Objective: To determine whether Border Collies (ATP binding cassette subfamily B1 gene [ABCB1] wildtype) were more likely than other breeds to develop vincristine-associated myelosuppression (VAM) and, if so, whether this was caused by a mutation in ABCB1 distinct from ABCB1-1Δ. Animals: Phase 1 comprised 36 dogs with the ABCB1 wildtype, including 26 dogs with lymphoma (5 Border Collies and 21 dogs representing 13 other breeds) treated with vincristine in a previous study; phase 2 comprised 10 additional Border Collies, including 3 that developed VAM and 7 with an unknown phenotype. Procedures: For phase 1, the prevalence of VAM in ABCB1-wildtype Border Collies was compared with that for ABCB1-wildtype dogs of other breeds with data from a previous study. For phase 2, additional Border Collies were included. Hematologic adverse reactions were graded with Veterinary Co-operative Oncology Group criteria. Genomic DNA was used to amplify and sequence all 27 exons of the canine ABCB1. Sequences from affected dogs were compared with those of unaffected dogs and dogs of unknown phenotype. Results: 3 of 5 Border Collies with the ABCB1 wildtype developed VAM; this was significantly higher than the proportion of other dogs that developed VAM (0/21). A causative mutation for VAM in Border Collies was not identified, although 8 single nucleotide polymorphisms in ABCB1 were detected. Conclusions and Clinical Relevance: Breed-associated sensitivity to vincristine unrelated to ABCB1 was detected in Border Collies. Veterinarians should be aware of this breed predisposition to VAM. Causes for this apparent breed-associated sensitivity should be explored.

Objective: To evaluate the cardiopulmonary effects of IV fentanyl administration in dogs during isoflurane anesthesia and during anesthetic recovery with or without dexmedetomidine or acepromazine. Animals: 7 sexually intact male purpose-bred hound-type dogs aged 11 to 12 months. Procedures: Dogs received a loading dose of fentanyl (5 μg/kg, IV) followed by an IV infusion (5 μg/kg/h) for 120 minutes while anesthetized with isoflurane and for an additional 60 minutes after anesthesia was discontinued. Dogs were randomly assigned in a crossover design to receive dexmedetomidine (2.5 μg/kg), acepromazine (0.05 mg/kg), or saline (0.9% NaCl) solution (1 mL) IV after anesthesia ceased. Cardiopulmonary data were obtained during anesthesia and for 90 minutes after treatment administration during anesthetic recovery. Results: Concurrent administration of fentanyl and isoflurane resulted in significant decreases in mean arterial blood pressure, heart rate, and cardiac index and a significant increase in Paco2. All but Paco2 returned to pretreatment values before isoflurane anesthesia was discontinued. During recovery, dexmedetomidine administration resulted in significant decreases in heart rate, cardiac index, and mixed venous oxygen tension and a significant increase in arterial blood pressure, compared with values for saline solution and acepromazine treatments. Acepromazine administration resulted in significantly lower blood pressure and higher cardiac index and Po2 in mixed venous blood than did the other treatments. Dexmedetomidine treatment resulted in significantly lower values for Pao2 and arterial pH and higher Paco2 values than both other treatments. Conclusions and Clinical Relevance: Fentanyl resulted in transient pronounced cardiorespiratory effects when administered during isoflurane anesthesia. During anesthetic recovery, when administered concurrently with an IV fentanyl infusion, dexmedetomidine resulted in evidence of cardiopulmonary compromise and acepromazine transiently improved cardiopulmonary performance.

Objective: To evaluate protein expression in bronchoalveolar lavage fluid (BALF) obtained from West Highland White Terriers with idiopathic pulmonary fibrosis (IPF), dogs with chronic bronchitis, and healthy control dogs to identify potential biomarkers for IPF. Samples: BALF samples obtained from 6 West Highland White Terriers with histologically confirmed IPF, 5 dogs with chronic bronchitis, and 4 healthy Beagles. Procedures: Equal amounts of proteins in concentrated BALF samples were separated via 2-D differential gel electrophoresis. Proteins that were differentially expressed relative to results for healthy control dogs were identified with mass spectrometry and further verified via western blotting. Results: Expression of 6 proteins was upregulated and that of 1 protein was downregulated in dogs with IPF or chronic bronchitis, compared with results for healthy dogs. Expression of proteins β-actin, complement C3, α-1-antitrypsin, apolipoprotein A-1, haptoglobin, and transketolase was upregulated, whereas expression of lysozyme C was downregulated. Conclusions and Clinical Relevance: Proteomics can be used to search for biomarkers and to reveal disease-specific mechanisms. The quantitative comparison of proteomes for BALF obtained from dogs with IPF and chronic bronchitis and healthy dogs revealed similar changes for the dogs with IPF and chronic bronchitis, which suggested a common response to disease processes in otherwise different lung diseases. Specific biomarkers for IPF were not identified.

Objective: To identify proteins with differential expression between healthy dogs and dogs with stifle joint osteoarthritis secondary to cranial cruciate ligament (CCL) disease. Sample: Serum and synovial fluid samples obtained from dogs with stifle joint osteoarthritis before (n = 10) and after (8) surgery and control dogs without osteoarthritis (9) and archived synovial membrane and articular cartilage samples obtained from dogs with stifle joint osteoarthritis (5) and dogs without arthritis (5). Procedures: Serum and synovial fluid samples were analyzed via liquid chromatography–tandem mass spectrometry; results were compared against a nonredundant protein database. Expression of complement component 3 in archived tissue samples was determined via immunohistochemical methods. Results: No proteins had significantly different expression between serum samples of control dogs versus those of dogs with stifle joint osteoarthritis. Eleven proteins (complement component 3 precursor, complement factor I precursor, apolipoprotein B-100 precursor, serum paraoxonase and arylesterase 1, zinc-alpha-2-glycoprotein precursor, serum amyloid A, transthyretin precursor, retinol-binding protein 4 precursor, alpha-2-macroglobulin precursor, angiotensinogen precursor, and fibronectin 1 isoform 1 preproprotein) had significantly different expression (> 2.0-fold) between synovial fluid samples obtained before surgery from dogs with stifle joint osteoarthritis versus those obtained from control dogs. Complement component 3 was strongly expressed in all (5/5) synovial membrane samples of dogs with stifle joint osteoarthritis and weakly expressed in 3 of 5 synovial membrane samples of dogs without stifle joint arthritis. Conclusions and Clinical Relevance: Findings suggested that the complement system and proteins involved in lipid and cholesterol metabolism may have a role in stifle joint osteoarthritis, CCL disease, or both.

Objective: To evaluate associations between economic and performance outcomes with the number of treatments after an initial diagnosis of bovine respiratory disease (BRD) in commercial feedlot cattle. Animals: 212,867 cattle arriving in a Midwestern feedlot between 2001 and 2006. Procedures: An economic model was created to estimate net returns. Generalized linear mixed models were used to determine associations between the frequency of BRD treatments and other demographic variables with economic and performance outcomes. Results: Net returns decreased with increasing number of treatments for BRD. However, the magnitude depended on the season during which cattle arrived at the feedlot, with significantly higher returns for cattle arriving during fall and summer than for cattle arriving during winter and spring. For fall arrivals, there were higher mean net returns for cattle that were never treated ($39.41) than for cattle treated once ($29.49), twice ($16.56), or ≥ 3 times (−$33.00). For summer arrivals, there were higher least squares mean net returns for cattle that were never treated ($31.83) than for cattle treated once ($20.22), twice ($6.37), or ≥ 3 times ($−42.56). Carcass traits pertaining to weight and quality grade were deemed responsible for differences in net returns among cattle receiving different numbers of treatments after an initial diagnosis of BRD. Conclusions and Clinical Relevance: Differences in economic net returns and performance outcomes for feedlot cattle were determined on the basis of number of treatments after an initial diagnosis of BRD; the analysis accounted for the season of arrival, sex, and weight class.

Objective-To evaluate the pharmacokinetics of diazepam administered per rectum via compounded (ie, not commercially available) suppositories and determine whether a dose of 2 mg/kg in this formulation would result in plasma concentrations shown to be effective for control of status epilepticus or cluster seizures (ie, 150 to 300 ng/mL) in dogs within a clinically useful interval (10 to 15 minutes). Animals-6 healthy mixed-breed dogs. Procedures-Dogs were randomly assigned to 2 groups of 3 dogs each in a crossover-design study. Diazepam (2 mg/kg) was administered IV or via suppository per rectum, and blood samples were collected at predetermined time points. Following a 6- or 7-day washout period, each group received the alternate treatment. Plasma concentrations of diazepam and nordiazepam were analyzed via reversed phase high-performance liquid chromatography. Results-Plasma concentrations of diazepam and nordiazepam exceeded the targeted range ≤ 3 minutes after IV administration in all dogs. After suppository administration, targeted concentrations of diazepam were not detected in any dogs, and targeted concentrations of nordiazepam were detected after 90 minutes (n = 2 dogs) or 120 minutes (3) or were not achieved (1). Conclusions and Clinical Relevance-On the basis of these results, administration of 2 mg of diazepam/kg via the compounded suppositories used in the present study cannot be recommended for emergency treatment of seizures in dogs.

Objective-To determine the effect of biopsy collection depth on the postprandial activation of mammalian target of rapamycin (mTOR) signaling factors, particularly protein kinase B, ribosomal protein S6 kinase, ribosomal protein S6, and eukaryotic initiation factor 4E binding protein 1 in middle-aged horses. Animals-6 healthy Thoroughbred mares (mean +/- SD age, 13.4 +/- 3.4 years). Procedures-Horses were fed a high-protein feed at 3 g/kg. Sixty minutes after horses were fed, the percutaneous needle biopsy technique was used to collect biopsy specimens from the gluteus medius muscle at 6, 8, and 10 cm below the surface of the skin. Muscle specimens were analyzed for the activation of upstream and downstream mTOR signaling factors, myosin heavy chain (MHC) isoform composition, and amino acid concentrations. Results-A 21% increase in MHC IIA isoform expression and a 21% decrease in MHC IIX isoform expression were identified as biopsy depth increased from 8 to 10 cm below the surface of the skin; however, no significant change was evident in the degree of MHC I expression with muscle depth. Biopsy depth had no significant effect on the phosphorylation of any of the mTOR signaling factors evaluated. Conclusions and Clinical Relevance-Postprandial mTOR signaling could be compared between middle-aged horses when biopsy specimens were collected between 6 and 10 cm below the surface of the skin. Optimization of muscle biopsy techniques for evaluating mTOR signaling in horses will facilitate the design of future investigations into the factors that regulate muscle mass in horses.

Objective-To investigate whether differences existed between clinically normal dogs and dogs with goniodysgenesis-related glaucoma (GDRG) in serum autoantibodies against optic nerve antigens. Animals-16 dogs with GDRG, 17 healthy dogs with unremarkable pectinate ligament and iridocorneal angle morphology, and 13 euthanized dogs with no major ocular abnormalities or underlying diseases. Procedures-Western blotting was performed with optic nerve extracts from the euthanized dogs as an antigen source and serum from clinically normal dogs and dogs with GDRG as a primary antibody (autoantibody) source. Blots were evaluated for presence and density of bands. Results-Multiple bands were identified on western blots from all dogs with GDRG and all clinically normal dogs, with a high degree of variability among individual dogs. Dogs with GDRG were significantly more likely than healthy dogs to have bands present at 38, 40, and 68 kDa. Dogs with GDRG had significant increases in autoreactivity at 40 and 53 kDa and a significant decrease in autoreactivity at 48 kDa. Conclusions and Clinical Relevance-Significant differences in serum autoantibodies against optic nerve antigens were found in dogs with versus without GDRG. Although it remains unclear whether these differences were part of the pathogenesis of disease or were sequelae to glaucomatous changes, these findings provide support for the hypothesis that immune-mediated mechanisms play a role in the development or progression of GDRG. However, the high degree of variability among individual dogs and the considerable overlap between groups suggest that the clinical usefulness of this technique for distinguishing dogs with GDRG from clinically normal dogs is likely limited.

A small population of resident T-lymphocytes is present in the normal epidermis of skin from humans, mice, sheep, and cattle. The objective of this study was to determine the prevalence of lymphocytes, CD3+ cells (T-lymphocytes) and CD79a+ cells (B-lymphocytes and plasma cells), in the epidermis and adnexal epithelia of alpacas. Skin-biopsy specimens from the normal skin of the dorsolateral thorax of 31 alpacas were examined histologically and immunohistochemically for the presence of CD3+ cells and CD79a+ cells in the epidermis and adnexal epithelia. CD3+ T-lymphocytes, but not CD79a+ cells, were present in the epidermis and adnexal epithelia. Therefore, in the absence of other signs of inflammation, the presence of lymphocytes in these structures in skin-biopsy specimens should be considered normal.

Objective-To determine the maximum amount of flexion and extension of the carpal, tarsal, metacarpophalangeal, and metatarsophalangeal joints and the percentage duration of the stance and swing phases of the stride for horses walking on an underwater treadmill in various water depths. Animals-9 healthy adult horses. Procedures-Zinc oxide markers were placed on the forelimbs and hind limbs of the horses. Video was recorded of horses walking (0.9 m/s) on an underwater treadmill during baseline conditions (< 1 cm of water) or in various amounts of water (level of the metatarsophalangeal, tarsal, and stifle joints). Maximum amount of joint flexion and extension, range of motion (ROM), and the percentage durations of the stance and swing phases of the stride were determined with 2-D motion analysis software. Results-The ROM was greater for all evaluated joints in any amount of water versus ROM for joints in baseline conditions (primarily because of increases in amount of joint flexion). The greatest ROM for carpal joints was detected in a tarsal joint water depth, for tarsal joints in a stifle joint water depth, and for metacarpophalangeal and metatarsophalangeal joints in metatarsophalangeal and tarsal joint water depths. As water depth increased, the percentage durations of the stance and swing phases of the stride significantly decreased and increased, respectively. Conclusions and Clinical Relevance-Results of this study suggested that exercise on an underwater treadmill is useful for increasing the ROM of various joints of horses during rehabilitation and that the depth of water affects the amount of flexion and extension of joints.