Author Correction: Development and performance of a targeted whole exome sequencing enrichment kit for the dog (Canis Familiaris Build 3.1).

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Evaluation of heart rate variability in dogs during standard and microburst vagus nerve stimulation: a pilot study.

Vagus nerve stimulation (VNS) is an established treatment for epilepsy and depression in human patients, but in both humans and dogs, optimal stimulation parameters remain unknown. Delivering afferent bursts of stimulation may be promising as a means of increasing efficacy, but evaluation of potential effects on the heart due to unavoidable efferent stimulation is required. The present study investigated heart rate variability (HRV) in healthy Beagle dogs treated with 1 h of sham, standard or microburst left-sided VNS in a crossover design. No significant differences were found between the stimulation paradigms for any of the cardiac parameters. Short-term left-sided VNS, including a novel bursting pattern (microburst VNS), had no statistically significant effect on HRV in ambulatory healthy dogs. Studies in a larger number of animals with long-term VNS are recommended.

Development and performance of a targeted whole exome sequencing enrichment kit for the dog (Canis Familiaris Build 3.1).

Whole exome sequencing is a technique that aims to selectively sequence all exons of protein-coding genes. A canine whole exome sequencing enrichment kit was designed based on the latest canine reference genome (build 3.1.72). Its performance was tested by sequencing 2 exome captures, each consisting of 4 pre-capture pooled, barcoded Illumina libraries on an Illumina HiSeq 2500. At an average sequencing depth of 102x, 83 to 86% of the target regions were completely sequenced with a minimum coverage of five and 90% of the reads mapped on the target regions. Additionally, it is shown that the reproducibility within and between captures is high and that pooling four samples per capture is a valid option. Overall, we have demonstrated the strong performance of this WES enrichment kit and are confident it will be a valuable tool in future disease association studies.

Surgical repair of a congenital sternal cleft in a cat.

OBJECTIVE: To describe the clinical findings, diagnosis, and treatment of an incomplete cleft of the 5th-8th sternebra and a cranioventral abdominal wall hernia in a 2 month old Ragdoll kitten and to evaluate the short- and long-term outcome. STUDY DESIGN: Clinical report. ANIMALS: Ragdoll cat (n = 1), 2 months old. METHODS: Sternal cleft was confirmed by thoracic radiographs. Computed tomography (CT) was used to plan an optimal surgical approach. A ventral median incision was made, starting at the 3rd sternebra and extended into the abdomen. Ostectomy of the proximal part of the 5th left sternebra was performed. Lateral periosteal flaps were created, unfolded, and absorbable monofilament sutures preplaced to facilitate closure and the repair was reinforced by 2 peristernal sutures. A bone graft was applied, and the free margin of the omentum was sutured to the cranial aspect of the wound. RESULTS: No major complications occurred. At 3 weeks, CT scan confirmed approximation of the hemisternebrae and at 10 months, complete fusion of the hemisternebrae had not occurred, but a strong connection of the sternal bars was present. CONCLUSION: Sternal cleft is a rare congenital abnormality that can be corrected surgically with favorable outcome.

Prospective evaluation of healthy Ragdoll cats for chronic kidney disease by routine laboratory parameters and ultrasonography.

Ragdoll breeder organisations often forewarn Ragdoll cat owners that renal problems may develop as a result of polycystic kidney disease (PKD), chronic interstitial nephritis, familial renal dysplasia or nephrocalcinosis. Healthy Ragdoll and non-Ragdoll cats were prospectively evaluated by measuring serum creatinine and urea concentrations, routine urinalysis and abdominal ultrasonography. All Ragdoll cats also underwent genetic PKD testing. One hundred and thirty-three Ragdoll and 62 control cats were included. Ragdoll cats had significantly lower serum urea concentrations and higher urinary specific gravity. However, median creatinine concentration, median urinary protein-to-creatinine ratio, and the proportion of cats with serum creatinine or urea concentration exceeding the reference interval did not differ. One or more renal ultrasonographical changes were detected in 66/133 (49.6%) Ragdoll and in 25/62 (40%) control cats. Ragdoll cats showed significantly more frequent segmental cortical lesions (7.5% versus 0%), abnormal renal capsule (19.5% versus 8%) and echogenic urine (51.9% versus 25.8%). Chronic kidney disease (CKD) was ultrasonographically suspected in 7/133 (5.3%) Ragdoll and in none of the control cats, which approached significance. Laboratory parameters confirmed kidney dysfunction only in 1/7 of these Ragdoll cats. All Ragdoll cats were PKD negative. In conclusion, first, breed-specific serum creatinine reference intervals are not likely required for Ragdoll cats. Second, renal ultrasonographical abnormalities are common, both in Ragdoll and non-Ragdoll cats. Third, healthy young Ragdoll cats are uncommonly affected by PKD and CKD, but an increased susceptibility of Ragdoll cats to develop CKD cannot be excluded. Finally, Ragdoll cats are predisposed to segmental cortical lesions, which may indicate renal infarction or cortical scarring.

Morphometric dimensions of the caudal cervical vertebral column in clinically normal Doberman Pinschers, English Foxhounds and Doberman Pinschers with clinical signs of disk-associated cervical spondylomyelopathy.

Client-owned, clinically normal Doberman Pinschers (n=20), English Foxhounds (n=17), and Doberman Pinschers with clinical signs of disk-associated cervical spondylomyelopathy (DA-CSM) (n=17) were prospectively studied. All dogs underwent magnetic resonance imaging (MRI) of the cervical vertebral column. To evaluate vertebral canal stenosis, the canal occupying ratios of the spinal cord and cerebrospinal fluid (CSF)-column were calculated from C5 to C7. To evaluate the degree of spinal cord compression and the amount of canal compromise, the compression ratio, remaining spinal cord and CSF-column area, and vertebral canal and dorsoventral vertebral canal compromise ratios were calculated at the site of most severe compression. For each canal occupying ratio, there was a significant higher value (implicating less space available for the spinal cord in the vertebral canal) at the level of C7 for clinically affected Doberman Pinschers compared with clinically normal English Foxhounds. The remaining spinal cord area was significantly smaller in dogs with clinically relevant spinal cord compression compared to dogs with clinically irrelevant spinal cord compression. Relative stenosis of the caudal cervical vertebral canal occurred more often in Doberman Pinschers with DA-CSM compared to English Foxhounds and a critical degree of spinal cord compression should be reached to result in clinical signs.

Detection of innocent systolic murmurs by auscultation and their relation to hematologic and echocardiographic findings in clinically normal Whippets.

OBJECTIVE: To determine murmur prevalence by auscultation of 105 apparently healthy Whippets without signs of cardiac disease, to determine the origin of these murmurs, and to evaluate the influence of sex, type of pedigree (ie, bred for showing or racing), and training on these murmurs. DESIGN: Cross-sectional study. ANIMALS: 105 client-owned Whippets. PROCEDURES: All dogs were auscultated by the first author and underwent a complete physical and cardiological examination, together with a hematologic assessment. Several RBC variables and echocardiographic variables were compared between dogs with or without a murmur at the level of the aortic valve. RESULTS: 44 of 105 (41.9%) dogs had no murmur. A soft systolic murmur was present with point of maximal intensity at the level of the aortic valve in 50 (47.6%) dogs, at the level of the pulmonic valve in 8 (7.6%) dogs, and at the level of the mitral valve in 3 (2.9%) dogs. No significant differences were found in heart rate, rhythm, murmur presence, point of maximal intensity, and murmur grade between males and females, between dogs with race- and show-type pedigrees, or between dogs in training and not in training. Dogs with a murmur at the level of the aortic valve had a significantly higher aortic and pulmonic blood flow velocity and cardiac output, compared with dogs without a murmur. CONCLUSIONS AND CLINICAL RELEVANCE: Whippets have a high prevalence of soft systolic murmurs in the absence of any structural abnormalities, which fit the description of innocent murmurs. No influence of sex, pedigree type, or training was found on the occurrence of these murmurs in Whippets.

Low-field magnetic resonance imaging findings of the caudal portion of the cervical region in clinically normal Doberman Pinschers and Foxhounds.

OBJECTIVE: To determine the spectrum and frequency of abnormalities for low-field magnetic resonance imaging (MRI) examinations of clinically normal Doberman Pinschers and Foxhounds. ANIMALS: 37 clinically normal dogs (20 Doberman Pinschers and 17 Foxhounds). PROCEDURES: For each dog, MRI of the cervical vertebrae (sagittal, dorsal, and transverse T1- and T2-weighted images) was performed. Variables assessed were intervertebral disk degeneration, disk-associated compression, compression of the dorsal portion of the spinal cord, vertebral body abnormalities, and changes in intraparenchymal signal intensity. Associations between these variables and age, breed, sex, and location of the assessed intervertebral disk spaces were evaluated. RESULTS: Severe MRI abnormalities were detected in 17 dogs, including complete disk degeneration (n = 4 dogs), spinal cord compression (3), or both (10). Vertebral body abnormalities were detected in 8 dogs, and hyperintense signal intensity was detected in 2 dogs. Severity of disk degeneration and disk-associated compression was significantly associated with increased age. There was a significant association between disk degeneration, disk-associated compression, and compression of the dorsal aspect of the spinal cord and location of the assessed intervertebral disk space, with the intervertebral disk spaces in the caudal portion of the cervical region being more severely affected. CONCLUSIONS AND CLINICAL RELEVANCE: Abnormalities were commonly seen on MRI examinations of the caudal portion of the cervical vertebral column and spinal cord of clinically normal Doberman Pinchers and Foxhounds. Such lesions were probably part of the typical spinal cord degeneration associated with the aging process of dogs.

Electrocardiographic reference values in whippets.

The aim of this study was to determine the electrocardiographic characteristics of whippets and to compare the results with published reference values for a general dog population. Electrocardiographic parameters from 105 healthy whippets were used to establish reference values for the breed. The most important differences compared to published reference values were the higher median R-wave amplitudes in leads II, CV(6)LL and CV(6)LU. For some parameters (P-wave amplitude, ST-segment deflection and T-wave amplitude in lead II; R-wave amplitude in CV(5)RL), a marked percentage of the whippet values were above the published maximum reference data. The results confirmed that whippets have electrocardiographic characteristics similar to those reported in athletic heart syndrome in humans. Some of these characteristics could be erroneously taken as evidence of cardiac disease and clinicians should be aware of these factors to prevent unnecessary investigations in healthy dogs.

Echocardiographic reference values in whippets.

The aim of the study was to establish reference echocardiographic values for whippets, to compare these values with previously published reference values for the general dog population, and to determine whether there is an influence of gender and breeding lines on echocardiographic measurements. Echocardiographic parameters from 105 apparently healthy whippets without cardiac symptoms were used to establish reference values for the breed and to compare these values with two previously reported reference ranges. The coefficients of the allometric equation Y= aM(b), useful to reconstruct normal M-mode and two-dimensional average values for whippets of varying weights, were calculated, as well as the lower and upper limits of the 95% prediction interval. First, we found that whippets have a significantly larger left ventricular diameter, increased left ventricular wall, and interventricular septum thickness than expected, in diastole as well as in systole. Fractional shortening was significantly lower than the reference value. Second, comparing males and females, taking body weight differences into account, females had a significantly larger left ventricular diameter in diastole and systole. Minor differences were found between racing and show pedigree dogs. In conclusion, the results of this study confirm that breed-specific reference values are needed in echocardiography. In whippets, the values found in this study can be used as references in order to avoid overinterpretation of cardiac dilation, hypertrophy, and/or decreased contractility in these dogs.

Serum thyroid hormone concentrations and thyroglobulin autoantibodies in trained and non-trained healthy whippets.

Numerous factors including non-thyroidal systemic diseases and drug administration can significantly alter canine thyroid function test results. Furthermore, the importance of breed specific variations has probably been underestimated. In this study, total thyroxine (TT4), free thyroxine (FT4), canine endogenous thyroid stimulating hormone (cTSH) serum concentrations and thyroglobulin autoantibodies (TgAA) were determined in a population of healthy whippets and compared to a control group of different breeds. Mean TT4 values were significantly lower in the whippets but no significant differences were seen between whippets and control dogs for FT4 and for cTSH. The prevalence of serum TgAA in the whippets was 2%, and this was not significantly different from the controls. The results suggest a breed variation for TT4, but not for FT4, cTSH and TgAA serum concentrations in whippets. Serum thyroid hormone concentrations were also compared between trained and non-trained whippets and it was concluded that regular training did not seem to have any significant influence.

Vertebral heart size ranges specific for whippets.

To assess the influence of breed, breeding lines, and training on heart size, the vertebral heart size (VHS) was evaluated on left-to-right lateral, right-to-left lateral, dorsoventral, and ventrodorsal thoracic radiographs from 44 whippets free from cardiac and pulmonary disease. In lateral views, the VHS was 11.0 +/- 0.5 vertebrae (mean +/- SD) on right-to-left lateral and 11.3 +/- 0.5 vertebrae on left-to-right lateral radiographs, being larger than the 9.7 +/- 0.5 vertebrae proposed by Buchanan (P<0.0001). The VHS on left-to-right lateral views was larger than on right-to-left lateral views (P<0.0001). The VHS was 10.5 +/- 0.6 vertebrae on dorsoventral radiographs and 11.1 +/- 0.6 vertebrae on ventrodorsal radiographs. Both values were larger than the 10.2 +/- 1.5 vertebrae (dorsoventral) (P<0.0082) or 10.2 +/- 0.8 vertebrae (ventrodorsal) (P<0.0001) proposed by Buchanan. In addition, the VHS on ventrodorsal views was larger than on dorsoventral views (P<0.0001). Dogs out of racing pedigree lines had a significantly larger VHS than those out of show pedigree lines, and trained dogs had a significantly larger VHS than nontrained dogs. Because most trained dogs came out of racing pedigree lines, and all nontrained dogs came out of show pedigree lines, however, it is difficult to determine whether the higher VHS for trained dogs is due to genetic influences or training, or both. In conclusion, it is important to take into account the breed and the radiographic view when evaluating heart size in thoracic radiographs of whippets to avoid overinterpretation of cardiac enlargement in these dogs.