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)
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
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)
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
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
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.