Facilitating collaboration using a clinical teams programme

The Clinical Teams Programme aims to develop clinical leadership. This article describes how it was used to improve teamworking at Reading PCT. The programme enhanced clinical leadership by improving confidence, allowing the development of effective teams and providing solutions to improve existing practice and patient care.     

The use of infrared aided photography in identification of sites of bruises after evidence of the bruise is absent to the naked eye

The purpose of the study was to determine whether Infrared imaging could play a role in the detection of previous blunt force injury after resolution of skin changes were no longer visible to the human eye. Investigations were performed using an adapted digital camera and the same standard Nikon camera body to photograph the bruises of ten volunteer adult subjects. The same lens was fitted to each camera body and each bruise was photographed until it was no longer possible to identify it with the naked eye.The results of photographing subjects over 6 months demonstrated that the median time the bruises persisted in both groups was approximately between 18 and 19 days. There was no statistically significant difference between groups of bruises photographed with both the infrared digital camera that had been adapted to capture only infrared light, and with the standard camera which had the same lens fitted to it.The two groups of photographs of bruises imaged at the same time with the two cameras were not significantly different with regard to what skin changes could be detected. The use of the near infrared spectrum, with wavelengths that are longer than the human eye can detect, did not reveal significant evidence of bruising after it had faded from view to both the human eye and to a standard camera.     

Anti-neutrophil cytoplasm antibody IgG subclasses in Wegener's granulomatosis: a possible pathogenic role for the IgG4 subclass

A characteristic feature of Wegener's granulomatosis is the presence of antineutrophil cytoplasm antibodies (ANCA) to proteinase 3 (PR3). In vitro, ANCA activate neutrophils by co-ligating PR3 and FcgammaRIIa/IIIb receptors. ANCA are predominantly of the IgG isotype, and IgG1, IgG3 and IgG4 subclasses are particularly represented. To address the pathogenic role of individual ANCA-IgG subclass antibodies, patients' sera were screened using indirect immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and subclass PR3-ELISA to identify patients with high titres of PR3-ANCA within the IgG1, IgG3 or IgG4 subclasses. Unfractionated ANCA-IgG and subclass fractions were isolated by affinity chromatography and compared for their capacities to stimulate superoxide production by primed human neutrophils. Donor neutrophils were analysed for constitutive and induced FcgammaRI expression by flow cytometry. The IgG1, IgG3 and IgG4 subclass fractions, isolated from three different ANCA sera, each stimulated superoxide production from neutrophils derived from multiple donors. Subsequently, IgG4 subclass fractions isolated from a further four ANCA positive sera demonstrated varying abilities to stimulate release of superoxide; unrelated to PR3-ANCA titre, neutrophil donor, or neutrophil FcgammaRI expression. The stimulation of superoxide release by IgG1- and IgG3-ANCA subclass fractions is consistent with the proposed mechanism of co-ligation of PR3 antigen and FcgammaRIIa/IIIb receptors. However, the demonstration of similar activity for the IgG4-ANCA subclass fractions isolated from some sera was unexpected. This activity was independent of neutrophil donor and expression of FcgammaRI, suggesting it was capable of activating neutrophils via constitutively expressed FcgammaRIIa/IIIb or co-ligation of other, unidentified, cell surface molecules.     

TSLP production by dendritic cells is modulated by IL‐1β and components of the endoplasmic reticulum stress response

Thymic stromal lymphopoietin (TSLP) produced by epithelial cells acts on dendritic cells (DCs) to drive differentiation of T_H2‐cells, and is therefore important in allergic disease pathogenesis. However, DCs themselves make significant amounts of TSLP in response to microbial products, but little is known about the key downstream signals that induce and modulate this TSLP secretion from human DCs. We show that human monocyte derived DC (mDC) secretion of TSLP in response to Candida albicans and β‐glucans requires dectin‐1, Syk, NF‐κB, and p38 MAPK signaling. In addition, TSLP production by mDCs is greatly enhanced by IL‐1β, but not TNF‐α, in contrast to epithelial cells. Furthermore, TSLP secretion is significantly increased by signals emanating from the endoplasmic reticulum (ER) stress response, specifically the unfolded protein response sensors, inositol‐requiring transmembrane kinase/endonuclease 1 and protein kinase R‐like ER kinase, which are activated by dectin‐1 stimulation. Thus, TSLP production by mDCs requires the integration of signals from dectin‐1, the IL‐1 receptor, and ER stress signaling pathways. Autocrine TSLP production is likely to play a role in mDC‐controlled immune responses at sites removed from epithelial cell production of the cytokine, such as lymphoid tissue.     

Autoreactive human peripheral blood CD8+ T cells with a regulatory phenotype and function

Despite substantial advances in our understanding of CD4+ CD25+ regulatory T cells, a possible equivalent regulatory subset within the CD8+ T cell population has received less attention. We now describe novel human CD8+/TCR alphabeta+ T cells that have a regulatory phenotype and function. We expanded and cloned these cells using autologous LPS-activated dendritic cells. The clones were not cytolytic, but responded in an autoreactive HLA class I-restricted fashion, by proliferation and production of IL-4, IL-5, IL-13 and TGFbeta1, but not IFN-gamma. They constitutively expressed CD69 and CD25 as well as molecules associated with CD4+ CD25+ regulatory T cells, including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and Foxp3. They suppressed IFN-gamma production and proliferation by CD4+ T cells in vitro in a cell contact-dependent manner, which could be blocked using a CTLA-4-specific mAb. They were more readily isolated from patients with ankylosing spondylitis and may therefore be up-regulated in response to inflammation. We suggest that they are the CD8+ counterparts of CD4+ CD25+ regulatory T cells. They resemble recently described CD8+ regulatory cells in the rat that were able to abrogate graft-versus-host disease. Likewise, human HLA-restricted CD8+ regulatory T cells that can be cloned and expanded in vitro may have therapeutic applications.     

Identification of two major virion protein genes of white spot syndrome virus of shrimp

White Spot Syndrome Virus (WSSV) is an invertebrate virus, causing considerable mortality in shrimp. Two structural proteins of WSSV were identified. WSSV virions are enveloped nucleocapsids with a bacilliform morphology with an approximate size of 275 x 120 nm, and a tail-like extension at one end. The double-stranded viral DNA has an approximate size 290 kb. WSSV virions, isolated from infected shrimps, contained four major proteins: 28 kDa (VP28), 26 kDa (VP26), 24 kDa (VP24), and 19 kDa (VP19) in size, respectively. VP26 and VP24 were found associated with nucleocapsids; the others were associated with the envelope. N-terminal amino acid sequences of nucleocapsid protein VP26 and the envelope protein VP28 were obtained by protein sequencing and used to identify the respective genes (vp26 and vp28) in the WSSV genome. To confirm that the open reading frames of WSSV vp26 (612) and vp28 (612) are coding for the putative major virion proteins, they were expressed in insect cells using baculovirus vectors and analyzed by Western analysis. A polyclonal antiserum against total WSSV virions confirmed the virion origin of VP26 and VP28. Both proteins contained a putative transmembrane domain at their N terminus and many putative N- and O-glycosylation sites. These major viral proteins showed no homology to baculovirus structural proteins, suggesting, together with the lack of DNA sequence homology to other viruses, that WSSV may be a representative of a new virus family, Whispoviridae.     

Implementation of Advanced Access in general practice: postal survey of practices

BACKGROUND: Advanced Access has been strongly promoted as a means of improving access to general practice. Key principles include measuring demand, matching capacity to demand, managing demand in different ways and having contingency plans. Although not advocated by Advanced Access, some practices have also restricted availability of pre-booked appointments. AIM: This study compares the strategies used to improve access by practices which do or do not operate Advanced Access. DESIGN OF STUDY: Postal survey of practices. SETTING: Three hundred and ninety-one practices in 12 primary care trusts. METHOD: Questionnaires were posted to practice managers to collect data on practice characteristics, supply and demand of appointments, strategies employed to manage demand, and use of Advanced Access. RESULTS: Two hundred and forty-five from 391 (63%) practices returned a questionnaire and 162/241(67%) claimed to be using Advanced Access. There were few differences between characteristics of practices operating Advanced Access or not. Both types of practice had introduced a wide range of measures to improve access. The proportion of doctors' appointments only available for booking on the same day was higher in Advanced Access practices (40 versus 16%, difference = 24%, 95% CI = 16% to 32%). Less than half the practices claiming to operate Advanced Access ((63/140; 45%) used all four of this model's key principles. CONCLUSION: The majority of practices in this sample claim to have introduced Advanced Access, but the degree of implementation is very variable. Advanced Access practices use more initiatives to measure and improve access than non-Advanced Access practices.     

Dopamine manipulations limited to preexposure are sufficient to modulate latent inhibition

Four experiments are reported that demonstrated that dopamine (DA) transmission is involved in the acquisition of latent inhibition (LI) of a conditioned taste aversion. LI refers to weaker conditioning as a consequence of nonreinforced preexposure (PE) of the future conditioned stimulus. Although it is known to depend on DA transmission during the conditioning phase, it is usually thought that the cognitive processes involved in the establishment of LI (during the PE phase) are DA independent. Either amphetamine (AMPH; 0.5 or 1.0 mg/kg) or haloperidol (HAL; 0.1 mg/kg) were injected before 1 or all of the 3 PE sessions. AMPH blocked the acquisition of LI if it was injected before each or before only the last PE session and HAL potentiated LI. ((c) 2006 APA, all rights reserved).