bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of glomerular filtration rate on clearance and myelotoxicity of carboplatin in cats with tumors
Authors: Bailey Dennis B. , Rassnick Kenneth M. , Erb Hollis N. , Dykes Nathan L. , Hoopes P. Jack , Page Rodney L.
Published: December 2005

Objective—To characterize the pharmacokinetic disposition of carboplatin and determine whether glomerular filtration rate (GFR) could be used to predict carboplatin clearance and myelotoxic effects in cats with tumors.

Animals—10 cats with tumors.

Procedure—Glomerular filtration rate was assessed in each cat by monitoring plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Each cat received carboplatin (200 mg/m2of body surface area) administered as an IV bolus. Plasma platinum concentrations were measured via atomic absorption spectrophotometry, and pharmacokinetic analysis was performed. A CBC was performed weekly for each cat, and the correlation between the area under the concentration-versus-time curve (AUC) and the severity of myelosuppression was calculated. Least squares regression analysis was performed to determine whether GFR could be used to predict plasma platinum clearance (ClPt).

Results—For all cats, AUC measurements ranged from 0.99 to 4.30 min·mg·mL–1. Neutrophil concentration nadirs were detected 1 to 3 weeks after treatment and ranged from 200 to 8,000 cells/µL. The absolute neutrophil concentration at the nadir was inversely correlated with AUC. The ClPtwas predicted by use of GFR measurements (ClPt = 2.60 × GFR). A carboplatin dose prescription model was derived involving AUC, estimated ClPt, and body weight in kilograms (BWkg), in which dose = AUC × 2.60(GFR) × BWkg.

Conclusions and Clinical Relevance—In cats, an individualized prescription strategy for carboplatin administration based on a targeted AUC and determination of GFR might more uniformly predict myelosuppression than that predicted by conventional dosing based on body surface area. (Am J Vet Res2004;65:1502–1507)
Dynamic computed tomographic evaluation of the pituitary gland in healthy dogs
Authors: van der Vlugt-Meijer Roselinda H. , Meij Björn P. , Voorhout George
Published: December 2005

Objective—To determine the contrast enhancement
pattern of the pituitary gland in healthy dogs via
dynamic computed tomography (CT).

Animals—17 dogs.

Procedure—With each dog in sternal recumbency,
transverse CT scans were made perpendicular to the
skull base from the rostral clinoid processes to the
dorsum sellae. At the position of the image that contained
the largest cross section of the pituitary gland,
a series of 9 to 11 scans was made during and after
IV injection of contrast medium (dynamic CT scans).
The contrast enhancement pattern of the pituitary
gland and surrounding arteries was assessed visually
and by use of time-density curves.

Results—After strong enhancement of the maxillary
arteries, the intracavernous parts of the internal
carotid arteries, and the communicating arteries of
the arterial cerebral circle, there was a strong
enhancement of the central part of the pituitary gland
followed by enhancement of its peripheral part. On
the last images of the dynamic series of the pituitary
gland, the central part was hypodense, compared
with the peripheral part. Time-density curves confirmed
an early, strong enhancement of the central
part and a delayed, less strong enhancement of the
peripheral part of the gland.

Conclusions and Clinical Relevance—The difference
in enhancement between the central and
peripheral parts of the pituitary gland was attributable
to a difference in vascularization of the neurohypophysis
and adenohypophysis, respectively. Distortion
or disappearance of the strong central enhancement
(pituitary flush) may be used for the detection and
localization of pituitary abnormalities in the adenohypophysis.
(Am J Vet Res 2004;65:1518–1524)
Evaluation of haplotypes associated with copper toxicosis in Bedlington Terriers in Australia
Authors: Hyun Changbaig , Lavulo Lopeti T. , Filippich Lucio J.
Published: December 2005

Objective—To evaluate the haplotype distribution associated with the copper toxicosis gene and the segregation of the mutated allele in a Bedlington Terrier population in Australia.

Animals—131 Bedlington Terriers.

Procedure—Samples of DNA and RNA were obtained from each dog. Genetic status of each dog was evaluated by use of the DNA markers C04107; single nucleotide polymorphism (SNP), which was adjacent to exon 2 ofMurr1; and a deletion marker for exon 2. A subgroup of the study population was evaluated by use of biochemical and histologic techniques to elucidate the correlation between genotype and phenotype.

Results—We identified a recombination between the C04107 marker andMurr1and a variation in a nucleotide in the splice site of exon 2 in our Bedlington Terrier cohort. Furthermore, we identified a novel haplotype associated with copper toxicosis in this cohort.

Conclusions and Clinical Relevance—Our findings indicate that the deletion of exon 2 was not the sole cause of copper toxicosis, although only exon 2 deletion ofMurr1has been responsible for copper toxicosis in Bedlington Terriers. Although we failed to find a novel mutation in our cohort, we identified an affected dog family with an intact exon 2. Furthermore, we found that an SNP in the 5' splicing site of exon 2 may or may not be associated with a novel mutation of theMurr1gene or other genes. Loss of linkage between the C04107 marker and theMurr1gene was also identified in a certain family of dogs. (Am J Vet Res2004;65:1573–1579)
Comparison of plasma disposition of alkaloids after lupine challenge in cattle that had given birth to calves with lupine-induced arthrogryposis or clinically normal calves
Authors: Gay Clive C. , Panter Kip E. , Mealey Katrina L. , Gay John M. , Hjartarson Steven W. , Tibary Ahmed , Motteram Ernie S. , Wierenga Terrie , James Lynn F.
Published: December 2005

Objective—To compare plasma disposition of alkaloids
after lupine challenge in cattle that had given
birth to calves with lupine-induced arthrogryposis and
cattle that had given birth to clinically normal calves
and determine whether the difference in outcome
was associated with differences in plasma disposition
of anagyrine.

Animals—6 cows that had given birth to calves with
arthrogryposis and 6 cows that had given birth to clinically
normal calves after being similarly exposed to
lupine during pregnancy.

Procedure—Dried lupine (2 g/kg) was administered
via gavage. Blood samples were collected before and
at various time points for 48 hours after lupine administration.
Anagyrine, 5,6-dehydrolupanine, and lupanine
concentrations in plasma were measured by use
of gas chromatography. Plasma alkaloid concentration
versus time curves were generated for each alkaloid,
and pharmacokinetic parameters were determined
for each cow.

Results—No significant differences in area under the
plasma concentration versus time curve, maximum
plasma concentration, time to reach maximum plasma
concentration, and mean residence time for the 3
alkaloids were found between groups.

Conclusions and Clinical Relevance—Because no
differences were found in plasma disposition of
anagyrine following lupine challenge between cattle
that had given birth to calves with arthrogryposis and
those that had not, our findings do not support the
hypothesis that between-cow differences in plasma
disposition of anagyrine account for within-herd differences
in risk for lupine-induced arthrogryposis.
(Am J Vet Res 2004;65:1580–1583)
Measurement of total antioxidant capacity in gingival crevicular fluid and serum in dogs with periodontal disease
Authors: Pavlica Zlatko , Petelin Milan , Nemec Alenka , Erzen Damjan , Skaleric Uroš
Published: December 2005

Objective—To determine whether gingival crevicular fluid (GCF) and serum total antioxidant capacities (TACs) correlate with the degree of severity of periodontal disease in dogs.

Animals—41 Toy and Miniature Poodles.

Procedure—After assessment of the degree of severity of naturally occurring periodontitis, GCF samples from both maxillary fourth premolars and a blood sample were collected from each dog. The condition of the periodontium of the entire dentition and at each site of GCF collection was recorded. Clinical parameters assessed included plaque index, gingival index, and probing depth. Radiographic analysis of alveolar bone level was also performed. Total antioxidant capacity was measured in GCF and serum samples by use of a commercial kit.

Results—Dogs with gingivitis and minimal periodontitis had significantly higher TAC in GCF than dogs with advanced periodontitis. Bivariate regression analysis revealed significant negative correlations between TAC in GCF and clinical parameters and age. The TAC in serum was significantly negatively correlated with the degree of gingival inflammation but was not significantly correlated with age.

Conclusions and Clinical Relevance—TAC in GCF is related to the degree of severity of periodontal disease in dogs. This is likely the result of release of reactive oxygen species by activated phagocytes and fibroblasts in the inflamed periodontal tissues. The results of our study suggest that the local delivery of antioxidants may be a useful adjunctive treatment for periodontitis in dogs. (Am J Vet Res2004;65:1584–1588)
Evaluation of a single injection of a sustained-release formulation of moxidectin for prevention of experimental heartworm infection after 12 months in dogs
Authors: Holm-Martin Merete , Atwell Rick
Published: December 2005

Objective—To evaluate the efficacy of a single injection
of a sustained-release formulation of moxidectin
in preventing heartworm (Dirofilaria immitis) infection
for 12 months in dogs.

Animals—14 healthy dogs.

Procedure—Group A (nontreated control dogs; n = 6)
received sterile vehicle administered SC, and group B
(treated dogs; n = 6) received a sustained-release formulation
of moxidectin administered SC. All dogs
were housed in a heartworm-endemic area for 11.5
months, and heartworm antigen and modified Knott
tests were performed monthly. All dogs (including 2
additional control dogs [group C]) were then inoculated
with infective-stage larvae (L3) of D immitis, and
4.5 months later, all dogs were euthanatized and postmortem
examinations were performed. Adult D immitis
were counted and measured, and their age was
estimated.

Results—All dogs in groups A and C were infected
with young (4- to 4.5-month old) adult male and
female D immitis. No dogs in group B were infected
with heartworms.

Conclusions and Clinical Relevance—The age of
heartworms recovered suggests that infection was
the result of experimental inoculation and not natural
exposure to mosquitoes during the 11.5-month period
the dogs resided in a heartworm-endemic area. A single
SC injection of a sustained-release formulation of
moxidectin was effective in providing protection
against heartworm infection after 12 months in dogs.
This formulation is a convenient method of heartworm
prophylaxis that could eliminate the problem of
poor owner compliance. (Am J Vet Res 2004;
65:1596–1599)
High-frequency ultrasonography of the skin of clinically normal dogs
Authors: Diana Alessia , Preziosi Rosario , Guglielmini Carlo , Degliesposti Paolo , Pietra Marco , Cipone Mario
Published: December 2005

Objective—To assess the applicability of high-frequency
diagnostic ultrasonography for evaluation and
accurate measurement of the skin thickness of clinically
normal dogs.

Animals—26 healthy dogs (12 sexually intact males,
13 sexually intact females, and 1 spayed female) of
various breeds and ages.

Procedure—Ultrasonographic examination of the
skin and histomorphometric analysis of skin biopsy
specimens obtained from the same site were performed.
A 13-MHz linear-array transducer was used to
obtain a series of ultrasonographic images of the skin
in the flank region; images were analyzed and measured
by use of imaging software. Cutaneous biopsy
specimens were placed in fixative and then stained
with H&E and Masson trichrome stains.
Histomorphometric analysis was performed by use of
an image analyzer. Thickness of the epidermis and
dermis of each specimen was evaluated by use of a
semiautomatic procedure of quantification. Data
obtained from ultrasonographic and histologic measurements
were compared by use of the Pearson correlation
test.

Results—The ultrasonographic pattern of canine skin
was consistently characterized by 3 distinct, defined
echogenic layers corresponding to the epidermal
entry echo, epidermis and dermis, and subcutaneous
tissues. A positive correlation was found between
ultrasonographic and histologic measurements of
skin thickness.

Conclusions and Clinical Relevance—Comparison
between ultrasonographic and histologic appearance
of the skin revealed that layering of canine skin (ie,
epidermis and dermis) and the subcutaneous tissues
may be recognized and measured by use of high-frequency
ultrasonography. Thus, diagnostic ultrasonography
may be a useful tool for the noninvasive evaluation
of cutaneous disorders in dogs. (Am J Vet Res
2004;65:1625–1630)
Assessment of changes in hemostatic markers in Cavalier King Charles Spaniels with myxomatous mitral valve disease
Authors: Tarnow Inge , Kristensen Annemarie T. , Olsen Lisbeth H. , Pedersen Henrik D.
Published: December 2005

Objective—To evaluate markers of hemostasis and their relationship to the degree of mitral regurgitation (MR) and platelet function in Cavalier King Charles Spaniels (CKCSs) with myxomatous mitral valve disease.

Animals—76 clinically healthy CKCSs and 24 control dogs.

Procedure—All dogs underwent echocardiographic examination; various hemostatic, hematologic, and biochemical variables were evaluated in blood. The CKCSs were allocated to 1 of 3 groups on the basis of MR severity. In 8 control dogs and 8 CKCSs, plasma von Willebrand factor (vWF) multimer analysis was performed.

Results—Compared with control dogs, plasma fibrinogen concentration was higher in all CKCSs and related to left ventricular end diastolic diameter and left atrial-to-aortic root ratio among all CKCSs. The activated partial thromboplastin times and plasma Ddimer concentration were similar among the 4 groups. Plasma vWF concentration was lower in CKCSs with moderate to severe MR, compared with that of CKCSs with no MR and control dogs. There was a relationship between plasma vWF concentration and platelet function in CKCSs but not in control dogs. In 4 CKCSs with moderate to severe MR and low plasma vWF concentration, amounts of vWF high-molecular-weight multimers (HMWMs) were low.

Conclusions and Clinical Relevance—In CKCSs, MR appeared to be associated with a low plasma vWF concentration and likely a loss of vWF HMWMs (possibly through their destruction via shear stress to the blood). The importance of the changes in plasma fibrinogen concentration and the thromboembolic risk in dogs with MR remain to be investigated. (Am J Vet Res2004;65:1644–1652)
Pharmacokinetics of a combination preparation of ampicillin and sulbactam in turkeys
Authors: Fernández-Varón Emilio , Cárceles Carlos M. , Espuny Alberto , Marín Pedro , Escudero Elisa
Published: December 2005

Objective—To investigate the disposition kinetics of
ampicillin and sulbactam after IV and IM administration
of an ampicillin-sulbactam (2:1) preparation and
determine the bioavailability of the combined preparation
after IM administration in turkeys.

Animals—10 healthy large white turkeys.

Procedure—In a crossover study, turkeys were
administered the combined preparation IV (20 mg/kg)
and IM (30 mg/kg). Blood samples were collected
before and at intervals after drug administrations.
Plasma ampicillin and sulbactam concentrations were
measured by use of high-performance liquid chromatography;
plasma concentration-time curves were
analyzed via compartmental pharmacokinetics and
noncompartmental methods.

Results—The drugs were distributed according to an
open 2-compartment model after IV administration
and a 1-compartment model (first-order absorption)
after IM administration. For ampicillin and sulbactam,
the apparent volumes of distribution were 0.75 ± 0.11
L/kg and 0.74 ± 0.10 L/kg, respectively, and the total
body clearances were 0.67 ± 0.07 L·kg–1·h–1 and 0.56
± 0.06 L·kg–1·h–1, respectively. The elimination half-lives
of ampicillin after IV and IM administration were 0.78
± 0.12 hours and 0.89 ± 0.17 hours, respectively,
whereas the corresponding half-lives of sulbactam
were 0.91 ± 0.12 hours and 0.99 ± 0.16 hours,
respectively. Bioavailability after IM injection was
58.87 ± 7.65% for ampicillin and 53.75 ± 5.35% for
sulbactam.

Conclusions and Clinical Relevance—Results indicated
that a regimen of loading and maintenance
doses of 300 mg of the ampicillin-sulbactam (2:1)
combination/kg every 8 hours could be clinically useful
in turkeys. This dosage regimen maintained plasma
concentrations of ampicillin > 0.45 µg/mL in
turkeys. (Am J Vet Res 2004;65:1658–1663)
Assessment of the effects of exogenous long-acting insulin on glucose tolerance in alpacas
Authors: Ueda Jaime , Cebra Christopher K. , Tornquist Susan J.
Published: December 2005

Objective—To evaluate the effects of long-acting insulin on glucose clearance in alpacas.

Animals—8 adult castrated alpacas.

Procedure—On 2 days, food was withheld from alpacas for 8 hours. Alpacas were randomly allocated to receive an SC injection of long-acting insulin (0.4 U/kg) or saline (0.9% NaCl) solution 1 hour before the first of 3 administrations of glucose (at 60, 480, and 1,200 minutes after treatment) on day 1 and the alternate treatment and procedure on day 2. Plasma glucose concentration was determined before and 15, 45, 120, and 240 minutes after each glucose administration, and fractional turnover rates were calculated. The data were compared between alpacas with and without insulin administration and among the 3 glucose administrations for each day.

Results—Compared with sham-treated alpacas, insulin-treated alpacas had significantly lower blood glucose concentrations from 180 to 600 minutes after treatment; they also had glucose concentrations significantly below baseline values from 120 to 480 minutes, at which time the mean glucose concentration was in the hypoglycemic range. Also, mean fractional turnover of glucose was significantly higher in insulintreated alpacas from 105 through 300 minutes.

Conclusions and Clinical Relevance—Compared with known effects of regular insulin in alpacas, the action of long-acting insulin was of slower onset but longer lasting; its administration may induce hypoglycemia, even in alpacas that receive glucose. To maintain the hypoglycemic effect, long-acting insulin may have to be administered more than once daily and blood glucose concentration should be monitored to avoid hypoglycemic complications in alpacas. (Am J Vet Res2004;65:1688–1691)
Investigation of in vitro transdermal absorption of fentanyl from patches placed on skin samples obtained from various anatomic regions of dogs
Authors: Mills Paul C. , Magnusson Beatrice M. , Cross Sheree E.
Published: December 2005

Objective—To investigate in vitro transdermal absorption of fentanyl from patches through skin samples obtained from various anatomic regions of dogs.

Sample Population—Skin samples from 5 Greyhounds.

Procedure—Skin samples from the dogs' thoracic, neck, and groin regions were collected postmortem and frozen. After samples were thawed, circular sections were cut and placed in Franz-type diffusion cells in a water bath (32°C). A commercial fentanyl patch, attached to an acetate strip with a circular hole, was applied to each skin sample. Cellulose strips were used as control membranes. Samples of receptor fluid in the diffusion cells were collected at intervals for 48 hours, and fentanyl concentrations were analyzed by use of high-performance liquid chromatography.

Results—Mean ± SD release rate of fentanyl from the patch, defined by its absorption rate through the non–rate-limiting cellulose membrane, was linear during the first 8 hours (2.01 ± 0.05 µg/cm2of cellulose membrane/h) and then decreased. Fentanyl passed through skin from the groin region at a faster rate and with a significantly shorter lag time, compared with findings in neck or thoracic skin samples.

Conclusions and Clinical Relevance—In vitro, fentanyl from a patch was absorbed more quickly and to a greater extent through skin collected from the groin region of dogs, compared with skin samples from the thoracic and neck regions. Placement of fentanyl patches in the groin region of dogs may decrease the lag time to achieve analgesia perioperatively; however, in vivo studies are necessary to confirm these findings.(Am J Vet Res2004;65:1697–1700)
Determination of functional and morphologic changes in palmar digital nerves after nonfocused extracorporeal shock wave treatment in horses
Authors: Bolt David M. , Burba Daniel J. , Hubert Jeremy D. , Strain George M. , Hosgood Giselle L. , Henk William G. , Cho Doo-Youn
Published: December 2005

Objective—To determine functional and morphologic
changes in palmar digital nerves after nonfocused
extracorporeal shock wave (ESW) treatment in horses.

Animals—6 horses.

Procedures—The medial and lateral palmar digital
nerves of the left forelimb were treated with nonfocused
ESWs. The medial palmar digital nerve of the
right forelimb served as a nontreated control nerve.
At 3, 7, and 35 days after treatment, respectively, 2
horses each were anesthetized and nerves were surgically
exposed. Sensory nerve conduction velocities
(SNCVs) of treated and control nerves were recorded,
after which palmar digital neurectomies were performed.
Morphologic changes in nerves were
assessed via transmission electron microscopy.

Results—Significantly lower SNCV in treated medial
and lateral nerves, compared with control nerves, was
found 3 and 7 days after treatment. A significantly lower
SNCV was detected in treated medial but not lateral
nerves 35 days after treatment. Transmission electron
microscopy of treated nerves revealed disruption of the
myelin sheath with no evidence of damage to Schwann
cell bodies or axons, 3, 7, and 35 days after treatment.

Conclusions and Clinical Relevance—Nonfocused
ESW treatment of the metacarpophalangeal area resulted
in lower SNCV in palmar digital nerves. This effect
likely contributes to the post-treatment analgesia
observed in horses and may result in altered peripheral
pain perception. Horses with preexisting lesions may be
at greater risk of sustaining catastrophic injuries when
exercised after treatment. (Am J Vet Res
2004;65:1714–1718)
Comparative assessment of bone mineral measurements obtained by use of dual-energy x-ray absorptiometry, peripheral quantitative computed tomography, and chemical-physical analyses in femurs of juvenile and adult dogs
Authors: Schneider Sigrid , Breit Sabine M. , Grampp Stephan , Künzel Wolfgang W. F. , Liesegang Annette , Mayrhofer Elisabeth , Zentek Jürgen
Published: December 2005

Objective—To compare bone mineral measurements obtained by use of dual-energy x-ray absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT), and chemical-physical analyses and determine effects of age and femur size on values obtained for the various techniques.

Sample Population—Femurs obtained from 15 juvenile and 15 adult large-breed dogs.

Procedure—In each femur, 7 regions of interest were examined by use of DEXA to measure the bone mineral content (BMC) and bone mineral density (BMD), and 5 were examined by use of pQCT to measure BMD. Among these, 1 region was examined by both noninvasive methods and an invasive method. Volume of the femur was determined by water displacement. Volumetric bone density (VBD) was calculated. Calcium (Ca), phosphorus (P), total Ca, and total P contents were determined.

Results—DEXA- and pQCT-derived results revealed that all values increased with age in juvenile dogs. In adults, VBD and pQCT-derived BMD decreased significantly and DEXA-derived BMD increased with increasing femur length. The pQCT-derived BMD correlated well with VBD and Ca content, whereas DEXA-derived BMC was strongly correlated with Ca content. In juveniles, values correlated regardless of the technique used, whereas in adult dogs, DEXA-derived BMD did not correlate with pQCT-derived BMD, Ca concentration, or VBD unless data were adjusted on the basis of femur length.

Conclusions and Clinical Relevance—DEXA-derived BMD adjusted for femur length yields approximately the same percentage variability in VBD as for pQCT-derived BMD. However, pQCT-derived BMD is still more sensitive for determining variability in Ca concentration, compared with DEXA-derived BMD adjusted for femur length. (Am J Vet Res2004;65:891–900)
Investigation of the facilitation of the nociceptive withdrawal reflex evoked by repeated transcutaneous electrical stimulations as a measure of temporal summation in conscious horses
Authors: Spadavecchia Claudia , Andersen Ole K. , Arendt-Nielsen Lars , Spadavecchia Luciano , Doherr Marcus , Schatzmann Urs
Published: December 2005

Objective—To investigate whether facilitation of the
nociceptive withdrawal reflex (NWR) can be evoked
and quantified as a measure of temporal summation
from the distal aspect of the left forelimb and hind
limb in standing nonsedated horses via repeated
stimulations of various subthreshold intensities and
frequencies.

Animals—10 adult horses.

Procedure—Surface electromyographic activity
evoked by stimulation of the digital palmar and plantar
nerves was recorded from the common digital
extensor and cranial tibial muscles. For each horse,
the NWR threshold intensity to a single stimulus was
determined for the forelimb and hind limb. Repeated
stimulations were performed at subthreshold intensities
and at frequencies of 2, 5, and 10 Hz. The reflex
amplitude was quantified, and the behavioral responses
accompanying the stimulations were scored.

Results—Repeated stimulations at subthreshold
intensities were able to summate and facilitate the
NWR in conscious horses. The reflex facilitation was
significantly related to the intensity of the repeated
stimuli, whereas no effect of stimulation frequency
was found. Reaction scores increased significantly for
increasing stimulation intensities.

Conclusions and Clinical Relevance—Temporal summation
obtained by repeated stimulations of subthreshold
intensity appears to represent a new tool for
investigating nociceptive pathophysiologic processes
in horses; this experimental model may be useful to
examine the mode of action and efficacy of analgesic
and anesthetic interventions and possibly to assess
sensory dysfunction in clinical settings. (Am J Vet Res 2004;65:901–908)
Assessment of repeatability, reproducibility, and effect of anesthesia on determination of radial and longitudinal left ventricular velocities via tissue Doppler imaging in dogs
Authors: Chetboul Valerie , Athanassiadis Nicolas , Carlos Carolina , Nicolle Audrey , Zilberstein Luca , Pouchelon Jean-Louis , Lefebvre Herve P. , Concordet Didier
Published: December 2005

Objective—To determine left ventricular free wall
(LVFW) motions and assess their intra- and interday
variability via tissue Doppler imaging (TDI) in healthy
awake and anesthetized dogs.

Animals—6 healthy adult Beagles.

Procedure—In the first part of the study, 72 TDI
examinations (36 radial and 36 longitudinal) were performed
by the same observer on 4 days during a 2-week period in all dogs. In the second part, 3 dogs
were anesthetized with isoflurane and vecuronium.
Two measurements of each TDI parameter were
made on 2 consecutive cardiac cycles when ventilation
was transiently stopped. The TDI parameters
included maximal systolic, early, and late diastolic
LVFW velocities.

Results—The LVFW velocities were significantly higher
in the endocardial than in the epicardial layers and
also significantly higher in the basal than in the midsegments
in systole, late diastole, and early diastole.
The intraday coefficients of variation (CVs) for systole
were 16.4% and 22%, and the interday CV values were
11.2% and 16.4% in the endocardial and epicardial layers,
respectively. Isoflurane anesthesia significantly
improved the intraday CV but induced a decrease in
LVFW velocities, except late diastolic in endocardial layers
and early diastolic in epicardial layers.

Conclusions and Clinical Relevance—Left ventricular
motion can be adequately quantified in dogs and
can provide new noninvasive indices of myocardial
function. General anesthesia improved repeatability
of the procedure but cannot be recommended
because it induces a decrease in myocardial velocities.
(Am J Vet Res 2004;65:909–915)
Comparison of hematologic values and transforming growth factor-β and insulin-like growth factor concentrations in platelet concentrates obtained by use of buffy coat and apheresis methods from equine blood
Authors: Sutter W. Wesley , Kaneps Andris J. , Bertone Alicia L.
Published: December 2005

Objective—To evaluate the buffy coat and apheresis methods for preparation of platelet concentrates from equine blood by comparing platelet and growth factor concentrations.

Animals—15 mature mixed-breed geldings.

Procedure—Whole blood samples were collected and processed by use of a buffy coat or apheresis method to obtain platelet poor and platelet concentrated fractions. The PCV, WBC count, and platelet count were compared among whole blood samples, platelet poor fractions, concentrates obtained by use of the apheresis method (ie, apheresis platelet concentrates), and concentrates obtained by use of the buffy coat method (ie, buffy coat platelet concentrates). Concentrations of transforming growth factor- β (ie, TGF-β1 and TGF-β2) and insulin-like growth factor were compared between buffy coat and apheresis platelet concentrates.

Results—Platelet concentrations were 8.9-fold and 5.2-fold greater in buffy coat and apheresis platelet concentrates, respectively, compared with whole blood. Platelet concentrations were 13.1-fold greater in filtered apheresis platelet concentrates, compared with whole blood. TGF-β1 concentrations were 2.8- fold and 3.1-fold greater in buffy coat and apheresis platelet concentrates, respectively, and TGF-β1 concentrations were 10.5-fold greater in filtered apheresis platelet concentrates, compared with whole blood. TGF-β2 concentrations were 3.6-fold greater in apheresis platelet concentrates, compared with whole blood. Platelet concentrations correlated with growth factor concentrations across all blood and platelet fractions. White blood cell counts had a significant positive correlation with TGF-β1 concentration in buffy coat platelet concentrates.

Conclusions and Clinical Relevance—Platelets and TGF-β1 can be concentrated reliably from equine blood by use of buffy coat or apheresis methods, without modification of the protocols used for humans. (Am J Vet Res2004;65:924–930)
Investigation of the expression and localization of glucose transporter 4 and fatty acid translocase/CD36 in equine skeletal muscle
Authors: van Dam Klien G. , van Breda Eric , Schaart Gert , van Ginneken Mireille M. E. , Wijnberg Inge D. , de Graaf-Roelfsema Ellen , van der Kolk Johannes H. , Keizer Hans A.
Published: December 2005

Objective—To investigate the expression and localization
of glucose transporter 4 (GLUT4) and fatty acid
translocase (FAT/CD36) in equine skeletal muscle.

Sample Population—Muscle biopsy specimens
obtained from 5 healthy Dutch Warmblood horses.

Procedures—Percutaneous biopsy specimens were
obtained from the vastus lateralis, pectoralis descendens,
and triceps brachii muscles. Cryosections were
stained with combinations of GLUT4 and myosin
heavy chain (MHC) specific antibodies or FAT/CD36
and MHC antibodies to assess the fiber specific
expression of GLUT4 and FAT/CD36 in equine skeletal
muscle via indirect immunofluorescent
microscopy.

Results—Immunofluorescent staining revealed that
GLUT4 was predominantly expressed in the cytosol
of fast type 2B fibers of equine skeletal muscle,
although several type 1 fibers in the vastus lateralis
muscle were positive for GLUT4. In all muscle fibers
examined microscopically, FAT/CD36 was strongly
expressed in the sarcolemma and capillaries. Type 1
muscle fibers also expressed small intracellular
amounts of FAT/CD36, but no intracellular FAT/CD36
expression was detected in type 2 fibers.

Conclusions and Clinical Relevance—In equine
skeletal muscle, GLUT4 and FAT/CD36 are expressed
in a fiber type selective manner. ( Am J Vet Res 2004;65:951–956)
Characterization of biological activities of feline eosinophil granule proteins
Authors: Fondati Alessandra , Carreras Esther , Fondevila M. Dolors , Ferrer Lluís , Cuchillo Claudi M. , Nogués M. Victòria
Published: December 2005

Objective—To characterize eosinophil granulederived proteins in cats.

Sample Population—Eosinophils collected via peritoneal lavage from 2 cats.

Procedure—The cats were infested orally withToxocara caniseggs and subsequently challengeexposed withT canisantigen injected IP to induce peritoneal eosinophilia; eosinophils were collected via peritoneal lavage. Eosinophil granule proteins were acid-extracted, separated by gel-filtration chromatography, and examined for their peroxidase, ribonuclease, and bactericidal activities; the N-terminal sequence of some of these proteins was determined and compared with homologue proteins from other species.

Results—3 protein peaks were separated in the chromatogram. The first peak had both peroxidase and bactericidal activities. The second peak had ribonuclease and bactericidal activities, and the N-terminal sequence of the major protein was homologous with that of proteins of the ribonuclease A superfamily, including eosinophil ribonucleases from humans and other animal species. The third protein peak had bactericidal activity, and the N-terminal sequence of the major protein was homologous with that of human and murine major basic proteins.

Conclusions and Clinical Relevance—Results indicated that feline eosinophil granules contain major basic protein and eosinophil-associated ribonuclease and the granule proteins have peroxidase, ribonuclease, and bactericidal activities. In cats, characterization of eosinophil granule proteins may be useful in elucidation of the mechanism of tissue damage in eosinophil-associated diseases and development of new treatment options for those diseases. In addition, the identification of conserved structure and function of eosinophil granule proteins in cats is relevant from an evolutionary viewpoint. (Am J Vet Res2004;65:957–963)
Pharmacologic evaluation of neurokinin-2 receptor antagonists in the guinea pig respiratory tract
Authors: Venugopal Changaram S. , Christopher Craig L. , Wilson Shawn M. , Polikepahad Sumanth , Dequeant Elizabeth , Holmes Earnestine P.
Published: December 2005

Objective—To evaluate 3 neurokinin-2 (NK2) receptor
antagonists on the basis of their ability to block neurokinin
A (NKA)-induced contractile responses in various
regions of the guinea pig respiratory tract.

Animals—48 clinically normal guinea pigs.

Procedure—After euthanasia, the trachea and lungs
were removed en bloc. The spirally cut trachea was
divided into lower, middle, and upper portions. The
main bronchus was spirally cut. A lung strip was cut
from the edge of the lung. Tissue strips were mounted
in organ baths containing Tyrode solution at 37°C
and attached to force transducers interfaced with a
polygraph. Lung strips were set at a tension of 1 g;
other tissue strips were set at 2 g. After 45 minutes
of equilibration, cumulative concentration-response
(CR) relationships to graded concentrations of NKA
were determined. In the treatment groups, tissues
were incubated (30 minutes) with antagonists (MEN
10376, SR 48968, and SR 144190) at 3 concentrations
(10–9, 10–7, and 10–5M) before CR relationships were
determined. Effectiveness of SR 48968 against NKA
was also tested in vivo.

Results—Lung strips failed to contract, but all others
responded in a concentration-dependent manner.
Bronchial spirals were most sensitive. SR 48968 had
the highest pA2 value and effectively blocked NKA.

Conclusions and Clinical Relevance—The bronchial
region where airflow resistance is high was the most
sensitive to NKA, suggesting the importance of NKA
in bronchoconstriction. Nonpeptide antagonists (SR
48968 and SR 144190) were more potent than the
peptide antagonist (MEN 10376), indicating their
greater therapeutic potential as antiasthmatic agents.
( Am J Vet Res 2004;65:984–991)
Pharmacokinetics of amoxicillin after oral administration in recently weaned piglets with experimentally induced Escherichia coli subtype O149:F4 diarrhea
Authors: Jensen Gerda M. , Lykkesfeldt Jens , Frydendahl Kai , Møller Kristian , Svendsen Ove
Published: December 2005

Objective—To measure the effect of Escherichia coli
subtype O149:F4-induced diarrhea on the pharmacokinetics
of orally administered amoxicillin in affected
piglets relative to that of uninfected piglets.

Animals—22 healthy 4-week-old recently weaned
Danish crossbred piglets.

Procedure—12 piglets were orally inoculated through
gastric intubation with 109 CFUs of an E coli O149:F4
strain and responded by developing diarrhea 12 to 16
hours later. Piglets were dosed with amoxicillin trihydrate
solution (20 mg/kg) by gastric intubation. A control
group of 10 age-matched piglets without signs of
diarrhea was dosed similarly. Blood samples were
obtained before amoxicillin administration and at 0.5,
1, 1.5, 2, 3, 6, 12, and 24 hours after amoxicillin administration.
The plasma concentration of amoxicillin was
analyzed by high-performance liquid chromatography.

Results—A significant 39% decrease in the area
under the plasma concentration versus time curve of
amoxicillin was observed in piglets with diarrhea relative
to that of control piglets. The maximum plasma
concentration (Cmax) was significantly (52%) lower in
piglets with diarrhea, compared with control piglets,
while the elimination rate constant, time to reach
Cmax, and elimination half-life were unchanged.

Conclusions and Clinical Relevance—Escherichia
coli-induced diarrhea may decrease systemic bioavailability
of amoxicillin. Escherichia coli bacteria attach to
the intestinal epithelial cells. Because it is assumed
that the concentration of the antimicrobial at the site
of infection reflects the systemic concentration, higher
doses of amoxicillin in the treatment of piglets with
E coli O149:F4-induced diarrhea may be appropriate.
( Am J Vet Res 2004;65:992–995)
Influence of normovolemic anemia on Doppler characteristics of the abdominal aorta and splanchnic vessels in Beagles
Authors: Koma Lee M. , Spotswood Tim C. , Kirberger Robert M. , Becker Piet J.
Published: December 2005

Objective—To ultrasonographically evaluate hemodynamics
in the abdominal aorta (AAo) and splanchnic
vessels in dogs with experimentally induced normovolemic
anemia.

Animals—11 healthy Beagles.

Procedure—The AAo, cranial mesenteric artery
(CMA), celiac artery (CA), hilar splenic artery (HSA),
and main portal vein (MPV) were evaluated in conscious
dogs immediately before and after experimental
induction of severe normovolemic anemia (Hct,
16%) and during recovery from moderate and mild
anemia (Hct, 26% and 34%, respectively). Peak systolic
velocity (PSV) or peak velocity (PV), time-averaged
mean velocity (TAVmean), pulsatility index (PI),
resistive index (RI), blood flow, congestion index (CI),
and heart rate (HR) were recorded. Results were
compared for anemic and control states.

Results—Severe anemia caused significant increases
in HR (25% to 70%), PSV (AAo, 45.8%; CMA, 56.1%;
and CA, 41.9%), PV (MPV, 84.2%), and TAVmean (AAo,
69.4%, CMA, 64.3%; CA, 29.7%; and MPV, 76.9%) and
significant decreases in PI (AAo, 26.1%; HSA, 19.3%)
and CI (MPV, 45.2%). There was no significant change
in PI of the CMA or CA, portal blood flow, or RI of any
artery. Significantly higher TAVmean persisted in all vessels
during moderate anemia, but higher PSV persisted
only in the CMA; PI (CMA and CA) and RI (CA)
decreased significantly, but portal blood flow increased
significantly. Significant increase in TAVmean (AAo and
CMA) persisted during mild anemia, and PI (AAo, CMA,
and HSA) but RI (CMA) were significantly lower.

Conclusions and Clinical Relevance—Doppler ultrasonography
revealed hyperdynamic circulation in the
AAo and splanchnic vessels in dogs with experimentally
induced normovolemic anemia. (Am J Vet Res 2005;66:187–195)
Culture of feline corneal epithelial cells and infection with feline herpesvirus-1 as an investigative tool
Authors: Sandmeyer Lynne S. , Keller Charlotte B. , Bienzle Dorothee
Published: December 2005

Objective—To isolate and characterize pure cultures
of feline corneal epithelial cells and to assess the
extent and nature of feline herpesvirus (FHV)-1 infection
in these cells.

Sample Population—Healthy eyes from 23 recently
euthanatized cats.

Procedure—Stroma and epithelium of the rostral
portion of the cornea were surgically isolated, and
epithelial cells were detached from the stroma by
enzymatic incubation. Epithelial cells were cultured in
hormone-supplemented media. Cells were passaged,
and cytokeratin expression was assessed. Cells were
then infected with FHV-1, and cytopathic effects were
determined.

Results—Cell cultures were readily established from
samples obtained from each eye and could be maintained
through 6 passages. Cultured cells expressed
cytokeratins 3 and 12 but not other cytokeratins.
Infection with FHV-1 was rapid and caused widespread
cytopathic effects.

Conclusions and Clinical Relevance—Feline corneal
cells cultured in vitro during multiple passages maintain
consistent morphologic characteristics and intermediate
filament expression. They are susceptible to
infection with FHV-1 and may provide a useful in vitro
model for investigation of ocular drugs. (Am J Vet Res 2005;66:205–209)
Effects of cidofovir on cell death and replication of feline herpesvirus-1 in cultured feline corneal epithelial cells
Authors: Sandmeyer Lynne S. , Keller Charlotte B. , Bienzle Dorothee
Published: December 2005

Objective— To assess the effect of cidofovir on viability
of feline corneal epithelial (FCE) cells, replication
of feline herpesvirus (FHV)-1, and virus-induced cytopathic
changes.

Sample Population—Healthy eyes from 14 recently
euthanatized cats.

Procedure—Cidofovir at concentrations ranging from
0.05 to 0.000005 mg/mL was added to primary cultures
of FCE cells, and cytopathic changes and effects
on cell proliferation and cell viability were determined
during the subsequent 48 hours. Efficacy of cidofovir
(0.02 and 0.05 mg/mL) to prevent in vitro infection of
FCE cells with FHV-1 was determined during 72 hours
of culture by assessing viral cytopathic effects and
viral titers.

Results—Cidofovir at concentrations of 0.05, 0.005,
and 0.0005 mg/mL significantly reduced mean viable
cell counts, and cidofovir at a concentration of 0.05
mg/mL significantly reduced the percentage viability
of cultured FCE cells. Minimal cytopathic changes
were observed at concentrations of 0.02 and 0.05 mg
of cidofovir/mL. Cidofovir at concentrations of 0.05
and 0.02 mg/mL abrogated the cytopathic effects
attributable to FHV-1 infection and reduced viral titers
from ≥ 1014 TCID50/mL to ≤ 103.5 TCID50/mL.

Conclusions and Clinical Relevance—Cidofovir in
vitro was highly efficacious against FHV-1 infection of a
primary culture of FCE cells but had cytostatic effects
on cultured cells. (Am J Vet Res 2005;66:217–222)
Plication of the free wall of the left ventricle in dogs with doxorubicin-induced cardiomyopathy
Authors: Andrade James N. B. M. de , Camacho Aparecido A. , Santos Paulo S. P. , Fantinatti Alexandra P. , Nunes Newton , Stopiglia Angelo J.
Published: December 2005

Objective—To evaluate plication of the free wall of
the left ventricle, which reduces the left ventricular
area and volume, as a method to improve the left ventricular
systolic function without cardiopulmonary
bypass.

Animals—8 mixed-breed adult dogs.

Procedure—Dilated cardiomyopathy (DCM) was
induced in each dog by administration of doxorubicin
(30 mg/m2, IV, q 21 d for 168 days). Two dogs died during
induction of cardiomyopathy. Plication surgery
was performed in 4 dogs. Two dogs did not ondergo
to surgery (control group). Values for cardiac output
(CO), 2-dimensional and M-mode echocardiography,
arterial blood pressure, electrocardiography, blood cell
counts, and serum biochemical analyses were recorded
after induction of DCM (baseline) and 1, 2, 7, 15,
21, 30, 60, 90, 120, 150, and 180 days after plication
surgery. Ambulatory ECG (Holter) recordings were
conducted for 24 hours on the day of surgery.

Results—1 dog died after plication surgery. The
remaining dogs undergoing ventricular plication had a
significant improvement in CO, ejection fraction, and
fractional shortening and reductions of left ventricular
area and volume after surgery. Electrocardiographic
and Holter recordings revealed premature ventricular
complexes, which resolved without treatment during
the first week after surgery. Clinical condition of the
control dogs declined, and these 2 dogs died approximately
40 days after induction of cardiomyopathy.

Conclusions and Clinical Relevance—Plication of
the free wall of the left ventricle improved left ventricular
systolic function in dogs with doxorubicininduced
cardiomyopathy. Additional studies are needed
to evaluate its application in dogs with naturally
developing DCM. (Am J Vet Res 2005;66:238–243)
Morphologic and physiologic changes induced by Clostridium perfringens type A α toxin in the intestine of sheep
Authors: Fernández Miyakawa Mariano E. , Uzal Francisco A.
Published: December 2005

Objective—To evaluate the morphologic and physiologic
changes induced by Clostridium perfringens
type A α toxin in the ileum and colon of sheep.

Sample Population—16 ligated intestinal loops in 4
Merino lambs and 18 explants of ileum and colon
from slaughtered lambs.

Procedure—α Toxin–induced fluid accumulation was
evaluated in ligated ileal and colonic loops of sheep.
Tissues were evaluated morphologically by use of
gross and histologic examination. Effects of toxin on
in vitro intestinal net water transport were tested in
modified Ussing chambers.

Results—Ovine ileal and colonic loops incubated with
C perfringens type A α toxin retained more fluid than
control loops. Histologically, in the ileum of lambs
inoculated with 300 LD50 of α toxin/mL, there was a
mild to moderate multifocal infiltration of neutrophils
in the lamina propria and submucosa. The colonic
loops of lambs inoculated with 30 or 300 LD50 of α
toxin/mL had excessive mucus in the lumen, a moderate
amount of neutrophils mixed with mucus in the
intestinal lumen, and moderate multifocal infiltration
of the lamina propria and submucosa with neutrophils;
the blood vessels of these layers were
engorged with neutrophils. In vitro measurements of
water transport also revealed inhibition of net epithelial
water absorption in ileum and colon incubated
with α toxin on the mucosal side.

Conclusions and Clinical Relevance—These results
indicate that α toxin induces alterations in sheep
intestine. Clostridium perfringens type A organisms
that produce α toxin could be responsible for diseases
of intestinal origin in some ruminants. (Am J Vet Res 2005;66:251–255)