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Biomedical subjects

P Emery

Publications and source records attributed to P Emery.

At least 235 records · Page 13Linked to original sources
PubMed1995

Innovative treatment approaches for rheumatoid arthritis. New cyclo-oxygenase and cytokine inhibitors.

A need remains for the development of more effective therapies for the treatment of rheumatoid arthritis (both NSAIDs and DMARDs). The NSAIDs remain the cornerstone of symptomatic therapy, but concern remains about their safety, potential for the delay in commencing definitive therapy and theoretical pro-inflammatory effects. Each of the NSAIDs reviewed here do provide an advantage over therapies previously available and should prove to be useful additions to the rheumatologists' therapeutic armament.

Animals↗
PubMed1995

The genetic origin of responses to drugs.

Individual variation in drug metabolism has been extensively investigated. Population studies have shown that there is a wide range in metabolising ability for all detoxification pathways; the distributions may be unimodal (Gaussian) or polymodal, with subsets of individuals who differ from the majority. These may be poor metabolisers (PM) or extensive metabolisers (EM). In many cases, these phenotypes can be linked with the genotype. Frequently the PM phenotype is more susceptible to drug toxicity, while the EM phenotype requires increased dosage for therapeutic benefit. In some cases, phenotypes or genotypes appear to have increased susceptibility to clinical disease. These ideas are discussed for the cytochrome P-450 isozymes, FMO system, cysteine dioxygenase-linked oxidations, glucuronidation, sulphation, acetylation, glutathione conjugation and methylation pathways.

Acetylation↗
PubMed1995

Needle arthroscopy.

Explore the source record for details and available documents.

Arthritis, Rheumatoid↗
PubMed1995

Clinical use of cyclosporin in rheumatoid arthritis.

Rheumatoid arthritis is a chronic immune-mediated disease characterised by an inflammatory synovitis and extra-articular manifestations. There is an expanding body of evidence to indicate that the activation of T lymphocytes is central in the initiation and perpetuation of this disease. Cyclosporin is an immunomodulator and a highly specific inhibitor of T-lymphocyte function, and has demonstrated disease-modifying properties in clinical studies in patients with rheumatoid arthritis. A concern with the use of cyclosporin has been the development of dose-dependent adverse effects, in particular renal dysfunction. Cyclosporin is lipophilic by nature and the conventional oral formulation (Sandimmun) was subject to incomplete and highly variable absorption, resulting in substantial inter- and intrasubject variations in peak concentrations and systemic bioavailability. A microemulsion-based formulation of cyclosporin (Neoral) has recently been developed, and possesses more predictable and improved absorption with a consequent increased peak concentration and systemic bioavailability. The improved predictability of absorption, and hence blood concentrations, facilitates the ability to 'tailor' therapy to an individual patient, which, in theory, could translate into an improved efficacy and safety profile.

Antirheumatic Agents↗
PubMed1995

Assessing the hypothalamo-pituitary-adrenal axis in patients on long-term glucocorticoid therapy: the short synacthen versus the insulin tolerance test.

The short synacthen test (SST) is an effective method of assessing the hypothalamo-pituitary-adrenal (HPA) axis in patients with pituitary disease. Chronic glucocorticoid therapy may result in suppression of the HPA axis, and use of the SST has not been evaluated in these patients. This study compares the SST with the insulin tolerance test (ITT) in patients on long-term corticosteroid therapy. Both tests were done on 22 patients on long-term, stable-dose prednisolone (< 10 mg/day). A pass was defined as a 30 minute plasma cortisol > 550 nmol/l for the SST and a maximal cortisol of > 500 nmol/l for the ITT. Five patients passed both tests; nine failed both. Eight patients had discrepant results; all passed the ITT but failed the SST. There was a significant correlation (p < 0.001) between the maximum cortisol level achieved during the ITT and the 30 min SST value and the incremental rise. There was an inverse correlation between the dose and duration of use of steroids and the cortisol response during both tests. The SST is a reliable, safe and easily performed initial assessment of the HPA axis in patients on long-term corticosteroids. The ITT remains a valuable test for those who fail the SST.

Adult↗
PubMed1995

Therapeutic approaches for early rheumatoid arthritis. How early? How aggressive?

A critical question for the management of patients with rheumatoid arthritis (RA) is the timing and extent of pharmacological intervention. There is good evidence that early disease is important, and data showing early intervention have particular advantages. However, in the past, several difficulties have arisen with this approach. The availability of patients seen in early arthritis clinics, the ability to predict outcome and the development of new methods of monitoring have made a large difference to the possibilities for therapy. This article describes why it is now reasonable to treat patients who have 'standard' RA with a disease-modifying antirheumatic drug (DMARD) at presentation. In those patients with a worse prognosis, a more aggressive regime is justified. For those who do not fulfil criteria laid down by the American College of Rheumatologists, treatment with a DMARD may still be appropriate on a cost-benefit analysis. Studies addressing these issues are currently being undertaken.

Antirheumatic Agents↗
PubMed1994

Cooperative binding between factors RFX and X2bp to the X and X2 boxes of MHC class II promoters.

Transcription of major histocompatibility complex (MHC) class II genes is controlled primarily by the promoter, which contains several conserved cis-acting elements, including the X, X2, and Y boxes. We show here that RFX, the X box-binding protein that is deficient in certain MHC class II regulatory mutants, binds cooperatively with an X2 box-binding protein (X2bp) to form an RFX.X2bp.DNA complex in which the interaction of the two factors with their target sites is strongly stabilized. A functional role of this RFX.X2bp complex is consistent with mutational analysis of the X and X2 boxes of the DRA and DRB1 class II promoters. Together with previous results demonstrating cooperative binding between RFX and the Y box-binding protein NF-Y, our results indicate that RFX plays a central role in promoting cooperative binding interactions required for stable occupation of the MHC class II promoter. This may explain why the highly specific defect in binding of RFX observed in certain MHC class II regulatory mutants is associated in vivo with a bare promoter in which all of the cis-acting elements, including the X, X2, and Y boxes, are unoccupied.

Base Sequence↗
PubMed1994

8-Hydroxydeoxyguanosine. A marker of oxidative DNA damage in systemic lupus erythematosus.

8-Hydroxydeoxyguanosine (80HDG) is a specific marker of oxidative damage to DNA. We have observed that patients with SLE (systemic lupus erythematosus), have undetectable levels of urinary 80HDG by HPLC. Further analysis by GC-MS confirmed that levels of 80HDG in SLE urine were 10(3)-fold lower than in an age- and sex-matched control group. Experiments utilising cultures of SLE and normal lymphocytes exposed to H2O2 confirmed the impaired ability of SLE lymphocytes to repair 80HDG. We subsequently observed in SLE patients that 80HDG had accumulated in low molecular weight DNA associated with circulating immune complexes. We suggest that oxygen radicals may induce pathology in SLE by maintaining the presence of an antigenic form of DNA in the circulation.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

Generalised bone loss in patients with early rheumatoid arthritis.

Generalised osteoporosis is a feature of established rheumatoid arthritis but whether this is a consequence of treatment, immobility, or disease activity has been unclear. We estimated bone mineral density by dual energy x-ray absorptiometry on 148 patients with early rheumatoid arthritis before treatment with corticosteroids or disease-modifying drugs and 730 normal controls. Scans were done at 12-month intervals in patients and at 0 and 12 months on 50 of the controls matched for menopausal status. At presentation, bone mineral density of patients did not differ from controls. However, patients with disease for less than 6 months had significantly higher spinal bone mineral density than those of longer duration. Over the next 12 months, bone mineral density loss was greater in patients with rheumatoid arthritis compared with controls; significantly so for early disease (eg, -2.4 [0.8] vs -0.6 [0.4] g/cm2, p < 0.05 in the spine and -4.3 [0.8] vs -0.4 [0.5] g/cm2, p < 0.001 in the trochanter). For the lumbar spine, only disease activity was significantly associated with this bone mineral density loss. For patients with active disease over 2 years, mean bone mineral density loss at each site was between 5.5 and 10% (p < 0.01 compared to patients with inactive disease). Suppression of disease activity stabilised this bone loss. In patients with rheumatoid arthritis significant amounts of generalised skeletal bone were lost early in the disease and the loss was associated with disease activity. These findings have implications for the management of patients with rheumatoid arthritis and possibly other inflammatory diseases.

Absorptiometry, Photon↗
PubMed1994

Genetic typing of patients with inflammatory arthritis at presentation can be used to predict outcome.

OBJECTIVE: To test the hypothesis that genetic characterization of patients at the time they present with inflammatory arthritis can predict subsequent destructive disease. METHODS: We evaluated 177 patients with early arthritis. Patients were serologically tested for rheumatoid factor (RF) and were DNA oligotyped for the presence of conserved base sequences in the third hypervariable region (HVR3) of the DRB1 gene, previously shown to be associated with severe rheumatoid arthritis (RA). Homozygosity in the patient's genotype was confirmed using restriction fragment length polymorphism analysis. The main outcome measure was radiologic erosions at 1 year. RESULTS: At presentation, 120 patients fulfilled the American College of Rheumatology 1987 criteria for RA, 64% of whom possessed the conserved base sequences, compared with 45% of 347 healthy controls (P < 0.001) and with 56% of 57 patients with other inflammatory arthritis (P not significant). Within the RA population, the frequency of Dw4/Dw14 compound heterozygotes was disproportionately increased. The presence of either HVR3 or RF had a relative risk of 13.49 for erosions, with a sensitivity of 95% (specificity 39%); the presence of both HVR3 and RF had a relative risk of 8.13, with a specificity of 88% (sensitivity 53%). All but 1 patient with the Dw4/Dw14 genotype developed erosions within 1 year. CONCLUSION: Knowledge of a patient's HLA-DR type and RF status allows clinically useful prediction of erosive disease; patients possessing Dw4/Dw14 represent a particularly high-risk subgroup.

Alleles↗
PubMed1994

Interleukin-1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus.

OBJECTIVE: We have previously described associations between an allele of the interleukin-1 receptor antagonist gene (IL1RN) and several inflammatory diseases. In this study we tested the IL1RN gene as a possible marker in patients with systemic lupus erythematosus (SLE). METHODS: Eighty-one SLE patients and 261 ethnically matched control subjects were genotyped by polymerase chain reaction. RESULTS: We found an increase in both frequency and carriage rate of IL1RN*2 in the SLE group. This association strengthened with extensive disease and particularly with the presence of photosensitivity and discoid skin lesions. CONCLUSION: We describe a novel association between IL1RN*2 and SLE. Carriage of the allele seems to influence severity rather than susceptibility to SLE. We postulate that the association of this polymorphism with disease severity is a widespread feature of common inflammatory and autoimmune diseases.

Base Sequence↗
PubMed1994

A genetic association between systemic lupus erythematosus and tumor necrosis factor alpha.

We have investigated the significance of tumor necrosis factor alpha (TNF-alpha) polymorphism in relation to systemic lupus erythematosus (SLE) and autoantibody production. Typing of HLA-B, -DR and TNF was performed in 81 Caucasian SLE patients and 168 Caucasian controls. The presence of anti-Ro and anti-La antibodies was also determined in patients. The frequency of the TNF2 allele increased in SLE compared with controls [0.24 vs. 0.17, p = 0.04, odds ratio (OR) = 1.6], as did HLA-DR3 (0.25 vs. 0.13, p < 0.01, OR = 2.3) and HLA-B8 (0.23 vs. 0.15, p = 0.02, OR = 2). Although HLA-DR3 showed the strongest disease association, we could not demonstrate association of HLA-DR3 or TNF2 with SLE independently of each other. Within SLE a much stronger association of TNF2 was seen with autoantibody production: anti-Ro antibody (0.39 vs. 0.16, p < 0.001, OR = 3.4) and anti-La antibody (0.43 vs. 0.19, p < 0.001, OR = 3.2). When analyzed independently of each other, however, HLA-DR3 remained significantly associated with autoantibodies, while TNF2 did not. These data suggest that on the B8-DR3 haplotype, TNF-alpha polymorphism may play a role in SLE susceptibility, but it is not primarily associated with autoantibody production.

Autoantibodies↗
PubMed1994

Correlation of blood levels of soluble vascular cell adhesion molecule-1 with disease activity in systemic lupus erythematosus and vasculitis.

Levels of soluble adhesion molecules have been shown to reflect their cell surface expression in vitro, and thus may provide a useful surrogate marker of surface expression at inflammatory sites. In patients with SLE and vasculitis, serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-Selection were determined by ELISA during different stages of disease activity. Levels of soluble(s) VCAM-1 correlated with disease activity in patients with SLE, being significantly higher during active compared with inactive disease (P = 0.003), and normalizing with clinical remission. By contrast, in patients with vasculitis, although sVCAM-1 levels were elevated in active disease, they fell but did not normalize in inactive disease, suggesting that treatment may be suppressing the clinical manifestations rather than targeting the underlying pathogenic mechanism. Soluble ICAM-1 and E-Selectin levels did not relfect disease activity in either SLE or vasculitis.

Adolescent↗
PubMed1994

Posterior scleritis--an unusual manifestation of Cogan's syndrome.

Cogan's syndrome is characterized by a non-luetic interstitial keratitis associated with vertigo, tinnitus and profound deafness. Evidence of a systemic vasculitis is found in up to 50% of patients. Atypical forms of Cogan's syndrome have been described in which the ocular inflammatory disease may be more severe. We describe a case of atypical Cogan's syndrome in association with bilateral posterior scleritis. Serial B-scan ultrasound measurements of posterior scleral thickness were found to be useful in assessing disease activity, in combination with clinical findings. Combination therapy with prednisolone and cyclosporin controlled the ocular disease but the deafness was irreversible. The length of follow-up of this case highlights the frequent relapses and difficult management problems which may be faced. This multisystem disease requires the close co-operation of ophthalmologist, physician and otorhinolaryngologist. Aggressive therapeutic intervention with high-dose combined immunosuppressive agents may be necessary to control severe ocular inflammatory disease.

Adult↗