Objective—To assess the use of a von Frey device as
a mechanical nociceptive stimulus for evaluation of
the antinociceptive effects of morphine in dogs and
its potential application in the pharmacodynamic modeling
of morphine in that species.
Animals—6 healthy Beagles.
Procedure—von Frey thresholds were measured in
all dogs before and at intervals after they received no
treatment (control dogs) and IV administration of morphine
sulfate (1 mg/kg; treated dogs) in a crossover
study. The von Frey device consisted of a rigid tip
(0.5 mm in diameter) and an electronic load cell; the
operator was unaware of recorded measurements.
Results—Application of the von Frey device was
simple and well tolerated by all dogs and caused no
apparent tissue damage. No significant changes in
thresholds were detected in the control dogs at 8
hourly measurements, indicating a lack of acquired
tolerance, learned aversion, or local hyperalgesia.
When assessed as a group, treated dogs had significantly
high thresholds for 4 hours following morphine
administration, compared with baseline values;
individually, thresholds decreased to baseline
values within (mean ± SE) 2.8 ± 0.6 hours. The
maximal effect (change from baseline values) was
213 ± 43%, and the plasma morphine concentration
to achieve 50% maximal effect was
13.92 ± 2.39 ng/mL.
Conclusions and Clinical Relevance—Data suggest
that, in dogs, evaluation of the antinociceptive effect
and pharmacodynamic modeling of a dose of morphine
sulfate (1 mg/kg, IV) can be successfully
achieved by use of a von Frey device. (Am J Vet Res
Objective—To evaluate the pharmacokinetics and pharmacodynamics
of morphine after IV administration as
an infusion or multiple doses in dogs by use of a von
Frey (vF) device.
Procedure—In the first 2 crossover experiments of a
3-way crossover study, morphine or saline (0.9%) solution
was administered via IV infusion. Loading doses
and infusion rates were administered to attain targeted
plasma concentrations of 10, 20, 30, and 40 ng/mL.
In the third experiment, morphine (0.5 mg/kg) was
administered IV every 2 hours for 3 doses. The vF
thresholds were measured hourly for 8 hours. Plasma
concentrations of morphine were measured by highpressure
Results—No significant changes in vF thresholds
were observed during infusion of saline solution. The
vF thresholds were significantly increased from 5 to 8
hours during the infusion phase, corresponding to targeted
morphine plasma concentrations > 30 ng/mL
and infusion rates ≥ 0.15 ± 0.02 mg/kg/h. The maximal
effect (EMAX) was 78 ± 11% (percentage change from
baseline), and the effective concentration to attain a
50% maximal response (EC50) was 29.5 ± 5.4 ng/mL.
The vF thresholds were significantly increased from 1
to 7 hours during the multiple-dose phase; the EC50
and EMAX were 23.9 ± 4.7 ng/mL and 173 ± 58%,
respectively. No significant differences in half-life, volume
of distribution, or clearance between the first and
last dose of morphine were detected.
Conclusions and Clinical Relevance—Morphine
administered via IV infusion (0.15 ± 0.02 mg/kg/h) and
multiple doses (0.5 mg/kg, IV, every 2 hours for 3
doses) maintained significant antinociception in dogs.
(Am J Vet Res 2005;66:1968–1974)
Objective—To characterize the antinociceptive
actions of several doses of butorphanol by use of a
thermal threshold testing device specifically designed
Animals—6 domestic shorthair cats.
Procedure—The study was a masked, randomized,
crossover design. Thermal thresholds were measured
by use of a thermal threshold-testing device specifically
developed for cats. A small probe containing a
heater element and temperature sensor was held
with consistent contact against a shaved area of the
cat's skin with an elasticized band. Skin temperature
was recorded before each test, prior to activation of
the heater. On detection of a response (eg, the cat
flinched, turned, or jumped), the stimulus was terminated
and the threshold temperature recorded. Three
baseline measurements were recorded before IV
injection of 0.1, 0.2, 0.4, or 0.8 mg of butorphanol/kg.
Each cat received all doses in a randomized order at
least 1 week apart. The investigator was unaware of
the treatment received. Thermal thresholds were
measured every 15 minutes for 6 hours.
Results—Mean ± SD pretreatment threshold temperature
for all cats was 40.8 ± 2.2°C. There were no
dose-related differences among treatments. There
was a significant increase in threshold values for all
treatments from 15 to 90 minutes after injection.
Mydriasis was detected in all cats after treatment
with butorphanol and dysphoric behavior was frequently
Conclusions and Clinical Relevance—Results
obtained by use of a thermal stimulus indicated that
the duration of antinociceptive action of butorphanol
was 90 minutes and there was no dose-response relationship
in cats. (Am J Vet Res 2004;65:1085–1089)
Objective—To evaluate factors associated with lameness severity and hip joint range of motion in dogs with hip dysplasia and to assess the association between hip joint range of motion and degree of lameness.
Design—Prospective case series.
Animals—60 client-owned Labrador Retrievers with hip dysplasia.
Procedures—Owners completed a questionnaire regarding their dogs' daily exercise duration and type (ie, low impact vs high impact) and lifestyle. Range of motion of affected hip joints was measured with a transparent plastic goniometer. The presence of subluxation or luxation of hip joints as a consequence of hip dysplasia and the size of the largest osteophytes or enthesophytes of hip joints on ventrodorsal radiographic images of the pelvis were recorded. Multivariate analyses were performed to identify factors associated with lameness, loss of hip joint flexion, and loss of hip joint extension and to identify factors associated with the presence of large osteophytes.
Results—Exercise was associated with a decrease in the severity of lameness in dogs with hip dysplasia. The strength of this inverse relationship increased with longer exercise duration. Lameness was more severe in dogs with hip joint luxation than in dogs without luxation. Hip joint extension was 1° lower for each year of age, and osteophyte or enthesophyte size was 1 mm larger with each 3-year increase in age.
Conclusions and Clinical Relevance—Longer daily exercise duration was associated with lower lameness scores in dogs with hip dysplasia. Dogs with hip joint luxation secondary to hip dysplasia had higher lameness scores than did dogs without hip joint luxation.
To develop methods to identify and characterize activity monitor (AM) data signatures for jumps performed by cats.
13 healthy, client-owned cats without evidence of osteoarthritis or degenerative joint disease.
Each cat was fitted with the same AM, individually placed in an observation room, then simultaneously recorded by 3 video cameras during the observation period (5 to 8 hours). Each cat was encouraged to jump up (JU), jump down (JD), and jump across (JA) during the observation period. Output from the AM was manually annotated for jumping events, each of which was characterized by functional data analysis yielding relevant coefficients. The coefficients were then used in linear discriminant analysis to differentiate recorded jumps as JUs, JDs, or JAs. To assess the model's ability to distinguish among the 3 jump types, a leave-one-out cross-validation method was used, and the misclassification error rate of the overall categorization of the model was calculated.
Of 731 jumping events, 29 were misclassified. Overall, the mean misclassification error rate per cat was 5.4% (range, 0% to 12.5%), conversely indicating a correct classification rate per cat of 94.6%.
CONCLUSIONS AND CLINICAL RELEVANCE
Results indicated that the model was successful in correctly identifying JUs, JDs, and JAs in healthy cats. With advancements in AM technology and data processing, there is potential for the model to be applied in clinical settings as a means to obtain objective outcome measures.
Objective—To compare and validate goniometric joint measurements obtained from nonsedated and sedated cats with measurements from radiographic evaluation.
Animals—20 adult cats with no evidence of joint disease.
Procedures—Measurements of flexion and extension of the carpus, elbow, shoulder, tarsus, stifle, and hip joints and of carpal and tarsal joints during varus and valgus angulation were made by a single investigator before and after sedation of cats. Measurements were made by use of a goniometer with a masked dial. Joint angle measurements were compared between nonsedated and sedated cats and also with measurements from radiographs made while cats were sedated. Each series of measurements was repeated 4 times. To evaluate repeatability, Cronbach α values were calculated for repeated measure results of goniometric joint measurements of nonsedated and sedated cats. An intraclass correlation was calculated to determine reliability among the 3 measurement types (ie, measurements from nonsedated and sedated cats and on radiographic evaluation).
Results—Joint measurements did not differ significantly by measurement type, when comparing radiographic measurements with goniometric measurements in sedated and nonsedated cats. Cronbach α values were > 0.99 for goniometric joint measurements within individual nonsedated and sedated cats and also for comparison of mean meaurements obtained from sedated cats versus nonsedated cats versus radiographs. An intraclass correlation of 0.999 revealed high reliability among measurement types.
Conclusions and Clinical Relevance—Results indicated that goniometric joint measurements in nonsedated and sedated cats are repeatable and valid.
OBJECTIVE To determine attitudes of small animal practitioners toward veterinary clinical trials and variables influencing their likelihood of participating in such trials.
DESIGN Cross-sectional survey.
SAMPLE Small animal practitioners with membership in 1 of 2 online veterinary communities (n = 163 and 652).
PROCEDURES An online survey was developed for each of 2 veterinary communities, and invitations to participate were sent via email. Each survey included questions designed to collect information on the respondents’ willingness to enroll their patients in clinical trials and to recommend participation to clients for their pets.
RESULTS More than 80% of respondents to each survey indicated that they spend no time in clinical research. A high proportion of respondents were likely or extremely likely to recommend clinical trial participation to clients for their pets when those trials involved treatments licensed in other countries, novel treatments, respected investigators, or sponsoring by academic institutions, among other reasons. Reasons for not recommending participation included distance, time restrictions, and lack of awareness of ongoing clinical trials; 28% of respondents indicated that they did not usually learn about such clinical trials. Most respondents (79% to 92%) rated their recommendation of a trial as important to their client's willingness to participate.
CONCLUSIONS AND CLINICAL RELEVANCE Participation in veterinary clinical trials by small animal practitioners and their clients and patients appeared low. Efforts should be increased to raise practitioner awareness of clinical trials for which patients might qualify. Specific elements of trial design were identified that could be modified to increase participation.
Objective—To identify factors associated with gastrointestinal
tract perforation in dogs being treated
with a selective cyclooxygenase-2 (COX-2) inhibitor
Procedure—The Novartis Animal Health pharmacovigilance
database was searched for records of
dogs treated with deracoxib in which gastrointestinal
tract perforation was documented.
Results—16 of the 29 (55%) dogs had received deracoxib
at a dosage higher than that approved by the
FDA for the particular indication being treated, with 25
(86%) dogs having received deracoxib at a dosage > 2
mg/kg/d (0.9 mg/lb/d). Seventeen (59%) dogs had
received at least 1 other nonsteroidal anti-inflammatory
drug (NSAID) or a corticosteroid in close temporal
association (within 24 hours) with deracoxib administration
(ie, immediately before or following). In all, 26
(90%) dogs had received deracoxib at a higher-than-approved
dosage or had received at least 1 other
NSAID or corticosteroid in close temporal association
with deracoxib administration. Twenty dogs died or
were euthanatized, and 9 survived.
Conclusions and Clinical Relevance—In dogs with
gastrointestinal tract perforation and that had been
treated with deracoxib, perforation was most likely
attributable to a number of factors. Deracoxib should
only be used at approved dosages. Cortico-steroids
and other less selective NSAIDs should not be administered
in close temporal association with selective
COX-2 inhibitors, including deracoxib. Further study is
required to define this problem. (J Am Vet Med Assoc 2005;227:1112–1117)
Objectives—To describe placement of hinged transarticular
external fixation (HTEF) frames and evaluate
their ability to protect the primary repair of unstable
joints while allowing joint mobility in dogs and cats.
Animals—8 cats and 6 dogs.
Procedure—HTEF frames were composed of metal
or epoxy connecting rods and a hinge. Measurements
of range of motion of affected and contralateral joints
and radiographs were made after fixator application
Results—9 animals (4 cats and 5 dogs) had tarsal and
5 (4 cats and 1 dog) had stifle joint injuries. Treatment
duration ranged from 45 to 100 days (median, 57
days). Ranges of motion in affected stifle and tarsal
joints were 57% and 72% of control while HTEF was
in place and 79% and 84% of control after frame
removal. Complications were encountered in 3 cats
and 2 dogs and included breakage of pins and connecting
rods, hinge loosening, and failure at the
Conclusions and Clinical Relevance—HTEF in animals
with traumatic joint instability provided adjunctive
joint stabilization during healing and protection of
the primary repair and maintained joint motion during
healing, resulting in early weight bearing of the affected
limb. (J Am Vet Med Assoc 2005;227:586–591)