Clinicopathological features of peripheral odontogenic fibromas in dogs and risk factors for their laboratory diagnosis.

OBJECTIVES: To explore clinicopathological features of peripheral odontogenic fibromas in dogs and risk factors for their diagnosis. MATERIALS AND METHODS: Data of cases with a histopathological diagnosis of peripheral odontogenic fibromas were obtained from a UK-based diagnostic laboratory and retrospectively reviewed. Prevalence amongst all biopsy submissions was assessed using binomial tests and Clopper-Pearson intervals. Age at diagnosis was assessed using t-test for independent samples. Lesion location, sex, and neuter status were assessed using χ2 and post hoc binomial tests. Breed odds ratios were calculated using univariable logistic regression modelling. RESULTS: The prevalence of peripheral odontogenic fibromas amongst all biopsy submissions was 2.8% (1001 of 35,328, 95% confidence interval [CI]: 2.7 to 3.0). The mean (sd) age was 8.1 (±2.7) years. The most affected quadrant was the rostral maxilla (40.1%). The ratio of maxillary to mandibular lesions was 1.3:1 (95% CI: 1.1 to 1.5), and for cases of multiple peripheral odontogenic fibromas the ratio of maxillary to mandibular lesions was 2.4:1 (95% CI: 1.1 to 5.6). Males had 1.2 times the odds of suffering of peripheral odontogenic fibromas compared to females (odds ratio [OR]: 1.2, 95% CI: 1.1 to 1.4). Neutering was associated with an increased risk of diagnosis (OR: 1.6, 95% CI: 1.3 to 1.9). Breeds with increased odds of peripheral odontogenic fibromas compared to crossbreed dogs included boxers (OR: 3.78, 95% CI: 2.80 to 5.09), border terriers (OR: 3.21, 95% CI: 2.10 to 4.91) and Basset Hounds (OR: 3.18, 95% CI: 1.58 to 6.44). Breeds with increased odds of multiple simultaneous peripheral odontogenic fibromas compared to crossbreed dogs included: Boxers (OR: 12.02, 95% CI: 7.13 to 20.24), border terriers (OR: 5.05, 95% CI: 2.32 to 11.43) and Staffordshire Bull terriers (OR: 2.42, 95% CI: 1.33 to 4.41). CLINICAL SIGNIFICANCE: Knowledge of clinicopathological features and at-risk breeds for peripheral odontogenic fibroma development can assist clinicians with making a diagnosis. The identification of risk factors provides targets for future research investigating peripheral odontogenic fibroma pathogenesis.

Stimulation-induced changes at the electrode-tissue interface and their influence on deep brain stimulation.

Objective. During deep brain stimulation (DBS) the electrode-tissue interface (ETI) forms a critical path between device and brain tissue. Although changes in the electrical double layer (EDL) and glial scar can impact stimulation efficacy, the effects of chronic DBS on the ETI have not yet been established.Approach. In this study, we characterised the ETI surrounding chronically implanted DBS electrodes in rats and compared the impedance and histological properties at the electrode interface in animals that received daily stimulation and in those where no stimulation was applied, up to 8 weeks post-surgery. A computational model was developed based on the experimental data, which allowed the dispersive electrical properties of the surrounding encapsulation tissue to be estimated. The model was then used to study the effect of stimulation-induced changes in the ETI on the electric field and neural activation during voltage- and current-controlled stimulation.Main results. Incorporating the observed changes in simulationsin silico, we estimated the frequency-dependent dielectric properties of the EDL and surrounding encapsulation tissue. Through simulations we show how stimulation-induced changes in the properties of the ETI influence the electric field and alter neural activation during voltage-controlled stimulation. A substantial increase in the number of stimulated collaterals, and their distance from the electrode, was observed during voltage-controlled stimulation with stimulated ETI properties.In vitroexamination of stimulated electrodes confirmed that high frequency stimulation leads to desorption of proteins at the electrode interface, with a concomitant reduction in impedance.Significance. The demonstration of stimulation-induced changes in the ETI has important implications for future DBS systems including closed-loop systems where the applied stimulation may change over time. Understanding these changes is particularly important for systems incorporating simultaneous stimulation and sensing, which interact dynamically with brain networks.

Secreted products of Fasciola hepatica inhibit the induction of T cell responses that mediate allergy.

There is evidence from epidemiology studies of a negative association between infection with helminth parasites and the development of allergy and asthma. Here, we demonstrate that the excretory/secretory products of the helminth Fasciola hepatica (FHES) protected mice against ovalbumin (OVA)-induced allergic asthma when administered at time of allergen sensitization. FHES reduced the accumulation of mucus, eosinophils and lymphocytes into the airways of allergen-challenged mice. Furthermore, FHES treatment suppressed Th2 responses in the airways. Interestingly, systemic administration of FHES at allergen challenge had no effect on airway inflammation, demonstrating that alum-induced Th2 response is set following initial allergen sensitization. Our findings highlight the immunomodulatory potential of molecules secreted by F. hepatica.

Bacterial Cholangitis, Cholecystitis, or both in Dogs.

BACKGROUND: Bacterial cholangitis and cholecystitis are rarely reported, poorly characterized diseases in the dog. OBJECTIVES: To characterize the clinical features of these conditions. ANIMALS: Twenty-seven client-owned dogs with bacterial cholangitis, cholecystitis, or both. METHODS: Multicenter, retrospective cases series of dogs with bacterial cholangitis, cholecystitis, or both, presenting January 2000 to June 2011 to 4 Veterinary Schools in Ireland/United Kingdom. Interrogation of hospital databases identified all cases with the inclusion criteria; histopathologically confirmed cholangitis or cholecystitis and bile culture/cytology results supporting a bacterial etiology. RESULTS: Twenty-seven dogs met the inclusion criteria with approximately 460 hepatitis cases documented over the same study period. Typical clinical pathology findings were increases in liver enzyme activities (25/26), hyperbilirubinemia (20/26), and an inflammatory leukogram (21/24). Ultrasound findings, although nonspecific, aided decision-making in 25/26 cases. The most frequent hepatobiliary bacterial isolates were Escherichia coli (n = 17; 16 cases), Enterococcus spp. (n = 8; 6 cases), and Clostridium spp. (n = 5; 5 cases). Antimicrobial resistance was an important feature of aerobic isolates; 10/16 E. coli isolates resistant to 3 or more antimicrobial classes. Biliary tract rupture complicated nearly one third of cases, associated with significant mortality (4/8). Discharged dogs had a guarded to fair prognosis; 17/18 alive at 2 months, although 5/10 re-evaluated had persistent liver enzyme elevation 2-12 months later. CONCLUSION AND CLINICAL SIGNIFICANCE: Bacterial cholangitis and cholecystitis occur more frequently than suggested by current literature and should be considered in dogs presenting with jaundice and fever, abdominal pain, or an inflammatory leukogram or with ultrasonographic evidence of gallbladder abnormalities.

Site-specific conjugation of drug-like fragments to an antimiR scaffold as a strategy to target miRNAs inside RISC.

We synthesized a miR-122 antimiR library in which drug-like fragments were site-specifically introduced to short 2'-O-methyl-RNAs. At some sites selected fragments elevated cellular antimiR activity to that of an unmodified 23mer antimiR, whereas at others the same fragments abolished activity. The potency of the antimiRs correlated with uptake into miRISC.

Mismatch repair mRNA and protein expression in intestinal adenocarcinoma in sika deer (Cervus nippon) resembling heritable non-polyposis colorectal cancer in man.

Intestinal adenocarcinomas seen in an inbred herd of farmed sika deer (Cervus nippon) morphologically resembled human hereditary non-polyposis colorectal cancer (HNPCC). Features common to both included multiple de novo sites of tumourigenesis in the proximal colon, sessile and non-polyposis mucosal changes, the frequent finding of mucinous type adenocarcinoma, lymphocyte infiltration into the neoplastic tubules and Crohn's-like lymphoid follicles at the deep margin of the tumour. HNPCC is defined by a germline mutation of mismatch repair (MMR) genes resulting in their inactivation and loss of expression. To test the hypothesis that similar MMR gene inactivation occurs in the deer tumours, the expression of the four most important MMR genes, MSH2, MLH1, MSH6 and PMS2, was examined at the mRNA level by reverse transcriptase polymerase chain reaction (n = 12) and at the protein level by immunohistochemistry (n = 40) in tumour and control tissues. All four genes were expressed equally in normal and neoplastic tissues, so MMR gene inactivation could not be implicated in the carcinogenesis of this tumour in sika deer.

Intestinal adenocarcinoma in a herd of farmed Sika deer (Cervus nippon): a novel syndrome.

Intestinal adenocarcinomas were identified in 76 adult deer from a closed herd of 193 breeding animals grazing pasture heavily infested with bracken fern (Pteridium aquilinum). Tumors were observed postmortem in 32 animals with rapid weight loss, and similar neoplasms were detected in a further 44 clinically normal deer at "cull." Tumors were located in distal ileum, cecum, and proximal colon and presented as single (26%) or multiple (74%), variably sized, pale-gray, firm, poorly circumscribed neoplasms with associated intestinal strictures. Histopathologically tumors were well-differentiated, locally infiltrative, low-grade adenocarcinomas of tubular (51%), mucinous (33.5%), or mixed (15.5%) types. Extraintestinal metastases were not observed. The high incidence of intestinal adenocarcinoma within this herd suggests a specific and novel syndrome, and genetic and/or environmental factors may be involved in the pathogenesis.

A histopathological study of bovine ganglia.

One hundred and sixty-eight ganglia from 54 cattle aged 10 days to 10 years were examined microscopically. Samples from six autonomic ganglia and one sensory ganglion were represented. Thirteen animals were clinically normal and 41 were submitted for post-mortem examination. Neuronal vacuolation, spheroid formation, lipofuscin accumulation and central chromatolysis were observed sporadically and were of varying magnitude. Neuronal vacuolation and spheroid formation were not age-related changes, while lipofuscin accumulation was more common in older animals and central chromatolysis was more common in younger cattle. Non-suppurative inflammation and neuronophagia were also common findings (23 out of 54 animals, 42.6%) in autonomic ganglia that did not contain herpesvirus DNA as determined by polymerase chain reaction. Renaut bodies, features of peripheral nerves, were most commonly noted in the vagus. None of the histopathological findings were related to any particular disease in which loss of autonomic nervous system function might be expected. Furthermore, all changes were as common in clinically normal animals as in animals with disease.

Investigation of the persistence and transmission of MRSA CC 5 in pigs following intra-nasal inoculation.

MRSA CC5 spa type t002 appears to have a broad host range, has been isolated from animals and in-contact humans in Ireland and could potentially become established in pigs in Ireland. The aims of this study were to determine if MRSA CC5 spa type t002 could persist in the tissues of the porcine upper respiratory tract following intra-nasal inoculation; to determine the relative importance of environmental and animal sources of the bacterium in the transmission cycle and to determine the importance of the pharynx as a carriage site of Staphylococcus aureus and MRSA. Twelve pigs were inoculated intra-nasally with MRSA CC5 t002. After 1 or 6 days, the inoculated pigs were removed from the contaminated environment, were washed in an antiseptic solution and placed in a clean house with a group of naive pigs (in-contact group). Another group of naive pigs was placed in the contaminated environment to assess transmission from the environment (environmental group). Nasal swabs, environmental swabs and tissue samples from the upper respiratory tract were taken for MRSA culture. Infection rates were calculated for each group of exposed pigs. MRSA persisted in the pharyngeal tissues of 6 inoculated pigs for at least 30 days and higher counts of S. aureus were found in pharyngeal tissues than in other sites. In this study we were able to demonstrate the establishment of colonisation by MRSA CC5 spa type t002 in commercially sourced pigs already colonised by S. aureus; however, colonisation was sporadic despite the inoculation of large doses. Onward transmission via pig-to-pig contact or environmental contamination was possible and a significant difference was found between the proportion of pigs infected in the environmental group and the proportion infected in the in-contact group during the first 5 days. However, no significant difference was detected in overall infection rates between the 2 groups. The tissues of the pharynx were found to carry greater numbers of S. aureus than other tissues of the upper respiratory tract; therefore, pharyngeal carriage of MRSA and S. aureus in pigs may be more significant than previously thought.

Post-mortem findings in Irish culled hounds.

Little is known of the common diseases of hunting dogs or of the reasons why they are culled. To address these questions, necropsy examinations were conducted on 52 hounds aged 1.5-12 years (mean 6.5 ± 2.5 years) and culled from 10 Irish hunting kennels over a 3-year period. Progressive systemic disease was seen in six dogs only and encompassed individual cases of tuberculosis caused by Mycobacterium bovis, bronchioalveolar carcinoma with metastasis to regional lymph nodes, renal amyloidosis, suppurative pneumonia, extramedullary plasmacytoma in the atrial wall of the heart and foreign body-induced hepatitis with focal peritonitis. Single or multiple localized tumours were identified in five dogs and, apart from the aforementioned, included two cutaneous haemangiomas, a trichoepithelioma, a lipoma and a mammary ductal adenoma. Three dogs were culled for lameness; one of these dogs had torn musculature, another had cellulitis and the third had a healed fracture of the tibia and fibula. Chronic renal changes were present in 48% of the dogs and included focal proliferative, exudative or crescentic glomerulonephritis (33%) or low-grade interstitial inflammatory changes (50%). The most frequently diagnosed skin lesions reported in this study were mild healed decubitus ulcers (33%), scars (33%) and stereotypic dermatitis (13%). These findings indicate that hounds are likely to be culled for reasons other than the presence of disease in most cases. In addition, this survey highlights different disease patterns in hounds than are typically observed in pet dogs.

Age-related and non-age-related changes in 100 surveyed horse brains.

Brains from 100 horses, aged 2-25 years, were systematically examined by histopathology at 46 different neuroanatomical sites. The horses were sourced from a slaughterhouse (group A, n = 57), from a kennel that collected dead animals, and from 2 diagnostic laboratories (group B, n = 43). All horses from group A and 26 horses from group B were examined by a veterinarian in the period before death. None of the horses were known to exhibit clinical signs suggestive of neurologic disease. Among the main changes identified were vacuolation in the neuropil (n = 73), neurons (n = 32), white matter (n = 31), and focal perivascular lymphoid cell infiltrates (n = 35). Spheroids were frequently seen (n = 91), and 10 horses each had more than 10 spheroids in the cuneate or gracile nucleus. Statistically significant age-related changes noted included intraneuronal (n = 97) and glial or extracellular lipofuscin deposition (n = 41), hemosiderin deposition around blood vessels (n = 60), and calcium depositions (n = 24). One horse had low-grade nonsuppurative meningoencephalitis; Alzheimer type II cells were detected in the brains of 2 horses. Hyalinized vessel walls in the cerebellum were observed in 1 horse. It was concluded that some histopathologic changes are a frequent feature in equine brains, which has implications for the pathologists involved in equine neurology and disease surveillance.

Survey for transmissible spongiform encephalopathies in Irish pigs fed meat and bone meal.

Samples of brain and lymphoid tissues from 1107 meat and bone meal-fed, culled adult pigs from 24 Irish farms were examined for evidence of transmissible spongiform encephalopathy (TSE) by histopathological, immunohistochemical and Western blotting techniques. No evidence of deposits of abnormal prion protein suggesting the presence of TSE was found. Neuropil vacuolation was apparent in the rostral colliculus in 64 per cent of the brains examined and neuronal vacuolation was present in the dorsal vagal nucleus in 15.4 per cent of the brains. However, similar lesions have been described in pigs used as controls in a bovine spongiform encephalopathy challenge experiment. Age-related changes were also observed, including spheroids in the funicular nucleus of 24.5 per cent of the pigs, deposits of lipofuscin in the trigeminal neurons of 13.75 per cent, and mineral deposits in the walls of vessels in the dorsal vagal nucleus of 0.6 per cent. Low-grade non-suppurative inflammatory changes of uncertain origin were observed in 4 per cent of the animals.