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Objective: To evaluate the effects of nanoparticle hyperthermia therapy on monocyte function and tumor-derived factors associated with macrophage polarization in a murine osteosarcoma model., Study Design: Experimental study., Animals: Female C3H mice., Methods: Peripheral blood monocyte cell surface phenotype, monocyte chemotaxis, tumor messenger RNA expression, and survival were compared among osteosarcoma (OS)-bearing mice treated with nanoparticle hyperthermia therapy, OS-bearing mice with osteomyelitis, OS-bearing mice, vehicle control mice, and normal control mice., Results: OS-bearing mice with osteomyelitis had a higher proportion of "nonclassical" monocytes (Ly6C lo ) compared with all other experimental groups. There were alterations in monocyte expression of multiple chemokine receptors among experimental groups including CXCR2, CCR2, and CXCR4. Monocytes from OS-bearing mice treated with hyperthermia therapy exhibited greater chemotaxis compared with monocytes from OS-bearing mice with osteomyelitis., Conclusion: OS likely induced alterations in monocyte phenotype and function. Nanoparticle hyperthermia therapy increased in vitro monocyte chemotaxis., Clinical Impact: Enhancing monocyte/macrophage function in dogs with OS may enhance antitumor immunity., (© 2018 The American College of Veterinary Surgeons.)

Background: Levetiracetam (LEV) is a common add-on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs., Hypothesis/objectives: To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs., Animals: Eighteen client-owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB-BR group, n = 6)., Methods: Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high-pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area-under-the-curve (AUC) calculated to the last measured time point., Results: Compared to the PB and PB-BR groups, the BR group had significantly higher peak concentration (Cmax ) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*μg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028)., Conclusions and Clinical Importance: Concurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add-on treatment with phenobarbital in dogs., (Copyright © 2015 by the American College of Veterinary Internal Medicine.)

Background: Medically refractory seizures are an important problem in both humans and dogs with epilepsy. Altered expression of ABCB1, the gene encoding for p-glycoprotein (PGP), has been proposed to play a role in drug-resistant epilepsy., Hypothesis: Heterogeneity of the ABCB1 gene is associated with seizure outcome in dogs with epilepsy., Animals: Twenty-nine Collies with epilepsy being treated with antiepileptic drugs (AEDs)., Methods: Prospective and retrospective cohort study. Dogs were classified as having a good outcome (≤ 1 seizure/month, no cluster seizures) or a poor outcome (>1 seizure/month, with or without cluster seizures) based on owner-completed questionnaire. Serum AED concentrations were measured, and ABCB1 genotyping was performed on buccal tissue samples. Association analyses were performed for genotype and seizure outcome, number of AEDs administered, serum AED concentrations, and incidence of adverse effects., Results: Fourteen dogs of 29 (48%) were homozygous for the ABCB1-1∆ mutation (M/M), 11 dogs (38%) were heterozygous (M/N), and 4 dogs (14%) had the wild-type genotype (N/N). Dogs with the M/M genotype were significantly more likely to have fewer seizures and have less AED-related sedation than M/N or N/N dogs (P = .003 and P = .001, respectively). Serum phenobarbital and bromide concentrations did not differ between groups, but the M/N and N/N groups received a larger number of AEDs than the M/M group (P = .014)., Conclusions and Clinical Importance: ABCB1 genotype is associated with seizure outcome in Collies with epilepsy. This cannot be attributed to differences in PGP function, but might be because of intrinsic variations in seizure severity among phenotypes., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Abdominal ultrasound (US) is used frequently as a first-line screening tool for abdominal disease. Although computed tomography (CT) is superior to US in the diagnosis of some abdominal diseases, a major impediment is the requirement of general anesthesia to prevent motion and for safe restraint. With multidetector helical CT, faster examinations allow general anesthesia to be avoided, while producing diagnostic-quality images. Abdominal US and CT were compared for lesion detection in 27 sedated dogs, divided into three even groups based on body weight. Lesions were categorized further as to subjective clinical relevance. In dogs less than 25 kg, there is no significant difference in lesion detection between CT and US. In dogs weighing greater than 25 kg, more lesions were detected with CT than with US (P = 0.0001), including clinically relevant lesions (P = 0.0277). From these results, it appears that CT has an advantage in lesion detection in dogs greater than 25 kg, making it a better screening test for abdominal disease in these patients., (© 2012 Veterinary Radiology & Ultrasound.)

Background: There is little evidence-based information available to guide treatment of refractory epilepsy in dogs. The antiepileptic drug levetiracetam (LEV) is administered to dogs, although its safety and efficacy are unknown., Objective: To evaluate the safety and efficacy of LEV as adjunctive therapy for refractory epilepsy in dogs., Animals: Thirty-four client-owned dogs with idiopathic epilepsy., Methods: Randomized, blinded trial involving dogs resistant to phenobarbital and bromide. Dogs received LEV (20 mg/kg PO q8h) or placebo for 16 weeks, and after a 4-week washout were crossed over to the alternate treatment for 16 weeks. Owners kept records on seizure frequency and adverse events. Hemogram, chemistry profile, urinalysis, and serum antiepileptic drug concentrations were evaluated at established intervals., Results: Twenty-two (65%) dogs completed the study. Weekly seizure frequency during the 1st treatment period decreased significantly during LEV administration relative to baseline (1.9 ± 1.9 to 1.1 ± 1.3, P = .015). The reduction in seizures with LEV was not significant when compared to placebo (1.1 ± 1.3 versus 1.5 ± 1.7, P = .310). The most common adverse event was ataxia, with no difference in incidence between LEV and placebo (45 versus 18%, P = .090). No changes in laboratory parameters were identified and owners reported an improved quality of life (QOL) with LEV compared to placebo (QOL score 32.7 ± 4.3 versus 29.4 ± 4.5, P = .028)., Conclusions and Clinical Importance: Adjunctive treatment with LEV appears safe in epileptic dogs. Efficacy of LEV over placebo was not demonstrated, although the power of the study was limited. Further evaluation of LEV as treatment for epilepsy in dogs is warranted., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Background: Urinary tract infection (UTI) is a common complication in people with spinal cord injury (SCI). Dogs with acute intervertebral disc extrusion (IVDE) have similar risk factors for UTI when compared with human SCI patients and have a high perioperative prevalence of UTI., Objectives: Determine the prevalence of UTI in dogs for 3 months after surgery for thoracolumbar IVDE and identify risk factors for development of UTI., Animals: Twenty-five dogs treated surgically for 26 acute disc extrusions., Methods: Prospective study. Urinalysis and urine culture were performed perioperatively. At home, owners monitored urine with dipsticks every 48 hours for 1 month then once a week until 3 months. Dogs returned for assessment of motor function, urinalysis, and urine culture at 1 and 3 months after surgery. Presence of UTI over the 3-month period was correlated to potential risk factors., Results: Ten dogs (38%) developed 12 UTIs over the 3-month period, with the majority occurring between weeks 1 and 6; 60% of the UTIs were occult. Hematuria in the absence of pyuria or UTI was a common finding in the perioperative period. Sex, breed, and ambulatory status influenced the risk of developing a UTI., Conclusions and Clinical Importance: There is a high prevalence of UTIs, many of which are occult, in the 3 months after surgery for thoracolumbar IVDE. These dogs should be routinely monitored for UTI with urine culture regardless of urinalysis results., (Copyright © 2010 by the American College of Veterinary Internal Medicine.)

Objective: To compare 5 radiographic views for the detection of osteochondritis dissecans (OCD) in dogs with signs of elbow joint pain., Animals: 53 dogs (100 elbow joints) with forelimb lameness and signs of elbow joint pain., Procedures: Mediolateral (ML), flexed ML, craniocaudal (CC), craniolateral-caudomedial oblique (Cr15L-CdMO), and distomedial-proximolateral oblique (Di35M-PrLO) radiographic views of the 100 elbow joints were obtained. Four examiners graded radiographs with regard to elbow joint OCD. Joints were assessed by use of arthroscopy. Receiver operating characteristic (ROC) curves, kappa measure of agreement, and Fisher exact tests for association between median diagnostic value and actual status were computed., Results: 47 joints had an abnormal medial aspect of the humeral condyle (MAHC), and among them, 11 had OCD. The presence of fractures of the medial coronoid process was significantly and positively correlated with the presence of abnormalities of the MAHC (r = 0.40), but was negatively correlated with the presence of OCD (r = -0.32). At 95% specificity, median sensitivities to detect OCD were 57% for Cr15L-CdMO, 56% for CC, 10% for flexed ML, 7% for ML, and 4% for Di35M-PrLO views. The areas under the ROC curves were significantly larger for the Cr15L-CdMO and CC views than for the ML, flexed ML, and Di35M-PrLO views for the detection of OCD. Only the Cr15L-CdMO and CC views allowed accurate detection of OCD., Conclusions and Clinical Relevance: In dogs with signs of elbow joint pain, the Cr15L-CdMO view is excellent and the CC view was good for detection of OCD.

Syringomyelia is an important morbidity source in Cavalier King Charles Spaniels. Although abnormal cerebrospinal fluid (CSF) flow secondary to Chiari malformations is thought to cause syringomyelia in humans, this relationship is unknown in dogs. We used phase-contrast magnetic resonance (MR) imaging to evaluate CSF flow in dogs. Fifty-nine Cavalier King Charles Spaniels were assigned a neurologic grade reflecting their neurologic status. Five normal control dogs of other breeding were imaged for comparison. The presence of syringomyelia was noted from sagittal MR images. The pattern and velocity of CSF flow were assessed using phase-contrast cine MRI at the foramen magnum, C2-C3 disc space, and within syrinxes. Flow was measured most easily with the neck flexed to mimic standing. CSF flow velocity in the dorsal aspect of the subarachnoid space at the foramen magnum was significantly higher in control dogs than Cavalier King Charles Spaniels (P = 0.035). Flow was obstructed at the foramen magnum in 41 of 59 Cavalier King Charles Spaniels. Turbulent flow and jets were associated with syringomyelia presence and severity, and CSF flow velocity at C2/3 dorsally was inversely related to the presence of syringomyelia (P = 0.0197). Peak dorsal subarachnoid space CSF flow velocity at the foramen magnum and C2-C3 were together highly predictive of syringomyelia. CSF flow can be assessed in dogs using phase-contrast cine MRI. Obstruction to flow at the foramen magnum is common in Cavalier King Charles Spaniels and CSF flow pattern and velocity are related to the presence of syringomyelia.

Chiari malformations and syringohydromyelia are an important disease complex in Cavalier King Charles Spaniels. Although abnormalities in caudal fossa morphology are considered major contributors to the development of this disease, limited information exists on the range of morphologies in Cavalier King Charles Spaniels and on the relationship of these to clinically evident disease. Sixty-four Cavalier King Charles Spaniels were studied. Each underwent a neurologic examination and magnetic resonance imaging of the cervical spine and brain. T2-weighted sagittal images were used to determine both the morphologic characteristics and volume of the caudal fossa in each dog. This volume was also analyzed as a percentage of total cranial cavity volume. Each attribute was correlated with neurological grade and presence of syringohydromyelia. Fifteen dogs had neurologic signs, and 59 had morphologic abnormalities of the craniocervical junction. While 27 dogs had syringohydromyelia, 13 of these were clinically normal. Cerebellar herniation and occipital dysplasia were common findings but were not associated with syringohydromyelia. Dorsal compressive lesions were noted at the first and second cervical vertebral junction. Factors associated with the presence of neurologic signs included syringohydromyelia and the ratio of caudal fossa/total cranial cavity volume; dogs with signs had significantly larger syringohydromyelia than asymptomatic dogs. Caudal fossa size was not associated with syringohydromyelia. A positive association was identified between foramen magnum size and length of cerebellar herniation. The prevalence of craniocervical junction abnormalities is high in Cavalier King Charles Spaniels. While several factors are associated with neurologic signs, occipital hypoplasia appears to be the most important factor.