Hepatotoxicity associated with CCNU (lomustine) chemotherapy in dogs

One hundred seventy-nine tumor-bearing dogs were treated with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) between 1995 and 2001. CCNU was given as a single dose of 50-110 mg/m2 body surface area PO. Treatment interval varied, but the minimal interval between CCNU doses was 3 weeks. After treatment, 11 dogs (6.1%) developed hepatic toxicity. The median number of CCNU doses and the median total cumulative CCNU dose were significantly higher in dogs that developed hepatic toxicity (4 doses; 350 mg/m2) than in dogs without hepatic damage (3 doses; 230 mg/m2). Median duration to detection of hepatic toxicity from the last dose of CCNU was 11 weeks (range 2-49 weeks). Common biochemical abnormalities were abnormally high serum liver enzyme activities and hypoalbuminemia. Six dogs with CCNU-associated hepatic toxicity had ascites, and 3 dogs had concurrent pleural effusion. Serum concentrations of bile acids were abnormally high in 4 of 5 dogs tested. Percutaneous ultrasound-guided liver biopsies were performed in 10 dogs, and findings were nonspecific and chronic in nature. Seven dogs were euthanized because of progressive liver failure, and their median survival from diagnosis of liver disease was 9 weeks. Three dogs died of other causes and 1 dog of unknown cause. Although clinical signs resolved in 3 dogs, biochemical abnormalities and histopathologic lesions persisted 4 to 38 months from the time of diagnosis of liver disease. Our findings suggest that CCNU can cause delayed, cumulative dose-related, chronic hepatotoxicity that is irreversible and can be fatal.     

Septic lens implantation syndrome in a cat

A 13-year-old female spayed domestic shorthair cat was presented initially for a change in the appearance of the left eye. On initial examination, a small penetrating wound was suspected as the cause for a corneal scar, an anterior cortical incipient cataract and mild iritis. The cat was not re-presented until 1 year later at which time ocular pain was marked. Severe anterior uveitis and glaucoma were diagnosed and the eye enucleated. Histopathology documented intralenticular coccoid bacteria and septic lens implantation syndrome.     

Use of alternating administration of carboplatin and doxorubicin in dogs with microscopic metastases after amputation for appendicular osteosarcoma: 50 cases (1999-2006)

OBJECTIVE:To evaluate the efficacy and toxicity of an alternating carboplatin and doxorubicin chemotherapy protocol in dogs with putative microscopic metastases after amputation for appendicular osteosarcoma and assess patient-, tumor-, and treatment-related factors for associations with prognosis. DESIGN: Retrospective case series. ANIMALS: 50 client-owned dogs. PROCEDURES: Records of dogs that underwent amputation for appendicular osteosarcoma and received an alternating carboplatin and doxorubicin chemotherapy protocol were reviewed. Dogs had full staging and were free of detectable metastases prior to chemotherapy. Data on disease-free interval (DFI), survival time, and toxicoses were retrieved from medical records and owner or referring veterinarian communications. RESULTS: Median DFI was 202 days. Median survival time was 258 days. Twenty-nine (58%) dogs completed the protocol as planned, and the rest were withdrawn typically because of metastases or toxicoses. Grade 3 or 4 myelosuppression was reported in 9 of 50 (18%) dogs and grade 3 or 4 gastrointestinal toxicosis in 6 of 50 (12%) dogs. There were no chemotherapy-related fatalities. Univariate factors associated with significant improvement in DFI included tumor location (radius), receiving doxorubicin as the first drug, starting chemotherapy more than 14 days after amputation, and no rib lesions on preamputation bone scans. Multivariate factors associated with a significant improvement in survival time were tumor location (radius) and completing chemotherapy. CONCLUSIONS AND CLINICAL RELEVANCE: Alternating administration of carboplatin and doxorubicin resulted in DFI and survival time similar to those reported for single-agent protocols. Clients should be counseled regarding the likelihood of toxicoses. Relevance of sequence and timing of starting chemotherapy should be further evaluated.     

Combined laparoscopic ovariectomy and laparoscopic-assisted gastropexy utilizing a 2-port technique in 10 dogs

A case series was selected retrospectively to evaluate the technique, outcome, and short-term complications associated with a combined laparoscopic ovariectomy (Lap OVX) and laparoscopic-assisted gastropexy (LAG) using a 2-port technique, and to compare it with previously published combined laparoscopic techniques for Lap OVX and LAG in dogs. Medical records of dogs undergoing elective, combined Lap OVX and LAG performed using a 2-port technique between 2017 and 2019 were reviewed. Total surgical time was compared to previously published combined Lap OVX and LAG techniques in dogs. Intraoperative and short-term complications were recorded. Ten dogs [median weight: 29.4 kg (range: 11.4 to 84.1 kg); mean: 37.4] met the inclusion criteria. Median surgical time to complete both the Lap OVX and LAG was 72.5 minutes (range: 47.0 to 120.0 minutes; mean: 77.4 minutes), which was not significantly different than that described in previous studies of combined Lap OVX and LAG (weighted mean average: 67.3 minutes; 95% confidence interval: 46.9 to 87.7, P = 0.3). No intraoperative or postoperative complications were reported. It is concluded that a 2-port technique for combined Lap OVX and LAG is feasible, has few complications, and requires similar time to perform compared to other previously published laparoscopic techniques.     

Blood gas analysis and cooximetry in retired racing Greyhounds

Objective – The purposes of this study were to evaluate the oxygen affinity of hemoglobin (Hb) in healthy retired racing Greyhounds via cooximetry, and to establish reference intervals for blood gases and cooximetry in this breed. Design – Prospective clinical study. Setting – University Teaching Hospital. Animals – Fifty‐seven Greyhounds and 30 non‐Greyhound dogs. Interventions – Venous blood samples were collected from the jugular vein and placed into heparinized tubes. The samples were analyzed within 30 minutes of collection using a blood gas analyzer equipped with a cooximeter. Measurements and Main Results – Greyhounds had significantly higher pH, PO₂, oxygen saturation, oxyhemoglobin, total Hb, oxygen content, and oxygen capacity and significantly lower deoxyhemoglobin and P₅₀ when compared with non‐Greyhound dogs. Conclusion – These findings support the fact that this breed is able to carry a higher concentration of total oxygen in the blood. As reported previously, this breed also has lower P₅₀ and, therefore, high oxygen affinity. In light of recent findings suggesting that in certain tissues a high affinity for oxygen is beneficial, this adaptation may be of benefit during strenuous exercise.     

In vitro efficacy of lufenuron against filamentous fungi and blood concentrations after PO administration in horses

Lufenuron is a benzoylphenyl urea-derived insecticide that has been recently introduced as a novel treatment for fungal infections in horses. The purposes of this study were to determine (1) the in vitro efficacy of lufenuron against Aspergillus and Fusarium spp. and (2) the ability of lufenuron to reach efficacious blood concentrations after PO administration in horses. Fungal colonies isolated from diseased equine corneas were tested against lufenuron solutions up to 700 microg/mL. Twenty-one adult horses received 1 of 3 PO lufenuron treatment regimens: 5 mg/kg body weight (BW) q24h for 3 days, 20 mg/kg BW q24h for 3 days, or 60 mg/ kg BW q24h for 1 day. Blood samples were collected up to 96 hours after drug administration and analyzed by high-performance liquid chromatography. Statistical analyses of lufenuron blood concentrations were performed by analysis of variance and Fischer's Least Significant Difference test, with statistical significance set at P < .05. Lufenuron showed no effect on the in vitro growth of Aspergillus or Fusarium spp. Lufenuron was detected in the blood of all but 1 horse and showed no adverse effects. The maximum blood lufenuron concentration (83.5 +/- 58.7 microg/L) was lower than the concentrations proven to be ineffective in vitro in this study. Further therapeutic use of lufenuron as an antifungal agent in horses should be based on proven efficacy against specific strains of clinically relevant fungi with pharmacokinetic data demonstrating sufficient lufenuron concentrations in target tissues.     

Absorption of Different Oral Formulations of Natural Vitamin E in Horses

The objective of this study was to determine the effect of vitamin E source on plasma vitamin E concentration. Five different formulations of natural source vitamin E (4,000 IU/day) were supplemented to Standardbred mares (n = 4 per group) for 14 days. Treatment 1 was given 10 g of 400 IU/g natural acetate (RRR-α-tocopheryl-acetate) powder, treatment 2 was given 6.66 g of 600 IU/g natural acetate powder, treatment 3 was given 6.66 g of 600 IU/g natural alcohol (RRR-α-tocopherol) powder, treatment 4 was given 20 g of 200 IU/g micellized natural alcohol powder, and treatment 5 was given 8 mL of 500 IU/mL micellized natural alcohol liquid. Blood samples were collected before supplementation (day 0), after day 7 and day 14 of supplementation, and analyzed for plasma α-tocopherol. Treatments 1, 2, and 3 increased (P < .05) from days 0 to 7, but remained similar at day 14. Treatments 4 and 5 also increased (P = .004, and P < .0001, respectively) from days 0 to 7 and were higher (P < .05) than treatment 1, 2, and 3. Plasma levels peaked at day 7 and either plateaued or decreased (treatment 5, P = .004) at day 14. The micellized alcohol formulations remained elevated (treatment 4) or decreased (treatment 5) after achieving peak blood concentration and, as hypothesized, tended to have plasma concentrations higher than the other vitamin E forms. Care should be taken to ensure that the most active biologically available form of vitamin E is provided in the diet to maximize its efficiency.