Questionnaire‐based Analysis of Owner‐reported Scratching and Pain Signs in Cavalier King Charles Spaniels Screened for Chiari‐like Malformation and Syringomyelia

Background

Chiari‐like malformation (CM) and syringomyelia (SM) cause a pain syndrome in Cavalier King Charles spaniels (CKCS). Clinical signs are not consistently apparent on neurologic examination, and owner reporting of signs provides vital clinical history. However, owner questionnaires for this disease are not well developed.

Objectives

To develop a tool to capture owner‐reported clinical signs for use in clinical trials and to compare owner‐reported signs with the presence of pain on neurologic examination and SM on magnetic resonance imaging (MRI).

Animals

Fifty client‐owned CKCS.

Methods

Owners completed a questionnaire and pain/scratch map. Each dog underwent a neurologic examination and craniocervical magnetic resonance imaging (MRI). Questionnaire responses were developed into scores, area of shading for pain/scratch maps was measured, and consistency of responses between these tools was assessed. Owner‐reported findings were compared with neurologic examination findings and presence and severity of SM on MRI.

Results

Thirty‐three dogs were symptomatic and 17 asymptomatic; 30 had SM. The most common sign of pain was crying out when lifted (n = 11). Extent of shaded areas on maps positively correlated with questionnaire scores for pain (r² = 0.213, P = 0.006) and scratch (r² = 0.104, P = 0.089). Owner‐reported findings were not significantly associated with presence or severity of SM or neurologic examination findings. Owner‐reported lateralization of signs was significantly associated with SM lateralization (P < 0.0001).

Conclusions

The questionnaire and maps may be useful for clinical trials. Lack of association of owner‐reported signs with SM highlights our lack of understanding of the pathophysiology of pain in this disease.     

Force Plate Gait Analysis in Doberman Pinschers with and without Cervical Spondylomyelopathy

Background

The most accepted means of evaluating the response of a patient with cervical spondylomyelopathy (CSM) to treatment is subjective and based on the owner and clinician's perception of the gait.

Objective

To establish and compare kinetic parameters based on force plate gait analysis between normal and CSM‐affected Dobermans.

Animals

Nineteen Doberman Pinschers: 10 clinically normal and 9 with CSM.

Methods

Force plate analysis was prospectively performed in all dogs. At least 4 runs of ipsilateral limbs were collected from each dog. Eight force platform parameters were evaluated, including peak vertical force (PVF) and peak vertical impulse (PVI), peak mediolateral force (PMLF) and peak mediolateral impulse, peak braking force and peak braking impulse, and peak propulsive force (PPF) and peak propulsive impulse. In addition, the coefficient of variation (CV) for each limb was calculated for each parameter. Data analysis was performed by a repeated measures approach.

Results

PMLF (P = .0062), PVI (P = .0225), and PPF (P = .0408) were found to be lower in CSM‐affected dogs compared with normal dogs. Analysis by CV as the outcome indicated more variability in PVF in CSM‐affected dogs (P = 0.0045). The largest difference in the CV of PVF was seen in the thoracic limbs of affected dogs when compared with the thoracic limbs of normal dogs (P = 0.0019).

Conclusions and Clinical Importance

The CV of PVF in all 4 limbs, especially the thoracic limbs, distinguished clinically normal Dobermans from those with CSM. Other kinetic parameters less reliably distinguished CSM‐affected from clinically normal Dobermans.     

Evaluation of S-adenosyl l-methionine in a double-blinded, randomized, placebo-controlled, clinical trial for treatment of presumptive osteoarthritis in the dog

Objective: To evaluate the efficacy of S‐adenosyl l ‐methionine (SAMe) in the treatment of clinically inferred canine osteoarthritis (OA). Study Design: Six weeks, double‐blinded, placebo‐controlled, clinical trial. Animals: Dogs (n=33) with clinical signs, history, and orthopedic exams consistent with OA. Methods: Dogs were block randomized by body condition score (<6/9, or ≥6/9) into either the placebo or SAMe group. Outcome was assessed using pressure platform gait analysis, examination score, goniometry, and the Canine Brief Pain Inventory (CBPI) at the time of study entrance and at 3 and 6 weeks after entry. Groups were compared using parametric and nonparametric paired tests as appropriate, and numbers needed to treat (NNT) were calculated for the CBPI and peak vertical force (PVF). Results: Both groups (n=15 placebo, n=18 SAMe) had a reduction in mean PVF (P=.02) and vertical impulse (VI; P=.06) from the 1st to 3rd visit. There was no significant difference between the placebo group and SAMe group for PVF, VI, or either part of the CBPI (Severity or Impact). The NNT at 6 weeks for the Severity score was 3, Impact score was 25, and PVF was 45. Conclusions: These data do not support the use of SAMe as an effective stand alone treatment for reducing clinical signs of OA, as measured by PVF, VI, goniometry, CBPI (both Severity and Impact), and examination score within 6 weeks of treatment.     

Feline Musculoskeletal Pain Index: Responsiveness and Testing of Criterion Validity

Background

Progress in establishing if therapies provide relief to cats with degenerative joint disease (DJD)‐associated pain is hampered by a lack of validated owner‐administered assessment methods.

Hypothesis

That an appropriately developed subjective owner‐completed instrument (Feline Musculoskeletal Pain Index‐FMPI) to assess DJD‐associated impairment would have responsiveness and criterion validity.

Animals

Twenty‐five client‐owned cats with DJD‐associated pain.

Methods

FMPI responsiveness (ability to detect the effect of an analgesic treatment) and validity (correlation with an objective measure) were explored through a stratified, randomized, double blinded, placebo‐controlled, crossover 10‐week clinical study. Meloxicam was administered to effect pain relief. A linear mixed model, backward stepwise regression, and Pearson correlations were used to assess responsiveness and criterion validity with the assumption that the NSAID would increase activity.

Results

Positive responses of cats to placebo (P = .0001) and meloxicam treatment (P = .0004) were detected; however, the instrument did not detect any difference between placebo and meloxicam (linear mixed model), even for the high impairment cases. Percent meloxicam target dose administered, temperament, and total baseline FMPI score were covariates that most affected FMPI scores. Controlling for significant covariates, most positive effects were seen for placebo treatment. Positive treatment effects on activity were detected, but only for the cases designated as most highly impaired.

Conclusions and Clinical Importance

Neither responsiveness nor criterion validity were detected by the inclusion criteria for cases in this study. The data suggest that further work is indicated to understand factors affecting activity in cats to optimize inclusion criteria.     

Plasma‐Free Metanephrine and Free Normetanephrine Measurement for the Diagnosis of Pheochromocytoma in Dogs

Background

Measurement of plasma‐free metanephrines is the test of choice to identify pheochromocytoma in human patients.

Objectives

To establish the sensitivity and specificity of plasma‐free metanephrine (fMN) and free normetanephrine (fNMN) concentrations to diagnose pheochromocytoma in dogs.

Animals

Forty‐five client‐owned dogs (8 dogs with pheochromocytoma, 11 dogs with adrenocortical tumors, 15 dogs with nonadrenal disease, and 11 healthy dogs.)

Methods

A prospective study. EDTA plasma was collected from diseased and healthy dogs and submitted for fMN and fNMN measurement by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS).

Results

Free MN concentration (median [range]) was significantly higher in dogs with pheochromocytoma (8.15 [1.73–175.23] nmol/L) than in healthy dogs (0.95 [0.68–3.08] nmol/L; P < .01) and dogs with adrenocortical tumors (0.92 [0.25–2.51] nmol/L; P < .001), but was not different from dogs with nonadrenal disease (1.91 [0.41–6.57] nmol/L; P ≥ .05). Free NMN concentration was significantly higher in dogs with pheochromocytoma (63.89 [10.19–190.31] nmol/L) than in healthy dogs (2.54 [1.59–4.17] nmol/L; P < .001), dogs with nonadrenal disease (3.30 [1.30–10.10] nmol/L; P < .001), and dogs with adrenocortical tumors (2.96 [1.92–5.01] nmol/L); P < 0.01). When used to diagnose pheochromocytoma, a fMN concentration of 4.18 nmol/L had a sensitivity of 62.5% and specificity of 97.3%, and a fNMN concentration of 5.52 nmol/L had a sensitivity of 100% and specificity of 97.6%.

Conclusions and Clinical Importance

Plasma fNMN concentration has excellent sensitivity and specificity for the diagnosis of pheochromocytoma in dogs, whereas fMN concentration has moderate sensitivity and excellent specificity. Measurement of plasma‐free metanephrines provides an effective, noninvasive, means of identifying dogs with pheochromocytoma.     

Gastrointestinal Hemodynamics in Dogs with Nonfood Induced Atopic Dermatitis

Background

Canine atopic dermatitis can be a result of exposure to aeroallergens or trophallergens. Hemodynamic alterations occur in dogs with food hypersensitivity.

Hypothesis/Objectives

To evaluate if hemodynamic alterations occur in dogs with NFICAD with lowered resistance to diastolic flow at fasting, after feeding, or both.

Animals

Ten healthy dogs and 22 dogs with NFICAD were included from the hospital population.

Methods

Blinded prospective study. Peak systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (MV), pulsatility index (PI), resistive index (RI) and PSV/EDV ratio were measured at fasting for both arteries (cranial mesenteric artery [CMA], celiac artery [CA]) and at 40 minutes after feeding in CMA and at 60 minutes in CA. The results were analyzed statistically with a mixed model.

Results

There was no difference detected between groups of dogs for any variable except EDV during fasting (P = .01).

Conclusions and Clinical Importance

There is no decrease in resistance in NFICAD to diastolic flow. This observation could be explained by the absence intestinal inflammation in NFICAD.     

Effect of oral administration of carprofen on intraocular pressure in normal dogs

The aim of this study was to determine the effect of oral administration of carprofen on intraocular pressure in normal dogs. Twelve young adult beagle dogs were randomly assigned to treatment (n = 6) or control (n = 6) groups. After an 11‐day acclimation period, the treatment group received approximately 2.2 mg/kg carprofen per os every 12 h for 7 days, and the control group received a placebo gel capsule containing no drug per os every 12 h for 7 days. Intraocular pressure (IOP) was measured by a rebound tonometer at three time points per day (8 am, 2 pm, and 8 pm) during the acclimation (days 1–11) and treatment (days 12–18) phases and for 48 h (days 19–20) after the completion of treatment. There was no statistically significant change in IOP for either eye in the dogs receiving oral carprofen during the treatment phase (days 12–18). After day 4, no significant daily IOP changes were seen in control group dogs. Carprofen administered orally every 12 h for 7 days had no effect on IOP in normal beagle dogs. An acclimation period to frequent IOP measurements of at least 5 days is necessary to establish baseline IOP values and minimize possible anxiety‐related effects on IOP measurements.     

Evaluation of the effect of mesotherapy in the management of back pain in police working dog

Objective

To evaluate the feasibility and effectiveness of mesotherapy in dogs compared with a positive control group.

A prospective,randomized, blinded,placebo-controlled multisite clinical study of bedinvetmab,a canine monoclonal antibody targeting nerve growth factor,in dogs with osteoarthritis

ObjectiveBedinvetmab is a canine monoclonal antibody targeting nerve growth factor. This study evaluated the efficacy and safety of bedinvetmab for alleviation of pain associated with osteoarthritis in dogs.Study designDouble-blind, randomized, multicentre, placebo-controlled study.AnimalsClient-owned dogs (n = 287) with osteoarthritis.MethodsDogs were randomized (1:1) to subcutaneous injection with placebo (saline, n = 146) or bedinvetmab (0.5–1.0 mg kg^–1, n = 141) administered monthly. After 3 months, 89 bedinvetmab-treated dogs that responded positively based on owner and veterinarian assessments were administered up to six additional doses of bedinvetmab in a single-armed open-label continuation phase. The primary efficacy end point was treatment success based on the owner-assessed canine brief pain inventory (CBPI) on day 28. Treatment success was defined as ≥ 1 reduction in pain severity score (0–10) and ≥ 2 in pain interference score (0–10).ResultsPercentage treatment success was significantly greater in the bedinvetmab group than in the placebo group from day 7 through all assessed time points (p ≤ 0.0025). On day 28, 43.5% of dogs achieved treatment success with bedinvetmab compared with placebo (16.9%) (p = 0.0017). Treatment success continued through days 56 (50.8%) and 84 (48.2%) in the bedinvetmab group and was < 25% in the placebo group at all time points. Sustained efficacy was demonstrated in the continuation phase. Adverse health events occurred at similar frequencies in both groups. They were considered typical for a population of dogs with osteoarthritis and not related to study treatment. Treatment with bedinvetmab demonstrated a significant effect on all three components of CBPI—pain interference, pain severity, quality of life.Conclusions and clinical relevanceThis study demonstrated the effectiveness and safety of bedinvetmab administered monthly for up to 9 months at 0.5–1.0 mg kg^–1 for alleviation of pain associated with canine osteoarthritis.     

Efficacy and Kinetics of Carprofen, Administered Preoperatively or Postoperatively, for the Prevention of Pain in Dogs Undergoing Ovariohysterectomy

Objective —To determine what effect the timing of carprofen administration has on the severity of postoperative pain in dogs undergoing ovariohysterectomy and to investigate the pharmacokinetics of carprofen under these conditions. Study Design —A prospective, randomized, double-blind, clinical trial. Animals —Sixty-two adult bitches weighing between 10 and 25 kgs, undergoing elective ovariohysterectomy. Methods —Examinations were performed for 20 hours postoperatively using subjective visual assessment scoring systems (DIVAS) and objective mechanical nociceptive threshold measurements. Forty dogs were assigned to one of three groups: (1) preoperative carprofen; (2) postoperative carprofen; and (3) no analgesics (saline injections). The dose of carprofen was 4.0 mg/kg subcutaneously. In another 22 bitches, the pharmacokinetics of carprofen given preoperatively or postoperatively at the same dose were examined. Results —The dogs given carprofen preoperatively had lower pain scores than the other groups, significantly so at 2 hours postextubation (P < .01 and P < .05, Kruskal-Wallis and post hoc Dunn's). Mechanical pain thresholds measured at the distal tibia showed the development of hyperalgesia at 12 and 20 hours postextubation; this was prevented by both the preoperative (P < .05 at 12 and 20 hours, Kruskal-Wallis) and postoperative (P <.05 at 20 hours, Kruskal-Wallis) administration of carprofen. Mechanical pain threshold testing at the wound showed a significant analgesic effect of carprofen. Plasma concentrations of carprofen were not directly related to analgesia; maximum plasma concentration, the area under the curve to the last data point, and area under the first moment curve up to the last data point were all significantly higher in the dogs given carprofen postoperatively (P < .05, Mann-Whitney). Conclusion—Preoperative administration of carprofen has a greater analgesic effect than postoperative administration in the early postoperative period in dogs undergoing ovariohysterectomy. Plasma levels of carprofen are not related to the degree of analgesia achieved. Clinical Relevance—Carprofen provides effective analgesia after canine ovariohysterectomy. The timing of analgesic administration is important to optimize the control of postoperative pain.     

Comparison of Histopathologic Findings in Duodenal and Ileal Endoscopic Biopsies in Dogs with Chronic Small Intestinal Enteropathies

Background

The current tendency when investigating dogs with chronic upper gastrointestinal signs is to perform endoscopy and biopsy only the duodenum. This approach could lead to overlooking important ileal lesions and affect the clinical management.

Objectives

To compare concurrent duodenal and ileal endoscopic biopsies in dogs with chronic enteropathies and evaluate their correlation with clinicopathologic findings.

Animals

Thirty‐eight dogs with chronic enteropathies.

Methods

Duodenal and ileal biopsies were retrospectively reviewed. Nine histologic variables, 5 structural (villous stunting, epithelial injury, crypt distension, lacteal dilatation, and mucosal fibrosis) and 4 inflammatory (intraepithelial lymphocytes, lamina propria lymphocytes and plasma cells, eosinophils, and neutrophils) were scored. Clinical severity scores and relevant clinicopathologic variables were evaluated.

Results

There was only slight agreement between duodenal and ileal histologic scores (κ = 0.003). There was slight agreement between the presence of any of the morphological and inflammatory variables, with the exception of mucosal fibrosis (κ = 0.44). Statistically significant correlation was found between clinical severity and duodenal crypt distension (P = .031), ileal lacteal dilatation (P = .038), and ileal mucosal lymphoplasmacytic inflammation (P = .035). A significant correlation was found between hypoalbuminemia and ileal lacteal dilatation (P = .033) and number of ileal intraepithelial lymphocytes (P = .019). A statistically significant correlation was found between hypocobalaminemia and number of ileal intraepithelial lymphocytes (P = .012).

Conclusions and Clinical Importance

When investigating dogs with chronic upper gastrointestinal signs, the collection of concurrent duodenal and ileal endoscopic biopsies is recommended.     

Relationships of Body Weight,Body Size,Subject Velocity,and Vertical Ground Reaction Forces in Trotting Dogs

Objective: To evaluate the relationship of body weight (BW) and size, dog velocity, and vertical ground reaction forces (GRF) from a large number of dogs of various sizes. Study Design: Clinical research. Animals: Orthopedically healthy dogs (n=129) Methods: BW and dog size, represented as height at the withers (WH), were obtained. Stance times (ST), vertical impulses (VI), and peak vertical forces (PVF) of thoracic and pelvic limbs were measured on a force plate at controlled trotting speed. They were evaluated against BW and WH using linear regression analysis in absolute (nonnormalized) values, and when normalized to BW and/or body size according to the theory of dynamic similarity. Relative velocities were calculated for each dog. Results: Absolute ST, VI, and PVF showed strong positive correlations with BW and/or body size. When GRFs were normalized to BW, correlations with body size were markedly reduced, but remained positive for VI, and turned negative for PVF. Normalizing the time‐dependent variables (ST and VI) also to WH eliminated most size influence. A small dependency of fully normalized GRF on body size remained that was because of differences in relative velocity between dogs of different sizes. Reference values for the fully normalized data are given. Conclusions: The inherent relationship between BW, body size, dog velocity, and vertical GRF was demonstrated. Clinical Relevance: BW, body size, and relative dog velocity must be accounted for when wanting to obtain GRF variables that are comparable between different dogs.     

Noninvasive Clinical Assessment of Systolic Torsional Motions by Two‐Dimensional Speckle‐Tracking Echocardiography in Dogs with Myxomatous Mitral Valve Disease

Background

Left ventricular torsional motion plays an important role for effective pump function. However, noninvasive clinical assessment of torsional deformations by two‐dimensional speckle‐tracking echocardiography (2D‐STE) in dogs with myxomatous mitral valve disease (MMVD) has not been reported.

Hypothesis

Left ventricular torsion is determined by the native orientation of the helical myocardial fibers, such that it might provide better assessment of myocardial function than conventional methods.

Animals

Sixty‐seven client‐owned dogs with MMVD were classified into 3 classes based on the International Small Animal Cardiac Health Council classification and 16 weight‐ and age‐matched healthy dogs.

Methods

Dogs were examined for myocardial deformations by 2D‐STE and were evaluated for peak systolic rotation and rotation rate at each basal and apical view. Dogs also were evaluated for peak systolic torsion and torsion rate.

Results

Peak systolic torsion was higher in class II than in class I (P < .001) dogs. Peak systolic torsion was lower in class III than in class II (P = .001) dogs and controls (P = .003).

Conclusions and Clinical Importance

Torsional deformations assessed by 2D‐STE differed among clinical classes of MMVD. Myocardial torsional deformations by 2D‐STE may provide more detailed assessment of contractile function in dogs with MMVD.     

A prospective,randomized, double-blind,placebo-controlled multisite,parallel-group field study in dogs with osteoarthritis conducted in the United States of America evaluating bedinvetmab,a canine anti-nerve growth factor monoclonal antibody

ObjectiveBedinvetmab, a fully canine anti-nerve growth factor monoclonal antibody, was evaluated in dogs for control of osteoarthritis-related pain in a study conducted to support registration in the USA.Study designRandomized, double-blind, placebo-controlled, multicenter, parallel-group study.AnimalsGeneral practice client-owned dogs with osteoarthritis (n = 272).MethodsDogs were block randomized 1:1 to placebo (saline, n = 137) or bedinvetmab (n = 135; 0.5–1.0 mg kg^–1) administered subcutaneously, once monthly. The primary end point, day 28 Canine Brief Pain Inventory (CBPI) treatment success (TS), required pain severity score (PSS; 0–10) decrease ≥1 and pain interference score (PIS; 0–10) decrease ≥ 2. CBPI TS rates [and number needed to treat (NNT)], change in scores [and standardized effect size (ES)], change in quality of life (QoL) and bedinvetmab half-life were calculated.ResultsSignificant (p < 0.05) improvement with bedinvetmab over placebo occurred (days 28, 42, 56, 84) for CBPI TS. Of cases evaluable for day 28 CBPI TS (placebo, n = 131; bedinvetmab, n = 128), success rates were 36.6% and 47.4%, respectively (p = 0.0410) (NNT, 9.3; PSS and PIS ES, 0.3). CBPI TS increased after the second dose in both groups, plateaued for bedinvetmab at day 42 and decreased for placebo beginning day 84. Day 84 NNT (4.3), PSS (0.4) and PIS (0.5) showed continued improvement with monthly dosing. After the first dose, mean (± standard deviation) bedinvetmab half-life was 19.1 (8.3) days. Adverse events were similar between groups and not considered treatment-related. There was a significant effect of bedinvetmab versus placebo on all CBPI components (PIS, PSS, QoL).Conclusions and clinical relevanceThese results corroborated those previously reported and provide further support of safety and effectiveness of bedinvetmab (0.5–1.0 mg kg^–1) administered subcutaneously at monthly intervals to dogs for control of osteoarthritis-related pain.     

Effect of N‐Acetylcysteine Supplementation on Intracellular Glutathione,Urine Isoprostanes,Clinical Score,and Survival in Hospitalized Ill Dogs

Background

Antioxidant depletion and lipid peroxidation have been correlated with disease severity and associated with poor outcomes.

Hypothesis/Objectives

Supplementing dogs with N‐acetylcysteine (NAC) during the first 48 hours of hospitalization will increase cysteine, normalize glutathione concentrations, and decrease the degree of lipid peroxidation associated with illness.

Animals

Sixty systemically ill hospitalized client‐owned dogs and 14 healthy control dogs.

Methods

Randomized investigator‐blinded, placebo‐controlled prospective study. Dogs were randomized to treatment with NAC (n = 30) versus placebo (n = 30). Antioxidants, urine 8‐isoprostane/creatinine (IP/Cr), and clinical score were determined before and after treatment with NAC. Glutathione, cysteine, and vitamin E concentrations were quantified using high‐performance liquid chromatography. Atomic absorption spectroscopy and enzyme‐linked immunosorbent assays were used to quantify selenium and isoprostane concentrations, respectively.

Results

Ill dogs had significantly lower vitamin E concentrations (27 versus 55 μg/mL; P = .0005) as well as elevated IP/Cr ratios (872 versus 399 pg/mg; P = .0007) versus healthy dogs. NAC supplementation significantly increased plasma cysteine (8.67 versus 15.1 μM; P < .0001) while maintaining glutathione concentrations. Dogs in the placebo group experienced a statistically significant decrease in glutathione concentrations (1.49 versus 1.44 mM; P = .0463). Illness severity and survival were unchanged after short duration NAC supplementation.

Conclusions

Ill dogs experience systemic oxidative stress. Supplementation with NAC during the first 48 hours of hospitalization stabilized erythrocyte glutathione concentrations. The clinical impact of this supplementation and glutathione concentration stabilization was undetermined.     

Cardiac Troponin‐I Concentration,Myocardial Arteriosclerosis,and Fibrosis in Dogs with Congestive Heart Failure because of Myxomatous Mitral Valve Disease

Background

Few previous studies have investigated the association between biomarkers and cardiac disease findings in dogs with naturally occurring myxomatous mitral valve disease (MMVD).

Aim

To investigate if histopathological changes at necropsy could be reflected by in vivo circulating concentrations of cTnI and aldosterone, and renin activity, in dogs with naturally occurring congestive heart failure because of MMVD.

Animals

Fifty privately owned dogs with MMVD and heart failure.

Methods

Longitudinal Study. Dogs were prospectively recruited and examined by clinical and echocardiographical examination twice yearly until time of death. Blood was stored for batched analysis of concentrations of cTnI and aldosterone, and renin activity. All dogs underwent a standardized necropsy protocol.

Results

cTnI were associated with echocardiographic left ventricular end‐diastolic dimension (P < .0001) and proximal isovolumetric surface area radius (P < .004). Furthermore, in vivo cTnI concentrations reflected postmortem findings of global myocardial fibrosis (P < .001), fibrosis in the papillary muscles (P < .001), and degree of arterial luminal narrowing (P < .001) Aldosterone or renin activity did not reflect any of the cardiac disease variables investigated.

Conclusion and clinical importance

Cardiac fibrosis and arteriosclerosis in dogs with MMVD are reflected by circulating cTnI concentration, but not by aldosterone concentration or renin activity. Cardiac troponin I could be a valuable biomarker for myocardial fibrosis in dogs with chronic cardiac diseases.     

Fecal alpha1-proteinase inhibitor concentration in dogs receiving long-term nonsteroidal anti-inflammatory drug therapy

Background: Fecal α₁‐proteinase inhibitor (α₁‐PI) clearance is a reliable, noninvasive marker for protein‐losing enteropathy (PLE) in human beings. An assay for measurement of this protein in the dog has been developed and validated and may be useful for the investigation of gastrointestinal disease in this species. Nonsteroidal anti‐inflammatory drugs (NSAIDs) frequently are administered to dogs and may have adverse effects on the gastrointestinal tract, including gastroduodenal ulceration and altered mucosal permeability. The value of fecal α₁‐PI measurement in detecting unrelated gastrointestinal disease may be limited in dogs on NSAID therapy, but α₁‐PI may be a useful marker for NSAID‐induced gastrointestinal damage. Objective: The aim of this study was to evaluate the effects of long‐term administration of NSAIDs on fecal α₁‐PI concentrations in dogs. Methods: Fecal samples were collected from 2 groups of dogs: 1) 21 clinically‐healthy client‐owned dogs without signs of gastrointestinal disease and receiving no NSAIDs and 2) 7 dogs referred for investigation and treatment of orthopedic disorders; the dogs had received either meloxicam or carprofen daily for at least 30 days. Fecal α₁‐PI concentration was measured by ELISA. Results: Fecal α₁‐PI concentrations, expressed as μg/g of feces, were not significantly different between groups 1 and 2 (median [range], group 1: 9.9 μg/g [0.0–32.1 μg/g]; group 2: 5.6 μg/g [1.1–32.3 μg/g]; P= .81). Conclusions: These results suggest that use of cyclooxygenase‐2‐selective NSAIDs, such as carprofen and meloxicam, does not significantly affect fecal α₁‐PI measurements. However, study numbers were small, and larger prospective trials are required to assess more accurately the gastrointestinal effects of NSAIDs in dogs.     

A 6‐bp Deletion Variant in a Novel Canine Glutathione‐S‐Transferase Gene (GSTT5) Leads to Loss of Enzyme Function

Objectives

Glutathione‐S‐transferases (GSTs) detoxify reactive xenobiotics, and defective GST gene polymorphisms increase cancer risk in humans. A low activity GST‐theta variant was previously found in research beagles. The purpose of our study was to determine the molecular basis for this phenotype and its allele frequency in pet dogs.

Methods

Banked livers from 45 dogs of various breeds were screened for low GST‐theta activity by the substrate 1,2‐dichloro‐4‐nitrobenzene (DCNB), and were genotyped for variants in a novel canine GST gene, GSTT5. Whole‐genome sequences from 266 dogs were genotyped at one discovered variant GSTT5 locus.

Results

Canine livers ranged 190‐fold in GST‐theta activities, and a GSTT5 exon coding variant 385_390delGACCAG (Asp129_Gln130del) was significantly associated with low activity (P < 0.0001) and a marked decrease in hepatic protein expression (P = 0.0026). Recombinant expression of variant GSTT5 led to a 92% decrease in V_max for DCNB (P = 0.0095). The minor allele frequency (MAF) for 385_390delGACCAG was 0.144 in 45 dog livers, but was significantly higher in beagles (0.444) versus nonbeagles (0.007; P = 0.0004). The homozygous genotype was significantly over‐represented in Pembroke Welsh corgis (P < 0.0001) based on available whole‐genome sequence data.

Conclusions

An Asp129_Gln130del variant in canine GSTT5 is responsible for marked loss of GST‐theta enzyme activity. This variant is significantly over‐represented in purpose‐bred laboratory beagles and in Pembroke Welsh corgis. Additional work will determine the prevalence of this variant among other purebred dogs, and will establish the substrate range of this polymorphic canine enzyme with respect to common environmental carcinogens.     

Adiposity,Plasma Insulin,Leptin, Lipids,and Oxidative Stress in Mature Light Breed Horses

Background

Increased blood insulin levels are associated with an increased risk of pasture‐associated laminitis in equids.

Objective

To determine the relationship between plasma insulin, leptin, and lipid levels, and measures of oxidative stress with adiposity in mature light breed horses.

Animals

300 randomly selected light breed horses, aged 4–20 years.

Methods

A random sample of horses (140 mares, 151 geldings, and 9 stallions) was drawn from the VMRCVM Equine Field Service practice client list. Evaluations occurred June 15 – August 15, 2006, with all sampling performed between 0600 and 1200 hours. Concentrate feed was withheld for at least 10 hours before sampling. Plasma was analyzed for insulin, glucose, leptin, triglycerides, nonesterified fatty acids, and measures of oxidative stress. Body condition score was determined as the average of 2 independent investigators.

Results

Overconditioned and obese horses had higher plasma insulin (P < .001) and leptin (P < .01) levels than optimally conditioned horses. Obese horses had higher triglyceride levels (P = .006) and lower red blood cell gluthathione peroxidase activities (P = .001) than optimally conditioned horses.

Conclusions and Clinical Importance

Maintaining horses at a BCS <7 might be important for decreasing the risk of pasture‐associated laminitis.