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.      

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.     

Weaning anorexia may contribute to local inflammation in the piglet small intestine

Compromising alterations in villus-crypt structure are common in pigs postweaning. Possible contributions of local inflammatory reactions to villus-crypt alterations during the weaning transition have not been described. This study evaluated local inflammatory responses and their relationship with morphological changes in the intestine in 21-d-old pigs (n = 112) killed either at weaning (Day 0) or 0.5, 1, 2, 4 or 7 d after weaning to either milk- or soy-based pelleted diets. Cumulative intake averaged <100 g during the first 2 d postweaning, regardless of diet. During this period of weaning anorexia, inflammatory T-cell numbers and local expression of the matrix metalloproteinase stromelysin increased while jejunal villus height, crypt depth and major histocompatibility complex (MHC) class I RNA expression decreased. Upon resumption of feed intake by the fourth d postweaning, villus height and crypt depth, CD8(+) T cell numbers, MHC class I RNA expression and local expression of stromelysin returned to Day 0 values. Together the results indicate that inadequate feed intake during the immediate postweaning period may contribute to intestinal inflammation and thereby compromise villus-crypt structure and function.     

Total parenteral nutrition alters molecular and cellular indices of intestinal inflammation in neonatal piglets

BACKGROUND: The adverse effects of TPN on systemic immunity are well-documented; however, the impact of IV feeding on neonatal intestinal immunity is unknown. METHODS: A piglet TPN model was used to compare immune cell composition within the intestinal epithelium and lamina propria of parenterally and orally fed piglets. RESULTS: Small intestinal weight of piglets maintained intravenously was reduced 50% after 7 days. Intestinal atrophy in piglets fed parenterally was evidenced by decreased width of intestinal villi and colon cuffs and reduced intestinal crypt depth. The numbers of CD4+ and CD8+ T lymphocytes were threefold greater within the lamina propria of jejunal and ileal villi of piglets supported intravenously. Inverse correlations were observed between villus height or width and T-lymphocyte numbers (r = -.80; p < .05). Major histocompatibility complex class II mRNA expression, an indicator of localized inflammation, was increased in the ileum and colon of piglets receiving parenteral nutrition. Goblet cell numbers were two-fold greater in jejunal and ileal villi, and mast cells were more abundant in the colon of piglets fed parenterally. Furthermore, jejunal T-lymphocyte numbers were correlated with goblet cell numbers (r = .80; p = .01). CONCLUSIONS: These data identify molecular and cellular indices of intestinal inflammation that are responsive to IV feeding in neonates and provide a novel framework to investigate mechanisms underlying gut atrophy during TPN.     

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     

Inflammatory bowel disease and predisposition to osteopenia

The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energy x ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids.