OBJECTIVES To describe the clinicopathologic findings and outcome in dogs with atypical hypoadrenocorticism (Group 1) and dogs with suspected atypical hypoadrenocorticism whose post-adrenocorticotropic hormone stimulation cortisol concentrations were greater than 55 nmol/L but below the laboratory reference interval (Group 2). METHODS Medical records were searched to identify dogs diagnosed with hypoadrenocorticism between January 2004 and June 2014. Dogs were excluded if their Na:K ratio was less than 27 or if they had received prior therapy that could interfere with adrenocorticotropic hormone stimulation testing. RESULTS Forty dogs were included in Group 1 and nine dogs in Group 2. In Group 1, the most common biochemical abnormalities were hypoalbuminaemia (87%) and hypocholesterolaemia (76%). Of 35 dogs in Group 1 with follow-up biochemistry results, five (14%) developed electrolyte abnormalities at 2 to 51 months post diagnosis. Of seven dogs in Group 2 with follow-up, glucocorticoid therapy was discontinued in two dogs without return of clinical signs, four dogs were subsequently diagnosed with inflammatory bowel disease and one dog continued to have clinical signs despite glucocorticoid treatment. CLINICAL SIGNIFICANCE Dogs with gastrointestinal signs and hypoalbuminaemia and, or, hypocholesterolaemia should be evaluated for atypical hypoadrenocorticism. Follow-up electrolyte monitoring is recommended because some will develop electrolyte abnormalities. Although dogs in Group 2 had a clinical presentation compatible with atypical hypoadrenocorticism, the diagnosis appears unlikely based on review of follow-up data. Dogs with equivocal adrenocorticotropic hormone stimulation results should be evaluated for other underlying diseases such as inflammatory bowel disease. The use of endogenous adrenocorticotropic hormone measurements in these dogs warrants investigation.

Background Ketones, including beta hydroxybutyrate (BHB), are produced in conditions of negative energy balance and decreased glucose utilization. Serum BHB concentrations in cats are poorly characterized in diseases other than diabetes mellitus. Hypothesis Serum BHB concentrations will be increased in cats with chronic kidney disease (CKD), hyperthyroidism (HT), or hepatic lipidosis (HL). Animals Twenty‐eight client‐owned cats with CKD, 34 cats with HT, and 15 cats with HL; 43 healthy cats. Methods Prospective observational study. Serum BHB concentrations were measured at admission in cats with CKD, HT, and HL, for comparison with a reference interval established using healthy cats. Results of dipstick urine ketone measurement, when available, were compared to BHB measurement. Results Beta hydroxybutyrate was above the reference interval (<0.11 mmol/L) in 6/28 cats (21%) with CKD, 7/34 cats (20%) with HT, and 11/15 cats (73%) with HL, significantly exceeding the expected 2.5% above the reference interval for healthy cats (P < .001 for all groups). Elevations were mild in CKD and HT groups (median BHB 0.1 mmol/L for both groups, 80th percentile 0.12 and 0.11 mmol/L, respectively), but more marked in HL cats (median BHB 0.2 mmol/L, 80th percentile 0.84 mmol/L). None of 11 cats with increased serum BHB concentration having urine dipstick analysis performed within 24 h of sampling for BHB were ketonuric. Conclusions and Clinical Importance Increases in serum BHB concentrations occur in cats with CKD, HT, and HL, and might provide an useful index of catabolism.

Background: Hypercalciuria and hyperoxaluria are risk factors for calcium oxalate ( CaOx) urolithiasis, but breed- specific reports of urinary metabolites and their relationship with stone status are lacking. Objective: To compare urinary metabolites ( calcium and oxalate) and blood ionized calcium ( iCa) concentrations between CaOx stone formers and breed- matched stone- free controls for the Miniature Schnauzer, Bichon Frise, and Shih Tzu breeds. Animals: Forty- seven Miniature Schnauzers ( 23 cases and 24 controls), 27 Bichons Frise ( 14 cases and 13 controls), and 15 Shih Tzus ( 7 cases and 8 controls). Methods: Prospective study. Fasting spot urinary calcium- to- creatinine and oxalate- to- creatinine ratios ( UCa/ Cr and UOx/ Cr, respectively) and blood iCa concentrations were measured and compared between cases and controls within and across breeds. Regression models were used to test the effect of patient and environmental factors on these variables. Results: UCa/ Cr was higher in cases than controls for each of the 3 breeds. In addition to stone status, being on a therapeutic food designed to prevent CaOx stone recurrence was associated with higher UCa/ Cr. UOx/ Cr did not differ between cases and controls for any of the breeds. Blood iCa was higher in cases than controls in the Miniature Schnauzer and Bichon Frise breeds and had a moderate correlation with UCa/ Cr.Conclusions and Clinical Importance: Hypercalciuria is associated with CaOx stone status in the Miniature Schnauzer, Bichon Frise, and Shih Tzu breeds. UOx/ Cr did not correlate with stone status in these 3 breeds. These findings may influence breed- specific stone prevention recommendations.

Background Mean platelet volume ( MPV ) and plateletcrit ( PCT ) are indices used in evaluating immune‐mediated thrombocytopenia ( IMT ) in humans and in dogs with congenital macrothrombocytopenia. These indices may provide clinically valuable information in acquired thrombocytopenia. Hypothesis/Objectives Dogs with presumed primary IMT will have increased MPV , and therefore platelet mass ( PCT ) will increase faster than platelet count ( PLT ) during recovery. Animals Forty‐nine dogs with automated PLT < 30,000/μL because of presumed primary IMT and hematocrit ( HCT ), PCT , MPV , and platelet distribution width determined from the same complete blood count ( CBC ), and 46 healthy controls. Methods Case‐control retrospective study; PLT , PCT , MPV , and platelet distribution width ( PDW ) were recorded from CBC s from 49 dogs, with 45 having data collected on the day of presentation. Fifteen were confirmed to have attained a PLT ≥ 75,000/μL on at least 1 CBC within 15 days after admission. The PCT equivalent to a PLT of 75,000/μL (assuming an average MPV ) was calculated for comparison with PLT in terms of time to achieve a threshold of platelet mass by the 2 measures. Results Mean platelet volume was higher in IMT dogs (17.3 fl) than the reference population (10.5 fl) ( P < .0001). The PDW was not significantly different among the groups. The median time for PCT to reach threshold in confirmed responders was faster (3 days) compared with PLT (4 days). Conclusions and Clinical Importance Immune‐mediated thrombocytopenia is characterized by increased MPV . Time to achieve a threshold PCT tended to be shorter than PLT , suggesting that PCT may be a useful platelet parameter for monitoring dogs with IMT .

Background A poorly understood protein‐losing enteropathy ( PLE ) disorder has been reported in Yorkshire Terrier dogs. Objectives To describe clinical features, intestinal histopathology, and outcome in Yorkshire Terrier dogs with PLE , and to identify variables predictive of outcome. Animals Thirty client‐owned Yorkshire Terrier dogs with PLE . Methods Retrospective study. Records of dogs with a diagnosis of PLE were reviewed. Intestinal histopathology was interpreted using the World Small Animal Veterinary Association gastrointestinal histopathology classification system. Discriminate analysis techniques were used to identify variables predictive of outcome. Results Females outnumbered males (20/30). Median age was 7 years (range 1–12). Common clinical signs were diarrhea (20/30), vomiting (11), ascites and abdominal distension (11), and respiratory difficulty (8). Histopathologic abnormalities included villous lymphatic dilatation, crypt lesions, villous stunting, and variable increases in cellularity of the lamina propria. All dogs were treated with glucocorticoids. Of 23 dogs with long‐term follow‐up, 9 had complete, and 3 had partial, resolution of signs, and 11 failed to respond to treatment. Median survival of responders was 44 months and of nonresponders was 12 months, with 4 dogs experiencing peracute death. Vomiting, monocytosis, severity of hypoalbuminemia, low blood urea nitrogen concentration, and villous blunting were predictive of survival <4 months. Conclusions In addition to classic GI signs, Yorkshire Terriers with PLE often show clinical signs associated with hypoalbuminemia and low oncotic pressure. Lymphatic dilatation, crypt lesions, and villous stunting are consistent histopathologic findings. Clinical outcomes are variable, but many dogs experience remission of clinical signs and prolonged survival.

BACKGROUND:Hyperthyroidism is common among older cats, but its pathogenesis remains poorly understood. Siamese and Himalayan cats have a reduced risk of hyperthyroidism compared with domestic short-hair cat breeds. A mechanism of risk reduction in pointed-coat breeds is unknown.OBJECTIVES:To determine if tyrosine, phenylalanine, iodine, or selenium blood concentrations are altered in hyperthyroid cats and to describe the plasma amino acid profiles of client-owned cats with naturally occurring hyperthyroidism.ANIMALS:Twenty-seven client-owned cats with (n = 12) and without (n = 15) hyperthyroidism were studied.METHODS:Cross-sectional study. Hyperthyroid cats were prospectively recruited among cats presenting for radioiodine therapy. Control cats were recruited among pets of hospital personnel. Blood was collected for total thyroxine, plasma amino acid, selenium, and iodine determination. Coat color (8 white or pointed; 19 dark), breed, and diet history were recorded.RESULTS:Tyrosine, phenylalanine, iodine, and selenium levels were not significantly different among light or dark cats or cats with or without hyperthyroidism (P > .05). Plasma amino acid profiles of hyperthyroid cats and control cats were similar, and neither group was deficient in any of the amino acids. L-glutamine was significantly lower in cats with hyperthyroidism (mean ± SD: 648 ± 193) compared with control cats (816 ± 134; P < .05).CONCLUSIONS AND CLINICAL IMPORTANCE:Altered tyrosine, iodine, and selenium metabolism were not associated with coat color or hyperthyroidism in pointed or light coat-colored cats.

In this study, we estimated insulin sensitivity and determined plasma concentrations of total-, low-molecular-weight (LMW), and high-molecular-weight (HMW) adiponectin and leptin in 72 domestic shorthair, neutered, client-owned cats. Glucose tolerance was assessed with an intravenous glucose tolerance test and body fat percentage (BF%) was measured with dual-energy x-ray absorptiometry. Total adiponectin was measured with 2 different ELISAs. Low-molecular-weight and HMW adiponectin plasma concentrations were determined by Western blot analysis after sucrose-gradient velocity centrifugation, and the adiponectin multimer ratio [SA = HMW/(HMW + LMW)] was calculated. Differences in glucose tolerance, leptin, total adiponectin, and multimer ratio among lean (BF% <35; n = 26), overweight (35 45; n = 18) cats as well as between male (n = 34) and female (n = 38) neutered cats were evaluated by linear regression and 2-way ANOVA. Sex and age were included as covariates for analysis of BF%, whereas BF%, fat mass, and lean body mass were covariates for analysis of sex differences. Increased BF% was negatively correlated with multimer ratio (SA, r = −45; P < 0.002), whereas no differences were found in total adiponectin concentrations among BF% groups (P > 0.01). Male cats had indices of decreased insulin tolerance and significantly lower total adiponectin concentrations than did female cats (mean ± SEM, 3.7 ± 0.4 vs 5.4 ± 0.5 μg/mL; P < 0.02). Altered SAs could contribute to an obesity-associated decreasing glucose tolerance in cats, and low total adiponectin concentrations may relate to increased risk of diabetes mellitus in neutered male cats.

BACKGROUND:Variants in the serine protease inhibitor Kazal type 1 (SPINK1) gene have been associated with pancreatitis in Miniature Schnauzers. Replication of the association in an independent population is necessary to determine if genetic screening for SPINK1 variants should be considered in clinical practice.HYPOTHESIS:An association between the SPINK1 exonic variant c.74A > C and pancreatitis exists in Miniature Schnauzers. In addition, the variant is absent or rare in Standard Schnauzers, a related breed that is not reported to have an increased risk for pancreatitis.ANIMALS:Case-control study. Seventeen Miniature Schnauzers with pancreatitis (cases), 60 mature Miniature Schnauzers with no substantial history of gastrointestinal signs in their lifetime (controls), and 31 Standard Schnauzers of unknown pancreatitis status.METHODS:A PCR-RFLP assay was used to genotype dogs for the c.74A > C SPINK1 variant. Allele and genotype frequencies were reported for Schnauzers and compared between case and control Miniature Schnauzers.RESULTS:The c.74A > C variant was the major allele in both Schnauzer breeds with a frequency of 0.77 in Miniatures and 0.55 in Standards. The allele and genotype frequencies were similar between Miniature Schnauzers with and without a history of pancreatitis and did not impart an increased risk for pancreatitis.CONCLUSIONS AND CLINICAL IMPORTANCE:Genotyping a larger population of the Miniature Schnauzer breed than a previous study, along with a Standard Schnauzer cohort, demonstrated that the SPINK1 c.74A > C variant is a common polymorphism in the Schnauzer lineage. Furthermore, we were unable to confirm a relationship between the variant and clinically detectable pancreatitis in Miniature Schnauzers.

BACKGROUND:A major cause of death in dogs with immune-mediated hemolytic anemia (IMHA) is thromboembolism. Previous studies suggest unfractionated heparin (UH) is not effective in preventing thromboembolism in IMHA; however, subtherapeutic dosing could explain the seeming lack of efficacy.HYPOTHESIS:Providing therapeutic plasma concentration of UH by individually adjusting doses based on antifactor Xa activity would improve survival in IMHA.ANIMALS:Fifteen dogs with primary IMHA.METHODS:Randomized, prospective, controlled clinical trial. Dogs received standardized therapy for IMHA and either constant dose (CD) (150 U/kg SC) (n = 7) or individually adjusted dose (IAD) (n = 8) UH, monitored via an anti-Xa chromogenic assay, adjusted according to a nomogram. UH was administered every 6 hours until day 7, and every 8 hours thereafter. UH dose was adjusted daily in IAD dogs until day 7, weekly until day 28, then tapered over 1 week. Dogs were monitored for 180 days.RESULTS:At day 180, 7 dogs in the IAD group and 1 in the CD group were alive (P= .01). Median survival time for the IAD group was >180 days, and 68 days for the CD group. Thromboembolic events occurred in 5 dogs in the CD group and 2 dogs in the IAD group. Doses of UH between 150 and 566 U/kg achieved therapeutic anti-Xa activity (0.35-0.7 U/mL).CONCLUSIONS AND CLINICAL IMPORTANCE:This study suggests that IAD UH therapy using anti-Xa monitoring reduced case fatality rate in dogs with IMHA when compared with dogs receiving fixed low dose UH therapy.

BACKGROUND The accumulation of frame-shift mutations in microsatellites (MS), termed microsatellite instability (MSI), is associated with certain tumors. MSI and its detection in urine samples has been used to aid in the detection of human bladder cancer. HYPOTHESIS Evaluation of MSI in urine is a useful assay test for diagnosis of transitional cell carcinoma (TCC) in dogs and is more specific than the commercially available, veterinary bladder tumor analyte (V-BTA) test. ANIMALS Seventy-three dogs: healthy controls (n=21), proteinuric (n=12), lower urinary tract disease excluding TCC (n=17), and TCC (n=23). METHODS Prospective observational study. Urine samples collected from each animal were evaluated for MSI and using the V-BTA. For MSI detection, 22 MS sequences were polymerase chain reaction amplified from urine and blood, subjected to capillary electrophoresis, and the MS genotypes were compared. Aberration in ≥15% of MS was considered indicative of MSI. RESULTS MSI was detected in 11 of 23 (48%) urine samples from dogs with TCC. MSI was also detected in 12 of 50 (24%) of the control animals, including 29, 16, and 24% of healthy, proteinuric, and lower urinary disease dogs, respectively. In this population, sensitivity and specificity of MSI analysis was 48 and 76%, respectively, compared with 83 and 64%, respectively, for the V-BTA test. CONCLUSIONS MS analysis as performed in this study is not useful in the diagnosis of TCC.

BACKGROUND:Immune-mediated thrombocytopenia (IMT) is a common hematologic disorder in dogs. Human intravenous immunoglobulin (hIVIG) may have a beneficial effect in canine IMT.HYPOTHESIS:A single hIVIG infusion (0.5 g/kg) in dogs with presumed primary IMT (pIMT) is a safe adjunctive emergency treatment to accelerate platelet count recovery and shorten hospitalization time without increasing the cost of patient care.ANIMALS:Eighteen client-owned dogs with a presumptive diagnosis of pIMT.METHODS:Prospective, randomized, double-blinded, placebo-controlled clinical trial.RESULTS:There were no identifiable immediate or delayed adverse reactions associated with hIVIG administration over a 6-month period. The median platelet count recovery time for the hIVIG group was 3.5 days (mean + or - SD: 3.7 + or - 1.3 days; range, 2-7 days) and 7.5 days (mean + or - SD: 7.8 + or - 3.9 days; range, 3-12 days) for the placebo group. The median duration of hospitalization for hIVIG group was 4 days (mean + or - SD: 4.2 + or - 0.4 days; range, 2-8 days) and 8 days (mean + or - SD: 8.3 + or - 0.6 days; range, 4-12 days) for the placebo group. There was no significant difference between groups with respect to expense of initial patient care, whereas significant reduction in platelet count recovery time (P= .018) and duration of hospitalization (P= .027) were detected in the hIVIG group.CONCLUSIONS AND CLINICAL IMPORTANCE:Compared with corticosteroids alone, adjunctive emergency therapy of a single hIVIG infusion was safe and associated with a significant reduction in platelet count recovery time and duration of hospitalization without increasing the expense of medical care in a small group of dogs with presumed pIMT.

Adiponectin has been investigated widely due to its association with adiposity and the metabolic syndrome in human beings. Adiponectin circulates as low- (LMW) and high-molecular weight (HMW) multimers and the latter are the more bioactive forms. There are no reports of the relative proportion (distribution) of adiponectin multimers in feline plasma. The aim of this study was to assess the association of dietary nutrient composition, body weight gain, meal feeding, and insulin sensitivity with HMW adiponectin concentration and adiponectin multimer distribution in cats.

OBJECTIVE:To determine clinical characteristics and mode of inheritance of idiopathic epilepsy (IE) in English Springer Spaniels.DESIGN:Original study.ANIMALS:45 dogs with IE and 74 siblings and their respective parents.PROCEDURE:IE was diagnosed on the basis of age at the time of seizure onset and results of laboratory testing and neurologic examinations. Simple segregation analysis was performed with the Davie method.RESULTS:Median age at the onset of seizures was 3 years; however, 9 (20%) dogs were between 5 and 6 years old at the time of the onset of seizures. Twenty-one dogs (47%) had generalized seizures, and 24 (53%) had focal onset seizures. Results of segregation analysis were consistent with partially penetrant autosomal recessive or polygenic inheritance. Simulated linkage indicated that there was a 58% chance of obtaining suggestive linkage with the available pedigrees.CONCLUSIONS AND CLINICAL RELEVANCE:Results of the present study suggest that in English Springer Spaniels, IE segregates in a manner that is consistent with partially penetrant autosomal recessive inheritance (ie, a single major locus with modifying genes) or polygenic inheritance. Given enough families with accurate phenotypic information and available DNA, it should be possible to use genetic linkage analysis to identify chromosomal segments containing the causative gene or genes.

The histopathologic and clinical features of feline inflammatory liver disease are incompletely under-stood. Results of recent studies indicate that feline inflammatory liver diseases can be classified as acute (suppurative) and chronic (nonsuppurative) cholangiohepatitis and lymphocytic portal hepatitis. Histopathologic features of cholangiohepatitis include infiltration of neutrophils into walls and lumens of bile ducts and portal areas, periportal necrosis, and variable degrees of fibrosis and bile duct hyperplasia. Lymphocytic portal hepatitis is characterized by increased numbers of lymphocytes and plasma cells in portal areas, bile duct hyperplasia, and fibrosis. Liver biopsy is needed to establish a definitive diagnosis but trends in clinical laboratory test results may be helpful in establishing a tentative diagnosis. Specific treatment for cholangiohepatitis include antibiotic therapy. Corticosteroids have been recommended for treatment of lymphocytic portal hepatitis.

BACKGROUND:Malignant hyperthermia (MH) is an inherited disorder of skeletal muscle characterized by hypercarbia, rhabdomyolysis, generalized skeletal muscle contracture, cardiac dysrhythmia, and renal failure, that develops on exposure to succinylcholine or volatile anesthetic agents. All swine and up to 50% of human MH events are thought to be associated with mutations in the calcium release channel of the sarcoplasmic reticulum, also known as the ryanodine receptor (RYR1). Events resembling MH have been reported in other species, but none have undergone genetic investigation to date.METHODS:To determine the molecular basis of canine MH, a breeding colony was established with a male, mixed-breed, MH-susceptible (MHS) dog that survived an in vivo halothane-succinylcholine challenge. He was mated to three unaffected females to produce four litters and back-crossed to an affected daughter to produce one litter. One of his MHS sons was mated to an unaffected female to produce an additional litter. Forty-seven dogs were phenotyped with an in vitro contracture test and diagnosed as MHS or MH normal based on the North American in vitro contracture test protocol. Nine microsatellite markers in the vicinity of RYR1 on canine chromosome 1 (CFA01) were tested for linkage to the MHS phenotype. Mutational analysis in two MHS and two MH-normal dogs was performed with direct sequencing of polymerase chain reaction products and of cloned fragments that represent frequently mutated human RYR1 regions. A restriction fragment length polymorphism was chosen to detect the candidate mutation in the pedigree at large.RESULTS:Pedigree inspection revealed that MHS in this colony is transmitted as an autosomal dominant trait. FH2294, the marker closest to RYR1, is linked to MHS at a theta = 0.03 with a LOD score of 9.24. A T1640C mutation gives rise to an alanine for valine substitution of amino acid 547 in the RYR1 protein, generating a maximum LOD score of 12.29 at theta = 0.00. All dogs diagnosed as MHS by in vitro contracture test were heterozygous for the mutation, and all MH-normal dogs were homozygous for the T1640 allele.CONCLUSIONS:These results indicate that autosomal dominant canine MH is caused by a mutation in the gene encoding the skeletal muscle calcium release channel and that the MHS trait in this pedigree of mixed-breed dogs is in perfect cosegregation with the RYR1 V547A mutation.