Few antimicrobials are licensed for use in sheep in Canada, and the range of indications is narrow. Treatment in an “extra-label” manner may be ineffective. In addition, potentially harmful drug residues in food-animal products and antimicrobial resistance in bacteria may be associated with extra-label drug use (ELDU). No data had been documented on drug use, specifically antimicrobial use (AMU), in Ontario sheep, although it was thought that much use was extra-label. This study investigated AMU and ELDU on 49 lamb-producing Ontario sheep farms. Data were prospectively collected over 12 months from the participating farms, and farm-level practices were ascertained with a questionnaire. Treatment-level and farm-level variables were investigated for associations with rates of AMU by means of Poisson rate regression models fit with a generalized estimating equation to control for clustering at the farm level. Antimicrobials with high mean exposure rates included chlortetracycline (in feed), penicillins, and oxytetracycline. The exposure rate in lambs was significantly lower (P < 0.01) with antimicrobial treatment of systemic signs, respiratory disease, or wound or injury than with treatment of other reported diseases or conditions; it was also significantly lower with 3 or more lambing periods per year (α = 0.05). The exposure rate in adult sheep was significantly lower with treatment of 5 of the 6 most prevalent diseases or conditions (α = 0.05) and significantly higher with producer decision to treat and producer experience of 20 y or greater. Rates of using antimicrobials not licensed for use in sheep were high, as was extra-label use of licensed antimicrobials. Diseases reportedly treated most often with antimicrobials (e.g., systemic signs, mastitis) were significantly associated with lower rates of ELDU (α = 0.05). Compared with the rates in adult sheep, the mean rate of use of nonlicensed antimicrobials was similar in the lambs, whereas the mean rate of extra-label use of licensed antimicrobials was lower among the lambs. The results are useful in determining if public health concerns about antimicrobial use in Ontario sheep are warranted and in creating drug use and licensure strategies for the Canadian sheep industry.

Objective—To evaluate the effects of pilot hole diameter and tapping on insertion torque and axial pullout strength of 4.0-mm cancellous bone screws in a synthetic canine cancellous bone substitute. Sample—75 synthetic cancellous bone blocks (15 blocks/group). Procedures—For groups 1 through 5, screw size-pilot hole diameter combinations were 3.5–2.5 mm (cortical screws), 4.0–2.5 mm, 4.0–2.5 mm, 4.0–2.0 mm, and 4.0–2.0 mm, respectively. Holes were tapped in groups 1, 2, and 4 only (tap diameter, 3.5, 4.0, and 4.0 mm, respectively). One 70-mm-long screw was inserted into each block; in a servohydraulic materials testing machine, the screw was extracted (rate, 5 mm/min) until failure. Mean group values of maximum insertion torque, axial pullout strength, yield strength, and stiffness were determined. Results—Mean maximum insertion torque differed significantly among the 5 groups; the group 5 value was greatest, followed by group 3, 4, 2, and 1 values. Group 3, 4, and 5 axial pullout strengths were similar and significantly greater than the group 2 value; all values were significantly greater than that for group 1. Group 5 and 4 yield strengths were similar and significantly greater than the group 3, 2, and 1 values. Stiffness in group 3 was similar to group 4 and 2 values but significantly greater than the group 5 value; all values were significantly greater than that for group 1. Conclusions and Clinical Relevance—These synthetic cancellous bone model findings suggested that tapping a 2.0-mm-diameter pilot hole when placing a 4.0-mm screw is the optimal insertion technique.

Objective—To evaluate the effect of administration of the labeled dosage of pimobendan to dogs with furosemide-induced activation of the renin-angiotensin-aldosterone system (RAAS). Animals—12 healthy hound-type dogs. Procedures—Dogs were allocated into 2 groups (6 dogs/group). One group received furosemide (2 mg/kg, PO, q 12 h) for 10 days (days 1 to 10). The second group received a combination of furosemide (2 mg/kg, PO, q 12 h) and pimobendan (0.25 mg/kg, PO, q 12 h) for 10 days (days 1 to 10). To determine the effect of the medications on the RAAS, 2 urine samples/d were obtained for determination of the urinary aldosterone-to-creatinine ratio (A:C) on days 0 (baseline), 5, and 10. Results—Mean ± SD urinary A:C increased significantly after administration of furosemide (baseline, 0.37 ± 0.14 µg/g; day 5, 0.89 ± 0.23 µg/g) or the combination of furosemide and pimobendan (baseline, 0.36 ± 0.22 µg/g; day 5, 0.88 ± 0.55 µg/g). Mean urinary A:C on day 10 was 0.95 ± 0.63 µg/g for furosemide alone and 0.85 ± 0.21 µg/g for the combination of furosemide and pimobendan. Conclusions and Clinical Relevance—Furosemide-induced RAAS activation appeared to plateau by day 5. Administration of pimobendan at a standard dosage did not enhance or suppress furosemide-induced RAAS activation. These results in clinically normal dogs suggested that furosemide, administered with or without pimobendan, should be accompanied by RAAS-suppressive treatment

Objective—To assess the suitability of the modified acetaminophen absorption test for evaluation of abomasal emptying rate in ruminating cattle. Animals—7 Holstein-Friesian heifers. Procedures—In a crossover study design, heifers consecutively underwent an IV infusion of 1 L of saline (0.9% NaCl) solution (control treatment), 1 L of saline solution containing metoclopramide (0.1 mg/kg), and 1 L of saline solution containing atropine (0.1 mg/kg), with an interval of 15 days between treatments. Immediately after each treatment, acetaminophen diluted in ethanol (50 mg/kg) was infused transcutaneously into the abomasum. Blood samples were obtained repeatedly for measurement of plasma acetaminophen concentration, and pharmacokinetic data were obtained. Results—Maximum plasma acetaminophen concentration was significantly lower after atropine treatment than after control or metoclopramide treatment, whereas no difference was identified between control and metoclopramide treatments. The interval to maximum plasma acetaminophen concentration was significantly longer in atropine-treated versus metoclopramide-treated heifers. The interval to maximum acetaminophen concentration obtained from a pharmacokinetic model was significantly longer for atropine than for control and metoclopramide treatment. Similarly, areas under the plasma acetaminophen concentration-time curves for the first 60, 90, 120, and 240 minutes after administration were significantly lower for atropine versus metoclopramide or control treatment, whereas differences between metoclopramide and control treatments were not identified. Conclusions and Clinical Relevance—The modified acetaminophen absorption test was a practical, minimally invasive, and reliable method to assess abomasal emptying in cattle. Metoclopramide administered at a dose of 0.1 mg/kg did not increase the abomasal emptying rate.

Objective--To test the hypotheses that preparation method, exposure to shear force, and exposure to collagen affect the release of growth factors from equine platelet-rich plasma (PRP). Sample Population--PRP obtained from 6 horses. Procedures--PRP was prepared via 2 preparation methods (tube and automated) and subjected to 6 treatment conditions (resting, detergent, exposure to shear via 21- and 25-gauge needles, and exposure to collagen [10 and 20 μg/mL]). Concentrations of platelet-derived growth factor, isoform BB (PDGF-BB); transforming growth factor β, isoform 1 (TGFβ1); and insulin-like growth factor, isoform 1 (IGF-1) were quantified by use of ELISAs. Statistical analysis was conducted via repeated-measures ANOVA. Results--Platelet numbers were significantly higher in tube-prepared PRP than in automated-prepared PRP Growth factor concentrations did not differ significantly between preparation methods. Mean PDGF-BB concentration ranged from 134 to 7,157 pg/mL, mean TGFβ1 concentration ranged from 1,153 to 22,677 pg/mL, and mean IGF-1 concentration ranged from 150 to 280 ng/mL. Shear force did not affect growth factor concentrations. Dose-dependent increases in PDGF-BB and TGFβ1 were detected in response to collagen, but equalled only 10% of the estimated total platelet content. Concentrations of IGF-1 were not significantly different among treatments and negative or positive control treatments. Serum concentrations of PDGF-BB and TGFβ1 exceeded concentrations in PRP for most treatment conditions. Conclusions and Clinical Relevance--Release of growth factors from equine PRP was negligible as a result of the injection process alone. Investigation of platelet-activation protocols is warranted to potentially enhance PRP treatment efficacy in horses.

Objective—To evaluate the safety and efficacy of an experimental adjuvanted DNA-plasmid vaccine against West Nile virus (WNV) in red-tailed hawks (Buteo jamaicensis). Animals—19 permanently disabled but otherwise healthy red-tailed hawks of mixed ages and both sexes without detectable serum antibodies against WNV. Procedures—Hawks were injected IM with an experimental WNV DNA-plasmid vaccine in an aluminum-phosphate adjuvant (n = 14) or with the adjuvant only (control group; 5). All birds received 2 injections at a 3-week interval. Blood samples for serologic evaluation were collected before the first injection and 4 weeks after the second injection (day 0). At day 0, hawks were injected SC with live WNV. Pre- and postchallenge blood samples were collected at intervals for 14 days for assessment of viremia and antibody determination; oropharyngeal and cloacal swabs were collected for assessment of viral shedding. Results—Vaccination was not associated with morbidity or deaths. Three of the vaccinated birds seroconverted after the second vaccine injection; all other birds seroconverted following the live virus injection. Vaccinated birds had significantly less severe viremia and shorter and less-intense shedding periods, compared with the control birds. Conclusions and Clinical Relevance—Use of the WNV DNA-plasmid vaccine in red-tailed hawks was safe, and vaccination attenuated but did not eliminate both the viremia and the intensity of postchallenge shedding following live virus exposure. Further research is warranted to conclusively determine the efficacy of this vaccine preparation for protection of red-tailed hawks and other avian species against WNV-induced disease.

Objective—To evaluate serum haptoglobin concentration at feedlot arrival and subsequent performance and morbidity and mortality rates of calves that developed bovine respiratory disease. Animals—360 heifer calves and 416 steer and bull calves. Procedures—Serum samples were obtained from cattle at the time of arrival to a feedlot (day −1) and analyzed for haptoglobin concentration. In experiment 1, calves were classified into groups with a low (< 1.0 μg/mL), medium (1.0 to 3.0 μg/mL), or high (> 3.0 μg/mL) serum haptoglobin concentration and allotted into pens on the basis of group. In experiment 2, calves were classified as having or not having detectable serum haptoglobin concentrations. Results—In experiment 1, average daily gain from days 1 to 7 decreased as haptoglobin concentration increased. Dry-matter intake (DMI) from days 1 to 21 decreased with increasing haptoglobin concentration, and DMI typically decreased from days 1 to 63. Total bovine respiratory disease morbidity rate typically increased with increasing haptoglobin concentration. At harvest, no differences in carcass characteristics were observed on the basis of haptoglobin concentration. In experiment 2, cattle with measureable serum haptoglobin concentrations at arrival weighed less throughout the experiment, gained less from days 1 to 7, and had lower DMI from days 1 to 42. Overall morbidity rate was not different between groups, but cattle with detectable serum haptoglobin concentrations had higher odds of being treated 3 times. Conclusions and Clinical Relevance—Serum haptoglobin concentration in cattle at the time of feedlot arrival was not associated with overall performance but may have limited merit for making decisions regarding targeted prophylactic treatment.

Objective—To assess expression pattern and subcellular compartmentalization of 5-lipoxygenase in cutaneous, UV radiation–induced, and oral squamous cell carcinomas (SCCs) in cats and determine the effects of cyclooxygenase or 5-lipoxygenase inhibition on proliferation or apoptosis in a feline oral squamous cell carcinoma (SCCF1) cell line. Sample—60 archived paraffin-embedded samples of SCCs from 60 cats and SCCF1 cells. Procedures—Retrospective immunohistochemical analysis of the archived samples of SCCs (20 cutaneous, 20 UV radiation–induced, and 20 oral tumors) was performed. Cell culture proliferation assays involving SCCF1 cells were performed, and tepoxalin-induced apoptosis and signaling were examined via western blotting and annexin V staining. Results—Immunohistochemically, staining for 5-lipoxygenase was most frequently of greatest intensity in oral SCCs, whereas staining of cutaneous and UV radiation–induced lesions had less consistent 5-lipoxygenase expression. Exposure of SCCF1 cells to the 5-lipoxygenase inhibitor tepoxalin resulted in apoptosis; the effect appeared to be mediated via alteration of cell signaling rather than via suppression of lipid mediators that are typically produced as a result of 5-lipoxygenase activity. Conclusions and Clinical Relevance—In cats, expression of 5-lipoxygenase in SCCs appeared to differ depending on tumor location. The influence of tepoxalin-induced 5-lipoxygenase inhibition on a poxygenase–expressing cell line coupled with the notable expression of 5-lipoxygenase in oral SCCs suggested that 5-lipoxygenase inhibition may have therapeutic benefits in affected cats. Although the safety of tepoxalin in cats has yet to be investigated, 5-lipoxygenase inhibitors should be evaluated for use as a potential treatment for SCCs in that species.

Objective—To determine effects of infection with bovine leukosis virus (BLV) on lymphocyte proliferation and apoptosis in dairy cattle. Animals—27 adult Holstein cows. Procedures—Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood from lactating Holstein cows seronegative for BLV (n = 9 cows), seropositive for BLV and aleukemic (aleukemic; 9), and seropositive for BLV and persistently lymphocytotic (PL; 9). Isolated PBMCs were assayed for mitogen-induced proliferation and were analyzed by means of flow cytometry. The PBMCs from a subset of each group were assayed for apoptosis, caspase-9 activity, and expression of selected genes related to apoptosis. Results—PL cows had significantly higher total lymphocyte counts and significantly lower proportions of T-lymphocyte populations than did BLV-negative and aleukemic cows. Both groups of BLV-infected cows had significantly higher proportions of B cells and major histocompatibility complex II–expressing cells than did BLV-negative cows. Proliferation with concanavalin A was significantly lower for PL cows, compared with proliferation for BLV-negative cows. Pokeweed mitogen–induced proliferation was significantly higher for aleukemic and PL cows than for BLV-negative cows. Gene expression of apoptosis-inhibitory proteins BCL2 and BCL2L1 was significantly higher for aleukemic cows and expression of BCL2 was significantly higher for PL cows than for BLV-negative cows. Conclusions and Clinical Relevance—Cattle infected with BLV had marked changes in PBMC populations accompanied by alterations in proliferation and apoptosis mechanisms. Because the relative distribution and function of lymphocyte populations are critical for immune competence, additional studies are needed to investigate the ability of BLV-infected cattle to respond to infectious challenge.

Objective-To determine efficacy of a modified-live virus (MLV) vaccine containing bovine viral diarrhea virus (BVDV) 1a and 2a against fetal infection in heifers exposed to cattle persistently infected (PI) with BVDV subtype 1 b. Animals-50 heifers and their fetuses. Procedures-Susceptible heifers received a placebo vaccine administered IM or a vaccine containing MLV strains of BVDV1a and BVDV2a administered IM or SC. On day 124 (64 to 89 days of gestation), 50 pregnant heifers (20 vaccinated SC, 20 vaccinated IM, and 10 control heifers) were challenge exposed to 8 PI cattle. On days 207 to 209, fetuses were recovered from heifers and used for testing. Results-2 control heifers aborted following challenge exposure; both fetuses were unavailable for testing. Eleven fetuses (8 control heifers and 1 IM and 2 SC vaccinates) were positive for BVDV via virus isolation (VI) and for BVDV antigen via immunohistochemical analysis in multiple tissues. Two additional fetuses from IM vaccinates were considered exposed to BVDV (one was seropositive for BVDV and the second was positive via VI in fetal tissues). A third fetus in the SC vaccinates was positive for BVDV via VI from serum alone. Vaccination against BVDV provided fetal protection in IM vaccinated (17/20) and SC vaccinated (17/20) heifers, but all control heifers (10/10) were considered infected. Conclusions and Clinical Relevance-1 dose of a BVDV1a and 2a MLV vaccine administered SC or IM prior to breeding helped protect against fetal infection in pregnant heifers exposed to cattle PI with BVDV1b.