Pharmacokinetic and Phase I Evaluation of Carboplatin in Dogs

Thirty dogs with spontaneously occurring malignant neoplasms were treated monthly with carboplatin (CBDCA) given as a 30-minute intravenous infusion in a dose escalation study. Twenty-eight dogs were considered evaluable for toxicity. The maximally tolerated dose of CBDCA was conceptually defined as that dose, determined by logistic regression analyses of toxicity data, resulting in a 50% incidence of moderate toxicity (MOD₅₀) or a 5% incidence of severe toxicity (SEV₅). Each designated maximally tolerated dose was calculated for the first course of treatment only and for the first and second courses of treatment combined to estimate cumulative drug toxicity. The MOD₅₀ and SEV₅ for the first treatment course were 340 and 278 mg/M², respectively. MOD₅₀ and SEV₅ values for the first plus second treatment courses were 327 and 231 mg/M², respectively. The nadir of neutrophil and platelet counts occurred approximately 14 days after treatment. The mean neutrophil and platelet values for all dogs experiencing myelosuppression during the first two treatment courses were 1541/μL and 62,600/μL, respectively. Nonparametric pharmacokinetic analysis of plasma CBDCA values suggested that half-life (T_1/2), area-under-the-curve and total body clearance (CL_b) were not dose dependent. Volume of distribution (VD_ss) significantly increased with dose only between 100 and 150 mg/M², not between 150 and 300 mg/M². Dose-independent serum CBDCA pharmacokinetic disposition indicates that detailed investigation of tissue CBDCA distribution would be warranted and may identify novel dosing strategies that could improve the therapeutic index of CBDCA by minimizing toxicity. (Journal of Veterinary Internal Medicine 1993; 7:235–240. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Detection of an epidermoid cyst in the foot of a horse by use of magnetic resonance imaging

CASE DESCRIPTION-A 4-year-old Quarter Horse stallion was evaluated because of a 10-month history of moderate (grade 3/5) left forelimb lameness (detectable during trotting over a smooth, hard surface). CLINICAL FINDINGS-No abnormalities were detected in either forelimb via palpation or application of hoof testers; however, lameness was eliminated after administration of a palmar digital nerve block in the left forelimb. Whereas radiography and ultrasonography did not identify any left forelimb foot abnormalities, magnetic resonance (MR) imaging revealed a circumscribed soft tissue mass in the distal aspect of the digital flexor tendon sheath (DFTS) dorsal to the lateral aspect of the deep digital flexor tendon. Subsequently, the left forelimb DFTS was injected with local anesthetic, which resulted in 90% improvement of the horse's lameness. TREATMENT AND OUTCOME-The distal aspect of the left forelimb DFTS was evaluated tenoscopically. The mass was removed under tenoscopic guidance, after which the distal digital annular ligament was transected. The horse received phenylbutazone orally for 10 days, and the left forelimb DFTS was injected with hyaluronic acid and methylprednisolone acetate 7 days after the surgery. Following a rehabilitation program, the horse was returned to full training at 6 months after surgery and competed successfully during a 2-year follow-up period. CLINICAL RELEVANCE-Use of MR imaging should be considered in all lame horses for which a definitive diagnosis cannot be made via radiography, ultrasonography, or other imaging techniques, especially when the lameness has been localized to a specific anatomic region by use of diagnostic anesthesia.     

Antibody-induced internalization of viral glycoproteins in pseudorabies virus-infected monocytes and role of the cytoskeleton: a confocal study

Addition of pseudorabies virus (PrV)-specific polyclonal immunoglobulins to PrV-infected monocytes induces internalization of plasma membrane anchored viral glycoproteins. This process may interfere with antibody-dependent cell lysis and resembles the well-studied physiological endocytosis process. A confocal study was designed to investigate whether the major cellular components, involved in physiological endocytosis (clathrin, actin, dynein and microtubules), play a role in this virological internalization process. In order to visualize the interaction of endosomes, which contain the internalized viral glycoproteins, with clathrin, actin, dynein and microtubules, a double labeling of viral glycoproteins and different cellular proteins was performed. Porcine monocytes were inoculated with the PrV-strain 89V87 at a multiplicity of infection of 50 for 13h. After the addition of FITC-labeled porcine polyclonal PrV-specific antibodies, cells were fixed with para-formaldehyde at different time points and afterwards permeabilized. The different cellular components were visualized with monoclonal antibodies and a Texas Red-conjugate, with the exception of actin, which was stained with phalloidin-Texas Red. The cells were analyzed by confocal microscopy. A clear co-localization was observed between the viral glycoproteins and clathrin and dynein during the internalization process. The microtubules were in close contact with the internalized vesicles. For actin no co-localization could be observed. It can be stated that clathrin, dynein and microtubules, important components during physiological endocytosis, are also of importance during the antibody-induced internalization of viral glycoproteins.     

MENSURATION OF THE NORMAL PITUITARY GLAND FROM MAGNETIC RESONANCE IMAGES IN 96 DOGS

The pituitary gland was measured from transverse magnetic resonance T1-weighted images after Gadolinium administration in 96 dogs weighing from 13 to 45 kg. The measurements were done by hand with calipers. The mean (+/- standard deviation) pituitary gland height was 5.1 mm (+/-0.9 mm). The mean width was 6.4 mm (+/- 1.1 mm). The correlation coefficient between pituitary and brain measurements, between pituitary measurement and body weight, and brain measurements and body weight was 0.0 to 0.3. A hyperintense region was present on T1-weighted images in the center of the pituitary gland in 64% of the dogs. At necropsy the pituitary glands were grossly and histologically normal. No pituitary gland measurements were performed at necropsy.