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Biomedical subjects

D J Veale

Publications and source records attributed to D J Veale.

At least 37 records · Page 2Linked to original sources
PubMed2000

Treatment of poor-prognosis early rheumatoid arthritis. A randomized study of treatment with methotrexate, cyclosporin A, and intraarticular corticosteroids compared with sulfasalazine alone.

OBJECTIVE: To determine whether a regimen of methotrexate, cyclosporin A, and corticosteroids introduced at onset in poor-prognosis rheumatoid arthritis (RA) can produce a significant improvement in outcome compared with standard monotherapy with sulfasalazine (SSZ). METHODS: Eighty-two consecutive patients presenting with new, untreated RA of less than 12 months' duration who fulfilled criteria for poor long-term outcome were randomized to receive either combination therapy (n = 40) or SSZ alone (n = 42). The primary outcome measures were remission and American College of Rheumatology (ACR) criteria for 20% improvement at 48 weeks. RESULTS: After 48 weeks, the numbers of patients who met the ACR criteria for 20% improvement were not significantly different between the two groups (combination 58% versus SSZ 45%), and similar numbers of patients had persisting clinical remission (approximately 10% both groups). During the first 3 months, there were significantly greater reductions in parameters of disease activity in the combination group. By 24 weeks, the swollen and tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates had fallen significantly in both groups, with a greater improvement in the swollen and tender joint count in the combination group. At 48 weeks, the radiographic damage score had increased by a median of 1 (range 0-42.5) in the combination group and 1.25 (range 0-72.5) in the SSZ group (P = 0.28; although there were significant differences in the scores for the right hand). There were significantly fewer withdrawals due to lack of efficacy in the combination group than in the SSZ group (1 of 40 versus 10 of 42; P = 0.007). In the combination group, dose reduction was needed in 22.5% because of hypertension and in 22.5% because of elevated creatinine levels. Over 48 weeks, serum creatinine increased in both groups, but particularly in the combination arm. CONCLUSION: In poor-prognosis RA patients, "aggressive" combination therapy led to more rapid disease suppression but did not result in significantly better ACR response or remission rates. This suggests that in poor-prognosis disease, an approach based on identifying patients with poor treatment responses before extra therapy is added ("step-up" approach) may be more appropriate than the use of combination therapy in all patients from the outset.

Adrenal Cortex Hormones↗
PubMed2000

Modulation of inflammation and metalloproteinase expression in synovial tissue by leflunomide and methotrexate in patients with active rheumatoid arthritis. Findings in a prospective, randomized, double-blind, parallel-design clinical trial in thirty-nine patients at two centers.

OBJECTIVE: Leflunomide and methotrexate have proven to be efficacious in reducing joint inflammation and slowing destruction in clinical trials of patients with rheumatoid arthritis (RA). This study was conducted to provide more insight into the mechanism of action of these agents in synovial tissue. METHODS: In a 2-center, prospective, randomized, double-blind clinical trial, we compared leflunomide (20 mg/day, after a 3-day 100 mg/day loading dose) and methotrexate (increased stepwise to 15 mg/week) treatment in patients with active RA. Paired synovial tissue biopsy samples were obtained by knee arthroscopy at baseline and after 4 months of treatment. Frozen synovial tissue sections were stained for macrophages (CD68), T cells (CD3), adhesion molecules (intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule 1 [VCAM-1]), cytokines (tumor necrosis factor alpha, interleukin-1beta [IL-1beta]), matrix metalloproteinase 1 (MMP-1), and tissue inhibitor of metalloproteinases 1 (TIMP-1). RESULTS: Paired synovial tissue sections were available in 35 patients (16 taking leflunomide, 19 taking methotrexate). Both drugs displayed equal clinical efficacy, with 8 leflunomide-treated patients (50%) and 10 methotrexate-treated patients (53%) fulfilling the American College of Rheumatology 20% response criteria. Both compounds showed similar effects on synovial tissue: reduced numbers of macrophages and reduced ICAM-1 and VCAM-1 expression were noted after 4 months of treatment. Both leflunomide- and methotrexate-treated patients exhibited a decreased MMP-1:TIMP-1 ratio in the synovial tissue. In the subset of patients fulfilling the 20% response criteria of the American College of Rheumatology, a more pronounced reduction in the expression of ICAM-1, VCAM-1, IL-1beta, and MMP-1 was found compared with the nonresponders. CONCLUSION: Leflunomide and methotrexate are clinically efficacious drugs that interfere with mechanisms involved in joint inflammation and destruction of joint integrity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

The value of sonography in the detection of bone erosions in patients with rheumatoid arthritis: a comparison with conventional radiography.

OBJECTIVE: The ability to make an early, accurate diagnosis of rheumatoid arthritis (RA) has become increasingly important with the availability of new, expensive, and targeted therapies. However, plain radiography, the traditional method of detecting the characteristic bone erosions and an important adjunct in establishing a diagnosis of RA, is known to be insensitive. This study compared sonography, a modern imaging technique, with conventional radiography for the detection of erosions in the metacarpophalangeal (MCP) joints of patients with RA. METHODS: One hundred RA patients (including 40 with early disease) underwent posteroanterior radiography and sonography of the MCP joints of the dominant hand. Twenty asymptomatic control subjects also underwent sonography. Erosion sites were recorded and subsequently compared using each modality. Magnetic resonance imaging (MRI) was performed on the second MCP joint in 25 patients with early RA to confirm the pathologic specificity of sonographic erosions. Intraobserver reliability of sonography readings was assessed using video recordings of 55 MCP joint scans of RA patients, and interobserver reliability was assessed by comparing 160 MCP joint scans performed sequentially by 2 independent observers. RESULTS: Sonography detected 127 definite erosions in 56 of 100 RA patients, compared with radiographic detection of 32 erosions (26 [81%] of which coincided with sonographic erosions) in 17 of 100 patients (P < 0.0001). In early disease, sonography detected 6.5-fold more erosions than did radiography, in 7.5-fold the number of patients. In late disease, these differences were 3.4-fold and 2.7-fold, respectively. On MRI, all sonographic erosions not visible on radiography (n = 12) corresponded by site to MRI abnormalities. The Cohen-kappa values for intra- and interobserver reliability of sonography were 0.75 and 0.76, respectively. CONCLUSION: Sonography is a reliable technique that detects more erosions than radiography, especially in early RA. Sonographic erosions not seen on radiography corresponded to MRI bone abnormalities. This technology has potential in the management of patients with early RA/inflammatory arthritis and is likely to have major implications for the future practice of rheumatology.

Adult↗
PubMed2000

What practical skills do rheumatologists of the future need?

In this chapter, we consider future practical skills required for rheumatologists. While difficult to predict against a background of rapid technological advance and successive changes to health-care provision world wide, a number of questions are examined. The first question is what core skills are essential in the curriculum? This has been addressed in at least one joint European effort by UEMS. Great diversity in both clinical practice and training was found across Europe; clearly, the difference across continents may prove even more significant. Second, the role of arthroscopy is considered, the evidence for its therapeutic benefit in clinical rheumatology practice being inconclusive. Issues concerning diagnostic methods including electrophysiology and ultrasound (US) are also discussed in this chapter. There is evidence to support the use of electrophysiology in routine diagnosis for specific diseases. US has become popular as technology improves. It is cheap but highly operator dependent, and the feasibility of rheumatologists using US in the clinic remains to be proved. In conclusion, health care is changing rapidly, and training must adapt, and is adapting, to meet its challenges. A number of opportunities will present to the rheumatologist of the future, but the feasibility of these in routine clinical practice remains to be seen.

Education, Medical↗
PubMed1999

Distinct vascular patterns of early synovitis in psoriatic, reactive, and rheumatoid arthritis.

OBJECTIVE: To examine the macroscopic vascular pattern of early synovitis in psoriatic arthritis (PsA), reactive arthritis (ReA), and rheumatoid arthritis (RA) and to assess the reliability of the grading features for synovitis. METHODS: Forty-four patients (14 PsA, 12 ReA, and 18 RA) with knee synovitis who were undergoing arthroscopy were assessed. Video recordings of the examination were scored independently by 3 arthroscopists who were blinded to the patient's identity and clinical details. Features of vascularity, villous formation, pannus, granularity, and capillary hyperemia were recorded and kappa values (-1 or =0.8) for features of vascularity, villous hypertrophy, and pannus. Seventy-three percent of the PsA and ReA patients had predominantly tortuous, bushy vessels; 89% of the RA patients had mainly straight, branching vessels. CONCLUSION: The distinct vascular patterns in PsA and ReA compared with those in RA may reflect different specific vascular factors in the pathogenesis of these arthritides. Vascularity and villous hypertrophy are the most reliable features of synovitis grading.

Adult↗
PubMed1999

Pharmacological effects of Agapanthus africanus on the isolated rat uterus.

The Agapanthus africanus plant is used by South African traditional healers as a phytomedicine in herbal remedies to treat pregnancy-related ailments and to augment labour. It has already been shown that an aqueous extract of A. africanus causes smooth muscle contractions in the isolated uterus and ileum preparations. In the present study, the effects of an aqueous extract of A. africanus leaves was examined on receptor systems involved in contraction of the uterine smooth muscle in order to determine the mechanism of its pharmacological effect relevant to its ethnic use to augment labour. The extract was tested on the isolated rat uterus preparation. The aqueous extract of A. africanus leaves was found to exhibit agonist activity on uterine muscarinic receptors and to promote the synthesis of prostaglandins in the oestrogenized rat uterus. Some pharmacological justification for the ethnic use of A. africanus as a herbal oxytocic in prolonged labour has been provided.

Acetylcholine↗
PubMed1999

Intra-articular primatised anti-CD4: efficacy in resistant rheumatoid knees. A study of combined arthroscopy, magnetic resonance imaging, and histology.

OBJECTIVES: CD4+ T cells sustain the chronic synovial inflammatory response in rheumatoid arthritis (RA). SB-210396/CE 9.1 is an anti-CD4 monoclonal antibody that has documented efficacy in RA when given intravenously. This study aimed to establish the safety and efficacy of the intra-articular administration of SB-210396/CE 9.1 compared with placebo, examining its mode of action using a combined imaging approach of arthroscopy, magnetic resonance imaging (MRI), and histology. METHODS: Thirteen RA patients with active, resistant knee synovitis, were randomised to intra-articular injection of placebo (n=3), 0.4 mg (n=3) or 40 mg (n=7) of anti-CD4 after sequential dynamic gadolinium enhanced MRI, followed by same day arthroscopy and synovial membrane biopsy. Imaging and arthroscopic synovial membrane sampling were repeated at six weeks. This study used a unique region of interest (ROI) analysis mapping the MRI area analysed to the specific biopsy site identified arthroscopically, thus providing data for all three modalities at the same synovial membrane site. RESULTS: 12 patients completed the study (one placebo treated patient refused further MRI). Arthroscopic improvement was observed in 0 of 2 placebo patients but in 10 of 10 patients receiving active drug (>20% in 6 of 10). Improvement in MRI was consistently observed in all patients of the 40 mg group but not in the other two groups. A reduction in SM CD4+ score was noted in the 40 mg group and in the 0.4 mg group. Strong correlations both before and after treatment, were identified between the three imaging modalities. Intra-articular delivery of SB-210396/CE 9.1 was well tolerated. CONCLUSIONS: SB-210396/CE 9.1 is safe when administered by intra-articular injection. A trend toward efficacy was found by coordinated MRI, arthroscopic, and histological imaging, not seen in the placebo group. The value of ROI analysis was demonstrated.

Adult↗
PubMed1998

Soluble cell adhesion molecules--P-selectin and ICAM-1, and disease activity in patients receiving sulphasalazine for active rheumatoid arthritis.

The aim of this pilot study was to examine soluble cell adhesion molecules before and after sulphasalazine (SSZ) therapy in active RA. Assessment of RA patients (n = 13) was undertaken before and after 3 months of SSZ. sICAM-1, sVCAM-1, sP- and sE-selectin were measured using an ELISA. The mean (+/-SEM) C-reactive protein (CRP) and sP-selectin levels were significantly reduced from 3.9(0.89) to 2.01(0.53) mg/dl and from 332.8 (48.2) to 116.2 (11.1) respectively, after 3 months of SSZ. The sICAM-1 and sP-selectin levels were significantly higher in RA patients at baseline and a reduction occurred of sICAM-1, sVCAM-1 and sE-selectin levels, however this was not significant. The fall in mean (SEM) sICAM-1, from 345.0 (29.8) to 333.5 (30.2), correlated with the change in CRP (r=0.66; p = 0.018), but the fall in sP-selectin did not. SSZ therapy reduced sP-selectin and sICAM-1 levels in active RA, sICAM-1 correlates with disease activity. SSZ may reduce platelet and/or endothelial activity in RA which may be a useful marker of response, however studies of longer duration and more patients are required.

Adult↗
PubMed1997

Oral L-arginine supplementation and cutaneous vascular responses in patients with primary Raynaud's phenomenon.

OBJECTIVE: To assess the effects of oral L-arginine supplementation on cutaneous vascular responses in patients with primary Raynaud's phenomenon (RP). METHODS: Double-blind, crossover comparison of placebo versus L-arginine (8 gm/day for 28 days). Cutaneous vascular responses in the fingers were assessed during iontophoresis of acetylcholine and sodium nitroprusside, which are endothelium-dependent and endothelium-independent vasodilators. RESULTS: In comparison with control subjects, patients with primary RP had diminished endothelium-dependent and -independent vasodilatation (P < 0.05, and P < 0.005, respectively, by analysis of variance). At the 3 doses used, vascular responses to acetylcholine were reduced by 71%, 64%, and 63%, respectively, and responses to sodium nitroprusside were reduced by 67%, 73%, and 66%, respectively. L-arginine had no significant effect on cutaneous vascular responses to acetylcholine or sodium nitroprusside in control subjects or patients with primary RP. CONCLUSION: Reduced vasodilator ability in primary RP is unlikely to be due to an impairment in the L-arginine/nitric oxide pathway.

Acetylcholine↗
PubMed1997

Isihlambezo: utilization patterns and potential health effects of pregnancy-related traditional herbal medicine.

Isihlambezo is a herbal decoction used by many Zulu women in South Africa as a preventative health tonic during pregnancy. Though the practice is cited by ethnographers and medical practitioners, few studies have focused on specific elements of isihlambezo use and preparation. Moreover, though some evidence exists suggesting negative effects of its ingestion, the maternal-fetal health impact and toxicity of isihlambezo have not been adequately studied. We examined two aspects of this traditional antenatal health practice: (1) the potential impact of urbanization and access to Western clinic-based care on popularity and utilization patterns of isihlambezo, and (2) the potential maternal-fetal health effects of its use. Interviews were conducted among rural and urban women in clinic and non-clinic settings regarding socio-behavioral aspects of isihlambezo use. The pharmacology of certain plant ingredients of isihlambezo was investigated through laboratory assays, literature review, and interviews with traditional healers. There were significant differences by area of interview in nearly all aspects of isihlambezo use examined. Though isihlambezo was most popular among urbanites and clinic non-attenders, it was considered an important antenatal health care alternative by the majority of women surveyed. Mixing traditional and clinic-based antenatal care was also strongly advocated. Pharmacological analysis suggested the possibility of both therapeutic and harmful consequences of isihlambezo. It was suggested that the following factors might contribute the popularity of isihlambezo among urban women: high cost and inferior quality of clinic care, use of isihlambezo as a means of adapting to urbanization-related stress, and socio-cultural transition.

Adolescent↗
PubMed1997

Preliminary screening of plants used in South Africa as traditional herbal remedies during pregnancy and labour.

Agapanthus africanus, Pentanisia prunelloides and Gunnera perpensa are indigenous plants which are used in traditional herbal remedies during pregnancy and childbirth. A crude decoction of each plant was tested on isolated rat uterus and ileum for pharmacological activity. Agapanthus africanus and Pentanisia prunelloides exhibited direct smooth muscle activity on the uterus and ileum preparations, while Gunnera perpensa showed direct smooth muscle activity on the uterus only. All the plant extracts potentiated the initial response of the uterus to oxytocin but Pentanisia prunelloides reduced the maximum response of the uterus to oxytocin. The Agapanthus africanus and Pentanisia prunelloides extracts potentiated the initial response of the ileum to acetylcholine but all the plant extracts inhibited the maximum response of the ileum to acetycholine.

Acetylcholine↗
PubMed1996

Adhesion molecules in untreated inflammatory arthritis: synovial expression and levels in synovial fluid and serum [corrected].

Adhesion molecules play a critical role in regulating leucocyte migration at sites of inflammation. The relationship of soluble forms in serum or synovial fluid (SF) to synovial membrane expression in inflammatory arthritis is controversial. We examined soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin levels in matched serum and SF, and their relationship to expression in synovium obtained at the same time in 13 patients with previously untreated inflammatory arthritis. Serum-soluble (s)ICAM-1 correlated with sedimentation rate (T = 0.45), Ritchie articular index (T = 0.47) and SF sICAM-1 (T = 0.48), and SF sICAM-1 correlated with membrane ICAM-1 expression (p < 0.02). sE-selectin and sVCAM-1 levels were unrelated to disease activity or membrane expression. Membrane E-selectin expression correlated inversely with ICAM-1 expression (T = -0.57) and serum sICAM-1 (T = -0.54). Serum sE-selectin correlated inversely with membrane ICAM-1 expression (T = -0.55). The correlations observed between ICAM-1 in serum, SF, synovium and disease activity suggest that ICAM-1 could be a useful target for immunotherapy. The inverse relationship of ICAM-1 and E-selectin suggest important differences in regulation and pathogenetic roles.

Adult↗
PubMed1996

Cell adhesion molecules in rheumatoid arthritis.

Rheumatoid arthritis is a systemic inflammatory disease of the joints and major internal organs that has an unknown aetiology. Cell adhesion molecules (CAMs) are expressed on the surface of cells, enabling homotypic and heterotypic cell-cell interactions that are fundamental in the process of the inflammatory reaction. Three major families of CAMs are now recognised, with numerous subtypes. Many of these molecules play an important role in the mechanism of disease in rheumatoid arthritis. E-Selectin and intercellular adhesion molecule (ICAM)-1 are upregulated on the synovial endothelium, while vascular cell adhesion molecule (VCAM)-1 plays an important role in the synovial lining layer cells and within the synovial stroma. The expression of CAMs may be blocked by monoclonal antibodies and modified by nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs. This has very important implications in the therapy of rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1995

Treatment of vasculitic leg ulcers in connective tissue disease with iloprost.

Leg ulcers are a recognised manifestation of cutaneous vasculitis in connective tissue diseases (CTDs) including rheumatoid arthritis (RA). Iloprost a stable prostacyclin analogue has been successfully used to treat Raynaud's phenomenon and digital ulcers associated with CTD's. Our aim was to assess iloprost in the treatment of vasculitic leg ulcers in CTD. In this paper we describe eight cases of vasculitic leg ulceration in association with RA and CTD, treated with intravenous iloprost. The iloprost was administered for 6-8 hours daily and continued for 21-28 days. Immunosuppressive therapy was required in three patients with severe necrotising vasculitis (RAnv). Complete ulcer healing was achieved in four patients within 6 weeks of commencing therapy while rapid improvement occurred in the other four patients. This suggests that iloprost may be useful as an adjunct to therapy for vasculitic leg ulcers. A double-blind placebo controlled study of iloprost therapy for RA leg ulcers is under way.

Aged↗
PubMed1995

Sulphasalazine-induced lupus in psoriatic arthritis.

Lupus syndromes have been described in rheumatoid arthritis and inflammatory bowel diseases treated with sulphasalazine. We describe two cases of lupus with clinical and serological disease, developing in seronegative, immunologically nude psoriatic arthritis following sulphasalazine treatment. On cessation of sulphasalazine the clinical and serologic features of lupus disappeared. This suggests that the lupus syndrome was induced by sulphasalazine rather than unmasked by it.

Adult↗