Standardised histological criteria are now available for the diagnosis of canine chronic hepatitis (CH). CH is common in dogs, but no studies have reported breed, age and gender distributions in the United Kingdom (UK). The objective of this study was to determine which breeds had an increased risk for developing CH in the UK and to report the age and gender distribution for those breeds. The databases of six veterinary histopathology laboratories were searched for cases with a histological diagnosis of CH according to standardised criteria. The breed, age and gender of dogs was recorded and compared to a control population to calculate the odds ratio and 95% confidence intervals for developing CH.A total of 551 cases of CH were identified, consisting of 61 breeds. Nineteen breeds were represented by five or more cases. Breeds with an increased risk for developing CH included the American cocker spaniel, Cairn terrier, Dalmatian, Dobermann pinscher, English cocker spaniel, English springer spaniel, Great Dane, Labrador retriever and Samoyed. The median age at diagnosis for all breeds with CH was 8 years (range 7 months to 16 years). Dalmatians, Dobermann pinschers and English springer spaniels with CH were significantly younger than Cairn terriers, English cocker spaniels and Labrador retrievers with CH. Females were over-represented when all cases were examined together. In conclusion, several breeds in the UK have an increased risk of CH, some of which have not been previously reported.
Lumpy skin disease is a high-consequence disease in cattle caused by infection with the poxvirus lumpy skin disease virus (LSDV). The virus is endemic in most countries in Africa and an emerging threat to cattle populations in Europe and Asia. As LSDV spreads into new regions, it is important that signs of disease are recognized promptly by animal caregivers. This study describes the gross, microscopic, and ultrastructural changes that occur over time in cattle experimentally challenged with LSDV. Four calves were inoculated with wildtype LSDV and monitored for 19 to 21 days. At 7 days after inoculation, 2 of the 4 cattle developed multifocal cutaneous nodules characteristic of LSD. Some lesions displayed a targetoid appearance. Histologically, intercellular and intracellular edema was present in the epidermis of some nodules. Occasional intracytoplasmic inclusion bodies were identified in keratinocytes. More severe and consistent changes were present in the dermis, with marked histiocytic inflammation and necrotizing fibrinoid vasculitis of dermal vessels, particularly the deep dermal plexus. Chronic lesions consisted of full-thickness necrosis of the dermis and epidermis. Lesions in other body organs were not a major feature of LSD in this study, highlighting the strong cutaneous tropism of this virus. Immunohistochemistry and electron microscopy identified LSDV-infected histiocytes and fibroblasts in the skin nodules of affected cattle. This study highlights the noteworthy lesions of LSDV and how they develop over time.
Despite extensive research over many decades, human breast cancer remains a major worldwide health concern. Advances in pre-clinical and clinical research has led to significant improvements in recent years in how we manage breast cancer patients. Although survival rates of patients suffering from localized disease has improved significantly, the prognosis for patients diagnosed with metastatic disease remains poor with 5-year survival rates at only 25%. In vitro studies using immortalized cell lines and in vivo mouse models, typically using xenografted cell lines or patient derived material, are commonly used to study breast cancer. Although these techniques have undoubtedly increased our molecular understanding of breast cancer, these research models have significant limitations and have contributed to the high attrition rates seen in cancer drug discovery. It is estimated that only 3-6% of drugs that show promise in these pre-clinical models will reach clinical use. Models that can reproduce human breast cancer more accurately are needed if significant advances are to be achieved in improving cancer drug research, treatment outcomes, and prognosis. Canine mammary tumors are a naturally-occurring heterogenous group of cancers that have several features in common with human breast cancer. These similarities include etiology, signaling pathway activation and histological classification. In this review article we discuss the use of naturally-occurring canine mammary tumors as a translational animal model for human breast cancer research.
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.
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 (Pearson's 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.
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.
Background Protein‐losing enteropathy (PLE) because of chronic inflammatory enteropathy (CIE) in dogs is often treated with a combination of glucocorticoids and second‐line immunosuppressant (SLI). This combined approach might not be necessary in all dogs. Hypothesis/objectives To describe diagnostic features and outcomes of dogs with PLE treated with glucocorticoids alone (group P) or with glucocorticoids and SLI (group S). Animals Thirty‐one dogs with PLE. Material and methods Retrospective analysis of signalment data from diagnostic procedures, treatment, and outcome of dogs with CIE/PLE (from 2015 to 2017), using the hospital's digital case database. Dogs with hypoalbuminemia and CIE were included. Because of a stepwise treatment algorithm, dogs were allocated to group P or S. Time to serum albumin concentrations ≥20 g/L and survival data were collected. Dogs were additionally categorized by their albumin and cobalamin serum concentrations. Multivariate and univariate analysis as well as Pearson's correlation and Kaplan‐Maier survival analysis were performed. Results Seventeen dogs were included in group P and 14 in group S. World Small Animal Veterinary Association score of the duodenum was different between groups (P = .05), but none of the other examined data. Median time until serum albumin reached >20 g/L was 13 days. Median survival time after start of treatment was 85 days (range, 13‐463 days) in group P and 166 days (range, 8‐390 days) in group S. Conclusion and Clinical Importance No routine diagnostic test was predictive of clinical response, treatment group, or outcome. Glucocorticoid treatment alone can be appropriate in dogs with PLE.
The incidence of peritonitis ranges from 1 episode every 24 patient treatment months to 1 episode every 60 patient treatment months [Keane WF, et al. ISPD Guidelines/Recommendations. Adult peritoneal dialysis-related peritonitis treatment recommendations: 2000 update. Perit Dial Int 2000; 20:396–411.]. Gram-positive organisms account for over 80% of continuous ambulatory peritoneal dialysis (PD)-associated peritonitis. Recent fear of vancomycin-resistant enterococci (VRE) has prompted suggestions of limiting vancomycin use. Fifty-one episodes of peritonitis in 30 patients studied over 2 years were evaluated. Cloudiness of the PD fluid and/or abdominal pain were considered suggestive of peritonitis and were confirmed by cell count and culture. Baseline cell count, Gram stain, and cultures were obtained, with periodic follow-up. Patients were randomized to receive either vancomycin 1 g/L intraperitoneally (IP) as loading dose, repeated on day 5 or day 8, depending on residual renal function, for 2 weeks, or cefazolin 1 g in the first PD bag and continued with 125 mg/L every exchange for 2 or 3 weeks, depending on culture results. All patients also received gentamicin 40 mg IP every day until the culture results were available. A similar randomized trial comparing vancomycin and cefazolin in the past used a lower concentration of cefazolin 50 mg/L [Flanigan MJ, Lim VS. Initial treatment of dialysis associated peritonitis: a controlled trial of vancomycin versus cefazolin. Perit Dial Int 1991; 11:31–7.]. Peritoneal dialysate fluid cultures revealed 31 (60.7%) gram-positive organisms, 7 (13.7%) gram-negative organisms, and 2 (3.9%) cultured yeast; 11 (21.5%) cultures yielded no growth. The incidence of peritonitis at our center was 1 episode every 42 patient treatment months. No case of VRE was noted. There was no statistical difference in clinical response or relapse rate for the two protocols. It was the authors’ and nurses’ observation that patient compliance and satisfaction was better with vancomycin, and the cost per treatment was 23% less than cefazolin. Based on these data we believe vancomycin should still be considered for first-line treatment of PD-associated peritonitis.
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