Promoting clinically effective practice: general practitioners' awareness of sources of research evidence

BACKGROUND: Practitioners are being encouraged to base their clinical practice on research evidence. In order to do this, they must be aware of and use the sources of evidence. METHODS: A questionnaire survey was undertaken to establish GPs' awareness of research evidence in their clinical practice and, in fundholding practices, its influence on purchasing plans. Questionnaires were sent to 360 lead fundholders in North Thames Region and 440 of a random sample of the remaining general practitioners in the region for comparison. RESULTS: Questionnaires were returned by 62% of lead fundholders and 63% of GPs in the random sample. There was limited use of the electronic sources of clinical effectiveness. There was greater reported awareness of published sources of research evidence and fundholding GPs were significantly more likely to have referred to publications summarizing research evidence. CONCLUSIONS: GPs seem to make more use of published clinical effectiveness sources than the electronic databases. Consequently, they need educational and technical support if they are to make full use of the available sources of research evidence available in other media.      

LcrV plague vaccine with altered immunomodulatory properties

Yersinia pestis, the causative agent of plague, secretes LcrV (low-calcium-response V or V antigen) during infection. LcrV triggers the release of interleukin 10 (IL-10) by host immune cells and suppresses proinflammatory cytokines such as tumor necrosis factor alpha and gamma interferon as well as innate defense mechanisms required to combat the pathogenesis of plague. Although immunization of animals with LcrV elicits protective immunity, the associated suppression of host defense mechanisms may preclude the use of LcrV as a human vaccine. Here we show that short deletions within LcrV can reduce its immune modulatory properties. An LcrV variant lacking amino acid residues 271 to 300 (rV10) elicited immune responses that protected mice against a lethal challenge with Y. pestis. Compared to full-length LcrV, rV10 displayed a reduced ability to release IL-10 from mouse and human macrophages. Furthermore, the lipopolysaccharide-stimulated release of proinflammatory cytokines by human or mouse macrophages was inhibited by full-length LcrV but not by the rV10 variant. Thus, it appears that LcrV variants with reduced immune modulatory properties could be used as a human vaccine to generate protective immunity against plague.     

Liver-infiltrating T helper cells in autoimmune chronic active hepatitis stimulate the production of autoantibodies against the human asialoglycoprotein receptor in vitro.

Autoantibodies against the human asialoglycoprotein receptor (ASGPR) occur in the sera of patients with autoimmune liver disorders. Liver-infiltrating T cell clones that specifically recognize the ASGPR have been described in patients with autoimmune chronic active hepatitis (AI-CAH) and primary biliary cirrhosis (PBC). Recently, we have shown that peripheral blood mononuclear cells (PBMC) from patients with AI-CAH or PBC but not chronic viral hepatitis secreted anti-ASGPR antibodies in vitro. In this study we characterized the influence of liver-infiltrating T cells on the secretion of ASGPR-specific autoantibodies by autologous B cells in cell culture supernatants. T cell clones from liver biopsies of three patients with chronic autoimmune liver disorders (one with AI-CAH, two with PBC) were isolated and investigated for their proliferative response to soluble ASGPR and their helper function provided to autoantibody-secreting B lymphocytes. PBMC from these patients secreted autoantibodies spontaneously in their cell culture supernatants and showed a proliferative response to ASGPR. T cell-depleted PBMC, however, lacked spontaneous antibody secretion. Four CD4+CD8- liver-infiltrating T cell clones showed a proliferative response to ASGPR and also induced spontaneous anti-ASGPR antibody production in cell culture supernatants when added to autologous T cell depleted PBMC. Activated supernatants of these T cell clones failed to induce antibody production. None of seven CD4+CD8- and two CD4-CD8+ T cell clones non-responding to ASGPR provided this help for antibody secretion. Anti-ASGPR secretion in vitro could not be inhibited by the addition of MoAbs raised against monomorphic determinants on HLA class II molecules. The addition of purified ASGPR or polyclonal-activating pokeweed mitogen showed no influence on the production of autoantibodies in these cultures. These data show that B lymphocytes require T cell help for the production of ASGPR-specific antibodies. This help can be provided by ASGPR-responsive T helper cells via cellular interactions.     

PREVENTION OF POST-OPERATIVE WOUND INFECTION IN ABDOMINAL OPERATIONS

One hundred patients undergoing abdominal surgery were included in this prospective study. The role of local application of Betadine, use of synthetic sutures, and use of low pressure subcutaneous suction drainage were evaluated in preventing post-operative wound infection. The infection rate was 15 per cent with Betadine, 15.4 per cent with prolene, 20 per cent with subcutaneous suction drainage and 30.8 per cent in the control group.KEY WORDS: Surgical wound infection, Betadine, Sutures, Infection control