Use of a corporate needs assessment to define the information requirements of an arthritis resource centre in Birmingham: comparison of patients' and professionals' views.

OBJECTIVES: Education and information are important components of the management of chronic disease, though provision of these in the routine clinic setting may be suboptimal. We carried out a corporate needs assessment, both to evaluate stakeholders' perceived usefulness of potential facilities that could be offered by a community-based arthritis resource centre in Birmingham and to compare the views of patients with rheumatological conditions and health professionals. METHODS: Rheumatology patients (n = 201 responders/309 contacted) and health professionals (n = 232/430) were asked to complete a questionnaire to assess both current rheumatology service provision and perceived needs for further information that could be offered within the proposed resource centre. Views of patients and professionals were compared using odds ratios. Logistic regression analysis determined patient characteristics associated with perceived usefulness of various information types. RESULTS: The overall response rate was 58%. Most patients were currently receiving medication but only 38% received written information on arthritis. Over 80% of responders felt that more information would be useful, particularly information in written leaflets. Compared with professionals, patients gave higher value to certain types of medical, non-medical, support and skills information, particularly individual information from trained volunteers, and specific information on benefits, diet and alternative therapy, and symptom management. Non-Caucasian patients gave higher value to the provision of material in different languages and the availability of multilingual volunteer staff. CONCLUSION: Rheumatology patients and professionals identified a relative lack of information for patients. There was wide interest in the provision of more information, with value placed on the provision of material in different languages, at an educational resource centre. This work has been used to develop the facilities currently offered at the Birmingham Arthritis Resource Centre. Further research is needed to investigate the effectiveness of the provision of good quality information to patients with arthritis.

The engineered human anti-tumor necrosis factor-alpha antibody CDP571 inhibits inflammatory pathways but not T cell activation in patients with rheumatoid arthritis.

OBJECTIVE: We investigated the effect of an engineered human anti-tumor necrosis factor-alpha antibody, CDP571, on immune functions as well as bone and cartilage turnover in patients with rheumatoid arthritis (RA) in a placebo controlled trial. We also assessed the effects of repeated treatment with CDP571 in an open label continuation study. METHOD: Thirty-six patients were treated with either placebo or 0.1, 1, or 10 mg/kg of CDP571 given as an intravenous infusion. The followup period was 8 weeks. Lymphocyte phenotype, soluble CD4 (sCD4), soluble interleukin 2 receptor (sIL-2R), IL-6, and stromelysin levels in the blood were measured before and after treatment; bone and cartilage markers (pyridinoline, deoxypyridinoline, N-terminal telopeptide) were similarly assessed in the urine. Patients who completed a placebo controlled trial of CDP571 were offered further treatment with CDP571. They received a maximum of 2 further doses of 1 mg/kg (7 patients) or 10 mg/kg (9 patients) in an open study. RESULTS: Plasma IL-6 level was statistically significantly reduced in the 1 and 10 mg/kg groups. In the 10 mg/kg group, there were also reductions in plasma stromelysin and urine bone markers, although there was no change in sCD4 and sIL-2R levels. Repeat doses of CDP571 were well tolerated and continued to suppress the acute phase response and disease activity. CONCLUSION: Treatment with 10 mg/kg of CDP571 reduced IL-6 and surrogate markers of bone turnover in RA, suggesting that CDP571 might prevent joint damage in RA. Since there was no effect on lymphocyte markers despite the marked reduction in inflammation, CDP571 appears to have no effect on ongoing CD4 T cell activation.

IgA deficiency and SLE: prevalence in a clinic population and a review of the literature.

An association between systemic lupus erythematosus (SLE) and immunoglobulin A (IgA) deficiency has been reported previously and may have therapeutic consequences for patients who require treatment with intravenous immunoglobulin. We report the prevalence of IgA deficiency in a clinic population of 96 patients with SLE. Five patients were found to be consistently IgA deficient. These patients were more likely to be West Indian, to have anti-Sm and anti-La antibodies and to have a speckled pattern of antinuclear antibody. There were no significant differences in clinical features between IgA deficient and other SLE patients, nor in SLE-related HLA alleles. We thus confirm the increased prevalence of IgA deficiency in patients with SLE. A review of the literature is presented and we speculate on the nature of the link between IgA deficiency and SLE.

The therapeutic effects of an engineered human anti-tumour necrosis factor alpha antibody (CDP571) in rheumatoid arthritis.

Pro-inflammatory cytokines such as tumour necrosis factor alpha (TNF alpha) have been implicated in the pathogenesis of rheumatoid arthritis (RA), and have therefore become therapeutic targets. An engineered human antibody, CDP571, that neutralizes human TNF alpha was administered intravenously in single doses of 0.1, 1.0 or 10 mg/kg to patients with active RA (n = 24). The effects of the antibody were compared in a double-blind fashion with those of placebo (n = 12). In an open continuation phase patients were given either 1.0 or 10 mg/kg. We found that CDP571 was well tolerated and caused reductions in markers of disease activity such as erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP): this was confirmed by a reduction in the disease activity score (DAS). There was a reduction in the number of tender joints, maximal in degree and duration after 10 mg/kg. Patients also documented a reduction of pain and relief of arthritis symptoms. The effects of 10 mg/kg CDP571 on ESR, CRP, tender joints, pain and symptom relief compared to placebo were statistically significant at weeks 1 or 2. The continuation phase, although open, confirmed both the safety and the beneficial effects of CDP571 in active RA. In conclusion CDP571, an engineered human anti-TNF alpha antibody, is well tolerated and, after a single dose of 10 mg/kg, provides improvements in symptoms, signs and serological markers of disease activity in patients with active RA.

Topographic refinement of the regenerating retinotectal projection of the goldfish in standard laboratory conditions: a quantitative WGA-HRP study.

The topographic precision of the regenerating retinotectal projection of the goldfish was studied between 18 and 524 days (at 20 degrees C) after optic nerve cut, using retrograde transport of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA-HRP) from one of two standardized tectal injection sites. All labelled ganglion cells in each flat-mounted retina were plotted individually, and their degree of dispersion was assessed by a statistical method based on distance to nearest neighbour. Labelled cells in normal fish were clustered tightly, covering on average only 1.3% of the retina. Early in regeneration (18-28 days) they were widely dispersed, covering up to 75.2%, and they did not begin to form recognizable clusters at appropriate sites until about 35 days after nerve cut. Between 18 and 70 days, the proportion of retina covered by labelled cells fell dramatically, halving about every 14 days. Between 70 and 524 days, no further reduction could be demonstrated: overall, clusters remained significantly larger than normal, though a few individual retinae were virtually normal. Several others, labelled from similar single injections between 56 and 524 days after nerve cut, showed pairs of cell clusters; a sign that persistent errors in topography are common. The very wide initial scatter of labelled cells reflects a striking lack of 'goal-directedness' in regenerative axon growth. Extensive branching in the optic nerve, tract and tectum, for which there is already evidence, must contribute to this. Though uptake of some WGA-HRP by nonsynaptic growth cones cannot be ruled out, other evidence for mislocated functional synapses at early stages encourages us to favour 'trial and error' synapse formation as the likely basis of map refinement.

Impaired refinement of the regenerated retinotectal projection of the goldfish in stroboscopic light: a quantitative WGA-HRP study.

The retinotectal projection of the goldfish was studied after regeneration of a cut optic nerve in stroboscopic light, constant light or diurnal light, with the lens removed to blur the retinal image. Retrograde transport of wheatgerm agglutinin, conjugated to horseradish peroxidase, from a standard tectal injection site was used to measure the topographic precision of the projection. The dispersion of labelled retinal ganglion cells, which reflects this precision, was assessed by a method based on distance to nearest neighbour. In normal fish treated similarly, these cells are known to be clustered into about 1% of the retinal area. Early in regeneration, however, they are widely dispersed. The projection map then re-acquires its precision over two or three months. In diurnal light, lens ablation had no effect on refinement of the regenerated map. Constant light increased the number of labelled cells but also had no significant effect on the map. But in stroboscopic light with a continuous pseudorandom pattern of flash intervals (average rate 4.8 Hz), much less refinement was seen. Even after 70-98 days of regeneration, labelled cells remained scattered, on average, over 20% of the retinal area. These retinae were indistinguishable by several criteria from those obtained in diurnal light after only 32-39 days. Mislocated axon terminals, which are largely eliminated during the second and third months of regeneration in diurnal light, evidently persist much longer in stroboscopic light that synchronizes ganglion cell activity across the retina. These results, like previous ones obtained by blocking the transmission of activity to the tectum, support a model of map refinement based on correlation in the firing of neighbouring neurons, which may have wide application within the nervous system.

Use of a lectin-peroxidase conjugate (WGA-HRP) to assess the retinotopic precision of goldfish optic terminals.

The lectin wheat-germ agglutinin (WGA), conjugated to horseradish peroxidase (HRP), is an effective tracer for goldfish optic axons. Under suitable conditions, WGA-HRP injected iontophoretically into the normal goldfish tectum is taken up by retinotopic optic terminals (but not by axons of passage) and labels a small, discoid patch of retinal ganglion cells. Under identical conditions, unconjugated HRP is mainly taken up by injured axons of passage. WGA-HRP injected into the tectum after regeneration of the contralateral optic nerve again labels a small patch of ganglion cells, demonstrating the extent to which regenerated terminals are also retinotopic.

A pattern of optic axons in the normal goldfish tectum consistent with the caudal migration of optic terminals during development.

Optic axons were cut in the goldfish optic nerve or tectum, filled with horseradish peroxidase and traced in tectal wholemounts. Many of them ran in conspicuous fascicles which curved across the tectum. Axons from central nasal retina, which ran in the most rostral fascicles, turned abruptly as they left these fascicles; ran caudally in a diffuse, parallel array for up to half the tectal length; and passed beneath more caudal fascicles to innervate the caudal half-tectum. Axons from peripheral nasal retina ran in the most caudal fascicles and terminated near their turning-points. Axons from temporal retina entered the tectum at its rostral margin and ran caudally from their points of entry to innervate the rostral half-tectum. The resultant pattern was entirely consistent with the proposal that a slow caudal migration of optic terminals compensates during normal development for disparate modes of retinal and tectal growth.