Infection of juvenile falcons (Falco spp.) with intestinal Lawsonia intracellularis.

Intestinal infection of many host species with Lawsonia intracellularis are widely reported. Analyses of infections among carnivorous falcons have not previously been reported. Fifty juvenile captive falcons (Falco spp.) with or without Lawsonia infection were investigated in the United Arab Emirates, including clinical laboratory methods. Fresh intestinal biopsy samples were analysed by microbiological techniques for Lawsonia and other bacteria and by standard parasitological and pathological methods. Lawsonia intracellularis infection was diagnosed by microbiological examination and qPCR in 10 of 50 juvenile falcons at case examination. Seven of these 10 falcons were of normal clinical appearance, and the other three had other contributing factors to ill-thrift. A range of other conditions were noted in 40 case control falcons. This first report of Lawsonia infection in falcons suggests that the agent may have a limited contribution to clinical disease in these birds, including ill-thrift syndromes. This lack of clinical disease association mimics that noted among Lawsonia infections recorded in other avian families.

Lung injury caused by aspiration of organophosphorus insecticide and gastric contents in pigs.

INTRODUCTION: Patients who require mechanical ventilation after self-poisoning with ingested organophosphorus (OP) insecticides often die. Aspiration of stomach contents may contribute to lung injury and lethality. This study was designed to assess the severity of direct and indirect pulmonary injury created by pulmonary instillation of mixtures of OP insecticide, solvent (Solv) and porcine gastric juice (GJ) compared to controls. METHODS: Terminally anaesthetised minipigs (groups n = 5) were exposed to sham bronchoscopy or given mixtures (0.5 mL/kg) of: saline, GJ, OP insecticide and GJ (OP + GJ), or Solv and GJ (Solv + GJ), placed into the right lung, and monitored for 48 h. Lung injury was assessed through analysis of bronchoalveolar lavage fluid (BALF), computed tomography and histopathology. RESULTS: OP + GJ created a direct lung injury consisting of neutrophil infiltration, oedema and haemorrhage, as well as indirect injury to the other lung. OP + GJ directly-injured lung parenchyma had increased concentrations of BALF protein, albumin, IL-6, IL-8 and C-reactive protein (CRP) at 24 h (p < 0.05), and BALF protein, albumin and CRP at 48 h (p < 0.05), when compared with controls. Aspiration of GJ produced similar direct effects to OP + GJ but less indirect lung injury. Lung injury was less severe after Solv + GJ, for combined lung histopathology scores (vs. OP + GJ, p < 0.05) and for the proportion of directly-injured lung that was poorly/non-aerated at 48 h. CONCLUSION: Pulmonary instillation of OP + GJ created more lung damage than controls or Solv + GJ. In patients with severe OP insecticide poisoning and reduced consciousness, early airway protection is likely to reduce pulmonary damage.

A previously undescribed cutaneous paraneoplastic syndrome in a cat with thymoma.

BACKGROUND: Exfoliative dermatitis is a well-recognized cutaneous paraneoplastic syndrome (PNS) associated with thymoma in cats, of which the clinical and histopathological presentation has been well-characterized. OBJECTIVES: To describe a novel clinical skin manifestation associated with thymoma in a cat. ANIMAL: A 14-year-old neutered female domestic short hair cat. METHODS AND MATERIALS: Physical, abdominal ultrasonographic, thoracic radiographic, ultrasonographic and computed tomographic examinations, histopathological assessment of the skin and mediastinal mass. RESULTS: The cat was presented with noninflammatory alopecia, with a dorsal multifocal distribution. Examination of the alopecic areas using a dermascope indicated an apparent lack of follicular ostia. Histopathological assessment of alopecic areas confirmed follicular and epidermal atrophy, trichilemmal keratinization and mild orthokeratotic hyperkeratosis. Diagnostic imaging revealed a mediastinal mass, which was surgically removed. Histopathological and immunohistopathological examination of the mass was consistent with a thymoma, associated with multiloculated cyst formation and multifocal cholesterol granulomas. Following surgery, hair re-growth was noted in the previously alopecic areas. The cat was euthanized 3.5 months later because of recurrent chylothorax suspected to be a postoperative complication. The alopecic lesions had improved markedly. CONCLUSIONS AND CLINICAL IMPORTANCE: Thymoma-associated PNS might not always manifest as an exfoliative dermatitis and should be considered in the differential diagnosis of multifocal noninflammatory alopecia.

Cross-species genomic landscape comparison of human mucosal melanoma with canine oral and equine melanoma.

Mucosal melanoma is a rare and poorly characterized subtype of human melanoma. Here we perform a cross-species analysis by sequencing tumor-germline pairs from 46 primary human muscosal, 65 primary canine oral and 28 primary equine melanoma cases from mucosal sites. Analysis of these data reveals recurrently mutated driver genes shared between species such as NRAS, FAT4, PTPRJ, TP53 and PTEN, and pathogenic germline alleles of BRCA1, BRCA2 and TP53. We identify a UV mutation signature in a small number of samples, including human cases from the lip and nasal mucosa. A cross-species comparative analysis of recurrent copy number alterations identifies several candidate drivers including MDM2, B2M, KNSTRN and BUB1B. Comparison of somatic mutations in recurrences and metastases to those in the primary tumor suggests pervasive intra-tumor heterogeneity. Collectively, these studies suggest a convergence of some genetic changes in mucosal melanomas between species but also distinctly different paths to tumorigenesis.

Nebulisation of synthetic lamellar lipids mitigates radiation-induced lung injury in a large animal model.

Methods to protect against radiation-induced lung injury (RILI) will facilitate the development of more effective radio-therapeutic protocols for lung cancer and may provide the means to protect the wider population in the event of a deliberate or accidental nuclear or radiological event. We hypothesised that supplementing lipid membranes through nebulization of synthetic lamellar lipids would mitigate RILI. Following pre-treatment with either nebulised lamellar lipids or saline, anaesthetised sheep were prescribed fractionated radiotherapy (30 Gray (Gy) total dose in five 6 Gy fractions at 3-4 days intervals) to a defined unilateral lung volume. Gross pathology in radio-exposed lung 37 days after the first radiation treatment was consistent between treatment groups and consisted of deep red congestion evident on the pleural surface and firmness on palpation. Consistent histopathological features in radio-exposed lung were subpleural, periarteriolar and peribronchial intra-alveolar oedema, alveolar fibrosis, interstitial pneumonia and type II pneumocyte hyperplasia. The synthetic lamellar lipids abrogated radiation-induced alveolar fibrosis and reduced alpha-smooth muscle actin (ASMA) expression in radio-exposed lung compared to saline treated sheep. Administration of synthetic lamellar lipids was also associated with an increased number of cells expressing dendritic cell-lysosomal associated membrane protein throughout the lung.

Real-time elastosonography of lipomatous vs. malignant subcutaneous neoplasms in dogs: Preliminary results.

Real-time elastography is a recently introduced ultrasound technique allowing the investigation of elastic properties of tissues. A diagnostic accuracy study was conducted to test the performance of this technique in the assessment of subcutaneous lesions in dogs. Fifty-two dogs were prospectively included in the preliminary study (34 malignant and 18 benign lesions). B-mode ultrasound was performed assessing the shape, margins, heterogeneity, and echotexture of the lesions. On elastosonography, assessment of the percentage of softness/hardness was recorded. A qualitative assessment was performed according to the Tsukuba elasticity score with a 1-5 score, representing the increased percentage of high stiffness areas. Results were compared with cytology/histopathology of the lesions. Receiver Operating Curves of the overall diagnostic sensitivity and specificity were obtained. Fisher's exact test and Pearsons's Chi-squared test estimated the relationship between the B-mode appearance of the lesions and final diagnosis. A hardness cutoff of 50.25% was identified between lesions, with malignant neoplasms having higher percentages. A 100% specificity and 89% sensitivity for correctly detecting the nature of the lesion on elastosonography was established. Qualitative assessment of the Tsukuba elasticity score established 1.5 as the cutoff between elastograms of lipomatous and malignant lesions, with 100% sensitivity and 61% specificity in differentiating them. Real-time elastosonography is a novel, noninvasive, and accurate technique for differentiating malignant from benign lipomatous lesions in dogs. This method could be considered as a complementary tool with additional diagnostic value for routine invasive procedures, such as fine needle aspirates.

A Comparison of Computed Tomographic, Radiographic, Gross and Histological, Dental, and Alveolar Findings in 30 Abnormal Cheek Teeth from Equine Cadavers.

BACKGROUND: Equine cheek teeth disorders, especially pulpar/apical infections, can have very serious consequences due to the frequent extension of infection to the supporting bones and/or adjacent paranasal sinuses. Limited studies have assessed the accuracy of computed tomographic (CT) imaging in the diagnosis of these disorders, and no study has directly compared imaging and pathological findings of the alveoli of diseased equine cheek teeth. OBJECTIVE: To validate the accuracy of CT and radiographic imaging of cheek teeth disorders by comparing CT and radiographic imaging, gross and histological findings in abnormal cheek teeth and their alveoli extracted from equine cadaver heads. STUDY DESIGN: Ex vivo original study. METHODS: Fifty-four cadaver heads from horses with unknown histories that had died or been euthanized on humane grounds obtained from a rendering plant had radiography, CT imaging, and gross pathological examinations performed. Based on imaging and gross examination findings, 30 abnormal cheek teeth (26 maxillary and 4 mandibular) identified in 26 heads were extracted along with their dental alveoli where possible, and further CT imaging, gross, and histological examinations were performed. Eight maxillary cheek teeth (including four with attached alveolar bone) from these heads, that were normal on gross and CT examinations, were used as controls. RESULTS: Gross pathological and histological examinations indicated that 28/30 teeth, including two supernumerary teeth, had pulpar/apical infection, including pulpar and apical changes. A further supernumerary and a dysplastic tooth were also identified. Abnormal calcified tissue architecture was present in all three supernumerary and in the dysplastic tooth. CT imaging strongly indicated the presence of pulpar/apical infection in 27 of the 28 (96.4%) pulpar/apically infected teeth, including the presence of intrapulpar gas (N = 19/28), apical clubbing (N = 20), periapical halo (N = 4), root lysis or fragmentation (N = 7), and periapical gas (N = 2). Also present were alveolar bone sclerosis (N = 20), alveolar bone thickening (N = 3), and lytic/erosive changes (N = 8). Radiographic abnormalities strongly indicative of pulpar/apical infection including periapical sclerosis (N = 8/28) and apical clubbing (N = 14/28) were found in 14/28 (50%) of apically infected teeth. Histological changes were present in alveolar bone of all 21 cases of apical infection where alveolus remained attached to the tooth and was marked in 16 cases, all which had CT alveolar changes. Histological changes included disruption of the normal trabecular pattern, increased osteoclastic activity, and the presence of islands of bone with a scalloped profile within the thickened attached periodontal ligament. No gross pathological or histological changes were present in the eight control teeth or their alveoli (N = 4). MAIN LIMITATIONS: No history or breed-related information was available on these cases. CONCLUSION: There was a 96.4% correlation between a CT diagnosis and confirmative pathological findings in 28 apically infected teeth confirming the accuracy of CT imaging in diagnosing equine pulpar/apical infections. There was also excellent correlation between CT and histological alveolar bone findings.

The safety profile of a cationic lipid-mediated cystic fibrosis gene transfer agent following repeated monthly aerosol administration to sheep.

Clinically effective gene therapy for Cystic Fibrosis has been a goal for over 20 years. A plasmid vector (pGM169) that generates persistent expression and reduced host inflammatory responses in mice has raised prospects for translation to the clinic. The UK CF Gene Therapy Consortium is currently evaluating long-term repeated delivery of pGM169 complexed with the cationic lipid GL67A in a large Multidose Trial. This regulatory-compliant evaluation of aerosol administration of nine doses of pGM169/GL67A at monthly intervals, to the sheep lung, was performed in preparation for the Multidose Trial. All sheep tolerated treatment well with no adverse effects on haematology, serum chemistry, lung function or histopathology. Acute responses were observed in relation to bronchoalveolar cellularity comprising increased neutrophils and macrophage numbers 1 day post-delivery but these increases were transient and returned to baseline. Importantly there was no cumulative inflammatory effect or lung remodelling with successive doses. Molecular analysis confirmed delivery of pGM169 DNA to the airways and pGM169-specific mRNA was detected in bronchial brushing samples at day 1 following doses 1, 5 and 9. In conclusion, nine doses of pGM169/GL67A were well tolerated with no significant evidence of toxicity that would preclude adoption of a similar strategy in CF patients.

A lung segmental model of chronic Pseudomonas infection in sheep.

BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep. METHODOLOGY/PRINCIPAL FINDINGS: Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>10(4) cfu/g). CONCLUSIONS/SIGNIFICANCE: The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches.

A role for solvents in the toxicity of agricultural organophosphorus pesticides.

Organophosphorus (OP) insecticide self-poisoning is responsible for about one-quarter of global suicides. Treatment focuses on the fact that OP compounds inhibit acetylcholinesterase (AChE); however, AChE-reactivating drugs do not benefit poisoned humans. We therefore studied the role of solvent coformulants in OP toxicity in a novel minipig model of agricultural OP poisoning. Gottingen minipigs were orally poisoned with clinically relevant doses of agricultural emulsifiable concentrate (EC) dimethoate, dimethoate active ingredient (AI) alone, or solvents. Cardiorespiratory physiology and neuromuscular (NMJ) function, blood AChE activity, and arterial lactate concentration were monitored for 12h to assess poisoning severity. Poisoning with agricultural dimethoate EC40, but not saline, caused respiratory arrest within 30 min, severe distributive shock and NMJ dysfunction, that was similar to human poisoning. Mean arterial lactate rose to 15.6 [SD 2.8] mM in poisoned pigs compared to 1.4 [0.4] in controls. Moderate toxicity resulted from poisoning with dimethoate AI alone, or the major solvent cyclohexanone. Combining dimethoate with cyclohexanone reproduced severe poisoning characteristic of agricultural dimethoate EC poisoning. A formulation without cyclohexanone showed less mammalian toxicity. These results indicate that solvents play a crucial role in dimethoate toxicity. Regulatory assessment of pesticide toxicity should include solvents as well as the AIs which currently dominate the assessment. Reformulation of OP insecticides to ensure that the agricultural product has lower mammalian toxicity could result in fewer deaths after suicidal ingestion and rapidly reduce global suicide rates.

Myeloperoxidase-positive acute megakaryoblastic leukemia in a dog.

A 16-month-old female spayed Labrador Retriever was referred to the University of Edinburgh for exercise intolerance, inappetence, and severe anemia. A CBC showed severe nonregenerative anemia and moderate numbers of atypical cells with morphologic features most consistent with megakaryoblastic origin. Similar cells were identified in a bone marrow aspirate and accounted for 23% of all nucleated cells. Atypical promegakaryocytes and megakaryocytes were also noted. Myelodysplastic syndrome affecting the megakaryocytic lineage was suspected. Cytologic examination of a fine-needle aspirate of the spleen revealed rare megakaryoblasts similar to those in blood and bone marrow. At necropsy, the bone marrow consisted of atypical megakaryoblasts and megakaryocytes that were also infiltrating spleen, liver, lymph nodes, renal perihilar tissue, and visceral adipose tissue, consistent with acute megakaryoblastic leukemia. Immunohistochemical analysis of splenic sections confirmed megakaryoblastic origin (immunoreactive for CD61 and von Willebrand factor). Some leukemic cells were also immunoreactive for myeloperoxidase (MPO). This aberrant immunophenotype suggested both megakaryocytic and granulocytic/monocytic differentiation of the leukemic cells. To our knowledge, this is the first report of MPO-positive acute megakaryoblastic leukemia in a dog.

A comparison of radiographic, arthroscopic and histological measures of articular pathology in the canine elbow joint.

Validation of radiographic and arthroscopic scoring of joint pathology requires their comparison with histological measures of disease from the same joint. Fragmentation of the medial coronoid process (FMCP) is a naturally occurring disease of the canine elbow joint that results in osteoarthritis, and the objectives of this study were to compare the severity of histopathological changes in the medial coronoid process (MCP) and medial articular synovial membrane with gross radiographic scoring of elbow joint osteophytosis and the arthroscopic assessment of the MCP articular cartilage surface. Radiographic scoring of osteophytosis and the arthroscopic scoring of visual cartilage pathology of the MCP correlated moderately well with the histopathological evaluation of cartilage damage on the MCP and synovial inflammation in the medial part of the joint, but not with bone pathology in the MCP. Marked cartilage pathology on the MCP was identified in joints with either no radiographic evidence of osteophytosis or with mild cartilage damage that was evident arthroscopically.

Tumors affecting the spinal cord of cats: 85 cases (1980-2005).

OBJECTIVE: To determine the prevalence of lymphosarcoma and other tumors affecting the spinal cord of cats and to relate specific types of tumors with signalment, history, and clinical findings. DESIGN: Retrospective case series. ANIMALS: 85 cats with tumors affecting the spinal cord. PROCEDURES: Medical records of cats with histologically confirmed primary or metastatic tumors of the spinal cord or tumors causing spinal cord disease by local extension from adjacent tissues examined between 1980 and 2005 were reviewed. Data on signalment; clinical history; results of neurologic examination, diagnostic imaging, and clinical pathologic evaluation; and location of tumor within the spinal cord were obtained from medical records and analyzed by use of logistic regression models. RESULTS: Lymphosarcoma was the most common tumor and affected the spinal cord in 33 (38.8%) cats, followed by osteosarcoma in 14 (16.5%) cats. Cats with lymphosarcoma were typically younger at initial examination, had a shorter duration of clinical signs, and had lesions in more regions of the CNS than did cats with other types of tumors. In 22 of 26 (84.6%) cats with lymphosarcoma, the tumor was also found in extraneural sites. CONCLUSIONS AND CLINICAL RELEVANCE: Data for spinal cord tumors in this population of cats were analyzed by logistic regression analysis, which effectively distinguished cats with lymphosarcoma from cats with other types of tumors. Additional clinical information reported here will help to increase the index of suspicion or definitive antemortem diagnosis of spinal cord tumors of cats.

Compressive cervical myelopathy in young Texel and Beltex sheep.

BACKGROUND: This investigation was prompted by the referral of increasing numbers of young Texel and Beltex rams with ataxia and weakness, or wobbler syndrome. HYPOTHESIS: The study aims were to describe the clinical and pathologic findings in affected sheep. ANIMALS: The animals evaluated in this study included 7 Texel sheep (6 male and 1 female) and 3 Beltex sheep (2 male and 1 female) referred from pedigree flocks. Typically, the sheep were 15-18 months of age at referral. METHODS: Diagnostic investigations included radiographic and computed tomographic (CT) myelography followed by gross postmortem and histopathologic examinations. RESULTS: Clinical findings typical of cervical spinal cord compression were present in all sheep but varied in severity. Myelography confirmed dorsal spinal cord compression in the region of C6-C7. No bony abnormalities were identified as described in cases of canine and equine wobbler syndrome. Postmortem examinations revealed discrete, smooth, nodular to polypoid projections of adipose tissue apparently prolapsing through the dorsolateral intervertebral space at C6-C7 and causing localized spinal cord compression. Histopathology of the nodules confirmed that they were composed of well-differentiated adipocytes typical of fatty tissue. Spinal cord lesions were similar in all sheep with marked Wallerian degeneration at the site of compression and mild Wallerian degeneration present cranial and caudal to the lesion. CONCLUSIONS AND CLINICAL IMPORTANCE: The findings of this study suggest a novel cervical myelopathy in these sheep breeds caused by the presence of fatty nodules encroaching into the dorsal vertebral canal at C6-C7. Additional investigations are required to establish the etiology and possible hereditary risk factors for this unique clinicopathologic syndrome.

Congestive heart failure associated with a large transverse left ventricular moderator band in a cat.

Cardiomyopathy associated with abnormal trabecular bands of tissue traversing one or both ventricles is reported rarely in cats. The case of a 9-year-old cat which presented in congestive heart failure is reported. Multiple cardiac abnormalities were found, including a large trabecular tissue bridge which bisected the left ventricle. Other findings included arrhythmia, thrombocytopaenia and raised serum creatine kinase. The cat was euthanased due to clinical deterioration. Necropsy findings included increased cardiac weight, the division of the left ventricle by a large trabecular band composed of connective tissue and cardiac myofibres consistent with a moderator band, nodular thickening of the mitral valve, left atrial dilation, and fibroplasia/fibrosis of the left ventricular myocardium associated with widespread myofibre necrosis due to infarction. Pathological findings in this case differ from previous reports of ventricular transverse bridging tissue in cats with cardiac disease.

Extradural spinal, bone marrow, and renal nephroblastoma.

A 1-year-old, female intact Shetland sheepdog presented with acute onset of neurological signs. Physical examination revealed a large abdominal mass. Neurological examination revealed multifocal disease with neck pain, short-strided forelimbs, and hind-limb paresis with loss of tail and anal tone. Blood work, imaging techniques, cytopathology, and histopathology led to a diagnosis of renal, bone-marrow, and extradural spinal nephroblastoma. This report documents potential clinical and pathological manifestations of canine nephroblastoma that have not been previously reported.