Plasma ammonia concentration after L-asparaginase therapy in 27 dogs with high-grade lymphoma or leukemia.

OBJECTIVES: To establish the occurrence of increased plasma ammonia concentration after L-asparaginase (L-asp) administration in dogs with high-grade lymphoma or leukemia; to identify risk factors for the development of hyperammonemia after L-asp administration; and to determine occurrence of adverse events related to hyperammonemia. DESIGN: Prospective case controlled study of sequentially enrolled dogs between May 2011 and March 2012. SETTING: A university veterinary teaching hospital. ANIMALS: Twenty-seven dogs with high-grade lymphoma or leukemia. INTERVENTIONS: All dogs received L-asp intramuscularly at a median dose of 400 IU/kg. MEASUREMENTS AND MAIN RESULTS: Plasma ammonia concentrations were measured at baseline, 16 hours, and 48 hours after L-asp therapy. Clinicopathological abnormalities were assessed to determine risk factors for the development of hyperammonemia. Adverse events following L-asp were recorded. Median plasma ammonia concentrations at baseline, 16 hours, and 48 hours were 26 µmol/L (44 µg/dL), 98 µmol/L (166.9 µg/dL), and 67 µmol/L (114 µg/dL), respectively. Median plasma ammonia concentrations at 16 and 48 hours after administration were significantly increased compared to baseline. Six dogs had adverse events following L-asp administration. No significant clinical signs were noted that could clearly be attributed to hyperammonemia. No risk factors for developing hyperammonemia were identified; however, there was a positive correlation between the development of hyperammonemia at 16- and 48-hour time points. CONCLUSIONS: Subclinical hyperammonemia in dogs with lymphoma or leukemia after L-asp administration appears to be common. No risk factors were identified for the development of hyperammonemia after L-asp treatment, and severe adverse events were rare.

Macrocytosis secondary to hydroxyurea therapy.

A 10-year-old, male neutered Shetland Sheepdog was presented to the University of Florida for evaluation of a well-granulated mast cell tumor. Hydroxyurea therapy was instituted and serial CBCs showed persistent mild anemia and macrocytosis without a corresponding increase in polychromasia. The dog's MCV increased progressively, reaching its highest value of 100.0 fL after 6 months of treatment, and a diagnosis of macrocytosis associated with hydroxyurea therapy was made. The dog's increase in MCV was prominent, and rapidly decreased after the drug was discontinued, consistent with previous observations in human and canine subjects treated with hydroxyurea. Hydroxyurea is a cytotoxic chemotherapeutic agent used in a variety of conditions in human and veterinary medicine, and megaloblastic changes associated with its use have been described in multiple species. This report shows that hydroxyurea treatment is a differential diagnosis for prominent macrocytosis in dogs in the absence of other signs of erythrocyte regeneration.

The effect of marker location variability on noninvasive canine stifle kinematics.

OBJECTIVE: Evaluate the effect of marker placement on kinematics of the canine stifle in 3 distinct hindlimb models. STUDY DESIGN: In vivo biomechanical study. ANIMALS: Normal adult mixed-breed dogs (n=5). METHODS: Ten retroreflective markers were affixed to the skin on the right rear leg of each dog to establish normal stifle kinematics. Four additional markers were placed around the greater trochanter (GT), 2 m cranial, caudal, dorsal, and ventral to evaluate single marker placement variability on kinematic model data. Dogs were walked and trotted 5 times through the calibrated space. Sagittal flexion and extension angle waveforms were acquired during each trial with 3 models that were produced simultaneously during each gait. The GT marker was reassigned to 1 of the 4 additional locations (cranial, caudal, dorsal, and ventral) to alter the kinematic model. Comparison of sagittal flexion and extension angle waveforms was performed with Generalized Indicator Function Analysis. RESULTS: Each model provided consistent equivalent sagittal flexion-extension data. Analysis revealed statistically significant differences between all GT locations. The differences were greatest in the cranial and caudal locations for all models. CONCLUSIONS: Deviation of the GT marker in the cranial/caudal direction from an anatomically normal position produces a greater degree of difference than deviation in a dorsal/ventral direction.

Comparison of canine stifle kinematic data collected with three different targeting models.

OBJECTIVE: To model the kinematics of the canine stifle in 3 dimensions using the Joint Coordinate System (JCS) and compare the JCS method with linear and segmental models. STUDY DESIGN: In vivo biomechanical study. ANIMALS: Normal adult mixed breed dogs (n=6). METHODS: Dogs had 10 retroreflective markers affixed to the skin on the right pelvic limb. Dogs were walked and trotted 5 times through the calibrated space and the procedure was repeated 5 days later. Sagittal flexion and extension angle waveforms acquired during each trial with all 3 models (JCS, Linear, and Segmental) were produced simultaneously during each gait. The JCS method provided additional internal/external and abduction/adduction angles. Comparison of sagittal flexion and extension angle waveforms was performed with generalized indicator function analysis (GIFA) and Fourier analysis. A normalization procedure was performed. RESULTS: Each model provided consistent equivalent sagittal flexion-extension data. The JCS provided consistent additional internal/external and abduction/adduction. Sagittal waveform differences were found between methods and testing days for each dog at a walk and a trot with both GIFA and Fourier analysis. After normalization, differences were less with Fourier analysis and were unaltered with GIFA. CONCLUSIONS: Whereas all methods produced similar flexion-extension waveforms, JCS provided additional valuable data. CLINICAL RELEVANCE: The JCS model provided sagittal plane flexion/extension data as well as internal/external rotation and abduction/adduction data.

Effects of firocoxib, meloxicam, and tepoxalin on prostanoid and leukotriene production by duodenal mucosa and other tissues of osteoarthritic dogs.

OBJECTIVE: To evaluate the in vivo effects of firocoxib, meloxicam, and tepoxalin on prostaglandin (PG) and leukotriene production in duodenal mucosa and other target tissues in dogs with chronic osteoarthritis (OA). ANIMALS: 8 dogs with chronic, unilateral OA of the stifle joint. PROCEDURES: In a crossover design, each dog received placebo (no treatment), firocoxib, meloxicam, or tepoxalin for 7 days, followed by a 21-day washout period. On the first day of treatment (day 0; baseline) and days 2, 4, and 7, samples of whole blood, synovial fluid, and gastric and duodenal mucosae were collected. Prostaglandin E2 concentrations were measured in synovial fluid of the stifle joint and after ex vivo stimulation of whole blood samples. Synthesis of PGE1 and PGE2 was measured in samples of gastric and duodenal mucosae. Concentrations of thromboxane B2 (TxB2) were measured in whole blood samples. Leukotriene B4 (LTB4) concentrations were measured in samples of whole blood (ex vivo stimulation) and gastric and duodenal mucosae. RESULTS: Firocoxib, meloxicam, and tepoxalin significantly suppressed whole blood concentrations of PGE2, compared with baseline and placebo concentrations, at days 2, 4, and 7. Tepoxalin significantly suppressed serum TxB2 concentrations, compared with baseline, firocoxib, meloxicam, and placebo, at all 3 time points. Production of PGE1 and PGE2 was significantly lower in duodenal versus gastric mucosa. Tepoxalin significantly decreased rates of PGE1 and PGE2 in duodenal and gastric mucosae, compared with baseline rates. CONCLUSIONS AND CLINICAL RELEVANCE: PG production was lower in the duodenum than in the stomach. Firocoxib had a COX-1-sparing effect in vivo.

Kinetic gait and subjective analysis of the effects of a tachykinin receptor antagonist in dogs with sodium urate-induced synovitis.

OBJECTIVE: To examine the ability of preemptive administration of a proprietary neurokinin-1 (NK(1)) receptor antagonist to attenuate limb dysfunction associated with monosodium urate-induced synovitis in the stifle joints of dogs. ANIMALS: 16 clinically normal adult mixed-breed dogs (8 males and 8 females). PROCEDURES: A crossover study was conducted in 2 phases. Dogs were assigned to 2 groups (8 dogs/group) and orally administered an NK(1) receptor antagonist (3 mg/kg) or a control substance once daily for 4 days. Synovitis was then induced in the left stifle joint by intra-articular injection of monosodium urate. Investigators were not aware of treatment group assignments. Dogs were evaluated by use of subjective lameness scores during standing, walking, and trotting and by use of ground reaction force data 3, 6, 9, 12, and 24 hours after urate injection. After a 21-day washout period, the experiment was repeated with each dog administered the other treatment and injected with monosodium urate in the contralateral stifle joint. RESULTS: No significant differences were detected between the NK(1) receptor antagonist and control treatments with regard to peak vertical force, vertical impulse area, or subjective evaluations of lameness during standing, walking, or trotting, except during walking 24 hours after monosodium urate injection. CONCLUSIONS AND CLINICAL RELEVANCE: Preemptive administration of an NK(1) receptor antagonist failed to significantly improve subjective or objective outcome measures in dogs with monosodium urate-induced synovitis.