Objective—To determine the optimal method for use of the Canine Brief Pain Inventory (CBPI) to quantitate responses of dogs with osteoarthritis to treatment with carprofen or placebo. Animals—150 dogs with osteoarthritis. Procedures—Data were analyzed from 2 studies with identical protocols in which owner-completed CBPIs were used. Treatment for each dog was classified as a success or failure by comparing the pain severity score (PSS) and pain interference score (PIS) on day 0 (baseline) with those on day 14. Treatment success or failure was defined on the basis of various combinations of reduction in the 2 scores when inclusion criteria were set as a PSS and PIS ≥ 1, 2, or 3 at baseline. Statistical analyses were performed to select the definition of treatment success that had the greatest statistical power to detect differences between carprofen and placebo treatments. Results—Defining treatment success as a reduction of ≥ 1 in PSS and ≥ 2 in PIS in each dog had consistently robust power. Power was 62.8% in the population that included only dogs with baseline scores ≥ 2 and 64.7% in the population that included only dogs with baseline scores ≥ 3. Conclusions and Clinical Relevance—The CBPI had robust statistical power to evaluate the treatment effect of carprofen in dogs with osteoarthritis when protocol success criteria were predefined as a reduction ≥ 1 in PIS and ≥ 2 in PSS. Results indicated the CBPI can be used as an outcome measure in clinical trials to evaluate new pain treatments when it is desirable to evaluate success in individual dogs rather than overall mean or median scores in a test population.

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 association between urine osmolality and specific gravity (USG) in dogs and to evaluate the effect of commonly measured urine solutes on that association. Animals—60 dogs evaluated by an internal medicine service. Procedures—From each dog, urine was obtained by cystocentesis and USG was determined with a refractometer. The sample was divided, and one aliquot was sent to a diagnostic laboratory for urinalysis and the other was frozen at −80°C until osmolality was determined. Urine samples were thawed and osmolality was measured in duplicate with a freezing-point depression osmometer. The correlation between mean urine osmolality and USG was determined; the effect of pH, proteinuria, glucosuria, ketonuria, bilirubinuria, and hemoglobinuria on this relationship was investigated with multiple regression analysis. Results—The Pearson correlation coefficient between urine osmolality and USG was 0.87. The final multivariable regression model for urine osmolality included USG and the presence of ketones; ketonuria had a small negative association with urine osmolality. Conclusions and Clinical Relevance—Results indicated a strong linear correlation between osmolality and USG in urine samples obtained from dogs with various pathological conditions, and ketonuria had a small negative effect on that correlation.

The objective of this study was to develop prediction models for the serum IgG concentration in critically ill calves based on indirect assays and to assess if the predictive ability of the models could be improved by inclusion of age, clinical covariates, and/or laboratory covariates. Seventy-eight critically ill calves between 1 and 13 days old were selected from 1 farm. Statistical models to predict IgG concentration from the results of the radial immunodiffusion test, the gold standard, were built as a function of indirect assays of serum and plasma protein concentrations, zinc sulfate (ZnSO4) turbidity and transmittance, and serum γ-glutamyl transferase (GGT) activity. For each assay 4 models were built: without covariates, with age, with age and clinical covariates (infection and dehydration status), and with age and laboratory covariates (fibrinogen concentration and packed cell volume). For the protein models, dehydration status (clinical model) and fibrinogen concentration (laboratory model) were selected for inclusion owing to their statistical significance. These variables increased the coefficient of determination (R2) of the models by ≥ 7% but did not significantly improve the sensitivity or specificity of the models to predict passive transfer with a cutoff IgG concentration of 1000 mg/dL. For the GGT assay, including age as a covariate increased the R2 of the model by 3%. For the ZnSO4 turbidity test, none of the covariates were statistically significant. Overall, the R2 of the models ranged from 34% to 62%. This study has provided insight into the importance of adjusting for covariates when using indirect assays to predict IgG concentration in critically ill calves. Results also indicate that ZnSO4 transmittance and turbidity assays could be used advantageously in a field setting.

Objective—To compare numbers of L cells in intestinal samples and blood concentrations of glucagon-like peptide (GLP)-1 between neonatal and mature alpacas. Sample—Intestinal samples from carcasses of 4 suckling crias and 4 postweaning alpacas for immunohistochemical analysis and blood samples from 32 suckling crias and 19 healthy adult alpacas for an ELISA. Procedures—Immunohistochemical staining was conducted in accordance with Oregon State University Veterinary Diagnostic Laboratory standard procedures with a rabbit polyclonal anti–GLP-1 primary antibody. Stained cells with staining results in ileal tissue were counted in 20 fields by 2 investigators, and the mean value was calculated. For quantification of GLP-1 concentrations, blood samples were collected into tubes containing a dipeptidyl peptidase-4 inhibitor. Plasma samples were tested in duplicate with a commercial GLP-1 ELISA validated for use in alpacas. Results—Counts of stained cells (mean ± SD, 50 ± 18 cells) and plasma GLP-1 concentrations (median, 0.086 ng/mL; interquartile range, 0.061 to 0.144 ng/mL) were higher for suckling alpacas than for postsuckling alpacas (stained cells, 26 ± 4 cells; plasma GLP-1 concentration, median, 0.034 ng/mL; interquartile range, 0.015 to 0.048 ng/mL). Conclusions and Clinical Relevance—Older alpacas had lower numbers of L cells in intestinal tissues and lower blood concentrations of GLP-1 than those in neonates. These findings suggested that there may be a decrease in the contribution of GLP-1 to insulin production in adult alpacas, compared with the contribution in neonates.

Objective—To determine whether inoculation of healthy dogs with a recombinant peptide containing 3 copies of ACTH would result in the production of antibodies against ACTH and whether this would affect pituitary-adrenocortical function. Animals—8 healthy dogs. Procedures—A recombinant peptide consisting of 3 copies of ACTH fused to a T-helper cell epitope was produced in Escherichia coli. The protein was inoculated into 4 dogs at 4-week intervals (total of 3 inoculations/dog). Four control dogs received inoculations of PBS solution mixed with adjuvant. Blood samples were collected for determination of antibody titers against ACTH and for measurement of basal and ACTH-stimulated plasma cortisol concentrations. Results—Inoculation with the ACTH vaccine resulted in production of anti-ACTH antibodies in all 4 dogs. Titers were initially high but declined by 15 weeks after the initial inoculation. Basal cortisol concentrations were unaffected by inoculation with the ACTH vaccine. Plasma cortisol concentrations in response to ACTH stimulation were reduced at 12 weeks, but not at 15 weeks, after the first inoculation. Conclusions and Clinical Relevance—Inoculation of dogs with a recombinant ACTH vaccine resulted in the production of antibodies against the hormone. Anti-ACTH titers were initially high but were not sustained. The only detectable endocrine effect in treated dogs was a reduction in cortisol concentration in response to ACTH stimulation in 2 of 4 dogs at 12 weeks after the first inoculation. The effect of vaccine administration on the pituitary-adrenal system was subtle and transient.

Objective: To determine the precision of a clinical illness score (CIS) system for identification of clinical signs in calves with experimentally induced Mycoplasma bovis pneumonia and to evaluate the accuracy of CISs in relation to pulmonary consolidation scores assigned at necropsy. Animals: 178 Holstein bull calves that were 52 to 91 days of age at the time of pneumonia induction. Procedures: 5 trials involved calves challenged with M bovis and scheduled for euthanasia and necropsy 12 to 24 days afterward. Nine veterinarian observers with various degrees of experience simultaneously assigned CISs to calves within 48 hours before necropsy. The precision of the CIS system among observers was evaluated via the Cohen κ statistic. The accuracy of each observer's CISs relative to 6 cutoffs (≥ 5%, ≥ 10%, ≥ 15%, ≥ 20%, ≥ 25%, and ≥ 30%) of percentage pulmonary consolidation was determined by comparing prenecropsy CISs with the gross pulmonary consolidation scores assigned at necropsy. Estimates for sensitivity and specificity were calculated relative to the 6 pulmonary consolidation cutoffs. Results: A slight level of agreement was evident among observers (κ range, 0.10 to 0.21 for the individual trials) and overall (κ = 0.16; 95% confidence interval, 0.10 to 0.24). Median sensitivity and specificity changed with pulmonary consolidation score cutoff. Median sensitivity for all observers ranged from 81.7% to 98.9%, and median specificity ranged from 80.8% to 94.9% over all cutoff values. Conclusions and Clinical Relevance: Agreement among observers assigning CISs to calves was low; the accuracy of the CIS system in relation to that of pulmonary consolidation scoring varied with the severity of consolidation considered to represent bovine respiratory disease.

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 determine the effect of large colon ischemia and reperfusion on concentrations of the inflammatory neutrophilic protein calprotectin and other clinicopathologic variables in jugular and colonic venous blood in horses. Animals—6 healthy horses. Procedures—Horses were anesthetized, and ischemia was induced for 1 hour followed by 4 hours of reperfusion in a segment of the pelvic flexure of the large colon. Blood samples were obtained before anesthesia, before induction of ischemia, 1 hour after the start of ischemia, and 1, 2, and 4 hours after the start of reperfusion from jugular veins and veins of the segment of the large colon that underwent ischemia and reperfusion. A sandwich ELISA was developed for detection of equine calprotectin. Serum calprotectin concentrations and values of blood gas, hematologic, and biochemical analysis variables were determined. Results—Large colon ischemia caused metabolic acidosis, a significant increase in lactate and potassium concentrations and creatine kinase activities, and a nonsignificant decrease in glucose concentrations in colonic venous blood samples. Values of these variables after reperfusion were similar to values before ischemia. Ischemia and reperfusion induced activation of an inflammatory response characterized by an increase in neutrophil cell turnover rate in jugular and colonic venous blood samples and calprotectin concentrations in colonic venous blood samples. Conclusions and Clinical Relevance—Results of this study suggested that large colon ischemia and reperfusion caused local and systemic inflammation in horses. Serum calprotectin concentration may be useful as a marker of this inflammatory response.