Evidence-based practice is an increasingly popular term, used in a variety of clinical settings and situations. Practitioners are encouraged to use best evidence as part of clinical decision-making when caring for individual patients. This evidence, combined with practitioner expertise and knowledge, aims to inform practice, ensuring that accurate, effective and safe treatment options are utilized.

To examine the expression of the apoptosis regulatory protein, Bcl-x(L), in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunohistochemistry for Bcl-x(L) was carried out on synovial samples from patients with RA and OA. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis were performed to qualitatively examine the expression of Bcl-x(L). Bcl-x(L) expression was detected in the lining, endothelium and inflammatory cells of both RA (n=20) and OA (n=10) samples. However, there was significantly more expression in the lining of RA synovium compared to OA (77 vs 61%, p<0.05). Many of the positive cells in the RA subsynovium were noted to be plasma cells. There was a significant correlation between Bcl-x(L) expression and the number of inflammatory cells in the subsynovium of RA and OA patients (r (s)=0.376, p<0.05, n=30). Age and disease duration did not correlate with Bcl-x(L) expression in rheumatoid patients. Bcl-x(L) may play a role in the extended survival of synoviocytes and inflammatory cells in rheumatoid synovium.

Lupus myocarditis is a life threatening complication of systemic lupus erythematosus (SLE). A case of left ventricular failure secondary to myocarditis occurring in a patient with SLE is reported. Despite resolution of the cardiac failure with pulsed cyclophosphamide and steroids, she eventually died of non-cardiac complications 18 months later. The literature is also reviewed.

Background: A significant cardiovascular (CV) mortality occurs in systemic sclerosis (SSc), though conventional risk factors including blood cholesterol, low density lipoprotein, triglycerides, glucose, thyroid and smoking status do not seem to account for this.Oxidised low density lipoprotein (oxLDL) and homocysteine(Hcy) however are increasingly being implicated in atherogenesis and we wished to investigate if these two factors might be relevant to the macrovascular disease of SSc.Methods: 91 SSc patients and 94 matched normal controls had ankle brachial blood pressure index (ABPI) measurements to identify peripheral artery obstructive disease (PAOD), and carotid artery duplex scanning to identify carotid artery narrowing.All subjects were screened for conventional atherosclerotic risk factors which included measurement of random blood cholesterol, high density lipoprotein, triglyceride and glucose levels as well as thyroid stimulating hormone.A smoking history was obtained.Serum Hcy was measured by fluorescence polarisation immunoassay and oxLDL was measured by ELISA.Results: Demographic details for the 91 SSc patients (24 diffuse: 67 limited) and 94 controls were similar, with no statistically significant differences between the two groups for female:male ratio and age.21%SSc patients had evidence of PAOD vs 1% controls (p=0.00002Chi-2 test).There were significantly more patients than controls with low ABPI < 1.0 i.e. 45% of SSc versus 21% of controls (p=0.0005Chi 2 test).The mean (SD) ABPI was also lower in SSc at 0.96 (0.15) versus controls at 1.02 (0.06) (p<0.0001Chi 2 test).65% SSc patients had carotid artery disease vs 34% controls (p=0.00003).Homocysteine was significantly higher in SSc patients with macrovascular disease (p=0.035), and carotid disease (p=0.04)compared to controls.Levels correlated with carotid disease severity.OxLDL was significantly higher in SSc-with-PAOD, mean/(SD) 48.8(36.0)Acu/ml versus SSc-without-PAOD at mean/(SD) 28.1(13.7)Acu/ml (p=0.045t-test).OxLDL was higher at mean/(SD) 48.1(35.7)m mol/l in diffuse SSc(dSSc) versus mean/(SD) 27.2(10.9)Acu/ml in limited SSc(lSSc), (p=0.025t-test).Conclusions: Hcy and oxLDL have been shown to contribute to macrovascular disease in the general population.We found significantly elevated levels of both in SSc patients with macrovascular disease, with a trend towards raised Hcy in SSc patients in general.These parameters may provide targets for future intervention in this patient group.One wonders if we should all consider supplementing our SSc patients (many of whom have sub-clinical malabsorbtion) with folic acid to prevent homocysteinaemia.

A 61-year-old man presented to the rheumatology clinic with a 2-year history of rightsided low back pain without radiation. There were no systemic features such as weight loss, pyrexia or sweats. He had been recently admitted with epididymo-orchitis. However, a chest X-ray was normal and acid and alcohol-fast bacilli (AAFB) were not demonstrated on microscopy of pus from a scrotal sinus. Clinical examination was unremarkable. Initial investigations revealed a mild microcytic anaemia (haemoglobin 11.1g/dl and mean cell volume 79.9 fl) and normal inflammatory parameters (C-reactive protein 6 mg/litre and erythrocyte sedimentation rate (ESR) 20 mm/hr). A white cell count was 9.8 x109/litre and rheumatoid factor was negative. Total globulin was elevated at 36 g/litre but immunoglobulins and prostate specific antigen were normal. A repeat chest X-ray was normal. Lumbar spine X-rays showed obliteration of the right sacroiliac joint with adjacent sclerosis and suspicion of erosive change. Magnetic resonance scan of the area demonstrated destructive change in the right sacroiliac joint and a possible soft tissue mass anteriorly, suggestive of either a low-grade tumour of cartilage or an infective process (Figure 1). Subsequent computed tomography-guided biopsy of the soft tissue mass was unsuccessful. The patient continued to experience increasing pain in the right lumbar area and underwent a right sacroiliac joint biopsy under image intensification at another centre. Histology of the biopsy specimen was consistent with low-grade active chronic osteomyelitis but no organism was isolated. Empirical treatment with flucloxacillin was started. Brucella serology was subsequently negative. A repeat magnetic resonance scan showed worsening of the right sacroiliac joint destruction with bone oedema and ring-enhancing lesions post-gadolinium. An open biopsy of the right sacroiliac joint was performed and histological examination of this specimen demonstrated AAFB on microscopy. Mycobacterium tuberculosis was eventually found on culture. Histology of the de-calcified specimen showed non-caseating granulomata and a Ziehl–Nielsen stain was negative. He was treated with antituberculous treatment for a total of 12 months. Repeat investigations on discontinuing therapy showed sclerosis of the affected joint on plain films with a normal haemoglobin level (15.0 g/dl) and ESR (8 mm/hr).

Background: Glucocorticoids (Gc) are the most potent anti-inflammatory agents known, and are important for the treatment of multiple inflammatory conditions, including rheumatoid arthritis. However, their use is limited by side effects such as hypertension and osteoporosis. Population based variation in response to Gc therapy has been described, but the genetic basis underlying this response has yet to be determined. The glucocorticoid receptor (GR) gene is a principle candidate for investigation of such variable Gc response. A polymorphism at codon 363 of GR is known to be associated with minimal changes in Gc sensitivity (1). Expression of the GR is determined by multiple tissue specific promoters. Recently, Breslin et al described a T lymphocyte specific promoter/enhancer, 31Kb upstream of the GR coding region, which, uniquely, is upregulated by Gc (2). As T cells are critical regulators of the immune response, and are key targets for Gc immunosuppression, nucleotide variation within this region may significantly influence the sensitivity of T lymphocytes to Gc, and as such be important in determining an individual’s response to Gc therapy. Aim: To determine if the T lymhocyte-specific GR promoter contains polymorphims which may influence Gc response. Methods: Polymorphism screening was performed using dHPLC (Wave,Transgenomic) in 36 unrelated UK caucasians. Overlapping PCR fragments were generated to cover the entire 2028bp of the lymphocyte-specific GR promoter. Each fragment was <700bp so allowing a 99% sensitivity for heteroduplex detection. The entire 2028bp region was also sequenced (BigDye ddNTP) for 20 of the individuals studied. Results: No nucleotide variation was found across the lymphocyte specific GR promoter in any of the 36 UK caucasian individuals investigated. Conclusions: No genetic variation was seen in the UK caucasian sample set studied. Single nucleotide polymophism (SNP) frequency varies throughout the genome, but on average a SNP is thought to occur every 1Kb (3). If any nucleotide changes do exist within the T lymphocyte specific promoter of the GR they will be present at a frequency of < 2.7%, so limiting their potential informativeness in genetic studies of Gc response.

Background: Glucocorticoids (Gc) are the most potent anti-inflammatory agents known, and are important for the treatment of multiple inflammatory conditions, including rheumatoid arthritis. However, their use is limited by side effects such as hypertension and osteoporosis. Population based variation in response to Gc therapy has been described, but the genetic basis underlying this response has yet to be determined. The glucocorticoid receptor (GR) gene is a principle candidate for investigation of such variable Gc response. A polymorphism at codon 363 of GR is known to be associated with minimal changes in Gc sensitivity (1). Expression of the GR is determined by multiple tissue specific promoters. Recently, Breslin et al described a T lymphocyte specific promoter/enhancer, 31Kb upstream of the GR coding region, which, uniquely, is upregulated by Gc (2). As T cells are critical regulators of the immune response, and are key targets for Gc immunosuppression, nucleotide variation within this region may significantly influence the sensitivity of T lymphocytes to Gc, and as such be important in determining an individual’s response to Gc therapy. Aim: To determine if the T lymhocyte-specific GR promoter contains polymorphims which may influence Gc response. Methods: Polymorphism screening was performed using dHPLC (Wave,Transgenomic) in 36 unrelated UK caucasians. Overlapping PCR fragments were generated to cover the entire 2028bp of the lymphocyte-specific GR promoter. Each fragment was <700bp so allowing a 99% sensitivity for heteroduplex detection. The entire 2028bp region was also sequenced (BigDye ddNTP) for 20 of the individuals studied. Results: No nucleotide variation was found across the lymphocyte specific GR promoter in any of the 36 UK caucasian individuals investigated. Conclusions: No genetic variation was seen in the UK caucasian sample set studied. Single nucleotide polymophism (SNP) frequency varies throughout the genome, but on average a SNP is thought to occur every 1Kb (3). If any nucleotide changes do exist within the T lymphocyte specific promoter of the GR they will be present at a frequency of < 2.7%, so limiting their potential informativeness in genetic studies of Gc response.

Poster Session 1.Heat shock proteins 43 pression of IκBα was without effect on hypoxia-or cytokine (IL-1, TGFb)induced VEGF production, showing that in these cells VEGF is not under the control of NFκB.Spontaneous VEGF release by RA synovial membrane cultures was significantly inhibited (70%) following infection with AdvIκBα.Complete inhibition of VEGF was not observed, most likely due to the FLS population in the cell mixture.Conclusions: Our results show that the transcription factor NFκB plays an important role in the regulation of VEGF in RA.Nevertheless the signalling mechanisms leading to VEGF production in RA are complex, and cell-as well as stimuli-specific.Understanding those mechanisms may provide new therapeutic strategies for the treatment of RA. 68.