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)
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 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 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.
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 assess intraobserver repeatability and interobserver and in vivo versus photographic agreement of a scoring system for the implant-skin interface (ISI) of external skeletal fixation (ESF).
SAMPLE 42 photographs of ISIs from 18 dogs for interobserver agreement and intraobserver repeatability and 27 photographs of ISIs from 6 dogs for in vivo versus photograph agreement.
PROCEDURES An ISI inflammation scoring system was developed. It included scales for 6 metrics (erythema, drainage amount, drainage type, swelling, hair loss or lack of hair regrowth, and granulation tissue). Photographs of the ISI of ESF were obtained by use of a standard protocol and evaluated to determine intraobserver repeatability and interobserver agreement (Cronbach α; 4 raters) of the ISI score. Agreement between in vivo and photographic ISI scores (2 raters) and correlation between median scores across metrics were evaluated.
RESULTS 42 photographs met the inclusion criteria. Overall intraclass correlation coefficients ranged from 0.922 to 0.975. Interobserver overall Cronbach α ranged from 0.835 to 0.943. For in vivo versus photographic assessment, 27 ISIs in 6 dogs and their photographs were evaluated. The Cronbach α for both raters ranged from 0.614 to 0.938. Overall, the Cronbach α ranged from 0.725 to 0.932. Mean photographic scores were greater than mean in vivo scores for each metric. Pearson correlation coefficients ranged from 0.221 to 0.923. Erythema, swelling, and granulation were correlated with all other metrics.
CONCLUSIONS AND CLINICAL RELEVANCE In this study, an ISI scoring system used in this study had high repeatability and agreement and may therefore be considered for use in clinical situations. Photographic scores were not equivalent to in vivo scores and should not be used interchangeably.
Objective—To determine whether clinically normal dogs have lesions in the pylorus and duodenum and to examine the expression of cyclooxygenase (COX) isoforms in the pylorus and duodenum of these dogs.
Animals—27 clinically normal dogs.
Procedures—Physical examination was performed on clinically normal dogs from animal shelters and research projects; the dogs were then euthanized. After the dogs were euthanized, the pylorus and duodenum were photographed and scored for gross appearance of lesions. Samples were obtained for histologic evaluation and determination of COX expression via western blot analyses. Tissues from the pylorus and duodenum were categorized as normal, inflamed, or eroded on the basis of histologic analysis. Each histologic category of tissue was then evaluated to determine the correlation with gross appearance and COX expression.
Results—Of the 27 dogs, 5 had unremarkable histologic findings in the pylorus and duodenum. Inflammation was found in the pylorus of 10 dogs and in the duodenum of 5 dogs. Epithelial erosion was detected in the pylorus of 1 dog and in the duodenum of 3 dogs. Gross appearance was not significantly correlated with histologic appearance. Expression of COX-1 was not upregulated by inflammation, whereas COX-2 expression was increased by inflammation or erosion.
Conclusions and Clinical Relevance—Dogs that appear to be clinically normal may have underlying gastroduodenal lesions associated with upregulation of COX-2. Because of the inability to determine this during routine physical examination, practitioners should be aware of this potential situation when prescribing COX inhibitors.
Objective—To assess in vivo effects of short-term administration of NSAIDs with varied cyclooxygenase (COX)-2 selectivity on pyloric and duodenal mucosa.
Animals—8 healthy dogs.
Procedures—Each dog received deracoxib (2 mg/kg, PO, q 24 h for 3 days), firocoxib (5 mg/kg, PO, q 24 h for 3 days), meloxicam (0.2 mg/kg, PO, q 24 h for 1 day followed by 0.1 mg/kg, PO, q 24 h for 2 days), or placebo orally for 3 days; there was a 4-week interval between successive treatments. Prior to and on day 3 of drug administration, pyloric and duodenal mucosae were assessed endoscopically and biopsy specimens obtained for histologic examination. Cyclooxygenase-1 and -2 protein expressions were assessed (western blotting) and prostanoid concentrations measured (ELISAs). Data were analyzed by use of an ANOVA.
Results—Drug administration did not significantly affect endoscopic mucosal scores, histologic scores, or COX-1 or -2 protein expression. The COX-1 protein expression was significantly higher in the pylorus than in the duodenum. Total prostaglandin and thromboxane B2 (TXB2) concentrations were significantly greater in pyloric than in duodenal mucosa. Drug administration had no effect on prostaglandin or TXB2 concentrations.
Conclusions and Clinical Relevance—Prostanoid concentrations in gastric and duodenal tissues, and gross and histologic appearances, were not significantly affected by drugs with varied COX-2 selectivity. These findings suggested that, for these experimental conditions, there were no differences among the preferential and selective COX-2 inhibitors with regard to adverse effects on the gastric and duodenal portions of the gastrointestinal tract of dogs.