Brendan Corcoran

Nonprimate hepaciviruses in domestic horses, United kingdom.

Viruses related to human hepatitis C virus infect horses in the United Kingdom without evidence of hepatic or other systemic disease.

Chronic pulmonary disease in West Highland white terriers

This paper describes the clinical features, and diagnostic findings of a chronic respiratory condition in 29 West Highland white terriers. Typically, the dogs were coughing chronically, had dyspnoea and tachypnoea of varying severity, and had deteriorated progressively over months to year. The mean (sem) survival time in months from the clinical signs being first noted by the owners was 17.9 (2.3). Most cases had a combination of respiratory signs, but coughing was the predominant sign in 18 cases. Inspiratory crackles were audible on chest auscultation in 28 cases, 10 of which were also wheezing. Rhonchi were the predominant sound in the remaining case. The main radiographic changes were mild to severe increased interstitial markings in all cases, with additional bronchial markings in 14 of the dogs. Right-sided cardiomegaly (cor pulmonale) was recorded in 15. Bronchoscopic findings in 17 of the dogs were either normal or involved a mild airway mucoid reaction in eight. Chronic mucosal changes were observed in eight, but in two this finding was equivocal. Dynamic changes to the lumen of the airway were present in seven cases. No significant haematological or biochemical changes could be detected in 20 cases, but four cases were hypercholestrolaemic. A histopathological assessment of four cases revealed alveolar septal fibrosis to be the predominant change. Prednisolone, with or without bronchodilators, was the most commonly used therapy, and the response was variable. The condition appears to be associated with significant pulmonary interstitial fibrosis of unknown aetiology and has clinical similarities to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in human beings.

Viraemic frequencies and seroprevalence of non-primate hepacivirus and equine pegiviruses in horses and other mammalian species

Non-primate hepacivirus (NPHV), equine pegivirus (EPgV) and Theilers disease associated virus (TDAV) are newly discovered members of two genera in the Flaviviridae family, Hepacivirus and Pegivirus respectively, that include human hepatitis C virus (HCV) and human pegivirus (HPgV). To investigate their epidemiology, persistence and clinical features of infection, large cohorts of horses and other mammalian species were screened for NPHV, EPgV and TDAV viraemia and for past exposure through serological assays for NPHV and EPgV-specific antibodies. NPHV antibodies were detected in 43% of 328 horses screened for antibodies to NS3 and core antibodies, of which three were viraemic by PCR. All five horses that were stablemates of a viraemic horse were seropositive, as was a dog on the same farm. With this single exception, all other species were negative for NPHV antibodies and viraemia: donkeys (n=100), dogs (n=112), cats (n=131), non-human primates (n=164) and humans (n=362). EPgV antibodies to NS3 were detected in 66.5% of horses, including 10 of the 12 horses that had EPgV viraemia. All donkey samples were negative for EPgV antibody and RNA. All horse and donkey samples were negative for TDAV RNA. By comparing viraemia frequencies in horses with and without liver disease, no evidence was obtained that supported an association between active NPHV and EPgV infections with hepatopathy. The study demonstrates that NPHV and EPgV infections are widespread and enzootic in the study horse population and confirms that NPHV and potentially EPgV have higher frequencies of viral clearance than HCV and HPgV infections in humans.

Doppler echocardiography in the dog: measurement variability and reproducibility

Serial Doppler echocardiographic examinations were carried out in random order on six boxer dogs, on 3 separate days, by two experienced Doppler echocardiographers, to assess measurement variability and reproducibility of 65 parameters. Large numbers of parameters exhibited significant differences for each of the categories of intraobserver, interobserver, interday and interoperator. The coefficients of variation for all parameters measured ranged from 5.03 to 46.43%, but most were less than 20%. In general, least variation was found for the intraobserver category, and the best reproducibility for M-mode and left ventricular volumetric data. The worst reproducibility was found for tricuspid inflow and pulmonary venous flow measurements. The results of this study suggest differences greater than 20% for serial scans must be achieved to document genuine change, although the specific data should be consulted. Furthermore, variability and reproducibility are improved if a single experienced operator/observer acquires and measures serial scans.

Distribution of myofibroblasts, smooth muscle-like cells, macrophages, and mast cells in mitral valve leaflets of dogs with myxomatous mitral valve disease.

OBJECTIVE To map the cellular distribution and phenotypic alteration of the predominant stromal cell population throughout the entire valve length of dogs with myxomatous mitral valve disease (MMVD). SAMPLE POPULATION 31 mitral valve complexes (ie, mitral valve leaflets) collected from 4 clinically normal dogs and 27 dogs with MMVD of varying severity. PROCEDURES A combination of standard histologic and immunohistochemical techniques was used to identify pathologic changes, the presence of mast cells, and the density and distribution of cells expressing vimentin, desmin, alpha-smooth muscle actin (alpha-SMA), smooth muscle myosin, and the macrophage marker MAC387. RESULTS Vimentin-positive cells predominated in the mitral valve leaflets from clinically normal dogs and were located throughout the leaflet, but cell density was appreciably decreased with disease progression, and minimal cell numbers were found in distinct myxomatous areas. Cells that were positive for alpha-SMA were uncommon in the mitral valve leaflets from clinically normal dogs and only seen in appreciable numbers in mitral valves of dogs with severe late-stage disease, in which cells were typically located close to the ventricularis valve surface. A slight increase in mast cell numbers was observed in the distal zone of affected leaflets. CONCLUSIONS AND CLINICAL RELEVANCE Activated-myofibroblasts (alpha-SMA-positive cells) were increased and inactive-myofibroblasts (vimentin-positive cells) were reduced in mitral valve leaflets of dogs with MMVD, compared with that of clinically normal dogs. Impact on Human Medicine-This is the first description of spatial and temporal alterations in mitral valve cells of any species with MMVD and has clinical importance in the understanding of disease development in dogs and humans.

Outcome in 55 dogs with pulmonic stenosis that did not undergo balloon valvuloplasty or surgery

OBJECTIVE To determine the outcome, independent predictors of cardiac death, and the Doppler-derived pressure gradient cut-off for predicting cardiac death in dogs with pulmonic stenosis, with or without tricuspid regurgitation, that do not undergo balloon valvuloplasty or valve surgery. METHODS Review of medical records of two UK referral centres between July 1997 and October 2008 for all cases of pulmonic stenosis that had no balloon valvuloplasty or valve surgery. Inclusion criteria included a diagnosis of pulmonic stenosis; spectral Doppler pulmonic velocity greater than 1·6 m/s; characteristic valve leaflet morphological abnormalities. Exclusion criteria included concurrent significant cardiac defects, including tricuspid dysplasia. Dogs with tricuspid regurgitation were included. Dogs were classified according to Doppler-derived pressure gradients into mild, moderate or severe pulmonic stenosis categories. RESULTS Presence of tricuspid regurgitation and severe stenosis were independent predictors of cardiac death. A pulmonic pressure gradient of more than 60 mmHg was associated with 86% sensitivity, and 71% specificity of predicting cardiac death. CLINICAL SIGNIFICANCE There is an increased probability of cardiac death in those cases which have a pulmonary pressure gradient greater than 60 mmHg and tricuspid regurgitation, though the effect of severity of tricuspid regurgitation on outcome was not measurable because of small sample sizes. These animals might benefit from intervention.

Molecular changes in fibrillar collagen in myxomatous mitral valve disease

INTRODUCTION Myxomatous mitral valve disease (MMVD) is the single most common acquired cardiac disease of dogs and is a disease of significant veterinary importance. It also bears close similarities to mitral valve prolapse in humans and therefore is a disease of emerging comparative interest. We have previously mapped the structure of collagen fibrils in valve leaflets using synchrotron X-rays and have demonstrated changes in collagen structure associated with the regions of disease. METHODS Differential scanning calorimetry (DSC),biochemical assay of collagen content, high-performance liquid chromatography (HPLC), and neutron diffraction were combined with further analysis of our previous X-ray data to elucidate molecular changes in fibrillar collagen in mild to moderately affected MMVD dogs. RESULTS Comparing diseases and adjacent grossly uninvolved areas in the same leaflets, there was a 20% reduction in collagen fibrils, but only a 10% depletion of collagen content. The enthalpy of collagen denaturation was reduced in affected areas. Chromatography showed a 25% decrease in mature nonreducible covalent cross-links in the affected samples, and neutron diffraction data showed fewer reducible immature covalent cross-links in grossly uninvolved tissue samples. CONCLUSIONS Mild to moderate MMVD in the dog is associated with a marginal decline in collagen content in overtly diseased areas of valves, but more importantly is associated with an increase in immature collagen content. These changes will contribute to the mechanical dysfunction of the leaflet, and this study provides important information on the structure-mechanical alterations associated with this disease. The data suggests MMVD involves a dyscollagenesis process in the development of valve pathology.

Characterisation and differentiation potential of bone marrow derived canine mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have potential for use in regenerative therapeutics, since they are capable of multi-lineage differentiation. In this study, primary canine MSCs (cMSCs) were isolated from bone marrow aspirates and characterised using marker expression and morphology. cMSCs expressed CD44 and STRO-1, but not CD34 or CD45. Morphologically, cMSCs were similar to previously described MSCs and were capable of chondrocyte differentiation towards articular type cartilage, characterised by increased collagen type II vs. collagen type I expression and expression of Sox-9. cMSCs demonstrated no significant alterations in marker profiles and failed to differentiate into cardiomyocytes in response to a cardiac differentiation protocol or when co-cultured with canine cardiac stem cells. The study indicated that cMSCs can be derived readily from bone marrow and are capable of differentiation into articular cartilage, but appear to have limited ability to differentiate into cardiomyocytes using current protocols.

Obstructive inflammatory laryngeal disease in three cats

Three cats with upper respiratory tract obstruction due to laryngeal inflammation are presented. Cervical radiography showed the presence of a soft tissue mass in the laryngeal region in all cases, and laryngoscopy allowed direct visualization of a mass associated with the larynx. Laryngeal samples were obtained by a combination of fine needle aspiration, cutting biopsy forceps, by ventral laryngotomy, and at post-mortem. Histopathology of the laryngeal samples showed the presence of a predominantly granulomatous inflammation, with macrophage and lymphocyte infiltration. One case was euthanased due to severe dyspnoea. The remaining two cases underwent combined medical (corticosteroid and antibiotic) and surgical (permanent tracheostomy or excision of laryngeal tissue by ventral laryngotomy) treatment. One case died of an undetermined cause 15 weeks after surgery while the other case remains clinically well 20 months after diagnosis. Recognition of the existence of granulomatous laryngitis is important as clinical signs and radiographic findings are indistinguishable from laryngeal neoplasia.

Pulsed-wave Doppler tissue imaging velocities in normal geriatric cats and geriatric cats with primary or systemic diseases linked to specific cardiomyopathies in humans, and the influence of age and heart rate upon these velocities.

Pulsed-wave Doppler tissue imaging (pw-DTI) techniques allow the non-invasive assessment of myocardial dynamics. pw-DTI has demonstrated regional and global diastolic impairment in various forms of human and feline cardiomyopathy. We hypothesise that in geriatric cats with systemic diseases that have been linked to specific cardiomyopathies in human beings, the myocardial velocity profile will be altered when compared to either normal or hypertrophic cardiomyopathy (HCM) cats; and that both age and heart rate have a significant affect upon pw-DTI velocities. The aims of this study were to determine whether the feline M-mode or myocardial velocity profile is altered in geriatric cats with disease states that have been linked to specific cardiomyopathies in humans when compared to normal geriatric cats or geriatric cats with HCM and to determine whether age or heart rate has a significant effect upon pw-DTI velocities within these groups of cats. Sixty-six cats aged 8 years or above were included in the study, and were divided as follows: Unaffected (n=8), basilar septal bulge (BSB) (17), HCM (14), hyperthyroid (HiT4) (12) and chronic renal failure (CRF) (15). Systolic blood pressure was normal in all the cats. pw-DTI systolic (S′), early (E′) and late diastolic (A′) velocities were assessed from standardised sites within the myocardium, and the relationships between these and disease group, age and heart rate were then assessed. In cats with HCM, the E′ velocity was decreased at various sites. Conversely, the HiT4 cats demonstrated increased S′ velocities. The only site at which the age of the cat was significantly related to myocardial velocities was the S′ velocity from the apical mid-septum. There were also significant positive relationships between heart rate and the magnitude of myocardial S′, E′ and A′ velocities of radial motion and S′ and A′ velocities of longitudinal motion. pw-DTI detected diastolic dysfunction in untreated cats with HCM and increased systolic function in HiT4 cats. The age of the cat was of little significance, whereas heart rate significantly influenced myocardial velocity profiles.