Inappropriate peripheral blood lymphocyte responses to herpes viruses in patients with behçet's syndrome

Specific antibody production and the proliferative response of peripheral blood lymphocytes (PBLs) to a variety of viruses, including herpes simplex virus-type-1 (HSV-1) and varicella zoster (VZ), were studied in 7 patients with Behçet's syndrome. None of the patients produced an antibody response against HSV-1 or VZ. Furthermore, none of the patients showed a proliferative response to VZ, and three of them also failed to mount a response to HSV-I. These results suggest that the PBLs of patients with Behçet's syndrome make an inappropriately poor antibody and proliferative response when stimulated by HSV-1 and VZ.     

Bacterial clearance and cytokine profiles in a murine model of postsurgical nosocomial pneumonia

The development of a nosocomial pneumonia is facilitated by alterations in host innate pulmonary antibacterial defenses following surgical trauma, which can result in decreased pulmonary bacterial clearance and increased morbidity and mortality. In a murine model of postoperative nosocomial infection, surgical stress (laparotomy) decreased Escherichia coli clearance from the lungs of animals that underwent surgery. Consistent with previous studies, (i) pulmonary levels of tumor necrosis factor alpha at 6 h and of interleukin-1beta (IL-1beta), IL-6, and gamma interferon (IFN-gamma) at 24 h post-bacterial infection (PBI) were decreased in animals that underwent laparotomy 24 h prior to E. coli infection (LAP/E. coli) compared to animals that received E. coli only; (ii) KC and macrophage inhibitory protein 2 were elevated at 6 h PBI in LAP/E. coli animals compared to E. coli-only animals; however, at 24 h PBI, levels were higher in the E. coli-only group; (iii) at 24 h PBI, monocyte chemoattractant protein 1 was lower in the LAP/E. coli group compared to the E. coli-only group; (iv) IL-10 levels were unaffected at all time points evaluated; and (v) the total number of neutrophils present in the lungs of LAP/E. coli animals at 6 h PBI was decreased in comparison to that in E. coli-only animals, resulting in decreased bacterial clearance and increased mortality in LAP/E. coli animals by 24 h PBI. Similar changes in cytokine profiles, pulmonary bacterial clearance, and mortality were consistent with reported findings in patients following surgical trauma. This model, therefore, provides a clinically relevant system in which the molecular and cellular mechanisms that lead to the development of nosocomial pneumonia can be further explored.     

A longitudinal study of maternal serum inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC and follistatin during pregnancy

Maternal serum concentrations of inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC-related inhibin forms, total follistatin, steroids and gonadotrophins were measured longitudinally in six normal singleton pregnancies. Maternal venous blood was collected randomly during a spontaneous follicular phase prior to donor insemination, at 5, 7, 9, 11, 16, 20, 24, 28, 32 and 36 weeks after the first missed menses and in the early puerperium. Steroid and gonadotrophin profiles conformed to previous reports. While at week 5 of gestation inhibin-A, activin-A and follistatin concentrations were similar to those at the follicular phase, all three increased progressively (P < 0.001) to maximal concentrations in week 36: approximately 48-fold (3740 +/- 1349 ng inhibin-A/ml), approximately 22-fold (6109 +/- 1443 ng activin-A/ml) and approximately 10-fold (3563 +/- 418 ng follistatin/ml) higher. Pro- alphaC concentrations reached a maximum in weeks 5 (approximately 5- fold, P < 0.001) and 36 (1027 +/- 174 pg/ml, P < 0.01). Inhibin-B (71 +/- 23 pg/ml prior to pregnancy) was undetectable (<12 pg/ml) between week 5-16 of gestation but increased slightly in the third trimester (26 +/- 7 pg/ml in week 36). Activin-AB was undetectable throughout pregnancy. Post-partum concentrations of inhibin-A (41 +/- 12 ng/ml), inhibin-B (<12 pg/ml), activin-A (950 +/- 149 pg/ml), pro-alphaC (128 +/- 22 pg/ml) and follistatin (990 +/- 79 ng/ml) were substantially lower than at week 36 of gestation. The activin-A:follistatin ratio increased from 0.5 in week 5 to 1.8 in week 36, suggesting that more free activin-A is available in the maternal circulation during late pregnancy.      

Immunopathologic Role of Proteoglycan Antigens in Rheumatoid Joint Disease

Cell-mediated immunity to proteoglycan antigens was assessed by leucocyte migration inhibition and by lymphocyte stimulation tests in patients with rheumatoid arthritis or with ankylosing spondylarthritis, in patients with relapsing synovitis after a single trauma to their knee joints, and in healthy donors. Both tests revealed a sensitization in most of the patients examined with various proteoglycan antigens derived from human cartilaginous tissues, rheumatoid synovial fluid, and species-common antigen of bovine nasal cartilage. Anybodies against proteoglycan antigens of human articular cartilage were detected by solid-phase radioimmunoassay in eleven out of twenty-nine sera from patients with rheumatoid arthritis and in four out of six rheumatoid synovial fluids. The results suggest that the cartilage antigenic components released by an inflammatory process or trauma may trigger a vicious circle of chronic inflammation and joint destruction.     

General practitioners and clinical guidelines: a survey of knowledge, use and beliefs.

BACKGROUND: Clinical practice guidelines are being developed for a variety of reasons. To date, there has been little investigation of the perspectives of those who are recommended to use them. AIM: The survey reported here set out to investigate how familiar general practitioners are with a range of published guidelines, to assess whether they have used them, and to describe their attitudes to the guidelines and the methods of implementing them. METHOD: A postal questionnaire was sent to a random sample of 559 general practitioners in the North and Yorkshire region in March 1995. Questions were organized around the topics of: knowledge; use; practice change; beliefs; pressure felt to use the guidelines; and methods of implementation. Basic classificatory data on gender; year of qualification; partnership and fundholding status were also collected. RESULTS: Replies were received from 300 doctors (54%). Knowledge and use of the three selected guidelines varied, but was generally towards the 'high' end of the scale. Doctors showed a high degree of homogeneity in their attitudes to guidelines, which were generally positive. Only single-handed practitioners varied from this pattern of responses. Most of the pressure to use the guidelines was felt to come from the Department of Health, and the least pressure from patients. Doctors felt that the methods of implementation that involved them in educational events and discussion with colleagues were most likely to have an impact on them. CONCLUSION: General practitioners are receptive to guideline initiatives, and their views are in line with existing or proposed implementation strategies. More investigation of the concept of 'use' is needed.     

Correlations of Monocyte Phagocytic Receptor Expressions with Serum Immune Complex Level in Systemic Lupus Erythematosus

The expression of FcγRI, FcγRII, and FcγRIII (the IgG receptors CD64, CD32, CD16) as well as CR3 (the C3bi receptor, CD11b) on monocytes in the blood of patients with systemic lupus erythematosus (SLE) was investigated. The relationship between the receptor expression and the serum immune complex (IC) concentration was analysed. The decrease in mean fluorescence intensity (FI) of the FcγRII of patients' monocytes stained by specific monoclonal antibodies (MoAb IV3) was very close to statistical significance ( P = 0.052). The expression (FI) of CR3 (using MoAb OKM1) on monocytes of patients was also decreased, but not significantly. The detected decrease of FcγRII and CR3 was inversely correlated with the high circulating immune complex level in patients' sera. At the same time, FcγRI expression on SLE monocytes (using MoAb 32) was significantly elevated and this change was in parallel with the serum IC concentration.