Objective: To evaluate use of a radiolabeled peptide nucleic acid–peptide conjugate (RaPP) targeting B-cell leukemia-lymphoma 2 (BCL2) mRNA for scintigraphic detection of neoplastic lymphocytes in dogs with B-cell lymphoma and to assess associations among RaPP uptake, time to tumor progression (TTP), and BCL2 mRNA expression. Animals: 11 dogs with B-cell lymphoma and 1 clinically normal dog. Procedures: Scintigraphic images were acquired 1 hour after IV injection of the RaPP. Regions of interest (ROIs) were drawn around lymph nodes, liver, and spleen; ROI intensity (relative to that of an equally sized region of muscle in the same image) was measured. Each ROI was also subjectively categorized as positive or negative for increased RaPP uptake. Expression of BCL2 mRNA was determined via quantitative reverse transcriptase PCR assay of a lymph node sample from dogs with lymphoma. Associations among imaging results, TTP, and BCL2 mRNA expression were evaluated. Results: Increased RaPP uptake was detected in affected tissues of dogs with lymphoma. Dogs with superficial cervical lymph node ROIs categorized as negative (n = 8) for increased RaPP uptake had a significantly longer TTP than did dogs for which this ROI was considered positive (2). Measured intensity of mandibular and superficial cervical lymph node ROIs was negatively associated with TTP. Associations among BCL2 mRNA and ROI intensity or TTP were not significant. Conclusions and Clinical Relevance: Increased RaPP uptake at mandibular or superficial cervical lymph node ROIs may be a negative prognostic indicator in dogs with lymphoma. A larger investigation is needed to determine clinical value of the RaPP for disease detection and prognostication.

Objective: To assess long-term effects and risk factors for the efficacy of hyperimmunization protocols against infectious bovine rhinotracheitis (IBR) during a longitudinal field study of dairy and dairy-beef mixed farms. Animals: Approximately 7,700 cows from 72 farms. Procedures: Farms were assigned to 3 treatment groups (hyperimmunization groups [HIGs] 1 and 2, which were hyperimmunized with glycoprotein E [gE]–deleted marker vaccines, and a nonintervention group [NIG]). Cattle in HIG 1 were initially vaccinated with an attenuated vaccine, whereas cattle in HIG 2 were initially vaccinated with an inactivated-virus vaccine. Cattle in both HIGs received booster inoculations with inactivated-virus vaccines at 6-month intervals. The risk for gE seroconversion was compared among experimental groups via a shared frailty model with a piecewise constant baseline risk to correct for seasonal and secular effects. Results: Risk for gE seroconversion significantly decreased over time for the HIGs, compared with the NIG. Seasonal changes in the risk of gE seroconversion were detected, with a higher risk during winter periods, compared with grazing periods. No significant difference was detected between HIGs 1 and 2. The only significant risk factor was the number of buildings for cattle on a farm; the higher the number of buildings, the lower the risk for gE seroconversion. Prevalence of IBR decreased over time in both HIGs but remained constant or increased in the NIG. Conclusions and Clinical Relevance: Hyperimmunization via repeated administration of attenuated and inactivated-virus gE-deleted marker vaccines as well as inactivated-virus vaccines may provide a method for control of IBR.

Objective: To determine whether incubation of cruciate ligament cells with acetylsalicylic acid, carprofen, meloxicam, or robenacoxib provides protection against apoptosis induced by sodium nitroprusside (SNP). Sample: Explants of cranial (CCL) and caudal (CaCL) cruciate ligaments from eight 1-day-old Beagles. Procedures: Primary cultures of CCL and CaCL cells were created via enzymatic dissociation of cruciate explants. Purified cell cultures were incubated for 2 hours without (controls) or with 1 of 3 concentrations of 1 of 4 NSAIDs (10, 100, or 200 μg of acetylsalicylic acid/mL; 0.1, 1, or 10 μg of carprofen/mL; 0.1, 1, or 10 μg of meloxicam/mL; or 0.1, 1, or 10 μg of robenacoxib/mL) and subsequently incubated for 18 hours with 1 of 3 concentrations of SNP in an attempt to induce mild, moderate, or severe cytotoxic effects. Cell viability and apoptosis were analyzed via a cell proliferation assay and flow cytometry, respectively. Prostaglandin E2 concentrations were measured via an ELISA. Results: Cytoprotective effects of NSAIDs were dependent on the extent of SNP-induced apoptosis and were greatest in CCL and CaCL cell cultures with moderate SNP-induced cytotoxic effects. Preincubation with an NSAID improved cell viability by 15% to 45% when CCL and CaCL cells were subsequently incubated with SNP. Carprofen (10 μg/mL) had the greatest cytoprotective effects for CCL and CaCL cells. Incubation with NSAIDs resulted in a nonsignificant decrease in PGE2 production from SNP-damaged cells. Conclusions and Clinical Relevance: Results indicated that carprofen, meloxicam, and robenacoxib may reduce apoptosis in cells originating from canine cruciate ligaments.

Objective: To investigate contrast-enhanced ultrasonography as a minimally invasive method for the subjective and quantitative assessment of pancreatic and duodenal perfusion in healthy adult dogs, with reference to perfusion in adjacent liver tissue. Animals: 8 clinically normal adult dogs. Procedures: Contrast-enhanced ultrasonograms of the right pancreatic limb, proximal portion of the descending duodenum, and adjacent liver were acquired after IV administration of a microbubble contrast medium. Following subjective evaluation, quantitative time-intensity curves were generated from regions of interest in the pancreas, duodenum, and liver. Five contrast medium characteristics representing perfusion parameters were determined for each organ and used for statistical analysis: interval to arrival, inflow rate, peak intensity (PI), time of peak intensity (TPI), and outflow rate. Results: Significant associations between pancreatic and duodenal values were found for interval to contrast medium arrival, PI, TPI, and outflow rate. Pancreatic and duodenal inflow rates were not correlated. Inflow and outflow rates were significantly faster and TPI significantly shorter for the pancreas and duodenum, compared with values for the liver. There was no significant difference among all 3 organs for interval to arrival and PI of contrast medium. Subjective evaluation findings corresponded to quantitative analysis results. Conclusions and Clinical Relevance: Results suggested that contrast-enhanced ultrasonography may be a useful, minimally invasive method for evaluating pancreatic and duodenal perfusion in dogs. The data from healthy dogs reported here could aid in the assessment of pancreatic and duodenal conditions and their response to medical treatment.

Objective: To compare the axial stiffness, maximum axial displacement, and ring deformation during axial loading of single complete and incomplete circular (ring) external skeletal fixator constructs. Sample: 32 groups of single ring constructs (5 constructs/group). Procedures: Single ring constructs assembled with 2 divergent 1.6-mm-diameter Kirschner wires were used to stabilize a 60-mm-long segment of 16-mm-diameter acetyl resin rod. Construct variables included ring type (complete or incomplete), ring diameter (50, 66, 84, or 118 mm), and fixation wire tension (0, 30, 60, or 90 kg). Axial loading was performed with a materials testing system. Construct secant stiffness and maximum displacement were calculated from the load-displacement curves generated for each construct. Ring deformation was calculated by comparing ring diameter during and after construct loading to ring diameter prior to testing. Results: Complete ring constructs had greater axial stiffness than did the 66-, 84-, and 118-mm-diameter incomplete ring constructs. As fixation wire tension increased, construct stiffness increased in the 66-, 84-, and 118-mm-diameter incomplete ring constructs. Maximum axial displacement decreased with increasing fixation wire tension, and complete ring constructs allowed less displacement than did incomplete ring constructs. Incomplete rings were deformed by wire tensioning and construct loading. Conclusions and Clinical Relevance: Mechanical performance of the 66-, 84-, and 118-mm-diameter incomplete ring constructs improved when wire tension was applied, but these constructs were not as stiff as and allowed greater displacement than did complete ring constructs of comparable diameter. For clinical practice, tensioning the wires placed on 84- and 118-mm-diameter incomplete rings to 60 kg is recommended.

Objective: To evaluate intraday and interday variations in glucose concentrations in cats and to test the utility of a continuous glucose monitoring system (CGMS). Animals: 6 lean and 8 long-term (> 5 years) obese cats. Procedures: Blood glucose concentrations were measured during the course of 156 hours by use of a laboratory hexokinase-based reference method and a handheld glucometer. Interstitial glucose concentrations were evaluated with a CGMS. Results: Paired measures of glucose concentrations obtained with the CGMS typically were marginally higher than concentrations for the reference method and less biased than concentrations obtained with the glucometer. This was partially confirmed by the concordance correlation coefficients of the concentration for the CGMS or glucometer versus the concentration for the reference method, although the correlation coefficients were not significantly different. Mean ± SD area under the curve for the glucose concentration (AUCG) did not differ significantly between lean (14.0 ± 0.5 g/dL•h) and obese (15.2 + 0.5 g/dL•h) cats during the 156-hour period, but one of the obese cats had a much higher AUCG. Within-day glucose variability was small in both lean and obese cats. Conclusions and Clinical Relevance: Glucose homeostasis was maintained, even in long-term obese cats, and intraday glucose fluctuations were small. One obese cat might have been classified as prediabetic on the basis of the AUCG, which was approximately 25% higher than that of the other obese and lean cats. The CGMS can be useful in the evaluation of long-term effects of drugs or diet on glucose homeostasis in cats.

Objective: To compare the ability of 2 partial IV anesthesia (PIVA) techniques to maintain anesthesia, compared with isoflurane alone, in horses. Animals: 45 horses. Procedures: Client-owned horses requiring general anesthesia for a variety of procedures of at least 1 hour's duration were randomly allocated to 3 groups (n = 15/group) that differed for the maintenance protocol. Anesthesia was maintained with isoflurane with a starting end-tidal isoflurane concentration of 1.3% (isoflurane group) or a concentration of 1% supplemented with an adjustable continuous infusion of guaifenesin-ketamine (IGK group) or romifidine-ketamine (IRK group). A predefined scoring system was used to assess anesthetic depth and to adjust anesthetic delivery. The need for rescue anesthetics and recovery quality were compared. Results: A mean ± SD end-tidal isoflurane concentration of 1.36 ± 0.16% was necessary to maintain a surgical plane of anesthesia in the isoflurane group. Mean infusion rates of 5.0 ± 1.3 μL/kg/min and 5.1 ± 0.8 μL/kg/min were necessary to maintain a surgical plane of anesthesia in the IRK and IGK groups, respectively. A lower need for ketamine as a rescue anesthetic was observed in the IGK group, compared with the isoflurane group. Higher blood pressure and lower heart rates were found at selected time points for the IRK group, compared with the IGK and isoflurane groups. Conclusions and Clinical Relevance: Both PIVA protocols were satisfactory to maintain smooth and stable surgical anesthesia in horses. The present study supports previous findings in which PIVA has isoflurane-sparing effects. Furthermore, PIVA did not impair recovery quality.

Objective: To determine expression of microRNA (miRNA) in urinary bladder samples obtained from dogs with grossly normal urinary bladders, inflammatory bladder disease, or transitional cell carcinoma (TCC) and in cells of established canine TCC cell lines. Sample: Samples of grossly normal bladders (n = 4) and bladders from dogs with inflammatory bladder disease (13) or TCC (18), and cells of 5 established canine TCC cell lines. Procedures: Expression of 5 miRNAs (miR-34a, let-7c, miR-16, miR-103b, and miR-106b) that target p53, Rb, or Bcl-2 protein pathways was determined for bladder samples and cells via quantitative real-time PCR assay. Effects of cisplatin (5μM) on proliferation and miRNA expression of cells were determined. Results: Expression of miR-34a and miR-106b was significantly higher in TCC samples than it was in samples of grossly normal bladders. Expression of miR-34a, miR-16, miR-103b, and miR-106b was higher in TCC samples than it was in bladder samples from dogs with inflammatory bladder disease. Cells of established canine TCC cell lines that had the lowest growth after cisplatin treatment had increased miR-34a expression after such treatment. Conclusions and Clinical Relevance: Findings of this study indicated results of miRNA expression assays can be used to distinguish between samples of grossly normal bladders and bladders of dogs with inflammatory bladder disease or TCC. This finding may have clinical relevance because currently available diagnostic tests cannot be used to differentiate these tissues, and inflammatory bladder disease and TCC are both prevalent in dogs. Validation of miRNA expression assays as diagnostic tests may be warranted.

Objective: To evaluate the pharmacokinetics and pharmacodynamics of zolpidem after oral administration of a single dose (0.15 or 0.50 mg/kg) and assess any associated antianxiety and sedative effects in dogs. Animals: 8 clinically normal sexually intact male dogs of various breeds. Procedures: Dogs were assigned to 2 groups (4 dogs/group) and administered zolpidem orally once at a dose of 0.15 or 0.50 mg/kg in a crossover study; each dog received the other treatment once after an interval of 1 week. Blood samples were collected before and at intervals during the 24-hour period following dose administration. For each time point, plasma zolpidem concentration was evaluated via a validated method of high-performance liquid chromatography coupled with fluorescence detection, and pharmacodynamics were assessed via subjective assessments of sedation and level of agitation and selected clinical variables. Results: The pharmacokinetic profile of zolpidem in dogs was dose dependent, and the plasma drug concentrations attained were lower than those for humans administered equivalent doses. The lower dose did not result in any clinical or adverse effects, but the higher dose generated paradoxical CNS stimulation of approximately 1 hour's duration and a subsequent short phase of mild sedation. This sedation phase was not considered to be of clinical relevance. The desired clinical effects were not evident at plasma zolpidem concentrations ≤ 30 ng/mL, and the minimal plasma concentration that induced adverse effects was 60 ng/mL. Conclusions and Clinical Relevance: Results indicated that zolpidem is not a suitable drug for inducing sedation in dogs.

Objective: To compare effects of sterilization with hydrogen peroxide gas plasma (HPGP), ethylene oxide, and steam on bioadhesive properties of nylon and polyethylene lines used for stabilization of canine stifle joints. Sample: Samples of a 36.3-kg test nylon leader line, 57.8-kg test nylon fishing line, and 2-mm ultrahigh–molecular weight polyethylene (UHMWPE) were used. Procedures: In this in vitro study, samples of nylon leader line, fishing line, and UHMWPE sterilized by use of HPGP, ethylene oxide, and steam or unsterilized samples were used. Bacterial adherence on unsterilized and sterilized samples was tested with Staphylococcus epidermidis and Escherichia coli. Five samples were examined for each line type and sterilization condition, and final colony counts were obtained. Results: Bacterial adherence was significantly affected by method of sterilization for all 3 line types. For most of the samples, bacterial adherence was similar or lower when HPGP sterilization was used, compared with results for sterilization via ethylene oxide and steam, respectively. Bacterial adherence was significantly higher for UHMWPE, compared with adherence for the nylon line, regardless of the sterilization method used. Bacterial adherence was higher for nylon fishing line than for nylon leader line for S epidermidis after ethylene oxide sterilization and for E coli after HPGP and ethylene oxide sterilization. Conclusions and Clinical Relevance: Effects of HPGP sterilization on bioadhesive properties of nylon and polyethylene lines compared favorably with those for ethylene oxide and steam sterilization. Also, nylon line may be a more suitable material than UHMWPE for suture prostheses on the basis of bacterial adherence properties.