Phase I Dose Escalation of Single‐Agent Vinblastine in Dogs

Background: Vinblastine (VBL) is commonly used in dogs at a dosage of 2.0 mg/m². The minimal toxicity observed at this dosage indicates that higher dosages might be well tolerated. Hypothesis: The maximum tolerated dosage (MTD) for a single VBL treatment is higher than the previously published dosage of 2.0 mg/m². Animals: Twenty‐three dogs with lymphoma or cutaneous mast cell tumors. Methods: Dogs received 1 single‐agent VBL treatment IV. The starting dosage was 3.0 mg/m², and dosages were increased in increments of 0.5 mg/m² in cohorts of 3 dogs. Hematologic toxicity was assessed with weekly CBCs. Gastrointestinal toxicity was assessed from medical histories from owners. Once the MTD was determined, additional dogs were treated with VBL at that dosage. Dogs whose cancers responded to VBL continued to receive treatments q2–3 weeks. Results: VBL dosages ranged from 3.0 to 4.0 mg/m². Neutropenia was the dose‐limiting toxicity, with the nadir identified 7 days after treatment and resolving by 14 days after treatment. The MTD was 3.5 mg/m². Sixteen dogs were treated at this dosage, and 3 experienced severe toxicity characterized by asymptomatic grade 4 neutropenia, febrile grade 4 neutropenia, and death. Gastrointestinal toxicity was mild and self‐limiting. Preliminary evidence of antitumor activity was identified in 2 of 12 dogs with lymphoma treated at the MTD. Conclusions and Clinical Importance: In dogs, single‐agent VBL is well tolerated at a dosage of 3.5 mg/m² IV. At this dosage, the minimum safe treatment interval is q2 weeks, and adjunct treatment with prophylactic antibiotics should be considered.     

Associations between health and productivity in cow-calf beef herds and persistent infection with bovine viral diarrhea virus, antibodies against bovine viral diarrhea virus, or antibodies against infectious bovine rhinotracheitis virus in calves

OBJECTIVE: To measure associations between health and productivity in cow-calf beef herds and persistent infection with bovine viral diarrhea virus (BVDV), antibodies against BVDV, or antibodies against infectious bovine rhinotracheitis (IBR) virus in calves. ANIMALS: 1,782 calves from 61 beef herds. PROCEDURES: Calf serum samples were analyzed at weaning for antibodies against type 1 and type 2 BVDV and IBR virus. Skin biopsy specimens from 5,704 weaned calves were tested immunohistochemically to identify persistently infected (PI) calves. Herd production records and individual calf treatment and weaning weight records were collected. RESULTS: There was no association between the proportion of calves with antibodies against BVDV or IBR virus and herd prevalence of abortion, stillbirth, calf death, or nonpregnancy. Calf death risk was higher in herds in which a PI calf was detected, and PI calves were more likely to be treated and typically weighed substantially less than herdmates at weaning. Calves with high antibody titers suggesting exposure to BVDV typically weighed less than calves that had no evidence of exposure. CONCLUSIONS AND CLINICAL RELEVANCE: BVDV infection, as indicated by the presence of PI calves and serologic evidence of infection in weaned calves, appeared to have the most substantial effect on productivity because of higher calf death risk and treatment risk and lower calf weaning weight.     

Evaluation of the effects of histone deacetylase inhibitors on cells from canine cancer cell lines

OBJECTIVE: To determine whether exposure of canine cancer cells to histone deacetylase (HDAC) inhibitors S(+)-N-hydroxy-4-(3-methyl-2-phenyl-butyrylamino)benzamide (OSU-HDAC42) or suberoylanilide hydroxamic acid (SAHA) results in increased histone acetylation and decreased cell viability and whether any changes in viability involve induction of apoptosis or alterations in progression of the cell cycle. Sample POPULATION: 9 canine cancer cell lines. PROCEDURES: Cells from 9 canine cancer cell lines were treated with dimethyl sulfoxide vehicle, OSU-HDAC42, or SAHA, then assays of cell viability were performed. Histone acetylation was assessed by use of western blot analysis. Apoptosis was assessed via ELISA to detect fragmentation of cytoplasmic nucleosomal DNA and western blot analysis to detect cleavage of caspase 3. Cell cycle analysis was performed by use of propidium iodide staining and flow cytometry. RESULTS-Concentrations of OSU-HDAC42 and SAHA required to achieve 50% inhibition of cell viability (IC(50)) were reached in cells of 6 and 4 canine cancer cell lines, respectively, and ranged from approximately 0.4 to 1.3 microM for OSU-HDAC42 and 0.6 to 4.8 microM for SAHA. Cells from T-cell lymphoma, mast cell tumor, osteosarcoma, and histiocytic sarcoma lines were most sensitive to HDAC inhibition, with IC(50)s of < 1 microM for OSU-HDAC42 and < 5 microM for SAHA. Induction of apoptosis was indicated via cleavage of caspase 3 and increases in cytoplasmic nucleosomes and the subG(1) cell population. CONCLUSIONS AND CLINICAL RELEVANCE: Micromolar concentrations of HDAC inhibitors OSU-HDAC42 and SAHA induced histone acetylation, cytotoxicity, and apoptosis in canine cancer cells. In general, OSU-HDAC42 was more potent than SAHA.     

Use of personal protective equipment in a radiology room at a veterinary teaching hospital

The use of personal protective equipment by veterinary workers during radiographic imaging is inconsistent. While the self‐reported use of leaded aprons and thyroid shields approaches 100% in some studies, the use of leaded gloves and eyeglasses is much lower. Previous studies describing personal protective equipment use are based on self‐reporting. Objectives of this prospective, observational study were to describe use of leaded personal protective equipment during radiographic imaging by veterinary workers, and to compare observed use with self‐reported use. Use of leaded personal protective equipment during radiographic imaging by veterinary workers was observed over a 10 week period using two motion‐triggered video cameras, and a questionnaire was then completed by workers on their use of personal protective equipment. Workers restrained the animal during 91.8% (753/820) of exposures. An apron and a securely closed thyroid shield were worn for >99% of studies. Gloves were used correctly for 43.6% (156/358) of radiographic studies. Leaded eyeglasses were worn for 1.7% (6/358) of studies. Correct glove use was more frequent during regular working hours than after‐hours for both veterinarians (odds ratio 32.7, P = 0.001) and veterinary students (odds ratio 75.1, P < 0.001). The number of workers in the room was lower when animals were sedated (P = 0.002) or anesthetized (P = 0.017). Workers overestimated their frequency of glove use (P <0.001). In conclusion, workers use personal protective equipment less frequently in an unsupervised environment, and overestimate their use of personal protective equipment. Use of sedation or anesthesia decreases worker exposure to ionizing radiation.     

The effect of a low molecular weight heparin on coagulation parameters in healthy cats

The low molecular weight heparin (LMWH), dalteparin sodium, was administered subcutaneously (100 IU/kg) to 8 healthy cats twice daily for 13 doses. Anti-activated factor X (anti-Xa) activity was measured prior to administration (time 0), and 4, 6, 8, and 12 h after the 1st dose, 4 h after administration of the 3rd dose, and at 4, 6, 8, and 12 h after the last dose. Four cats developed measurable anti-Xa activity 4 h following a single dose, returning to baseline by 6 h. Anti-Xa activity was not detected at any time point in 4 cats. Prothrombin time (PT), activated partial thromboplastin time (APTT), and antithrombin (AT) concentrations were unaffected by LMWH administration. Dalteparin, at 100 IU/kg SC, did not achieve anti-Xa activity in 4 out of 8 cats and failed to maintain anti-Xa activity beyond 4 h in the other 4 healthy cats.     

Prediction of human cases of West Nile virus by equine cases, Saskatchewan, Canada, 2003

In 2003, an outbreak of West Nile virus (WNV) occurred in Saskatchewan, Canada from July to September. One-hundred thirty-three horse cases and 947 human cases were recorded and data were analyzed retrospectively for evidence of clustering to determine if clinical infection in the horse population could be used to estimate human risk of infection with WNV. Kulldorff's scan statistic was used to identify spatial-temporal clusters in both the human and horse cases. In most areas, human clusters were not preceded by horse clusters. In one area, a significant cluster of horse cases preceded human cases by 1 week; however, 1 week does not provide sufficient time for human-health authorities to act and provide advance warning for the public.     

Neurologic signs and hyperammonemia in a horse with colic

A 23-year-old Thoroughbred gelding was referred for the evaluation of acute onset of ataxia and depression, and a 2-day history of fever. On physical examination, the gelding was profoundly depressed and 10-12% dehydrated. The horse appeared very unstable, with a wide-based stance in the hind limbs, severe symmetric ataxia in all 4 limbs, and proprioceptive deficits in both hind limbs. Nasogastric intubation produced 4 L of brown, fetid reflux, and rectal examination revealed mild small intestinal and cecal distention. Hematologic abnormalities included neutropenia with toxic change, compatible with acute inflammation and endotoxemia, and prolonged coagulation times. Serum biochemical abnormalities included prerenal azotemia. metabolic acidosis, and electrolyte abnormalities consistent with enteritis. Blood ammonia concentration was markedly increased (406 micromol/L; reference interval 4-49 micromol/L), however, serum bile acids concentration and hepatic enzyme activities were within reference intervals. Histopathologic examination of a liver biopsy revealed no abnormalities and results of tests for several infectious agents were negative. Clinical signs resolved with correction of the dehydration and electrolyte abnormalities and with antibiotic therapy. The horse was diagnosed with hyperammonemic neuropathy associated with gastrointestinal disease. In such cases, hyperammonemia is caused by increased production of ammonia by organisms in the gastrointestinal tract in combination with increased gut permeability that facilitates ammonia absorption.