Toward the most ideal case-control design with related and unrelated dogs in whole-exome sequencing studies.

With the recent development of whole-exome sequencing enrichment designs for the dog, a novel tool for disease-association studies became available. The aim of disease-association studies is to identify one or a very limited number of putative causal variants or genes from the large pool of genetic variation. To maximize the efficiency of these studies and to provide some directions of what to expect, we evaluated the effect on variant reduction for various combinations of cases and controls for both dominant and recessive types of inheritance assuming variable degrees of penetrance and detectance. In this study, variant data of 14 dogs (13 Labrador Retrievers and one Dogue de Bordeaux), obtained by whole-exome sequencing, were analyzed. In the filtering process, we found that unrelated dogs from the same breed share up to 70% of their variants, which is likely a consequence of the breeding history of the dog. For the designs tested with unrelated dogs, combining two cases and two controls gave the best result. These results were improved further by adding closely related dogs. Reduced penetrance and/or detectance has a drastic effect on the efficiency and is likely to have a profound effect on the sample size needed to elucidate the causal variant. Overall, we demonstrated that sequencing a small number of dogs results in a marked reduction of variants that are likely sufficient to pinpoint causal variants or genes.

Assessment of medial coronoid disease in 180 canine lame elbow joints: a sensitivity and specificity comparison of radiographic, computed tomographic and arthroscopic findings.

BACKGROUND: Diagnostic imaging is essential to assess the lame patient; lesions of the elbow joint have traditionally been evaluated radiographically, however computed tomography (CT) has been suggested as a useful technique to diagnose various elbow pathologies. The primary objective of this study was to determine the sensitivity and specificity of CT to assess medial coronoid disease (MCD), using arthroscopy as gold standard. The secondary objective was to ascertain the radiographic sensitivity and specificity for MCD compared with CT. METHODS: For this study 180 elbow joints were assessed, of which 141 had been examined with radiography, CT and arthroscopy; and 39 joints, had radiographic and CT assessment. Sensitivity and specificity were calculated for CT and radiographic findings using available statistical software. RESULTS: Sensitivity and specificity of CT using arthroscopy as gold standard resulted in high values for sensitivity (100 %) and specificity (93 %) for the assessment of MCD. For the radiographic evaluation, a sensitivity of 98 % and specificity of 64 - 69 % using CT as the technique of reference, were found. DISCUSSION: These results suggest that in case of doubt during radiographic assessment, CT could be used as a non-invasive technique to assess the presence of MCD. CONCLUSION: Based on the high sensitivity and specificity obtained in this study it has been considered that CT, rather than arthroscopy, is the preferred noninvasive technique to assess MCD lesions of the canine elbow joint.

Observational study of the clinical value of the canine osteoarthritis staging tool.

The aim of this multi-centred, cohort, prospective, observational study was to evaluate the clinical application of the canine osteoarthritis staging tool (COAST), in dogs affected by osteoarthritis (OA). In all dogs, a COAST stage was obtained based on the Liverpool Osteoarthritis in Dogs (LOAD) score and a complete orthopaedic and radiographic examination. The severity of OA (COAST stage) was scored as 1 (preclinical), 2 (mild), 3 (moderate), and 4 (severe). These scores were compared with the overall subjective opinion of experienced orthopaedic surgeons who examined the dogs (Clinical Opinion). Data were analysed with descriptive statistic, multiple regression analysis, chi-square and Bland-Altman tests (P < 0.05). In total, 362 evaluations were performed in 202 dogs. Clinical Opinion had a greater proportion of stage 1 and 2 cases compared to COAST (P < 0.0001). The proportion of stage 4 cases was higher in COAST compared to Clinical Opinion (P < 0.0001). The proportions of Stage 3 cases were similar in the two evaluation systems. COAST had a strong correlation (r = 0.79; P < 0.01) with Clinical Opinion. Overall, the two evaluation systems exhibited strong agreement (mean bias 0.51). Stages 1 and 2 had weaker agreement (mean bias 1.04 and 0.75, respectively), than stage 3 and stage 4 (mean bias 0.46 and 0.0, respectively).

Medial humeral epicondylar lesions in the canine elbow. A review of the literature.

A calcified fragment near the medial epicondyle of the humerus was originally described as an ununited medial epicondyle in 1966. Since then several papers reported similar lesions as a cause of elbow lameness. The aetiology and clinical significance of those lesions is poorly known. This paper gives an overview of the veterinary and human literature in an attempt to explain the aetiology and to suggest a diagnostic protocol and treatment plan.

Detection of osteoarthritis in dogs by metabolic, pro-inflammatory and degenerative synovial fluid biomarkers and traditional radiographic screening: A pilot study.

Secondary osteoarthritis (OA) is a slow progressive, common disorder of synovial joints in dogs. It is characterized by a loss of balance between the synthesis and degeneration of articular cartilage components. Its diagnosis is currently based on the presence of clear radiographic changes, which only occur in the later stages of the disease. Hence, early diagnosis of OA remains a major problem. Therefore, interest in synovial fluid (SF) biomarkers has emerged. Besides pro-inflammatory and degenerative markers, i.e. tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), tenascin-c (TN-C) and matrix metalloproteinase-2 (MMP-2), metabolic parameters, i.e. pH, glucose and lactate, can potentially be used to detect OA. The current study demonstrated statistically significant differences in the SF levels of pH, glucose and lactate between OA-affected and normal joints. In addition, the in-house validated immuno-assays for TNF-alpha, IL-1beta, TN-C and MMP-2 allowed to demonstrate also statistically significant differences in the SF concentrations for all these biomarkers - except TNF-alpha - between OA-affected and normal joints. However, no correlation was found between any of these biomarkers and the currently used radiographic scoring system for OA in dogs. Future research is warranted to explore the potential of these biomarkers in the early detection of OA and in the severity characterization of this disease.

A review of the human and veterinary literature on local anaesthetics and their intra-articular use. Relevant information for lameness diagnosis in the dog.

Lameness in dogs is often a diagnostic challenge. In many cases it is difficult to determine the exact localisation of lameness because of the absence of palpable changes, or because of unreliable pain response due to high pain tolerance, stress or aggression of the dog. In horses and humans, intra-articular administration of local anaesthetics is commonly used for diagnostic purposes. In this review, information from human and veterinary studies on different local anaesthetic agents and their application for diagnostic intra-articular anaesthesia is given. Based on this information, a protocol for diagnostic intra-articular anaesthesia in the dog can be developed and evaluated in future studies.

Long-term follow-up after arthroscopic tenotomy for partial rupture of the biceps brachii tendon.

OBJECTIVE: To report the long-term clinical outcomes and radiographic results in dogs diagnosed with partial bicipital rupture and treated by arthroscopic tenotomy. MATERIALS AND METHODS: The medical records of dogs that had undergone arthroscopic tenotomy were retrospectively reviewed. Inclusion criteria for this study were: performance of an arthroscopic tenotomy between August 1999 and July 2007, availability of arthroscopic records data for review, and ability to obtain follow-up data for more than one year after arthroscopic tenotomy. In all cases, owners were interviewed during follow-up appointments or via telephone to determine perceived outcome after surgery. RESULTS: Forty-seven arthroscopic tenotomies were performed on 40 dogs without any major surgical complications. Long-term follow-up examinations, ranging from 12 months to 48 months (mean 26 months) after the tenotomy, were obtained for 24 dogs (25 shoulders). Clinical outcome was assessed as excellent in 22 shoulders, with each dog showing a full return of limb function. A total of 10 dogs (11 joints) were evaluated radiographically; six joints revealed no progression of pathology, and five joints showed a limited progression of pathology. CONCLUSION: Arthroscopic tenotomy in the treatment of bicipital partial rupture yields favourable long-term clinical results and a high degree of owner satisfaction. The feasibility of this technique and the long-term clinical and radiographic outcome from our study indicate that this technique can be considered a reliable and safe treatment for partial bicipital rupture.

Elbow lameness in dogs of six years and older: arthroscopic and imaging findings of medial coronoid disease in 51 dogs.

OBJECTIVES: To report on the frequency and distribution of lesions of the medial coronoid process in dogs of six years of age and older, and to describe the arthroscopic findings in the affected joints. To compare those lesions seen in 'old' dogs with those seen in 'young' dogs between the ages of five and 18 months. METHODS: A retrospective study of dogs six-years-old and older admitted for elbow lameness and subsequent elbow arthroscopy. The dogs were divided into groups according to the lesions of the medial coronoid process diagnosed during arthroscopic examination and computed tomography (CT). The radiographic degree of osteoarthritis (OA) and arthroscopically diagnosed lesions on the medial humeral condyle are described. RESULTS: In 51 'old' dogs, five types of lesions could be identified on arthroscopy and CT: chondromalacia-like lesions (2%), fissures (27.5%), non-displaced fragments (12%), displaced fragments (27.5%), and erosions within the medial compartment without fragmentation (31%). A significantly different distribution of lesions was seen in 'young' dogs: fissures (23%), non-displaced fragments (45%), displaced fragments (29%), and erosions within the medial compartment without fragmentation (3%). No difference in radiographic degree of OA was seen between the two groups. CLINICAL SIGNIFICANCE: This study demonstrates the relatively high incidence of medial coronoid disease in dogs older than six years of age, and it highlights one particular problem in 'old' dogs: the complete erosion of the medial compartment.

Single-phase bone scintigraphy in dogs with obscure lameness.

OBJECTIVES: To evaluate the diagnostic merits of scintigraphy in dogs with clinically obscure lameness origin. METHODS: In 43 dogs, the scintigraphic findings were compared with the results of subsequent radiological, computed tomography and/or arthroscopic findings and/or additional neurological examination. RESULTS: In all dogs, focal increased uptake was found in one or more joints or bones. The presence of associated pathology was confirmed by radiography, computed tomography and/or arthroscopy of the limb region of interest. Additional neurological examination was performed when indicated. In cases of elbow pathology, unilateral involvement of the elbow was confirmed with computed tomography/arthroscopy in 14 cases, while bilateral increased uptake could not be confirmed with radiography or computed tomography in three cases. Three dogs showed an increased activity in one joint on the bone scan, while computed tomography, arthroscopy or radiography revealed bilateral joint disease. Generalised mild increased radionuclide uptake in all joints and bones was observed in the lame limb in 15 forelimbs and five hindlimbs. Generalised prominent uptake of an entire limb was noted in three cases suffering from neurological disease. CLINICAL SIGNIFICANCE: Scintigraphy may provide information on areas of increased radionuclide uptake, thereby aiding in the localisation of obscure lameness. Generalised mild increased uptake of radionuclide in all joints and bones in the lame limb may occur in the older dog. The generalised prominent uptake, seen in three cases with neurological disease, may resemble reflex sympathetic dystrophy syndrome seen in human beings.

Comparison of subchondral lesion size between clinical and non-clinical medial trochlear ridge talar osteochondritis dissecans in dogs.

In this retrospective study of nine dogs exhibiting bilateral medial trochlear ridge talar osteochondritis dissecans (MTRT-OCD) and unilateral hind limb lameness, we compared subchondral lesion size in limbs with visible lameness, with contralateral lesions that were not associated with any visible lameness. All MTRT-OCD lesions were imaged by radiography and computed tomography (CT). The dimensions of subchondral bone lesions were measured (length, width and depth) using CT software. Similar to a method used in humans, the estimated volume (length x width x depth) and cross sectional area (length x width) were calculated and compared. We found that MTRT-OCD lesions causing visible lameness were significantly larger, and were associated with more joint thickening and degenerative joint disease than contralateral lesions that were not associated with any apparent lameness. As in the disease of shoulder osteochondritis dissecans, there is probably a correlation between the size of MTRT-OCD lesions and the symptoms of lameness.

Diagnostic findings in a lame-free dog with complete rupture of the biceps brachii tendon. A case report in a unilaterally affected working Labrador Retriever.

A case of a complete rupture of the biceps brachii tendon in a lame-free three-year-old Labrador Retriever is described. The dog had a history of chronic lameness following a trauma, but had become lame-free shortly before presentation. Clinical examination, biceps tendon test and shoulder instability tests under general anaesthesia were inconspicuous for shoulder instability. Routine radiographs, arthrography and ultrasound were suspicious for bicipital tendopathy. The definite diagnosis of a complete rupture of the biceps brachii tendon was made upon arthroscopic inspection of the glenohumeral joint.

Review of the literature: elbow incongruity in the dog.

Elbow incongruity is the term to describe bad alignment of the joint surfaces of the elbow. Two features illustrate incongruity of the elbow: an abnormal shape of the ulnar trochlear notch and a step between the radius and ulna, caused by either a short radius or a short ulna. It has been suggested that both an elliptical notch, and a step, can cause increased local pressure within the joint, resulting in loose fragments at different locations: ununited anconeal process (UAP), fragmented coronoid process (FCP), osteochondritis dissecans of the humeral condyle (OCD). These lesions are grouped under the term 'elbow dysplasia' and are the most frequent causes of front leg lameness in the dog. Although several radiographic features to diagnose incongruity have been described, the 'scoring' of incongruity is subjective because there is currently no objective method to measure the degree of incongruity. Because superimposition is avoided, CT is suggested as a standard technique to measure incongruity. Arthroscopy on the other hand, allows the direct visualisation of the intra-articular structures and their abnormalities. Information on both techniques are still relatively new. Several surgical techniques have been proposed to restore joint congruity; the one most frequently used is an ulnar osteotomy. But because of possible complications, other techniques are being developed. Reports evaluating the results of the different techniques are not yet available.

Computerized tomography compared with radiography in the diagnosis of lateral trochlear ridge talar osteochondritis dissecans in dogs.

In this retrospective study, we compared the value of radiographic and computerized tomographic (CT) imaging for the diagnosis of lateral trochlear ridge talar osteochondritis dissecans (LTRT-OCD) in 11 tarsocrural joints. The flexed dorsoplantar skyline and the planta-rolateral-dorsomedial projections were the most reliable for radiographic detection of OCD fragments (in 7 of the 11 joints). Overall, radiography detected OCD fragments in 8 of 11 joints. By contrast, the OCD fragments could be visualized and exactly localized by CT in all 11 joints. Computerized tomography allowed the talar ridges to be inspected without superimposition of any bony structures. This information may be very useful when minimal invasive techniques are used to treat LTRT-OCD lesions. The findings of this study suggest that CT is superior to radiography for making a diagnosis of LTRT-OCD in the dog.

Erosion of the medial compartment of the canine elbow: occurrence, diagnosis and currently available treatment options.

Erosion of the medial compartment of the elbow joint refers to full thickness cartilage loss with exposure of the subchondral bone (modified Outerbridge grades 4-5) of the medial part of the humeral condyle (MHC) and the corresponding ulnar contact area. This finding may appear in the absence of an osteochondral fragment or a cartilage flap, or in combination with fragmentation of the medial coronoid process (MCP) or osteochondritis dissecans (OCD) of the MHC. With regard to the prognosis, it is important to diagnose these severe erosions. Imaging of cartilage lesions by means of radiography, ultrasonography, computed tomography or magnetic resonance imaging is challenging in dogs. In contrast, direct arthroscopic inspection provides detailed information about the cartilage. The treatment of these severe erosions is difficult because of the limited regenerative capacity of cartilage and presumed mechanical or physical triggering factors. Several conservative and surgical treatment methods have been proposed to treat elbows with severe cartilage defects. However, due to irreversible loss of cartilage, the prognosis in these cases remains guarded.

The ligaments of the canine hip joint revisited.

Numerous conventional anatomical textbooks describe the canine hip joint, but many contradictions, in particular regarding the ligament of the femoral head, are present. This paper presents a brief overview of the different literature descriptions. These are compared with own observations that have resulted in a revised description of the anatomy of the ligament of the femoral head in the dog. To this purpose, the hip joints of 41 dogs, euthanized for reasons not related to this study and devoid of lesions related to hip joint pathology, were examined. It was observed that the ligament of the femoral head is not a single structure that attaches only to the acetabular fossa, as generally accepted, but it also connects to the transverse acetabular ligament and is complemented by a strong accessory ligament that courses in caudal direction to attach in the elongation of the acetabular notch that extends on the cranioventral surface of the body of the ischium. The description of this accessory ligament in conventional anatomical handbooks is incomplete. This description of the accessory ligament of the femoral head could support the research unravelling the etiopathogenesis of hip instability.

Elbow arthroscopy in clinically normal dogs.

After a detailed anatomic study to determine puncture sites, 10 cadaver elbows from 5 dogs were examined arthroscopically to study the normal intraarticular anatomy, as viewed from the medial side. Subsequent dissection revealed absence of neurovascular injury and only minor iatrogenic damage to the cartilage. The technique was clinically applied and evaluated in 13 dogs (26 joints). The dogs recovered without complications. The technique proved to be safe and reliable for direct examination of nearly the entire joint. More specifically, it allowed systematic inspection of the medial and lateral humeral condyles, the medial and lateral coronoid processes, the caudal and middle parts of the head of the radius, the olecranon (including the anconeal process), and the medial collateral ligament.

Magnetic resonance arthrography of the scapulohumeral joint in dogs, using gadopentetate dimeglumine.

Six scapulohumeral joints (3 normal joints and 3 joints with radiographic evidence of osteochondrosis) underwent conventional magnetic resonance (MR) imaging and MR scapulohumeral arthrography to evaluate delineation of the articular cartilage. The MR arthrography was performed, using 5 ml of 500 microM gadopentetate dimeglumine (Gd-DTPA) as a contrast medium. Delineation of normal articular cartilage and cartilage defects was less accurate after intra-articular administration of Gd-DTPA. Therefore, it was concluded that MR arthrography with Gd-DTPA is unrewarding for evaluation of osteochondrosis lesions.

Pathologic correlations with magnetic resonance images of osteochondrosis lesions in canine shoulders.

Twelve shoulders in 6 dogs with clinical and radiographic evidence of osteochondrosis were examined by magnetic resonance imaging performed on a 0.5-T superconductive system. Scans were obtained with 5-mm-thick slices and 0.75-mm pixel size. Unenhanced T1-weighted spin-echo and unenhanced T2*-weighted gradient-echo images were obtained, using a high-resolution surface coil. The T1-weighted sequences were repeated after IV injection of 0.1 mmol of gadopentetate dimeglumine/kg of body weight (0.2 ml/kg). In 6 joints, histologic examination of synovia and articular cartilage was carried out. The magnetic resonance images were correlated with arthrographic, arthroscopic, and histologic findings. Magnetic resonance imaging was useful in evaluating the extent of subchondral lesions and the severity of inflammatory changes within the subchondral bone. Areas of low signal (visible subchondrally on T1-weighted images that were enhanced by administration of contrast medium) indicated active inflammatory changes within the subchondral bone. Although articular cartilage discontinuity could be detected, loose cartilage flaps could not always be reliably demonstrated. Signal inhomogeneity within the articular cartilage was presumed to correspond with zones of cartilage degeneration.

Diagnostic and surgical arthroscopy in osteochondrosis lesions.

In the dog, as in man and the horse, arthroscopy has an important role in treatment of joint disease. In the shoulder, elbow, and stifle joints, surgical arthroscopy can and should replace the classical surgical methods of treating osteochondrosis lesions. In elbow and tarsocrural joint disorders, the diagnostic potentials of arthroscopy are evident. With the established techniques, not only can the lesions be diagnosed with accuracy, but they can also be treated within the same procedure, making arthroscopy the treatment of choice to deal with osteochondrosis lesions. Without a doubt, arthroscopy will play an important role in the understanding of the etiopathology of different joint diseases, especially within the elbow joint, where so many questions remain unresolved. The advantages of arthroscopy in the diagnosis and treatment of osteochondrosis have also encouraged other veterinary surgeons to adopt the technique. In the developmental stage of arthroscopy in the dog, a frequently expressed comment was that arthrotomy was as valuable and as easy (or easier) to perform as arthroscopy. Now that the advantages of arthroscopy have been demonstrated, the skepticism has changed into enthusiasm. The same evolution is noted with arthroscopy in both man and the horse.

Arthroscopic findings in 100 dogs with elbow lameness.

Elbow arthroscopy was performed in 100 dogs with foreleg lameness localised to the elbow joint, bilaterally in 48 of them, making a total of 148 joints examined. Lesions in the area of the medial coronoid process varied from cartilage fissures in 13 to fragmentation in 91, chondromalacia-like lesions in 27. This last lesion has not been reported previously in the veterinary literature. Kissing lesions on the medial side of the humeral condyle were present in 83 joints, whereas lesions of osteochondritis dissecans were found in only three. All these lesions were associated with varying signs of synovitis and arthrosis. Arthroscopic signs of arthrosis and/or synovitis without associated medical coronoid lesions were found in 14 elbow joints.