OBJECTIVE To evaluate accuracy of quantification of right ventricle volume (RVV) by use of 3-D echocardiography (3DE) and ECG-gated multidetector CT (MDCT). ANIMALS 6 healthy hound-cross dogs. PROCEDURES ECG-gated MDCT and complete 3DE examinations were performed on each dog. Right ventricular end-diastolic volumes (EDVs), end-systolic volumes (ESVs), stroke volume (SV), and ejection fraction (EF) were measured for 3DE and MDCT data sets by use of software specific for RVV quantification. Correlation and level of agreement between methods were determined. Intraobserver and interobserver variability were assessed for 3DE. RESULTS No significant differences were detected between SV and EF obtained with MDCT and 3DE. Significant differences were detected between right ventricular EDV and ESV obtained with MDCT and 3DE. No significant difference in heart rate was detected between methods. The correlation between MDCT and 3DE was very good (r = 0.87) for EDV and ESV, moderate (r = 0.60) for EF, and poor (r = 0.31) for SV. Bland-Altman analysis revealed a systematic underestimation of RVV derived by use of 3DE, compared with the RVV derived by use of MDCT (mean bias, 15 and 10.3 mL for EDV and ESV, respectively). Intraobserver (EDV, 12%; ESV, 18%) and interobserver (EDV, 14%; ESV, 11%) variability were acceptable for 3DE. CONCLUSIONS AND CLINICAL RELEVANCE There was substantial variance for RVV measured by use of 3DE in healthy dogs and a significant underestimation of volumes, compared with results for MDCT, despite the fact there were no significant differences in SV and EF.

OBJECTIVE To determine the prognostic value of CD44 variant isoform expression in dogs with multicentric high-grade B-cell lymphoma (BCL). ANIMALS 45 dogs with multicentric BCL and 10 healthy control Beagles. PROCEDURES The medical record database of a veterinary teaching hospital was searched to identify dogs with BCL that were treated between November 2005 and April 2015. Information regarding overall response to chemotherapy, progression-free survival (PFS) time, and overall survival time was extracted from each record. Archived lymph node aspirate specimens from dogs with BCL and lymph node aspirate specimens from the 10 control dogs underwent real-time PCR analysis to determine mRNA expression of CD44 variant isoforms of exons 3, 6, and 7 and the CD44 whole isoform. For each isoform, mRNA expression was compared between dogs with BCL and control dogs. The mean relative expression of each isoform was used to classify dogs with BCL into either a high- or low-expression group, and overall response rate, PFS time, and overall survival time (ie, indices of prognosis) were compared between the 2 groups. RESULTS For all isoforms evaluated, mean relative mRNA expression for dogs with BCL was numerically lower than that for control dogs. Dogs with BCL and high CD44 isoform expression had a lower overall response rate, median PFS time, and median overall survival time, compared with dogs with BCL and low CD44 isoform expression. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that, for dogs with BCL, high expression of exons 3, 6, and 7 was associated with a poor prognosis.

OBJECTIVE To compare the plasma pharmacokinetics of tulathromycin between 3-week-old (preweaned) and 6-month-old (weaned) calves and to characterize the distribution of tulathromcyin into pulmonary epithelial lining fluid (PELF) and interstitial fluid (ISF) of preweaned and weaned calves following SC administration of a single dose (2.5 mg/kg). ANIMALS 8 healthy 3-week-old and 8 healthy 6-month-old Holstein steers. PROCEDURES A jugular catheter and SC ultrafiltration probe were aseptically placed in the neck of each calf before tulathromycin administration. Blood, ISF, and bronchoalveolar lavage fluid samples were collected at predetermined times before and after tulathromycin administration for quantification of drug concentration. A urea dilution method was used to estimate tulathromycin concentration in PELF from that in bronchoalveolar lavage fluid. Tulathromycin–plasma protein binding was determined by in vitro methods. Plasma pharmacokinetics were determined by a 2-compartment model. Pharmacokinetic parameters and drug concentrations were compared between preweaned and weaned calves. RESULTS Clearance and volume of distribution per fraction of tulathromycin absorbed were significantly greater for weaned calves than preweaned calves. Tulathromycin–plasma protein binding was significantly greater for weaned calves than preweaned calves. Maximum PELF tulathromycin concentration was significantly greater than the maximum plasma and maximum ISF tulathromycin concentrations in both groups. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that age affected multiple pharmacokinetic parameters of tulathromycin, likely owing to physiologic changes as calves mature from preruminants to ruminants. Knowledge of those changes may be useful in the development of studies to evaluate potential dose adjustments during treatment of calves with respiratory tract disease.

OBJECTIVE To determine whether target values for pharmacokinetic-pharmacodynamic (PK-PD) indices against selected canine pathogens were achievable for pradofloxacin in various canine fluids and leukocytes. ANIMALS 8 healthy adult hounds (experiments 1 and 2) and 6 healthy adult dogs (experiment 3). PROCEDURES In 3 experiments, pradofloxacin (3, 6, or 12 mg/kg) and enrofloxacin (5 or 10 mg/kg) were orally administered once a day for 5 days, and blood, interstitial fluid (ISF), and other fluid samples were collected at various points. Sample drug concentrations were measured, and noncompartmental pharmacokinetic analysis was performed; then, PK-PD indices (ratios between maximum observed concentration [Cmax] and minimum inhibitory or mutant prevention concentrations) were determined for 7 bacterial species. RESULTS PK-PD values for pradofloxacin at 3 mg/kg were approximately 5 times as high in leukocyte versus plasma and were lowest in CSF, synovial fluid, and aqueous humor. No significant differences were noted between serum and ISF. Value ratios for serum versus other body fluids were numerically higher for pradofloxacin (vs enrofloxacin) for all fluid types except CSF and aqueous humor. Target PK-PD values were exceeded for pradofloxacin against all 7 bacterial species in leukocytes and against all species except Bacteroides spp in serum and ISF. Enrofloxacin achieved the target Cmax-to-minimum inhibitory concentration ratio against Pasteurella multocida in serum, ISF, and leukocytes and for Staphylococcus pseudintermedius in serum and leukocytes. A Cmax-to-mutant prevention concentration ratio ≥ 1 against Eschericha coli was achieved for pradofloxacin at 6 mg/kg. CONCLUSIONS AND CLINICAL RELEVANCE These findings supported once-daily oral administration of pradofloxacin to dogs at the currently recommended dose (7.5 mg/kg).

Studies in humans have shown that the ubiquitin-proteasome pathway and the insulin-like growth factor axis are involved in carcinogenesis, thus, components of these systems might be useful as prognostic markers and constitute potential therapeutic targets. In veterinary medicine, only a few studies exist on this topic. Here, serum concentrations of 26S proteasome (26SP) and insulin-like growth factor-1 (IGF-1) were measured by canine enzyme-linked immunosorbent assay (ELISA) in 43 dogs suffering from malignant tumors and 21 clinically normal dogs (control group). Relationships with tumor size, survival time, body condition score (BCS), and tumor entity were assessed. The median 26SP concentration in the tumor group was non-significantly higher than in the control group. However, dogs with mammary carcinomas displayed significantly increased 26SP levels compared to the control group and dogs with tumor size less than 5 cm showed significantly increased 26SP concentrations compared to dogs with larger tumors and control dogs. 26SP concentrations were not correlated to survival time or BCS. No significant difference in IGF-1 levels was found between the tumor group and the control group; however, IGF-1 concentrations displayed a larger range of values in the tumor group. Dogs with tumors greater than 5 cm showed significantly higher IGF-1 levels than dogs with smaller tumors. The IGF-1 concentrations were positively correlated to survival time, but no correlation with BCS was found. Consequently, serum 26SP concentrations seem to be increased in some dogs suffering from malignant tumors, especially in dogs with mammary carcinoma and smaller tumors. Increased serum IGF-1 concentrations could be an indication of large tumors and a poor prognosis.

OBJECTIVE To evaluate the effect of a bovine albumin–derivatized glutaraldehyde (BA-DG) biopolymer sealant on leakage pressures of intestinal anastomoses in jejunal tissue collected from fresh canine cadavers and to evaluate changes in circumference and cross-sectional area of the anastomotic site resulting from sealant application. SAMPLE 24 jejunal anastomoses from 4 fresh canine cadavers. PROCEDURES Jejunal tissue specimens were collected, and adjacent segment anastomoses were created within 12 hours after euthanasia of each dog. The tissue constructs were randomly assigned to 1 of 2 groups in which sealant was or was not applied. The outer circumference of all anastomoses in the sealant group was measured before and after application of the sealant; the cross-sectional area at the anastomotic site was then calculated at each time point. Tissue constructs were pressure tested, and leakage pressure and site were recorded. All testing was completed within 24 hours after tissue collection. RESULTS Compared with preapplication findings, there were no significant changes in outer circumference or cross-sectional area at the anastomotic site after sealant application. Leakage pressures in the sealant group were significantly higher than those in the no-sealant group. CONCLUSIONS AND CLINICAL RELEVANCE The use of surgical sealant on fresh canine cadaver jejunal anastomoses resulted in significantly higher leakage pressure at the anastomotic site; no immediate tissue deformation of the outer circumference or cross-sectional area occurred after sealant application. Future in vivo investigations are warranted to evaluate the effects of this sealant and potential benefits for clinical patients undergoing enterectomy.

OBJECTIVE To assess effects of buprenorphine hydrochloride (BH), sustained-release buprenorphine (SRB), and high-concentration buprenorphine (HCB) formulations in healthy rats. ANIMALS 8 Sprague-Dawley rats. PROCEDURES In a crossover-design study, rats received BH (0.05 mg/kg), SRB (1.2 mg/kg), HCB (0.30 mg/kg), or 5% dextrose solution (0.2 mL/kg), SC, once. Self-injurious behavior and thermal sensitivity (hind limb withdrawal latencies) were assessed prior to injection (time 0) and 1, 4, 8, 12, and 24 hours after injection. Food intake, kaolin intake, and fecal output were measured over 12-hour light and dark periods before and after each treatment. Values were compared among treatments and time points. RESULTS Self-injurious behavior was detected with all buprenorphine treatments; scores were greater at all time points during the 12 hours after HCB and 24 hours after SRB administration than at time 0. Percentage change in hind limb withdrawal latencies from time 0 was higher with BH and HCB 1 hour after injection than at other time points. Postinjection light-period food intake was higher (BH and HCB) and dark-period food intake was lower (BH, HCB, and SRB), compared with preinjection values for the same treatments. For SRB, postinjection light-period kaolin intake was greater than the preinjection value, and postinjection light- and dark-period kaolin intake was greater than that for other treatments. CONCLUSIONS AND CLINICAL RELEVANCE Hypoalgesic effects were briefly observed after administration of BH or HCB in healthy rats; adverse effects were detected in some rats with all buprenorphine formulations. Studies comparing effects of BH, SRB, and HCB in rats undergoing surgery or other noxious stimuli are indicated to determine clinical benefits in this species.

The objectives of the study were to: i) determine baseline microvascular perfusion indices (MPI) and assess their repeatability in healthy horses under general anesthesia, and ii) compare the MPIs of 3 microvascular beds (oral mucosa, colonic serosa, and rectal mucosa). Healthy adult horses were anesthetized and sidestream dark field microscopy was used to collect video loops of the oral mucosa, rectal mucosa, and colonic serosa under normotensive conditions without cardiovascular support drugs; videos were later analyzed to produce MPIs. Baseline MPI values were determined for each site, which included the total vessel density (TVD), perfused vessel density (PVD), portion perfused vessels (PPV), and microcirculatory flow index (MFI). Differences in MPIs between microvascular beds were not statistically significant. Repeatability of the measurements varied for each MPI. In particular, the site of sampling had a profound effect on the repeatability of the PPV measurements and should be considered in future studies.

The use of antibiotics in livestock production in North America and possible association with elevated abundance of detectable antimicrobial resistance genes (ARG) is a growing concern. Real-time, quantitative PCR (RT-qPCR) was used to determine the relative abundance and diversity of ARG in fecal composite and catch basin samples from 4 beef feedlots in Alberta. Samples from a surrounding waterway and municipal wastewater treatment plants were also included to compare the ARG profile of urban environments and fresh water with that of feedlots. The relative abundance of 18 resistance genes across 5 antibiotic families including sulfonamides, tetracyclines, macrolides, fluoroquinolones, and β-lactams was examined. Sulfonamide, fluoroquinolone, and β-lactam resistance genes predominated in wastewater treatment samples, while tetracycline resistance genes predominated in cattle fecal composite samples. These results reflect the types of antibiotic that are used in cattle versus humans, but other factors such as co-selection of ARG and variation in the composition of bacterial communities associated with these samples may also play a role.

OBJECTIVE To assess pharmacokinetics of tranexamic acid (TXA) in dogs and assess antifibrinolytic properties of TXA in canine blood by use of a thromboelastography-based in vitro model of hyperfibrinolysis. ANIMALS 6 healthy adult dogs. PROCEDURES Dogs received each of 4 TXA treatments (10 mg/kg, IV; 20 mg/kg, IV; approx 15 mg/kg, PO; and approx 20 mg/kg, PO) in a randomized crossover-design study. Blood samples were collected at baseline (time 0; immediately prior to drug administration) and predetermined time points afterward for pharmacokinetic analysis and pharmacodynamic (thromboelastography) analysis by use of an in vitro hyperfibrinolysis model. RESULTS Maximum amplitude (MA [representing maximum clot strength]) significantly increased from baseline at all time points for all treatments. The MA was lower at 360 minutes for the 10-mg/kg IV treatment than for other treatments. Percentage of clot lysis 30 minutes after MA was detected was significantly decreased from baseline at all time points for all treatments; at 360 minutes, this value was higher for the 10-mg/kg IV treatment than for other treatments and higher for the 20-mg/kg IV treatment than for the 20-mg/kg PO treatment. Maximum plasma TXA concentrations were dose dependent. At 20 mg/kg, IV, plasma TXA concentrations briefly exceeded concentrations suggested for complete inhibition of fibrinolysis. Oral drug administration resulted in a later peak antifibrinolytic effect than did IV administration. CONCLUSIONS AND CLINICAL RELEVANCE Administration of TXA improved clot strength and decreased fibrinolysis in blood samples from healthy dogs in an in vitro hyperfibrinolysis model. Further research is needed to determine clinical effects of TXA in dogs with hyperfibrinolysis.