The objective of this retrospective study was to evaluate the expression of receptor tyrosine kinases (RTKs) in canine adrenal tumors and correlate this expression with features of tumor aggressiveness and survival in dogs undergoing adrenalectomy. Forty-three canine adrenal tumors were evaluated for expression of c-kit, fms-like tyrosine kinase 3 (flt-3), platelet-derived growth factor receptor-β (PDGFR-β), and vascular endothelial growth factor receptor 2 (VEGFR2) using immunohistochemistry. Tumor RTK staining characteristics were compared to normal adrenals. Medical records were reviewed for data regarding patient outcome and tumor characteristics. Expression of c-kit, flt-3, PDGFR-β, and VEGFR2 was detected in 26.9%, 92.3%, 96.2%, and 61.5% of cortical tumors and 0%, 63.2%, 47.4%, and 15.8% of pheochromocytomas, respectively. Expression of RTKs was not significantly increased when compared to normal adrenals and did not correlate with survival after adrenalectomy. Receptor tyrosine kinases are not overexpressed in canine adrenal tumors compared to normal adrenal tissue. Therapeutic inhibition of these receptors may still represent an effective approach in cases where receptor activation is present.

OBJECTIVE To determine the in vitro effects of epinephrine, norepinephrine, and dobutamine on lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in blood from healthy dogs. SAMPLES Blood samples from 9 healthy dogs. PROCEDURES Blood samples were incubated with LPS from Escherichia coli O127:B8 or PBSS (control) for 1 hour. Afterward, the samples were incubated with 10μM epinephrine, norepinephrine, or dobutamine or with saline (0.9% NaCl) solution (control) for 23 hours. Leukocyte viability was assessed by use of trypan-blue exclusion in blood from 2 dogs to ensure cell viability was not altered by the catecholamines. Tumor necrosis factor-α, IL-6, and IL-10 concentrations were measured in the supernatant in duplicate with a canine-specific multiplex bead-based assay. Blood samples from 2 dogs were used to create dose-response curves to evaluate whether the observed cytokine modulation was dependent on catecholamine concentration. RESULTS Incubation of blood with epinephrine and norepinephrine significantly increased LPS-stimulated production of IL-10, compared with the control. Epinephrine and norepinephrine significantly decreased LPS-stimulated production of TNF-α, compared with the control. Epinephrine and norepinephrine did not significantly alter LPS-stimulated production of IL-6. Dobutamine did not alter catecholamine production. CONCLUSIONS AND CLINICAL RELEVANCE Epinephrine and norepinephrine, but not dobutamine, had immunomodulatory effects on LPS-stimulated TNF-α and IL-10 production in blood from healthy dogs in this in vitro model of sepsis. Data suggested that dobutamine may have immune system-sparing effects in dogs with sepsis.

In humans and other mammals, general anesthesia impairs thermoregulation, leading to warm core blood redistributing to the periphery. This redistribution is an important contributor to hypothermia that can be reduced with pre-warming before anesthesia. Additionally, sedation following premedication has been associated with hypothermia in dogs. In a prospective, randomized, cross-over study, 8 adult male and female rats (weighing 388 to 755 g) were sedated with intramuscular ketamine-midazolam-hydromorphone, then placed in an unwarmed cage or warmed box for 14 minutes, followed by 30 minutes of isoflurane anesthesia with active warming. Core body temperature was monitored throughout. After sedation, warmed rats gained 0.28°C ± 0.13°C and unwarmed rats lost 0.19°C ± 0.43°C, a significant difference between groups (P = 0.004). After anesthesia, warmed rats maintained higher core temperatures (P < 0.0001) with 2/8 and 6/8 of warmed and unwarmed rats becoming hypothermic, respectively. Pre-warming during sedation and active warming during general anesthesia is effective in minimizing hypothermia.

OBJECTIVE To evaluate whether cell-based and tissue-based immunofluorescent assays (IFAs) run in parallel could be used to detect glial fibrillary acidic protein (GFAP) autoantibodies in the CSF of dogs with meningoencephalitis of unknown origin (MUO) and other CNS disorders ANIMALS 15 CSF samples obtained from dogs with presumed MUO (n = 5), CNS disease other than MUO (5), and idiopathic epilepsy (5). PROCEDURES All CSF samples underwent parallel analysis with a cell-based IFA that targeted the α isoform of human GFAP and a tissue-based IFA that involved mouse brain cryosections. Descriptive data were generated. RESULTS Only 1 CSF sample yielded mildly positive results on the cell-based IFA; that sample was from 1 of the dogs with presumed MUO. The remaining 14 CSF samples tested negative on the cell-based IFA. All 15 CSF samples yielded negative results on the tissue-based IFA. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that concurrent use of a cell-based IFA designed to target the human GFAP-α isoform and a tissue-based IFA that involved mouse tissue cryosections was inadequate for detection of GFAP autoantibodies in canine CSF samples. Given that GFAP autoantibodies were likely present in the CSF samples analyzed, these findings suggested that epitopes differ substantially between canine and human GFAP and that canine GFAP autoantibody does not bind to mouse GFAP. Without a positive control, absence of GFAP autoantibody in this cohort cannot be ruled out. Further research is necessary to develop a noninvasive and sensitive method for diagnosis of MUO in dogs.

Although glucocorticoid administration has produced impressive results in treating canine mast cell tumors (MCTs), in some cases, glucocorticoids fail to reduce the tumor volume, leading to tumor relapse even after treatment. To date, mechanisms involved in glucocorticoid resistance in canine MCTs remain poorly defined. The objective of this study was to establish glucocorticoid-resistant canine MCT cell lines derived from glucocorticoid-sensitive cell lines after prolonged treatment with dexamethasone (Dex). Real-time polymerase chain reaction (RT-PCR) revealed that elevation of glucocorticoid receptor (GR)-regulated gene expression was suppressed in Dex-resistant cell lines after Dex stimulation compared with parent Dex-sensitive cell lines. This indicated that GR-regulated transcription was suppressed in Dex-resistant cell lines. Insufficient expression of GRs was not detected in Dex-resistant cell lines. Possible inhibitors of GR-regulated transcription were increased in mRNA expression in Dex-resistant cell lines. In addition, it was determined that mRNA expression of drug efflux pumps and anti-apoptosis factors was higher in Dex-resistant cell lines. In conclusion, glucocorticoid-resistant canine MCT cell lines have been established that are derived from glucocorticoid-sensitive cell lines. These cell lines suggest that multiple mechanisms contribute to glucocorticoid resistance in canine MCT cells. The mechanisms of glucocorticoid resistance after long-term treatment can be further investigated using these cell lines and a novel therapeutic strategy for glucocorticoid-resistant canine MCT cells can be developed.

OBJECTIVE To investigate the effects of orally administered trazodone on intraocular pressure (IOP), pupil diameter measured in the vertical plane (ie, vertical pupil diameter [VPD]), selected physical examination variables, and sedation level in healthy equids. ANIMALS 7 horses and 1 pony. PROCEDURES Food was withheld for 12 hours prior to drug administration. After baseline (time 0) sedation scoring, physical examination, and measurement of IOP and VPD, equids received 1 dose (approx 6 mg/kg) of trazodone orally. Examination and measurement procedures were repeated 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Blood samples were collected at each time point for analysis of plasma trazodone concentrations. Repeated-measures analysis was used to compare examination results between downstream time points and baseline. RESULTS 7 of 8 equids had mild sedation from 0.5 to 8 hours after treatment; compared with baseline values, mean IOP was significantly lower from 0.5 hours to 8 hours, mean VPD was significantly smaller at 0.5 hours, and mean rectal temperature was significantly lower from 1 to 8 hours after drug administration. Adverse effects (signs of excitement in 1 equid and sweating in 4) were self-limiting and considered minor. Mean maximum plasma concentration of trazodone was 1,493 ng/mL 0.75 hours after administration, and terminal half-life of the drug was 9.96 hours. CONCLUSIONS AND CLINICAL RELEVANCE The described oral dose of trazadone elicited sedation with a few self-limiting adverse effects in the study sample. Drug effects on IOP and VPD may alter ocular examination findings. Further investigation is warranted prior to use of trazodone for sedation in equids, particularly those with ophthalmic conditions.

Dogs with lower airway pathology that present in respiratory distress often receive oxygen therapy as the first line of treatment regardless of the underlying cause. Conventional "low-flow" systems deliver oxygen with a maximum flow rate of 15 L/minute. Traditionally, when an animal's respiratory status does not improve with conventional oxygen therapy and treatments for underlying disease, options might be limited to either intubation and mechanical ventilation or humane euthanasia. High-flow oxygen therapy (HFOT) has been gaining popularity in veterinary medicine as an alternative route of oxygen supplementation for animals that require support beyond conventional therapy. High-flow oxygen therapy can supply a mixture of air and oxygen via a heated and humidified circuit. It is user friendly and can be used in an environment in which mechanical ventilation is unavailable. This review article is written for emergency doctors and general practitioners who lack access to mechanical ventilation. This article briefly reviews pertinent respiratory physiology, traditional oxygen supplementation techniques, the physiology of HFOT, and the limited evidence available in veterinary medicine regarding the use of HFOT, its applications, and limitations. Guidelines for the use of HFOT are suggested and HFOT is compared to conventional therapy.

OBJECTIVE To evaluate the ability of novel legwear designed to limit extension of the metacarpophalangeal joint (MCPJ) to redirect loading forces from the flexor apparatus during walk, trot, and canter on a treadmill and during unrestrained and restrained activity in a stall. ANIMALS 6 adult horses without musculoskeletal disease. PROCEDURES Legwear-derived force data were recorded under 4 conditions: inactive state (unlimited legwear extension) and 3 active (restrictive) states (mild, 30° extension; moderate, 20° extension; or maximum, 10° extension). Associations between peak legwear loads and torques among legwear states and treadmill gaits and stall activities were assessed. The hair coat and skin of the forelimbs were examined for any legwear-induced adverse effects after testing. RESULTS During the treadmill exercises, moderate restriction of legwear extension resulted in significantly higher peak load and torque than mild restriction, and faster speeds (canter vs walk or trot and trot vs walk) yielded significantly higher peak load and torque. During in-stall activity, maximum restriction of legwear extension yielded significantly higher peak load and torque than moderate restriction. Unrestrained in-stall activity resulted in significantly higher peak load and torque than restrained activity. The legwear caused minimal adverse effects on the hair coat and skin of the forelimbs. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that the legwear variably reduced peak loads on the flexor apparatus. Extension of the MCPJ may be incrementally adjusted through the legwear such that return to activity may be controlled, and controlled return to activity is crucial for rehabilitating flexor apparatus injuries.

OBJECTIVE To compare efficacy and duration of desensitization of oral structures with a lidocaine-bupivacaine mixture administered via a lateral percutaneous or modified infraorbital approach. ANIMALS 6 healthy adult hound-type female dogs. PROCEDURESIn this crossover study, dogs were randomized for side (left or right) and maxillary nerve approach (lateral percutaneous or infraorbital), with a 2-week washout period. Dogs were anesthetized, and a 2-mL mixture of 2% lidocaine and 0.5% bupivacaine (50:50 [vol/vol]) was administered with a 22-gauge, 4.5-cm-long catheter inserted through the infraorbital canal (infraorbital approach) or with a shielded stimulating needle to the maxillary nerve (percutaneous approach). Reflex-evoked motor potentials were measured for the maxillary canine tooth, fourth premolar tooth, second molar tooth, and hard palate mucosa ipsilateral to the injected mixture and for the contralateral maxillary canine tooth (control) at three 10-minute intervals before injection (baseline) and at predetermined times after injection for up to 6.7 hours. For each oral structure, the proportion of dogs with desensitization (efficacy) and time to onset and duration of desensitization were compared between approaches. RESULTS The proportion of dogs with successful nerve blockade did not significantly differ between infraorbital and percutaneous approaches and among the 4 oral structures. Time to onset of desensitization did not differ between approaches, but duration was significantly longer with the infraorbital approach. CONCLUSIONS AND CLINICAL RELEVANCE A modified infraorbital approach with the lidocaine-bupivacaine mixture had similar effects to a lateral percutaneous approach but provided a longer duration of desensitization. Neither approach was universally successful at desensitizing all oral structures.

OBJECTIVE To assess the effect of horseshoes with and without traction adaptations on the gait kinetics of nonlame horses during a trot on a concrete runway. ANIMALS 5 nonlame adult light-breed horses. PROCEDURES Kinetic data were obtained for each horse when it was trotted across a force platform within a concrete runway unshod (control) and shod with standard horseshoes; standard horseshoes with high profile–low surface area calks, with low profile–high surface area calks, and coated with a thin layer of tungsten carbide (TLTC); and plastic-steel composite (PSC) horseshoes. Kinetic data were obtained for the control treatment first, then for each of the 5 shoe types, which were applied to each horse in a random order. Kinetic variables were compared among the 6 treatments. RESULTS Body weight distribution did not differ among the 6 treatments. Compared with the control, the greatest increase in forelimb peak vertical force was observed when horses were shod with PSC shoes. In the hind limbs, the greatest increase in peak braking force was observed when horses were shod with PSC shoes, followed by the TLTC and low profile–high surface area calked shoes. The PSC shoes yielded the greatest coefficient of friction in both the forelimbs and hind limbs. Stance time was longest when horses were shod with standard shoes. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that PSC and TLTC shoes provided the best hoof protection and traction and might be good options for horses that spend a large amount of time traversing paved surfaces.