The impact of carboplatin and toceranib phosphate on serum vascular endothelial growth factor (VEGF) and metalloproteinase-9 (MMP-9) levels and survival in canine osteosarcoma.

In this pilot study, 10 dogs with osteosarcoma (OSA) were treated with amputation and subsequent carboplatin chemotherapy (300 mg/m2 IV q3wk × 4 doses) followed by toceranib phosphate (2.75 mg/kg PO q48h starting at day 14 post carboplatin). Monthly clinical monitoring and serum measurements of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were acquired. No dogs were removed from the study due to toxicity. Levels of VEGF and MMP-9 did not change over time. Seven dogs died related to local recurrence and/or pulmonary or bone metastasis and the remainder died of other causes. Median OSA-free survival was 238 d with 34% 1-year progression-free survival. Median overall survival was 253 d with 30% alive at 1.5 y and 10% alive at 2 y. Although this regimen was well-tolerated, survival times did not exceed previously published data from dogs treated with amputation plus chemotherapy alone.

Dans cette étude pilote, 10 chiens avec un ostéosarcome (OSA) ont été traités par amputation et chimiothérapie subséquente avec du carboplatin (300 mg/m2 IV q3sem × 4 doses) suivi de phosphate de toceranib (2,75 mg/kg PO q48h débutant au jour 14 suivant le carboplatin). Un suivi clinique mensuel et une mesure des taux sériques du facteur de croissance de l'endothélium vasculaire (FCEV) et de la matrice de la métalloprotéinase-9 (MMP-9) ont été obtenus. Aucun chien ne fut retiré de l'étude pour cause de toxicité. Les niveaux de FCEV et MMP-9 n'ont pas changé dans le temps. Sept chiens sont décédés dues à une rechute locale et/ou des métastases osseuses et les autres sont morts d'autres causes. La durée médiane de survie libre d'OSA était de 238 j avec 34 % de survie sans progression de la condition après 1 an. La durée de survie médiane était de 253 j avec 30 % en vie après 1,5 an et 10 % en vie après 2 ans. Bien que ce traitement ait été bien toléré, les temps de survie n'ont pas excédé les résultats publiés antérieurement pour des chiens traités par amputation et chimiothérapie uniquement.(Traduit par Docteur Serge Messier).

Assessment of the prevalence and clinical features of cryptogenic epilepsy in dogs: 45 cases (2003-2011).

OBJECTIVE: To determine the prevalence and clinical features of cryptogenic epilepsy among dogs. DESIGN: Retrospective case series. ANIMALS: 214 client-owned dogs with onset of epileptic seizures at ≥ 7 years of age. PROCEDURES: A diagnostic imaging database was searched for dogs with symptomatic or cryptogenic epilepsy. Signalment, seizure history, and diagnostic information were recorded. Information regarding seizure frequency, administration of antiepileptic drugs (AEDs), owners' perceptions regarding quality of life, survival times, and causes of death for dogs with cryptogenic epilepsy was obtained via questionnaire. Variables were compared among dogs grouped according to diagnosis and age. RESULTS: 45 (21%) dogs had a diagnosis of cryptogenic epilepsy, and 169 (79%) had symptomatic epilepsy. In dogs 7 to 9 years and ≥ 10 years of age at the time of seizure onset, 31 of 106 (29%) and 14 of 108 (13%), respectively, had a diagnosis of cryptogenic epilepsy. At last follow-up, most (40 [89%]) dogs with cryptogenic epilepsy were receiving ≥ 1 AED. Thirty-one of 37 (84%) dogs typically had ≤ 1 seizure/mo following hospital discharge. Death was confirmed in 20 (44%) dogs with cryptogenic epilepsy and was related to seizures or AEDs in 7 Median survival time from onset of seizures was 52 months for all dogs with cryptogenic epilepsy. Median quality-of-life score (scale, 1 [poor] to 10 [excellent]) indicated by 34 owners of dogs with cryptogenic epilepsy was 10 before diagnosis and initiation of AED treatment and 8 afterward. CONCLUSIONS AND CLINICAL RELEVANCE: Cryptogenic epilepsy was diagnosed in a substantial proportion of dogs with an onset of epileptic seizures at ≥ 7 years of age. Seizure control was considered acceptable in most dogs.

Levetiracetam pharmacokinetics in healthy dogs following oral administration of single and multiple doses.

OBJECTIVE: To measure pharmacokinetics of levetiracetam (LEV) after single-dose oral administration in healthy dogs and determine whether pharmacokinetics changed after repeated oral dosing. ANIMALS: 6 healthy adult dogs. PROCEDURES: Pharmacokinetics were calculated following administration of a single dose (mean, 21.7 mg/kg, PO; day 1) and after administration of the last dose following administration for 6 days (20.8 to 22.7 mg/kg, PO, q 8 h; days 2 to 7). Plasma LEV concentrations were determined by use of high-pressure liquid chromatography. Pharmacokinetic data were analyzed by use of a 1-compartment model with first-order absorption. RESULTS: Peak concentration occurred 0.6 hours after administration of the first dose, with an absorption half-life of 0.06 hours. Minimal accumulation occurred over the 7 days, with only a slight increase in total area under the concentration-versus-time curve from 268.52 +/- 56.33 h x microg/mL (mean +/- SD) to 289.31 +/- 51.68 h x microg/mL after 7 days. Terminal half-life was 2.87 +/- 0.21 hours after the first dose and 3.59 +/- 0.82 hours after the last dose on day 7. Trough plasma concentrations were variable, depending on the time of day they were measured (morning trough concentration, 18.42 +/- 5.16 microg/mL; midday trough concentration, 12.57 +/- 4.34 microg/mL), suggesting a diurnal variation in drug excretion. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the pharmacokinetics of LEV did not change appreciably after administration of multiple doses over 7 days. Administration of LEV at a dosage of 20 mg/kg, PO, every 8 hours to healthy dogs yielded plasma drug concentrations consistently within the therapeutic range established for LEV in humans.

Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh).

OBJECTIVE: To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots. ANIMALS: 20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh). PROCEDURES: In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments). RESULTS: Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group. CONCLUSIONS AND CLINICAL RELEVANCE: In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole < or = 0.4 microg/mL. Higher doses may be needed to maintain plasma voriconazole concentrations during long-term treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.

A model for improving student confidence and experience in diagnostic sample collection and interpretation.

Confidence and proficiency in diagnosing and treating a variety of diseases is of obvious importance to veterinary students. Traditional teaching methods relying on live-animal laboratories or teaching-hospital cases may not provide the breadth and depth of experience necessary to promote optimal development of confidence and skills. These settings also raise concerns about expense, about animal welfare when animals are used in teaching laboratories, and about the stress and potential risks associated with client-owned pets in the teaching hospital. A one-week course implemented in our veterinary curriculum provides the opportunity for students to develop self-assurance and experience in sample collection and interpretation skills in a realistic, clinical-model setting. This course provides students with significantly improved levels of confidence when performing procedures and interpreting results from a variety of procedures and helps prepare them to become clinicians entering the practice of veterinary medicine.