Abstract Feline infectious peritonitis (FIP) is a severe feline coronavirus-associated syndrome in cats, which is invariably fatal without anti-viral treatment. In the majority of non-effusive FIP cases encountered in practice, confirmatory diagnostic testing is not undertaken and reliance is given to the interpretation of valuable, but essentially non-specific, clinical signs and laboratory markers. We hypothesised that it may be feasible to develop a machine learning (ML) approach which may be applied to the analysis of clinical data to aid in the diagnosis of disease. A dataset encompassing 1939 suspected FIP cases was scored for clinical suspicion of FIP on the basis of history, signalment, clinical signs and laboratory results, using published guidelines, comprising 683 FIP (35.2%), and 1256 non-FIP (64.8%) cases. This dataset was used to train, validate and evaluate two diagnostic machine learning ensemble models. These models, which analysed signalment and laboratory data alone, allowed the accurate discrimination of FIP and non-FIP cases in line with expert opinion. To evaluate whether these models may have value as a diagnostic tool, they were applied to a collection of 80 cases for which the FIP status had been confirmed (FIP: n = 58 (72.5%), non–FIP: n = 22 (27.5%)). Both ensemble models detected FIP with an accuracy of 97.5%, an area under the curve (AUC) of 0.969, sensitivity of 95.45% and specificity of 98.28%. This work demonstrates that, in principle, ML can be usefully applied to the diagnosis of non-effusive FIP. Further work is required before ML may be deployed in the laboratory as a diagnostic tool, such as training models on datasets of confirmed cases and accounting for inter-laboratory variation. Nevertheless, these results illustrate the potential benefit of applying ML to standardising and accelerating the interpretation of clinical pathology data, thereby improving the diagnostic utility of existing laboratory tests.
Samples for diagnostic procedures often require some form of pre-analytical preparation for preservation or safe handling during transportation prior to analysis in the laboratory. This is particularly important for milk samples which frequently need preservatives to retain milk composition as close to that found in freshly collected samples as possible.
Renal dysplasia and nephrosclerosis in six calves, which were aged three to six months and from different farms in western Scotland and north‐west England, was characterised clinically by stunted growth and renal failure with uraemia. Affected animals were depressed and one case exhibited severe neurological signs. Reduced erythrocyte counts were evident in three of four animals from which blood samples were submitted for haematology. At postmortem examination, the kidneys were bilaterally small, pale and firm, with marked fibrosis and sometimes contraction of the capsule. Histologically, affected calves had disorganised atrophic glomeruli, dilatation of tubules, loss of nephrons, areas of undifferentiated mesenchyme and diffuse interstitial and periglomerular fibrosis. There was minimal inflammation. Renal dysplasia and nephrosclerosis is a form of juvenile nephropathy of unknown aetiology that occurs sporadically in calves in the UK.
Crohn's disease is a chronic, progressive granulomatous enteritis of young humans. Analogies have been made with Johne's disease of cattle, especially following the isolation of the organism, Mycobacterium avium subsp. paratuberculosis, from some Crohn's patients. Much research has been conducted to define the aetiological agent of Crohn's disease. However, the cause remains unclear. The aim of the project was to investigate the likelihood of clinical cases of Johne's disease passing meat hygiene inspection, following current fresh meat legislation and guidelines. Carcasses considered fit for human consumption underwent post-mortem examination to investigate gross pathological changes. The extent of spread of the organism was investigated by cytological and histological examination and also by polymerase chain reaction of lymph nodes, intestines and selected tissues. All the confirmed Johne's disease carcasses set and would pass meat hygiene inspection. The most consistent findings at post-mortem were dilation of the mesenteric and gut lymphatics, and thickening of the terminal ileum, with cobblestoning of the ileal mucosa. The most significant laboratory result was a prescapular lymph node of animal 136334 being positive for IS900, a genetic element of DNA unique to the organism. Moreover this animal had numerous granulomatous lesions throughout many lymph nodes and organs in the body, suggesting systemic spread of the organism. The second part of this thesis describes a pilot study, conducted in an over thirty month scheme abattoir, investigating the application of a more thorough examination of the carcass within the abattoir. It was found that inspection of the gut mucosa was feasible within the time constraints of the slaughterline and if conducted within the gut room, posed minimal threat to hygiene.
Abstract Canine lymphoma represents a heterogeneous group of lymphoid neoplasms, with multicentric nodal lymphoma being the most common presentation. Musculoskeletal involvement is uncommon, and primary muscular lymphoma is a very rare presentation. Only a few cases have been described in dogs, which were of variable classification and immunophenotype. Here, we report the case of a 5‐year‐old female neutered Beagle that presented with an intramuscular mass on the right shoulder and associated lameness and lethargy. One month after initial presentation, multiple cutaneous nodules appeared on the head, and staging with advanced imaging revealed additional masses affecting other muscles. Cytology, histopathology, immunohistochemistry, and PCR for antigen receptor rearrangements of one of the muscle masses and skin lesions supported a diagnosis of peripheral T‐cell lymphoma with large granular lymphocytes at both sites. The dog was euthanized after diagnosis due to the poor prognosis. This is the first report of primary muscular peripheral T‐cell lymphoma with large granular lymphocytes and cutaneous involvement in the dog. Despite being a rare presentation, lymphoma must be considered a differential in dogs presenting with a discrete, intramuscular, soft tissue mass.
A 12-year-old female neutered, black, standard poodle was presented to the referring veterinary surgeon for a firm, hairless skin mass on her distal metatarsus. There were no other clinical abnormalities at the time of presentation. A single smear was prepared from a fine-needle aspirate biopsy of the lesion was submitted to Veterinary Diagnostic Services, University of Glasgow for cytologic evaluation (Figure 1 and 2). Cytological Interpretation: Pigmented follicular tumor (trichoepithelioma, trichofolliculoma, tricholemmoma, pilomatricoma, infundibular keratinizing acanthoma), cyst of follicular origin, or melanocytic tumor (melanocytoma, malignant melanoma). The slide was mildly to markedly cellular in some areas and moderately blood contaminated. Many anucleated squamous epithelial cells, keratin bars, keratinaceous debris, and scattered brown/black pigment (melanin) were present in a variably proteinaceous background. A small number of cholesterol clefts were also noted. Many melanin-containing cells were present, with some too granular to discern lineage. Where examinable, some appeared to be melanophages, which also showed erythrophagocytosis. Small numbers of plump, spindle-shaped cells with dark cytoplasmic granules (melanocytes) were also seen. Rare nucleated squamous epithelial cells were also scattered throughout. Excision and histopathology were performed (Figures 3 and 4). There was a focal, well-circumscribed, unencapsulated, expansile dermal mass composed of cords and trabeculae of neoplastic epithelial cells. These cells surrounded cystic areas containing eosinophilic material and amorphous and laminar keratin and were supported by moderate amounts of fibrovascular stroma. Neoplastic cells had indistinct cell borders, moderate amounts of eosinophilic cytoplasm, and round to oval nuclei with basophilic finely stippled chromatin, often with a prominent nucleolus. Anisocytosis and anisokaryosis were mild, and the mitotic activity was low (less than one in 10 high power fields). Surrounding and infiltrating within the trabeculae of neoplastic epithelial cells and the stroma were variable numbers of a second population of neoplastic polygonal cells. These cells had variably distinct cell borders, abundant cytoplasm, and frequently contained abundant brown pigment (melanocytes) and round to oval nuclei with finely stippled chromatin that occassionally had a prominent nucleolus. Anisocytosis was moderate, anisokaryosis was mild, and mitoses were rare. The first population of neoplastic cells was strongly positive for cytokeratin, whereas the second population demonstrated moderate positivity for Melan A. The histomorphologic diagnosis was melanoacanthoma. Melanoacanthomas are considered benign tumors, and surgical excision is curative. In this case, surgical excision was achieved with small margins. On follow-up, the lesion had not returned after 18 months. Melanoacanthoma, or melanocytoma-acanthoma, is a rare neoplasm in the dog, with only four previously described cases in the literature.1-4 However, gross and histologic lesion descriptions are available, and detailed descriptions of the clinical and histologic features have been published.5 This phenomenon is included in the International Histologic Classification of Skin tumors of domestic animals,6 and the tumors have features of both compound melanocytic tumors and benign epithelial neoplasia. From the limited number of published descriptions, lesions are typically solitary well-circumscribed, pigmented dome-shaped masses ≤ 1cm2, 4, 5 in diameter on gross examination. Some reports also describe alopecia2, 4 similar what we saw in this case. Given the infrequency of reports about these lesions, age, breed, and predilection sites have yet to be ascertained. However, in the four previously reported cases, three occurred on the head,1-3 and one occurred on the dorsal trunk.4 In the case of this report the tumor occurred in the distal metatarsal area. To the authors' knowledge, this lesion has not been reported in the cat. Histologically, the tumors typically have cords and anastomosing trabeculae of neoplastic epithelial cells with cystic structures containing amorphous and laminated keratin. The melanocytic component lines the peripheral layer of the trabeculae and cysts in nests and clusters. The lesion described in this report demonstrated these characteristics. The cytology did not completely mirror the characteristics observed on histopathology. Anucleate and nucleated squamous epithelial cells and keratin debris were observed on cytology rather than polygonal epithelial cells. These might represent the laminar and amorphous keratin from cystic structures. Additionally, the melanocytes were spindle shaped on the cytologic sample yet polygonal on histopathology. Melanocytes are pleomorphic cells with round, stellate, and spindle shapes possible. The difference in shape could be attributed to the different sampling methods and different regions of the tumor. Erythrophagocytosis was noted in melanophages, which is indicative of previous intralesional hemorrhage. Hemorrhage has not been described in previous reports or texts; thus, the authors speculate that the distal metatarsal location of the lesion could make it more prone to trauma. There is no human counterpart; in people, the term melanoacanthoma describes a different lesion. Cutaneous melanoacanthoma in people is considered a variant of seborrheic keratosis, a benign lesion that is typically an epidermal plaque comprising predominantly epithelial cells with some infiltrating melanocytes. Common locations are the head and trunk.7 The presence of both the squamous and melanocytic components in the cytologic preparations led to an extensive differential list. Keratin debris and anucleated squamous epithelial cells are common in several follicular tumors such as trichoepithelioma, trichofolliculoma, tricholemmoma, pilomatricoma, and also cysts of follicular origin. Consequently, these tumors cannot be distinguished cytologically. Melanin pigment can also be present in these lesions; however, it is found in melanophages or melanized squamous epithelial cells and is not due to a neoplastic melanocytic component. In aspirates with cytologic features consistent with a follicular cyst or tumor and an accompanying melanocyte population, melanoacanthoma should be considered a possible differential. To the authors' knowledge, this is the first cytologic description of a melanoacanthoma in the dog. The authors have indicated that they have no affiliations or financial involvement with any organization or entity with a financial interest in, or in financial competition with, the subject matter or materials discussed in this article.
Serum Amyloid A (SAA) is a major acute phase protein in cats, increasing rapidly in response to various inflammatory diseases. An automated latex-enhanced immunoturbidimetric assay for human SAA (LZ-SAA, Eiken), previously validated for use in cats, has had further major modification (VET-SAA, Eiken) for specific use in veterinary diagnostic laboratories but has yet to be validated in cats.Intra-assay and inter-assay CVs for the VET-SAA assay ranged from 1.88-3.57% and 3.98-6.74%, respectively. Linearity under dilution was acceptable with no prozone effect observed. Limit of detection was 1.65 mg/L and limit of quantification was 6 mg/L. Haemoglobin and triglyceride showed no adverse interference, but bilirubin produced positive bias in samples with low SAA. Comparison with the LZ-SAA assay showed significant correlation with proportional bias increasing as SAA concentration increased, likely related to differing calibration standards. SAA was significantly higher in patients with inflammatory disease compared with non-inflammatory disease, and in patients with moderate to highly elevated α1-AGP compared with patients with normal α1-AGP. Improvement of the assay range may be required to fully evaluate differences between disease groups at low SAA levels. Based on ROC curve analysis, at a cut-off point of 20.1 mg/L the VET-SAA assay discriminated between inflammatory and non-inflammatory disease with sensitivity of 0.93 and specificity of 0.99.The automated VET-SAA assay is a robust, precise, and accurate method for measurement of feline SAA which can clearly identify patients with inflammatory disease. It should be a valuable biomarker for use in feline medicine.
In order to identify the extent of protein changes in milk during mastitis as a guide to detecting markers for prompt management of the disease, milk from cows in which clinical mastitis was experimentally induced were subjected to difference gel electrophoresis (DiGE) analysis. Pooled samples from 6 udders (from 6 cows) were analysed at selected time points: 0, 81 and 312 hours post-challenge with Streptococcus uberis mastitis. These corresponded to samples from the pre-infection, peak and resolution phases of the mastitis challenge. After the preliminary sample preparation, concentration and pooling steps, samples were labelled with CyDyes (Cydye 2, 3 and 5), after which isoelectric focusing and gel electrophoresis were carried out respectively. DiGE gels were subsequently scanned and ImageQuant, ImageJ and DeCyder™ 2D (version 7.0) softwares were used to crop, obtain jpeg images and carry out 2-D differential analysis and processing of the images, respectively. Biological variation analysis (BVA) software (GE Healthcare Life Sciences, Buckinghamshire, UK) was also used to analyse the gels and create gel to gel matching of spots (qualitatively and quantitatively) within the three gels produced. Overall, a total of 521 protein spots were identified as significantly differentially expressed (qualitatively or quantitatively) in mastitis milk during the course of the intramammary infection. This demonstrates the large repertoire of protein biomarker candidates available, revealed through this technique. Further studies are required to elucidate the merits and demerits of these changing proteins in order to identify the one most suitable for clinical application in mastitis diagnosis.
A three year old, second lactation Holstein dairy cow presented to the Scottish Centre for Production Animal Health and Food Safety, Glasgow University Veterinary School in November 2014 with a history of post-calving vulval/vaginal bleeding nine days prior to presentation, followed by a sudden reduction in milk yield. Subsequent investigations resulted in a diagnosis of immune-mediated haemolytic anaemia secondary to infection with Mycoplasma wenyonii.This report of a novel presentation of Mycoplasma wenyonii in a dairy cow illustrates the need to consider M.wenyonii as a potential differential diagnosis when a cow presents with anaemia and will discuss the potential implications of the condition at herd-level.
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