Anti-CCP2 should be included in the work-up of patients with early symptoms of rheumatoid arthritis.

The aims of this study are to ascertain the prevalence of anxiety and depressive disorders in an outpatient population with osteoarthritis (OA), examine the interrelationships between severity of OA, pain, disability, and depression, and evaluate the Hospital Anxiety and Depression Scale (HADS) as a screening tool for this population. Patients with lower limb OA were evaluated with the Short Form McGill Pain and Present Pain Index Questionnaires, and a visual analogue scale, WOMAC Osteoarthritis Index-section C, and the HADS. Participants underwent a structured clinical interview by a liaison psychiatrist (AB). X-rays of affected joints were rated for disease severity. Fifty-four patients (42 females; mean age 63.3) were investigated. The prevalence of clinically significant anxiety and/or depression was 40.7% (95% confidence interval (CI), 27.6-55.0%). HADS was a good predictor of anxiety and depression with a sensitivity and specificity of 88% (95%CI, 64% to 99%) and 81% (95%CI, 65% to 92%), respectively. Pain correlated with HADS anxiety and depression scores (e.g. Rank correlation coefficients (Kendall's tau-b) between total HADS scores and Pain VAS scores 0.29; p=0.003). Disability was greater in patients with depression and/or anxiety (e.g. total HADS score; Kendall's rank correlation coefficient tau-b=0.26, p=0.007) OA severity as determined by radiological score was not a good predictor for anxiety nor depression and only weakly associated with disability. Anxiety and depression are very common in OA patients. HADS anxiety was a better predictor of diagnosed anxiety than HADS depression was of diagnosed depression. HADS is a valid and reliable screening instrument for detecting mood disorder, but not a diagnostic tool or a substitute for asking about symptoms of depression. The interrelationship between mental health, pain and disability is strong. We should therefore adopt a multidisciplinary approach to the management of OA.

Summary. The changes in bone marrow (BM) stem cell reserve and function and stromal cell function in patients with active systemic lupus erythematosus (SLE) were investigated. The study was carried out on seven SLE patients and 28 healthy controls using flow cytometry and in vitro cell culture assays. We found that patients had low CD34 1 cells, compared with the control group, reflecting the decrease of both CD34 1 cells in SLE patients. Moreover, we found that patients had low numbers of granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E), compared with the control group, and that the generation of colonyforming cells in long-term BM cultures was significantly reduced. Patient BM stroma failed to support allogeneic progenitor cell growth. In one patient, CD341 cells were increased, apoptotic CD341 /Fas 1 cells were normalized and defective stromal cell function was restored after autologous stem cell transplantation. We concluded that defective haemopoiesis in SLE patients is probably caused, at least in part, to the presence of autoreactive lymphocytes in BM.

SummaryHuman endogenous retroviruses (HERVs) are remnants of ancient retroviral infections within the human genome. These molecular fossils draw parallels with present-day exogenous retroviruses and have been linked previously with immunopathology within rheumatoid arthritis (RA). Mechanisms of pathogenesis for HERV-K in RA such as molecular mimicry were investigated. To clarify a role for HERVs in RA, potential autoantigens implicated in autoimmunity were scanned for sequence identity with retroviral epitopes. Short retroviral peptides modelling shared epitopes were synthesized, to survey anti-serum of RA patients and disease controls. A novel real-time polymerase chain reaction (PCR) assay was also developed to quantify accurately levels of HERV-K (HML-2) gag expression, relative to normalized housekeeping gene expression. Both serological and molecular assays showed significant increases in HERV-K (HML-2) gag activity in RA patients, compared to disease controls. The real-time PCR assay identified significant up-regulation in HERV-K mRNA levels in RA patients compared to inflammatory and healthy controls. Exogenous viral protein expression and proinflammatory cytokines were also shown to exert modulatory effects over HERV-K (HML-2) transcription. From our data, it can be concluded that RA patients exhibited significantly elevated levels of HERV-K (HML-2) gag activity compared to controls. Additional factors influencing HERV activity within the synovium were also identified. The significant variation in RA patients, both serologically and transcriptionally, may be an indication that RA is an umbrella term for a number of separate disease entities, of which particular HERV polymorphisms may play a role in development.

No abstract

To investigate potential mechanisms controlling protein glycosylation we have studied the interrelationship between lymphocytic galactosyltransferase (GTase) activity and serum agalactosylated immunoglobulin G levels (G(0)) in healthy individuals and patients with rheumatoid arthritis and non-autoimmune arthritis. In RA there was reduced GTase activity and increased G(0). A positive linear correlation between B and T cell GTase was found in all individuals. The relationship between GTase and G(0) was found to be positive and linear in the control population and negative and linear in the RA population. Sulphasalazine therapy maintained normal levels of GTase and caused a reduction in G(0) in the RA population. IgG anti-GTase antibodies (abs) were significantly increased in the RA population, whereas IgM anti-GTase abs were significantly decreased in both the RA and the non-autoimmune arthritis groups. These data describe a defect in RA lymphocytic

The clinical relevance of glycobiology has become the focus of considerable research, as the role of glycosylation in the development, regulation and progression of disease is, slowly but surely, being unveiled. Recent strides in the design and refinement of analytical techniques-sugar profiling, glyco-arrays and functional studies-have helped us gain a better understanding of the complexity and richness of diversity that bestow sugars with an unsurpassed, biospecific coding capacity. Cracking this 'sugar code', and unravelling the structural frameworks and recognition strategies of sugar-based interactions in biological systems that relate to both health and disease, holds tremendous promise for deciphering disease mechanisms. It will also provide a cutting edge potential for the development of novel diagnostic and therapeutic interventions.

This report should be referenced as follows: Lord J, Victor C, Littlejohns P, Ross FM, Axford JS. Economic evaluation of a primary carebased education programme for patients with osteoarthritis of the knee. Health Technol Assess 1999;3(23). Health Technology Assessment is indexed in Index Medicus/MEDLINE and Excerpta Medica/ EMBASE. Copies of the Executive Summaries are available from the NCCHTA web site (see overleaf). NHS R&D HTA Programme T he overall aim of the NHS R&D Health Technology Assessment (HTA) programme is to ensure that high-quality research information on the costs, effectiveness and broader impact of health technologies is produced in the most efficient way for those who use, manage and work in the NHS. Research is undertaken in those areas where the evidence will lead to the greatest benefits to patients, either through improved patient outcomes or the most efficient use of NHS resources. The Standing Group on Health Technology advises on national priorities for health technology assessment. Six advisory panels assist the Standing Group in identifying and prioritising projects. These priorities are then considered by the HTA Commissioning Board supported by the National Coordinating Centre for HTA (NCCHTA). This report is one of a series covering acute care, diagnostics and imaging, methodology, pharmaceuticals, population screening, and primary and community care. It was identified as a priority by the Primary and Community Care Panel and funded as project number 94/39/01. The views expressed in this publication are those of the authors and not necessarily those of the Standing Group, the Commissioning Board, the Panel members or the Department of Health. The editors wish to emphasise that funding and publication of this research by the NHS should not be taken as implicit support for the recommendations for policy contained herein. In particular, policy options in the area of screening will be considered by the National Screening Committee. This Committee, chaired by the Chief Medical Officer, will take into account the views expressed here, further available evidence and other relevant considerations. Reviews in Health Technology Assessment are termed 'systematic' when the account of the search, appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others.