Spontaneous oral tumours in 18 rabbits (2005-2015).

This retrospective study of a series of 18 cases aimed to describe the clinical and pathological findings of oral tumours in rabbits, as there have been few reports detailing spontaneous oral tumours in this species. A total of 13 different tumour types were diagnosed: squamous cell carcinoma (three), ameloblastoma (two), fibrosarcoma (two), osteosarcoma (two), cementoma (one), complex odontoma (one), giant cell epulis (one), sarcoma (one), chondrosarcoma (one), trichoepithelioma (one), papilloma (one), malignant melanoma (one) and basal cell carcinoma (one). Odontogenic tumours were relatively common in this study as compared to the oral tumours typically identified in dogs and cats. The most common clinical sign in this study was feeding abnormalities. Surgical excision and radiation therapy were found to be effective in rabbits.

Spontaneous intranasal tumours in rabbits: 7 cases (2007-2019).

OBJECTIVES: Neoplasms that arise in the nasal cavity are reported infrequently in rabbits. This case series aims to review and determine the clinical behaviour of neoplasms in the nasal cavity in rabbits. MATERIALS AND METHODS: A retrospective study was conducted on seven pet rabbits diagnosed with intranasal tumours to describe the clinical and histopathological findings and prognoses after surgery and/or radiotherapy. RESULTS: The most common clinical signs were nasal snoring when breathing, nasal discharge, and subsequent dyspnoea and anorexia. Six different histopathological types of tumours were diagnosed: intranasal adenocarcinoma, squamous cell carcinoma, osteosarcoma, carcinoid tumour, osteoma, and lymphoma. Skull radiography only revealed the abnormalities in three of seven cases but on CT, the intranasal masses were more clearly identified in all cases. All cases received tumour resection through rhinostomy and four cases received radiotherapy after surgery. In the six cases with a known outcome, the survival time after surgery was more than 13 months. CLINICAL SIGNIFICANCE: This case series provides an insight of the behavior of intranasal neoplasms in rabbits. Surgical treatment and radiotherapy could improve their clinical sings.

Histological and Immunohistochemical Features of Normal Histiocytes and Langerhans Cells, and Histiocytic Sarcomas in Four-Toed Hedgehogs (Atelerix albiventris).

Histiocytic sarcoma (HS) is a haematopoietic tumour of histiocyte origin that has been sporadically reported in four-toed hedgehogs (Atelerix albiventris). The present study aimed to investigate clinical, gross, histopathological and immunohistochemical features of HS in eight hedgehogs. Histological and immunohistochemical features of normal histiocytes and Langerhans cells (LCs) of hedgehogs were also investigated. HLA-DR-, Iba-1- and E-cadherin-positive LCs were observed in the epidermis, while Iba-1- and CD204-positive histiocytes were detected in the lymph nodes and spleen of normal hedgehogs. Localized HS (six cases) developed in the skin and spleen, while disseminated HS (two cases) occurred in the intestine. Tumour cells of disseminated HS were also distributed within the mesenteric lymph nodes, liver, kidney, spleen, lung and adrenal glands. Tumour cells of both localized and disseminated HS were composed of histiocytic cells, spindle to pleomorphic cells, multinucleated giant cells and erythrophagocytic cells. Most tumour cells were immunopositive for Iba-1, CD204 and lysozyme. A small number of tumour cells were positive for E-cadherin and CD208, and the tumour cells in one case were positive for HLA-DR. These results suggest that the tumour cells have variable features of histiocyte origin, including dendritic cells, LCs and macrophages. The behaviour of HS in the hedgehog was very aggressive, and 50% of cases died within 90 days of resection. The present study also highlighted the tendency for local tumour recurrence in localized cutaneous HS cases, suggesting a requirement for a long-term follow-up after excision.

The suppressive effect on CD4 T cell alloresponse against endothelial HLA-DR via PD-L1 induced by anti-A/B ligation.

While donor-specific human leukocyte antigen (HLA) antibodies are a frequent cause for chronic antibody-mediated rejection in organ transplantation, this is not the case for antibodies targeting blood group antigens, as ABO-incompatible (ABO-I) organ transplantation has been associated with a favorable graft outcome. Here, we explored the role of CD4 T cell-mediated alloresponses against endothelial HLA-D-related (DR) in the presence of anti-HLA class I or anti-A/B antibodies. CD4 T cells, notably CD45RA-memory CD4 T cells, undergo extensive proliferation in response to endothelial HLA-DR. The CD4 T cell proliferative response was enhanced in the presence of anti-HLA class I, but attenuated in the presence of anti-A/B antibodies. Microarray analysis and molecular profiling demonstrated that the expression of CD274 programmed cell death ligand 1 (PD-L1) increased in response to anti-A/B ligation-mediated extracellular signal-regulated kinase (ERK) inactivation in endothelial cells that were detected even in the presence of interferon-γ stimulation. Anti-PD-1 antibody enhanced CD4 T cell proliferation, and blocked the suppressive effect of the anti-A/B antibodies. Educated CD25+ CD127- regulatory T cells (edu.Tregs ) were more effective at preventing CD4 T cell alloresponses to endothelial cells compared with naive Treg ; anti-A/B antibodies were not involved in the Treg -mediated events. Finally, amplified expression of transcript encoding PD-L1 was observed in biopsy samples from ABO-I renal transplants when compared with those from ABO-identical/compatible transplants. Taken together, our findings identified a possible factor that might prevent graft rejection and thus contribute to a favorable outcome in ABO-I renal transplantation.

Pharmacokinetics, Pharmacodynamic Efficacy Prediction Indexes and Monte Carlo Simulations of Enrofloxacin Hydrochloride Against Bacterial Strains That Induce Common Clinical Diseases in Broiler Chickens.

Pharmacokinetic parameters and efficacy prediction indexes (Cmax/MIC90 and AUC0-24/MIC90) of an enrofloxacin hydrochloride (ENR-HCl) veterinary product soluble in water were determined in healthy broiler chickens of both sexes after a single oral dose of ENR-HCl (equivalent to 10 mg ENR base/kg bw). Monte Carlo simulations targeting Cmax/MIC90 = 10 and AUC0-24/MIC90 =125 were also performed based on a set of MIC (minimum inhibitory concentration) values of bacterial strains that induce common clinical diseases in broiler chickens and that showed to be susceptible to ENR-HCl. Plasma concentrations of ENR and its main metabolite ciprofloxacin (CIP) were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma concentration-time curves were found to fit a non-compartmental open model. The ratio of the area under the plasma concentration-time curve (AUC) of CIP/ENR was 4.91%. Maximum plasma concentrations of 1.35 ± 0.15 µg/mL for ENR-HCl and 0.09 ± 0.01 µg/mL for CIP were reached at 4.00 ± 0.00 h and 3.44 ± 1.01 h, respectively. Areas under the plasma vs. time concentration curve in 24 h (AUC0-24) were 18.91 ± 1.91 h × µg/mL and 1.19 ± 0.12 h × µg/mL for ENR-HCl and CIP, respectively. Using a microbroth dilution method, the minimum inhibitory concentration (MIC90) values were determined for ENR-HCl for 10 bacterial strains (Mycoplasma gallisepticum, Mycoplasma synoviae, Avibacterium paragallinarum, Clostridium perfringens, Escherichia coli, Pseudomonas aeruginosa, Salmonella ser. Enteritidis, Salmonella ser. Gallinarum, Salmonella ser. Pullorum, and Salmonella ser. Typhimurium), which are the most common causes of infectious clinical diseases in broiler chickens. In summary, the PK/PD ratios and Monte Carlo simulation were carried out for ENR-HCl in poultry, which due to its solubility was administered in drinking water. The PK/PD efficacy prediction indexes and Monte Carlo simulations indicated that the ENR-HCl oral dose used in this study is useful for bacterial infections in treating C. perfringens (Gram-positive), E. coli and S. ser. Enteritidis (Gram-negative) and M. gallisepticum bacteria responsible for systemic infections in poultry, predicting a success rate of 100% when MIC ≤ 0.06 µg/mL for E. coli and S. ser. Enteritidis and MIC ≤ 0.1 µg/mL for M. gallisepticum. For C. perfringens, the success rate was 98.26% for MIC ≤ 0.12. However, clinical trials are needed to confirm this recommendation.

Broad-spectrum antibiotic prescriptions are discontinued unevenly throughout the week.

In order to investigate prescribing patterns of in-hospital broad-spectrum antibiotics (antimeticillin-resistant Staphylococcus aureus drugs, carbapenems and piperacillin/tazobactam), data on the distribution of antibiotic initiation and discontinuation throughout the week were analysed at Osaka University Hospital, Japan. No significant differences in the number of initiations were found between weekdays. However, broad-spectrum antibiotics were disproportionately discontinued on Tuesdays or on the second day after a holiday. This study suggests that broad-spectrum antibiotics tend to be continued over weekends or holidays and discontinued thereafter; this is likely to be due to behavioural factors beyond medical indications, and needs to be addressed in future antimicrobial stewardship initiatives.

Amyloid-producing Odontoameloblastoma in a Black-tailed Prairie Dog (Cynomys ludovicianus).

A 6-year-old female black-tailed prairie dog (Cynomys ludovicianus) was presented with a space-occupying lesion in the left submandibular region. On computed tomography, a low attenuating, poorly circumscribed mass infiltrated the left mandibular bone, with osteolytic change. Microscopically, the lesion was composed of odontogenic epithelium proliferating in nests and embedded in abundant dental papilla-like ectomesenchyme, including dentine and enamel. Multifocal amyloid deposition was observed. Immunohistochemically, the neoplastic epithelial cells were positive for cytokeratin (CK) AE1/AE3, CK14 and p63. Some epithelial cells were positive for amelogenin and some adjacent to the amyloid deposits co-expressed S100. The ectomesenchymal cells expressed vimentin and strong S100 immunoreactivity was observed in odontoblast-like cells. The amyloid was immunolabelled with amelogenin. The tumour was diagnosed as amyloid-producing odontoameloblastoma.

Histopathological and Immunohistochemical Study of Trichoblastoma in the Rabbit.

Trichoblastoma is the most common skin tumour in the rabbit. The aim of the present study was to characterize the histological and immunohistochemical features of trichoblastoma in 27 rabbits. Common sites of tumour occurrence were the neck (6/30, 20%), head (5/30, 16.7%), flank (4/30, 13.3%) and hindlimb (4/30, 13.3%). Histologically, rabbit trichoblastoma was categorized into ribbon (10/30, 33.3%), trabecular (8/30, 26.7%) and mixed types (12/30, 40%). The tumour tissue showed close interaction with the surrounding stroma where prominent fibroblastic aggregation, known as papillary mesenchymal bodies, was frequently observed (24/30; 80%). Peritumoural stroma of all cases was stained by Alcian blue (at pH 2.5 with weaker staining at pH 1.0). Immunohistochemically, the peripheral palisading basal-type cells of the tumour were positive for cytokeratin (CK) 14 while the inner cells were typically positive for CK17, differing from the immunohistochemical profile of the rabbit epidermis and hair follicle. The present study suggests that uncontrolled embryonic trichogenesis is involved in the development of trichoblastoma in the rabbit.

Lachrymal Gland Basal Cell Adenocarcinoma in a Ferret (Mustela putorius furo).

A 1 cm diameter mass was detected in the caudal superotemporal area of the left eye of a 6-year-old neutered male ferret (Mustela putorius furo). The mass and the left eye were removed surgically. Microscopical examination revealed a tumour of the adnexal gland of the eye that had invaded the surrounding ocular muscle. The tumour was composed of basal-type epithelial cells arranged in a solid, or occasionally tubular, pattern. Immunohistochemically, the tumour cells expressed cytokeratin and p63, but not smooth muscle actin. Based on these findings, the tumour was diagnosed as a basal cell adenocarcinoma of the lachrymal gland. In addition to the tumour, the retina of the left eye was detached and folded at the centre of the globe. This is the first report of a non-human case of basal cell adenocarcinoma of the lachrymal gland.

A Concept of Cross-Ferroic Plasma Turbulence.

The variety of scalar and vector fields in laboratory and nature plasmas is formed by plasma turbulence. Drift-wave fluctuations, driven by density gradients in magnetized plasmas, are known to relax the density gradient while they can generate flows. On the other hand, the sheared flow in the direction of magnetic fields causes Kelvin-Helmholtz type instabilities, which mix particle and momentum. These different types of fluctuations coexist in laboratory and nature, so that the multiple mechanisms for structural formation exist in extremely non-equilibrium plasmas. Here we report the discovery of a new order in plasma turbulence, in which chained structure formation is realized by cross-interaction between inhomogeneities of scalar and vector fields. The concept of cross-ferroic turbulence is developed, and the causal relation in the multiple mechanisms behind structural formation is identified, by measuring the relaxation rate and dissipation power caused by the complex turbulence-driven flux.

The effect of aprepitant and dexamethasone combination on paclitaxel-induced hypersensitivity reaction.

PURPOSE OF INVESTIGATION: Dexamethasone (DEX) is often administered to prevent paclitaxel (PTX)-induced hypersensitivity reactions (HSR). The DEX dose is reduced when administered in combination with aprepitant (APR). However, the influence of that dose reduction on PTX-induced HSR has not been thoroughly studied. The present authors aimed to investigate the effects of the combined administration of APR and DEX on PTX-induced HSR. MATERIALS AND METHODS: Fifty-one patients who received a three-week PTX regimen in combination with APR and DEX were retrospectively analysed. The authors compared the dose of DEX with the incidence of HSR and other toxicities. RESULTS: Patients were stratified into two groups depending on the DEX dose, > 20 mg (group D, 33 patients), and < 12 mg (group reD, 26 patients). The incidence of HSR in Groups D and reD were 51.5% (17/33) and 53.8% (14/26), respectively. The frequencies of other toxicities between the groups were comparable. CONCLUSION: The findings suggest that although a reduction in DEX dose is possible when APR is co-administered, this does not affect the PTX-induced HSR. However, adverse effect should be closely monitored.

Industry and regulatory performance in 2012: a year in review.

2012 was a robust year for new molecular entity (NME) approvals in the major geographic regions. What is behind this apparent improved performance? Has the pharmaceutical industry turned the tide in research and development productivity? In this analysis, we look not only at the number of approvals in 2012 but also at their clinical and market potential. We discuss how changes in the regulatory and reimbursement environment impact current industry performance and how this might evolve.

Young adult preferences for physician decision-making style in Japan and the United States.

Studies in Japan and the United States investigate preferences for patient-physician decision-making style among young adults in the context of a primary care clinic visit for an upper respiratory infection. A treatment scenario described 1 of 3 decision-making styles: a young adult and doctor using a passive (physician decides), shared (patient and physician decide together), or autonomous (patient decides from a set of medically appropriate alternatives) decision-making style. Unexpectedly, Japanese respondents evaluated the autonomous interaction most positively. US respondents evaluated the shared decision-making scenario most positively. Overall, despite large cultural differences, both country samples favored higher participation in decision making. These results suggest that passive patient approaches are falling out of favor as patient-centered care expectations diffuse globally, even in traditionally hierarchic societies with high levels of respect for authority. The implications of these findings along with managerial implications and suggestions for future research are presented.

Clinical and pathologic features of neuronal ceroid-lipofuscinosis in a ferret (Mustela putorius furo).

Clinical and pathologic features of neuronal ceroid-lipofuscinosis in a 4-month-old ferret are reported. Clinical signs including neurological symptoms appeared at 3 months of age and progressed rapidly. By magnetic resonance imaging, severe cerebral atrophy was recognized. Histopathologically, there was severe neuronal loss and diffuse astrogliosis with macrophage accumulations; lesions were found predominantly in the cerebral cortex. Intracytoplasmic pigments were observed in surviving neurons and macrophages throughout the brain. The pigments were intensely positive for periodic acid-Schiff, Luxol fast blue, and Sudan black B and exhibited a green autofluorescence. Electron microscopic examination revealed the accumulation of electron-dense granular material within lysosomes of neurons and macrophages. Immunohistochemically, a large number of saposin-positive granules accumulated in the neuronal cells, astrocytes, and macrophages of the lesions, but significant immunoreactivity for subunit c of mitochondrial adenosine triphosphate synthase was not observed. Based on these findings, the animal was diagnosed as affected by neuronal ceroid-lipofuscinosis.

Association of insulin-like growth factor-1 receptor gene polymorphisms with left ventricular mass and geometry in essential hypertension.

Stimulation of insulin-like growth factor (IGF)-1 receptor by IGF-1 and insulin strongly induces cardiomyocyte hypertrophy. In this study, we assessed the hypothesis that genetic variations of the IGF-1 receptor may be linked to the diversity of left ventricular (LV) structure in hypertensive patients. Genotypes in 12 single nucleotide polymorphisms (SNPs) of the IGF-1 receptor gene identified by direct sequencing were determined in 795 Japanese patients with essential hypertension. In echocardiographic examinations, LV mass index (LVMI) and relative wall thickness (RWT) were measured. Among 12 SNPs, promoter -328C>T and intron-13 275124A>C polymorphisms were significantly associated with LV hypertrophy (LVMI> or =125 g m(-2)) and concentric change (RWT> or =0.44), respectively. In allele frequencies, the C allele of -328C>T was related to LV hypertrophy, and the A allele of 275124A>C was related to LV concentric change. In fact, LVMI and prevalence of LV hypertrophy increased in CC genotype of -328C>T. RWT and prevalence of LV concentric change increased in AA genotype of 275124A>C. A multiple logistic regression analysis revealed that the presence of CC genotype of -328C>T or AA genotype of 275124A>C was an independent determinant for LV hypertrophy or concentric change, respectively. Furthermore, the combination of CC of -328C>T and AA of 275124A>C genotypes was significantly associated with abnormal LV geometry, especially concentric hypertrophy. Our findings show that two SNPs of the IGF-1 receptor gene are related to LV hypertrophy in patients with essential hypertension, suggesting that the genetic variation of the IGF-1 receptor may be involved in the diversity of LV structure in hypertensives.

Pretransplant pharmacodynamic analysis of immunosuppressive agents using CFSE-based T-cell proliferation assay.

The impact of pretransplant T-cell sensitivity testing using carboxylfluorescein diacetate succinimidyl ester (CFSE)-based flow cytometry was studied in 32 patients with chronic renal failure. There was considerable interindividual variation in the inhibitory effects of cyclosporine (CSA), tacrolimus (TAC), and prednisolone (PRD) but only a small amount of interindividual variation for mycophenolic acid (MPA). Patients with high sensitivity to CSA tended to experience viral reactivation. In addition to post-transplant blood-level monitoring, pretransplant pharmacodynamics could provide useful information on optimal and safe immunosuppressive therapy.

Safety studies of LP20 powder produced from heat-killed Lactobacillus plantarum L-137.

The safety of LP20 and its prototype, a powder, with potential use in food, produced from a mixture of dextrin and heat-killed Lactobacillus plantarum L-137, was assessed in an acute study in mice, and in an in vitro bacterial reverse mutation assay, an in vitro chromosome aberration assay, and an in vivo mouse micronucleus assay. LP20 prototype was not acutely toxic when administered to male and female Slc:ICR mice by single gavage at 2000mg/kg bw. Dosing was not associated with mortality, clinical signs, changes in bodyweight, or macroscopic abnormalities. The LD(50) in mice was greater than 2000mg/kg bw. There was no evidence of genotoxicity of LP20 in the Ames assay (0-5000microg/plate) or in the in vitro chromosome aberration assay with Chinese hamster lung fibroblasts (0-5000microg/mL). Administration of two consecutive daily doses of 500, 1000, or 2000mg/kg bw by gavage to male Crlj:CD-1 mice was not associated with an increased incidence of micronuclei and did not alter the ratio of polychromatic to normochromatic erythrocytes. These studies show that LP20 powder is not acutely toxic and is without genotoxic activity both in vitro and in vivo.

Elevated serum levels of soluble CX3CL1 in patients with microscopic polyangiitis.

OBJECTIVES: To test the hypothesis that CX3CL1 contributes to the pathogenesis of microscopic polyangiitis. METHODS: Serum samples from 18 patients with microscopic polyangiitis (MPA), who fulfilled the revised criteria of the American College of Rheumatology (ACR), were collected during both the newly diagnosed, untreated active disease states and inactive disease states. Also serum was from patients with large vessel vasculitis (LVV), including giant cell arteritis (n=4) and Takayasu arteritis (n=3), and from 52 healthy individuals. Soluble (s)CX3CL1 levels in serum were measured using an enzyme-linked immunosorbent assay. Disease activity was assessed using Birmingham vasculitis activity scores (BVAS). Expression of CX3CR1 was examined by flow cytometry. RESULTS: Serum sCX3CL1 levels were significantly higher in MPA patients than in either LVV group or healthy individuals. The elevated sCX3CL1 levels seen in MPA patients correlated positively with BVAS, as well as with CRP levels and ESR, and similarly increased expression of cell-surface CX3CR1 was seen on peripheral blood CD4 and CD8 T cells from patients with MPA. Notably, sCX3CL1 levels and CX3CR1 expression were diminished during clinical remission following treatment. CONCLUSION: Our findings suggest that CX3CL1 may be involved in the pathogenesis of MPA, and may serve as a useful serologic marker of disease activity in systemic vasculitis.

Localised radiotherapy for a ferret with possible anal sac apocrine adenocarcinoma.

A seven-year-old, neutered male ferret was referred to our hospital with two perianal masses (2.4x3.0 and 2.4x3.5 cm, respectively) that had recurred after initial surgical excision. Complete resection of the masses was impossible as there was deep invasion along the rectum. On histopathology, the masses were diagnosed as apocrine adenocarcinoma possibly of anal gland origin based on tumour location. There was marked response to localised radiotherapy using an orthovoltage unit at 4 Gy, twice weekly. No visible mass was detectable after six doses of radiation. However, at that time, pleural effusion was diagnosed and radiotherapy was discontinued. Cytology of a sample of the pleural effusion suggested mesothelioma, and no obvious pulmonary metastasis of anal sac adenocarcinoma were identified on thoracic radiography. The ferret died at home on day 71 after the first admission.