bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh)
Authors: Flammer Keven , Nettifee Osborne Julie A. , Webb Donna J. , Foster Laura E. , Dillard Stacy L. , Davis Jennifer L.
Published: January 2008

Objective—To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots.

Animals—20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh).

Procedures—In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments).

Results—Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group.

Conclusions and Clinical Relevance—In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole ≤ 0.4 μg/mL. Higher doses may be needed to maintain plasma voriconazole concentrations during long-term treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.
Hypertension and insulin resistance in a mixed-breed population of ponies predisposed to laminitis
Authors: Bailey Simon R. , Habershon-Butcher Jocelyn L. , Ransom Kathryn J. , Elliott Jonathan , Menzies-Gow Nicola J.
Published: January 2008

Objective—To determine the metabolic phenotype of a group of laminitis-prone ponies when at pasture in summer, compared with when at pasture in winter.

Animals—40 ponies of various breeds predisposed to recurrent pasture-associated laminitis and 40 unaffected control ponies.

Procedures—Body condition score and size of the crest of the neck were assessed, blood samples obtained, and blood pressure measured by use of an indirect oscillometric technique, while ponies were kept on winter pasture (last week of November or beginning of December) and again on summer pasture (June). Serum insulin concentration and plasma glucose, triglyceride, uric acid, and ACTH concentrations were measured. Insulin sensitivity was calculated with proxies derived from basal serum insulin and plasma glucose concentrations.

Results—No significant differences were apparent between ponies predisposed to laminitis and control ponies during winter. However, in June, laminitis-prone ponies had increased serum insulin concentration and plasma triglyceride and uric acid concentrations, compared with control ponies. Also, laminitis-prone ponies were relatively insulin resistant, compared with control ponies. Mean blood pressure was significantly higher during summer in laminitis-prone ponies (median [interquartile range], 89.6 mm Hg [78.3 to 96.9 mm Hg]), compared with control ponies (76.8 mm Hg [69.4 to 85.2 mm Hg]).

Conclusions and Clinical Relevance—Summer pastures appear to induce metabolic responses in some ponies, leading to expression of the prelaminitic phenotype, which includes hypertension as well as insulin resistance. Signs of this metabolic syndrome may not be apparent in affected ponies during periods of grazing winter pasture. Understanding this syndrome may enable improved countermeasures to be devised to prevent laminitis.
Induction and recovery characteristics and cardiopulmonary effects of sevoflurane and isoflurane in bald eagles
Authors: Joyner Priscilla H. , Jones Michael P. , Ward Daniel , Gompf Rebecca E. , Zagaya Nancy , Sleeman Jonathan M.
Published: January 2008

Objective—To compare induction and recovery characteristics and cardiopulmonary effects of isoflurane and sevoflurane in bald eagles.

Animals—17 healthy adult bald eagles.

Procedures—Anesthesia was induced with isoflurane or sevoflurane delivered in oxygen via a facemask in a crossover design with 4 weeks between treatments. Eagles were intubated, allowed to breathe spontaneously, and instrumented for cardiopulmonary measurements. Time to induction, extubation, and recovery, as well as smoothness of recovery, were recorded.

Results—Administration of sevoflurane resulted in a significantly quicker recovery, compared with isoflurane. Temperature, heart rate, and respiratory rate significantly decreased over time, whereas systolic (SAP), diastolic (DAP), and mean arterial blood pressure (MAP) significantly increased over time with each treatment. Temperature, heart rate, SAP, DAP, and MAP were significantly higher with isoflurane. Blood pH significantly decreased, whereas PaCO2 significantly increased over time with each treatment. Bicarbonate and total carbon dioxide concentrations significantly increased over time with each treatment; however, there was a significant time-treatment interaction. The PaO2 and arterial oxygen saturation increased over time with isoflurane and decreased over time with sevoflurane with a significant time-treatment interaction. Six eagles developed cardiac arrhythmias with isoflurane, as did 4 with sevoflurane anesthesia.

Conclusions and Clinical Relevance—Isoflurane and sevoflurane administration resulted in smooth, rapid induction of and recovery from anesthesia similar to other species. Isoflurane administration resulted in tachycardia, hypertension, and more arrhythmias, compared with sevoflurane. Sevoflurane was associated with fewer adverse effects and may be particularly beneficial in compromised bald eagles.
Effects of systemic inflammation on insulin sensitivity in horses and inflammatory cytokine expression in adipose tissue
Authors: Vick Mandi M. , Murphy Barbara A. , Sessions Dawn R. , Reedy Stephanie E. , Kennedy Erin L. , Horohov David W. , Cook R. Frank , Fitzgerald Barry P.
Published: January 2008

Objective—To determine whether an inflammatory challenge induces insulin resistance in horses and examine possible contributions of adipose tissue to inflammatory cytokine production.

Animals—15 adult mares.

Procedures—Lipopolysaccharide (0.045 μg/kg, IV) or saline solution was administered, and insulin sensitivity was determined by means of the hyperinsulinemic, euglycemic clamp procedure or an adipose tissue biopsy was performed. Adipose tissue samples were collected, and mature adipocytes were obtained. Mature adipocytes were stimulated with lipopolysaccharide or dedifferentiated into preadipocytes and then stimulated with lipopolysaccharide. Interleukin-1, interleukin-6, and tumor necrosis factor A expression in blood, adipose tissue, and adipocytes was quantified with a real-time, reverse transcriptase– PCR assay.

Results—Lipopolysaccharide induced a transient increase in insulin sensitivity followed by a reduction in insulin sensitivity at 24 hours. Increased cytokine expression was observed in blood and adipose tissue following administration of lipopolysaccharide, and adipocytes and preadipocytes stimulated with lipopolysaccharide stained positive for tumor necrosis factor A. Expression of interleukin-1, interleukin-6, and tumor necrosis factor A was detected in preadipocytes stimulated with lipopolysaccharide, and interleukin-6 and tumor necrosis factor A were detected in mature adipocytes stimulated with lipopolysaccharide.

Conclusions and Clinical Relevance—Results indicated that insulin resistance develops following systemic inflammation in horses and suggested that adipose tissue may contribute to this inflammatory response. Methods to regulate insulin sensitivity may improve clinical outcome in critically ill patients.
Comparison of intratesticular injection of zinc gluconate versus surgical castration to sterilize male dogs
Authors: Levy Julie K. , Crawford P. Cynda , Appel Leslie D. , Clifford Emma L.
Published: January 2008

Objective—To compare castration of dogs by use of intratesticular injection of zinc gluconate with traditional surgical procedures in terms of acceptance by pet owners, ease of use, and short-term outcomes on Isabela Island of the Galápagos Islands.

Animals—161 privately owned male dogs admitted to a neuter program.

Procedures—Medical records of male dogs neutered during a 4-week animal control campaign were reviewed to collect information regarding signalment, method of castration, complication rate, and treatment outcomes.

Results—Of the 161 dogs admitted for castration, 58 were surgically castrated and 103 were treated with zinc gluconate. Dogs were returned to their owners for observation following castration. Wound dehiscence occurred in 2 skin incisions, representing 3.4% of the 58 dogs that underwent bilateral orchiectomy. Necrotizing zinc-gluconate injection-site reactions occurred in 4 dogs receiving injection volumes near the maximum label dose (0.8 to 1.0 mL), representing 3.9% of the zinc-gluconate procedures. Surgical wound complications were treated by superficial wound debridement and resuturing, in contrast to zinc-gluconate injection-site reactions, which all required orchiectomy and extensive surgical debridement, including scrotal ablation in 2 dogs.

Conclusions and Clinical Relevance—Low cost, ease of use, and cultural acceptance of a castration technique that does not require removal of the testes make zinc gluconate a valuable option for large-scale use in dogs, particularly in remote locations lacking sophisticated clinical facilities or skilled surgeons and staff. Further investigation is needed to identify risk factors in dogs for adverse reactions to zinc gluconate and to develop strategies for avoidance.
Effects of hyperbaric oxygen on full-thickness meshed sheet skin grafts applied to fresh and granulating wounds in horses
Authors: Holder Troy E. C. , Schumacher Jim , Donnell Robert L. , Rohrbach Barton W. , Adair H. Steve A.
Published: January 2008

Objective—To determine the effects of hyperbaric oxygen therapy (HBOT) on full-thickness skin grafts applied to fresh and granulating wounds of horses.

Animals—6 horses.

Procedures—On day 0, two 4-cm-diameter circular sections of full-thickness skin were removed from each of 2 randomly selected limbs of each horse, and two 4-cm-diameter circular skin grafts were harvested from the pectoral region. A skin graft was applied to 1 randomly selected wound on each limb, leaving the 2 nongrafted wounds to heal by second intention. On day 7, 2 grafts were harvested from the pectoral region and applied to the granulating wounds, and wounds grafted on day 0 were biopsied. On day 14, 1 wound was created on each of the 2 unwounded limbs, and the wounds that were grafted on day 7 were biopsied. All 4 ungrafted wounds (ie, 2 fresh wounds and 2 wounds with 1-week-old granulation beds) were grafted. The horses then received HBOT for 1 hour daily at 23 PSI for 7 days. On day 21, the grafts applied on day 14 were biopsied.

Results—Histologic examination of biopsy specimens revealed that grafts treated with HBOT developed less granulation tissue, edema, and neovascularization, but more inflammation. The superficial portion of the graft was also less viable than the superficial portion of those not treated with HBOT.

Conclusions and Clinical Relevance—The use of HBOT after full-thickness skin grafting of uncompromised fresh and granulating wounds of horses is not indicated.
In vitro and in vivo comparison of five biomaterials used for orthopedic soft tissue augmentation
Authors: Cook James L. , Fox Derek B. , Kuroki Keiichi , Jayo Manuel , De Deyne Patrick G.
Published: January 2008

Objective—To compare biomaterials used in orthopedics with respect to in vitro cell viability and cell retention and to in vivo tissue healing and regeneration.

Animals—65 adult female Sprague-Dawley rats and synovium, tendon, meniscus, and bone marrow specimens obtained from 4 adult canine cadavers.

Procedures—Synovium, tendon, meniscus, and bone marrow specimens were used to obtain synovial fibroblasts, tendon fibroblasts, meniscal fibrochondrocytes, and bone marrow–derived connective tissue progenitor cells for culture on 5 biomaterials as follows: cross-linked porcine small intestine (CLPSI), non–cross-linked human dermis, cross-linked porcine dermis, non–cross-linked porcine small intestine (NCLPSI), and non–cross-linked fetal bovine dermis. After 1 week of culture, samples were evaluated for cell viability, cell density, and extracellular matrix production. Biomaterials were evaluated in a 1-cm2 abdominal wall defect in rats. Each biomaterial was subjectively evaluated for handling, suturing, defect fit, and ease of creating the implant at the time of surgery, then grossly and histologically 6 and 12 weeks after surgery.

Results—All biomaterials allowed for retention of viable cells in culture; however, CLPSI and NCLPSI were consistently superior in terms of cell viability and cell retention. Cell infiltration for NCLPSI was superior to other biomaterials. The NCLPSI appeared to be replaced with regenerative tissue most rapidly in vivo and scored highest in all subjective evaluations of ease of use.

Conclusions and Clinical Relevance—These data suggested that NCLPSI and CLPSI have favorable properties for further investigation of clinical application in orthopedic tissue engineering.
Virus-specific antiviral treatment for controlling severe and fatal outbreaks of feline calicivirus infection
Authors: Smith Alvin W. , Iversen Patrick L. , O'Hanley Peter D. , Skilling Douglas E. , Christensen Janet R. , Weaver Sherry S. , Longley Kimberli , Stone Michael A. , Poet Steve E. , Matson David O.
Published: January 2008

Objective—To test the life-sparing and therapeutic effect of a parenterally administered virus-specific antiviral phosphorodiamidate morpholino oligomer (PMO) for treating kittens during outbreaks of severe viral disease.

Animals—112 kittens of various sex and age in 4 trials involving 3 outbreaks of naturally developing caliciviral disease.

Procedures—Each trial provided an opportunity to investigate the disease. A calicivirus isolated from the liver of a cat that died with hemorrhage and hepatitis was sequenced, and a PMO that had sequence specificity complementary to a 5' region was synthesized. In vitro efficacy of the PMO was tested against the isolate, followed by 3 trials in outbreaks of severe caliciviral disease. The PMO was administered starting on day 1 of disease onset (0.7 to 5.0 mg/kg, SC, q 24 h) and continuing for up to 7 days. Survival time, clinical recovery, and caliciviral shedding were compared by use of various antiviral dosages. In a fourth trial involving nonfatal disease, a control treatment was administered for comparison.

Results—In vitro blockage of caliciviral replication by the PMO was dose dependent. In trials 1 to 3 in which survival was the endpoint, 47 of 59 cats receiving PMO survived but only 3 of 31 survived without PMO treatment. Antiviral treatment reduced viral shedding and hastened clinical recovery, as measured by weight gains and clinical condition.

Conclusions and Clinical Relevance—These data provided evidence that virus-specific PMOs were effective in treating kittens with severe Vesivirus disease and suggested a broader application for other viruses and species, including humans.
Volume loading–related changes in tissue Doppler images derived from the tricuspid valve annulus in dogs
Authors: Hori Yasutomo , Ukai Yoshimi , Hoshi Fumio , Higuchi Sei-ichi
Published: January 2008

Objective—To investigate the relationship between preload and tricuspid valve annulus–derived tissue Doppler imaging (TDI) as an index of right ventricular (RV) filling in dogs.

Animals—7 Beagles.

Procedures—Peak systolic RV pressure and RV end-diastolic pressure (RVEDP) were measured in anesthetized dogs. Pulsed Doppler was used to measure tricuspid valve inflow and pulmonary valve outflow velocities. The TDI velocities were measured at the lateral corner of the tricuspid valve annulus. Lactated Ringer's solution was infused at 200 mL/kg/h for 60 minutes via the cephalic vein.

Results—IV infusion significantly increased heart rate, RV pressure, and RVEDP. Early diastolic flow (E-wave) and ejection time significantly increased. The myocardial performance index (MPI) significantly decreased. Intravenous infusion significantly increased the ratio of the E'-wave (peak myocardial velocity during early diastole) to the A'-wave (peak myocardial velocity during late diastole; E':A' ratio) and myocardial velocity during systole (S'), early diastole (E'), and late diastole (A'). The TDI-isovolumic relaxation time and TDI-MPI decreased significantly. The RVEDP was correlated with late diastolic flow (A-wave), ratio of the E-wave to the A-wave (E:A ratio), E'-wave, A'-wave, S'-wave (peak myocardial velocity during systole), TDI-isovolumic relaxation time, TDI-MPI, and ratio of the E-wave to the E'-wave (E: E' ratio). The A-wave and E:A ratio and TDI-derived isovolumic relaxation time, S' duration, and E'-wave could predict the RVEDP.

Conclusions and Clinical Relevance—The TDI velocities were affected by RV filling pressure in healthy dogs, whereas other TDI profiles, such as MPI and E':A' ratio, were independent of acute filling abnormalities.
Comparison of pharmacodynamic variables following oral versus transdermal administration of atenolol to healthy cats
Authors: MacGregor John M. , Rush John E. , Rozanski Elizabeth A. , Boothe Dawn M. , Belmonte Albert A. , Freeman Lisa M.
Published: January 2008

Objective—To describe the disposition of and pharmacodynamic response to atenolol when administered as a novel transdermal gel formulation to healthy cats.

Animals—7 healthy neutered male client-owned cats.

Procedures—Atenolol was administered either orally as a quarter of a 25-mg tablet or as an equal dose by transdermal gel. Following 1 week of treatment, an ECG and blood pressure measurements were performed and blood samples were collected for determination of plasma atenolol concentration at 2 and 12 hours after administration.

Results—2 hours after oral administration, 6 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 579 ± 212 ng/mL. Two hours following transdermal administration, only 2 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 177 ± 123 ng/mL. The difference in concentration between treatments was significant. Trough plasma atenolol concentrations of 258 ± 142 ng/mL and 62.4 ± 17 ng/mL were achieved 12 hours after oral and transdermal administration, respectively. A negative correlation was found between heart rate and plasma atenolol concentration.

Conclusions and Clinical Relevance—Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol.
Quantitative assessment of blood volume, blood flow, and permeability of the brain of clinically normal dogs by use of dynamic contrast-enhanced computed tomography
Authors: Peterson Kristi L. , MacLeod Alexander G. , Wisner Erik R. , Larson Richard F. , Pollard Rachel E.
Published: January 2008

Objective—To determine effects of regional variation, interobserver variability, and vessel selection on quantitative vascular variables derived by dynamic contrast-enhanced computed tomography (DCE-CT) of the brain of clinically normal dogs.

Animals—14 adult dogs with no evidence of CNS dysfunction.

Procedures—Dogs were randomly assigned to 4 groups, and DCE-CT was performed at the level of the frontal lobe, rostral portion of the parietal-temporal lobes, caudal portions of the parietal-temporal lobes, or occipital lobe–cerebellum for groups 1 to 4, respectively. Cerebral blood flow (CBF), cerebral blood volume (CBV), and permeability in gray and white matter for both a large and small artery were calculated and compared. Values among 3 observers and 4 regions of the brain were calculated and compared.

Results—Significant interobserver variability was detected for CBF and permeability in white matter. Values calculated for large and small arteries were correlated for CBV and CBF but not for permeability. Overall mean ± SD for CBF, CBV, and permeability in gray matter was 53.5 ± 27.7 mL/min/100 g, 2.9 ± 1.4 mL/100 g, and 1.4 ± 2.2 mL/min/100 g, respectively. Mean for CBF, CBV, and permeability in white matter was 44.2 ± 28.5 mL/min/100 g, 2.5 ± 1.5 mL/100 g, and 0.9 ± 0.7 mL/min/100 g, respectively. Values did not differ significantly among brain regions.

Conclusions and Clinical Relevance—Significant regional variations were not detected for quantitative vascular variables in the brain of clinically normal dogs. However, interobserver variability and vessel selection have an important role in variable estimation.
Effects of dexamethasone administration on insulin resistance and components of insulin signaling and glucose metabolism in equine skeletal muscle
Authors: Tiley Heather A. , Geor Raymond J. , McCutcheon L. Jill
Published: January 2008

Objective—To determine the effects of dexamethasone treatment on selected components of insulin signaling and glucose metabolism in skeletal muscle obtained from horses before and after administration of a euglycemic-hyperinsulinemic clamp (EHC).

Animals—6 adult Standardbreds.

Procedures—In a balanced crossover study, horses received either dexamethasone (0.08 mg/kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution, IV, for 21 days. A 2-hour EHC was administered for measurement of insulin sensitivity 1 day after treatment. Muscle biopsy specimens obtained before and after the EHC were analyzed for glucose transporter 4, protein kinase B (PKB), glycogen synthase kinase (GSK)-3α/β protein abundance and phosphorylation state (PKB Ser473 and GSK-3α/β Ser21/9), glycogen synthase and hexokinase enzyme activities, and muscle glycogen concentration.

Results—Dexamethasone treatment resulted in resting hyperinsulinemia and a significant decrease (70%) in glucose infusion rate during the EHC. In the dexamethasone group, increased hexokinase activity, abrogation of the insulin-stimulated increase in glycogen synthase fractional velocity, and decreased phosphorylation of GSK-3α Ser21 and GSK-3B Ser9 were detected, but there was no effect of dexamethasone treatment on glucose transporter 4 content and glycogen concentration or on PKB abundance and phosphorylation state.

Conclusions and Clinical Relevance—In horses, 21 days of dexamethasone treatment resulted in substantial insulin resistance and impaired GSK-3 phosphorylation in skeletal muscle, which may have contributed to the decreased glycogen synthase activity seen after insulin stimulation.
Transmission of relaxin and estrogens to suckling canine pups via milk and possible association with hip joint laxity
Authors: Steinetz Bernard G. , Williams Alma J. , Lust George , Schwabe Christian , Büllesbach Erika E. , Goldsmith Laura T.
Published: January 2008

Objective—To determine whether abnormal laxity of hip joints of canine pups with genetic predisposition to hip dysplasia (HD+) is related to ingestion of milk-borne hormones.

Animals—7 female Labrador Retrievers with HD+ and 8 with low predisposition to hip dysplasia (HD–) and their offspring.

Procedures—Immunoactive relaxin, estrogen, and estrogen precursor concentrations in milk of HD+ lactating bitches and in serum of their pups were compared with those of HD– bitches and pups. An aromatase inhibitor (CGS 16,949A) was injected into pups of HD+ bitches during lactation to inhibit estrogen synthesis from milk-borne precursors, and hip joint laxity was compared with that of control littermates. Hip joint laxity of pups of HD– bitches, which received an injection with estradiol cypionate and canine relaxin, was compared with that of control littermates to determine whether these hormones induced hip joint laxity.

Results—High concentrations of estrogens and relaxin were found in milk of HD+ and HD– bitches throughout lactation. Serum concentrations of milk-derived relaxin and total estrogens were similar in all pups, but estradiol-17B was detected only in pups of HD+ bitches. Hip joint laxity was reduced in pups that received CGS 16,949A. Hip joint laxity was increased in pups of HD– bitches that received estradiol cypionate and relaxin.

Conclusions and Clinical Relevance—Milk-borne maternal hormones and precursors were absorbed into the circulation of canine neonates and may play a role in hip joint laxity in HD+ pups. Phenotypic expression of hip dysplasia may therefore be preventable by antihormone treatment.
Effects of long-term oral administration of levothyroxine sodium on serum thyroid hormone concentrations, clinicopathologic variables, and echocardiographic measurements in healthy adult horses
Authors: Frank Nicholas , Buchanan Benjamin R. , Elliott Sarah B.
Published: January 2008

Objective—To determine the effects of long-term oral levothyroxine sodium (L-T4) administration on serum thyroid hormone concentrations, thyroid gland function, clinicopathologic variables, and echocardiographic examination measurements in adult euthyroid horses.

Animals—6 healthy adult mares.

Procedures—Horses received L-T4 (48 mg/d) orally for 48 weeks. Every 4 weeks, physical examinations were performed; blood samples were collected for CBC, plasma biochemical analyses, and assessments of serum total triiodothyronine (tT3) and thyroxine (tT4) concentrations. Plasma creatine kinase MB activity and cardiac troponin I concentration were also measured. Echocardiographic examinations were performed before and at 16, 32, and 48 weeks during the treatment period.

Results—During the treatment period, mean body weight decreased significantly; heart rate varied significantly, but the pattern of variation was not consistent. Significant time effects were detected for certain clinicopathologic variables, but mean values remained within reference ranges. Cardiac troponin I was only detectable in 8 of 24 plasma samples (concentration range, 0.01 to 0.03 ng/mL). Serum creatine kinase MB activity did not change significantly over time. Compared with the pretreatment value, 5.4-, 4.0-, and 3.7-fold increases in mean serum tT4 concentrations were detected at 16, 32, and 48 weeks, respectively. Some cardiac measurements changed significantly over time, but mean values remained within published reference ranges. Mean fractional shortening was lower than the pretreatment mean value at 16 and 32 weeks.

Conclusions and Clinical Relevance—In horses, long-term oral administration of 48 mg of L-T4/d significantly increased serum tT4 concentrations and did not appear to adversely affect health.
Effects of long-term oral administration of levothyroxine sodium on glucose dynamics in healthy adult horses
Authors: Frank Nicholas , Elliott Sarah B. , Boston Raymond C.
Published: January 2008

Objective—To determine the effects of long-term oral administration of levothyroxine sodium (L-T4) on glucose dynamics in adult euthyroid horses.

Animals—6 healthy adult mares.

Procedures—Horses received L-T4 (48 mg/d) orally for 48 weeks. Frequently sampled IV glucose tolerance test procedures were performed on 3 occasions (24-hour intervals) before and at 16, 32, and 48 weeks during the treatment period. Data were assessed via minimal model analysis. The repeatability of measurements was evaluated.

Results—During treatment, body weight decreased significantly from the pretreatment value; mean ± SD weight was 49 ± 14 kg, 43 ± 7 kg, and 25 ± 18 kg less than the pretreatment value at weeks 16, 32, and 48, respectively. Compared with pretreatment findings, 1.8-, 2.4-, and 1.9-fold increases in mean insulin sensitivity (SI) were detected at weeks 16, 32, and 48, respectively; SI was negatively correlated with body weight (r = −0.42; P < 0.001). During treatment, glucose effectiveness increased and the acute insulin response to glucose decreased. Overall mean within-horse coefficients of variation were 5% and 29% for plasma glucose and serum insulin concentrations, respectively, and 33%, 26%, and 23% for SI, glucose effectiveness, and the acute insulin response to glucose, respectively.

Conclusions and Clinical Relevance—Long-term administration of L-T4 was associated with weight loss and increased SI in adult euthyroid horses, although other factors may have confounded results. Levothyroxine sodium may be useful for the treatment of obesity and insulin resistance in horses, but further studies are required.
Effects of an intravenous endotoxin challenge on glucose and insulin dynamics in horses
Authors: Tóth Ferenc , Frank Nicholas , Elliott Sarah B. , Geor Raymond J. , Boston Raymond C.
Published: January 2008

Objective—To evaluate the effects of endotoxin administered IV on glucose and insulin dynamics in horses.

Animals—16 healthy adult mares.

Procedures—Each week of a 2-week randomized crossover study, each horse received an IV injection (duration, 30 minutes) of Escherichia coli O55:B5 lipopolysaccharide (LPS) in 60 mL of sterile saline (0.9% NaCl) solution (20 ng/kg) or sterile saline solution alone (control treatment). Frequently sampled IV glucose tolerance test procedures were performed at 24 hours before (baseline) and 24 and 48 hours after injection; glucose and insulin dynamics were assessed via minimal model analysis.

Results—13 of 16 horses had a clinical response to LPS, which was characterized by mild colic and leukopenia. Before treatment, mean ± SD insulin sensitivity was 2.9 ± 1.9 × 10−4 L·min−1·mU−1; this significantly decreased to 0.9 ± 0.9 × 10−4 L·min−1·mU−1 24 hours after treatment (69% reduction) and was 1.5 ± 0.9 × 10−4 L·min−1·mU−1 48 hours after treatment. At baseline, mean ± SD acute insulin response to glucose was 520 ± 196 mU·min·L−1; this significantly increased to 938 ± 620 mU·min·L−1 (80% increase) and 755 ± 400 mU·min·L−1 (45% increase) at 24 and 48 hours after LPS treatment, respectively.

Conclusions and Clinical Relevance—Compared with baseline values, insulin sensitivity was decreased for 24 hours after IV injection of LPS, and affected horses had a compensatory pancreatic response. These disturbances in glucose and insulin dynamics may contribute to development of laminitis in horses.
Radiographic morphology of the cranial portion of the cervical vertebral column in Cavalier King Charles Spaniels and its relationship to syringomyelia
Authors: Stalin Catherine E. , Rusbridge Clare , Granger Nicolas , Jeffery Nick D.
Published: January 2008

Objective—To compare radiographic morphology of the atlantoaxial region between Cavalier King Charles Spaniels (CKCSs) and dogs of other breeds and determine whether there was an association between radiographic morphology of the atlantoaxial region and syringomyelia in CKCSs.

Animals—65 CKCSs and 72 dogs of other breeds.

Procedures—The amount that the spinous process of the axis overlapped the dorsal arch of the atlas, the relative size of the spinous process of the axis, and the amount of widening of the atlantoaxial joint that occurred when the neck was moved from a neutral to a flexed position were measured on lateral radiographic projections of the atlantoaxial region. Magnetic resonance images were reviewed to identify CKCSs with syringomyelia.

Results—The amount of overlap of the atlas and axis and the relative size of the spinous process of the axis were significantly smaller in CKCSs than in dogs of other breeds. However, the amount of widening of the atlantoaxial joint that occurred when the neck was moved from a neutral to a flexed position was not significantly different between groups, and no association was detected between syringomyelia and excessive atlantoaxial joint space widening or between syringomyelia and an excessively small axial spinous process.

Conclusions and Clinical Relevance—Results suggested that radiographic morphology of the atlantoaxial region in CKCSs differs from morphology of that region in dogs of other breeds, but that these differences do not account for why some CKCSs develop syringomyelia and others do not.
Effect of grape polyphenols on oxidative stress in canine lens epithelial cells
Authors: Barden Curtis A. , Chandler Heather L. , Lu Ping , Bomser Joshua A. , Colitz Carmen M. H.
Published: January 2008

Objective—To evaluate whether the effects of oxidative stress could be attenuated in cultures of canine lens epithelial cells (LECs) by incubation with grape seed proanthocyanidin extract (GSE), resveratrol (RES), or a combination of both (GSE+RES).

Sample Population—Primary cultures of canine LECs.

Procedures—LECs were exposed to 100MM tertiary butyl-hydroperoxide (TBHP) with or without GSE, RES, or GSE+RES. The dichlorofluorescein assay was used to detect production of reactive oxygen species (ROS), and immunoblot analysis was used to evaluate the expression of stress-induced cell-signaling markers (ie, the mitogen-activated protein kinase [MAPK] and phosphoinositide-3 kinase [PI3K] pathways).

Results—GSE and GSE+RES significantly reduced ROS production after a 30-minute exposure to TBHP. Only GSE significantly reduced ROS production after a 120-minute exposure to TBHP. Incubation with GSE reduced TBHP-induced activity of the MAPK and PI3K pathways.

Conclusions and Clinical Relevance—GSE inhibited key components associated with cataractogenesis, ROS production, and stress-induced cell signaling. On the basis of the data reported here, there is strong evidence that GSE could potentially protect LECs from the damaging effects of oxidative stress.
Evaluation of neoadjuvant prednisone administration and surgical excision in treatment of cutaneous mast cell tumors in dogs
Authors: Stanclift Rebecca M. , Gilson Stephen D.
Published: January 2008

Objective—To determine response rate and reduction in tumor burden and effect of dose on tumor response in dogs treated with neoadjuvant prednisone for cutaneous mast cell tumors (MCTs).

Design—Combined prospective clinical study and retrospective case series.

Animals—49 dogs with MCT.

Procedures—Medical records were retrospectively reviewed for dogs with primary untreated cutaneous MCT managed with neoadjuvant prednisone administration and surgery. Tumor characteristics and response to treatment were recorded. A subset of dogs assigned to low-dose (LD) treatment with neoadjuvant prednisone (1.0 mg/kg [0.45 mg/lb], PO, q 24 h) or high-dose (HD) treatment (2.2 mg/kg [1.0 mg/lb], PO, q 24 h) was used to determine the effects of dose.

Results—The overall objective response rate was 70% for dogs treated with neoadjuvant prednisone; prednisone dose was not significantly associated with response. Prospectively, the median sum maximal diameter (MaxD) reduction was 45.2%, and reduction in tumor volume was 80.6%. In both treatment groups, the mean percentage MaxD reduction and tumor volume reduction were significant. The difference in response between the LD and HD groups was not significant. The LD group had mean MaxD and tumor volume reductions of 35.4% and 52.5%, respectively, compared with mean reductions of 48.8% in MaxD and 78% in tumor volume in the HD group.

Conclusions and Clinical Relevance—Treatment with neoadjuvant prednisone appears to be useful for inducing reduction of MCTs and may facilitate resection when adequate surgical margins cannot be confidently attained because of mass location or size or both.
Serum liver enzyme activities in healthy Miniature Schnauzers with and without hypertriglyceridemia
Authors: Xenoulis Panagiotis G. , Suchodolski Jan S. , Levinski Melinda D. , Steiner Jörg M.
Published: January 2008

Objective—To determine whether hypertriglyceridemia in healthy Miniature Schnauzers is associated with high serum liver enzyme activities.

Design—Cross-sectional study.

Animals—65 Miniature Schnauzers with serum triglyceride concentrations within the reference range (group 1), 20 Miniature Schnauzers with slightly high serum triglyceride concentrations (group 2), and 20 Miniature Schnauzers with moderately to severely high serum triglyceride concentrations (group 3).

Procedures—Questionnaires regarding each dog's medical history were completed, and serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and G-glutamyltransferase (GGT) activities were measured.

Results—Median serum ALP activity was significantly higher in group 3 than in group 1 or 2 dogs, but was not significantly higher in group 2 than in group 1 dogs. Median serum ALT activity was significantly higher in group 3 than in group 1 dogs, but was not significantly different between any of the other groups. Compared with group 1 dogs, group 2 and 3 dogs were significantly more likely to have high serum ALP activity (odds ratio, 26.2 and 192.6, respectively). Group 3 dogs also were significantly more likely to have high serum ALT activity (odds ratio, 8.0), serum AST activity (odds ratio, 3.7), and serum GGT activity (odds ratio, 11.3), compared with group 1 dogs. Group 3 dogs were significantly more likely (odds ratio, 31.0) to have ≥ 2 high serum liver enzyme activities than were group 1 dogs.

Conclusions and Clinical Relevance—Results suggested that moderate to severe hypertriglyceridemia was associated with high serum liver enzyme activities in Miniature Schnauzers.
Use of radiographic measures and three-dimensional computed tomographic imaging in surgical correction of an antebrachial deformity in a dog
Authors: Dismukes David I. , Fox Derek B. , Tomlinson James L. , Essman Stephanie C.
Published: January 2008

Case Description—A 1-year-old 7.4-kg (16.3-lb) castrated male mixed-breed dog was evaluated because of intermittent lameness and an antebrachial angular limb deformity.

Clinical Findings—The left forelimb had gross antebrachial external rotation (approx 90°) and marked procurvatum. Radiography revealed a severe partially compensated biapical antebrachial angular limb deformity. Measurements of medial proximal radial angle (MPRA) and lateral distal radial angle (LDRA) were obtained from orthogonal radiographs of the proximal and distal segments of the radius, respectively. Elbow joint-to-carpus translation was quantified. Deformities were localized and quantified by the center of rotation of angulation (CORA) method. Computed tomographic 3-dimensional image reconstructions of the antebrachium and carpus were completed to create 3 life-size stereolithographic models.

Treatment and Outcome—2 closing wedge radial osteotomies were performed at the level of the CORAs and stabilized with bone plates and screws.

Results—Frontal and sagittal plane alignments were corrected to 8° and 15°, respectively (reference limits, 0° to 8° and 8° to 35°, respectively). The MPRA was corrected from 55° to 68°, and LDRA was corrected from 32° to 76° (values considered normal are approx 85° and 87°, respectively). Elbow joint-to-carpus translation was improved by 42.5%. After 8 weeks, radiography revealed bone union. Owners considered the outcome acceptable, on the basis of limb appearance and lack of lameness at 1 year after surgery.

Conclusions and Clinical Relevance—A segmental radiographic planning technique combined with the CORA method, computed tomography, and stereolithography may be useful in the characterization of and planning corrective surgery for forelimb deformities in dogs.
Disseminated histoplasmosis in an African pygmy hedgehog
Authors: Snider Timothy A. , Joyner Priscilla H. , Clinkenbeard Kenneth D.
Published: January 2008

Case Description—A 2-year-old captive-bred sexually intact female African pygmy hedgehog (Atelerix albiventris) was evaluated because of vague signs of illness including inappetence, weakness, lethargy, and weight loss over a 20-day period.

Clinical Findings—Abnormalities detected via initial clinicopathologic analyses included anemia, thrombocytopenia, leukopenia, hypoproteinemia, and hypoglycemia. Results of a fecal flotation test were negative. Three weeks after the initial evaluation, splenomegaly was detected via palpation and ultrasonography.

Treatment and Outcome—The hedgehog was treated with broad-spectrum antibacterial agents, resulting in an initially favorable response. Fenbendazole was also administered against possible occult parasitic infestation. After 3 weeks of illness, the hedgehog's condition had worsened and supportive care and administration of additional antibacterial agents were instituted. The hedgehog died, and pathologic examinations revealed severe splenomegaly; granulomatous infiltrates were evident in multiple organs, and Histoplasma capsulatum yeasts were detected intralesionally.

Clinical Relevance—Histoplasmosis can develop in a wide range of mammalian species. African pygmy hedgehogs are becoming increasingly popular as exotic pets, and vague signs of illness and splenomegaly are often attributed to hemolymphatic malignancies, which are somewhat common in this species. Practitioners should be aware that similar clinical signs may be associated with histoplasmosis in these animals. Although the hedgehog of this report was confined indoors, it originated from an area where histoplasmosis was endemic; this indicates that the disease should be included as a differential diagnosis for hedgehogs that develop vague signs of illness and are known to originate from such geographic regions.
Evaluation of prognostic factors in the surgical treatment of adrenal gland tumors in dogs: 41 cases (1999–2005)
Authors: Schwartz Pamela , Kovak Janet R. , Koprowski Alexandra , Ludwig Lori L. , Monette Sebastien , Bergman Philip J.
Published: January 2008

Objective—To identify preoperative predictors of survival and assess intraoperative and postoperative complications and survival rates for dogs undergoing adrenalectomy.

Design—Retrospective case series.

Animals—41 dogs that underwent adrenalectomy.

Procedures—Records were reviewed to collect data regarding preoperative variables. Intraoperative and postoperative variables were also recorded. Variables were evaluated for association with survival duration via log-rank analysis for categoric variables and by use of Cox proportional hazards. Median survival times were calculated by use of Kaplan-Meier life table analysis.

Results—9 (22.0%) dogs did not survive to discharge. Intraoperative mortality rate was 4.8%. Overall Kaplan-Meier median survival time was 690 days. Variables significantly associated with shorter survival times included preoperative weakness or lethargy, thrombocytopenia, increased BUN concentration, increased partial thromboplastin time (PTT), increased aspartate transaminase (AST) activity, hypokalemia, intraoperative hemorrhage, and concurrent nephrectomy. Postoperative variables significantly associated with shorter survival times included pancreatitis and renal failure. In multivariate analysis, preoperative hypokalemia, preoperative increased BUN concentration, and concurrent nephrectomy were significantly associated with a shorter survival time.

Conclusions and Clinical Relevance—A high mortality rate was associated with adrenalectomy in dogs; however, those that survived until discharge from a hospital had long survival times. Preoperative factors associated with a shorter survival time were weakness or lethargy, thrombocytopenia, increased BUN concentration, increased PTT, increased AST activity, and hypokalemia. Studies are needed to evaluate how treatment for these factors may affect or change outcome after adrenalectomy. Dogs with adrenal masses that require concurrent nephrectomy and cause intraoperative hemorrhage have a guarded prognosis.
Lameness, athletic performance, and financial returns in yearling Thoroughbreds bought for the purpose of resale for profit
Authors: Preston Stephanie A. , Trumble Troy N. , Zimmel Dana N. , Chmielewski Terese L. , Brown Murray P. , Hernandez Jorge A.
Published: January 2008

Objective—To characterize lameness during training and compare exercise variables and financial returns among yearling Thoroughbreds that were bought for the purpose of resale for profit.

Animals—40 yearling Thoroughbreds.

Design—Prospective study.

Procedures—Horses purchased at yearling sales (summer 2004) were trained prior to resale at 2-year-olds in training sales (spring 2005). Horses were monitored daily for diagnosis and treatment of lameness during training. Selected variables, including sex, age, purchase price, lameness, distance (No. of furlongs) galloped during training, and financial returns, were compared among horses that had performance speeds (assessed at 2-year-olds in training sales) classified as fast, average, or slow.

Results—37 of 40 horses became lame during training, most commonly because of joint injury. Eighteen of the lame horses had hind limb injuries only; 5 horses had injuries in forelimbs and hind limbs. The frequency of new cases of lameness increased as the date of the 2-year-olds in training sales approached. At the sales, 4, 21, and 15 horses were classified as fast, average, or slow, respectively; median financial return was slightly (but significantly) different among horses classified as fast ($14,000), average ($0), or slow (–$8,000).

Conclusions and Clinical Relevance—Incidence of lameness during training in yearling horses purchased for the purpose of resale for profit was high. Lameness more commonly affected hind limbs than forelimbs and was attributable to joint injury in most horses. Financial returns differed between horses classified as fast and average or slow at the 2-year-olds in training sales.
Comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis
Authors: Doucet Michèle Y. , Bertone Alicia L. , Hendrickson Dean , Hughes Faith , MacAllister Charles , McClure Scott , Reinemeyer Craig , Rossier Yves , Sifferman Roger , Vrins André A. , White Gary , Kunkle Bruce , Alva Roberto , Romano Davida , Hanson Peter D.
Published: January 2008

Objective—To compare efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis.

Design—Randomized controlled clinical trial.

Animals—253 client-owned horses with naturally occurring osteoarthritis.

Procedures—Horses were treated with firocoxib (0.1 mg/kg [0.045 mg/lb], PO, q 24 h) or phenylbutazone (4.4 mg/kg [2 mg/lb], PO, q 24 h) for 14 days. Physical examinations and lameness evaluations were performed prior to treatment and after 7 and 14 days. Clinical improvement was defined as a reduction of at least 1 lameness grade or a combined reduction of at least 3 points in scores for pain during manipulation or palpation, joint swelling, joint circumference, and range of motion.

Results—Proportion of horses clinically improved on day 14 for the firocoxib group (104/123 [84.6%]) was not significantly different from the proportion for the phenylbutazone group (103/119 [86.6%]). Proportion of horses that were improved on day 14 was significantly greater for horses treated with firocoxib than for horses treated with phenylbutazone with regard to score for pain on manipulation or palpation (P = 0.028), joint circumference score (P = 0.026), and range of motion score (P = 0.012), but not for overall lameness score or joint swelling score. No direct treatment-related adverse effects were detected during the study.

Conclusions and Clinical Relevance—Results suggested that overall clinical efficacy of a paste formulation of firocoxib in horses with naturally occurring osteoarthritis was comparable to efficacy of a paste formulation of phenylbutazone.