Jonathan Dyce

Retrospective evaluation of the effectiveness of epsilon aminocaproic acid for the prevention of postamputation bleeding in retired racing Greyhounds with appendicular bone tumors: 46 cases (2003–2008)

OBJECTIVES To determine the frequency of delayed postoperative bleeding in retired racing Greyhounds with appendicular bone tumors undergoing limb amputations. To identify if administration of epsilon-aminocaproic acid (EACA) was effective on the prevention of postoperative bleeding. DESIGN Retrospective study from December 2003 to December 2008. SETTING Veterinary university teaching hospital. ANIMALS Forty-six retired racing Greyhounds (RRGs) diagnosed with primary appendicular bone tumors that underwent limb amputation were included in the study. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Thirteen of 46 RRGs (28%) included in the study had delayed postoperative bleeding starting 48-72 h after surgery. Bleeding episodes included cutaneous, subcutaneous, and external bleeding that extended from the area of the surgical site that became widespread within hours, and that required administration of blood components. A paired t-test suggests that there was a significant decrease in PCV postoperatively for both dogs that bled and dogs that did not bleed (P < 0.0001). Forty of 46 RRGs (86%) received either fresh frozen plasma (FFP) or EACA or both, for the prevention of postoperative bleeding. A logistic regression model determined that dogs that did not receive EACA were 5.7 times more likely to bleed than dogs that did receive EACA, when controlling for whether or not they received FFP (95% CI: 1.02-32.15, P = 0.047). CONCLUSION This retrospective study suggests that preemptive postoperative administration of EACA appears to be efficacious in decreasing the frequency of bleeding in RRGs undergoing limb amputation; however, a prospective study is warranted to corroborate its effectiveness.

Detectable reporter gene expression following transduction of adenovirus and adeno-associated virus serotype 2 vectors within full-thickness osteoarthritic and unaffected canine cartilage in vitro and unaffected guinea pig cartilage in vivo

This study quantified and compared the transduction efficiencies of adenoviral (Ad), Arg‐Gly‐Asp (RGD)‐modified Ad, adeno‐associated viral serotype 2 (AAV2), and self‐complementary AAV2 (scAAV2) vectors within full‐thickness osteoarthritic (OA) and unaffected canine cartilage explants in vitro. Intraarticular administration of Ad and scAAV2 vectors was performed to determine the ability of these vectors to transduce unaffected guinea pig cartilage in vivo. Following explant exposure to vector treatment or control, the onset and surface distribution of reporter gene expression was monitored daily with fluorescent microscopy. At termination, explants were divided: one half was digested for analysis using flow cytometry; the remaining portion was used for histology and immunohistochemistry (IHC). Intact articular joints were collected for real‐time RT‐PCR and IHC to detect reporter gene expression following injection of selected vectors. Ad vector transduced focal areas along the perimeters of explants; the remaining vectors transduced chondrocytes across 100% of the surface. Greater mean transduction efficiencies were found with both AAV2 vectors as compared to the Ad vector (p ≤ 0.026). Ad and Ad‐RGD vectors transduced only superficial chondrocytes of OA and unaffected cartilage. Uniform reporter gene expression from AAV2 and scAAV2 was detected in the tangential and transitional zones of OA cartilage, but not deeper zones. AAV2 and scAAV2 vectors achieved partial and full‐thickness transduction of unaffected cartilage. In vivo work revealed that scAAV2 vector, but not Ad vector, transduced deeper zones of cartilage and menisci. This study demonstrates that AAV2 and scAAV2 are reliable vectors for use in cartilage in vitro and in vivo.

Distal femoral lateral closing wedge osteotomy as a component of comprehensive treatment of medial patellar luxation and distal femoral varus in dogs

OBJECTIVE To describe a cohort of dogs with medial patellar luxation managed with a distal femoral lateral closing wedge ostectomy (DFO) as a component of comprehensive treatment, and to report radiographic and long-term clinical outcome of this technique. METHODS Medical records of dogs that had a lateral closing wedge DFO as part of management of medial patellar luxation at three veterinary teaching hospitals were reviewed. Surgical reports as well as the preoperative, postoperative, and follow-up radiographs were reviewed. The anatomical lateral distal femoral angle (aLDFA) was determined. Long-term clinical outcome was assessed by telephone interview with the owner. RESULTS A lateral closing wedge DFO was performed on 66 limbs. The mean pre- and postoperative aLDFA was 107.6° ± 5.8° and 94.1° ± 4.2°, respectively. Cranial cruciate ligament disease was identified in 28/66 affected limbs. Tibial angular deformity, torsional deformity, or both was identified in nine of the 66 limbs. Ostectomy healing was confirmed radiographically in 51/66 limbs. The mean time to union was 73 ± 37 days. All patellae were in the normal position and stable. Complications included infection (2/51), fixation failure (1/51), delayed healing (2/51), and persistent lameness (1/51). CLINICAL SIGNIFICANCE In this cohort of cases, DFO was a highly successful and repeatable component of surgical treatment for dogs with medial patellar luxation associated with femoral varus. This study also provides more evidence of the high rate of concurrent cranial cruciate ligament disease in cases of medial patellar luxation complicated by femoral varus, and supports an association between stifle instability and medial patellar luxation.

Postoperative comparison of four perioperative analgesia protocols in dogs undergoing stifle joint surgery

OBJECTIVE To compare 4 analgesic protocols in dogs undergoing stifle joint surgery. DESIGN Randomized, blinded, prospective clinical trial. Animals-48 client-owned dogs that underwent stifle joint surgery. PROCEDURES Dogs undergoing tibial plateau leveling osteotomy were randomly assigned to receive a constant rate infusion of a combination of morphine, lidocaine, and ketamine; a lumbosacral epidural with morphine and ropivacaine; both treatments (ie, constant rate infusion and lumbosacral epidural); or only IM premedication with morphine. Indices of cardiorespiratory function and isoflurane requirement were recorded at 5-minute intervals during anesthesia. A validated sedation scoring system and the modified Glasgow composite measure pain score were used to assess comfort and sedation after surgery and anesthesia once the swallowing reflex returned and a body temperature of ≥ 36.7°C (98.1°F) was attained. Pain and sedation scores were acquired at 60-minute intervals for 4 hours, then at 4-hour intervals for 24 hours. Dogs with a postoperative pain score > 5 of 24 were given morphine as rescue analgesia. RESULTS No differences in heart rate, respiratory rate, systolic arterial blood pressure, end-tidal Pco2, end-tidal isoflurane concentration, and vaporizer setting were detected among groups. No differences in pain score, sedation score, rescue analgesia requirement, or time to first rescue analgesia after surgery were detected. CONCLUSIONS AND CLINICAL RELEVANCE Pain scores were similar among groups, and all 4 groups had similar rescue analgesia requirements and similar times to first administration of rescue analgesia. All 4 analgesic protocols provided acceptable analgesia for 24 hours after stifle joint surgery.

Fibular osteotomy to facilitate proximal tibial rotation during tibial plateau leveling osteotomy

OBJECTIVE To identify factors that restrict proximal tibial rotation during tibial plateau leveling osteotomy (TPLO) and report on the outcome of concurrent fibular osteotomy (TPLO-FO). STUDY DESIGN Retrospective case-control study. ANIMALS Dogs undergoing TPLO-FO (n = 23) and dogs undergoing routine TPLO (n = 49). METHODS Medical records and radiographs of dogs that had undergone TPLO-FO were reviewed. Data that were collected included signalment, preoperative tibial plateau angle (TPA), mechanical medial proximal tibial angle (mMPTA), postoperative and recheck TPA and mMPTA, ratio of fibular width to tibial width (FW:TW), presence of tibiofibular synostosis, tibial osteotomy location, and use of additional implants. RESULTS The odds of exhibiting rotational constraints requiring FO during TPLO were 62-fold greater in dogs with tibiofibular synostosis than in dogs without synostosis. Dogs with FW:TW greater than 0.24 were 7.8-fold more likely to exhibit rotational constraints. After TPLO-FO, the postoperative increase in TPA was greater after single-plate fixation (mean, 5.4 ° ± 4.5 °) compared with fixation with 2 plates (mean, 1.4 ° ± 0.6 °). CONCLUSION Proximal tibiofibular synostosis and a relatively wide fibula restricted tibial plateau rotation. In these dogs, concurrent fibular osteotomy allowed adequate rotation. Adjunct plate fixation limited loss of rotation after TPLO-FO. CLINICAL SIGNIFICANCE Successful TPLO relies on adequate rotation of the proximal tibial segment. Fibular osteotomy and adjunct plate fixation are recommended to achieve and maintain adequate rotation of the osteotomized tibia in dogs with rotational constraints.

Pharmacokinetics and pharmacodynamics after oral administration of tapentadol hydrochloride in dogs

OBJECTIVE To evaluate pharmacokinetic and pharmacodynamic characteristics of 3 doses of tapentadol hydrochloride orally administered in dogs. ANIMALS 6 healthy adult mixed-breed dogs. PROCEDURES In a prospective, randomized crossover study, dogs were assigned to receive each of 3 doses of tapentadol (10, 20, and 30 mg/kg, PO); there was a 1-week washout period between subsequent administrations. Plasma concentrations and physiologic variables were measured for 24 hours. Samples were analyzed by use of high-performance liquid chromatography-tandem mass spectrometry. RESULTS Tapentadol was rapidly absorbed after oral administration. Mean maximum plasma concentrations after 10, 20, and 30 mg/kg were 10.2, 19.7, and 31 ng/mL, respectively. Geometric mean plasma half-life of the terminal phase after tapentadol administration at 10, 20, and 30 mg/kg was 3.5 hours (range, 2.7 to 4.5 hours), 3.7 hours (range, 3.1 to 4.0 hours), and 3.7 hours (range, 2.8 to 6.5 hours), respectively. Tapentadol and its 3 quantified metabolites (tapentadol sulfate, tapentadol-O-glucuronide, and desmethyltapentadol) were detected in all dogs and constituted 0.16%, 2.8%, 97%, and 0.04% of the total area under the concentration-time curve (AUC), respectively. Plasma AUCs for tapentadol, tapentadol sulfate, and tapentadol-O-glucuronide increased in a dose-dependent manner. Desmethyltapentadol AUC did not increase in a linear manner at the 30-mg/kg dose. Sedation scores and heart and respiratory rates were not significantly affected by dose or time after administration. CONCLUSIONS AND CLINICAL RELEVANCE Oral administration of tapentadol was tolerated well, and the drug was rapidly absorbed. Adverse events were not apparent in any dogs at any doses in this study.

Comparison of the effects of two screw insertion patterns on bone fragment translocation in a 3.5 mm dynamic compression plate and a 3.5 mm limited-contact dynamic compression plate.

OBJECTIVE To compare the effects of screw insertion pattern, plate type, application of bone reduction forceps, and additional load screw insertion in an 8-hole 3.5 mm dynamic compression plate (DCP) and limited-contact dynamic compression plate (LC-DCP) on bone fragment translocation (BFT) in a fracture gap model. STUDY DESIGN In vitro mechanical study. METHODS Two screw insertion patterns were tested in the DCP and newly redesigned LC-DCP using gap model synthetic bone constructs. In Pattern 1, screws were first inserted into the holes at each end of the plate, then screws were inserted into the holes adjacent to the fracture gap. In Pattern 2, screws were only inserted into the holes adjacent to the fracture gap. The effects of tight or loose bone forceps securing the plate, loosening a neutral screw in Pattern 1, and inserting up to 4 additional load screws with each pattern were tested. Changes in the fracture gap were measured after insertion of all neutral screws and after each load screw. RESULTS Pattern 2 BFT was significantly greater than Pattern 1 BFT when bone forceps were loose with both plates (P < .001). In the DCP, the BFT was significantly increased by loosening the bone forceps with Pattern 2 (P < .001) and by loosening 1 neutral screw in Pattern 1 (P < .001). The BFT for each additional load screw inserted was significantly less than 1.0 mm. CONCLUSIONS A tight neutral screw in the same bone fragment as the load screw or bone clamps that tightly secure the plate to the bone can limit BFT.

Image-Based Macro-Micro Finite Element Models of a Canine Femur with Implant Design Implications

In this paper, a comprehensive model of a bone-cement-implant assembly is developed for a canine cemented femoral prosthesis system. Various steps in this development entail profiling the canine femur contours by computed tomography (CT) scanning, computer aided design (CAD) reconstruction of the canine femur from CT images, CAD modeling of the implant from implant blue prints and CAD modeling of the interface cement. Finite element analysis of the macroscopic assembly is conducted for stress analysis in individual components of the system, accounting for variation in density and material properties in the porous bone material. A sensitivity analysis is conducted with the macroscopic model to investigate the effect of implant design variables on the stress distribution in the assembly. Subsequently, rigorous microstructural analysis of the bone incorporating the morphological intricacies is conducted. Various steps in this development include acquisition of the bone microstructural data from histological serial sectioning, stacking of sections to obtain 3D renderings of void distributions, microstructural characterization and determination of properties and, finally, microstructural stress analysis using a 3D Voronoi cell finite element method. Generation of the simulated microstructure and analysis by the 3D Voronoi cell finite element model provides a new way of modeling complex microstructures and correlating to morphological characteristics. An inverse calculation of the material parameters of bone by combining macroscopic experiments with microstructural characterization and analysis provides a new approach to evaluating properties without having to do experiments at this scale. Finally, the microstructural stresses in the femur are computed using the 3D VCFEM to study the stress distribution at the scale of the bone porosity. Significant difference is observed between the macroscopic stresses and the peak microscopic stresses at different locations.