Objective-To determine and compare the ratio of uracil (U) to dihydrouracil (UH2) concentrations in plasma as an indicator of dihydropyrimidine dehydrogenase activity in clinically normal dogs and dogs with neoplasia or renal insufficiency. Animals-101 client-and shelter-owned dogs. Procedures-Study dogs included 74 clinically normal dogs, 17 dogs with neoplasia, and 10 dogs with renal insufficiency. For each dog, a blood sample was collected into an EDTA-containing tube; plasma U and UH2 concentrations were determined via UV high-performance liquid chromatography, and the U:UH2 concentration ratio was calculated. Data were compared among dogs grouped on the basis of sex, clinical group assignment, reproductive status (sexually intact, spayed, or castrated), and age. Results-Mean +/- SEM U:UH2 concentration ratio for all dogs was 1.55 +/- 0.08 (median, 1.38; range, 0.4 to 7.14). In 14 (13.9%) dogs, the U:UH2 concentration ratio was considered abnormal (ie, > 2). Overall, mean ratio for sexually intact dogs was significantly higher than that for neutered dogs; a similar difference was apparent among males but not females. Dogs with ratios > 2 and dogs with ratios less than 2 did not differ significantly with regard to sex, clinical group, reproductive status, or age. Conclusions and Clinical Relevance-Determination of the U:UH2 concentration ratio was easy to perform. Ratios were variable among dogs, possibly suggesting differences in dihydropyrimidine dehydrogenase activity. However, studies correlating U:UH2 concentration ratio and fluoropyrimidine antimetabolite drug tolerability are required to further evaluate the test's validity and its appropriate use in dogs.

Objective-To design and fabricate fiberglass-reinforced composite (FRC) replicas of a canine radius and compare their mechanical properties with those of radii from dog cadavers. Sample-Replicas based on 3 FRC formulations with 33%, 50%, or 60% short-length discontinuous fiberglass by weight (7 replicas/group) and 5 radii from large (> 30-kg) dog cadavers. Procedures-Bones and FRC replicas underwent nondestructive mechanical testing including 4-point bending, axial loading, and torsion and destructive testing to failure during 4-point bending. Axial, internal and external torsional, and bending stiffnesses were calculated. Axial pullout loads for bone screws placed in the replicas and cadaveric radii were also assessed. Results-Axial, internal and external torsional, and 4-point bending stiffnesses of FRC replicas increased significantly with increasing fiberglass content. The 4-point bending stiffness of 33% and 50% FRC replicas and axial and internal torsional stiffnesses of 33% FRC replicas were equivalent to the cadaveric bone stiffnesses. Ultimate 4-point bending loads did not differ significantly between FRC replicas and bones. Ultimate screw pullout loads did not differ significantly between 33% or 50% FRC replicas and bones. Mechanical property variability (coefficient of variation) of cadaveric radii was approximately 2 to 19 times that of FRC replicas, depending on loading protocols. Conclusions and Clinical Relevance-Within the range of properties tested, FRC replicas had mechanical properties equivalent to and mechanical property variability less than those of radii from dog cadavers. Results indicated that FRC replicas may be a useful alternative to cadaveric bones for biomechanical testing of canine bone constructs.

Objective: To identify ventilatory protocols that yielded good image quality for thoracic CT and hemodynamic stability in cats. Animals: 7 healthy cats. Procedures: Cats were anesthetized and ventilated via 4 randomized protocols (hyperventilation, 20 seconds [protocol 1]; single deep inspiration, positive inspiratory pressure of 15 cm H2O [protocol 2]; recruitment maneuver [protocol 3]; and hyperventilation, 20 seconds with a positive end-expiratory pressure of 5 cm H2O [protocol 4]). Thoracic CT was performed for each protocol; images were acquired during apnea for protocols 1 and 3 and during positive airway pressure for protocols 2 and 4. Heart rate; systolic, mean, and diastolic arterial blood pressures; blood gas values; end-tidal isoflurane concentration; rectal temperature; and measures of atelectasis, total lung volume (TLV), and lung density were determined before and after each protocol. Results: None of the protocols eliminated atelectasis; the number of lung lobes with atelectasis was significantly greater during protocol 1 than during the other protocols. Lung density and TLV differed significantly among protocols, except between protocols 1 and 3. Protocol 2 TLV exceeded reference values. Arterial blood pressure after each protocol was lower than before the protocols. Mean and diastolic arterial blood pressure were higher after protocol 3 and diastolic arterial blood pressure was higher after protocol 4 than after protocol 2. Conclusions and Clinical Relevance: Standardization of ventilatory protocols may minimize effects on thoracic CT images and hemodynamic variables. Although atelectasis was still present, ventilatory protocols 3 and 4 provided the best compromise between image quality and hemodynamic stability.

Objective: To determine the effects of clenbuterol, at a dosage of up to 3.2 μg/kg for 14 days, PO, on skeletal and cardiac muscle in healthy horses undergoing treadmill exercise. Animals: 12 healthy horses from 3 to 10 years old. Procedures: Horses were randomly assigned to a control group (n = 6) or clenbuterol group (6) and received either saline (0.9% NaCl) solution or clenbuterol, PO, every 12 hours for 14 days. Horses were subjected to submaximal treadmill exercise daily during treatment. Muscle biopsy specimens were collected before and after treatment for determination of apoptosis. Echocardiographic measurements, serum clenbuterol and cardiac troponin I concentrations, and serum activities of creatine kinase and aspartate aminotransferase were measured before, during, and after treatment. Jugular venous blood samples were collected every 3 days during treatment. Echocardiography was repeated every 7 days after beginning treatment. Response variables were compared between treatment groups and across time periods. Results: No significant effect of clenbuterol or exercise on response variables was found between treatment and control groups at any time point or within groups over time. Conclusions and Clinical Relevance: Results did not reveal any adverse effects of treatment with an approved dose of clenbuterol on equine cardiac or skeletal muscle in the small number of horses tested.

Objective: To compare results of single-point kinetic gait analysis (peak and impulse) with those of complete gait waveform analysis. Animals: 15 healthy adult mixed-breed dogs. Procedures: Dogs were trotted across 2 force platforms (velocity, 1.7 to 2.1 m/s; acceleration and deceleration, 0.5 m/s2). Five valid trials were recorded on each testing day. Testing days 1 and 2 were separated by 1 week, as were days 3 and 4. Testing days 1 and 2 were separated from days 3 and 4 by 1 year. A paired t test was performed to evaluate interday and interyear differences for vertical and craniocaudal propulsion peak forces and impulses. Vertical and craniocaudal propulsion force-time waveforms were similarly compared by use of generalized indicator function analysis (GIFA). Results: Vertical and craniocaudal propulsion peak forces and impulses did not differ significantly between days 1 and 2 or days 3 and 4. When data were compared between years, no significant differences were found for vertical impulse and craniocaudal propulsion peak force and impulse, but differences were detected for vertical peak force. The GIFA of the vertical and craniocaudal force-time waveforms identified significant interday and interyear differences. These results were identical for both hind limbs. Conclusions and Clinical Relevance: Findings indicated that when comparing kinetic data overtime, additional insight may be gleaned from GIFA of the complete waveform, particularly when subtle waveform differences are present.

Objective: To determine the effects of hypothyroidism on insulin sensitivity, glucose tolerance, and concentrations of hormones counter-regulatory to insulin in dogs. Animals: 8 anestrous mixed-breed bitches with experimentally induced hypothyroidism and 8 euthyroid control dogs. Procedures: The insulin-modified frequently sampled IV glucose tolerance test and minimal model analysis were used to determine basal plasma insulin and glucose concentrations, acute insulin response to glucose, insulin sensitivity, glucose effectiveness, and disposition index. Growth hormone response was assessed by stimulation and suppression tests. Additionally, basal serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentrations and urine cortisol-to-creatinine concentration ratios were measured and dual energy x-ray absorptiometry was performed to evaluate body composition. Results: Insulin sensitivity was lower in the hypothyroid group than in the euthyroid group, whereas acute insulin response to glucose was higher. Glucose effectiveness and disposition index were not different between groups. Basal serum GH and IGF-1 concentrations as well as abdominal fat content were high in hypothyroid dogs, but urine cortisol-to-creatinine concentration ratios were unchanged. Conclusions and Clinical Relevance: Hypothyroidism appeared to negatively affect glucose homeostasis by inducing insulin resistance, but overall glucose tolerance was maintained by increased insulin secretion in hypothyroid dogs. Possible factors affecting insulin sensitivity are high serum GH and IGF-1 concentrations and an increase in abdominal fat. In dogs with diseases involving impaired insulin secretion such as diabetes mellitus, concurrent hypothyroidism can have important clinical implications.

Objective: To assess the transmission of bovine viral diarrhea virus (BVDV) from experimentally infected white-tailed deer fawns to colostrum-deprived calves by use of a BVDV strain isolated from hunter-harvested white-tailed deer. Animals: 5 white-tailed deer (Odocoileus virginianus) fawns and 6 colostrum-deprived calves. Procedures: Fawns were inoculated intranasally with a noncytopathic BVDV-1a isolate (2 mL containing 10(6.7) TCID(50)/mL), and 2 days after inoculation, animals were commingled until the end of the study. Blood and serum samples were obtained on days −6, 0, 7, 14, and 21 after inoculation for reverse transcriptase PCR assay, virus neutralization, and BVDV-specific antibody ELISA. Nasal, oral, and rectal swab specimens were collected on days 0, 3, 7, 14, 17, and 21 for reverse transcriptase PCR testing. By 21 days after inoculation, all animals were euthanized and necropsied and tissues were collected for histologic evaluation, immunohistochemical analysis, and virus isolation. Results: All fawns became infected and shed the virus for up to 18 days as determined on the basis of reverse transcriptase PCR testing and virus isolation results. Evidence of BVDV infection as a result of cohabitation with acutely infected fawns was detected in 4 of the 6 calves by means of reverse transcriptase PCR testing and virus isolation. Conclusions and Clinical Relevance: On the basis of these findings, BVDV transmission from acutely infected fawns to colostrum-deprived calves appeared possible.

Objective: To immunohistochemically evaluate matrix metalloproteinase (MMP)-9 expression in benign and malignant mammary gland tumors (MMTs) in dogs and relate expression to prognostic factors and patient outcome. Animals: 118 female dogs with naturally occurring mammary gland tumors and 8 dogs without mammary gland tumors. Procedures: 24 benign mammary gland tumors and 94 MMTs (1/affected dog) were obtained during surgical treatment; control mammary gland tissue samples were collected from unaffected dogs after euthanasia for reasons unrelated to the study. Tumors were evaluated for proliferation, invasive growth, histologic grade, and metastatic capacity; expression of MMP-9 was determined immunohistochemically, and its relationship with clinical and histologic findings was investigated. For dogs with MMTs, follow-up continued for 2 years; data were used to compute overall survival time and disease-free interval and construct survival curves. Results: MMTs had significantly higher MMP-9 expression in stromal cells and in neo-plastic cells than did the benign neoplasms. Stromal MMP-9 expression was also higher in highly proliferative tumors and in tumors with invasive growth, high histologic grade, and metastatic capacity. Furthermore, tumors from patients with shorter overall survival times and disease-free intervals had higher expression of MMP-9 in stromal cells. Conclusions and Clinical Relevance: In dogs with MMTs, level of MMP-9 expression by stromal cells was related to factors of poor prognosis and shorter overall survival times and disease-free intervals. These results suggested that MMP-9 produced by tumor-adjacent stromal cells contributed to MMT progression in female dogs and that assessment of MMP-9 expression may be a valuable prognostic factor.

Objective: To determine reference values for kaolin-activated thromboelastography in echocardiographically normal cats. Animals: 30 healthy cats without evidence of cardiomyopathy on echocardiographic examination. Procedures: All cats underwent echocardiographic examination, the findings of which were reviewed by a board-certified cardiologist. Cats that struggled (n = 10) received mild sedation with butorphanol and midazolam IM to permit phlebotomy without interruption in jugular venous blood flow. Blood samples were collected for analysis of thromboelastography variables, PCV, total solids concentration, platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen concentration, and antithrombin concentration. Results: All 4 thromboelastography variables had < 5% mean intra-assay variability. Mean values were as follows: reaction time, 4.3 minutes; clotting time, 1.6 minutes; α angle, 66.5°; and maximum amplitude, 56.4 mm. Compared with nonsedated cats, cats that required sedation had a significantly shorter clotting time and greater α angle, whereas reaction time and maximum amplitude were not significantly different. Conclusions and Clinical Relevance: Kaolin-activated thromboelastography was a reliable test with unremarkable intra-assay variability in echocardiographically normal cats. Sedation may affect certain thromboelastography variables, but the effect is unlikely to be clinically important. It remains unknown whether subclinical cardiomyopathy has a significant effect on thromboelastography variables in cats.

Objective: To identify cardiac mechanisms that contribute to adaptation to high altitudes in Tibetan antelope (Pantholops hodgsonii). Animals: 9 male Tibetan antelope and 10 male Tibetan sheep (Ovis aries). Procedures: Tibetan antelope and Tibetan sheep inhabiting a region with an altitude of 4,300 m were captured, and several cardiac variables were measured. Expression of genes for atrial natriuretic peptide, brain natriuretic peptide, and calcium-calmodulin–dependent protein kinase II δ was measured via real-time PCR assay. Results: Ratios of heart weight to body weight for Tibetan antelope were significantly greater than those of Tibetan sheep, but ratios of right-left ventricular weights were similar. Mean ± SD baseline heart rate (26.33 ± 6.15 beats/min) and systolic arterial blood pressure (97.75 ± 9.56 mm Hg) of antelope were significantly lower than those of sheep (34.20 ± 6.57 beats/min and 130.06 ± 17.79 mm Hg, respectively). The maximum rate of rise in ventricular pressure in antelope was similar to that in Tibetan sheep, but after exposure to air providing a fraction of inspired oxygen of 14.6% or 12.5% (ie, hypoxic conditions), the maximum rate of rise in ventricular pressure of the antelope increased significantly to 145.1% or 148.1%, respectively, whereas that of the sheep decreased to 68.4% or 70.5%, respectively. Gene expression of calcium-calmodulin–dependent protein kinase II δ and atrial natriuretic peptide, but not brain natriuretic peptide, in the left ventricle of the heart was significantly higher in antelope than in sheep. Conclusions and Clinical Relevance: Hearts of the Tibetan antelope in this study were well adapted to high-altitude hypoxia as shown by higher heart weight ratios, cardiac contractility in hypoxic conditions, and expression of key genes regulating cardiac contractility and cardiac hypertrophy, compared with values for Tibetan sheep.