Methods. Twenty-two patients with phantom limb pain, or pain related to spinal cord or nerve injury, performed a single MVF procedure. Before and after the MVF procedure, we evaluated phantom limb awareness, movement representation of the phantom or affected/paralysed limb, pain intensity on an 11-point numerical rating scale (0–10) and the qualities of the pain [skin surface-mediated (superficial pain) vs deep tissue-mediated (deep pain)] using lists of pain descriptors for each of the two categories.

Results. Fifteen of the patients perceived the willed visuomotor imagery of the phantom or affected/paralysed limb after the MVF procedure. In most of the patients, a reduction in pain intensity and a decrease in the reporting of deep-pain descriptors were linked to the emergence of willed visuomotor imagery.

Conclusions. In this pilot study, we roughly classified the pain descriptor items into two types for evaluating the qualities of deafferentation pain. We found that visually induced motor imagery by MVF was more effective for reducing deep pain than superficial pain. This suggests that the analgesic effect of MVF treatment does depend on the qualities of the pain. Further research will be required to confirm that this effect is a specific consequence of MVF.

Methods. OASFs were stimulated with BCP crystals in vitro. mRNA expression was measured by real-time PCR, PG production by EIA and protein production by western blot.

Results. Maximal (19-fold) up-regulation of COX-1 mRNA occurred 32 h after stimulation with BCP crystals; increased COX-1 protein production was also seen. At 32 h post-stimulation with BCP crystals, PGE₂ (and prostacyclin) production was COX-1 dependent. In contrast, maximal (17-fold) up-regulation of COX-2, with corresponding COX-2-dependent PG production, occurred 4 h after BCP crystal stimulation. There was no appreciable increased production of other PGs such as PGF₂, thromboxane A₂ or cyclopentanone PGs including 15d-PGJ₂. Inhibition of protein kinase C (PKC) and extracellular regulated kinase 1/2 (ERK1/2) signal transduction pathways blocked BCP crystal-induced COX-1 mRNA expression. Bafilomycin A1, an inhibitor of intra-lysosomal BCP crystal dissolution, diminished BCP crystal-induced COX-1 mRNA expression.

Conclusions. These findings indicate that BCP crystals can augment PG production in OASF through induction of COX-1 and COX-2. Intra-lysosomal BCP crystal dissolution and activity of the PKC and ERK1/2 signal transduction pathways are required for BCP crystal-induced COX-1 up-regulation. These data add to the evidence suggesting that the constitutive COX-1/inducible COX-2 concept is an over-simplification and suggest that non-selective COX inhibition may be preferable to COX-2 selective inhibition in BCP crystal-associated OA.

Methods. The frequency of calcinosis was derived from a national UK database of 212 cases of JDM. Serum fetuin-A and plasma osteopontin levels were determined using ELISA in 15 JDM patients with calcinosis and 15 JDM patients without calcinosis. Healthy controls were 19 age-matched children, 24 adolescents and 13 adults. Sixteen patients with juvenile idiopathic arthritis (JIA) were additional paediatric disease controls.

Results. Of the 212 JDM cases 10% had calcinosis. Calcinosis patients had younger age of disease onset than those without calcinosis (mean age of 5.3 yrs vs 7.1 yrs, respectively, P = 0.016). No significant difference in fetuin-A or osteopontin could be detected between the two JDM groups. Fetuin-A levels in all groups of children and the adolescent group were much lower than described previously in adults, and there was a significant positive correlation between age and fetuin-A level, and also between osteopontin levels in plasma and serum fetuin-A.

Conclusions. Children who develop JDM at an younger age may have increased risk of developing calcinosis. Physiologically low levels of fetuin-A in young children combined with an additional negative acute-phase effect on fetuin-A due to chronic inflammation could explain in part the propensity to develop ectopic calcification observed in JDM patients, and why calcinosis is less frequent in adults with dermatomyositis.

Methods. A modified Delphi technique was used for clinicians to develop preliminary core sets of teaching topics for each profession. Telephone interviews with educationalists explored their views on these, and challenges and solutions for delivering them. Inter-professional workshops enabled clinicians and educationalists to finalize the core set together, and generate methods for delivery.

Results. Thirty-nine rheumatology clinicians (12N, 14OT, 13PT) completed the Delphi consensus, proposing three preliminary core sets (N71 items, OT29, PT26). Nineteen educationalists (6N, 7OT, 6PT) participated in telephone interviews, raising concerns about disease-specific vs generic teaching and proposing many methods for delivery. Three inter-professional workshops involved 34 participants (clinicians: N12, OT9, PT5; educationalists: N2, OT3, PT2; Patient 1) who reached consensus on a single core set comprising six teaching units: Anatomy and Physiology; Assessment; Management and Intervention; Psychosocial Issues; Patient Education; and the Multi-disciplinary Team, recommending some topics within the units receive greater depth for some professions. An innovative range of delivery options was generated plus two brief interventions: a Rheumatology Chat Show and a Rheumatology Road Show.

Conclusions. Working together, clinicians and educationalists proposed a realistic core set of rheumatology topics for undergraduate health professionals. They proposed innovative delivery methods, with collaboration between educationalists, clinicians and patients strongly recommended. These potential interventions need testing.

Methods. Skin hardness was calculated by measuring the depth of an indenter pressed onto the skin. The Voigt model was used to calculate skin elasticity, viscosity, visco–elastic ratio and relaxation time by analysing the waveform of skin surface behaviour. The results were compared with the modified Rodnan skin score (mRSS) obtained at 17 sites on the bodies of 20 SSc patients and 20 healthy controls. A functional assessment questionnaire was administered to determine how skin hardness represents a patient's disability. We also examined intra- and inter-observer variability to determine the reliability of this method.

Results. The crude hardness obtained with this device correlated well with the standard hardness specified by the American Society for Testing and Materials (ASTM, r = 0.957). A close relationship between hardness and total mRSS was also observed (r = 0.832). Skin elasticity correlated positively, and relaxation time negatively with mRSS. Functional disability correlated more closely with skin hardness (r = 0.643) than with mRSS (r = 0.517). Intra- and inter-observer variabilities were 7.63 and 19.76%, respectively, which were lower than those reported for mRSS.

Conclusions. Increases in hardness and elasticity as well as shortening of relaxation time constitute objective characteristics of skin involvement in SSc. The system devised by us proved to be able to assess skin abnormalities of SSc with high reliability.

Methods. FSV was investigated by means of spectral Fourier analysis of finger skin laser Doppler flowmetry (LDF) tracing, recorded before and following acetylcholine (ACh) or sodium nitroprusside (SNP) iontophoresis in 26 SSc patients and in 20 age-matched healthy controls. The power spectral density (PSD) of the 0.01–0.02, 0.02–0.06 and 0.06–0.2 Hz LDF oscillations (related to endothelial-, sympathetic- and myogenic-dependent FSV, respectively) was measured in PU² (perfusion units)/Hz.

Results. Compared with controls, SSc patients exhibited a significantly lower post-ACh and/or post-SNP percentage increase in PSD of 0.01–0.02 Hz (492 ± 297% vs 283 ± 167%; P < 0.005), of 0.02–0.06 Hz (336 ± 205% vs 239 ± 170%; P < 0.05) and of 0.06–0.2 Hz (223 ± 91% vs 194 ± 227%; P < 0.01) skin LDF oscillations. The post-SNP normalized PSD value of the 0.01–0.02 Hz and of the 0.02–0.06 Hz LDF oscillations was negatively related to SSc severity index (r = –0.407, P < 0.05 and r = –459, P < 0.05, respectively).

Conclusions. This study showed a selective abnormality of the endothelial, sympathetic and myogenic-dependent FSV in SSc patients, consistent with a parallel endothelial, sympathetic and myogenic macrovascular dysfunction. This study also suggests a possible role of endothelial and sympathetic dysfunction in the progression of SSc.

Methods. Questionnaires about timetable and working conditions were sent to all consultants on the BSR/ARC UK Workforce Register in January 2007, along with the personal and job-related details currently held about them on the register to update. The questionnaire included a visual analogue scale asking ‘how concerned are you that your current post might be under threat’ ranging from 0 ‘Not at all’ to 100 ‘Extremely’.

Results. The response rate of the 2005 and 2007 surveys were 89 and 87%, respectively. Levels of optimal provision now exceed 70% in England and Wales, and 50% in Scotland and Northern Ireland. Levels of provision remain substantially higher in London than anywhere else. The median level of perceived job threat in the UK was 31 (interquartile range 11–61). Consultants in areas where provision is highest and a higher proportion of services are run in conjunction with Clinical Assessment and Treatment (CAT) centres report higher perceived job threat.

Conclusions. Provision of rheumatology services has continued to expand over the past decade; however, inequalities persist at national and sub-national level. There is evidence of improvement in regions with the lowest provision, but there are indications of increased perceived job threat in areas with traditionally higher provision and where CAT centres have been introduced.

Methods. Analysis was limited to RA patients with inefficacy to a first anti-TNF based on (i) clinician opinion and/or (ii) disease activity score in 28 joints and had an HAQ measured at time of non-response and 12 months later. Patients were classified into three groups based on treatment during the next 12 months: (i) continued anti-TNF despite non-response; (ii) stopped anti-TNF with no further biologics; and (iii) switched to a second anti-TNF. Mean improvement in HAQ was compared among the groups using multivariable linear regression models.

Results. As of July 2006, 868 patients met the inclusion for this analysis. Four hundred and seventy-nine patients stopped anti-TNF of whom 331 switched to a second anti-TNF. Three hundred and eighty-nine continued treatment. Patients who continued and those who switched had improvements in HAQ over the 12 months, unlike patients who discontinued all biologic therapy. The best improvement was seen in those who switched [adjusted mean improvement in HAQ 0.15 (95% CI 0.26, 0.05)].

Conclusion. There is a significant improvement in HAQ in patients who switch to a second anti-TNF, providing an effective next choice of therapy for some patients who fail to respond to their first anti-TNF.

Patients. In a population-based Norwegian study, the physicians were asked to refer all children with suspected arthritis. The arthritis patients were followed up at 6 weeks, 6 months and 18 months. The presence of S. pyogenes was based on throat smear or antibodies. Echocardiography was performed in the patients with ARF or PSRA.

Results. Thirty-two (18%) of the 173 children with arthritis tested positive for S. pyogenes. The percentage of positive tests rose steadily with age and peaked at ages 8–11 (35%). Six weeks after admission arthritis was present in 33% of the PSRA patients, which was less frequent than in the juvenile idiopathic arthritis (JIA) patients (P < 0.001), but more frequent than in the transient arthritis patients (P = 0.012). Hip arthritis was more frequent and knee/ankle arthritis, ANA and HLA-B27 were less frequent in PSRA than in JIA (P < 0.001, P = 0.009 and P = 0.029, respectively). The PSRA patients were older than those with transient arthritis (P = 0.007). One child with ARF had carditis.

Conclusions. Streptococcus pyogenes was present in 18% of children with arthritis. The patient characteristics, clinical presentation and early disease course in PSRA was different from that of JIA and transient arthritis.

Methods. A total of 532 SLE patients and 521 healthy controls belonging to the Korean population were enrolled into this study. Sequencing of the entire coding region of the DNase IV gene (including the promoter region) was carried out using a DNA analyser. Autoantibodies including anti-Sm, anti-Ro, anti-La, anti-RNP and anti-dsDNA were determined either by indirect immunofluorescence or double immunodiffusion methods. Multiple logistic regression analysis was performed to examine the genetic association with SLE and autoantibodies.

Results. We found three single-nucleotide polymorphisms (SNPs): –2753G->A, +147T->G (Gly49Gly) and +1466G->T. The –2753G->A and +147T->G (Gly49Gly) SNPs were selected for larger scale genotyping based on linkage disequilibria and haplotype-tagging status. Although the –2753G->A SNP was more common than the +147T->G (Gly49Gly) SNP (frequencies: 0.330 and 0.002, respectively), its association with the risk of SLE was not statistically significant. However, –2753G->A SNP was significantly associated with the production of anti-Sm antibody [odds ratio (95% CI): co-dominant model, 1.89 (1.28–2.79); dominant model, 2.17 (1.20–3.90) and recessive model, 2.62 (1.33–5.17)].

Conclusions. We did not find significant relationships between DNase IV polymorphisms and the risk of SLE, but the association of the common –2753G->A allele in the promoter region with the production of anti-Sm antibody implicates DNase IV as a putative candidate gene of SLE.

Methods. Children ≤16 yrs with inflammatory arthritis persisting ≥2 weeks were recruited from five UK hospitals. Data including demographics, disease features, Childhood Health Assessment Questionnaire (CHAQ), physician and parent global assessment and blood tests were collected at the first appointment with PRh (baseline). The association between symptom duration (defined as time from first reported symptom onset to presentation at PRh) and baseline disease characteristics was evaluated using non-parametric descriptive statistics and multivariable logistic regression analyses.

Results. Five hundred and seven children (65% female) were included: median age at onset was 6.8 yrs. Two hundred and thirty-three had oligoarthritis, 68 had RF-negative polyarthritis, 27 had systemic onset arthritis and 29 had arthritis that was not JIA. The median symptom duration was 4.6 months. Median symptom duration was shortest for children presenting with systemic arthritis (1.6 months) and longest for those with PsA (8.6 months). Children with a longer duration of symptoms were older and had higher median active joint counts but lower median ESR. Symptom duration did not correlate with CHAQ score at presentation.

Conclusions. Children who have systemic arthritis had the shortest delay to PRh presumably because they are profoundly unwell. Children with joint pain/stiffness but normal ESR had longer delays suggesting that if blood tests do not indicate inflammation, the diagnosis of JIA may be overlooked.

Methods. The Childhood Arthritis Prospective Study (CAPS) is an ongoing longitudinal study recruiting children with inflammatory arthritis from four UK hospital centres. Included children are newly diagnosed, ≤16 years old with inflammatory arthritis of one or more joints, which has persisted for at least 2 weeks. Health service resource use data were collected as part of routine clinical care at study entry, 6 months and 1 year. Reference unit costs were applied to these data and the cost of treatment per child calculated for the first year from diagnosis.

Results. A total of 297 children attended a 12-month follow-up visit. The mean annual total cost per child was £1649 (s.d. £1093, range £401–£6967). The highest cost component was for appointments with paediatric rheumatologists. Mean total costs were highest for children with enthesitis-related, systemic JIA or extended oligoarthritis.

Conclusions. In the first 12 months after diagnosis, children with all JIA disease subtypes consume large, but highly variable quantities of health service resources. Individual patient costs are required to reflect the wide variation in cost between patients and allow appropriate recouping of costs for contracted services and for assessing the economic impact of interventions.

Methods. The study used data from a prospective RA cohort of 916 RA patients with disease duration ≤24 months. Data pertained to standard clinical measures and patients’ self-reports, such as functional capacity, pain and MS. Multivariate logistic regression analyses were performed to determine the association between MS and early retirement at 3 yrs, adjusting for sex, age, baseline working status, functional capacity, pain and 28-joint disease activity score (DAS28).

Results. MS was strongly associated with pain and functional capacity and to a lesser degree with joint counts and active phase responses. Severe MS in early disease had a significant impact on early retirement within the following 3 yrs. Of the 389 patients who were ≤61 yrs old and working at baseline, 80 (21%) had to take early retirement until the end of the study. Early retirement concerned 46% of the patients with severe and 10% of those with mild MS at study entry. Baseline working status was the strongest predictor and was severe compared with mild MS, the second strongest predictor of early retirement (adjusted odds ratio 6.0; 95% CI 2.9, 12.6).

Conclusions. Severe MS in the early course of the disease has a high impact on RA patients’ decision to withdraw from working life. Great attention should be paid to the effective treatment of MS in early RA, to prevent patients from possible untimely decisions that will have long-lasting and costly consequences.

Methods. Cross-sectional study including patients fulfilling ACR criteria for the classification of SLE. Serum 25(OH)D levels at 30 and 10 ng/ml were the cut-off values for vitamin D insufficiency and vitamin D deficiency, respectively. SLE activity was measured by SLEDAI and irreversible organ damage by the SLICC-ACR index. Fatigue was quantified using a 0–10 visual analogue scale (VAS).

Results. Ninety-two patients (90% women, 98% white) were included in the study. Sixty-nine (75%) and 14 (15%) patients presented with vitamin D insufficiency and deficiency, respectively. Female sex (P = 0.001), treatment with HCQ (P = 0.014) and treatment with calcium and vitamin D (P = 0.049) predicted higher levels of 25(OH)D. Photosensitivity [odds ratio (OR) 3.5] and photoprotection (OR 5.7) predicted vitamin D insufficiency and deficiency, respectively. Higher age (OR 0.95) and HCQ use (OR 0.29) protected against vitamin D deficiency. Patients with vitamin D deficiency had a higher degree of fatigue as quantified by a 0–10 VAS (mean 5.32 vs 4.03, P = 0.08). No relation was seen between vitamin D insufficiency or deficiency and disease duration, SLEDAI or SLICC-ACR indexes.

Conclusions. Vitamin D insufficiency and deficiency are common in patients with SLE and are associated with sun avoidance. HCQ prevented vitamin D deficiency. Vitamin D deficiency was related to a higher degree of fatigue. Vitamin D levels had no relation with SLE severity.

Methods. The expression of TLR2, TLR4 and CD16 on monocytes was detected by flow cytometric analysis and RT-PCR. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured in the patients with BD, psoriasis and healthy controls, and then the expression of TLRs was correlated with the value of serum 25(OH)D levels. To assess the influence of vitamin D₃ on expression and function of TLRs in vitro, human monocytes were treated with increasing concentrations of 1,25(OH)₂D₃.

Results. We found that the monocytes of active BD patients showed higher expressions of TLR2 and TLR4 than those of controls, and serum 25(OH)D levels tended to be lower in active BD. Furthermore, 25(OH)D levels were inversely correlated with the expressions of TLR2, TLR4 and clinical indicators. In vitro analysis showed that vitamin D₃ was found to dose-dependently suppress the protein and mRNA expressions of TLR2 and TLR4. TNF- synthesis was also decreased upon TLR ligand stimulation in vitamin D₃-treated monocytes.

Conclusion. These results suggest that the inflammation triggered through TLR2 and TLR4 is important in the pathogenesis of BD. And it seems possible that vitamin D may be used as a therapeutic option by modulating TLR2 and TLR4 expression of monocytes in BD.

Methods. Thirty-eight pSS patients and 200 population-based controls were studied for presence and severity of AD symptoms using the Autonomic Symptom Profile (ASP), a validated self-completed questionnaire evaluating various AD symptoms. In addition, patients were investigated by three different objective autonomic nervous function tests.

Results. pSS patients scored significantly higher in the parasympathetic [secretomotor disorder, urinary disorder, gastroparesis (females only) and pupillomotor disorder] as well as sympathetic (orthostatic intolerance and vasomotor disorder) ASP domains compared with controls. Consequently, the standardized ASP total score was significantly increased in pSS patients [1.77 (0.57, 3.15) vs – 0.21 (–0.82, 0.72); P = 0.00] and 45% of pSS patients had an ASP total score ≥2 s.d. Furthermore, the autonomic nervous function tests showed signs of objective parasympathetic and sympathetic dysfunction as well. However, the ASP domain and total scores showed limited associations with the objective autonomic nervous function test parameters as well as clinical and serological factors of pSS.

Conclusions. pSS patients showed subjective and objective signs of both a parasympathetic and a sympathetic dysfunction. However, AD symptoms showed limited associations with objective autonomic nervous function as well as other clinical features of the disease.

Methods. Using a customized low-density cDNA microarray with 747 genes and a reliable data collection system, we monitored the mRNA expression profiles of whole blood cells from 18 RA patients before and after the infusion of infliximab for up to 22 weeks. The clinical response to treatment with infliximab was determined using the ACR response criteria, the disease activity score of 28 joints (DAS28), and individual clinical parameters. The patients were classified as responders or non-responders based on their ACR50% response at 22 weeks.

Results. Approximately 15% of the total genes were found to exhibit a >1.5-fold change, compared with their reference values, at one or more time points during the 22 weeks of infliximab therapy. The expression of inflammatory genes, such as IFN-related genes, was strongly correlated with the serum level of CRP and the DAS28. The increased expression of inflammatory genes in responders was normalized within 2 weeks and then remained at a normal level during the treatment period. In contrast, in the non-responders, the elevated expression at baseline, although it was significantly decreased at 2 weeks, returned to the baseline level after 14 weeks. In addition to inflammatory genes, we identified several groups of genes with distinct differences in expression between the responders and non-responders.

Conclusions. Our results suggest that a customized low-density microarray is useful for monitoring mRNA expression profiles in peripheral blood cells, enabling us to identify a unique set of genes with differentially regulated expressions in responders and non-responders to a TNF inhibitor among patients with RA.

Methods. Five patients with IP received UT inhibitor (3 x 10⁵ U) infusion into the internal jugular vein, three times in a single day. The response to this therapy was assessed clinically and by chest CT, PaO₂ and serum KL-6. The kinetics of UT inhibitor was determined in arterial blood. We measured serum levels of monocyte chemotactic protein-1 and TGF-β1, which are thought to be involved in the pathogenesis of IP.

Results. Serum concentrations of UT inhibitor increased immediately to >150 U/ml after infusion of 3 x 10⁵ U of UT inhibitor. The treatment resulted in clinical and radiological improvements in four patients, and allowed reduction of oxygen therapy following improvement of hypoxaemia within 1 month. UT inhibitor decreased serum levels of KL-6 in all patients and had no adverse effects. MCP-1 and TGF-β1 concentrations were higher in the patients than in normal subjects, and infusion of 3 x 10⁵ U of UT reduced the concentrations within 3 h of infusion.

Conclusion. UT inhibitor bolus infusion therapy is a potentially useful therapeutic strategy for intractable IP based on the different mechanism of action relative to conventional immunosuppressive therapy and lack of serious treatment-related adverse effects.

Methods. A postal survey was sent to rheumatology specialist registrars (SpRs) on the Joint Committee for Higher Medical Training (JCHMT) database between December 2005 and January 2006, and concurrently by e-mail to the Rheumatologists at Training e-mail list.

Results. Seventy-three percent (165/227) of trainees responded. Of them, 89.1% had previous senior house officer (SHO) experience in rheumatology and 81.8% made a career decision in favour of rheumatology during their SHO post. The top four ranked factors influencing choice of rheumatology were SHO experience, subject matter, inspirational consultants and lifestyle aspects; 89.1% would still choose rheumatology now. Factors felt to be negatively influencing future trainees came under three key themes: poor student or postgraduate exposure, employment and service delivery issues (including concern over the future place of rheumatology in primary vs secondary care), and perceived poor profile of rheumatology. Factors positively influencing future candidates were subject matter, work/life balance and prior exposure to the speciality.

Conclusions. Early postgraduate experience is key to choice of speciality. An overwhelming majority of trainees decide speciality during SHO experience. With ongoing changes in career structure, it is critical that rheumatology is incorporated into foundation and speciality training programmes and essential that continued measures are taken to improve the image of rheumatology.

Methods. All patients prescribed TNF-blocking therapies for AS between 1999 and 2006 were studied. Response was evaluated using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and CRP results.

Results. A total of 113 patients (84 males: 29 females, mean age 45 yrs, median disease duration 16 yrs, 87% HLA-B27 positive) were identified. At baseline they had a mean BASDAI of 6.57, BASFI 6.57 and CRP of 31 g/dl. At the end of follow-up, these values had reduced to mean BASDAI of 3.12, BASFI 4.16 and CRP of 7 g/dl. Improvements were sustained for 24 months and beyond with no loss of effect. Only nine patients (8%) suffered side-effects leading to cessation or switching of first-line therapy and non-response occurred in 15 patients (13%) in the long term. Fifteen patients (13%) switched to a second drug and 14 of these (93%) had a significant and sustained response. Outcomes were similar regardless of drug used, duration of disease and HLA-B27 status.

Conclusion. Treatment of active AS with TNF blockers according to the British Society of Rheumatology guidelines leads to a sustained response for over 2 yrs with most patients tolerating the drugs well. The rate of non-response is significantly lower than that seen in RA and nearly all of these patients respond well to a second-line agent.

Methods. We studied 36 patients, 18 with a diagnosis of PAPS and 18 healthy volunteers. All patients underwent a two-phase (rest–stress) ¹³N-ammonia PET. Myocardial perfusion images were acquired and then analysed by two experts in the field.

Results. We found ischaemia in 7/18 asymptomatic PAPS patients (38.8%). The anterolateral wall was the most commonly affected cardiac territory [5/7 PAPS patients (71.4%)]. In a severity analysis, we found that five patients (71.4%) had mild ischaemia, one patient (14.2%) had moderate ischaemia and another one (14.2%) had severe defects. All the healthy volunteers studied showed normal myocardial perfusion images.

Conclusion. An important proportion of PAPS patients, even when asymptomatic, showed myocardial perfusion defects assessed with PET. Most of the ischaemic patients had mild defects and the anterolateral wall was the territory mainly affected.

Methods. In a multicentre controlled randomized study, participants were recruited with a clinical diagnosis of unilateral subacromial syndrome from six rehabilitation medicine departments belonging to the Public Health System in two Spanish regions. All participants received 15 sessions of physiotherapy during the 3 weeks that the treatment lasted and were randomized to additionally receive, once a week, acupuncture or mock TENS (transcutaneous electrical nerve stimulation). The primary outcome measure was the change in the Constant–Murley Score (CMS) for functional assessment of the shoulder, at 4 weeks after randomization. This study is registered as an International Standard Randomized Controlled Trial, number ISRCTN28687220.

Results. A total of 425 patients were recruited. The mean score (s.d.) on the CMS had increased by 16.6 (15.6) points among the acupuncture group, compared with 10.6 (13.5) points in the control group, and the mean difference between the two groups was statistically significant (6.0 points; 95% CI 3.2, 8.8 points; P < 0.001). By the end of the treatment, 53% of the patients in the acupuncture group had decreased their consumption of analgesics, compared with a corresponding 30% among the control group (P < 0.001).

Conclusions. Single-point acupuncture in association with physiotherapy improves shoulder function and alleviates pain, compared with physiotherapy as the sole treatment. This improvement is accompanied by a reduction in the consumption of analgesic medicaments.

Methods. Adults with ANCA-SVV (n = 202) completed a self-administered questionnaire that assessed eight self-management behaviours (adherence to recommendations for medication, health service use, diet, exercise, infection avoidance and symptom monitoring; prompt reporting of symptoms and side effects; and adjusting activities in response to symptoms), perceptions about these behaviours, socio-demographics, clinical factors and social desirability bias. Descriptive statistics were generated to characterize patients’ perceptions about difficulty of, importance of, and specific barriers to performing each behaviour. Regression analyses explored whether these variables were associated with performing each behaviour, controlling for potential confounders.

Results. With few exceptions, higher perceived importance and lower perceived difficulty of each behaviour were associated with more frequent performance of the behaviour. For each behaviour, several specific barriers were frequently endorsed by patients and a number of these were associated with lower levels of self-management.

Conclusion. This study reveals that patient perceptions about the illness and its treatment influence ANCA-SVV self-management. Perceived barriers to medication, health services, diet and exercise adherence were similar to those in other illnesses. This study also provides insight into barriers experienced by patients in performing behaviours (infection avoidance, symptom monitoring, reporting symptoms and side-effects and adjusting activities) not often previously studied. How the identification of these barriers can help inform future interventions for ANCA-SVV patients is to be discussed.

Methods. RA FLS were transfected with either a plasmid that expresses HIF-1 or an empty vector as a control, and then cultured under normoxia (21% O₂). Also, FLS were transfected with either HIF-1 small interfering RNA (siRNA) or control siRNA, and cultured under hypoxic conditions (1% O₂). Following transfection, the amounts of MMP and cytokine mRNAs and HIF-1 protein were examined using real-time RT–PCR and western blotting, respectively.

Results. The expression of HIF-1, MMP-1, MMP-3, IL-6 and IL-8 was markedly enhanced in FLS that were cultured under hypoxia. We confirmed that transient transfection of HIF-1 overexpressing vector or siRNA had occurred using western blotting, and in vitro studies conducted using FLS transfected with HIF-1 overexpression vector showed that they had significantly increased MMP-1, MMP-3 and IL-8 expression levels. Further, hypoxia-induced MMP-3 expression was significantly attenuated by knock-down of HIF-1, whereas hypoxia-induced IL-8 or MMP-1 expression was not significantly repressed by HIF-1 siRNA.

Conclusions. Hypoxia-induced MMP-3 expression is exclusively regulated by HIF-1, and hypoxia-induced MMP-1 or IL-8 expression appears to have salvage pathways other than the HIF-1 pathway. Together, these data provide new insight regarding the mechanism by which hypoxia participates in joint inflammation and destruction in RA.

Methods. For all five patients intravenous infliximab was initially given at a dose of 3 mg/kg. Further doses were then given at weeks 2, 6 and every 8 weeks thereafter. The dose and frequency were tailored in accordance with clinical response. Clinical and laboratory data were collected prospectively.

Results. We report results between 8 and 30 months after starting infliximab. Improvements were seen in all five patients as shown by positive changes in physician visual analogue scale (VAS), Childhood Myositis Assessment Score (CMAS), Childhood Health Assessment Questionnaire (CHAQ), joint range of movement and, in some, regression of calcinosis and skin signs. There were no major side effects observed with addition of infliximab to the therapeutic regime.

Conclusions. Major clinical benefit was demonstrated after the initiation of infliximab in all five cases of refractory JDM.

Methods. Purified IgGs were obtained from the sera of seven SS patients (six primary and one secondary SS) and two normal persons. We examined whether SS IgG inhibits M3R function and identified the epitope using six synthetic peptides covering all the extracellular domains of M3R by microspectrofluorimetry and surface plasmon resonance-based optical biosensor system (BIAcore system).

Results. A volume of 0.5 mg/ml SS IgG inhibited carbachol (CCh)-induced [Ca²⁺]_i transient (CICT) in human submandibular gland (HSG) cells. However, co-incubation of SS IgG with the 6th peptide (514–527 amino acid region) corresponding to the third extracellular loop of M3R, recovered CICT. The result was further confirmed by BIAcore analysis. We found that the 6th peptide interacts with IgGs from three primary SS patients in a concentration-dependent manner. The synthetic peptide which consists of amino acids 228–237 corresponding to the COOH-terminus of the second extracellular loop of M3R also bound to SS IgG. However, normal IgGs did not interact with the 6th peptide.

Conclusions. The results suggest that the third extracellular loop of M3R represents a functional epitope bound by SS IgG, and thereby partly inhibits M3R function.

Methods. All consecutive new outpatients with peripheral PsA requiring second-line drugs and RA observed between January 2000 and December 2005 were included in a prospective, case-control study. Primary end point was to assess the frequency of remission in peripheral PsA compared with RA. Secondary end points were to compare the duration of clinical remission during treatment and after therapy interruption, ACR 20, 50, 70 response rates and to detect any remission predictor at diagnosis. Treatment regimen was standardized in both groups. From January 2003 to December 2005, therapy was suspended in PsA patients and controls if achieving remission.

Results. One or more episodes of remission occurred in 57/236 (24.1%) PsA patients and in 20/268 (7.5%) controls (P < 0.001). The mean duration of remission was of 13 ± 9.4 months in PsA patients and 4 ± 3.7 in controls (P > 0.001). Remission episodes were more frequent in PsA patients treated with anti-TNF compared with those receiving traditional DMARDs (P > 0.001), with no differences regarding the duration. After therapy interruption, the remission duration was 12 ± 2.4 months in PsA and 3 ± 1.5 in RA (P < 0.001). No remission predictor at diagnosis resulted by multivariate analysis.

Conclusion. Remission is possible in up to 24% of patients with peripheral PsA. It is significantly more frequent, but not longer, in patients receiving anti-TNF drugs compared with those treated with traditional DMARDs. Patients remain in remission for a long period after therapy interruption, thus suggesting an intermittent therapeutic strategy.

Methods. Data of the 281 completers of a 2-yr randomized controlled trial (Rheumatoid Arthritis Patients In Training; RAPIT) comparing the effects of usual care physical therapy with high-intensity weight-bearing exercises were analysed. The primary outcome variable was defined as the change in radiological joint damage (Larsen score) of the large joints. Potential predictors of outcome were defined: baseline and change in serum level of COMP after 3 months, baseline radiological damage of the large and small joints, number of months on glucocorticoids, change in disease activity and in physical capacity (aerobic fitness and muscle strength) after 2 yrs, and participation in the exercise group.

Results. In cross-sectional evaluation of baseline data, we found strong association between the high serum COMP level and current damage of the large joints. Serum COMP level at baseline, however, was not associated with an increased rate of radiological joint damage after 2 yrs of follow-up. Furthermore, neither interaction between baseline COMP level and participation in exercises, nor change in COMP level after 3 months of exercising were associated with future damage of the large joints.

Conclusion. Neither baseline serum COMP level nor its individual change after 3 months from start of intensive exercise predict longitudinal progression of damage of the large joints in this population.

Methods. Rituximab was infused intravenously, weekly 4 times in a dose-escalating fashion at three different doses of 100, 250 or 375 mg/m² to three patients each. Immunological parameters were monitored at certain points until 12 months after the treatment.

Results. Rituximab was well tolerated and safe in these patients. Seven out of eight SLE patients and one with Evans’ syndrome clinically responded completely or partially to the treatment. Four patients achieved long-term remission (18–30 months) without any additional treatment. In these patients, a significant decrease in circulating B cells continued for 6 months after the treatment. The mean fluorescence intensities of CD19, CD21, CD40 and BR3 on the residual B cells as well as the percentage of CD69+ CD4+ T cells decreased significantly. Serum TNF- levels decreased significantly on day 2. The Th1/Th2 balance of CD4+ T cells gradually shifted towards a Th1 type by 6 months.

Conclusion. In addition to B-cell depletion, modification of B-cell and T-cell phenotypes as well as cytokine profiles may be involved in the action of rituximab.

Methods. Expression of IL-19, IL-20 receptor 1 (IL-20R1) and IL-20R2 was examined by RT-PCR and immunohistochemical analysis in rheumatoid synovium. The effects of IL-19 on synovial cells established from rheumatoid synovium (RASCs), with regard to IL-6 production and signal transducers and activators of transcription3 (STAT3) activation, were examined by ELISA and western blot analysis, respectively. The effect of IL-19 on RASC apoptosis was examined by Hoechst staining, flow cytometry analysis of annexin V binding and caspase-3 activity.

Results. IL-19, IL-20R1 and IL-20R2 mRNA were detected by RT-PCR in synovial tissues from RA patients. Immunohistochemical analysis showed IL-19 was predominantly expressed in the hyperplastic lining layers of RA synovial tissues. The majority of IL-19-positive cells were vimentin-positive and CD68-positive synovial cells, serving as markers of fibroblasts and macrophages, respectively. IL-20R1 and IL-20R2 (IL-20Rs) were expressed in both the lining and sublining layers of RA synovium. In RASC, IL-19 was induced by lipopolysaccharide stimulation and constitutive expression of IL-20Rs was observed, suggesting IL-19 has an autocrine action. In terms of this function, IL-19 induced STAT3 activation and increased IL-6 production by RASC above the medium control. Moreover, IL-19 significantly reduced RASC apoptosis induced by serum starvation.

Conclusions. These data suggest that IL-19, produced by synovial cells, promotes joint inflammation in RA by inducing IL-6 production and decreasing synovial cell apoptosis.

Methods. In situ zymography (ISZ) has been used to investigate the role of IL-1 and TNF in the matrix degradation characterizing symptomatic IVD degeneration. ISZ employed three substrates (gelatin, collagen II, casein) and four different challenges, IL-1β, IL-1 receptor antagonist (IL-1Ra), TNF- and anti-TNF.

Results. We have shown for the first time that whilst IL-1β will stimulate and IL-1 receptor antagonist will inhibit matrix degradation in intact human IVD tissue, neither TNF- nor anti-TNF have any measurable effect on degradation of these matrices.

Conclusion. This study has addressed a current area of controversy in IVD biology, namely, whether either IL-1 or TNF or both are involved in driving matrix degradation. Our data indicate that IL-1 is a key cytokine mediating matrix degradation in the IVD and therefore a therapeutic target.

Methods. Forty patients with CSS diagnosed according to ACR 1990 criteria, 30 healthy controls (HC) and 57 disease controls (28 asthma, 20 small vessel vasculitis, 9 hypereosinophilic syndrome) were studied. Clinical data were collected and serum levels of eotaxin-1, -2 and -3 were determined by ELISA. Further, immunohistochemistry was applied to identify eotaxin-3 expression in tissue biopsies from patients with CSS.

Results. In contrast to eotaxin-1 and -2, eotaxin-3 was highly elevated in serum samples of active CSS patients and correlated highly significantly with eosinophil counts, total immunoglobulin E (IgE) levels and acute-phase parameters. Moreover, eotaxin-3 was not elevated in other eosinophilic and vasculitic diseases. Immunohistochemical analysis revealed strong expression of eotaxin-3 in endothelial and inflammatory cells in affected tissues of active CSS patients.

Conclusions. This study reveals the specific association of elevated eotaxin-3 expression with high disease activity and eosinophilia in CSS patients. Eotaxin-3 might thus be a pathogenic player, biomarker and potential therapeutic target in CSS.

Methods. Human SFs were obtained from 19 knee joints with anterior cruciate ligament injury around the time of reconstruction surgery, and from three healthy volunteers. SF was plated, cultured and examined for colony-forming number, in vitro differentiation, surface epitopes and gene profiles. Also, rabbit synovium-MSCs were injected into the knee joint in a rabbit partial anterior cruciate ligament defect model, and the injected cells were traced.

Results. SF-MSCs from IA ligament injury patients were 100 times more in number than those from healthy volunteers. Total colony number was positively correlated with post-injury period. No significant differences were observed among the cells derived from SF around the time of the surgery in relation to surface epitopes and differentiation potentials. Cluster analysis of gene profiles demonstrated that SF-MSCs were more similar to synovium MSCs than bone marrow MSCs. In rabbit experiments, the MSCs injected into the knee in which IA ligament was partially defective were observed more on the defected area than on the intact area of the ligament at 24 h.

Conclusion. We demonstrated that SF-MSCs, similar to synovium MSCs, increased in number after IA ligament injury and surgery without marked alteration of the properties.

Methods. Thirty-nine patients with active RA who had failed at least one DMARD received two rituximab infusions 2 weeks apart. Seventeen patients received two 1000 mg doses, and 22 received the 500 mg regimen. The 28-joint disease activity index (DAS28) and European League against Rheumatism (EULAR) response criteria were recorded at baseline, 3, 6, 9 and 12 months. RF and ANA were recorded at baseline and at 6 and 12 months.

Results. There was a significant improvement in the DAS28 at all time points, and EULAR response was observed in 29 of 33 patients (87.9%) at 3 months, 25 of 33 patients (75.8%) at 6 months, 22 of 29 patients (75.9%) at 9 months and 23 of 30 patients (76.7) at 12 months. Improvement was also noted in CRP, and both RF and ANA were generally reduced after treatment. Patients who were on the higher regimen of two 1000 mg doses appeared to respond slightly better compared with the lower dose regimen.

Conclusions. Rituximab is well tolerated in everyday clinical practice and may represent a good short-term treatment option where anti-TNF therapy is either unavailable or relatively contraindicated.

Methods. Peripheral blood (PB) and clinical data were obtained from 37 AS, 36 RA patients and 37 healthy controls. We also generated IL-4-producing CD8+ T cell lines and clones by co-culture with autologous dendritic cells. Using flow cytometry, we evaluated intracellular cytokine expression by T cells following stimulation with PMA and calcium ionophore. The phenotype and ability of the IL-4-producing CD8+ T cell clones to suppress IFN- production were examined.

Results. The percentages of IL-4+ CD8+ T cells were higher in PB of patients with AS and RA than controls (medians 0.90 and 0.84% vs 0.30%). In RA, patients with active inflammation had an increased percentage of IL-4+ CD8+ T cells. Higher frequencies of IL-4+ CD8+ T cells were also found in CD8+ T cell lines established from patients with arthritis. Interestingly, most IL-4+ CD8+ T cells produced TNF-. Cloning the CD8+ T cell lines yielded more IL-4-producing clones from AS (23%) and RA patients (14%) than from controls (7%). The ability to suppress IFN- production was observed in 56% (AS) and 85% (RA) of IL-4-producing clones. Suppressive IL-4+ CD8+ T cell clones from RA patients showed a similar regulatory phenotype to the clones previously isolated from AS patients.

Conclusions. Expansion of IL-4+ CD8+ T cells, which may include precursors of a regulatory CD8+ T cell subset, may represent a general response to chronic joint inflammation.

Methods. Ten healthy subjects were initially enrolled to compare axon reflex-dependent thermal hyperaemia between the finger and forearm cutaneous circulations. Then, 10 patients with primary RP and 16 patients with SSc participated in a similar protocol focusing on the finger circulation only. Lidocaine/prilocaine cream was applied for 1 h to produce local blockade of cutaneous sensory nerves. After lidocaine/prilocaine pre-treatment, laser Doppler probes were heated from skin temperature to 42°C for 30 min, and 44°C for 5 min to achieve maximal skin blood flow. Data were expressed as a percentage of maximal cutaneous vascular conductance.

Results. In healthy volunteers, we observed a significantly higher initial peak on the finger compared with the forearm, with both responses blunted following topical anaesthesia. In primary RP patients, we observed a decreased initial peak following lidocaine/prilocaine pre-treatment in the finger circulation [96.7% (33.4) vs 75.9% (29.5) with anaesthesia, P = 0.02]. In contrast, pre-treatment did not alter the initial peak in patients with SSc. A minute-by-minute analysis showed no delay of the initial peak.

Conclusions. We show an abnormal digital neurovascular response to local heating in SSc. Thermal hyperaemia could be monitored as a clinical test for neurovascular function in SSc. Further studies are required to test whether the abnormal digital neurovascular response correlates to the degree of peripheral vascular involvement.

Methods. A prospective epidemiological study has been carried out on 1471 AS patients treated with repeated intravenous injections of ²²⁴Ra between 1948 and 1975. These patients have been followed together with a control group of 1324 AS patients not treated with radioactive drugs and/or X-rays. Numbers of malignancies expected in a normal population were computed from German and Danish cancer registry data.

Results. After a mean follow-up time of 26 yrs in the exposed group or 25 yrs in the control group, causes of death have been ascertained for 1006 exposed patients and 1072 controls. In particular, 19 cases of leukaemia were observed in the exposure group (vs 6.8 cases expected, P < 0.001) compared to 12 cases of leukaemia in the control group (vs 7.5 cases expected). Further subclassification of the leukaemia cases demonstrated a high increase of myeloid leukaemia in the exposure group (11 cases observed vs 2.9 cases expected, P < 0.001), especially a high excess of acute myeloid leukaemias (7 cases observed vs 1.8 cases expected, P = 0.003), whereas in the controls the observed cases are within the expected range (4 myeloid leukaemias vs 3.1 cases expected).

Conclusions. The enhanced leukaemia incidence in the exposed group is in line with results from experiments in mice injected with varying amounts of the bone-seeking -emitter ²²⁴Ra. In these studies, in animals exposed to lower doses of ²²⁴Ra, i.e.