Use of 64Copper Measurements to Diagnose Canine Copper Toxicosis

Inherited canine copper toxicosis is a serious problem in Bedlington terriers and West Highland White terriers, and may also be a problem in other less-studied breeds. Affected dogs become ill at midlife with progressive and ultimately fatal liver disease. Treatments for removal of copper and prevention of copper accumulation are available, but are most effective if begun before the dog becomes ill. Until recently diagnosis has not been available until the dog is 1 year of age, and then only by an invasive liver biopsy with determination of liver copper concentration. The authors studied the use of 64copper for early diagnosis of canine copper toxicosis. Two procedures were evaluated. The first involved measuring the concentration of 64copper in blood 24 hours after oral administration of the radioisotope. At this time, 64copper was associated primarily with ceruloplasmin secreted into the blood by the liver. This procedure is useful in the diagnosis of the human counterpart, Wilson's disease. However, the authors found it to be nondiscriminatory between affected and unaffected dogs. In contrast, the second procedure, which involved measuring 64copper excreted in stool during 48 hours after an intravenous dose of radioisotope, yielded results that differentiated most affected and unaffected dogs.     

Chemotactic response of bovine neutrophils to Pasteurella haemolytica culture fluid

Bovine neutrophil chemotactic activity was detected in the supernatant fluid of logarithmic phase cultures of P. haemolytica serotype 1. The chemoattractant was produced under culture conditions suitable for P. haemolytica leukotoxin production. An inverse correlation existed between the leukotoxin LC50 and the chemotactic activity in the culture fluid. Elimination of leukotoxin activity by heating, dilution or ultrafiltration, exposed the chemotactic activity in the culture fluid. The chemoattractant was partially resistant to heating (60 degrees C, 30 min), and had an apparent molecular weight greater than 100,000. Detection of chemotactic activity in both the concentrate and filtrate after XM300 filtration suggested that there might be more than one component with chemotactic activity or else that polymerization was occurring. Production of a potent neutrophil chemoattractant by P. haemolytica may explain the rapid infiltration of neutrophils that occurs during the early stages of bovine pneumonic pasteurellosis.     

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.)     

Comparison of plasma aldosterone concentration among clinical status groups of dogs with chronic heart failure

The plasma aldosterone concentration (PAC) among clinical status groups of 23 dogs with chronic heart failure was compared at various times after diagnosis of the problem. Eighteen dogs admitted in New York Heart Association (NYHA) class IV clinical status had significant elevations in PAC (P<0.0001), when compared with clinically normal dogs. Five dogs admitted in NYHA class III status and 4 dogs that responded with a change to NYHA class III status had significant elevations in PAC (P<0.01), when compared with clinically normal dogs. In patients with NYHA class IV status, the PAC was significantly greater (P<0.01) than in patients in NYHA class III status. For patients with the poorest prognosis, ie, severe signs of NYHA class IV status, the PAC was not markedly different, when compared with that for patients with a favorable prognosis, ie, recent onset of signs of NYHA class IV status. Patients treated with captopril had significantly lower PAC after therapy (P<0.01), whereas patients treated with hydralazine had significantly higher PAC (P<0.05) after therapy. It was concluded that heart failure in the dog increases PAC, most likely because of renin-angiotensin-aldosterone-system activation, and that the increase is related directly to the clinical status of the patient. Further, it was concluded that treatment of dogs in heart failure with captopril causes a decrease in circulating PAC, whereas treatment with hydralazine causes an increase in circulating PAC.     

Bilirubin excretion and bile flow in fed and fasted Brazilian squirrel monkeys (Saimiri sciureus)

Fasted Brazilian squirrel monkeys (BrSMs) exhibited slightly higher serum bilirubin levels (0.30±0.05 mg/dl) than others in the fed state (0.13±0.01). The mean liver weight was 50% lower following a 22 h fast. The rate of bile flow was unaffected by fasting and averaged 13.8 l/min/kg and 47.5 l/min/100g liver in six BrSMs. No significant difference in mean bilirubin excretion/min was observed on a body weight basis following fasting. When the mean rate of bilirubin excretion was calculated as a function of liver weight, a two-fold higher rate was present in fasted monkeys, but only at the p=0.06 level of statistical significance. From data collected in this and earlier studies, it would appear that BrSMs represent the best animals studied to date to serve as experimental controls in comparative studies with Bovilian squirrel monkeys which exhibit a Gilbert-like syndrome.     

Characterisation of a maize-infecting potyvirus from Spain

In order to characterise and classify an unknown maize-infecting potyvirus isolated from fields in northeast Spain, the entire coat protein gene and the C-terminal twothirds of the large nuclear inclusion protein (NIb) gene were cloned and sequenced. Protein sequencing enabled the cleavage site between the two proteins to be deduced and also revealed that on storage the viral coat protein undergoes a specific degradation in which the N-terminal 39 amino acids are removed. Comparison of the nucleotide sequence of the 3 non-coding region of the viral RNA and the predicted amino acid sequence of the coat protein with the equivalent regions of other members of the potyvirus group revealed that the Spanish virus is closely related to maize dwarf mosaic virus strain A.     

Growth Stasis and Limited Shell Calcification in Larvae of Cymatium parthenopeum During Trans-Atlantic Transport

Larvae of the shallow-water marine gastropod Cymatium parthenopeum show no appreciable shell calcification and no demonstrable growth as they disperse across the Atlantic Ocean. Evidence of what appears to be physiological specialization for prolonged delay of metamorphosis was found in larvae of this prosobranch gastropod.