Incidence,Timing, and Risk Factors of Azathioprine Hepatotoxicosis in Dogs

Background

The use of azathioprine (AZA) in dogs is limited by the development of hepatotoxicosis and cytopenias.

Hypothesis and Objectives

To characterize the observed incidence, timing, and risk factors for AZA hepatotoxicosis in dogs treated clinically, and to determine the relationship between the development of hepatotoxicosis and cytopenias.

Animals

Fifty‐two dogs treated with AZA with clinical and biochemical follow‐up, with a subset of 34 dogs available for determination of changes in liver enzyme activities in serum.

Methods

Retrospective medical record review, from January 2009 through December 2013.

Results

Hepatotoxicosis (as defined by a >2‐fold increase in serum ALT) was observed in 5 of 34 dogs (15%) within a median onset of 14 days (range, 13–22 days). Dogs had a median 9‐fold increase in ALT and 8‐fold increase in ALP, which stabilized or resolved with drug discontinuation or dose reduction. German shepherds were significantly over‐represented (3 of 5 dogs with hepatotoxicosis; P = .0017). Thrombocytopenia or neutropenia were seen in 4 of 48 dogs with CBC follow‐up (8% of dogs), but occurred significantly later in treatment (median onset, 53 days; range 45–196 days) compared to hepatotoxicosis (P = .016).

Conclusions and Clinical Importance

These results support the routine monitoring of liver enzymes during the first 1–4 weeks of AZA treatment in dogs, with continued monitoring of the CBC. Additional studies are warranted to characterize the apparently higher risk of AZA hepatotoxicosis in German shepherds.     

Association of Vitamin D Status and Clinical Outcome in Dogs with a Chronic Enteropathy

Background

Dogs with a chronic enteropathy (CE) have a lower vitamin D status, than do healthy dogs. Vitamin D status has been associated with a negative clinical outcome in humans with inflammatory bowel disease.

Objectives

To examine the relationship between serum 25 hydroxyvitamin D (25(OH)D) concentrations at diagnosis and clinical outcome in dogs with a CE.

Animals

Forty‐one dogs diagnosed with CE admitted to the Royal Dick School of Veterinary Studies, Hospital for Small Animals between 2007 and 2013.

Methods

Retrospective review. Serum 25(OH)D concentrations were compared between dogs which were alive at follow up or had died because of non‐CE‐related reasons (survivors) and dogs which died or were euthanized due to their CE (non‐survivors). A binary logistic regression analysis was performed to determine significant predictors of death in dogs with CE.

Results

Serum concentrations of 25(OH)D at the time a CE was diagnosed were significantly lower in nonsurvivors (n = 15) (median nonsurvivors 4.36 ng/mL, interquartile range 1.6–17.0 ng/mL), median survivors (n = 26) (24.9 ng/mL interquartile range 15.63–39.45 ng/mL, P < .001). Serum 25(OH)D concentration was a significant predictor of death in dogs with CE (odds ratio 1.08 [95% CI 1.02–1.18)]).

Conclusions

Serum 25(OH)D concentrations at diagnosis are predictive of outcome in dogs with CE. The role of vitamin D in the initiation and outcome of chronic enteropathies in dogs is deserving of further study.     

Serial Evaluation of Abdominal Fluid and Serum Amino‐terminal pro‐C‐type Natriuretic Peptide in Dogs with Septic Peritonitis

Background

Serum N‐terminal pro‐C‐natriuretic peptide (NT‐proCNP) has shown promise as a diagnostic biomarker for sepsis. Its sensitivity to detect dogs with septic peritonitis (SP) is reportedly low, perhaps attributable to the compartmentalization of NT‐proCNP in the abdominal cavity.

Objectives

To evaluate the use of an ELISA for the measurement of NT‐proCNP in canine abdominal fluid and to describe the peri‐operative pattern of abdominal fluid and serum NT‐proCNP concentrations in dogs with SP.

Animals

Five client‐owned dogs with nonseptic abdominal effusion of varying etiologies and 12 client‐owned dogs with SP undergoing abdominal surgery and placement of a closed‐suction abdominal drain (CSAD). Six dogs were included upon hospital admission; 6 were included the day after surgery.

Methods

Prospective pilot study. A commercially available ELISA kit was analytically validated for use on canine abdominal fluid. The NT‐proCNP concentrations were measured in the abdominal fluid of control dogs, and in serum and abdominal fluid of dogs with SP from admission for CSAD removal.

Results

In dogs with SP, admission abdominal fluid NT‐proCNP concentrations were lower than the concurrent serum concentrations (P = 0.031), and lower than control canine abdominal fluid concentrations (P = 0.015). Postoperatively, abdominal fluid NT‐proCNP concentrations remained lower than serum concentrations (P < 0.050), except on day 4.

Conclusions and Clinical Importance

The ELISA kit was able to measure NT‐proCNP in canine abdominal fluid. In dogs with SP, low serum NT‐proCNP concentrations cannot be explained by abdominal compartmentalization.     

Relationship of Plasma N‐terminal Pro‐brain Natriuretic Peptide Concentrations to Heart Failure Classification and Cause of Respiratory Distress in Dogs Using a 2nd Generation ELISA Assay

Background

Cardiac biomarkers provide objective data that augments clinical assessment of heart disease (HD).

Hypothesis/Objectives

Determine the utility of plasma N‐terminal pro‐brain natriuretic peptide concentration [NT‐proBNP] measured by a 2nd generation canine ELISA assay to discriminate cardiac from noncardiac respiratory distress and evaluate HD severity.

Animals

Client‐owned dogs (n = 291).

Methods

Multicenter, cross‐sectional, prospective investigation. Medical history, physical examination, echocardiography, and thoracic radiography classified 113 asymptomatic dogs (group 1, n = 39 without HD; group 2, n = 74 with HD), and 178 with respiratory distress (group 3, n = 104 respiratory disease, either with or without concurrent HD; group 4, n = 74 with congestive heart failure [CHF]). HD severity was graded using International Small Animal Cardiac Health Council (ISACHC) and ACVIM Consensus (ACVIM‐HD) schemes without knowledge of [NT‐proBNP] results. Receiver‐operating characteristic curve analysis assessed the capacity of [NT‐proBNP] to discriminate between dogs with cardiac and noncardiac respiratory distress. Multivariate general linear models containing key clinical variables tested associations between [NT‐proBNP] and HD severity.

Results

Plasma [NT‐proBNP] (median; IQR) was higher in CHF dogs (5,110; 2,769–8,466 pmol/L) compared to those with noncardiac respiratory distress (1,287; 672–2,704 pmol/L; P < .0001). A cut‐off >2,447 pmol/L discriminated CHF from noncardiac respiratory distress (81.1% sensitivity; 73.1% specificity; area under curve, 0.84). A multivariate model comprising left atrial to aortic ratio, heart rate, left ventricular diameter, end‐systole, and ACVIM‐HD scheme most accurately associated average plasma [NT‐proBNP] with HD severity.

Conclusions and Clinical Importance

Plasma [NT‐proBNP] was useful for discriminating CHF from noncardiac respiratory distress. Average plasma [NT‐BNP] increased significantly as a function of HD severity using the ACVIM‐HD classification scheme.     

Effect of Chronic Administration of Phenobarbital,or Bromide,on Pharmacokinetics of Levetiracetam in Dogs with Epilepsy

Background

Levetiracetam (LEV) is a common add‐on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs.

Hypothesis/Objectives

To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs.

Animals

Eighteen client‐owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB–BR group, n = 6).

Methods

Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high‐pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area‐under‐the‐curve (AUC) calculated to the last measured time point.

Results

Compared to the PB and PB–BR groups, the BR group had significantly higher peak concentration (C _max) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*μg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028).

Conclusions and Clinical Importance

Concurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add‐on treatment with phenobarbital in dogs.     

Randomized Phase III Trial of Piroxicam in Combination with Mitoxantrone or Carboplatin for First‐Line Treatment of Urogenital Tract Transitional Cell Carcinoma in Dogs

Background

Reported response rates of transitional cell carcinoma (TCC) in dogs to piroxicam in combination with either mitoxantrone or carboplatin are similar; however, it is unknown whether either drug might provide superior duration of response.

Hypothesis/Objectives

To determine if the progression‐free interval (PFI) of dogs with TCC treated with mitoxantrone and piroxicam was different than that of dogs receiving carboplatin and piroxicam. The hypothesis was that the efficacy of mitoxantrone is no different from carboplatin.

Animals

Fifty dogs with TCC without azotemia.

Methods

Prospective open‐label phase III randomized study. Either mitoxantrone or carboplatin was administered every 3 weeks concurrently with piroxicam with restaging at 6‐week intervals. Twenty‐four dogs received carboplatin and 26 received mitoxantrone.

Results

Response was not different between groups (P = .56). None of the dogs showed complete response. In the mitoxantrone group, there were 2 (8%) partial responses (PR) and 18 (69%) dogs with stable disease (SD). In the carboplatin group, there were 3 PR (13%) and 13 (54%) dogs with SD. The PFI was not significantly different between groups (mitoxantrone = 106 days; carboplatin = 73.5 days; P = .62; hazard ratio 0.86; 95% confidence interval 0.47–1.56). Dogs with prostatic involvement experienced a shorter survival (median, 109 days) compared to dogs with urethral, trigonal, or apically located tumors; this difference was significant (median 300, 190, and 645 days, respectively; P = .005).

Conclusions and Clinical Importance

This study did not detect a different in outcome in dogs with TCC treated with either mitoxantrone or carboplatin in combination with piroxicam.     

Prevalence and Prognostic Importance of Pulmonary Hypertension in Dogs with Myxomatous Mitral Valve Disease

Background

Pulmonary hypertension (PH) is common in dogs with myxomatous mitral valve disease (MMVD) but its effect on clinical outcome has not been investigated.

Hypothesis/objectives

The presence of PH worsens the outcome in dogs with MMVD. To compare survival times of dogs with MMVD and PH to those without PH.

Animals

Two hundred and twelve client‐owned dogs.

Methods

Case review study. Medical records of dogs diagnosed with ACVIM stage B2 and C MMVD between January 2010 and December 2011 were retrospectively reviewed. Long‐term outcome was determined by telephone interview or from the medical record. End of the observation period was March 2013. PH was identified if tricuspid regurgitation peak velocity was >3 m/s.

Results

Two hundred and twelve were identified. Eighty‐three dogs (39%) had PH. PH was more commonly identified in stage C compared to B2 (P < .0001). One hundred and five (49.5%) dogs died during the observation period. Median survival time for the entire study population was 567 days (95% CI 512–743). Stage C (P = .003), the presence of PH (P = .009), left atrial to aortic root ratio (LA/Ao) >1.7 (P = .0002), normalized left‐ventricular end‐diastolic diameter (LVEDn) >1.73 (P = .048), and tricuspid regurgitation pressure gradient (TRPG) >55 mmHg (P = .009) were associated with worse outcomes in the univariate analyses. The presence of TRPG >55 mmHg (HR 1.8 95% CI 1–2.9; P = .05) and LA/Ao > 1.7 (HR 2 95% CI 1.2–3.4; P = .01) remained significant predictors of worse outcome in the multivariate analysis.

Conclusions and Clinical Importance

In dogs with MMVD, moderate to severe PH worsens outcome.     

Efficacy of Intravenous Administration of Combined Acid Suppressants in Healthy Dogs

Background

Short‐term intravenous co‐administration of famotidine and pantoprazole is used by some veterinarians to treat gastrointestinal bleeding in critically ill dogs. However, clinical studies have not evaluated the efficacy of combination acid suppressant treatment in dogs.

Hypothesis/Objectives

To compare the effect of intravenous co‐administration of famotidine and pantoprazole to monotherapy with pantoprazole on intragastric pH in dogs. We hypothesized that single agent pantoprazole would be more effective than combination with famotidine.

Animals

Twelve healthy adult colony dogs.

Methods

Randomized, 2‐way crossover design. All dogs received placebo (0.9% saline) for 24 hours followed by 1.0 mg/kg IV q12h pantoprazole or combination treatment with famotidine and pantoprazole for 3 consecutive days. Intragastric pH monitoring was used to continuously record intragastric pH for 96 hours beginning on day 0 of treatment. Mean percentage time (MPT) that intragastric pH was ≥3 and ≥4 were compared between groups using ANOVA with a posthoc Tukey‐Kramer test (α = 0.017).

Results

The MPT ± standard deviation intragastric pH was greater than ≥3 and 4 were 79 ± 17% and 68 ± 17% for pantoprazole and 74 ± 19% and 64 ± 23% for combination treatment, respectively. There were no significant differences in MPT intragastric pH was ≥3 and 4 between groups. Pantoprazole administered alone achieved pH goals established for humans with acid‐related disorders.

Conclusions and Clinical Importance

These results suggest that short‐term combination treatment with famotidine and pantoprazole is not superior to pantoprazole alone for increasing intragastric pH in dogs.     

Usefulness of Conventional and Tissue Doppler Echocardiography to Predict Congestive Heart Failure in Dogs with Myxomatous Mitral Valve Disease

Background

Systolic and diastolic functions have been evaluated to predict outcome in congestive heart failure (CHF). Recently, tissue Doppler imaging (TDI) has become useful for the estimation of myocardial function in cardiac diseases of humans and animals.

Objective

This study was designed to assess whether myocardial function as assessed by TDI is associated with the occurrence of CHF in dogs with myxomatous mitral valve disease (MMVD) and whether additional information is gained over conventional Doppler variables.

Animals

Forty‐one privately owned dogs (15 healthy dogs and 26 dogs with MMVD) were included. Dogs with MMVD were divided into non‐CHF (n = 10) and CHF groups (n = 16).

Methods

Conventional echocardiographic examinations were performed. In addition, TDI‐derived variables, including radial and longitudinal velocities, strain, and strain rate were assessed.

Results

Several (12 of 47, 26%) conventional and tissue Doppler echocardiography variables were significant predictors of CHF in a univariate analysis (P < .05). However, TDI‐derived E/E _{m sept} was the only load‐independent significant predictor of CHF (P < .05) after multivariate logistic regression analysis. The E/E _{m sept} cut‐off value of >18.7 had a sensitivity of 56% and specificity of 90% in predicting CHF in dogs with MMVD.

Conclusions and Clinical Importance

The combination of TDI of the mitral annulus and mitral inflow velocity provided better estimates of diastolic dysfunction in dogs with MMVD and CHF. Additional study is warranted to assess TDI‐derived E/E _{m sept}, an index of diastolic function that could contribute to the management of dogs with MMVD and CHF.     

Plasma Vitamin D Metabolites and C‐Reactive Protein in Stage‐Stop Racing Endurance Sled Dogs

Background

Dogs are a unique model for examining the effects of exercise on vitamin D status because of their lack of vitamin D synthesis by UV exposure. In addition, the inflammatory response may be associated with hypovitaminosis D.

Objectives

To investigate the effects of several days of endurance exercise on plasma vitamin D (25‐(OH)D₃, 24,25‐(OH)D₃ and 1,25(OH)D₃) and serum C‐reactive protein (CRP) concentrations in stage‐stop racing sled dogs.

Animals

12 racing sled dogs and 8 control dogs.

Methods

Blood was collected before the race and immediately after racing on days 2 and 8. Plasma vitamin D metabolites and serum CRP concentrations were measured.

Results

Racing dogs showed a significant increase in 25(OH)D₃ on day 2 (P = .027) and day 8 of the race (P < .001), whereas no increases were observed in control dogs. The plasma concentration of 24,25(OH)D₃ showed a significant increase by day 8 (P < .001). There were no significant changes in 1,25(OH) D₃ concentrations across all time points and groups. Racing dogs had significantly increased CRP concentrations by day 2 (39.3 ± 30.1 μg/mL; P < .001).

Conclusions and Clinical Importance

Increases in vitamin D metabolites as well as increases in CRP concentrations were observed in racing sled dogs. This finding was contrary to the hypothesis that decreases in vitamin D status in athletes may be related to the acute phase inflammatory response during exercise. In addition, the increased 24,25(OH)D₃ concentrations compared to what is observed in other species suggests metabolic variations in dogs that lead to enhanced disposal of vitamin D.     

Vitamin D Status in Different Stages of Disease Severity in Dogs with Chronic Valvular Heart Disease

Background

In humans with heart disease, vitamin D deficiency is associated with disease progression and a poor prognosis. A recent study showed that serum 25‐hydroxyvitamin D [25(OH)D] concentration, the hallmark of vitamin D status, was lower in dogs with heart failure than in normal dogs, and a low concentration was associated with poor outcome in dogs with heart failure.

Objectives

To elucidate the vitamin D status of dogs with chronic valvular heart disease (CVHD) at different stages of disease severity.

Animals

Forty‐three client‐owned dogs with CVHD.

Methods

In this cross‐sectional study, dogs were divided into 3 groups (14 dogs in Stage B1, 17 dogs in Stage B2, and 12 dogs in Stage C/D) according to ACVIM guidelines. Dogs underwent clinical examination including echocardiography. Serum 25(OH)D concentrations were measured in each dog.

Results

Serum 25(OH)D concentration was significantly lower in Stage B2 (median, 33.2 nmol/L; range, 4.9–171.7 nmol/L) and C/D (13.1 nmol/L; 4.9–58.1 nmol/L) than in Stage B1 (52.5 nmol/L; 33.5–178.0 nmol/L) and was not significantly different between Stage B2 and Stage C/D. Among clinical variables, there were significant negative correlations between 25(OH)D concentration and both left atrial‐to‐aortic root ratio and left ventricular end‐diastolic diameter normalized for body weight.

Conclusions and Clinical Importance

These results indicate that vitamin D status is associated with the degree of cardiac remodeling, and the serum 25(OH)D concentration begins to decrease before the onset of heart failure in dogs with CVHD.     

Cortisol Response in Healthy and Diseased Dogs after Stimulation with a Depot Formulation of Synthetic ACTH

Background

The ACTH stimulation test is used to evaluate the adrenocortical reserve. Recently, the availability of the synthetic ACTH formulation was limited, causing major problems in clinical practice.

Objectives

The objective of this study was to evaluate poststimulation peak cortisol concentrations and the duration of the stimulatory effect of a depot ACTH preparation in dogs.

Animals

Twenty‐two healthy dogs, 10 dogs with suspected hypoadrenocorticism (HA) and 15 dogs with suspected hyperadrenocorticism (HC).

Methods

Prospective study. An ACTH stimulation test using a synthetic depot tetracosactide, administered intramuscularly (5 μg/kg or at least 0.1 mL) was performed. Blood samples for determination of cortisol were taken immediately before and 1, 2, 3, 4, 6, and 24 hours after stimulation.

Results

Peak cortisol concentrations were reached after 2–4 hours in all dogs. Cortisol concentrations 1 hour after stimulation were >9 μg/dL in all healthy dogs and >5 μg/dL in all dogs in which HA was excluded. None of the dogs with HA showed a cortisol‐increase above the detection‐limit of the assay. After 6 hours, cortisol concentrations had decreased in the healthy and HC group and were back to baseline after 24 hours.

Conclusions and Clinical Importance

The depot formulation can be used in place of the short‐acting ACTH to evaluate the adrenocortical reserve. Blood for peak cortisol concentrations should be drawn 3 hours after stimulation in cases in which HC is suspected; in HA‐suspected cases, blood sampling can take place after 1 hour. As the stimulatory effect is gone after 24 hours, interference with other hormonal tests is unlikely after that time.     

The Clinical and Serological Effect of a Gluten‐Free Diet in Border Terriers with Epileptoid Cramping Syndrome

Background

Canine epileptoid cramping syndrome (CECS) is a paroxysmal movement disorder of Border Terriers (BTs). These dogs might respond to a gluten‐free diet.

Objectives

The objective of this study was to examine the clinical and serological effect of a gluten‐free diet in BTs with CECS.

Animals

Six client‐owned BTs with clinically confirmed CECS.

Methods

Dogs were prospectively recruited that had at least a 6‐month history of CECS based on the observed phenomenology (using video) and had exhibited at least 2 separate episodes on different days. Dogs were tested for anti‐transglutaminase 2 (TG2 IgA) and anti‐gliadin (AGA IgG) antibodies in the serum at presentation, and 3, 6, and 9 months after the introduction of a gluten‐free diet. Duodenal biopsies were performed in 1 dog.

Results

Serum TG2 IgA titers were increased in 6/6 BTs (P = .006) and AGA IgG titers were increased in 5/6 BTs at presentation compared to those of controls (P = .018). After 9 months, there was clinical and serological improvement in all BTs with CECS strictly adhering to a gluten‐free diet (5/5). One dog had persistently increased antibody titers. This dog scavenged horse manure. On the strict introduction of a gluten‐free diet this dog also had an improved clinical and serological response. The diet‐associated improvement was reversible in 2 dogs on completion of the study, both of which suffered a relapse of CECS on the re‐introduction of gluten.

Conclusions

Canine epileptoid cramping syndrome in BTs is a gluten‐sensitive movement disorder triggered and perpetuated by gluten and thus responsive to a gluten‐free diet.     

Effect of Screening Abdominal Ultrasound Examination on the Decision to Pursue Advanced Diagnostic Tests and Treatment in Dogs with Neurologic Disease

Background

Abdominal ultrasound examinations (AUS) are commonly performed before advanced neurodiagnostics to screen for diseases that might affect diagnostic plans and prognosis.

Objectives

Describe the type and frequency of abnormalities found by AUS in dogs presenting with a neurological condition, identify risk factors associated with abnormalities, and evaluate treatment decisions based on findings.

Animals

Seven hundred and fifty‐nine hospitalized dogs.

Methods

Retrospective study. Medical records of dogs presented from 2007 to 2009 for neurologic disease were searched for signalment, neuroanatomic localization, and AUS findings. Whether dogs had advanced neurodiagnostics and treatment was analyzed.

Results

Fifty‐eight percent of dogs had abnormal findings on AUS. Probability of abnormalities increased with age (P < 0.001). Nondachshund breeds had higher probability of abnormal AUS than dachshunds (odds ratio [OR] = 1.87). Eleven percent of dogs did not have advanced neurodiagnostics and in 1.3%, this was because of abnormal AUS. Dogs with ultrasonographic abnormalities were less likely than dogs without to have advanced neurodiagnostics (OR = 0.3 [95% confidence interval [CI]: 0.17, 0.52]), however, the probability of performing advanced diagnostics was high regardless of normal (OR = 0.95 [95% CI: 0.92, 0.97]) or abnormal (OR = 0.85 [95% CI: 0.81, 0.88]) AUS. Treatment was more often pursued in small dogs and less often in dogs with brain disease.

Conclusions and Clinical Importance

Findings from screening AUS had a small negative effect on the likelihood of pursuing advanced neurodiagnostics. Although it should be included in the extracranial diagnostic workup in dogs with significant history or physical examination abnormalities, AUS is considered a low‐yield diagnostic test in young dogs and dachshunds.     

Quantitative Contrast‐enhanced Ultrasonographic Assessment of Naturally Occurring Pancreatitis in Dogs

Background

Quantitative contrast‐enhanced ultrasonography (CEUS) can detect pancreatic perfusion changes in experimentally induced canine pancreatitis. However, its usefulness in detecting perfusion changes in naturally occurring pancreatitis is unclear.

Hypothesis/Objectives

To determine the feasibility of using CEUS to detect pancreatic and duodenal perfusion changes in naturally occurring canine pancreatitis.

Animals

Twenty‐three client‐owned dogs with pancreatitis, 12 healthy control dogs.

Methods

Dogs diagnosed with pancreatitis were prospectively included. CEUS of the pancreas and duodenum were performed. Time‐intensity curves were created from regions of interest in the pancreas and duodenum. Five perfusion parameters were obtained for statistical analyses: time to initial up‐slope, peak time (Tp), time to wash‐out (TTW), peak intensity (PI), and area under the curve (AUC).

Results

For the pancreas, Tp of the pancreatitis group was prolonged when compared to controls (62 ± 11 seconds versus 39 ± 13 seconds; P < .001). TTW also was prolonged but not significantly (268 ± 69 seconds versus 228 ± 47 seconds; P = .47). PI and AUC were increased when compared to controls (95 ± 15 versus 78 ± 13 MPV; P = .009 and 14,900 ± 3,400 versus 11,000 ± 2,800 MPV*s; P = .013, respectively). For the duodenum, PI and AUC were significantly increased in the pancreatitis group when compared to controls.

Conclusions and Clinical Importance

Contrast‐enhanced ultrasonography can detect pancreatic perfusion changes in naturally occurring canine pancreatitis characterized by delayed peak with prolonged hyperechoic enhancement of the pancreas on CEUS. Additionally, duodenal perfusion changes secondary to pancreatitis were observed.     

Dorsal Compressive Atlantoaxial Bands and the Craniocervical Junction Syndrome: Association with Clinical Signs and Syringomyelia in Mature Cavalier King Charles Spaniels

Background

Dorsal compressive lesions at the atlantoaxial junction (ie, AA bands) occur in dogs with Chiari‐like malformations (CMs), but their clinical relevance is unclear.

Objective

Investigate the influence of AA bands on clinical status and syringomyelia (SM) in mature cavalier King Charles spaniels (CKCS).

Animals

Thirty‐six CKCS, 5–12 years of age, including 20 dogs with neuropathic pain.

Methods

Dogs were examined and assigned a neurologic grade. Magnetic resonance imaging (MRI) of the craniocervical junction was performed with the craniocervical junction extended and flexed (ie, normal standing position). Imaging studies were assessed for the presence of an AA band, CM, SM or some combination of these findings. Band and SM severity were quantified using an objective compression index and ordinal grading scale, respectively.

Results

Of 36 CKCS imaged, 34 had CM. Atlantoaxial bands were present in 31 dogs and were more prominent in extended than flexed positions. Syringomyelia was found in 26 dogs, 23 of which also had AA bands. Bands were associated with both the presence (P = .0031) and severity (P = .008) of clinical signs and SM (P = .0147, P = .0311, respectively). Higher compression indices were associated with more severe SM (P = .0137).

Conclusions

Prevalence of AA bands in older CKCS is high. Positioning of dogs in extension during MRI enhances the sensitivity of the study for detecting this important abnormality. There were significant associations among AA bands, clinical signs, and SM in dogs with CM; additional work is needed to understand whether or not this relationship is causal.     

Medullary Position at the Craniocervical Junction in Mature Cavalier King Charles Spaniels: Relationship with Neurologic Signs and Syringomyelia

Background

Medullary elevation (ie, medullary kinking) at the craniocervical junction (CCJ) is reported in dogs with Chiari‐like malformations (CM), but its diagnostic criteria and clinical relevance are unclear.

Objective

To describe the position of the medulla at the CCJ in mature cavalier King Charles spaniels (CKCS), and evaluate its relationship with clinical status and the presence of syringomyelia.

Animals

Thirty‐six CKCS, 5–12 years of age, including 16 asymptomatic dogs.

Methods

Dogs were assigned a neurologic grade; magnetic resonance imaging (MRI) of the CCJ then was performed. The presence of a CM and syringomyelia was recorded and syringomyelia severity was quantified. Medullary position was quantified using the medullary kinking index, the elevation angle and obex position relative to the foramen magnum. The relationship between medullary position measures and presence and severity of neurologic signs and syringomyelia was investigated.

Results

Chiari‐like malformation was found in 33 dogs; 26 of them had syringomyelia. Mean medullary kinking index was 46.4% (SD, 10.3), elevation angle was 132° (SD, 12) and obex position was 3.5 mm (SD, 0.8). A higher medullary kinking index was associated with the presence of neurologic signs (P = .0368). Obex position was associated with the presence (P = .0018) and severity of syringomyelia (P = .0164).

Conclusions and clinical importance

There is a significant association between medullary elevation and clinical signs, whereas more caudal brainstem positions appear related to the presence of syringomyelia.     

Association of Tricuspid Annular Plane Systolic Excursion with Survival Time in Boxer Dogs with Ventricular Arrhythmias

Background

Tricuspid annular plane systolic excursion (TAPSE) is a useful estimate of right ventricular function in humans. Reference intervals for dogs have been generated, but the value of measuring TAPSE in other diseases, or investigating the association between TAPSE and outcome, is unknown.

Hypothesis

TAPSE is lower in Boxer dogs with ≥50 VPCs/24 h on Holter than in dogs with fewer ventricular ectopics, and lower TAPSE is associated with a shorter survival time.

Animals

Fifty Boxer dogs that presented for investigation of syncope or suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) at a veterinary teaching hospital (2004–2011).

Methods

Retrospective study. Clinical records, Holter, and echocardiographic data were reviewed. TAPSE was measured in a blinded manner on stored echocardiographic cine‐loops using anatomic M‐mode. Outcome information was obtained and death was classified as cardiac or noncardiac. Survival analysis was performed using Kaplan‐Meier curves and Cox proportional hazards models.

Results

TAPSE was lower in Boxers with ≥50 VPCs/24 h (13.9 ± 4.04 mm) than Boxers with <50 VPCs/24 h (16.8 ± 3.21 mm; P < .001). TAPSE <15.1 mm was associated with shorter cardiac survival time in all dogs (P = .004) and also in dogs without left ventricular dysfunction (P = .035). When controlling for other variables, including ventricular tachycardia on Holter and left ventricular systolic dysfunction, multivariable analysis showed that TAPSE remained an independent predictor of time to cardiac death (HR >4.09, 95%CI 1.15–16.9, P < .029).

Conclusions and Clinical Importance

TAPSE offers prognostic value for Boxer dogs, including those with apparently normal systolic function and ≥50 VPCs/24 h on Holter analysis.     

Pulse‐Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs

Background

Nonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy.

Hypothesis/Objectives

The primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse‐administered toceranib phosphate (TOC) combined with lomustine.

Animals

Forty‐seven client‐owned dogs with measurable MCT.

Methods

Toceranib phosphate was given PO on days 1, 3 and 5 of a 21‐day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m². All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone.

Results

The MTD of lomustine was established at 50 mg/m² when combined with pulse‐administered TOC; the dose‐limiting toxicity was neutropenia. Forty‐one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression‐free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy.

Conclusions and clinical importance

Combined treatment with pulse‐administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT.     

Early Tumor Response to Intraarterial or Intravenous Administration of Carboplatin to Treat Naturally Occurring Lower Urinary Tract Carcinoma in Dogs

Background

Survival times and tumor responses associated with malignant neoplasia of the lower urinary tract are poor despite the vast array of current treatments. Therefore, the evaluation of alternative treatments, such as intraarterial administration of chemotherapy (IAC) should be considered.

Objective

To describe a technique for superselective catheterization for IAC and to evaluate initial tumor response by ultrasonography after both IAC and intravenous administration of chemotherapy (IVC).

Animals

Client‐owned dogs with lower urinary tract neoplasia treated with either IVC (n = 15) or IAC (n = 11).

Methods

Retrospective study. An arterial approach via the carotid or femoral artery was utilized to obtain superselective access and administer chemotherapy in the IAC cases. Medical record review was performed, data were recorded, and recorded variables were evaluated statistically.

Results

Intraarterial chemotherapy was successfully administered in all cases. There was a significantly greater decrease in longest unidimensional measurement in the IAC group as compared to the IVC group (P = .013). The IAC group was also significantly more likely to have a tumor response as assessed by modified RECIST guidelines (P = .049). Dogs in the IAC group were significantly less likely to develop anemia (P = .001), lethargy (P = .010) and anorexia (P = .024).

Conclusion and Clinical Importance

This study demonstrated the feasibility and efficacy of performing IAC for lower urinary tract neoplasia. Further investigation is necessary as the follow‐up time was short and the impact on long‐term outcome and survival was not determined.