Linda Morrison

Expression of epidermal growth factor receptor (EGFR) and Ki67 in feline oral squamous cell carcinomas (FOSCC)

The aims of this study were to establish expression of epidermal growth factor receptor (EGFR) and Ki67 in 67 archived biopsy samples of feline oral squamous cell carcinomas (FOSCCs) and to establish if the expression of either markers was predictive of survival. Samples were immunohistochemically labelled for the two proteins and scored. Statistical analyses of data, including Kaplan-Meier survival curves, were performed. All samples expressed both markers although levels differed between samples. Median overall survival was 46 days and 1-year survival was 5%. There was no correlation between Ki67 and EGFR scores (Pearsons correlation coefficient, P = 0.861). Low cellular proliferation (low Ki67 score) was positively correlated with an overall longer survival (Log Rank, P = 0.02) and a trend towards better survival for the high EGFR group was observed (Log Rank, P = 0.076). Ki67 and EGFR immunostaining in FOSCC may be of value as biochemical markers for screening of biopsies from cases of FOSCC.

Idiopathic bovine neonatal pancytopenia in a Scottish beef herd

PANCYTOPENIA, due to hypoplastic or aplastic bone marrow, has historically been uncommon in cattle. Fatal haemorrhagic pancytopenia has been reported in cattle due to the ingestion of trichloroethylene-extracted soya oil meal (TCESOM) ([Rundles 1958][1]), bracken fern ( Pteridium species) ([Hirono

Arrhythmogenic right ventricular cardiomyopathy as a cause of unexpected cardiac death in two horses

Postmortem and histological examination of the hearts from two horses, a five-yearold Clydesdale gelding and a 15-year-old cob gelding, revealed changes characteristic of arrhythmogenic right ventricular cardiomyopathy. In both cases, on gross examination, the right ventricular endocardium and interventricular septum were almost entirely replaced with a gelatinous yellow fibroareolar tissue. This tissue was histologically a combination of fibrous and adipose tissue that had replaced the normal myofibres and disrupted the Purkinje fibres.

Lymphoproliferative disease with features of lymphoma in the Central Nervous System of a horse

Lymphoma (malignant lymphoma, lymphosarcoma) is uncommon in horses in the United Kingdom. This report describes an unusual form of lymphoproliferative disease with features of lymphoma restricted to the central nervous system (CNS) and with no evidence of a primary lesion elsewhere. Immunohistochemical examination defined an overwhelming predominance of T lymphocytes with admixed B lymphocytes and activated macrophages. This case exemplifies the challenges associated with definitive diagnosis of lymphoproliferative disease of the equine CNS.

WT1 expression in breast cancer disrupts the epithelial/mesenchymal balance of tumour cells and correlates with the metabolic response to docetaxel

WT1 is a transcription factor which regulates the epithelial-mesenchymal balance during embryonic development and, if mutated, can lead to the formation of Wilms’ tumour, the most common paediatric kidney cancer. Its expression has also been reported in several adult tumour types, including breast cancer, and usually correlates with poor outcome. However, published data is inconsistent and the role of WT1 in this malignancy remains unclear. Here we provide a complete study of WT1 expression across different breast cancer subtypes as well as isoform specific expression analysis. Using in vitro cell lines, clinical samples and publicly available gene expression datasets, we demonstrate that WT1 plays a role in regulating the epithelial-mesenchymal balance of breast cancer cells and that WT1-expressing tumours are mainly associated with a mesenchymal phenotype. WT1 gene expression also correlates with CYP3A4 levels and is associated with poorer response to taxane treatment. Our work is the first to demonstrate that the known association between WT1 expression in breast cancer and poor prognosis is potentially due to cancer-related epithelial-to-mesenchymal transition (EMT) and poor chemotherapy response.

Presence of Systemic Inflammatory Response Syndrome Predicts a Poor Clinical Outcome in Dogs with a Primary Hepatitis

Primary hepatopathies are a common cause of morbidity and mortality in dogs. The underlying aetiology of most cases of canine hepatitis is unknown. Consequently, treatments are typically palliative and it is difficult to provide accurate prognostic information to owners. In human hepatology there is accumulating data which indicates that the presence of systemic inflammatory response syndrome (SIRS) is a common and debilitating event in patients with liver diseases. For example, the presence of SIRS has been linked to the development of complications such as hepatic encephalopathy (HE) and is associated with a poor clinical outcome in humans with liver diseases. In contrast, the relationship between SIRS and clinical outcome in dogs with a primary hepatitis is unknown. Seventy dogs with histologically confirmed primary hepatitis were enrolled into the study. Additional clinical and clinicopathological information including respiratory rate, heart rate, temperature, white blood cell count, sodium, potassium, sex, presence of ascites, HE score, alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin and red blood cell concentration were available in all cases. The median survival of dogs with a SIRS score of 0 or 1 (SIRS low) was 231 days compared to a median survival of 7 days for dogs with a SIRS score of 2, 3 or 4 (SIRS high) (p<0.001). A Cox proportional hazard model, which included all other co-variables, revealed that a SIRS high score was an independent predictor of a poor clinical outcome. The effect of modulating inflammation on treatment outcomes in dogs with a primary hepatitis is deserving of further study.

Thromboembolism in Dogs with Protein-Losing Enteropathy with Non-Neoplastic Chronic Small Intestinal Disease.

Dogs with protein-losing enteropathy (PLE) are suggested to be at increased risk of developing thromboembolic events. However, with some exceptions, there are very few reports of thromboembolism in such dogs. This multicentre retrospective observational study describes a case series of thromboembolism (TE) in eight dogs with PLE secondary to non-neoplastic, chronic small intestinal disease. Seven dogs had poorly controlled PLE when the thromboembolic event occurred. Pulmonary thromboembolism (PTE) occurred in six dogs, while one dog developed splenic vein thrombosis and another had concurrent splenic vein and aortic TE. Six dogs died, all with PTE. Antithrombin activity was decreased in one of two dogs in which it was measured. Serum cobalamin and folate concentrations were measured in three dogs and cobalamin was subnormal in all three. Serum magnesium, measured in two dogs, was low in both. Dogs with uncontrolled chronic small intestinal disease and PLE are at risk for developing serious life-threatening TE, mostly PTE.

A Rare Case of Deep Digital Flexor Tendinopathy Following Centesis of the Navicular Bursa

Navicular bursa (NB) centesis is a common diagnostic and therapeutic procedure in equine practice. This case report documents the clinical, diagnostic imaging and histological findings in a horse with a suspected iatrogenic deep digital flexor tendon (DDFT) injury following centesis of the NB via a modified distal plantar approach (placement of two needles in a weight bearing position). Although it cannot be proven with absolute certainty, the authors believe that this is the first reported case where NB centesis is the likely cause of a DDFT lesion, and with magnetic resonance imaging performed both pre- and post-centesis. With this potential, though rare, complication of the procedure, alternative tendon sparing injection techniques should be considered prior to NB centesis in certain cases.

Endocarditis and ventricular wall abscessation in a vasectomised Herdwick ram

A four-year-old vasectomised Herdwick ram presented with a two-day history of inappetence, lethargy, weakness and exercise intolerance. Clinical examination revealed mild tachypnoea and hyperpnoea and marked tachycardia and pallor. No anaemia was present. Thoracic ultrasonography revealed thickening of the right ventricular wall and increased pericardial and peritoneal fluid. A diagnosis of congestive heart failure was made and the animal was euthanased. Necropsy revealed a subendocardial abscess adjacent to the right atrioventricular valve, the leaflets of which were distorted. The gross appearance of this lesion is similar to that described for valvular ring abscesses in human beings.

A Pre-clinical Animal Model of Trypanosoma brucei Infection Demonstrating Cardiac Dysfunction

African trypanosomiasis (AT), caused by Trypanosoma brucei species, results in both neurological and cardiac dysfunction and can be fatal if untreated. Research on the pathogenesis and treatment of the disease has centred to date on the characteristic neurological symptoms, whereas cardiac dysfunction (e.g. ventricular arrhythmias) in AT remains largely unstudied. Animal models of AT demonstrating cardiac dysfunction similar to that described in field cases of AT are critically required to transform our understanding of AT-induced cardiac pathophysiology and identify future treatment strategies. We have previously shown that T. brucei can interact with heart muscle cells (cardiomyocytes) to induce ventricular arrhythmias in ex vivo adult rat hearts. However, it is unknown whether the arrhythmias observed ex vivo are also present during in vivo infection in experimental animal models. Here we show for the first time the characterisation of ventricular arrhythmias in vivo in two animal models of AT infection using electrocardiographic (ECG) monitoring. The first model utilised a commonly used monomorphic laboratory strain, Trypanosoma brucei brucei Lister 427, whilst the second model used a pleomorphic laboratory strain, T. b. brucei TREU 927, which demonstrates a similar chronic infection profile to clinical cases. The frequency of ventricular arrhythmias and heart rate (HR) was significantly increased at the endpoint of infection in the TREU 927 infection model, but not in the Lister 427 infection model. At the end of infection, hearts from both models were isolated and Langendorff perfused ex vivo with increasing concentrations of the β-adrenergic agonist isoproterenol (ISO). Interestingly, the increased frequency of arrhythmias observed in vivo in the TREU 927 infection model was lost upon isolation of the heart ex vivo, but re-emerged with the addition of ISO. Our results demonstrate that TREU 927 infection modifies the substrate of the myocardium in such a way as to increase the propensity for ventricular arrhythmias in response to a circulating factor in vivo or β-adrenergic stimulation ex vivo. The TREU 927 infection model provides a new opportunity to accelerate our understanding of AT-related cardiac pathophysiology and importantly has the required sensitivity to monitor adverse cardiac-related electrical dysfunction when testing new therapeutic treatments for AT.