Objective-To compare daily endogenous cortisol production rate and the pharmacokinetics of an IV bolus of hydrocortisone between neonatal foals and adult horses. Animals-10 healthy full-term 2- to 4-day-old foals and 7 healthy adult horses. Procedures-Blood samples were collected from each horse every 15 to 20 minutes for 24 hours for determination of 24-hour mean cortisol concentration. Afterward, dexamethasone (0.08 mg/kg) was administered IV to suppress endogenous cortisol production. Twelve hours afterward, hydrocortisone sodium succinate (1.0 mg/kg) was administered as a rapid IV bolus and serial blood samples were collected to determine hydrocortisone pharmacokinetics. Cortisol concentrations, daily cortisol production rate, and hydrocortisone pharmacokinetics were determined, and results were compared between adult horses and foals. Results-The mean +/- SD 24-hour cortisol concentration was significantly lower in foals (20 +/- 4 ng/mL) than in horses (26 +/- 6 ng/mL), but the daily cortisol production rate was significantly greater in foals (6,710 +/- 320 ng/kg/d) than in horses (2,140 +/- 400 ng/kg/d). For hydrocortisone, foals had a significantly greater volume of distribution at steady state (1.92 +/- 1.11 L/kg) and total body clearance (1.39 +/- 0.108 L/kg/h) and significantly lower peak plasma concentration (1,051 +/- 343 ng/mL) than did horses (0.58 +/- 0.15 L/kg, 0.349 +/- 0.065 L/kg/h, and 8,934 +/- 3,843 ng/mL, respectively). Conclusions and Clinical Relevance-Important differences were detected in cortisol production and metabolism between neonatal foals and adult horses consistent with lower plasma protein binding of cortisol in foals. This decrease may contribute to cortisol insufficiency during prolonged critical illness in neonatal foals.

Objective: To evaluate effects of a single dose of enrofloxacin (5 mg/kg, IV) on body temperature and tracheobronchial neutrophil count in healthy Thoroughbreds premedicated with interferon-α and undergoing long-distance transportation. Animals: 32 healthy Thoroughbreds. Procedures: All horses received interferon-α (0.5 U/kg, sublingually, q 24 h) as an immunologic stimulant for 2 days before transportation and on the day of transportation. Horses were randomly assigned to receive enrofloxacin (5 mg/kg, IV, once; enrofloxacin group) or saline (0.9% NaCl) solution (50 mL, IV, once; control group) ≤ 1 hour before being transported 1,210 km via commercial vans (duration, approx 26 hours). Before and after transportation, clinical examination, measurement of temperature per rectum, and hematologic analysis were performed for all horses; a tracheobronchial aspirate was collected for neutrophil quantification in 12 horses (6/group). Horses received antimicrobial treatment after transportation if deemed necessary by the attending clinician. Results: No adverse effects were associated with treatment. After transportation, WBC count and serum amyloid A concentration in peripheral blood samples and neutrophil counts in tracheobronchial aspirates were significantly lower in horses of the enrofloxacin group than in untreated control horses. Fever (rectal temperature, ≥ 38.5°C) after transportation was detected in 3 of 16 enrofloxacin group horses and 9 of 16 control horses; additional antimicrobial treatment was required in 2 horses in the enrofloxacin group and 7 horses in the control group. Conclusions and Clinical Relevance: In horses premedicated with interferon-α, enrofloxacin appeared to provide better protection against fever and lower respiratory tract inflammation than did saline solution.

Objective: To establish and validate an objective method of radiographic diagnosis of anatomic changes in laminitic forefeet of donkeys on the basis of data from a comprehensive series of radiographic measurements. Animals: 5 donkeys with and 85 without forelimb laminitis for baseline data determination; a cohort of 44 donkeys with and 18 without forelimb laminitis was used for validation analyses. Procedures: For each donkey, lateromedial radiographic views of 1 weight-bearing forelimb were obtained; images from 11 laminitic and 2 nonlaminitic donkeys were excluded (motion artifact) from baseline data determination. Data from an a priori selection of 19 measurements of anatomic features of laminitic and nonlaminitic donkey feet were analyzed by use of a novel application of multivariate statistical techniques. The resultant diagnostic models were validated in a blinded manner with data from the separate cohort of laminitic and nonlaminitic donkeys. Results: Data were modeled, and robust statistical rules were established for the diagnosis of anatomic changes within laminitic donkey forefeet. Component 1 scores ≤ −3.5 were indicative of extreme anatomic change, and scores from −2.0 to 0.0 denoted modest change. Nonlaminitic donkeys with a score from 0.5 to 1.0 should be considered as at risk for laminitis. Conclusions and Clinical Relevance: Results indicated that the radiographic procedures evaluated can be used for the identification, assessment, and monitoring of anatomic changes associated with laminitis. Screening assessments by use of this method may enable early detection of mild anatomic change and identification of at-risk donkeys.

Objective: To determine the effects of intratumoral injection of a hyaluronan-cisplatin nanoconjugate on local and systemic platinum concentrations and systemic toxicosis. Animals: 5 dogs with spontaneous soft tissue sarcomas (STSs). Procedures: For each dog, approximately 1.5 mL of hyaluronan nanocarrier conjugated with 20 mg of cisplatin was injected into an external STS. Blood samples were collected immediately before (0 hours) and at 0.5, 1, 2, 3, 4, 24, and 96 hours after hyaluronan-cisplatin injection for pharmacokinetic analyses. Urine samples were obtained at 0 and at 96 hours after hyaluronan-cisplatin injection for urinalysis. Each treated STS and its sentinel lymph nodes were surgically removed 96 hours after the hyaluronan-cisplatin injection. Inductively coupled plasma mass spectrometry was used to measure platinum concentrations in blood samples, tumors, and lymph nodes. Results: No tissue reactions were detected 96 hours after hyaluronan-cisplatin injection. Mean ± SD area under the curve, peak concentration, and terminal half-life for unbound (plasma) and total (serum) platinum were 774.6 ± 221.1 ng•h/mL and 3,562.1 ± 2,031.1 ng•h/mL, 56.5 ± 20.9 ng/mL and 81.6 ± 40.4 ng/mL, and 33.6 ± 16.1 hours and 51.2 ± 29.1 hours, respectively. Platinum concentrations ranged from 3,325 to 8,229 ng/g in STSs and 130 to 6,066 ng/g in STS-associated lymph nodes. Conclusions and Clinical Relevance: Intratumoral injection of the hyaluronan-cisplatin nanoconjugate was well tolerated in treated dogs. Following intratumoral hyaluronan-cisplatin injection, platinum concentration was 1,000-fold and 100-fold greater within treated tumors and tumor-draining lymphatics, respectively, compared with that in plasma.

Objective: To evaluate the expression of Ki67 and epidermal growth factor receptor (EGFR), mitotic index (MI), and microvascular density (MVD) in feline oral squamous cell carcinoma (SCC) via immunohistochemical staining on archival tumor tissues and to seek a correlation between these markers and clinical variables. Sample: 22 archived tumor samples of feline oral SCC. Procedures: Immunohistochemical staining for Ki67, MVD, and EGFR was performed and scored. Patient survival information was obtained from the medical records. These molecular markers as well as MI were correlated with tumor locations and patient survival time. Results: The 22 tumors had wide variation in Ki67 expression, MI, MVD, and EGFR expression. Tongue SCC had higher MVD than did mandibular and maxillary SCC. Tumor expression of EGFR was inversely proportional to survival time. Conclusions and Clinical Relevance: Results suggested that EGFR expression might be a valuable prognostic factor for treatment outcome in feline oral SCC. It also identified higher angiogenesis in tongue SCC, compared with mandibular and maxillary SCC, which may account for a different clinical outcome. Further prospective characterization of feline oral SCC may provide a better understanding of the underlying molecular factors that drive its behavior and offer the possibility for future patient-specific treatment plans.

Objective: To determine whether an interferon (IFN)-γ response sufficient to categorize cattle as positive for tuberculosis can be detected in blood collected at commencement of exsanguination at slaughter. Animals: 15 Holstein cows. Procedures: 12 cows were experimentally sensitized by SC injection with inactivated Mycobacterium bovis in mineral oil, which induced an immune response that mimicked natural infection with M bovis. Three nonsensitized control cows were injected SC with mineral oil alone. By 5 weeks after injection, only the 12 sensitized cows had positive results for tuberculosis with whole blood IFN-γ assay. At that time, all 15 cows were sent to slaughter and samples of blood were collected from each cow immediately before stunning and at commencement of exsanguination (within 90 seconds after stunning). A whole blood IFN-γ assay was performed on the samples. Conditional probability and paired t tests were used to analyze changes in the categorical test interpretation and qualitative IFN-γ production, respectively. Results: All 12 sensitized cows had positive results for tuberculosis in samples obtained immediately before stunning, and 9 retained positive results for samples obtained at commencement of exsanguination. There was a significant decrease in the mean background-corrected IFN-γ ELISA optical density values for samples obtained at commencement of exsanguination. Conclusions and Clinical Relevance: IFN-γ response sufficient to classify cattle as positive for tuberculosis could be detected in blood collected at commencement of exsanguination. These findings support further development and use of the IFN-γ assay on blood samples collected at exsanguination as part of a bovine tuberculosis surveillance program.

Objective: To retrospectively assess the safety and efficacy of recombinant human granulocyte colony-stimulating factor (G-CSF) used as part of autologous bone marrow transplantation in dogs with lymphoma. Animals: 21 dogs with lymphoma at any disease stage. Procedures: Medical records of dogs with lymphoma that underwent intensified chemotherapy and received an autologous bone marrow transplant following owner administration of recombinant human G-CSF (5 μg/kg, SC, q 12 h) for 7 days between January 2007 and July 2009 were reviewed. Results of physical examinations and CBCs performed before and at intervals during a 24-month period after G-CSF treatment were assessed. The safety of recombinant human G-CSF administration was determined via assessment of both short-term (ie, during the 7-day G-CSF treatment period) and long-term adverse effects. Results: None of the dogs developed any adverse effect attributable to the administration of recombinant human G-CSF during G-CSF administration or during follow-up periods of 1 month to 2 years (median follow-up period, 4 months). Among the 18 dogs for which CBC results were available for analysis, mean circulating neutrophil count significantly increased after administration of recombinant human G-CSF, compared with value before treatment. Conclusions and Clinical Relevance: Results indicated that recombinant human G-CSF administered SC at a dosage of 5 μg/kg every 12 hours for 7 days appeared to be safe and effective when used in dogs with lymphoma that were undergoing autologous bone marrow transplant.

Objective: To determine alterations of serum biochemical variables in relation to changes of near- and far-field mean grayscale histogram (MGSH) and attenuation rates in liver ultrasonograms of periparturient cows. Animals: 67 Holstein cows. Procedures: Cows were allocated on the basis of body condition score into underconditioned (n = 21), moderately conditioned (23), and overconditioned (23) groups. Serum samples (obtained every 10 days from 30 days before to 30 days after calving) were analyzed for aspartate aminotransferase, alanine aminotransferase, and γ-glutamyltransferase activities and BUN, albumin, calcium, and inorganic phosphorus concentrations along with digital estimation of near- and far-field MGSH values of liver ultrasonograms and deep attenuation. Values were compared among groups and within each group, and their correlations were determined in the pre- and postpartum periods. Results: Serum biochemical variables did not differ significantly among groups. Aspartate aminotransferase and γ-glutamyltransferase activities increased in the postpartum period. Fluctuations of alanine aminotransferase activity were not significant; BUN decreased significantly in the peripartum period. Albumin concentration decreased prior to parturition and remained low, but significantly increased after parturition. Calcium concentration decreased on day 10 but subsequently increased. Phosphorus concentration decreased stepwise until day 10 after calving. Postpartum biochemical variables had weak correlations with near- and far-field MGSH values in overconditioned cows. The highest levels of sound attenuation were found in overconditioned cows on calving day. Conclusions and Clinical Relevance: Liver ultrasonographic features were poorly correlated with changes of serum biochemical variables. This suggests that liver ultrasonography is not a good technique for estimating functional liver abnormalities in periparturient cows.

Objective: To evaluate the analgesic efficacy of ABT-116, a transient receptor potential cation channel vanilloid subfamily V member 1 antagonist, and compare it with that of buprenorphine by measurement of mechanical and thermal nociceptive thresholds in dogs. Animals: Six 7- to 8-month-old dogs (3 males and 3 females). Procedures: In a crossover study design, all dogs received ABT-116 (30 mg/kg, PO) and buprenorphine (0.03 mg/kg, orotransmucosally), with each treatment separated by 1 week. Physiologic variables were recorded prior to and 1, 6, and 24 hours after drug administration. Thermal (thoracic) and mechanical (dorsolateral aspect of the radius [proximal] and dorsopalmar aspect of the forefoot [distal]) nociceptive thresholds were assessed prior to (baseline) and 15 minutes and 1, 2, 4, 6, 12, 18, and 24 hours after treatment. Results: Buprenorphine administration resulted in higher overall thermal and proximal mechanical nociceptive thresholds, compared with ABT-116. Distal mechanical nociceptive thresholds after treatment were higher than baseline values for both treatments, but the magnitude of change was greater for buprenorphine at 1 hour after administration. Whereas HR and RR sporadically differed from baseline values after ABT-116 administration, rectal temperature increased from a baseline value of 39 ± 0.2°C (mean ± SD) to a peak of 40.6 ± 0.2°C at 6 hours. Conclusions and Clinical Relevance: In dogs without inflammation or nerve injury, PO administration of ABT-116 did not consistently result in an increase in nociceptive thresholds. However, clinically relevant increases in rectal temperature were identified after ABT-116 administration.

Objective: To determine the minimal electric threshold of neurostimulation dorsally and ventrally to the interarcuate ligament in the lumbosacral area necessary to cause muscle contraction of the hind limb or tail and determine whether a continuous electrical stimulation applied to an insulated needle during lumbosacral epidural needle placement could be used to distinguish the epidural from the intrathecal space in rabbits. Animals: 24 New Zealand white rabbits. Procedures: Rabbits received iohexol (0.2 mL/kg) either dorsally (group 1) or ventrally to the interarcuate ligament in the lumbosacral area (groups 2 and 3). Correct placement of the needle was determined by use of the loss of resistance to injection technique (group 2) or a continuous electrical stimulation (group 3) and confirmed by examination of the iohexol distribution pattern on radiographs. Results: In all rabbits of group 1, iohexol was injected in the lumbosacral area, outside the epidural space. In groups 2 and 3, iohexol was injected intrathecally. No pure iohexol epidural migration of iohexol was observed. Mean ± SD minimal electric threshold to elicit a motor response was 1.2 ± 0.3 mA, 0.3 ± 0.1 mA, and 0.3 ± 0.1 mA in groups 1, 2, and 3, respectively. Conclusions and Clinical Relevance: Neurostimulation was a useful technique to determine correct intrathecal needle placement in rabbits but failed to detect the lumbosacral epidural space when the common technique, used in dogs and cats for the lumbosacral epidural approach, was used.