Activating mutations in the catalytic or juxtamembrane domain of c-kit in splenic mast cell tumors of cats

OBJECTIVE: To evaluate splenic mast cell tumors (MCT) of cats for activating mutations in the proto-oncogene c-kit. SAMPLE POPULATION: 10 formalin-fixed, paraffin-embedded splenic MCT from cats in the pathology database of the Veterinary Medical Teaching Hospital at the University of California, Davis. PROCEDURE: Genomic DNA was isolated from tumor specimens, and the polymerase chain reaction (PCR) procedure was performed for exons 11, 12, and 17. The PCR products were analyzed by use of agarose gel electrophoresis and then directly sequenced. RESULTS: We did not identify mutations in the juxtamembrane domain (encoded by exons 11 and 12) or catalytic domain (encoded by exon 17) of c-kit in any of the splenic MCT specimens. CONCLUSIONS AND CLINICAL RELEVANCE: Although mutations in the proto-oncogene c-kit occur frequently in naturally developing MCT in dogs and aggressive mastocytosis in humans, the data reported here documented that dysregulation of Kit function through activating mutations is unlikely in splenic MCT of cats. Therapeutic strategies aimed at inhibiting Kit signaling (ie, kinase inhibitors such as imatinib [STl571]) may not be of benefit for the treatment of this disease in cats.     

Factors affecting breeding soundness classification of beef bulls examined at the Western College of Veterinary Medicine

Breeding soundness evaluation records from 2110 beef bulls, for the period of 1986 to 1999, were analyzed to determine the prevalence and importance of factors affecting breeding soundness classification. The percentage of all bulls classified as satisfactory ranged from 49.0% in January to 73.3% in May. The percentage of physically normal bulls with satisfactory semen quality ranged from 65.7% in January to 87.5% in June. Poor body condition or excessive body condition, below average or below the recommended minimum scrotal circumference, lameness, and severe scrotal frostbite significantly reduced the probability of a satisfactory breeding soundness classification. The percentage of sperm with midpiece defects declined significantly and the percentage of sperm with head defects increased significantly with the approach of summer. Photoperiod, cold stress, poor or excessive body condition, and reduced feed quality may interact to reduce semen quality in the winter months.     

Comparison of Fine-Needle Aspiration and Surgical-Tissue Biopsy in the Diagnosis of Canine Brain Tumors

OBJECTIVE: To compare the diagnoses obtained using fine-needle aspiration (FNA) and surgical-tissue biopsy of focal cerebral masses with the histologic diagnoses obtained via necropsy. STUDY DESIGN: A prospective case series. SAMPLE POPULATION: Ten client-owned adult dogs of various breeds. All dogs had clinical signs of cerebral disease and had a focal brain mass identified using magnetic resonance imaging; all were eventually euthanatized. METHODS: Immediately after euthanasia, the brains were removed en bloc from the cranial cavity. FNAs were obtained from each mass using a 22-gauge hypodermic needle and a 12-mL syringe. Cytologic preparations were made from each aspirate. A 14-gauge Tru-cut biopsy needle was used to obtain a core tissue sample from each mass. The biopsy specimens were fixed in 10% buffered formalin and submitted for histologic evaluation. The brains were similarly fixed and stained. Six-micrometer-thick transverse sections of the brain were examined microscopically. RESULTS: Neoplasia was confirmed in all dogs histologically in the 6-microm transverse sections. Four meningiomas, 2 astrocytomas, 2 oligodendrogliomas, 1 pituitary adenocarcinoma, and 1 neurofibrosarcoma were identified. FNA correctly identified all of the masses as neoplastic. Cytologic diagnoses correlated with the histologic interpretation in 5 of the masses (50%). Tru-cut biopsy specimens identified all 10 masses as neoplastic; in 9 of the 10 (90%), the diagnosis correlated with the histologic diagnosis. CONCLUSIONS AND CLINICAL RELEVANCE: FNA is a sensitive method that can be used to determine the presence of neoplasia in the brain, but is not as definitive as the Tru-cut biopsy in determining the specific type of cerebral neoplasm.     

The role of small molecule inhibitors for veterinary patients.

Advances in molecular biology over the past several years have permitted a much more detailed understanding of cellular dysfunction at the biochemical level in cancer cells. This has resulted in the identification of novel targets for therapeutic intervention, including proteins that regulate signal transduction, gene expression, and protein turnover. In many instances, small molecules are used to disrupt the function of these targets, often through competitive inhibition of ATP binding or the prevention of necessary protein-protein interactions. Future challenges lie in identifying appropriate targets for intervention and combining small molecule inhibitors with standard treatment modalities, such as radiation therapy and chemotherapy.     

Generalized calcinosis cutis associated with disseminated paecilomycosis in a dog

A 4‐year‐old spayed female mixed breed dog was referred to the Michigan State University, Veterinary Teaching Hospital (MSU‐VTH) with vomiting, lethargy and anorexia of 2 weeks duration. Abdominal radiographs and ultrasonography showed hepatosplenomegaly. Cytological evaluation of ultrasound‐guided fine needle aspirates of the liver and spleen revealed fungal organisms and pyogranulomatous inflammation; fungal culture documented Paecilomyces variotii infection. The dog received antifungal therapy and supportive care. Multiple firm plaque‐like skin lesions, predominantly involving the inguinal region, developed 18 days after initial presentation and were diagnosed histopathologically as calcinosis cutis. While generalized calcinosis cutis has been reported in three dogs with blastomycosis and one dog with leptospirosis, the association with disseminated Paecilomyces spp. infection is novel.     

Oral bioavailability of etoposide after administration of a single dose to tumor-bearing dogs

OBJECTIVE: To characterize oral bioavailability and pharmacokinetic disposition of etoposide when the IV formulation was administered orally to dogs. ANIMALS: 8 tumor-bearing dogs. PROCEDURES: An open-label, single-dose, 2-way crossover study was conducted. Dogs were randomly assigned to initially receive a single dose of etoposide (50 mg/m2) IV or PO. A second dose was administered via the alternate route 3 to 7 days later. Medications were administered before IV administration of etoposide to prevent hypersensitivity reactions. Oral administration of etoposide was prepared by reconstituting the parenteral formulation with 0.9% NaCl solution and further diluting the reconstituted mixture 1:1 with a sweetening agent. Plasma samples were obtained after both treatments. Etoposide concentrations were measured with a high-performance liquid chromatography assay, and plasma etoposide concentration-time profiles were analyzed by use of noncompartmental methods. RESULTS: 4 dogs had hypersensitivity reactions during IV administration of etoposide. No adverse effects were detected after oral administration. Plasma etoposide concentrations were undetectable in 2 dogs after oral administration. Oral administration of etoposide resulted in significantly lower values for the maximum plasma concentration and the area under the plasma etoposide concentration-versus-time curve, compared with results for IV administration. Oral bioavailability of etoposide was low (median, 13.4%) and highly variable among dogs (range, 5.7% to 57.3%). CONCLUSIONS AND CLINICAL RELEVANCE-Vehicle-related toxicosis can limit the IV administration of etoposide in dogs. The parenteral formulation of etoposide can be safely administered orally to dogs, but routine use was not supported because of low and variable oral bioavailability in this study.     

Diagnosis and treatment of dynamic closed-mouth jaw locking in a dog

CASE DESCRIPTION: A 5-year-old neutered male English Bulldog was evaluated for intermittent closed-mouth jaw locking of approximately 1 week's duration. CLINICAL FINDINGS: Initial physical examination revealed a nonpainful inability to open the jaw with and without manual assistance; however, manipulation of the jaw after the dog was sedated for diagnostic imaging restored jaw function. Anesthesia was subsequently induced, and computed tomography was performed with the jaw open and closed; contrast agent-enhanced images of the closed jaw were also obtained. No abnormalities of the temporomandibular joints or retrobulbar space were detected. Fluoroscopic examination of movement of the temporomandibular joints revealed a dynamic interference of the rostrodorsal aspect of the coronoid process of the left mandibular ramus with the medial surface of the frontal process of the left zygomatic bone or the left orbital ligament. TREATMENT AND OUTCOME: Partial excision of the coronoid process of the left mandibular ramus was performed. The dog recovered without complication and was able to open and close its jaw and eat within 6 hours after surgery. No additional episodes of jaw locking were detected during the 6 months after surgery. CLINICAL RELEVANCE: To the authors' knowledge, closed-mouth jaw locking in animals attributable to dynamic interference of the rostrodorsal aspect of the coronoid process of a mandibular ramus with the medial surface of the frontal process of a zygomatic bone or an orbital ligament has not been described. Surgical excision of the coronoid process of the mandibular ramus appeared to provide a successful outcome in the dog of this report.     

Canine immune-mediated polyarthritis: Clinical and laboratory findings in 83 cases in western Canada (1991–2001)

A hospital-based, case-control study was used to describe clinical and laboratory findings in 83 dogs diagnosed with noninfectious, nonerosive, immune-mediated polyarthritis (IMPA) in western Canada. Case medical records were reviewed. Cases were analyzed as total IMPA cases and as subgroups [breed, systemic lupus erythematosus (SLE), reactive, and idiopathic] and compared with the general canine hospital population. Dogs with IMPA differed in age (P = 0.004) and weight (P = 0.01) from other hospital admissions. Idiopathic IMPA cases were older (4–10 y; P < 0.05), compared with the general canine hospital population, and their common laboratory abnormalities included the following: leukocytosis, nonregenerative anemia, increased alkaline phosphatase, and hypoalbuminemia. The SLE cases were seen more often in summer and fall (P = 0.04), raising concern of an undiagnosed etiologic agent. The hock joint appeared to be the most reliable for diagnosis of IMPA, and arthrocentesis of both hock joints may aid in case identification.