Platelet Activation in Cats with Hypertrophic Cardiomyopathy

Background

Cats with hypertrophic cardiomyopathy (HCM) are at risk for development of systemic thromboembolic disease. However, the relationship between platelet activation state and cardiovascular parameters associated with HCM is not well described.

Objectives

To characterize platelet activation by flow cytometric evaluation of platelet P‐selectin and semiquantitative Western blot analysis of soluble platelet‐endothelial cell adhesion molecule‐1 (sPECAM‐1).

Animals

Eight normal healthy cats (controls) owned by staff and students of the School of Veterinary Medicine and 36 cats from the UC Davis Feline HCM Research Laboratory were studied.

Methods

Platelet‐rich plasma (PRP) was used for all flow cytometry studies. Platelet surface CD41 and P‐selectin expression were evaluated before and after ADP stimulation. sPECAM‐1 expression was evaluated by Western blot analysis of platelet‐poor plasma that had been stabilized with aprotinin. Standard echocardiographic studies were performed.

Results

Resting platelets from cats with severe HCM had increased P‐selectin expression compared to controls, and expressed higher surface density of P‐selectin reflected by their increased mean fluorescence intensities (MFI). Stimulation with ADP also resulted in significantly increased P‐selectin MFI of platelets from cats with severe HCM. Increased P‐selectin expression and MFI correlated with the presence of a heart murmur and end‐systolic cavity obliteration (ESCO). sPECAM‐1 expression from cats with moderate and severe HCM was significantly increased above those of control cats.

Conclusions and Clinical Importance

P‐selectin and sPECAM expression may be useful biomarkers indicating increased platelet activation in cats with HCM.     

Breed Differences in Natriuretic Peptides in Healthy Dogs

Background

Measurement of plasma concentration of natriuretic peptides (NPs) is suggested to be of value in diagnosis of cardiac disease in dogs, but many factors other than cardiac status may influence their concentrations. Dog breed potentially is 1 such factor.

Objective

To investigate breed variation in plasma concentrations of pro‐atrial natriuretic peptide 31‐67 (proANP 31‐67) and N‐terminal B‐type natriuretic peptide (NT‐proBNP) in healthy dogs.

Animals

535 healthy, privately owned dogs of 9 breeds were examined at 5 centers as part of the European Union (EU) LUPA project.

Methods

Absence of cardiovascular disease or other clinically relevant organ‐related or systemic disease was ensured by thorough clinical investigation. Plasma concentrations of proANP 31‐67 and NT‐proBNP were measured by commercially available ELISA assays.

Results

Overall significant breed differences were found in proANP 31‐67 (P < .0001) and NT‐proBNP (P < .0001) concentrations. Pair‐wise comparisons between breeds differed in approximately 50% of comparisons for proANP 31‐67 as well as NT‐proBNP concentrations, both when including all centers and within each center. Interquartile range was large for many breeds, especially for NT‐proBNP. Among included breeds, Labrador Retrievers and Newfoundlands had highest median NT‐proBNP concentrations with concentrations 3 times as high as those of Dachshunds. German Shepherds and Cavalier King Charles Spaniels had the highest median proANP 31‐67 concentrations, twice the median concentration in Doberman Pinschers.

Conclusions and Clinical Importance

Considerable interbreed variation in plasma NP concentrations was found in healthy dogs. Intrabreed variation was large in several breeds, especially for NT‐proBNP. Additional studies are needed to establish breed‐specific reference ranges.     

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.     

Cardiac Biomarkers in Hyperthyroid Cats

Background

Hyperthyroidism has substantial effects on the circulatory system. The cardiac biomarkers NT‐proBNP and troponin I (cTNI) have proven useful in identifying cats with myocardial disease but have not been extensively investigated in hyperthyroidism.

Hypothesis

Plasma NT‐proBNP and cTNI concentrations are higher in cats with primary myocardial disease than in cats with hyperthyroidism and higher in cats with hyperthyroidism than in healthy control cats.

Animals

Twenty‐three hyperthyroid cats, 17 cats with subclinical hypertrophic cardiomyopathy (HCM), and 19 euthyroid, normotensive healthy cats ≥8 years of age. Fourteen of the hyperthyroid cats were re‐evaluated 3 months after administration of radioiodine (¹³¹I).

Methods

Complete history, physical examination, complete blood count, serum biochemistries, urinalysis, blood pressure measurement, serum T4 concentration, plasma concentrations of NT‐proBNP and cTNI, and echocardiogram were obtained prospectively from each cat.

Results

Hyperthyroid cats and cats with HCM had plasma NT‐proBNP and cTNI concentrations that were significantly higher than those of healthy cats, but there was no significant difference between hyperthyroid cats and cats with HCM with respect to the concentration of either biomarker. In hyperthyroid cats that were re‐evaluated 3 months after ¹³¹I treatment, plasma NT‐proBNP and cTNI concentrations as well as ventricular wall thickness had decreased significantly.

Conclusions and Clinical Importance

Although there may be a role for NT‐proBNP in monitoring the cardiac response to treatment of hyperthyroidism, neither NT‐proBNP nor cTNI distinguish hypertrophy associated with hyperthyroidism from primary HCM. Therefore, the thyroid status of older cats should be ascertained before interpreting NT‐proBNP and cTNI concentrations.     

Prognostic Value of Left Atrial Function in Dogs with Chronic Mitral Valvular Heart Disease

Background

A strong correlation between left atrial (LA) dysfunction and the severity of cardiac disease has been described in human patients with various cardiac diseases. The role of LA dysfunction in dogs with chronic mitral valvular heart disease (CMVHD) has not been addressed.

Objectives

To investigate the correlation between LA function and the prognosis of dogs with CMVHD.

Animals

Thirty‐eight client‐owned dogs with CMVHD.

Methods

Prospective clinical cohort study. Dogs were divided into 2 groups (survivors and nonsurvivors) based on the onset of cardiac‐related death within 1 year. Physical examination and echocardiographic variables were compared between the groups. For the assessment of the comparative accuracy in identifying patients with cardiac‐related death, receiver operating characteristic (ROC) curves and multivariate logistic analysis were used.

Results

The highest accuracy was obtained for the LA active fractional area change (LA‐FAC _act), with an area under the ROC curve (AUC) of 0.95, followed by the left atrial to aortic root ratio (LA/Ao), with an AUC of 0.94; peak early diastolic mitral inflow velocity (E), with an AUC of 0.85; and LA total fractional area change (LA‐FAC _total), with an AUC of 0.85. In the multivariate logistic regression analysis, LA‐FAC _act emerged as the only independent correlate of cardiac‐related death within 1 year (odds ratio = 1.401, P = .002).

Conclusions and Clinical Importance

Regarding both the size and function, the LA has a strong correlation with the prognosis of dogs with CMVHD. The most significant independent predictor of mortality in this study was LA‐FAC _act.     

Expression and Activity of Collagenases in the Digital Laminae of Horses with Carbohydrate Overload‐Induced Acute Laminitis

Background

Matrix metalloproteinases (MMP) are hypothesized to degrade structurally important components of the laminar extracellular matrix (ECM) in horses with laminitis.

Objective

To compare levels of expression of stromelysin‐1 (MMP‐3), collagenases (MMP‐1, ‐13), and membrane type‐MMPs (MMP‐14, ‐15, ‐16), and the distribution of their ECM substrates, in laminae of healthy horses and horses with carbohydrate overload laminitis.

Animals

Twenty‐five adult horses.

Methods

Gene and protein expression were determined in extracts of laminae using real‐time quantitative polymerase chain reaction and Western blotting after sodium dodecylsulfate polyacrylamide gel electrophoresis. Distribution of MMP‐13 and ECM components was determined using indirect immunofluorescent microscopy of nonfixed frozen sections. ECM morphology was assessed by hematoxylin and eosin staining.

Results

Of the genes studied, only those encoding MMP‐1 and ‐13 were upregulated in CHO‐induced laminitis; MMP‐1 at Obel grade (OG)1 lameness and MMP‐13 at OG3 lameness. Laminar MMP‐1 was present as 52 kDa proenzyme only. MMP‐13 was present as pro‐ (61 kDa) and processed (48 kDa) enzyme. MMP‐13 localized to the basal epithelium of the secondary epidermal laminae and its increased expression were accompanied by the appearance in secondary dermal laminae (SDL) of multiple foci that were devoid of collagen I, fibronectin, chondroitin and keratan sulfate glycosaminoglycans, and eosin‐staining material.

Conclusions and Clinical Relevance

MMP‐13 is upregulated in laminae of horses with CHO‐induced OG3 lameness and, by degrading components of the ECM, may contribute to the formation of ECM‐free lesions (gaps or tears) that appear in the SDL with OG3 lameness.     

Serum Lipoprotein Changes in Dogs with Renal Disease

Background

People with renal disease develop a dyslipidemia that contributes to progression of renal injury and development of cardiovascular disease. Lipoproteins in dogs with renal disease have not been investigated.

Hypothesis

Dogs with chronic kidney disease (CKD) have dyslipidemia characterized by increased lower density lipoproteins and decreased high‐density lipoproteins (HDLs). The degree of dyslipidemia is positively correlated with severity of disease, as reflected by serum creatinine concentration.

Animals

Prospective study of client‐owned dogs presented to the Cornell University Hospital for Animals: 29 dogs with confirmed CKD, 5 dogs with nephrotic syndrome (NS), and 12 healthy control dogs presented for routine vaccinations, dental cleaning, or owned by students.

Methods

Lipoprotein electrophoresis was used to quantify relative proportions of the 3 main classes of lipoproteins in canine serum: low‐density lipoproteins (LDL), very low‐density lipoproteins (VLDL), and HDL. Serum cholesterol and creatinine concentrations; urinalysis and urine protein‐to‐creatinine ratio were measured by standard methods.

Results

Dyslipidemia was consistently found in dogs with CKD and NS and was characterized by a decrease in HDL and variable increases in LDL and VLDL. Dogs with NS had a proportionately greater increase in the VLDL fraction, as compared with dogs with CKD.

Conclusion and Clinical Importance

Dyslipidemia similar to that documented in people with renal disease occurs in dogs with CKD, despite serum cholesterol concentrations often being within the reference interval. The contribution of altered lipoproteins to the pathogenesis of renal disease in dogs warrants additional study.     

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.     

The Clinical Efficacy of Dietary Fat Restriction in Treatment of Dogs with Intestinal Lymphangiectasia

Background

Intestinal lymphangiectasia (IL), a type of protein‐losing enteropathy (PLE), is a dilatation of lymphatic vessels within the gastrointestinal tract. Dietary fat restriction previously has been proposed as an effective treatment for dogs with PLE, but limited objective clinical data are available on the efficacy of this treatment.

Hypothesis/Objectives

To investigate the clinical efficacy of dietary fat restriction in dogs with IL that were unresponsive to prednisolone treatment or showed relapse of clinical signs and hypoalbuminemia when the prednisolone dosage was decreased.

Animals

Twenty‐four dogs with IL.

Methods

Retrospective study. Body weight, clinical activity score, and hematologic and biochemical variables were compared before and 1 and 2 months after treatment. Furthermore, the data were compared between the group fed only an ultra low‐fat (ULF) diet and the group fed ULF and a low‐fat (LF) diet.

Results

Nineteen of 24 (79%) dogs responded satisfactorily to dietary fat restriction, and the prednisolone dosage could be decreased. Clinical activity score was significantly decreased after dietary treatment compared with before treatment. In addition, albumin (ALB), total protein (TP), and blood urea nitrogen (BUN) concentration were significantly increased after dietary fat restriction. At 2 months posttreatment, the ALB concentrations in the ULF group were significantly higher than that of the ULF + LF group.

Conclusions and Clinical Importance

Dietary fat restriction appears to be an effective treatment in dogs with IL that are unresponsive to prednisolone treatment or that have recurrent clinical signs and hypoalbuminemia when the dosage of prednisolone is decreased.     

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.     

Prevalence of Chiari‐like Malformations in Clinically Unaffected Dogs

Background

The importance of Chiari‐like malformation (CM) in the generation of clinical signs or the formation of syringomyelia in dogs is incompletely understood, partly because the prevalence of various CM definitions in unaffected dogs is unknown.

Hypothesis/Objectives

The aims were: to estimate the prevalence of CM in dogs asymptomatic for CM or syringomyelia, according to 3 currently used definitions; and, to investigate the effect of brachycephaly and head position during magnetic resonance (MR) imaging on estimates of the prevalence of CM.

Animals

One ninety‐nine client‐owned dogs without apparent signs of CM or syringomyelia.

Methods

Blinded, retrospective analysis. Archived MR images were analyzed for evidence of cerebellar indentation and impaction into or herniation through the foramen magnum. Logistic regression analysis was used to investigate the relationship of CM diagnosis with head position and the cranial index (a measure of brachycephaly).

Results

In 185 non‐Cavalier King Charles Spaniel (CKCS) dogs, indentation was identified in 44% (95% CI, 47–51%) and impaction in 22% (95% CI, 16–28%). No asymptomatic, non‐CKCS dogs showed herniation. Regression analysis showed a significant increase in the odds of indentation and impaction in an extended head position and as the cranial index increased (became more brachycephalic).

Conclusions and Clinical Importance

The high prevalence of cerebellar indentation and impaction suggests that they may be normal anatomical variations and therefore unsuitable as definitions of CM. We suggest that future research into CM in dogs should define cases and controls more strictly so that overlap between normal and abnormal animals is minimized.     

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.     

Oxidant‐Antioxidant Status in the Blood of Horses with Symptomatic Recurrent Airway Obstruction (RAO)

Background

Systemic oxidative stress in horses with recurrent airway obstruction (RAO) is poorly characterized.

Objectives

The goal of this study was to investigate whether equine RAO is associated with systemic disturbances in the oxidant‐antioxidant equilibrium.

Animals

Seven healthy horses and 7 horses with symptomatic RAO.

Methods

A prospective study. Healthy and RAO‐affected horses were exposed to a 48‐hour challenge with moldy hay and straw to induce clinical exacerbation of RAO. Venous blood was collected and the activities of the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in equine erythrocyte lysates were measured. The concentration of thiobarbituric acid‐reactive substances (TBARSs) was assessed both in erythrocyte lysates and in plasma.

Results

A significant increase in the activities of GPx and SOD was detected in RAO‐affected horses compared with the control animals. There was no significant difference between groups in terms of the erythrocyte lysate activities of CAT, GR, or TBARs or the plasma concentration of TBARs.

Conclusion and Clinical Importance

Our results support the hypothesis that RAO in horses is associated with systemic oxidative stress. Future studies are needed to assess whether horses suffering from RAO can benefit from antioxidant supplementation.     

Phenotypic Characterization of Canine Intestinal Intraepithelial Lymphocytes in Dogs with Inflammatory Bowel Disease

Background

Many dogs suffering from inflammatory bowel disease (IBD) are presented to veterinary clinics. These patients are diagnosed based on a history of chronic gastrointestinal signs and biopsy‐confirmed histopathologic intestinal inflammation. Intestinal intraepithelial lymphocytes (IEL) are part of the first line of defense in the gastrointestinal immune system. Alterations in IEL subsets may play a role in the pathogenesis of IBD.

Hypothesis

The aim of this study was to characterize the phenotypes of IEL in dogs with IBD compared with healthy control dogs.

Animals

Intestinal intraepithelial lymphocytes subpopulations of control dogs (n = 5) obtained from endoscopic biopsies (EB) were compared to those obtained from full thickness biopsies (FTB) on the same day. In addition, the phenotypes of IEL from FTB of control dogs (n = 10) were compared with EB of IBD dogs (n = 10). Each participant was scored clinically using the canine inflammatory bowel disease activity index (CIBDAI), and all samples were graded histopathologically. Three‐color flow cytometry of isolated IEL was performed using monoclonal antibodies against T‐ and B‐lymphocyte subpopulations.

Results

No significant differences in the composition of IEL subpopulations were found in control dogs based on method of biopsy. The IBD dogs had significantly higher CIBDAI and histopathologic scores compared with control dogs and their IEL contained a significantly higher frequency TCRγδ T‐cells.

Conclusions and Clinical Importance

Endoscopic biopsies provide suitable samples for 3‐color flow cytometry when studying canine intestinal IEL and IBD patients show significant changes of major T‐cell subsets compared to healthy control dogs.     

Urinary Corticoid Concentrations Measured by 5 Different Immunoassays and Gas Chromatography‐Mass Spectrometry in Healthy Dogs and Dogs with Hypercortisolism at Home and in the Hospital

Background

Determination of the urinary corticoid‐to‐creatinine ratio (UCCR) is an important screening test in the diagnosis of hypercortisolism (HC). However, urinary cortisol metabolites interfere with cortisol measurement in immunoassays, leading to decreased specificity. Gas chromatography‐mass spectrometry (GC‐MS) is considered the gold standard for steroid hormone analysis, because it provides a high level of selectivity and accuracy.

Objectives

To prospectively compare the UCCR of healthy dogs and dogs with HC determined by 5 different immunoassays and by GC‐MS and to evaluate the influence of veterinary care on UCCR.

Animals

Twenty healthy dogs; 18 dogs with HC.

Methods

Urine was collected in the hospital and again after 6 days at home. Three chemiluminescence immunoassays (Access 2, Beckmann; Immulite 2000, DPC Siemens, with and without trichloromethane extraction) and 2 RIAs (Utrecht in house; Access Beckmann) were used. GC‐MS analyses were performed with Agilent 6890N/5973N. Urinary corticoid concentrations were related to urinary creatinine concentrations.

Results

Immunoassay results were significantly higher compared to GC‐MS results. Evaluation of bias plots and clinical assessment made on the basis of the assay results of each dog indicated substantial disagreement among the assays. Sensitivity varied from 37.5 to 75% and with selected assays was lower in samples from day 6 compared to day 0. GC‐MS was not superior to the immunoassays in discriminating healthy from HC dogs.

Conclusions and Clinical Importance

Considerable variation must be anticipated comparing different urinary cortisol assays. Establishing an assay‐ and laboratory‐specific reference range is critical when using UCCR.     

Prevalence and Heritability of Symptomatic Syringomyelia in Cavalier King Charles Spaniels and Long‐term Outcome in Symptomatic and Asymptomatic Littermates

Background

Syringomyelia (SM) is common in the Cavalier King Charles Spaniel (CKCS). Dogs with syringes express clinical signs or might be clinically silent.

Objectives

To investigate the prevalence and heritability of symptomatic SM, the association between clinical signs and magnetic resonance imaging (MRI) findings, and long‐term outcome.

Animals

All CKCS registered in the Danish Kennel Club in 2001 (n = 240).

Methods

A cross‐sectional questionnaire‐based prevalence study validated by telephone interviews and clinically investigated clinical signs of SM. Dogs were 6 years at the time of investigation. A prospective observational litter study including clinical investigations, MRI and 5‐year follow‐up of symptomatic and asymptomatic siblings. Heritability was estimated based on the scale of liability in the study population and litter cohort.

Results

The cross‐sectional study estimated a prevalence of symptomatic SM at 15.4% in the population. Thirteen symptomatic and 9 asymptomatic siblings participated in the litter study. Spinal cord syringes were confirmed in 21 of 22 littermates (95%). Syrinx diameter and mean syrinx : spinal cord ratio were significantly correlated with clinical signs (P < .01). Estimated heritability of symptomatic SM was 0.81. Symptomatic SM motivated euthanasia in 20%. Dogs with syringes, which expressed no clinical signs at the age of 6, remained asymptomatic in 14/15 cases (93%).

Conclusions and Clinical Importance

The prevalence of symptomatic SM is high and genetics have a high impact on clinical disease expression. Further investigations of factors influencing the outbreak threshold of clinical signs of SM are desirable.     

Use of the Cortisol‐to‐ACTH Ratio for Diagnosis of Primary Hypoadrenocorticism in Dogs

Background

The ACTH stimulation test is currently required for definitive diagnosis of hypoadrenocorticism. Increased cost of synthetic ACTH (cosyntropin) has prompted a search for alternative diagnostic methods.

Objective

The purpose of this study was to determine whether a cortisol‐to‐ACTH ratio (CAR) can be used to differentiate dogs with hypoadrenocorticism from normal dogs and those with nonadrenal illness.

Animals

Eight healthy dogs (H), 19 dogs with nonadrenal illness (NAI), and 15 dogs with hypoadrenocorticism (HAD).

Methods

Dogs in the HAD group were retrospectively identified from PUVTH medical records. The NAI group consisted of hospitalized dogs with clinical signs, clinicopathologic findings, or both, consistent with a diagnosis of hypoadrenocorticism, but in which hypoadrenocorticism was ruled out based on ACTH stimulation test results. Healthy dogs were recruited from hospital staff and students. Endogenous ACTH concentrations and cortisol concentrations before and after ACTH stimulation were measured in all dogs.

Results

Baseline cortisol concentration was significantly lower, and ACTH concentration was significantly higher, in the HAD group versus the H and NAI group (P < .001). However, there was overlap among groups. Cortisol‐to‐ACTH ratio was significantly lower in the HAD group versus the H and NAI groups (P < .001), and there was no overlap between the HAD group and the other 2 groups.

Conclusions and Clinical Importance

CAR can be used for definitive diagnosis of primary hypoadrenocorticism.     

Relationship among Insulin Resistance,Growth Hormone,and Insulin‐Like Growth Factor I Concentrations in Diestrous Swedish Elkhounds

Background

In the dog, the normal estrous cycle includes a prolonged luteal phase. Progesterone stimulates local canine mammary growth hormone (GH) production, which may act systemically and contribute to insulin resistance. Swedish Elkhounds are predisposed to progesterone‐related diabetes mellitus, and the relationship among insulin resistance, GH, and insulin‐like growth factor I (IGF‐I) is of particular interest.

Objective

To study insulin resistance in relation to GH and IGF‐I in nondiabetic Swedish Elkhounds during diestrus. We also assessed whether alterations in these hormones could predict diestrus‐linked diseases and all‐cause mortality.

Animals

Eighty‐four privately owned female intact Swedish Elkhounds >4 years of age.

Methods

Blood sampling and clinical examination during luteal phase, with a follow‐up questionnaire after 20 months. Insulin resistance was calculated by homeostasis model assessment (HOMA‐IR).

Results

In multivariable regression analysis, GH was positively associated with HOMA‐IR (P = .009). An increase in GH of 1 ng/mL was associated with a 12.7% increase in HOMA‐IR. Moreover, C‐peptide was positively associated with IGF‐I (P = .04), and an increase in C‐peptide of 0.1 ng/mL was associated with a 6.9% increase in IGF‐I. Structural equation modeling supported these results. Twenty‐three animals were found to have previously unrecognized mammary masses and had higher GH (P < .0001) and IGF‐I (P = .007) than dogs without mammary masses (n = 61). There was no association between high GH and IGF‐I concentrations at sampling and future mammary masses.

Conclusion

We showed that GH was strongly associated with insulin resistance in older Swedish Elkhounds during diestrus.     

Comparison of 4 Direct Coombs' Test Methods with Polyclonal Antiglobulins in Anemic and Nonanemic Dogs for In‐Clinic or Laboratory Use

Background

Difficulties with the direct antiglobulin test (DAT) and its apparent lack of sensitivity and specificity for immune‐mediated hemolytic anemia (IMHA) in dogs have raised skepticism regarding its diagnostic value.

Objective

To compare different DATs and other hematologic parameters in dogs.

Animals

Anticoagulated blood samples from 59 nonanemic and 46 anemic dogs (± IMHA) from a research colony and veterinary clinics.

Methods

Prospective observational study: Immunochromatographic strip, gel microcolumn, and capillary techniques were compared with standard microtiter DAT using 2 polyvalent antiglobulins. Spherocytosis, autoagglutination, osmotic fragility, and clinical data were assessed.

Results

Blood samples from all 59 nonanemic dogs were DAT‐. Among 46 anemic dogs, 33 were suspected of IMHA, but only 20 were DAT+. Old and new DAT methods yielded comparable and consistent results even after storage of chilled blood samples for 1 week. Spherocytosis and autoagglutination (that did not persist after washing) were noted in 15 and 16 DAT+ dogs, respectively. The other 26 anemic dogs, including 21 previously transfused dogs and 4 with autoagglutination, tested DAT‐ by the other methods. Osmotic fragility was increased in 70% (19/27) of anemic and all 15 DAT+ dogs tested. Limited follow‐up testing revealed DAT+ results for 3–70 days.

Conclusions and Clinical Importance

The novel strip and capillary DAT methods are promising adjunct in‐clinic tools. Despite prior immunosuppressive treatment and presence of autoagglutination, the DAT was positive in anemic dogs with IMHA. Transfusion did not cause false DAT+ results. Our results support DAT as a cornerstone in the diagnosis of canine IMHA.