12 months after transection of the right CCL. In 7 dogs, data were also collected 24, 32, 38, 42, and 48 months after transection. RESULTS: Vertical peak force and impulse were significantly decreased in the right hind limb at all times after transection, compared with baseline values. From 10 through 48 months after transection, vertical GRF remained essentially static. Ground reaction forces in the unoperated (left) hind limb also changed significantly during the study. Left vertical impulse significantly increased 3 months after transection, whereas at 24, 38, 42, and 48 months after transection, left vertical peak force was significantly decreased, compared with the baseline value. Mean intradog coefficients of variation (CV) for peak vertical force and impulse ranged from 738 and 9.32, respectively, 1 month after transection to 1.96 and 2.76, respectively, at 42 months. CONCLUSIONS AND CLINICAL RELEVANCE: Vertical GRF in the affected hind limb equilibrated approximately 10 months after CCL transection. Prior to this, force transmission across the affected stifle joint changed significantly over time. Intradog CV were small, indicating that GRF may be an appropriate outcome measurement for evaluation of OA development induced by CCL transection in dogs.

Bone formation into surface phosphonylated polymeric implants.

Through the use of two animal models, the present study demonstrates the ability of phosphonylated surfaces to bind bone. In one model, surface-treated polypropylene (PP) and polyethylene (PE) were implanted in the medial cortex of the goat tibia. In the second model, surface-treated poly(ether-ether ketone) (PEEK) and carbon fiber-reinforced PEEK (CFR-PEEK) were implanted through both cortices of the goat mandible. Selected rods of all material types were microtextured using crystallization induced microphase separation, a method for the formation of continuous, open-cell microporous surfaces in thermoplastic polymers. Microtextured and smooth rods were phosphonylated, and calcium was subsequently introduced to the phosphonylated surface by incubating the samples in a saturated solution of calcium oxide. For all substrate materials tested, phosphonylation and calcium posttreatment resulted in an increased propensity for bone binding and apposition, as measured by push out test. Microtextured PP, PE, and CFR-PEEK surfaces that were further phosphonylated and calcium treated resulted in test samples with an increased interfacial strength.

Effect of polysulfated glycosaminoglycan on DNA content and proteoglycan metabolism in normal and osteoarthritic canine articular cartilage explants.

OBJECTIVE: To study the effect of polysulfated glycosaminoglycan (PSGAG) on proteoglycan metabolism and DNA content of control and osteoarthritic (OA) cartilage. STUDY DESIGN: An in vitro study comparing the effects of PSGAG on articular cartilage explants from canine stifle joints with and without chronic OA after transection of the left cranial cruciate ligament. SAMPLE POPULATION: Five large cross-breed dogs. METHODS: Cartilage explants (6 to 13 per treatment group) from the medial side of the femoral trochlea and medial femoral condyle from both stifles of each dog were incubated in a defined medium containing 0, 0.05, 0.5, or 5 mg/mL of PSGAG. After 72 hours in culture, explants were pulsed for 6 hours with sodium [35S]sulfate. Aminophenylmercuric acetate (APMA) was used to activate endogenous neutral matrix metalloproteinases (MMPs) and induce proteoglycan degradation in the radiolabeled explants. DNA content and radioactivity were measured in papain-digested explants, and radioactivity was measured in the medium by liquid scintillation counting. Proteoglycan synthesis and degradation were calculated. Cartilage was examined histologically for signs of OA. A mixed model analysis of variance and linear contrasts were used to test for significant (P < .05) effects of OA and treatment with PSGAG. RESULTS: Transection of the cranial cruciate ligament produced OA in operated joints. DNA content and proteoglycan synthesis of OA cartilage were significantly lower than in cartilage from control joints. For both DNA content and proteoglycan synthesis, significant interactions occurred between the concentration of PSGAG and whether the articular cartilage was from OA or control joints. The two lower concentrations of PSGAG (0.05 and 0.5 mg/mL) predominantly increased DNA content in OA cartilage (7 and 18%, respectively, compared with 0 mg/mL PSGAG) while the highest concentration (5 mg/mL) predominantly increased DNA content in control cartilage (30% compared with 0 mg/mL PSGAG). PSGAG at .05 mg/mL predominantly decreased proteoglycan synthesis in OA cartilage (19% reduction compared with 0 mg/mL PSGAG) while PSGAG at .5 and 5 mg/mL predominantly decreased proteoglycan synthesis in control cartilage (17 and 55% reduction, respectively, compared with 0 mg/mL PSGAG). Following activation of MMPs, PSGAG caused a dose-dependent decrease in degradation of radiolabeled proteoglycan in both OA and control cartilage. CONCLUSIONS: OA cartilage was responsive to treatment with PSGAG at 100-fold lower concentration than control cartilage. When treated with PSGAG, articular cartilage explants maintained or increased DNA content at the expense of proteoglycan synthesis. Following MMP activation, proteoglycan degradation was inhibited in OA and control explants in a dose-dependent manner. CLINICAL RELEVANCE: If the results of this study extend to in vivo use, treatment with PSGAG may modify the progression of OA in articular cartilage by maintaining chondrocyte viability or stimulating chondrocyte division as well as protecting against extracellular matrix degradation.

Evaluation of a method for experimental induction of osteoarthritis of the hip joints in dogs.

OBJECTIVE: To evaluate a method for experimental induction of osteoarthritis in the hip joints of dogs. ANIMALS: 12 mixed-breed dogs. PROCEDURE: A unilateral triple pelvic osteotomy was performed. In 6 dogs, the iliac osteotomy was repaired with 45 degrees of internal rotation, reducing coverage of the femoral head by the acetabulum. In the other 6 dogs, the fragments were repaired in anatomic alignment. Radiography, force plate evaluations, and subjective lameness evaluations were performed before and after surgery. Dogs were euthanatized 7 months after surgery, and samples of cartilage and joint capsule were examined histologically. RESULTS: Subjective lameness scores, radiographic appearance of the hip joints, and Norberg angles were not significantly different between groups; however, force plate evaluations did reveal significant differences in vertical ground reaction forces. Femoral head coverage was significantly decreased with rotation of the acetabulum. Mild inflammatory changes were discernible in the joint capsule and articular cartilage of some dogs in both groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that 45 degrees internal rotation of the acetabulum does not consistently induce biologically important osteoarthritic changes in the hip joints of dogs.

Contrast radiographic findings in canine bacterial discospondylitis: a multicenter, retrospective study of 27 cases.

A multicenter, retrospective study was undertaken to evaluate contrast radiographic findings in canine bacterial discospondylitis. Records and myelograms or epidurograms of 27 patients were obtained from five colleges of veterinary medicine. Fifteen cases (56%) were evaluated as having some degree of spinal cord compression. The majority (73.3%) of the cases had only soft tissue as the compressive mass. The median compression for all cases was 5% of the vertebral canal. No difference was noted for compression based on anatomical site (i.e., cervical versus thoracolumbar versus lumbosacral). No significant correlation between degree of lesion compression and clinical outcome was noted, but there was a trend toward increased mortality with greater compression. There was no correlation between the ambulatory status and the ultimate outcome. Three of the 15 (20%) cases showed vertebral subluxation. Results of this study indicate that static spinal cord compression is not a significant component of the neurological dysfunction associated with bacterial discospondylitis. Identification of vertebral subluxation in some patients may indicate a dynamic lesion that should be evaluated with stress radiography.

Breed, sex, and body weight as risk factors for rupture of the cranial cruciate ligament in young dogs.

OBJECTIVE: To describe clinical features of dogs < 2 years old with rupture of the cranial cruciate ligament (CCL) and to evaluate breed, sex, and body weight as risk factors. DESIGN: Case-control study. ANIMALS: 201 dogs < 2 years old with rupture of the CCL and 804 age-matched control dogs. PROCEDURE: Medical records were reviewed for breed, sex, and body weight, and results were compared with results of age-matched control dogs. RESULTS: Breed predisposition was detected for Neapolitan Mastiff, Akita, Saint Bernard, Rottweiler, Mastiff, Newfoundland, Chesapeake Bay Retriever, Labrador Retriever, and American Staffordshire Terrier. Increased risk was detected for neutered males and neutered females, compared with sexually intact males and sexually intact females, respectively. Differences in prevalence of rupture of the CCL were not detected between all males and females, sexually intact males and sexually intact females, or neutered males and neutered females. Body weights of dogs with ruptured CCL were significantly greater than those of control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Several large breeds of dogs are predisposed to rupture of the CCL at a young age.

Comparison of stance time and velocity as control variables in force plate analysis of dogs.

OBJECTIVE: To investigate effects of the use of stance time or velocity as control variables on ground reaction forces in lame dogs. ANIMALS: 12 dogs with pelvic osteotomies. PROCEDURE: Data for ground reaction forces were obtained preoperatively and at 2, 4, 6, 8, 12, 16, 20, 24, and 28 weeks postoperatively, using velocity and stance time as control variables. Ground reaction forces obtained were compared between the 2 methods of data collection, as were velocities and stance times of the trials. RESULTS: Significant differences in ground reaction forces were not found between the use of velocity or stance time as a control variable at any time. Also, significant differences in stance times or velocities were not found between the 2 methods of data collection. Greatest variation in stance time and velocity was found during periods of greatest lameness. CONCLUSIONS AND CLINICAL RELEVANCE: Use of stance time as a control variable in force plate analysis does not lead to significantly different results from use of velocity as a control variable, indicating that either method may be used in force plate analysis of dogs.