OBJECTIVE To determine whether walking at specific ranges of absolute and relative (V*) velocity would aid efficient capture of gait trial data with low ground reaction force (GRF) variance in a heterogeneous sample of dogs. ANIMALS 17 clinically normal dogs of various breeds, ages, and sexes. PROCEDURES Each dog was walked across a force platform at its preferred velocity, with controlled acceleration within 0.5 m/s2. Ranges in V* were created for height at the highest point of the shoulders (withers; WHV*). Variance effects from 8 walking absolute velocity ranges and associated WHV* ranges were examined by means of repeated-measures ANCOVA. RESULTS The individual dog effect provided the greatest contribution to variance. Narrow velocity ranges typically resulted in capture of a smaller percentage of valid trials and were not consistently associated with lower variance. The WHV* range of 0.33 to 0.46 allowed capture of valid trials efficiently, with no significant effects on peak vertical force and vertical impulse. CONCLUSIONS AND CLINICAL RELEVANCE Dogs with severe lameness may be unable to trot or may have a decline in mobility with gait trial repetition. Gait analysis involving evaluation of individual dogs at their preferred absolute velocity, such that dogs are evaluated at a similar V*, may facilitate efficient capture of valid trials without significant effects on GRF. Use of individual velocity ranges derived from a WHV* range of 0.33 to 0.46 can account for heterogeneity and appears suitable for use in clinical trials involving dogs at a walking gait.

OBJECTIVE To evaluate the effect of gadoxetic acid (contrast) dose on biliary tract enhancement, determine the optimal time after contrast injection for CT image acquisition, and assess the feasibility of CT cholangiography in sedated dogs. ANIMALS 8 healthy dogs. PROCEDURES The study had 2 parts. In part 1, 4 dogs were anesthetized and underwent CT cholangiography twice. Gadoxetic acid was administered IV at a low dose (0.025 mmol/kg) for the first procedure and high dose (0.3 mmol/kg) for the second procedure. Serial CT scans were obtained at predetermined times after contrast injection. In part 2, 4 dogs were sedated and underwent CT angiography 85 minutes after IV administration of the high contrast dose. Contrast enhancement of the biliary tract on all scans was objectively assessed by measurement of CT attenuation and qualitatively assessed by use of a subjective 4-point scoring system by 3 independent reviewers. All measurements were compared over time and between contrast doses for the dogs of part 1. Subjective measurements were compared between the sedated dogs of part 2 and anesthetized dogs of part 1. RESULTS Enhancement of the biliary tract was positively associated with contrast dose and time after contrast injection. Optimal enhancement was achieved 65 minutes after contrast injection. Subjective visualization of most biliary structures did not differ significantly between sedated and anesthetized dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated CT cholangiography with gadoxetic acid was feasible in sedated dogs. The high contrast dose provided better visualization of biliary structures than the low dose; CT scans should be obtained 65 minutes after contrast injection.

OBJECTIVE To compare stroke volume (SV) calculated on the basis of cardiac morphology determined by MRI and results of phase-contrast angiography (PCA) of ventricular inflow and outflow in dogs. ANIMALS 10 healthy Beagles. PROCEDURES Cardiac MRI was performed twice on each Beagle. Cine gradient echo sequences of both ventricles in short-axis planes were used for morphological quantification of SVs by assessment of myocardial contours. From the long-axis plane, SVs in 4-chamber and left ventricular 2-chamber views were acquired at end diastole and end systole. For calculation of SV on the basis of blood flow, PCA was performed for cardiac valves. RESULTS Mean ± SD values for SV quantified on the basis of blood flow were similar in all valves (aortic, 17.8 ± 4.1 mL; pulmonary, 17.2 ± 5.4 mL; mitral, 17.2 ± 3.9 mL; and tricuspid, 16.9 ± 5.1 mL). Morphological quantification of SV in the short-axis plane yielded significant differences between left (13.4 ± 2.7 mL) and right (8.6 ± 2.4 mL) sides. Morphological quantification of left ventricular SV in the long-axis plane (15.2 ± 3.3 mL and 20.7 ± 3.8 mL in the 4- and 2-chamber views) yielded variable results, which differed significantly from values for flow-based quantification, except for values for the morphological 4-chamber view and PCA for the atrioventricular valves, for which no significant differences were identified. CONCLUSIONS AND CLINICAL RELEVANCE In contrast to quantification based on blood flow, calculation on the basis of morphology for the short-axis plane significantly underestimated SV, probably because of through-plane motion and complex right ventricular anatomy.

OBJECTIVE To quantify plasma fentanyl concentrations (PFCs) and evaluate antinociceptive and respiratory effects following application of transdermal fentanyl patches (TFPs) and assess cerebrospinal μ-opioid receptor mRNA expression in ball pythons (compared with findings in turtles). ANIMALS 44 ball pythons (Python regius) and 10 turtles (Trachemys scripta elegans). PROCEDURES To administer 3 or 12 μg of fentanyl/h, a quarter or whole TFP (TFP-3 and TFP-12, respectively) was used. At intervals after TFP-12 application in snakes, PFCs were measured by reverse-phase high-pressure liquid chromatography. Infrared heat stimuli were applied to the rostroventral surface of snakes to determine thermal withdrawal latencies after treatments with no TFP (control [n = 16]) and TFP-3 (8) or TFP-12 (9). Breathing frequency was measured in unrestrained controls and TFP-12–treated snakes. μ-Opioid receptor mRNA expression in brain and spinal cord tissue samples from snakes and turtles (which are responsive to μ-opioid receptor agonist drugs) were quantified with a reverse transcription PCR assay. RESULTS Mean PFCs were 79, 238, and 111 ng/mL at 6, 24, and 48 hours after TFP-12 application, respectively. At 3 to 48 hours after TFP-3 or TFP-12 application, thermal withdrawal latencies did not differ from pretreatment values or control treatment findings. For TFP-12–treated snakes, mean breathing frequency significantly decreased from the pretreatment value by 23% and 41% at the 24- and 48-hour time points, respectively. Brain and spinal cord tissue μ-opioid receptor mRNA expressions in snakes and turtles did not differ. CONCLUSIONS AND CLINICAL RELEVANCE In ball pythons, TFP-12 application resulted in high PFCs, but there was no change in thermal antinociception, indicating resistance to μ-opioid-dependent antinociception in this species.

OBJECTIVE To characterize CT findings and outcomes in dogs with head trauma and design a prognostic scale. ANIMALS 27 dogs admitted to the Koret School Veterinary Teaching Hospital within 72 hours after traumatic head injury that underwent CT imaging of the head. PROCEDURES Data were extracted from medical records regarding dog signalment, history, physical and neurologic examination findings, and modified Glasgow coma scale scores. All CT images were retrospectively evaluated by a radiologist unaware of dog status. Short-term (10 days after trauma) and long-term (≥ 6 months after trauma) outcomes were determined, and CT findings and other variables were analyzed for associations with outcome. A prognostic CT-based scale was developed on the basis of the results. RESULTS Cranial vault fractures, parenchymal abnormalities, or both were identified via CT in 24 of 27 (89%) dogs. Three (11%) dogs had only facial bone fractures. Intracranial hemorrhage was identified in 16 (59%) dogs, cranial vault fractures in 15 (56%), midline shift in 14 (52%), lateral ventricle asymmetry in 12 (44%), and hydrocephalus in 7 (26%). Hemorrhage and ventricular asymmetry were significantly and negatively associated with short- and long-term survival, respectively. The developed 7-point prognostic scale included points for hemorrhage, midline shift or lateral ventricle asymmetry, cranial vault fracture, and depressed fracture (1 point each) and infratentorial lesion (3 points). CONCLUSIONS AND CLINICAL RELEVANCE The findings reported here may assist in determining prognoses for other dogs with head trauma. The developed scale may be useful for outcome assessment of dogs with head trauma; however, it must be validated before clinical application.

Programmed cell death protein 1 (PD-1), a costimulatory molecule of the CD28 family, has 2 ligands, PD-L1 and PD-L2. Our previous studies showed that the expression of PD-1 and PD-L1 is up-regulated during viral infection in pigs. Extensive studies have shown that blockade of the PD-1/PD-L1 pathways by anti-PD-L1 antibody or soluble PD-1 restores exhausted T-cells in humans and mice. In the present study the extracellular domains of PD-1 and PD-L1 were used to evaluate the binding of PD-1 and PD-L1 with peripheral blood mononuclear cells (PBMCs). We amplified the cDNA encoding the extracellular domains of PD-1 and PD-L1 to construct recombinant expression plasmids and obtain soluble recombinant proteins, which were then labeled with fluorescein isothiocyanate (FITC). The His-ExPD-1 and His-ExPD-L1 recombinant proteins were expressed in the form of inclusion bodies with a relative molecular weight of 33.0 and 45.0 kDa, respectively. We then prepared polyclonal antibodies against the proteins with a multi-antiserum titer of 1:102 400. Binding of the proteins with PBMCs was evaluated by flow cytometry. The fluorescence signals of His-ExPD-1-FITC and His-ExPD-L1-FITC were greater than those for the FITC control. These results suggest that the soluble recombinant proteins may be used to prepare monoclonal antibodies to block the PD-1/PD-L1 pathway.

International comparisons of animal antimicrobial use (AMU) have typically been based on total national estimates of antimicrobials sales standardized by the national animal biomass calculated as the population correction unit (PCU). The objective of this paper was to compare the currently accepted PCU calculation with that of the adjusted population correction unit (APCU), which re-evaluates the standard animal weights used in the calculation and accounts for animal lifespan. The APCU calculation resulted in substantial changes to the 2009 national biomass estimates for cattle, pigs, and poultry in 8 European countries and Canada. The estimated national biomass for cattle increased 35% to 43%, while the estimated national biomass of pigs and poultry typically decreased by approximately 51% and 87%, respectively. Among the 9 countries, the total national APCU ranged from an increase of 1% to a decrease of 40% relative to PCU, and these differences were statistically significant. Adjusted population correction unit is preferred over PCU in comparing and contrasting AMU among animals with different lifespans because it is more transparently derived and is a reasonable approximation of the animal biomass at risk of antimicrobial treatment.

OBJECTIVE To compare stiffness and resistance to cyclic fatigue of two 3.5-mm locking system plate-rod constructs applied to an experimentally created fracture gap in femurs of canine cadavers. SAMPLE 20 femurs from cadavers of 10 mixed-breed adult dogs. PROCEDURES 1 femur from each cadaver was stabilized with a conical coupling plating system-rod construct, and the contralateral femur was stabilized with a locking compression plate (LCP)-rod construct. An intramedullary Steinmann pin was inserted in each femur. A 40-mm gap then was created; the gap was centered beneath the central portion of each plate. Cyclic axial loading with increasing loads was performed. Specimens that did not fail during cyclic loading were subjected to an acute load to failure. RESULTS During cyclic loading, significantly more LCP constructs failed (6/10), compared with the number of conical coupling plating system constructs that failed (1/10). Mode of failure of the constructs included fracture of the medial or caudal aspect of the cortex of the proximal segment with bending of the plate and pin, bending of the plate and pin without fracture, and screw pullout. Mean stiffness, yield load, and load to failure were not significantly different between the 2 methods of stabilization. CONCLUSIONS AND CLINICAL RELEVANCE Both constructs had similar biomechanical properties, but the conical coupling plating system was less likely to fail than was the LCP system when subjected to cyclic loading. These results should be interpreted with caution because testing was limited to a single loading mode.

OBJECTIVE To evaluate pharmacokinetics of cefazolin after IV injection of cefazolin (22 mg/kg) and after simultaneous IV and IM injections of cefazolin (total dose, 44 mg/kg) to dogs. ANIMALS 12 adult Beagles. PROCEDURES Dogs (6/group) were assigned to receive a single injection of cefazolin (IV group; 22 mg/kg, IV) or simultaneous injections (IV + IM group; 22 mg/kg, IV, and 22 mg/kg, IM). Interstitial fluid was collected over a 5-hour period by use of ultrafiltration probes for pharmacokinetic analysis. RESULTS Mean cefazolin concentration in the interstitial fluid at 1, 1.5, 2, 3, 4, and 5 hours after injection was 39.6, 29.1, 21.2, 10.3, 6.4, and 2.7 μg/mL, respectively, for the IV group and 38.3, 53.3, 46.4, 31.7, 19.1, and 8.9 μg/mL, respectively, for the IV + IM group. Mean area under the concentration-time curve extrapolated to infinity, maximum concentration, half-life, and time to maximum concentration was 74.99 and 154.16 h·μg/mL, 37.3 and 51.5 μg/mL, 0.96 and 1.11 hours, and 1.28 and 1.65 hours, respectively, for the IV and IV + IM groups. CONCLUSIONS AND CLINICAL RELEVANCE Cefazolin concentrations in interstitial fluid of dogs were maintained at > 4 μg/mL for 4 hours after a single IV injection and for 5 hours after simultaneous IV and IM injections. Therefore, simultaneous IV and IM administration of cefazolin 30 to 60 minutes before surgery should provide interstitial fluid concentrations effective against the most common commensal organisms (Staphylococcus spp and Streptococcus spp) on the skin of dogs for surgical procedures lasting ≤ 4 hours.

The objectives of the present study were to determine if diagnosis and treatment of equine pituitary pars intermedia dysfunction (PPID) vary by geographic region and to report the prevalence of PPID in horses as observed by veterinarians across locations. An online questionnaire was developed for veterinarians who treat horses. Veterinary associations, especially equine specialty subgroups, were contacted and a survey link was sent to members of each organization. Generalized linear models were used to examine whether the method of diagnosis and treatment of this condition, as well as its reported prevalence, differed by geographic region. Veterinarians from 426 separate clinics in 20 countries returned surveys. Diagnosis of PPID varied by region, but was usually based on clinical signs and an adjunct endocrine test. Horses with PPID were treated medically by 63% of veterinarians and 75% of these used pergolide mesylate as treatment. The median prevalence estimated was 1% and this did not differ by geographic location. Half the veterinarians were caring for 5 or more animals with PPID. Overall, diagnostic approach differed in geographic regions. In general, European veterinarians were more likely than those in North America to diagnose PPID based on clinical signs alone, without using an adjunct laboratory test. Veterinarians reported that cost and management responsibilities were their clients' primary concerns associated with the long-term treatment of this disease, which indicates a need for additional treatment options for PPID.