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  • Author or Editor: A. Simon Turner x
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Abstract

Objective—To determine microradiographic appearance, bone histomorphometry, and mineral density of the long bones of the metacarpophalangeal joint in horses after immobilization followed by remobilization.

Animals—5 healthy horses.

Procedure—One forelimb of each horse was immobilized in a fiberglass cast for 7 weeks, followed by 8 weeks of increasing exercise. Calcein and oxytetracycline were administered IV during the immobilization and exercise phases, respectively, for bone labeling and analysis after euthanasia. Sagittal sections of metacarpal bones and proximal phalanges were examined via radiography, dual energy x-ray absorptiometry, histomorphometry, and bone label analysis.

Results—Radiography revealed loss of bone mineral opacity in the subarticular regions of the immobilized metacarpal bones and phalanges and subchondral lesions in metacarpal bones in 2 horses. In phalanges, a significant decrease in subarticular volumetric bone mineral density was detected. There was significantly less bone volume and calcein-labeled bone surface and more vascular volume and oxytetracycline-labeled bone surface in immobilized phalanges, compared with contralateral phalanges.

Conclusions and Clinical Relevance—Eight weeks of exercise after single-limb immobilization is insufficient for recovery of volumetric bone mineral density. During immobilization and remobilization, the subchondral and trabecular bone appear to be actively remodeling. (Am J Vet Res 2002;63:276–281)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine effects of various diets on the pharmacokinetics of phenobarbital and the interactive effects of changes in body composition and metabolic rate.

Design—Prospective study.

Animals—27 healthy sexually intact adult female Beagles.

Procedure—Pharmacokinetic studies of phenobarbital were performed before and 2 months after dogs were fed 1 of 3 diets (group 1, maintenance diet; group 2, protein-restricted diet; group 3, fat- and protein-restricted diet) and treated with phenobarbital (approx 3 mg/kg [1.4 mg/lb] of body weight, PO, q 12 h). Pharmacokinetic studies involved administering phenobarbital (15 mg/kg [6.8 mg/lb], IV) and collecting blood samples at specific intervals for 240 hours. Effects of diet and time were determined by repeated-measures ANOVA.

Results—Volume of distribution, mean residence time, and half-life (t1/2) of phenobarbital significantly decreased, whereas clearance rate and elimination rate significantly increased with time in all groups. Dietary protein or fat restriction induced significantly greater changes: t1/2 (hours) was lower in groups 2 (mean ± SD; 25.9 ± 6.10 hours) and 3 (24.0 ± 4.70) than in group 1 (32.9 ± 5.20). Phenobarbital clearance rate (ml/kg/min) was significantly higher in group 3 (0.22 ± 0.05 ml/kg/min) than in groups 1 (0.17 ± 0.03) or 2 (0.18 ± 0.03). Induction of serum alkaline phosphatase activity (U/L) was greater in groups 2 (192.4 ± 47.5 U/L) and 3 (202.0 ± 98.2) than in group 1 (125.0 ± 47.5).

Conclusions and Clinical Relevance—Clinically important differences between diet groups were observed regarding pharmacokinetics of phenobarbital, changes in CBC and serum biochemical variables, and body composition. Drug dosage must be reevaluated if a dog's diet, body weight, or body composition changes during treatment. Changes in blood variables that may indicate liver toxicosis caused by phenobarbital may be amplified by diet-drug interactions. (J Am Vet Med Assoc 2000;217:847–852)

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate changes in resting energy expenditure (REE) as well as protein and carbohydrate metabolism in dogs with osteosarcoma (OSA).

Animals—15 weight-stable dogs with OSA that did not have other concurrent metabolic or endocrine illness and twelve 1-year-old sexually intact female Beagles (control dogs).

Procedures—Indirect calorimetry was performed on all dogs to determine REE and respiratory quotient (RQ). Stable isotope tracers (15N-glycine, 4.5 mg/kg of body weight, IV; 6,6-deuterium-glucose, 4.5 mg/kg, IV as a bolus, followed by continuous-rate infusion at 1.5 mg/kg/h for 3 hours) were used to determine rate of protein synthesis and glucose flux in all dogs. Dualenergy x-ray absorptiometry (DEXA) scans were performed to determine total body composition.

Results—Accounting for metabolic body size, REE in dogs with OSA was significantly higher before and after surgery, compared with REE of healthy control dogs. The RQ values did not differ significantly between groups. Dogs with OSA also had decreased rates of protein synthesis, increased urinary nitrogen loss, and increased glucose flux during the postoperative period.

Conclusions and Clinical Relevance—Alterations in energy expenditure, protein synthesis, urinary nitrogen loss, and carbohydrate flux were evident in dogs with OSA, similar to results documented in humans with neoplasia. Changes were documented in REE as well as protein and carbohydrate metabolism in dogs with OSA. These changes were evident even in dogs that did not have clinical signs of cachexia. (Am J Vet Res 2001;62:1234–1239)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effect of dietary n-3 fatty acids on the pharmacokinetics of doxorubicin in dogs with lymphoma.

Animals—23 dogs with lymphoma in stages IIIa, IVa, and Va.

Procedure—Dogs receiving doxorubicin chemotherapy were randomly allocated to receive food with a high (test group) or low (control group) content of n-3 fatty acids. Serum doxorubicin and doxorubicinol concentrations were measured via high-performance liquid chromatography before and 6 to 9 weeks after initiation of the diets. Lymph node concentrations of doxorubicin were assessed 6 hours after the initial treatment. Dogs' body composition was assessed by means of dual-energy x-ray absorptiometry scans.

Results—No significant differences in doxorubicin pharmacokinetics were detected between treatment groups. Significant differences existed between the first and second sampling times among all dogs for area under the curve, maximum serum concentration, and clearance. Differences in body composition did not affect measured pharmacokinetic variables. The terminal elimination half-life was longer in dogs in which a long-term remission was achieved than in dogs that did not have remission.

Conclusions and Clinical Relevance—Dietary supplementation of n-3 fatty acids is common in veterinary patients with neoplasia, but supplementation did not affect doxorubicin pharmacokinetics in this population of dogs. Explanations for the beneficial effects of n-3 fatty acids other than alterations in the pharmacokinetics of chemotherapy drugs should be investigated. Dogs may metabolize drugs differently prior to remission of lymphoma than when in remission. The pharmacokinetics of doxorubicin at the time of the first administration may predict response to treatment.

Full access
in American Journal of Veterinary Research