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Abstract

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° 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° internal rotation of the acetabulum does not consistently induce biologically important osteoarthritic changes in the hip joints of dogs. (Am J Vet Res 2000;61:484–491)

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To investigate the effectiveness of tramadol for treatment of osteoarthritis in dogs.

DESIGN Randomized, blinded, placebo-controlled crossover study.

ANIMALS 40 dogs with clinical osteoarthritis of the elbow or stifle joint.

PROCEDURES Dogs orally received 3 times/d (morning, midday, and night) for a 10-day period each of 3 identically appearing treatments (placebo; carprofen at 2.2 mg/kg [1 mg/lb], q 12 h [morning and night], with placebo at midday; or tramadol hydrochloride at 5 mg/kg [2.3 mg/lb], q 8 h) in random order, with treatment sessions separated by a minimum 7-day washout period. Vertical ground reaction forces (vertical impulse [VI] and peak vertical force [PVF]) were measured and Canine Brief Pain Inventory (CBPI) scores assigned prior to (baseline) and at the end of each treatment period. Repeated-measures ANOVA was performed to compare VI and PVF data among and within treatments, and the χ2 test was used to compare proportions of dogs with a CBPI-defined positive response to treatment.

RESULTS 35 dogs completed the study. No significant changes from baseline in VI and PVF were identified for placebo and tramadol treatments; however, these values increased significantly with carprofen treatment. Changes from baseline in VI and PVF values were significantly greater with carprofen versus placebo or tramadol treatment. A significant improvement from baseline in CBPI scores was identified with carprofen treatment but not placebo or tramadol treatment.

CONCLUSIONS AND CLINICAL RELEVANCE 10 days of treatment with tramadol as administered (5 mg/kg, PO, q 8 h) provided no clinical benefit for dogs with osteoarthritis of the elbow or stifle joint.

Restricted access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate effects of zoledronate on markers of bone metabolism in dogs after transection of the cranial cruciate ligament (CrCL).

Animals—21 adult dogs.

Procedure—Unilateral CrCL transection was performed arthroscopically. Dogs were allocated to 3 groups (control group, low-dose zoledronate [10 µg/kg, SC, q 90 d for 12 months], and high-dose zoledronate [25 µg/kg, SC, q 90 d for 12 months]). Serum osteocalcin (OC), serum bone-specific alkaline phosphatase (BAP), and urine pyridinoline and deoxypyridinoline concentrations were measured at 0, 1, 3, 6, 9, and 12 months after surgery. Bone mineral density (BMD) was determined in the distal portion of the femur and proximal portion of the tibia via computed tomography at each time point. Data were analyzed by a repeated-measures ANOVA.

Results—Zoledronate inhibited OC in the high-dose group at 9 and 12 months and at 12 months in the low-dose group, compared with the control group. High-dose zoledronate decreased BAP concentrations 3 and 9 months after surgery. In the control group, BMD was decreased in the femoral condyle and caudal tibial plateau. Zoledronate prevented significant BMD decreases starting 1 month after transection, compared with control dogs. In the caudomedial aspect of the tibial plateau, both zoledronate groups had significant increases in BMD after 3 months, compared with control dogs.

Conclusions and Clinical Relevance—Zoledronate may reduce subchondral bone loss and effect markers of bone metabolism in dogs with experimentally induced instability of the stifle joint and subsequent development of osteoarthritis. (Am J Vet Res 2005;66:1487–1495)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To investigate the effect of therapeutic dosages of meloxicam on the plasma clearance of iohexol in healthy, euvolemic, conscious cats fed a sodium-replete diet.

Animals—6 healthy adult neutered male cats.

Procedures—For each treatment period in a masked, randomized, crossover study, cats were administered either no treatment or meloxicam. Iohexol clearance studies were performed before the treatment period began (baseline) and on the final day of the treatment period. Iohexol concentrations were determined by use of a high-performance liquid chromatography assay, and plasma iohexol clearance as a marker of glomerular filtration rate was calculated by use of a 1-compartment model.

Results—No significant treatment effect was detected. Mean ± SE iohexol clearance for cats administered meloxicam (3.31 ± 0.27 mL/min/kg) was not significantly different from mean baseline value for the meloxicam treatment period (3.07 ± 0.32 mL/min/kg).

Conclusions and Clinical Relevance—In this study, short-term meloxicam administration did not measurably alter the glomerular filtration rate as assessed via plasma clearance of iohexol. This suggests that renal prostaglandins in cats did not have a measurable effect on glomerular filtration rates in healthy, euvolemic, conscious states as determined on the basis of methods used in this study.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To assess effects of zoledronic acid on biomarkers, radiographic scores, and gross articular cartilage changes in dogs with induced osteoarthritis.

Animals—21 purpose-bred hound-type dogs.

Procedures—The left stifle joint of each dog was examined arthroscopically to determine initial articular cartilage status, which was followed by cranial cruciate ligament (CrCL) transection to induce osteoarthritis. Dogs were assigned to 3 groups (control group, low dose [10 μg of zoledronic acid/kg], or high dose [25 μg of zoledronic acid/kg). Treatments were administered SC every 3 months for 1 year beginning the day after CrCL transection. Serum and synovial fluid samples and radiographs were obtained 0, 1, 3, 6, 9, and 12 months after transection. At 12 months, each joint was scored for cartilage defects. Serum and synovial fluid biomarkers of bone and cartilage turnover (bone-specific alkaline phosphatase, type I and II collagen, carboxy-propeptide of type II collagen, and chondroitin sulfate 846) were analyzed with ELISAs.

Results—The high-dose group had fewer total articular defects and lower severity scores in CrCL-transected stifle joints than did the control group. In addition, the high-dose group had significantly less change in collagenase cleavage of type I or II collagen in the synovial fluid at 1 and 3 months after CrCL transection than did the control group and also had greater changes in bone-specific alkaline phosphatase in synovial fluid at 3 months after CrCL transection than did the control group.

Conclusions and Clinical Relevance—Zoledronic acid had a chondroprotective effect in dogs with a transected CrCL.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare overground and treadmill-based gaits of dogs.

Animals —5 clinically normal adult mixed-breed dogs.

Procedures—To obtain dynamic gait data, 30 retroreflective markers were affixed bilaterally to specific regions of the hind limbs and pelvis of each dog. For each dog, 3-D joint motion data (sagittal [flexion and extension], transverse [internal and external rotation], and frontal [abduction and adduction] planes of motion) for the hip, femorotibial, and tarsal joints were acquired during walking and trotting through a calibrated testing space overground or on a treadmill. Comparison of data was performed via generalized indicator function analysis and Fourier analysis.

Results—Both overground and treadmill-based gaits produced similar waveforms in all planes of motion. Fourier analysis revealed no difference between overground and treadmill-based gaits in the sagittal plane of motion; however, small differences were detected between overground and treadmill-based gaits in the other 2 planes of motion. Additionally, femorotibial joint motion during walking did not differ among planes of motion. Generalized indicator function analysis was able to detect differences between overground and treadmill-based gait waveforms in all planes of motion for all joints during walking and trotting.

Conclusions and Clinical Relevance—In dogs, overground and treadmill-based gaits produced similar waveform shapes. Of the 3 planes of motion evaluated, only sagittal plane kinematic gait data were unaffected by mode of ambulation as determined via Fourier analysis. Sagittal kinematic gait data collected from dogs during overground or treadmill-based ambulation were comparable. However, analysis methods may affect data comparisons.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To assess effects of in vitro meloxicam exposure on metabolism in articular chondrocytes from dogs with naturally occurring osteoarthritis

Sample—Femoral head cartilage from 16 dogs undergoing total hip replacement

Procedures—Articular cartilage samples were obtained. Tissue sulfated glycosaminoglycan (SGAG), collagen, and DNA concentrations were measured. Collagen, SGAG, chondroitin sulfate 846, NO, prostaglandin E2 (PGE2), and matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, and MMP-13 concentrations in culture medium were analyzed. Aggrecan, collagen II, MMP-2, MMP-3, MMP-9, MMP-13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4, ADAMTS-5, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, TIMP-3, interleukin-1β, tumor necrosis factor-α, cyclooxygenase-1, cyclooxygenase-2, and nducible nitric oxide synthase gene expression were evaluated. Comparisons between tissues cultured without (control) and with meloxicam at concentrations of 0.3, 3.0, and 30.0 μg/mL for up to 30 days were performed by means of repeated-measures analysis.

Results—Meloxicam had no effect on chondrocyte SGAG, collagen, or DNA concentrations. Expression of ADAMTS-5 was significantly decreased in all groups on all days, compared with the day 0 value. On day 3, culture medium PGE2 concentrations were significantly lower in all meloxicam-treated groups, compared with values for controls, and values remained low. Culture medium MMP-3 concentrations were significantly lower on day 30 than on day 3 in all meloxicam-treated groups.

Conclusions and Clinical Relevance—Results suggested that in vitro meloxicam treatment of osteoarthritic canine cartilage for up to 30 days did not induce matrix degradation or stimulate MMP production. Meloxicam lowered PGE2 release from this tissue, and effects on tissue chondrocyte content and matrix composition were neutral.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To examine the ability of preemptive administration of a proprietary neurokinin-1 (NK1) receptor antagonist to attenuate limb dysfunction associated with monosodium urate–induced synovitis in the stifle joints of dogs.

Animals—16 clinically normal adult mixed-breed dogs (8 males and 8 females).

Procedures—A crossover study was conducted in 2 phases. Dogs were assigned to 2 groups (8 dogs/group) and orally administered an NK1 receptor antagonist (3 mg/kg) or a control substance once daily for 4 days. Synovitis was then induced in the left stifle joint by intra-articular injection of monosodium urate. Investigators were not aware of treatment group assignments. Dogs were evaluated by use of subjective lameness scores during standing, walking, and trotting and by use of ground reaction force data 3, 6, 9, 12, and 24 hours after urate injection. After a 21-day washout period, the experiment was repeated with each dog administered the other treatment and injected with monosodium urate in the contralateral stifle joint.

Results—No significant differences were detected between the NK1 receptor antagonist and control treatments with regard to peak vertical force, vertical impulse area, or subjective evaluations of lameness during standing, walking, or trotting, except during walking 24 hours after monosodium urate injection.

Conclusions and Clinical Relevance—Preemptive administration of an NK1 receptor antagonist failed to significantly improve subjective or objective outcome measures in dogs with monosodium urate–induced synovitis.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare preoperative administration of meloxicam and butorphanol to perioperative administration of butorphanol alone for control of postoperative signs of pain in dogs.

Animals—40 client-owned dogs scheduled for surgical repair of a cranial cruciate ligament rupture.

Procedure—Group-1 dogs received butorphanol (0.2 mg/kg, IV) and meloxicam (0.2 mg/kg, IV) just prior to surgery. Group-2 dogs received butorphanol just prior to surgery (0.2 mg/kg, IV) and at incision closure (0.1 mg/kg, IV). Pain assessment began 1 to 2 hours before surgery and from extubation until 24 hours after surgery by obtaining the following measurements: the visual analog scale (VAS) score, cumulative pain score (CPS), adjusted cumulative pain score, modified cumulative pain score, and the adjusted modified cumulative pain score (AMCPS). Serum cortisol concentration was measured between 12 to 24 and between 1 to 2 hours prior to surgery, and at 30 minutes, and 1, 2, 4, 8, 18, and 24 hours after extubation.

Results—No significant differences between treatment groups were observed in CPS or VAS score. At 8, 9, 10, and 11 hours after extubation, meloxicambutorphanol- treated dogs had a significantly lower AMCPS, compared with butorphanol-alone-treated dogs. Total serum cortisol concentration (area under the curve) during the measurement period was significantly lower in meloxicam-butorphanol-treated dogs, compared with butorphanol-alone treated dogs.

Conclusions and Clinical Relevance—Preoperative single dose administration of meloxicam-butorphanol is equivalent to or slightly better than the administration of 2 perioperative doses of butorphanol for the control of postoperative signs of pain in dogs. (Am J Vet Res 2002;63:1557–1563)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the plasma pharmacokinetics of imipenem (5 mg/kg) after single-dose IV, IM, and SC administrations in dogs and assess the ability of plasma samples to inhibit the growth of Escherichia coli in vitro.

Animals—6 adult dogs.

Procedure—A 3-way crossover design was used. Plasma concentrations of imipenem were measured after IV, IM, and SC administration by use of high-performance liquid chromatography. An agar well antimicrobial assay was performed with 3 E coli isolates that included a reference strain and 2 multidrug-resistant clinical isolates.

Results—Plasma concentrations of imipenem remained above the reported minimum inhibitory concentration for E coli (0.06 to 0.25 µg/mL) for a minimum of 4 hours after IV, IM, and SC injections. Harmonic mean and pseudo-standard deviation halflife of imipenem was 0.80 ± 0.23, 0.92 ± 0.33, and 1.54 ± 1.02 hours after IV, IM, and SC administration, respectively. Maximum plasma concentrations (Cmax) of imipenem after IM and SC administration were 13.2 ± 4.06 and 8.8 ± 1.7 mg/L, respectively. Time elapsed from drug administration until Cmax was 0.50 ± 0.16 hours after IM and 0.83 ± 0.13 hours after SC injection. Growth of all 3 E coli isolates was inhibited in the agar well antimicrobial assay for 2 hours after imipenem administration by all routes.

Conclusions and Clinical Relevance—Imipenem is rapidly and completely absorbed from intramuscular and subcutaneous tissues and effectively inhibits in vitro growth of certain multidrug-resistant clinical isolates of E coli. (Am J Vet Res 2003;64:694–699)

Full access
in American Journal of Veterinary Research