Polycythemia in dogs with chronic hypoxic pulmonary disease.

BACKGROUND: Prolonged tissue hypoxia caused by chronic pulmonary disease is commonly regarded as an important mechanism in the development of secondary polycythemia, but little clinical data are available to support this hypothesis. OBJECTIVE: To study the prevalence and severity of erythrocytosis accompanying chronic hypoxic pulmonary disease in dogs. ANIMALS: Forty-seven dogs with hypoxic chronic pulmonary disease, 27 dogs with nonhypoxic chronic pulmonary disease, and 60 healthy controls. METHODS: Dogs with chronic pulmonary disease and chronic hypoxemia (partial pressure of arterial oxygen [PaO2 ] < 80 mm Hg on at least 2 arterial blood gas measurements a minimum of 1 month apart) were identified retrospectively from patient records. Association between arterial oxygen and red blood cell parameters was analyzed using Pearson's correlation coefficients and multivariable linear regression analysis. RESULTS: Red blood cell parameters measured at the end of the hypoxemia period were within the laboratory reference range in most dogs. In chronically hypoxemic dogs, hematocrit (Hct) was increased in 4/47 (8.5%; 95% confidence interval [CI], 0-17) dogs, erythrocyte count (Erytr) was increased in 12/47 (26%; 95%CI, 13-38) dogs and hemoglobin concentration (Hb) was increased in 3/47 (6.4%; 95%CI, 0-14) dogs. No marked polycythemia (Hct ≥65%) was noted in any of the dogs. Red blood cell parameters were not associated with the severity of hypoxemia (correlation to PaO2 : Erytr, r = -.14; Hb, r = -.21; Hct, r = -.14; P > .05 for all). CONCLUSIONS AND CLINICAL IMPORTANCE: Polycythemia is uncommon, and usually mild if present, in dogs with chronic hypoxia caused by pulmonary disease.

Breed-typical front limb angular deformity is associated with clinical findings in three chondrodysplastic dog breeds.

Angular front limb deformity (ALD) refers to an excessively curved limb conformation, which is seen in some chondrodysplastic dog breeds. Common characteristics of ALD include carpal valgus (VALG), front limb rotation (ROT), elbow incongruity, and lateral radial head subluxation. These may cause lameness and discomfort in affected dogs. The clinical impact and breed-specific characteristics of front limb conformation in chondrodysplastic breeds are unknown. This prospective and cross-sectional study aimed to investigate differences in front limb conformation between three chondrodysplastic breeds. We further evaluate whether front limb conformation is associated with clinical findings and limb function. We propose novel methods to classify findings in the interosseous space and to quantify lateral radial head subluxation. Data from a total of 224 front limbs from 112 dogs of three chondrodysplastic dog breeds (30 Standard Dachshunds, 29 Skye terriers, and 53 Glen of Imaal terriers) were included in the study. Front limb VALG and ROT were measured with a goniometer. From the radiographs, the elbow joint was graded for incongruity (INC), and the humeroradial angle (HRA) was measured to assess lateral radial subluxation. The association of front limb conformation with clinical signs and limb function was investigated using orthopedic examination, goniometric and kinetic measurements, and radiography. The breeds differed significantly in their front limb conformation. The Dachshund had the least ROT and the least radial head subluxation. The Skye terrier had the most VALG, the most radial head subluxation, and the largest prevalence of moderate and severe INC. The Glen of Imaal terrier had the most ROT. In addition, INC, ROT, VALG, and HRA were found to be independent of each other and were associated with several measurable clinical abnormalities and limb function such as pain, lameness, limited range of motion, and elbow joint osteoarthritis. This implies that VALG, ROT, and HRA could be used in addition to INC grading when choosing musculoskeletal characteristics of dogs suitable for breeding.

Persistent fontanelles in Chihuahuas. Part I. Distribution and clinical relevance.

BACKGROUND: The Chihuahua dog breed is known for frequent occurrence of a bregmatic fontanelle on the dorsal skull. A common conception is that this skull defect is a clinically irrelevant finding. No studies, however, describe its prevalence or whether it is accompanied by other persistent fontanelles (PFs). Although Chihuahuas are predisposed to Chiari-like malformation (CM) and syringomyelia (SM), it is unknown whether PFs occur more commonly in dogs with clinical signs that are caused by CM or SM. HYPOTHESIS/OBJECTIVES: To describe the number and location of PFs at cranial sutures (CSs) and to compare the occurrence of these PFs in dogs with and without CM/SM-related clinical signs. We hypothesized that PFs also occur commonly at lateral and caudal cranial surfaces, affect a higher number of CSs, and are larger in dogs with CM/SM-related clinical signs. ANIMALS: Fifty client-owned Chihuahuas with or without CM/SM-related clinical signs. RESULTS: Of the 50 dogs evaluated, 46 (92%) had either 1 or several PFs. The mean ± SD number of PFs was 2.8 ± 3.0 (range, 0-13). A total of 138 PFs occupied 118 CSs with 57 (48%) located dorsally, 44 (37%) caudally, and 17 (14%) laterally. The number of CSs affected by PFs was significantly higher (P ≤ .001) and total PF area was significantly larger (P = .003) in dogs with CM/SM-related clinical signs. CONCLUSIONS AND CLINICAL IMPORTANCE: Persistent fontanelles are very common in this group of Chihuahuas and appear at dorsal, lateral, and caudal cranial surfaces. They are more numerous and larger in Chihuahuas with CM/SM-related clinical signs.

Persistent fontanelles in Chihuahuas. Part II: Association with craniocervical junction abnormalities, syringomyelia, and ventricular volume.

BACKGROUND: Persistent fontanelles (PFs) are, in Chihuahuas, almost ubiquitous. Furthermore, Chihuahuas are predisposed to other craniomorphological abnormalities, including syringomyelia (SM), ventriculomegaly, and craniocervical junction (CCJ) overcrowding resulting in neural tissue deviation. It is, however, undetermined if PFs are more common in dogs with these structural abnormalities, and their etiology is unknown. HYPOTHESIS/OBJECTIVES: Persistent fontanelles are more numerous and larger in Chihuahuas with low body weight, older age, SM, dilated fourth ventricle, ventriculomegaly, and CCJ overcrowding. ANIMALS: Fifty client-owned Chihuahuas. METHODS: Cross-sectional study evaluating the association of both the number of cranial sutures affected by PFs (NAS) and total fontanelle area (TFA), based on computed tomography with SM, fourth ventricle dilatation, lateral ventricle volume, and extent of neural tissue compression at the CCJ based on magnetic resonance images. RESULTS: The NASs was higher and TFA larger in dogs with low body weight (NAS: P = .007; 95% confidence interval [CI] = 0.384-0.861; TFA: P = .002; 95% CI = -1.91 to -0.478), larger lateral ventricles (NAS: P ≤ .001; 95% CI = 1.04-1.15; TFA: P ≤ .001; 95% CI = 0.099-0.363), and more severe neural tissue compression at the CCJ (NAS: P ≤ .001; 95% CI = 1.26-2.06; TFA: P = .03; 95% CI = 0.066-1.13). Similarly, dogs with SM (NAS: P = .004; 95% CI = 1.26-3.32; TFA: mean ± SD, 130 ± 217 mm2 ; P = .05) had higher NAS and larger TFA than did dogs without SM (43.7 ± 61.0 mm2 ). Age was not associated with NAS (P = .81; 95% CI = 0.989-1.01) or TFA (P = .33; 95% CI = -0.269 to 0.092). CONCLUSIONS AND CLINICAL IMPORTANCE: Persistent fontanelles are associated with small size, SM, ventriculomegaly, and CCJ overcrowding.

Reliability of a New Bite Force Measure and Biomechanics of Modified Long Attack in Police Dogs.

Information on the biomechanics of police dogs' tasks is important in understanding their work-related injuries and dysfunctions. This study aimed to develop and test a measurement tool for dogs' functional bite force and to report modified long attack-related kinetic and kinematic values. Twenty Finnish male police dogs, 7 German Shepherd Dogs (GSDs) and 13 Belgian Shepherd Dogs, Malinois (BSDMs), were included. Dogs accelerated 25 m and bit the helper's sleeve, fitted with three force sensors. Dogs were wearing a 3D accelerometer and were videotaped with a high-speed camera. The sleeve's reliability for measuring the dog's bite force was evaluated via intraclass correlation and Cronbach's alpha. Otherwise, a Mann-Whitney U-test was used, with significance set at p = 0.05. The sleeve's test-retest reliability was moderate to good (intraclass correlation of 0.75), and internal consistency was high (Cronbach's alpha 0.75). The GSDs' median bite force was 360.4 N (interquartile range (IQR) 628.6 N) and BSDMs' 247.0 N (IQR 289.8 N). Median acceleration maximum was 7.1 gravitational force equivalent (g) and median deceleration maximum was 11.6 g, with highest recorded forces being 9.2 g and 13.1 g, respectively. The measurement sleeve was a reliable tool for measuring functional bite force in GSDs and BSDMs. Forces related to bite, approach and impact in the two breeds were reported.

Canine DVL2 variant contributes to brachycephalic phenotype and caudal vertebral anomalies.

A frameshift deletion variant in the Wnt pathway gene dishevelled 2 (DVL2) is associated with a truncated, kinked tail ("screw tail") in English Bulldogs, French Bulldogs and Boston Terriers. These breeds are also characterized by distinctive morphological traits, including a wide head, flat face and short-limbed dwarfism, which are characteristic of Robinow syndrome in humans, caused by defects in genes such as DVL1 and DVL3. Based on these phenotypic and genetic similarities, it has previously been hypothesized that the canine DVL2 variant results in a syndromic phenotype called the Robinow-like syndrome. In our study, we investigated the distribution of the DVL2 variant in 1954 dogs from 15 breeds, identifying breeds with allele variation and enabling the dissection of the genotype-phenotype correlation for the first time. With CT examinations in American Staffordshire Terriers, we confirmed that the DVL2 allele is associated with caudal vertebral malformations and a brachycephalic phenotype. We also hypothesize that the variant may be linked to additional health conditions, including brachycephalic obstructive airway syndrome and congenital heart defects. Altogether, our study strengthens the role of DVL2 as one of the contributors to the "bulldog type" morphology and features on the spectrum of human Robinow syndrome.

An across-breed validation study of 46 genetic markers in canine hip dysplasia.

BACKGROUND: Canine hip dysplasia (CHD) is a common disease, with a complex genetic background. Dogs with severe CHD sometimes also suffer from osteoarthritis (OA), an inflammatory, often painful and incurable condition. Previous studies have reported breed-specific genetic loci associated with different hip dysplasia and OA phenotypes. However, the independent replication of the known associations within or across breeds has been difficult due to variable phenotype measures, inadequate sample sizes and the existence of population specific variants. RESULTS: We execute a validation study of 46 genetic markers in a cohort of nearly 1600 dogs from ten different breeds. We categorize the dogs into cases and controls according to the hip scoring system defined by the Fédération Cynologique Internationale (FCI). We validate 21 different loci associated on fourteen chromosomes. Twenty of these associated with CHD in specific breeds, whereas one locus is unique to the across-breed study. We show that genes involved in the neddylation pathway are enriched among the genes in the validated loci. Neddylation contributes to many cellular functions including inflammation. CONCLUSIONS: Our study successfully replicates many loci and highlights the complex genetic architecture of CHD. Further characterisation of the associated loci could reveal CHD-relevant genes and pathways for improved understanding of the disease pathogenesis.

Aural CT characteristics of American Cocker Spaniels have features of both mesaticephalic and brachycephalic breeds.

Otitis externa and otitis media are common in American Cocker Spaniels, however breed-specific aural CT descriptions are currently lacking. This prospective and retrospective, observational, analytical study aimed to describe quantitative CT characteristics of the horizontal ear canal and the tympanic bulla in American Cocker Spaniels versus similar-sized mesaticephalic dogs. We prospectively performed clinical examinations and aural CT scanning for 38 American Cocker Spaniels. Computed tomographic transverse area of the osseous horizontal ear canal (TA1), transverse area of the widest air-filled part of the cartilaginous horizontal ear canal (TA2), tympanic bulla volume, and tympanic bulla wall thickness were measured. The TA1 and TA2 measurements were compared with those of 23 retrospectively recruited, similar-sized mesaticephalic dogs that had undergone CT-scanning of the head for non-ear-related reasons. The TA1 and TA2 did not differ for healthy American Cocker Spaniels and mesaticephalic dogs. Severely affected American Cocker Spaniels had significantly smaller TA2 (P < .001). The intraclass correlation coefficient for intraobserver and interobserver repeatability was 0.972 and 0.983 for TA1 and 0.994 and 0.998 for TA2, respectively. Variation between individuals was subjectively noted in healthy and affected American Cocker Spaniels, but mean tympanic bulla volume was slightly smaller in relation to body weight, and the tympanic bulla wall was thicker than in previous reports for mesaticephalic dogs. The tympanic bulla wall appeared thicker rostro-ventrally than caudo-ventrally in 44% of the dogs. Our results imply that a relatively thick tympanic bulla wall may be a normal CT variation and should be interpreted cautiously in this breed.

The intra- and intertester repeatability of radiographic elbow incongruity grading is high in chondrodystrophic dog breeds.

Elbow incongruity is a form of elbow dysplasia that causes osteoarthritis, pain, and lameness, and it is common in chondrodystrophic dog breeds. The objective of this retrospective secondary analysis study was to evaluate the intra- and interobserver repeatability of a novel radiographic incongruity grading system for assessing elbow incongruity in three chondrodystrophic dog breeds-the dachshund, Skye Terrier, and Glen of Imaal Terrier. We conducted an observer agreement study that included 220 mediolateral antebrachial radiographs from 110 dogs with the elbow in 90° flexion. The radiographs were independently assessed by three observers at three time points, using a four-stepped grading scale. The proportion of agreement and Kappa coefficient were calculated. Both the intra- and interobserver proportions of agreement were substantial when three grades were required to be identical (.705-.777 and .609, respectively), and almost perfect for two identical grades (.991-1.000 and .991, respectively). Some differences in repeatability between breeds were noted; specifically, the intraobserver repeatability was higher in the dachshund, and the interobserver repeatability was lower in the Glen of Imaal Terrier. Our study showed that the radiographic imaging protocol and incongruity grading system have high repeatability when assessing elbow incongruity in chondrodystrophic dog breeds.

The Finnish Canine Stifle Index: responsiveness to change and intertester reliability.

BACKGROUND: The responsiveness and the intertester reliability of the Finnish Canine Stifle Index (FCSI) were tested, and a cut-off between compromised and severely compromised performance level was set. METHODS: Three groups of dogs were used, 29 with any stifle dysfunction (STIF), 17 with other musculoskeletal disease except stifle (OTHER) and 11 controls (CTRL). All dogs were tested with the FCSI by the same physiotherapist at three occasions, at baseline, at six weeks and 10 weeks, and once also by another physiotherapist. RESULTS: Dogs in the STIF group demonstrated significantly higher (P<0.001) FCSI scores than in OTHER or CTRL groups at baseline. Only the STIF group showed a significant (P<0.001) change in FCSI score at all time points, indicating responsiveness to change. There were no significant differences between the evaluators (P=0.736), showing good intertester reliability, supported by moderate to good (0.78) intraclass correlation coefficient (ICC). The evaluator performing the FCSI did not have a significant effect when comparing the groups of dogs (P=0.214). The 95 per cent confidence intervals of the ICC per group were 0.79 (0.60, 0.91) for STIF, 0.83 (0.53, 0.96) for OTHER 0.78 (0.64, 0.88) for all dogs. A cut-off differentiating a severely compromised from a compromised performance was set at 120, having sensitivity of 83 per cent and specificity of 89 per cent. CONCLUSION: The FCSI is a recommendable measure of dogs' stifle functionality.

Genetic dissection of canine hip dysplasia phenotypes and osteoarthritis reveals three novel loci.

BACKGROUND: Hip dysplasia and osteoarthritis continue to be prevalent problems in veterinary and human medicine. Canine hip dysplasia is particularly problematic as it massively affects several large-sized breeds and can cause a severe impairment of the quality of life. In Finland, the complex condition is categorized to five classes from normal to severe dysplasia, but the categorization includes several sub-traits: congruity of the joint, Norberg angle, subluxation degree of the joint, shape and depth of the acetabulum, and osteoarthritis. Hip dysplasia and osteoarthritis have been proposed to have separate genetic etiologies. RESULTS: Using Fédération Cynologique Internationale -standardized ventrodorsal radiographs, German shepherds were rigorously phenotyped for osteoarthritis, and for joint incongruity by Norberg angle and femoral head center position in relation to dorsal acetabular edge. The affected dogs were categorized into mild, moderate and severe dysplastic phenotypes using official hip scores. Three different genome-wide significant loci were uncovered. The strongest candidate genes for hip joint incongruity were noggin (NOG), a bone and joint developmental gene on chromosome 9, and nanos C2HC-type zinc finger 1 (NANOS1), a regulator of matrix metalloproteinase 14 (MMP14) on chromosome 28. Osteoarthritis mapped to a long intergenic region on chromosome 1, between genes encoding for NADPH oxidase 3 (NOX3), an intriguing candidate for articular cartilage degradation, and AT-rich interactive domain 1B (ARID1B) that has been previously linked to joint laxity. CONCLUSIONS: Our findings highlight the complexity of canine hip dysplasia phenotypes. In particular, the results of this study point to the potential involvement of specific and partially distinct loci and genes or pathways in the development of incongruity, mild dysplasia, moderate-to-severe dysplasia and osteoarthritis of canine hip joints. Further studies should unravel the unique and common mechanisms for the various sub-traits.

Novel protective and risk loci in hip dysplasia in German Shepherds.

Canine hip dysplasia is a common, non-congenital, complex and hereditary disorder. It can inflict severe pain via secondary osteoarthritis and lead to euthanasia. An analogous disorder exists in humans. The genetic background of hip dysplasia in both species has remained ambiguous despite rigorous studies. We aimed to investigate the genetic causes of this disorder in one of the high-risk breeds, the German Shepherd. We performed genetic analyses with carefully phenotyped case-control cohorts comprising 525 German Shepherds. In our genome-wide association studies we identified four suggestive loci on chromosomes 1 and 9. Targeted resequencing of the two loci on chromosome 9 from 24 affected and 24 control German Shepherds revealed deletions of variable sizes in a putative enhancer element of the NOG gene. NOG encodes for noggin, a well-described bone morphogenetic protein inhibitor affecting multiple developmental processes, including joint development. The deletion was associated with the healthy controls and mildly dysplastic dogs suggesting a protective role against canine hip dysplasia. Two enhancer variants displayed a decreased activity in a dual luciferase reporter assay. Our study identifies novel loci and candidate genes for canine hip dysplasia, with potential regulatory variants in the NOG gene. Further research is warranted to elucidate how the identified variants affect the expression of noggin in canine hips, and what the potential effects of the other identified loci are.

Thoracic high resolution CT using the modified VetMousetrap™ device is a feasible method for diagnosing canine idiopathic pulmonary fibrosis in awake West Highland White Terriers.

Canine idiopathic pulmonary fibrosis is a chronic, progressive interstitial lung disease particularly prevalent in West Highland White Terriers. In the present prospective pilot study, we evaluated the feasibility of modified VetMousetrap™ device in high resolution CT to detect idiopathic pulmonary fibrosis in West Highland White Terriers. Twelve awake West Highland White Terriers with canine idiopathic pulmonary fibrosis and 24 clinically healthy West Highland White Terriers were scanned using a helical dual slice scanner utilizing VetMousetrap™ device without or with minimal chemical restraint with butorphanol. Three evaluators blindly assessed the images for image quality and the presence of canine idiopathic pulmonary fibrosis related imaging findings such as ground glass opacity and reticular opacities. Additionally, the attenuation of the lung was quantified with ImageJ software using histogram analysis of density over the lung fields. Computed tomography was successfully completed and motion artifact ranked in statistical analysis barely noticeable to mild in all dogs. The agreement between imaging findings and clinical status was very good with overall κ value 0.91 and percentage of agreement of 94%. There was also very good intraobserver (κrange = 0.79-0.91) and interobserver agreement (κ = 0.94). Moderate to severe ground glass opacity was present in all affected dogs. In the ImageJ analysis, a significant difference in lung attenuation between the study groups was observed. We conclude that modified VetMousetrap™ device is applicable in diagnosing canine idiopathic pulmonary fibrosis in awake West Highland White Terriers avoiding anesthetic risk in these often severely hypoxic patients.

Skin and ear health in a group of English bulldogs in Finland - a descriptive study with special reference to owner perceptions.

BACKGROUND: Dermatological conditions are common in English bulldogs (EBs). HYPOTHESIS/OBJECTIVES: This cross-sectional study describes the dermatological health status of a group of EBs and compares the results with owner perceptions and its possible impact on quality of life (QoL). Computed tomographic (CT) findings of the ear canals were compared between EBs and mesaticephalic dogs. ANIMALS: Twenty-seven EBs participating in a health study in Finland. METHODS AND MATERIALS: A QoL questionnaire was completed for EBs with owner-reported clinical signs referable to the skin or ear. Clinical evaluation included recording the Canine Atopic Dermatitis Extent and Severity Index, the Otitis Index Score, false paw pad grading and the presence of interdigital furunculosis. These were summed to form a total clinical score (TCS). The cross-sectional surface areas of the horizontal ear canals were measured from CT images and compared with respective images of 14 mesaticephalic dogs collected from a patient database. RESULTS: All 27 EBs had abnormal findings on dermatological examination, but 37% of the owners had not recognized skin or ear signs. The median QoL score was 5.0 (range 0-12) and correlated with TCS (correlation coefficient = 0.507, P < 0.05). English bulldogs had narrower horizontal ear canals than mesaticephalic dogs (P < 0.001). CONCLUSIONS AND CLINICAL IMPORTANCE: All EBs had abnormal dermatological findings that were unnoticed or considered to be of minor significance to the QoL by most owners. Narrow ear canals were common, possibly related to the brachycephalic conformation of the breed.

A homozygous missense variant in the alkaline phosphatase gene ALPL is associated with a severe form of canine hypophosphatasia.

Inherited skeletal disorders affect both humans and animals. In the current study, we have performed series of clinical, pathological and genetic examinations to characterize a previously unreported skeletal disease in the Karelian Bear Dog (KBD) breed. The disease was recognized in seven KBD puppies with a variable presentation of skeletal hypomineralization, growth retardation, seizures and movement difficulties. Exome sequencing of one affected dog revealed a homozygous missense variant (c.1301T > G; p.V434G) in the tissue non-specific alkaline phosphatase gene, ALPL. The identified recessive variant showed full segregation with the disease in a cohort of 509 KBDs with a carrier frequency of 0.17 and was absent from 303 dogs from control breeds. In humans, recessive and dominant ALPL mutations cause hypophosphatasia (HPP), a metabolic bone disease with highly heterogeneous clinical manifestations, ranging from lethal perinatal hypomineralization to a relatively mild dental disease. Our study reports the first naturally occurring HPP in animals, resembling the human infantile form. The canine HPP model may serve as a preclinical model while a genetic test will assist in breeding programs.

Recurrent bacterial pneumonia in Irish Wolfhounds: Clinical findings and etiological studies.

BACKGROUND: Increased incidence of bacterial pneumonia (BP) has been reported in Irish Wolfhounds (IWHs), and recurrence of BP is common. The etiology of recurrent pneumonia in IWHs is largely unknown. OBJECTIVES: To describe clinical findings in IWHs with recurrent BP and investigate possible etiologies. ANIMALS: Eleven affected IWHs, 25 healthy IWHs, 28 healthy dogs of other Sighthound breeds, and 16 healthy dogs of other breeds. METHODS: Prospective cross-sectional observational study. All affected IWHs underwent thorough clinical examinations including thoracic radiographs, thoracic computed tomography, electron microscopic evaluation of ciliary structure, and bronchoscopy and bronchoalveolar lavage fluid (BALF) cytology and culture. Serum and BALF immunoglobulin concentrations were measured using an ELISA method, and peripheral blood lymphocyte subpopulations were analyzed using flow cytometry. Esophageal function was assessed by fluoroscopy (n = 2). RESULTS: Median age of onset was 5.0 years (range, 0.4-6.5 years), and when presented for study, dogs had experienced a median of 5 previous episodes of BP (range, 2-6). The following predisposing factors to BP were detected: focal bronchiectasis (10/11), unilateral (2/9) and bilateral (1/9) laryngeal paralysis, and esophageal hypomotility (2/2). Local or systemic immunoglobulin deficiencies or primary ciliary defects were not detected. CONCLUSIONS AND CLINICAL IMPORTANCE: Recurrent BP affects mostly middle-aged and older IWHs without any evident immune deficit or primary ciliary defects. Focal BE was a frequent finding in affected dogs and likely contributed to the development of recurrent respiratory infections. Laryngeal and esophageal dysfunction identified in a minority of dogs may contribute to recurrent BP.

Cross-sectional area and fat content in dachshund epaxial muscles: an MRI and CT reliability study.

MRI and CT are frequently used to diagnose spinal diseases in dogs. These modalities have detected epaxial muscle degeneration in dachshunds with intervertebral disc herniation. However, research on the reliability of epaxial muscular measurements is limited in veterinary medicine. The aims of the study were to assess the intrarater and inter-rater reliability of epaxial muscle cross-sectional area (CSA) and fat content measurements on MRI and CT images in dachshunds, and to compare the CSA measurement between the two modalities. MRI and CT images of 10 healthy dachshunds were evaluated. Two blinded observers assessed MRI CSA, MRI fat content, CT CSA and CT muscle attenuation of three thoracolumbar epaxial muscles using OsiriX. The results showed 'substantial' to 'almost perfect' intrarater reliability (intraclass correlation coefficient (ICC) 0.828-0.998) and inter-rater reliability (ICC 0.685-0.854) for all variables. When individual spinal segments were analysed, the intrarater and inter-rater reliability decreased and the confidence intervals increased. There was positive correlation (r= 0.719-0.841, P=0.001) and high agreement (0.824-0.894) for the measured CSA between MRI and CT. Epaxial muscle CSA and fat content can be reliably measured on MRI and CT, bearing in mind that measurement of certain segments requires adequate training.

Comparison of submaximal exercise test results and severity of brachycephalic obstructive airway syndrome in English bulldogs.

Canine brachycephalic obstructive airway syndrome (BOAS) is a complex respiratory disease related to congenitally flattened facial and skull anatomy. BOAS causes respiratory distress, heat and exercise intolerance, and gastrointestinal signs. English bulldogs (EB) have a high prevalence of BOAS. Currently, the severity of BOAS signs in veterinary practice is assessed subjectively. To reduce BOAS in brachycephalic breeds, an objective and easy-to-use tool could help breeders select healthier animals. Exercise tests, such as the 6 min walk test (distance walked measured) or the 1000 m walk test (duration measured), could be used to assess the severity of BOAS, as exercise intolerance and impaired recovery are key features of BOAS. This study evaluated the severity of signs and anatomic components of BOAS in a group of prospectively recruited young adult EBs (n = 28) and investigated the correlations of the 6 min walk test or the 1000 m walk test with a veterinary assessment of BOAS severity, using an ordinal 4 level scale of respiratory signs. EBs with more severe BOAS walked a shorter distance, more slowly and their recovery from exercise took longer than those with only mild signs of BOAS. Control dogs of different breeds (n = 10) performed the exercise tests significantly better (i.e. longer distance, faster time and recovery) than EBs. Increases in body temperature during exercise were significantly higher in EBs than in controls. The results of this study support the use of exercise tests for objective evaluation of the severity of BOAS in EBs.

Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions.

Precision of spinal radiographs as a screening test for intervertebral disc calcification in Dachshunds.

Among dog breeds, the Dachshund has the highest lifetime incidence of intervertebral disc disease (IVDD). Intervertebral disc (IVD) calcification is an indicator of severe degeneration that predisposes to disc herniation. IVDD is heritable in Dachshunds, and in some countries, breeding candidates are screened to reduce IVDD occurrence by selecting dogs according to their score of radiographically detectable intervertebral disc calcification (RDIDC) and excluding dogs with ≥5 RDIDCs from breeding. This study evaluated the precision of scoring spinal radiographs for IVD calcification and subsequent classification of Dachshund dogs for breeding based on their RDIDC score. Digital radiographs of the spine were obtained in 19 clinically healthy, young adult Dachshunds, and scored for RDIDC independently by five scorers with varying levels of experience, three times each. Within scorer (repeatability) and between scorer (reproducibility) variability was estimated both at the individual IVD level and at the whole dog level for breeding classification purposes. At the IVD level, some degree of scorer effect was supported by the pairwise repeatability (92.3%; 95% CI: 88.8-94.7%) being marginally higher than the reproducibility (89.2%; 95% CI: 85.7-91.8%). Scorer-specific patterns confirmed the presence of scorer subjectivity. Repeatability significantly increased with scorer experience but the reproducibility did not. RDIDC scoring repeatability and reproducibility substantially decreased at the cervicothoracic spine region, likely due to anatomical superimpositions. At the dog level, a breeding classification could be repeated by the same scorer for 83.6% (95% CI: 73.8-90.2%) of the dogs, and was reproduced between two scorers for 80.2% (95% CI: 66.6-89.1%) of the dogs. The repeatability of breeding classification also seemed to increase with scorer experience but not the reproducibility. Overall, RDIDC scoring revealed some degree of inconsistency explained by scorer subjectivity and inexperience, and anatomical superimpositions. Scorer training and experience is strongly recommended to improve test precision and ensure appropriate classification of Dachshunds for breeding.