81 research outputs found

    Immunopathogenesis of canine atopic dermatitis

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    Atopic dermatitis (AD) is a chronic inflammatory and pruritic skin disease commonly seen in dogs and humans. Most cases involve hypersensitivity to the house dust mites Dertnatophagoides farinae and D. pteronyssinus. This study has shown that Dermatophagoides specific IgE and peripheral blood mononuclear cell (PBMC) responses were largely restricted to skin test positive atopic dogs. Furthermore, immunoblotting and PBMC proliferation studies demonstrated that the major target of immune recognition is a 98/104kD protein, rather than the low molecular weight group 1 and 2 proteins important in humans. The close association between serological findings and PBMC proliferation implies that T-cells participate in the pathogenesis of canine AD by supporting IgE production. Human AD is associated with T-helper 2 (TH2) type responses, although THi cytokines are present in chronic lesions. In contrast, tolerance in healthy individuals is mediated by regulatory T-cells. Using semi-quantitative reverse transcriptase-polymerase chain reactions, this study found that canine AD is associated with over-production of the TH2 cytokine interleukin (IL)-4, whilst tolerance in healthy individuals is associated with the immuno-suppressive cytokines transforming growth factor beta and EL-10. Higher levels of the THi cytokines interferon gamma, tumour necrosis factor alpha and IL-2 seen in lesional compared to non-lesional and healthy skin could be induced by subsequent self-trauma and secondary infections. These results characterise the first spontaneously occurring animal model of human AD

    Real-world experience of Ibrutinib therapy in relapsed chronic lymphocytic leukaemia: results of a single-centre retrospective analysis

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    Background: Ibrutinib is a Bruton’s tyrosine-kinase (BTK) inhibitor that is approved as a second-line treatment in chronic lymphocytic leukemia (CLL). While recent trials have demonstrated impressive results for ibrutinib, there remains a paucity of real-world data on its use in the clinical setting. Methods: In this single-center study carried out at Brighton and Sussex University Hospitals, we retrospectively compared outcomes in 38 patients with relapsed CLL who received ibrutinib versus those who received conventional first- and second-line therapies. Results: Our results demonstrate improved progression-free survival (PFS, p=0.022) with ibrutinib versus conventional second-line therapies and survival comparable to conventional first-line therapies. However, there was a high frequency (81.6%) of adverse events associated with ibrutinib therapy, including 2 cases of death secondary to sepsis and a further 7 cases of discontinuation of treatment due to adverse events. We also identify del13q14.3 as an adverse predictor of response to ibrutinib with respect to both overall survival (p=0.014) and PFS (p=0.008), suggesting that these patients may be better suited to receiving the BCL2 inhibitor venetoclax. Conclusion: Whilst there is robust evidence for improved outcomes with ibrutinib, we find that survival in patients with del13q14.3 is reduced and that the rate of adverse events and discontinuation in clinical practice is higher than anticipated from clinical trials

    Carriage of antimicrobial resistant Escherichia coli in dogs: prevalence, associated risk factors and molecular characteristics

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    Resistance to antimicrobials, in particular that mediated by extended spectrum β-lactamases (ESBL) and AmpC β-lactamases are frequently reported in bacteria causing canine disease as well as in commensal bacteria, which could be a potential health risk for humans they come into contact with. This cross-sectional study aimed to estimate the prevalence and investigate the molecular characteristics of ESBL and plasmid encoded AmpC (pAmpC)-producing E. coli in the mainland UK vet-visiting canine population and, using responses from detailed questionnaires identify factors associated with their carriage. Faecal samples were cultured for antimicrobial resistant (AMR), ESBL and pAmpC-producing E. coli. A subset of ESBL and pAmpC-producing isolates were subjected to multi-locus sequence typing and DNA microarray analyses. Multivariable logistic regression analysis was used to construct models to identify risk factors associated with multidrug resistant (MDR, resistance to three or more antimicrobial classes), fluoroquinolone resistant, ESBL and AmpC-producing E. coli. AMR E.coli were isolated from 44.8% (n = 260) of samples, with 1.9% and 7.1% of samples carrying ESBL and pAmpC-producing E. coli, respectively. MDR E. coli were identified in 18.3% of samples. Recent use of antimicrobials and being fed raw poultry were both identified as risk factors in the outcomes investigated. A number of virulence and resistance genes were identified, including genes associated with extra-intestinal and enteropathogenic E. coli genotypes. Considering the close contact that people have with dogs, the high levels of AMR E. coli in canine faeces may be a potential reservoir of AMR bacteria or resistance determinants

    Esophageal feeding tube placement and the associated complications in 248 cats

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    Abstract Background Esophageal feeding tubes are commonly used to provide enteral nutrition to cats, but their use is associated with adverse effects. Objectives To evaluate the complications associated with e‐tube placement in cats and to identify factors predisposing to these complications. Animals Cats that had an esophageal feeding tube placed (n = 248). Methods This was a retrospective case review in which clinical records were interrogated across 2 referral centers to identify records of cats that had esophageal tubes placed. Clinical data were collected for signalment, clinical indication, method of placement, time of removal, and any complications. Logistic regression was then employed to assess the odds of an increase in complications, including infection and death. Results For those cats that survived to discharge, tubes were in place for a median of 11 days, ranging from 1 to 93 days. Complications occurred in 35.8% of the cats, with the most common being tube dislodgement (14.5%), followed by stoma site infections (12.1%). Cats receiving glucocorticoids or oncolytic agents (OR = 3.91; 95% CI, 1.14‐13.44) and with discharge at the stoma site (OR = 159.8; CI, 18.9‐1351) were at an increased odds of developing a stoma site infection, whereas those with a lower weight (OR = 1.33; 95% CI, 1.02‐1.75) or (pancreatic [OR = 4.33; 95% CI, 1.02‐18.47], neoplastic [OR = 15.44; 95% CI, 3.67‐65.07], respiratory [OR = 19.66; 95% CI, 2.81‐137.48], urogenital [OR = 5.78; 95% CI, 1.15‐28.99], and infectious diseases [OR = 11.57; 95% CI, 2.27‐58.94]) had an increased odds of death. The duration of time in place and the cat being discharged with the tube in place were not associated with an increased risk of infection or death. Conclusions and clinical importance Owners should be made aware of the potential risks involved and their predisposing factors

    Protocol for 'Seal or Varnish' (SoV) trial: A randomised controlled trial to measure the relative cost and effectiveness of pit and fissure sealants and fluoride varnish in preventing dental decay

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    Background Dental caries remains a significant public health problem, prevalence being linked to social and economic deprivation. Occlusal surfaces of first permanent molars are the most susceptible site in the developing permanent dentition. Cochrane reviews have shown pit and fissure sealants (PFS) and fluoride varnish (FV) to be effective over no intervention in preventing caries. However, the comparative cost and effectiveness of these treatments is uncertain. The primary aim of the trial described in this protocol is to compare the clinical effectiveness of PFS and FV in preventing dental caries in first permanent molars in 6-7 year-olds. Secondary aims include: establishing the costs and the relative cost-effectiveness of PFS and FV delivered in a community/school setting; examining the impact of PFS and FV on children and their parents/carers in terms of quality of life/treatment acceptability measures; and examining the implementation of treatment in a community setting. Methods/design The trial design comprises a randomised, assessor-blinded, two-arm, parallel group trial in 6–7 year old schoolchildren. Clinical procedures and assessments will be performed at 66 primary schools, in deprived areas in South Wales. Treatments will be delivered via a mobile dental clinic. In total, 920 children will be recruited (460 per trial arm). At baseline and annually for 36 months dental caries will be recorded using the International Caries Detection and Assessment System (ICDAS) by trained and calibrated dentists. PFS and FV will be applied by trained dental hygienists. The FV will be applied at baseline, 6, 12, 18, 24 and 30 months. The PFS will be applied at baseline and re-examined at 6, 12, 18, 24, and 30 months, and will be re-applied if the existing sealant has become detached/is insufficient. The economic analysis will estimate the costs of providing the PFS versus FV. The process evaluation will assess implementation and acceptability through acceptability scales, a schools questionnaire and interviews with children, parents, dentists, dental nurses and school staff. The primary outcome measure will be the proportion of children developing new caries on any one of up to four treated first permanent molars. Discussion The objectives of this study have been identified by the National Institute for Health Research as one of importance to the National Health Service in the UK. The results of this trial will provide guidance on which of these technologies should be adopted for the prevention of dental decay in the most susceptible tooth-surface in the most at risk children

    Fibro-Vascular Coupling in the Control of Cochlear Blood Flow

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    Transduction of sound in the cochlea is metabolically demanding. The lateral wall and hair cells are critically vulnerable to hypoxia, especially at high sound levels, and tight control over cochlear blood flow (CBF) is a physiological necessity. Yet despite the importance of CBF for hearing, consensus on what mechanisms are involved has not been obtained.We report on a local control mechanism for regulating inner ear blood flow involving fibrocyte signaling. Fibrocytes in the super-strial region are spatially distributed near pre-capillaries of the spiral ligament of the albino guinea pig cochlear lateral wall, as demonstrably shown in transmission electron microscope and confocal images. Immunohistochemical techniques reveal the inter-connected fibrocytes to be positive for Na+/K+ ATPase β1 and S100. The connected fibrocytes display more Ca(2+) signaling than other cells in the cochlear lateral wall as indicated by fluorescence of a Ca(2+) sensor, fluo-4. Elevation of Ca(2+) in fibrocytes, induced by photolytic uncaging of the divalent ion chelator o-nitrophenyl EGTA, results in propagation of a Ca(2+) signal to neighboring vascular cells and vasodilation in capillaries. Of more physiological significance, fibrocyte to vascular cell coupled signaling was found to mediate the sound stimulated increase in cochlear blood flow (CBF). Cyclooxygenase-1 (COX-1) was required for capillary dilation.The findings provide the first evidence that signaling between fibrocytes and vascular cells modulates CBF and is a key mechanism for meeting the cellular metabolic demand of increased sound activity

    Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers

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    We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20h10m54.71s+33°33′25.29′′, and the other (B) is 7.45° in diameter and centered on 8h35m20.61s-46°49′25.151′′. We explored the frequency range of 50-1500 Hz and frequency derivative from 0 to -5×10-9 Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h0 of 6.3×10-25, while at the high end of our frequency range we achieve a worst-case upper limit of 3.4×10-24 for all polarizations and sky locations. © 2016 American Physical Society
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