Immunohistochemical Expression of Potential Therapeutic Targets in Canine Thyroid Carcinoma

Background

Thyroid carcinoma is a common endocrine tumor in the dog. Local invasive growth frequently precludes surgical excision and, in up to 38% of dogs, the tumor has already metastasized by the time of diagnosis. Therefore, it is important to investigate new treatment modalities that may be useful for the large number of dogs with inoperable tumors or metastatic disease.

Hypothesis/Objectives

To investigate the immunohistochemical expression of potential therapeutic targets in canine thyroid tumors.

Animals

74 dogs with thyroid neoplasia.

Methods

Immunohistochemistry was performed for thyroglobulin, calcitonin, vascular endothelial growth factor (VEGF), p53, cycloxygenase‐2 (cox‐2), and P‐glycoprotein (P‐gp).

Results

Fifty‐four (73%) tumors were classified as follicular cell thyroid carcinomas (FTCs) and 20 (27%) as medullary thyroid carcinomas (MTCs). Eighty percent of FTCs and all MTCs had a high percentage (76–100%) of neoplastic cells immunopositive for VEGF. Thirteen percent of FTCs and 50% of MTCs expressed cox‐2. Seven percent of FTCs and 70% of MTCs expressed P‐gp. No tumor was immunopositive for p53 expression. Expression of VEGF (P = .034), cox‐2 (P = .013), and P‐gp (P < .001) was significantly higher in MTCs compared to FTCs.

Conclusions and Clinical Importance

VEGF is a potential therapeutic target in both FTC and MTC in dogs. Cox‐2 and P‐gp may be useful molecular targets in canine MTC.     

Hepatic Hepcidin Gene Expression in Dogs with a Congenital Portosystemic Shunt

Background

Microcytic anemia is common in dogs with a congenital portosystemic shunt (cPSS) and typically resolves after surgical attenuation of the anomalous vessel. However, the pathophysiology of the microcytic anemia remains poorly understood. Hepcidin has been a key role in controlling iron transport in both humans and animals and in mediating anemia of inflammatory disease in humans. The role of hepcidin in the development of microcytic anemia in dogs with a cPSS has not been examined.

Hypothesis

To determine whether hepatic hepcidin mRNA expression decreases, while red blood cell count (RBC) and mean corpuscular volume (MCV) increase in dogs after surgical attenuation of a cPSS.

Animals

Eighteen client‐owned dogs with confirmed cPSS undergoing surgical attenuation.

Method

Prospective study. Red blood cell count (RBC) and mean corpuscular volume (MCV), together with hepatic gene expression of hepcidin, were measured in dogs before and after partial attenuation of a cPSS.

Results

There was a significant increase in both RBC (median pre 6.17 × 10¹²/L, median post 7.08 × 10¹²/L, P < .001) and MCV (median pre 61.5fl, median post 65.5fl, P = .006) after partial surgical attenuation of the cPSS. Despite the increase in both measured red blood cell parameters, hepatic gene expression of hepcidin remained unchanged.

Conclusions and Clinical Importance

This study found no evidence that dysregulated production of hepcidin was associated with anemia in dogs with a cPSS.     

Chiari‐Like Malformation and Syringomyelia in American Brussels Griffon Dogs

Background

Although Chiari‐like malformation (CM) and syringomyelia (SM) have been described in many small breed dogs, the prevalence and clinical manifestations of this complex have not been documented in a large cohort of American Brussels Griffon (ABG) dogs.

Objectives

To characterize the clinical and magnetic resonance imaging (MRI) features of CM and SM in the ABG breed.

Animals

Eighty‐four American Kennel Club registered ABG dogs were recruited.

Methods

Prospective study. Complete histories and neurologic examinations were obtained before MRI. Images were blindly reviewed and calculations were made by using OsiriX. All analyses were performed by Student''s t‐test, Spearman''s correlation, ANOVA, and chi‐square test where appropriate.

Results

Chiari‐like malformation and SM were present in 65% and 52% of dogs, respectively. Twenty‐eight percent of dogs had neurologic deficits and 20% had neck pain. Mean central canal (CC) transverse height was 2.5 mm with a mean length of 3.6 cervical vertebrae. Neurologic deficits were significantly associated with a larger syrinx (P = .04, P = .08) and syrinx size increased with age (P = .027). SM was associated with a smaller craniocervical junction (CCJ) height (P = .04) and larger ventricles (P = .0001; P < .001).

Conclusions and Clinical Importance

Syringomyelia and CM are prevalent in American Brussels Griffon dogs. Syrinx size is associated with neurologic deficits, CM, larger ventricles, a smaller craniocervical junction height, neurologic deficits, and cerebellar herniation. Fifty‐two percent of dogs with a SM were clinically normal.     

Comparative Analysis of mRNA Expression of Surface Antigens between Histiocytic and Nonhistiocytic Sarcoma in Dogs

Background

Definitive diagnosis of histiocytic sarcoma (HS) in dogs is relatively difficult by conventional histopathological examination because objective features of HS are not well defined.

Hypothesis

Quantitative analysis of mRNA expression of selected cellular surface antigens (SAs) specific to HS in dogs can facilitate objective and rapid diagnosis.

Animals

Dogs with HS (n = 30) and dogs without HS (n = 36), including those with other forms of lymphoma (n = 4), inflammatory diseases (n = 6), and other malignant neoplasias (n = 26).

Methods

Retrospective clinical observational study. Specimens were collected by excisional biopsy, needle core biopsy, or fine needle aspiration. To determine HS detection efficacy, mRNA expression levels of selected SAs specific to HS in dogs, including MHC class IIα, CD11b, CD11c, and CD86, were quantitatively analyzed using real‐time quantitative polymerase chain reaction.

Results

Each SA mRNA expression level was significantly higher in HS dogs than in non‐HS dogs (P = .0082). Cutoff values for discriminating between HS and non‐HS dogs based on these expression levels were calculated on the basis of receiver‐operating characteristic analysis. Accuracy of the cutoff values, including MHC class IIα, CD11b, CD11c, and CD86, was 87.9, 86.4, 86.4, and 84.8%, respectively.

Conclusions and Clinical Importance

Our results suggest that quantitative analysis of mRNA expression of the selected SAs could be an adjunctive diagnostic technique with high diagnostic accuracy for HS in dogs. Substantial investigation is required for exclusion of diseases with similar cell types of origin to lymphoma.     

Acute Effects of Ivabradine on Dynamic Obstruction of the Left Ventricular Outflow Tract in Cats with Preclinical Hypertrophic Cardiomyopathy

Background

Ivabradine is a negative chronotropic drug with minimal effects on central hemodynamics. Its effect on dynamic obstruction of the left ventricular outflow tract (LVOT) in cats with hypertrophic cardiomyopathy (HCM) remains unknown.

Hypothesis/Objectives

Ivabradine reduces dynamic obstruction of the LVOT in cats with HCM.

Animals

Twenty‐eight client‐owned cats with preclinical HCM and dynamic LVOT obstruction.

Methods

Randomized, double‐blind, active‐control single dose study. Cats received a single dose of either ivabradine (0.3 mg/kg PO) or atenolol (2 mg/kg PO). Heart rate, echocardiographic variables, and systolic blood pressure (SBP) were recorded before and 3 hours after drug administration. Statistical comparisons were made using ANCOVA.

Results

Peak velocity in the LVOT was significantly decreased compared to baseline for both drugs; however, the effect was more prominent with atenolol (mean reduction 2.53 m/s; 95% CI 2.07–3.13 m/s) compared to ivabradine (mean reduction 0.32 m/s; 95% CI −0.04 to 0.71 m/s; P < .0001). Echocardiographic indices of systolic function were largely unchanged by ivabradine, but significantly reduced by atenolol.

Conclusions and Clinical Importance

A single dose of ivabradine decreases dynamic LVOT obstruction in cats with HCM, but the clinical effect is negligible and inferior compared to that achieved by atenolol.     

Comparison of Forelimb and Hindlimb Systolic Blood Pressures and Proteinuria in Healthy Shetland Sheepdogs

Background

The prevalence of systemic hypertension (SHT) in Shetland Sheepdogs has not been reported.

Hypothesis/Objectives

SHT is common in Shetland Sheepdogs and positively correlated with proteinuria. Measurements of forelimb and hindlimb systolic arterial pressure (SAP) are comparable.

Animals

Seventy‐two clinically healthy, client‐owned Shetland Sheepdogs.

Methods

Forelimb and hindlimb SAP were recorded by Doppler ultrasonography. Proteinuria was quantified by urine dipstick, microalbuminuria, and protein:creatinine ratio (UPC). The relationship of UPC, anxiety, age, weight, and heart rate with forelimb SAP was evaluated.

Results

The mean forelimb and hindlimb SAP were 132 ± 20 and 118 ± 20 mmHg, respectively. The SAP exceeded 160 mmHg in 9 dogs, suggesting 13% prevalence of SHT. Four dogs had a UPC above 0.5; 2 of these had forelimb SAP exceeding 160 mmHg. Correlation of forelimb and hindlimb SAP was poor (r ² = 0.09; P = .011). Bland–Altman plots revealed substantial bias (−14 mmHg) between limb measurements with clinically unacceptable 95% limits of agreement (−60 to 33 mmHg). There was no correlation between forelimb SAP and UPC (P = .06) or anxiety level (P = .49). Age (P < .0001) and heart rate (P = .038) were significant predictors of forelimb SAP; weight (P = .73) was not.

Conclusions

Prevalence of SHT was 13% and not correlated with proteinuria. Forelimb and hindlimb SAP were poorly correlated; therefore, trends in an individual animal should be monitored using the same measurement site. Additionally, values for Doppler SAP were determined in Shetland Sheepdogs.     

Diagnostic and Predictive Capability of Routine Laboratory Tests for the Diagnosis and Staging of Equine Inflammatory Disease

Background

A wide spectrum of laboratory tests is available to aid diagnosis and classification of equine inflammatory disease.

Objectives

To compare diagnostic efficacy and combined predictive capability of the myeloperoxidase index (MPXI), and plasma fibrinogen, iron and serum amyloid A (SAA) concentrations for the diagnosis of inflammation.

Animals

Twenty‐six hospitalized horses with systemic inflammation (SI), 114 with local inflammation (LI) and 61 healthy horses or those with noninflammatory disease (NI) were included.

Methods

A retrospective study was performed; clinicopathologic data from horses were compared between groups. Receiver‐operator characteristic (ROC) curves were used to evaluate diagnostic efficacy; classification and regression tree analysis (CART) and logistic regression analysis were used to generate diagnostic algorithms.

Results

Horses with SI had significantly higher SAA than horses with LI (P = .007) and NI (P < .001) and lower iron concentrations than horses with LI (P < .001) and NI (P < .001). Fibrinogen concentration was higher in horses with inflammation than in those without inflammation (P = .002). There was no difference between the SI and LI groups. White blood cell count, neutrophil count and MPXI were similar between groups. SAA had the highest accuracy for diagnosing inflammation (area under ROC curve [AUC], 0.83 ± 0.06) and iron and SAA concentration had the highest accuracy for differentiating SI from LI (AUC, 0.80 ± 0.09 and 0.73 ± 0.10 respectively). Predictive modeling failed to generate useful algorithms and classification of cases was moderate.

Conclusions and Clinical Importance

Very high SAA and low iron concentrations may reflect SI, but diagnostic guidelines based on quantitative results of inflammatory markers could not be formulated.     

Comparison of Serum Concentrations of Symmetric Dimethylarginine and Creatinine as Kidney Function Biomarkers in Cats with Chronic Kidney Disease

Background

Symmetric dimethylarginine (SDMA) has been shown to be an accurate and precise biomarker for calculating estimated glomerular filtration rate (GFR) in humans, as well as a more sensitive biomarker than serum creatinine concentration (sCr) for assessing renal dysfunction.

Objectives

The purpose of this retrospective study was to report on the utility of measuring serum SDMA concentrations in cats for detection of chronic kidney disease (CKD) before diagnosis by conventional measurement of sCr.

Animals

Chronic kidney disease cats (n = 21) included those persistently azotemic for ≥3 months (n = 15), nonazotemic cats with GFR >30% decreased from median GFR of normal cats (n = 4), and nonazotemic cats with calcium oxalate kidney stones (n = 2). Healthy geriatric cats (n = 21) were selected from the same colony.

Methods

Symmetric dimethylarginine concentrations (liquid chromatography‐mass spectroscopy) and sCr (enzymatic colorimetry) were determined retrospectively from historical data or banked serum samples in azotemic cats or at the time GFR (iohexol clearance) was measured in nonazotemic cats.

Results

Serum SDMA (r = −0.79) and sCr (r = −0.77) concentrations were significantly correlated to GFR (both P < .0001). Symmetric dimethylarginine became increased before sCr in 17/21 cats (mean, 17.0 months; range, 1.5–48 months). Serum SDMA had higher sensitivity (100%) compared with sCr (17%), but lower specificity (91% versus 100%) and positive predictive value (86% versus 100%).

Conclusion and Clinical Importance

Using serum SDMA as a biomarker for CKD allows earlier detection of CKD in cats compared with sCr, which may be desirable for initiating renoprotective interventions that slow progression of CKD.     

Arterial Thromboembolism in 250 Cats in General Practice: 2004–2012

Background

Population characteristics and outcome of cats with arterial thromboembolism (ATE) managed in general practice (GP) have been poorly described.

Hypothesis

Cats with ATE presenting to GP are usually euthanized at presentation, but survival times >1 year are possible.

Animals

Cats with ATE managed by 3 GP clinics in the United Kingdom.

Methods

Records of cases presenting to GP over a 98‐month period (2004–2012) were reviewed. Cats with an antemortem diagnosis of limb ATE were included. Outcome information was obtained.

Results

Over 98 months, 250 cats were identified with ATE. Prevalence was approximately 0.3%. At presentation, 153 cats (61.2%) were euthanized, with 68/97 (70.1%) of the remaining cats (27.2% of the total population) surviving >24 hours after presentation. Of these, 30/68 (44.1%) survived for at least 7 days. Hypothermia (HR, 1.44; 95% CI, 1.002–2.07; P = .049) and management by Clinic 2 (HR, 5.53; 95% CI, 1.23–24.8; P = .026) were independent predictors of 24‐hour euthanasia or death. For cats surviving >24 hours, hypothermia (HR, 2.25; 95% CI, 1.12–4.48; P = .021) and failure to receive aspirin, clopidogrel, or both (HR, 8.26; 95% CI, 1.39–50; P = .001) were independent predictors of euthanasia or death within 7 days. For cats that survived ≥7 days, median survival time was 94 (95% CI, 42–164) days, with 6 cats alive 1 year after presentation.

Conclusions

Although 153/250 cats were euthanized at presentation, 6 cats survived >12 months. No factors were identified that predicted euthanasia on presentation.     

Cervical Vertebral Trabecular Bone Mineral Density in Great Danes With and Without Osseous‐Associated Cervical Spondylomyelopathy

Background

Great Danes (GDs) with osseous‐associated cervical spondylomyelopathy (CSM) have osteoarthritis (OA) of the cervical vertebrae. OA is often associated with increases in bone mineral density (BMD) in people and dogs.

Hypothesis/Objectives

To compare the trabecular BMD of the cervical vertebrae between clinically normal (control) GDs and GDs with osseous‐associated CSM by using computed tomography (CT). We hypothesized that the vertebral trabecular BMD of CSM‐affected GDs would be higher than that of control GDs.

Animals

Client‐owned GDs: 12 controls, 10 CSM affected.

Methods

Prospective study. CT of the cervical vertebral column was obtained alongside a calibration phantom. By placing a circular region of interest at the articular process joints, vertebral body, pedicles, and within each rod of the calibration phantom, trabecular BMD was measured in Hounsfield units, which were converted to diphosphate equivalent densities. Trabecular BMD measurements were compared between CSM‐affected and control dogs, and between males and females within the control group.

Results

Differences between CSM‐affected and control dogs were not significant for the articular processes (mean = −39; P = .37; 95% CI: −102 to 24), vertebral bodies (mean = −62; P = .08; 95% CI: −129 to 6), or pedicles (mean = −36; P = .51; 95% CI: −105 to 33). Differences between female and male were not significant.

Conclusions and Clinical Importance

This study revealed no difference in BMD between control and CSM‐affected GDs. Based on our findings no association was detected between cervical OA and BMD in GDs with CSM.     

Clinical Findings and Survival in 56 Sick Neonatal New World Camelids

Background

Information pertaining to clinical presentation and outcome of neonatal New World camelids (NWC) is limited when compared to calves and foals.

Hypothesis

Values of variables at admission and subsequent treatment would predict survival in sick neonatal NWC.

Animals

Fifty‐six client‐owned sick neonatal NWC presented over a 10‐year period to the Purdue University Veterinary Teaching Hospital.

Methods

A retrospective study was performed. Inclusion criteria were NWC less than 30 days of age with complete medical records that presented between 2000 and 2010.

Results

The median age at presentation was 1 day (range 1–20). The most common diagnoses were systemic inflammatory response syndrome (50%), congenital defects (41%), ophthalmic lesions (21%), sepsis (16%), and gastrointestinal diseases (16%). Sixty‐six percent of NWC survived to discharge. Clinicopathologic findings on admission were variable and not specific for disorders. Factors associated with survival were absence of choanal atresia (P = .001, OR: 55.9 [2.5–1,232]), administration of llama plasma (P = .013, OR: 4.9 [1.4–17.7]), and antimicrobial treatment with trimethoprim‐sulfamethoxazole (TMS) (P = .016, OR: 6.5 [1.3–32.2]).

Conclusions and Clinical Importance

The use of antibiotics, particularly TMS, and llama plasma are recommended in sick neonatal NWC. Results from this study could contribute toward defining a NWC‐specific sepsis scoring system.     

Dobutamine Stress Echocardiography for Assessment of Systolic Function in Dogs with Experimentally Induced Mitral Regurgitation

Background

Systolic dysfunction is associated with poor outcomes in dogs with myxomatous mitral valve disease. However, assessment of systolic variables by conventional echocardiographic methods is difficult in these dogs because of mitral regurgitation (MR).

Hypothesis

We hypothesized that assessment of systolic function by dobutamine stress may identify systolic dysfunction in dogs with MR, and that 2‐dimensional speckle‐tracking echocardiography (2D‐STE) could quantitatively evaluate myocardial function.

Animals

Anesthetized dogs with experimentally induced MR.

Methods

Dogs were examined for systolic myocardial deformations using 2D‐STE during dobutamine infusion before and 3 and 6 months after MR induction. We evaluated peak systolic rotation and rotation rate in each basal and apical view; peak systolic torsion and torsion rate were also calculated.

Results

Invasive peak positive first derivatives of left ventricular pressure (dp/dt) were significantly decreased in dogs 6 months after induction of MR compared with pre‐MR results. After 3 and 6 months of MR, dogs had diminished peak systolic torsion values and torsion rates in response to dobutamine infusion compared with pre‐MR results (3 months, P < .001 and P = .006; 6 months, P = .003 and P = .021). These results were significantly correlated with overall invasive dp/dt (r = 0.644, P < .001; r = 0.696, P < .001).

Conclusions and Clinical Importance

Decreased torsion during dobutamine infusion in dogs with MR may reflect latent systolic dysfunction. Dobutamine infusion, therefore, may be useful for the assessment of systolic function in dogs with MR.     

Omega‐3 Fatty Acid Supplementation Provides an Additional Benefit to a Low‐Dust Diet in the Management of Horses with Chronic Lower Airway Inflammatory Disease

Background

Omega‐3 polyunsaturated fatty acid (PUFA) may benefit humans and animals with chronic inflammatory diseases.

Hypothesis

Omega‐3 PUFA supplementation improves clinical signs, lung function, and airway inflammation in horses with recurrent airway obstruction (RAO) and inflammatory airway disease (IAD).

Animals

Eight research horses and 35 client‐owned horses.

Methods

A pilot study examined the dose of PUFA that can alter plasma PUFA composition. Then, a randomized, controlled clinical trial was performed in horses with RAO and IAD. Horses were fed a complete pelleted diet with no hay and randomly assigned to 1 of 3 daily treatments for 2 months: 30 or 60 g of the supplement or 30 g of placebo. Clinical signs, lung function, plasma PUFA composition, and bronchoalveolar lavage fluid (BALF) cytology were evaluated. Data were expressed as median (25–75th percentiles). P < .05 was considered significant.

Results

Polyunsaturated fatty acid supplementation resulted in increased plasma docosahexaenoic acid (DHA) that peaked at 4 weeks. Clinical improvement was noted in all horses involved in the clinical trial, but the group that received PUFA had greater improvement in clinical signs (cough score improved 60%), lung function (respiratory effort decreased 48%), and BALF (neutrophils decreased from 23 to 9%) when compared to placebo (cough score improved 33%, respiratory effort decreased 27%, BALF neutrophils increased from 11 to 17%; P < .05).

Conclusions and Clinical Importance

Feeding horses with RAO and IAD a PUFA supplement containing 1.5–3 g DHA for 2 months provides an additional benefit to low‐dust diet.     

The Impact of Demographic,Social, and Environmental Factors on the Development of Steroid‐Responsive Meningitis‐Arteritis (SRMA) in the United Kingdom

Background

Steroid‐responsive meningitis‐arteritis (SRMA) is an inflammatory disease of dogs that is suspected to be immune‐mediated. The development of other immune‐mediated diseases has been linked to vaccinations, time of the year, geographic location, sex, neuter status, and breed.

Hypothesis/Objectives

To identify if the development of SRMA is associated with time of year, vaccination, geographic location, sex, neuter status, and breed.

Animals

Sixty SRMA cases and 180 controls, all ≤24 months of age and matched for year of presentation, from a referral hospital population in the United Kingdom.

Methods

Retrospective case‐control study with unconditional logistic regression analysis.

Results

Beagles (P = .001), Border Collies (P = .001), Boxers (P = .032), Jack Russell Terriers (P = .001), Weimaraners (P = .048), and Whippets (P < .001) had significantly greater odds of developing SRMA in this population of dogs. Vaccination, time of year, geographic category, sex, and neuter status did not increase the odds of developing SRMA.

Conclusions and Clinical Importance

Only breed increased the odds of developing SRMA. It would be prudent to investigate the genetics of the identified breeds to help elucidate the etiopathogenesis of SRMA.     

Prognostic Value of Early Magnetic Resonance Imaging in Dogs after Traumatic Brain Injury: 50 Cases

Background

The prognostic value of early magnetic resonance imaging (MRI) in dogs after traumatic brain injury (TBI) remains unclear.

Objectives

Determine whether MRI findings are associated with prognosis after TBI in dogs.

Animals

Fifty client‐owned dogs.

Methods

Retrospective study of dogs with TBI that underwent 1.5T MRI within 14 days after head trauma. MRI evaluators were blinded to the clinical presentation, and all images were scored based on an MRI grading system (Grade I [normal brain parenchyma] to Grade VI [bilateral lesions affecting the brainstem with or without any lesions of lesser grade]). Skull fractures, percentage of intraparenchymal lesions, degree of midline shift, and type of brain herniation were evaluated. MGCS was assessed at presentation. The presence of seizures was recorded. Outcome was assessed at 48 h (alive or dead) and at 3, 6, 12, and 24 months after TBI.

Results

Sixty‐six percent of the dogs had abnormal MRI findings. MRI grade was negatively correlated (P < .001) with MGCS. A significant negative correlation of MRI grade, degree of midline shift, and percentage of intraparenchymal lesions with follow‐up scores was identified. The MGCS was lower in dogs with brain herniation (P = .0191). Follow‐up scores were significantly lower in dogs that had brain herniation or skull fractures. The possibility of having seizures was associated with higher percentage of intraparenchymal lesions (P = 0.0054) and 10% developed PTE.

Conclusions and Clinical Importance

Significant associations exist between MRI findings and prognosis in dogs with TBI. MRI can help to predict prognosis in dogs with TBI.     

Neutrophil Gelatinase–Associated Lipocalin in Dogs with Naturally Occurring Renal Diseases

Background

Neutrophil gelatinase–associated lipocalin (NGAL) is released from renal tubular cells after injury and serves in humans as a real‐time indicator of active kidney damage, including acute kidney injury (AKI) and chronic kidney disease (CKD). However, NGAL concentrations in dogs with naturally occurring AKI or CKD rarely have been explored in detail.

Hypothesis/Objectives

The goal of this study was to evaluate whether NGAL can serve as a useful biomarker in dogs with naturally occurring renal disease.

Animals

Client‐owned dogs with renal disease (57) and control dogs without any disease (12) were examined.

Methods

Serum NGAL (sNGAL) and urine NGAL (uNGAL) concentrations were measured in each animal by a newly developed ELISA system. Demographic, hematologic, and serum biochemical data were recorded. Survival attributable to AKI and CKD was evaluated at 30 days and 90 days, respectively.

Results

Serum and urine NGAL concentrations in azotemic dogs were significantly higher than in nonazotemic dogs and were highly correlated with serum creatinine concentration (P < .05). Among CKD dogs, death was associated with significantly higher sNGAL and uNGAL concentrations compared with survivors. Receiver‐operating characteristic curve (ROC) analysis showed that sNGAL was better than serum creatinine concentration when predicting clinical outcomes for CKD dogs (P < .05). The best cutoff point for sNGAL was 50.6 ng/mL, which gave a sensitivity and a specificity of 76.9 and 100%, respectively. Furthermore, dogs that had higher concentrations of sNGAL survived for a significantly shorter time.

Conclusion

sNGAL is a useful prognostic marker when evaluating dogs with CKD.     

Relationship between Serum Symmetric Dimethylarginine Concentration and Glomerular Filtration Rate in Cats

Background

Direct measurement of glomerular filtration rate (GFR) is the preferred method to assess renal function in cats, but it is not widely used in the diagnosis of chronic kidney disease (CKD). In cats with CKD, symmetric dimethylarginine (SDMA) has been shown to increase and to correlate with plasma creatinine concentrations.

Hypothesis

In cats, reduced GFR corresponds with increased serum SDMA concentration.

Animals

The study group consisted of ten client‐owned cats whose GFR had been measured previously. Cats ranged in age from 11.1 to 16.9 years; both azotemic and nonazotemic animals were included.

Methods

Glomerular filtration rate was determined for each cat by plasma iohexol clearance using the three sample slope‐intercept method, and serum SDMA concentration was measured by liquid chromatography‐mass spectrometry.

Results

A linear relationship was observed between GFR and the reciprocal of serum SDMA concentration (R ² = 0.82, P < .001). A similar relationship was found between GFR and the reciprocal of plasma creatinine concentration (R ² = 0.81, P < .001).

Conclusions and Clinical Importance

Increased serum SDMA concentrations were observed in cats with reduced renal function as determined by direct measurement of GFR. This finding indicates that SDMA could have clinical applications in the diagnosis of CKD in cats.     

ISO‐Based Assessment of Accuracy and Precision of Glucose Meters in Dogs

Background

Portable blood glucose meters (PBGMs) allow easy glucose measurements. As animal‐specific PBGMs are not available everywhere, those for humans are widely used.

Objectives

To assess the accuracy and precision of 9 PBGMs in canine whole blood (WB) and plasma, based on the ISO 15197:2013.

Animals

Fifty‐nine client‐owned dogs attending the Veterinary Teaching Hospital.

Methods

Analytical evaluation of 100 blood samples was performed for accuracy and 23 for precision (glucose 29–579 mg/dL) following ISO recommendations. A PBGM was considered accurate if 95% of the measurements were within ±15 mg/dL from the reference when glucose was <100 mg/dL and within ±15% when it was ≥100 mg/dL, and if 99% of them were within zones A and B in error grid analysis (EG). A hexokinase‐based analyzer was used as reference. Ninety samples were assessed for hematocrit interferences.

Results

Accuracy requirements were not fulfilled by any PBGM in WB (74% of measurements within the limits for the most accurate) and by 1 only in plasma. However, the EG analysis in WB was passed by 6 PBGM and by all in plasma. The most accurate were also the most precise, with coefficients of variation <5% in WB and <3% in plasma. Hematocrit correlated with bias against the reference method in 4 PBGM (r = −0.243 − [−0.371]; P < .021).

Conclusions and Clinical Importance

This disparity among PBGM suggests that meters approved for humans need to be evaluated before use in other species.     

Detection of Clinically Relevant Pain Relief in Cats with Degenerative Joint Disease Associated Pain

Background

Detection of clinically relevant pain relief in cats with degenerative joint disease (DJD) is complicated by a lack of validated outcome measures and a placebo effect.

Hypothesis/Objectives

To evaluate a novel approach for detection of pain relief in cats with DJD.

Animals

Fifty‐eight client‐owned cats.

Methods

Prospective, double‐masked, placebo‐controlled, stratified, randomized, clinical study. Enrolled cats were 6–21 years of age, with owner‐observed mobility impairment, evidence of pain in at least 2 joints during orthopedic examination, and overlapping radiographic evidence of DJD, and underwent a 2‐week baseline period, 3‐week treatment period with placebo or meloxicam, and 3‐week masked washout period. Outcome measures were evaluated at days 0, 15, 36, and 57.

Results

Both groups significantly improved after the treatment period (day 36) on client‐specific outcome measures (CSOM) and feline musculoskeletal pain index (FMPI) (P < .0001 for both); there was no difference between the groups on CSOM or FMPI score improvement. After the masked washout period, more cats that received meloxicam during the treatment period had a clinically relevant decrease in CSOM score (P = .048) and FMPI score (P = .021) than cats that received placebo.

Conclusions and Clinical Importance

Using both a client‐specific and a general clinical metrology instrument, owners of cats with DJD were able to detect evident recurrence of clinical signs after withdrawal of active medication than after withdrawal of placebo, and that this study design might be a novel and useful way to circumvent the placebo effect and detect the efficacy of pain‐relieving medications.     

Comparison of Manual and Suction Pump Aspiration Techniques for Performing Bronchoalveolar Lavage in 18 Dogs with Respiratory Tract Disease

Background

Different aspiration techniques to retrieve bronchoalveolar lavage fluid (BALF) affect sample quality in healthy dogs. Studies evaluating these techniques in dogs with respiratory disease are lacking.

Objectives

To compare sample quality of BALF acquired by manual aspiration (MA) and suction pump aspiration (SPA).

Animals

Eighteen client‐owned dogs with respiratory disease.

Methods

Randomized, blinded prospective clinical trial. Manual aspiration was performed with a 35‐mL syringe attached directly to the bronchoscope biopsy channel and SPA was performed with a maximum of 50 mmHg negative pressure applied to the bronchoscope suction valve using the suction trap connection. Both aspiration techniques were performed in each dog on contralateral lung lobes, utilizing 2 mL/kg lavage volumes per site. Samples of BALF were analyzed by percentage of retrieved infusate, total nucleated cell count (TNCC), differential cell count, semiquantitative assessment of slide quality, and diagnosis score. Data were compared by paired Student''s t‐test, Wilcoxon signed‐rank test, chi‐squared test, and ANOVA. Cohen''s kappa coefficient was used to assess agreement.

Results

The percentage of retrieved BALF (P = .001) was significantly higher for SPA than MA. Substantial agreement was found between cytologic classification of BALF obtained with MA and SPA (kappa = 0.615). There was no significant difference in rate of definitive diagnosis achieved with cytologic assessment between techniques (P = .78).

Conclusions and Clinical Importance

Suction pump aspiration, compared to MA, improved BALF retrieval, but did not significantly affect the rate of diagnostic success of bronchoalveolar lavage (BAL) in dogs with pulmonary disease.