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.     

Relationship Between Degenerative Joint Disease,Pain, and Bartonella spp. Seroreactivity in Domesticated Cats

Background

Recently, a potential association was identified between Bartonella exposure and arthritides in mammalian species other than cats.

Hypothesis/Objectives

We hypothesized that Bartonella exposure is associated with more severe degenerative joint disease (DJD) and a greater burden of DJD‐associated pain in client‐owned cats.

Animals

Ninety‐four client‐owned cats (6 months to 20 years old), ranging from clinically unaffected to severely lame because of DJD.

Methods

Using physical examination and radiography, pain and radiographic scores were assigned to each part of the bony skeleton. Sera were tested for Bartonella henselae, B. koehlerae, and B. vinsonii subsp. berkhoffii (genotypes I, II, and III) antibodies using immunofluorescence antibody assays. Variables were categorized and logistic regression used to explore associations.

Results

Seropositivity to Bartonella was identified in 33 (35.1%) cats. After multivariate analysis controlling for age, total DJD score (OR, 0.51; 95% CI, 0.26–0.97; P = .042), appendicular pain score (OR, 0.33; 95% CI, 0.17–0.65; P = .0011), and total pain score (OR, 0.35; 95% CI, 0.17–0.72; P = .0045) were significantly inversely associated with Bartonella seroreactivity status, indicating that cats with higher DJD and pain scores were less likely to be Bartonella seropositive.

Conclusions and Clinical Importance

Based upon this preliminary study, Bartonella spp. seropositivity was associated with decreased severity of DJD and decreased DJD‐associated pain in cats. Additional studies are needed to verify these findings, and if verified, to explore potential mechanisms.     

Antimicrobial Susceptibilities of Aerobic Isolates from Respiratory Samples of Young New Zealand Horses

Background

Decreased efficacy of antimicrobials and increased prevalence of multidrug resistance (MDR) is of concern worldwide.

Objectives

To describe and analyze bacterial culture and antimicrobial susceptibilities from respiratory samples submitted from young horses (4 weeks to 3 years old).

Animals

Samples from 289 horses were submitted to a commercial laboratory.

Methods

A retrospective database search of submissions made to a New Zealand veterinary laboratory between April 2004 and July 2014. The results of in vitro susceptibility testing by Kirby‐Bauer disc diffusion were described and tabulated for the major bacterial species isolated. Multiple correspondence analysis (MCA) was used to describe the clustering of MDR isolates and selected demographic variables.

Results

Overall, 774 bacterial isolates were cultured from 237 horses, the majority of these isolates were gram‐positive (67.6%; 95% CI 64.3–70.9%). Streptococcus spp. were the most common genus of bacteria isolated and were 40.1% (95% CI 36.6–43.5%) of the isolates cultured. Susceptibility of Streptococcus spp. to penicillin, gentamicin, and ceftiofur was >85%. Overall, gram‐negative susceptibility to ceftiofur, tetracycline, and TMPS was <75%. MDR was defined as resistance to 3 or more antimicrobials, and was found in 39.2% of horses (93/237; 95% CI 33.0–45.5%).

Conclusions and clinical importance

Culture and susceptibility results have highlighted that MDR is an emerging problem for young horses in New Zealand (NZ), where a bacterial respiratory infection is suspected. This should be considered when prescribing antimicrobials, and emphasizes the need for submission of samples for culture and susceptibility.     

Voluntary Surveillance Program for Equine Influenza Virus in the United States from 2010 to 2013

Background

Recent surveillance studies for equine respiratory viruses have shown that equine influenza virus (EIV) continues to be a prevalent respiratory virus of equids throughout the United States and Europe.

Objectives

To gain a better understanding of the prevalence and epidemiology of EIV shed by horses, mules and donkeys in the United States from March 2010 to November 2013.

Animals

2,605 equids.

Methods

Nasal secretions from index cases with acute onset of respiratory disease were tested by qPCR for EIV. Multilevel logistic regression was used to model the association between EIV status and prevalence factors. Furthermore, observations from EIV‐positive study horses were compared to previous data from March 2008 to February 2010.

Results

A total of 230 (9.7%) index cases tested qPCR positive for EIV. A higher‐than‐expected proportion of EIV qPCR‐positive horses occurred in the 1–5, 6–10, and 11–15 age groups when compared to the <1 year of age group. Fever, nasal discharge and coughing were positively associated with EIV‐positive horses. EIV qPCR‐positive study cases were significantly older and more often vaccinated against EIV compared to EIV qPCR‐positive animals from the 2008‐2010 study period.

Conclusions and Clinical Importance

This study provides valuable and contemporary information on the frequency of EIV detected by qPCR in the United States. The results also underscore that older and previously vaccinated horses were susceptible to EIV.     

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.     

Physicochemical Approach to Determine the Mechanism for Acid–Base Disorders in 793 Hospitalized Foals

Background

The quantitative effect of strong electrolytes, unmeasured strong anions (UAs), pCO ₂, and plasma protein concentrations in determining plasma pH can be demonstrated using the physicochemical approach. Plasma anion gap (AG) and strong ion gap (SIG) are used to assess UAs in different species.

Hypotheses

Strong ions are a major factor influencing changes in plasma pH of hospitalized foals. AG and SIG accurately predict severe hyper‐l‐lactatemia ([l‐lac⁻] > 7 mmol/L).

Animals

Seven hundred and ninety three hospitalized foals < 7 days old.

Methods

Retrospective study. The relationship between measured pH and physicochemical variables, and the relationship between plasma [l‐lac⁻] and AG and SIG, were determined using regression analyses. Optimal AG and SIG cut points to predict hyper‐l‐lactatemia were identified using an ROC curve analysis.

Results

Combined, the measured strong ion difference and SIG accounted for 54–69% of the changes in the measured arterial pH of hospitalized foals. AG and SIG were significantly associated with plasma [l‐lac⁻] (P < .0001). The receiver operator characteristics (ROC) AUC of AG and SIG for prediction of severe hyper‐l‐lactatemia were 0.89 (95%CI, 0.8–0.95; P < .0001) and 0.90 (95%CI, 0.81–0.96; P < .0001), respectively. Severe hyper‐l‐lactatemia was best predicted by AG > 27 mmol/L (sensitivity 80%, 95%CI, 56–94, specificity 85%, 95%CI, 73–93; P < .0001) and SIG <−15 mmol/L (sensitivity 90%, 95%CI, 68–98; specificity 80%; 95%CI, 68–90; P < .0001).

Conclusion and clinical relevance

Altered concentrations of strong ions (Na⁺, K⁺, Cl⁻) and UAs were the primary cause of acidemia of hospitalized foals. AG and SIG were good predictors of hyper‐l‐lactatemia and could be used as surrogate tests.     

Free Thyroxine Concentrations by Equilibrium Dialysis and Chemiluminescent Immunoassays in 13 Hypothyroid Dogs Positive for Thyroglobulin Antibody

Objective

To determine if concentrations of free thyroxine (FT4) measured by semi‐automated chemiluminescent immunoassay (CLIA) correspond to FT4 determined by equilibrium dialysis (ED) in hypothyroid dogs positive for thyroglobulin antibody (TGA).

Animals

Thirteen TGA‐positive dogs classified as hypothyroid based on subnormal FT4 concentrations by ED.

Methods

Qualitative assessment of canine TGA was performed using an enzyme‐linked immunosorbent assay. Serum total thyroxine and total triiodothyronine concentrations were measured by radioimmunoassay. Serum FT4 concentration was determined by ED, and also by semi‐automated CLIA for human FT4 (FT4h) and veterinary FT4 (FT4v). Canine thyroid stimulating hormone concentration was measured by semi‐automated CLIA.

Results

Each dog''s comprehensive thyroid profile supported a diagnosis of hypothyroidism. For detection of hypothyroidism, sensitivities of CLIA for FT4h and FT4v were 62% (95% CI, 32–85%) and 75% (95% CI, 36–96%), respectively, compared to FT4 by ED. Five of 13 (38%) dogs had FT4h and 2 of 8 (25%) dogs had FT4v concentrations by CLIA that were increased or within the reference range. Percentage of false‐negative test results for FT4 by CLIA compared to ED was significantly (P < .0001 for FT4h and P < .001for FT4v) higher than the hypothesized false‐negative rate of 0%.

Conclusions and Clinical Importance

Caution should be exercised in screening dogs for hypothyroidism using FT4 measured by CLIA alone. Some (25–38%) TGA‐positive hypothyroid dogs had FT4 concentrations determined by CLIA that did not support a diagnosis of hypothyroidism.     

Brainstem Auditory Evoked Responses in Foals: Reference Values,Effect of Age,Rate of Acoustic Stimulation,and Neurologic Deficits

Background

Age and rate of acoustic stimulation affect peak latencies in brainstem auditory evoked responses (BAER) in humans. Those effects are unknown in foals.

Hypothesis/Objectives

Our goals were to (1) establish reference values for BAER in foals by using 3 different stimulation protocols, (2) evaluate the effects of age and stimulation frequencies on BAER tracing in foals up to 6 months old, and (3) compare the data with BAER obtained from foals with central nervous system (CNS) disorders.

Animals

Thirty‐nine neurologically normal foals and 16 foals with neurologic diseases.

Methods

Prospective observational clinical study. BAER recorded by using 3 protocols of stimulation (11.33 repetitions per second [Hz]/70 decibel normal hearing level [dBNHL]; 11.33 Hz/90 dBNHL; 90 Hz/70 dBNHL).

Results

No effect of age was observed in normal foals (P > .005). No significant difference was observed for latencies and interpeak latencies (IPL) when comparing foals with neurologic diseases and normal foals (P > .05), but 78.6% of foals with neurologic diseases had an asymmetry in their tracing, reflecting a difference in conduction time between the left and right side of the brainstem. Increasing the stimulation rate did not improve detection of CNS disorders.

Conclusions and Clinical Importance

We propose BAER reference values for foals up to 6 months of age by using 3 protocols. Most foals with neurologic deficits had abnormal BAER tracing.     

Pasireotide for the Medical Management of Feline Hypersomatotropism

Background

Feline hypersomatotropism (HST) is a cause of diabetes mellitus in cats. Pasireotide is a novel multireceptor ligand somatostatin analog that improves biochemical control of humans with HST.

Hypothesis/Objectives

Pasireotide improves biochemical control of HST and diabetes mellitus in cats.

Animals

Hypersomatotropism was diagnosed in diabetic cats with serum insulin‐like growth factor‐1 (IGF‐1) concentration >1,000 ng/mL by radioimmunoassay and pituitary enlargement.

Methods

Insulin‐like growth factor 1 was measured and glycemic control assessed using a 12‐hour blood glucose curve on days 1 and 5. On days 2, 3, and 4, cats received 0.03 mg/kg pasireotide SC q12h. IGF‐1, insulin dose, and estimated insulin sensitivity (product of the area under the blood glucose curve [BGC] and insulin dose) were compared pre‐ and post treatment. Paired t‐tests or Wilcoxon signed rank tests were employed for comparison where appropriate; a linear mixed model was created to compare BGC results.

Results

Insulin‐like growth factor 1 decreased in all 12 cats that completed the study (median [range] day 1: 2,000 ng/mL [1,051–2,000] and day 5: 1,105 ng/mL [380–1,727], P = .002, Wilcoxon signed rank test). Insulin dose was lower on day 5 than on day 1 (mean reduction 1.3 [0–2.7] units/kg/injection, P = .003, paired t‐test). The product of insulin dose and area under the BGC was lower on day 5 than day 1 (difference of means: 1,912; SD, 1523; u × mg/dL × hours, P = .001; paired t‐test). No clinically relevant adverse effects were encountered.

Conclusions

Short‐acting pasireotide rapidly decreased IGF‐1 in cats with HST and insulin‐dependent diabetes. The decrease in IGF‐1 was associated with increased insulin sensitivity.     

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.