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Objective—To evaluate response rate and duration of malignant melanomas in dogs treated with carboplatin.
Animals—27 client-owned dogs with spontaneously occurring measurable malignant melanomas.
Procedure—Records of dogs with melanomas treated with carboplatin from October 1989 to June 2000 were reviewed. Carboplatin was administered IV at doses of 300 or 350 mg/m2 of body surface area. Response to treatment and evidence of drug toxicity were determined.
Result—Response to treatment could be evaluated in 25 dogs. Of those, overall response rate was 28%. One dog had a complete response, 6 (24%) dogs had a partial response (> 50% reduction in tumor burden). Median duration of partial response was 165 days. Eighteen dogs had stable disease (n = 9; 36%) or progressive disease (9; 36%). Response to treatment was significantly associated with carboplatin dose on a milligram per kilogram basis (15.1 mg/kg [6.9 mg/lb] of body weight vs 12.6 mg/kg [5.7 mg/lb]). Evidence of gastrointestinal toxicosis could be assessed in 27 dogs. Mean body weight of 5 dogs that developed gastrointestinal toxicosis was significantly less than that of 22 dogs without gastrointestinal toxicosis (9.9 kg [21.8 lb] vs 19.3 kg [42.5 lb]).
Conclusions and Clinical Relevance—Carboplatin had activity against macroscopic spontaneously occurring malignant melanomas in dogs and should be considered as an adjunctive treatment for microscopic local or metastatic tumors. Gastrointestinal toxicosis was associated with body weight. Because small dogs are more likely to have adverse gastrointestinal effects, gastrointestinal protectants should be considered for these patients. (J Am Vet Med Assoc 2001;218:1444–1448)
OBJECTIVE To investigate the impact of age and inferred prior vaccination history on the persistence of vaccine-induced antibody against rabies in horses.
DESIGN Serologic response evaluation.
ANIMALS 48 horses with an undocumented vaccination history.
PROCEDURES Horses were vaccinated against rabies once. Blood samples were collected prior to vaccination, 3 to 7 weeks after vaccination, and at 6-month intervals for 2 to 3 years. Serum rabies virus–neutralizing antibody (RVNA) values were measured. An RVNA value of ≥ 0.5 U/mL was used to define a predicted protective immune response on the basis of World Health Organization recommendations for humans. Values were compared between horses < 20 and ≥ 20 years of age and between horses inferred to have been previously vaccinated and those inferred to be immunologically naïve.
RESULTS A protective RVNA value (≥ 0.5 U/mL) was maintained for 2 to 3 years in horses inferred to have been previously vaccinated on the basis of prevaccination RVNA values. No significant difference was evident in response to rabies vaccination or duration of protective RVNA values between horses < 20 and ≥ 20 years of age. Seven horses were poor responders to vaccination. Significant differences were identified between horses inferred to have been previously vaccinated and horses inferred to be naïve prior to the study.
CONCLUSIONS AND CLINICAL RELEVANCE A rabies vaccination interval > 1 year may be appropriate for previously vaccinated horses but not for horses vaccinated only once. Additional research is required to confirm this finding and characterize the optimal primary dose series for rabies vaccination.
Objective—To investigate individual- and community-level contextual variables as risk factors for submission of calcium oxalate (CaOx) uroliths or magnesium ammonium phosphate (ie, struvite) uroliths for dogs to a national urolith center, as determined on the basis of urolith submission patterns.
Sample Population—Records of 7,297 dogs from Ontario, Canada, with CaOx or struvite uroliths submitted to the Canadian Veterinary Urolith Centre from 1998 through 2006.
Procedures—Data were analyzed via multilevel multivariable logistic regression.
Results—Individual-level main effects and interactions significantly associated with the risk of submission of CaOx uroliths rather than struvite uroliths included age, sex, breed group, neuter status, body condition, dietary moisture content, diet type, sex-neuter status interaction, sex-age interaction, body condition-age interaction, and breed group—dietary moisture content interaction. In addition, median community family income and being located within a major urban center (ie, Toronto) were significant risk factors for submission of CaOx uroliths, compared with submission of struvite uroliths.
Conclusions and Clinical Relevance—Individual-level and dietary factors for dogs affected the risk of submission of CaOx uroliths, relative to that of struvite uroliths. Interactions among these variables need to be considered when assessing the impact of these risk factors. In addition, community-level or contextual factors (such as community family income and residing in a densely populated area of Ontario) also affected submission patterns, although most of the variance in the risk for submission of CaOx uroliths, compared with the risk for submission of struvite uroliths, was explained by individual-level factors. (Am J Vet Res 2010;71:1045–1054)
Objective—To evaluate anti-inflammatory effects of several novel adenosine receptor agonists and to determine their specificity for various adenosine receptor subtypes on neutrophils, cells heterologously expressing equine adenosine receptors, or equine brain membranes.
Sample Population—Neutrophils isolated from 8 healthy horses.
Procedures—Radioligand binding experiments were performed to compare binding affinities of adenosine receptor agonists to equine adenosine A1, A2A, and A3 receptor subtypes. Effects of these agonists on endotoxin-induced production of reactive oxygen species (ROS) by equine neutrophils and roles of specific adenosine receptor subtypes and cAMP production in mediating these effects were determined.
Results—Radioligand binding experiments yielded a ranked order of affinity for the brain equine A2A receptor on the basis of 50% inhibitory concentrations (IC50) of the agonists as follows: ATL307 (IC50 = 1.9nM) and ATL313 > ATL309 and ATL310 > ATL202 > 2-([p-2- carboxyethyl] phenylethylamino)-5′-N-ethylcarboxyamidoadenosine > 5′-N-ethylcarboxamidoadenosine. Furthermore, ATL313 had approximately 100-fold greater selectivity for A2A over A1 and A3 receptors. In functional assays with equine neutrophils, the compounds inhibited endotoxin-induced ROS production and stimulated production of cAMP with the same ranked order of potency. Results of experiments performed with selective adenosine receptor antagonists indicated that functional effects of ATL313 were via stimulation of A2A receptors.
Conclusions and Clinical Relevance—Results indicated that activation of A2A receptors exerted anti-inflammatory effects on equine neutrophils and that stable, highly selective adenosine A2A receptor agonists may be developed for use in management of horses and other domestic animals with septic and nonseptic inflammatory diseases.
Objective—To evaluate systemic effects of IV infusion of ATP-MgCl2 subsequent to infusion of a low dose of endotoxin in horses.
Animals—12 adult horses.
Procedure—Horses were administered endotoxin (lipopolysaccharide [LPS]) or saline (0.9% NaCl) solution, IV, during a 30-minute period. Immediately thereafter, horses in each group were infused IV with ATP-MgCl2 or saline solution. Two weeks later, horses were administered the opposite solution (LPS or saline solution), but it was followed by the same infusion as 2 weeks previously (ie, ATP-MgCl2 or saline solution). Cardiopulmonary and clinicopathologic variables, cytokine activity, and endothelin (ET) concentrations were recorded.
Results—IV infusion of ATP-MgCl2 after administration of a low dose of endotoxin failed to attenuate the cardiopulmonary, clinicopathologic, and cytokine alterations that develop secondary to endotoxin exposure. The combination of LPS and ATP-MgCl2 potentiated pulmonary hypertension, leukopenia, and neutropenia when compared with the combination of LPS and saline solution. The combination of LPS and ATP-MgCl2 resulted in thrombocytopenia. Endothelin concentration was increased in jugular venous and pulmonary arterial plasma in horses receiving LPS and ATP-MgCl2. Similar increases were not observed with LPS and saline solution.
Conclusions and Clinical Relevance—Administration of ATP-MgCl2 did not protect horses from systemic effects of experimentally induced endotoxemia. Furthermore, the use of ATP-MgCl2 during endotoxemia may worsen the cardiopulmonary and clinicopathologic status of affected horses. Because ATP and other adenine nucleotides are released from cells during shock, their potential role in the development of hemodynamic derangements, leukocyte adherence, and coagulopathies during endotoxemic episodes warrants further investigation. (Am J Vet Res 2004;65: 225–237)
Objective—To determine synovial fluid gentamicin concentrations and evaluate adverse effects on the synovial membrane and articular cartilage of tarsocrural joints after implantation of a gentamicin-impregnated collagen sponge.
Animals—6 healthy adult mares.
Procedures—A purified bovine type I collagen sponge impregnated with 130 mg of gentamicin was implanted in the plantarolateral pouch of 1 tarsocrural joint of each horse, with the contralateral joint used as a sham-operated control joint. Gentamicin concentrations in synovial fluid and serum were determined for 120 hours after implantation by use of a fluorescence polarization immunoassay. Synovial membrane and cartilage specimens were collected 120 hours after implantation and evaluated histologically.
Results—Median peak synovial fluid gentamicin concentration of 168.9 μg/mL (range, 115.6 to 332 μg/mL) was achieved 3 hours after implantation. Synovial fluid gentamicin concentrations were < 4 μg/mL by 48 hours. Major histologic differences were not observed in the synovial membrane between control joints and joints implanted with gentamicin-impregnated sponges. Safranin-O fast green stain was not reduced in cartilage specimens obtained from treated joints, compared with those from control joints.
Conclusions and Clinical Relevance—Implantation of a gentamicin-impregnated collagen sponge in the tarsocrural joint of horses resulted in rapid release of gentamicin, with peak concentrations > 20 times the minimum inhibitory concentration reported for common pathogens that infect horses. A rapid decrease in synovial fluid gentamicin concentrations was detected. The purified bovine type I collagen sponges did not elicit substantial inflammation in the synovial membrane or cause mechanical trauma to the articular cartilage.
Objective—To compare measurements of myeloperoxidase (MPO) in plasma, laminar tissues, and skin obtained from control horses and horses given black walnut heartwood extract (BWHE).
Animals—22 healthy 5- to 15-year-old horses.
Procedures—Horses were randomly assigned to 4 groups as follows: a control group given water (n = 5) and 3 experimental groups given BWHE (17) via nasogastric intubation. Experimental groups consisted of 5, 6, and 6 horses that received BWHE and were euthanatized at 1.5, 3, and 12 hours after intubation, respectively. Control horses were euthanatized at 12 hours after intubation. Plasma samples were obtained hourly for all horses. Laminar tissue and skin from the middle region of the neck were harvested at the time of euthanasia. Plasma and tissue MPO concentrations were determined via an ELISA; tissue MPO activity was measured by use of specific immunologic extraction followed by enzymatic detection.
Results—Tissues and plasma of horses receiving BWHE contained significantly higher concentrations of MPO beginning at hour 3. Laminar tissue and skin from horses in experimental groups contained significantly higher MPO activity than tissues from control horses. Concentrations and activities of MPO in skin and laminar tissues were similar over time.
Conclusions and Clinical Relevance—In horses, BWHE administration causes increases in MPO concentration and activity in laminar tissue and skin and the time of increased MPO concentration correlates with emigration of WBCs from the vasculature. These findings support the hypothesis that activation of peripheral WBCs is an early step in the pathogenesis of acute laminitis.