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Biomedical subjects

P Emery

Publications and source records attributed to P Emery.

At least 181 records · Page 10Linked to original sources
PubMed1999

Granisetron (Kytril) suppresses methotrexate-induced nausea and vomiting among patients with inflammatory arthritis and is superior to prochlorperazine (Stemetil).

OBJECTIVE: Methotrexate (MTX) is an increasingly popular anti-rheumatic drug with its usefulness limited by toxicity, most commonly gastrointestinal (GI). The aim of the study was to study the effectiveness of the 5-HT3 receptor antagonist granisetron (GR) in the therapy of MTX-induced nausea. METHODS: A single-blind 8 week pilot study with random allocation to either GR 1 mg or prochlorperazine (Stemetil; PCh) 10 mg was undertaken in 13 patients who were taking or had taken MTX for either rheumatoid arthritis (10) or psoriatic arthritis (3). RESULTS: One in six patients treated with PCh completed the 8 week study compared to 7/7 treated with GR. After switching of symptomatic patients, 11 completed the study on GR and median improvement was by two grades (P < 0.001) with a significantly better visual analogue scale score for patient satisfaction compared to PCh. CONCLUSION: Treatment with GR may be useful in establishing and maintaining some patients on MTX where GI toxicity would have precluded such therapy.

Antiemetics↗
PubMed1999

A preliminary study of ultrasound aspiration of bone erosion in early rheumatoid arthritis.

OBJECTIVE: To develop a new technique to assess the primary lesion in early rheumatoid arthritis (RA). METHODS: Ten patients with early RA and radiographically or MRI confirmed erosions had a needle introduced into the base of the erosion under sonographic guidance. Material was then aspirated from this site. RESULTS: The procedure was well tolerated with no complications. Small samples of necrotic bone and tissue were obtained in five out of 10 cases. In one case, a distinctive population of pleomorphic CD34 + cells with characteristics of bone marrow progenitors was isolated. Tissue invading bone with a characteristic appearance of pannus was not seen. CONCLUSION: A new method of sampling the earliest lesion in RA is described. The findings raise questions about the nature of bone damage in early RA.

Antigens, CD34↗
PubMed1999

Interpreting the clinical significance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2.

The International Consensus Meeting on the Mode of Action of COX-2 Inhibition (ICMMAC) brought together 17 international experts in arthritis, gastroenterology and pharmacology on 5 6 December 1997. The meeting was convened to provide a definition of COX-2 specificity and to consider the clinical relevance of COX-2-specific agents. These compounds are a new class of drugs that specifically inhibit the enzyme COX-2 while having no effect on COX-1 across the whole therapeutic dose range. The objectives of the meeting were to review the currently available data regarding the roles and biology of COX-1 and COX-2, and to foster a consensus definition on COX-2 specificity. At the present time, no guidelines exist for the in vitro and in vivo assessment of COX specificity, and it was felt that consensus discussion might clarify some of these issues. The meeting also reviewed recent clinical data on COX-2-specific inhibitors. The following article reflects discussion at this meeting and provides a consensus definition of COX-2-specific inhibitors.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Enthesitis in spondyloarthropathy.

Inflammation at the insertions of ligaments, tendons, or joint capsules to bone, which is termed enthesitis, is a characteristic feature of spondyloarthropathy. Because of the relative inaccessibility of the enthesis, the inflammatory, microbiologic, and immunologic events at that site have been poorly defined. Recent magnetic resonance imaging studies have drawn attention to the ubiquitous nature of enthesitis in spondyloarthropathies, especially adjacent to synovial joints. This may have implications for the mechanisms of synovitis in spondyloarthropathies. Magnetic resonance imaging studies also suggest that enthesitis lesions may be extensive, which could explain the diffuse nature of bone changes seen in some patients with spondyloarthropathies. The importance of enthesitis as a skeletal phenomenon in spondyloarthropathies has gained further support from transgenic models in which either tumor necrosis factor-alpha or bone morphogenetic protein-6 overexpression result in entheseal-associated polyarthropathy.

Animals↗
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↗
PubMed1999

Management of patients with newly diagnosed rheumatoid arthritis.

The traditional pyramidal approach to treatment of rheumatoid arthritis (RA) has the unfortunate effect of treating patients with early RA--those patients with the greatest potential for clinical response--with the least effective agents during the most prolonged and most damaging period of inflammation. Given the wide variety of therapies now available, and the fact that the disease itself can be more destructive than the toxicity of drug therapy, it is important to know the likely outcome for an individual patient so that therapy can be targeted accordingly. The rapid development of new imaging techniques has enabled joint damage to be assessed at a very early stage. The correlation of data obtained from these techniques with clinical data, such as the presence of rheumatoid factor and the shared epitope, may provide a basis on which therapies in the future can be tailored for individual patients.

Antirheumatic Agents↗
PubMed1998

CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity.

Light is a major environmental signal for circadian rhythms. We have identified and analyzed cry, a novel Drosophila cryptochrome gene. All characterized family members are directly photosensitive and include plant blue light photoreceptors. We show that cry transcription is under circadian regulation, influenced by the Drosophila clock genes period, timeless, Clock, and cycle. We also show that cry protein levels are dramatically affected by light exposure. Importantly, circadian photosensitivity is increased in a cry-overexpressing strain. These physiological and genetic data therefore link a specific photoreceptor molecule to circadian rhythmicity. Taken together with the data in the accompanying paper, we propose that CRY is a major Drosophila photoreceptor dedicated to the resetting of circadian rhythms.

ARNTL Transcription Factors↗
PubMed1998

The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila.

A new rhythm mutation was isolated based on its elimination of per-controlled luciferase cycling. Levels of period or timeless clock gene products in the mutant are flat in daily light-dark cycles or constant darkness (although PER and TIM oscillate normally in temperature cycles). Consistent with the fact that light normally suppresses TIM, cryb is an apparent null mutation in a gene encoding Drosophila's version of the blue light receptor cryptochrome. Behaviorally, cryb exhibits poor synchronization to light-dark cycles in genetic backgrounds that cause external blindness or demand several hours of daily rhythm resets, and it shows no response to brief light pulses. cryb flies are rhythmic in constant darkness, correlating with robust PER and TIM cycling in certain pacemaker neurons.

Animals↗
PubMed1998

Classification of inflammatory arthritis by enthesitis.

Imaging studies of early synovitis suggest that the first abnormality to appear in swollen joints associated with spondyloarthropathy is an enthesitis (inflammation at sites where ligaments, tendons, or joint capsules are attached to bone). We propose that the synovitis of spondyloarthropathy is secondary to liberation of proinflammatory mediators from the enthesis, whereas the synovitis of rheumatoid arthritis is primary. This suggestion allows a classification of arthritis as either primary synovial (rheumatoid-like) or entheseal (spondyloarthropathy-like) and allows differentiation of presentation of a polyarthritis with a good prognosis (spondyloarthropathy-like), from that with a bad prognosis (rheumatoid arthritis). Pathogenesis of spondyloarthropathy, in particular the part played by HLA-B27 and micro-organisms, should be assessed at the enthesis rather than in the synovium.

Arthritis↗
PubMed1998

DNA binding properties of a chemically synthesized DNA binding domain of hRFX1.

The RFX DNA binding domain (DBD) is a novel highly conserved motif belonging to a large number of dimeric DNA binding proteins which have diverse regulatory functions in eukaryotic organisms, ranging from yeasts to human. To characterize this novel motif, solid phase synthesis of a 76mer polypeptide corresponding to the DBD of human hRFX1 (hRFX1/DBD), a prototypical member of the RFX family, has been optimized to yield large quantities (approximately 90 mg) of pure compound. Preliminary two-dimensional1H NMR experiments suggested the presence of helical regions in this sequence in agreement with previously reported secondary structure predictions. In gel mobility shift assays, this synthetic peptide was shown to bind in a cooperative manner the 23mer duplex oligodeoxynucleotide corresponding to the binding site of hRFX1, with a 2:1 stoichoimetry due to an inverse repeat present in the 23mer. The stoichiometry of this complex was reduced to 1:1 by decreasing the length of the DNA sequence to a 13mer oligonucleotide containing a single half-site. Surface plasmon resonance measurements were achieved using this 5'-biotylinated 13mer oligonucleotide immobilized on an avidin-coated sensor chip. Using this method an association constant (K a = 4 x 10(5)/M/s), a dissociation constant (K d = 6 x 10(-2)/s) and an equilibrium dissociation constant (K D = 153 nM) were determined for binding of hRFX1/DBD to the double-stranded 13mer oligonucleotide. In the presence of hRFX1/DBD the melting temperature of the 13mer DNA was increased by 16 degreesC, illustrating stabilization of the double-stranded conformation induced by the peptide.

Amino Acid Sequence↗
PubMed1998

Quantitative microscopic analysis of inflammation in rheumatoid arthritis synovial membrane samples selected at arthroscopy compared with samples obtained blindly by needle biopsy.

OBJECTIVE: To evaluate microscopic measures of inflammation in rheumatoid arthritis synovial tissue samples selected at arthroscopy compared with those obtained blindly by needle biopsy from the suprapatellar pouch (SPP) of the same joint. METHODS: Samples were selected at knee arthroscopy from the SPP and the lateral and medial gutters. Immediately following arthroscopy, a biopsy needle was inserted through the same portal into the SPP by a second investigator, and 3 further samples were obtained blindly. Using standard immunohistologic methods, all samples were analyzed by a single investigator without knowledge of the original tissue location and biopsy technique. Following staining with anti-CD3 and anti-CD68 monoclonal antibodies, T lymphocyte and macrophage infiltration were measured by quantitative analysis. RESULTS: Synovial tissues from 14 patients were analyzed. In comparing microscopic measures of inflammation using the 2 procedures, mean scores of lining cell depth and the percentage of CD68+ cells in the lining layer correlated positively (tau = 0.59, P = 0.003 and tau = 0.73, P = 0.0003, respectively). In the sublining layer, CD3+ cell counts also correlated significantly (tau = 0.71, P = 0.0004). Sublining CD68+ cell counts did not correlate. This was explained by the observation that CD68+ cell infiltration in areas adjacent to articular cartilage was significantly greater than in the SPP (P = 0.01), suggesting preferential trafficking to this site by macrophages, but not by T lymphocytes. Macroscopic appearance at arthroscopy did not predict microscopic features. CONCLUSION: Most microscopic measures of inflammation in synovial tissue samples obtained blindly from the SPP were similar to those determined in samples selected at arthroscopy. However, measurements in samples from the SPP may underestimate the intensity of macrophage infiltration in areas more adjacent to cartilage. These observations have important implications for future study of macrophage function in synovial tissue.

Arthritis, Rheumatoid↗
PubMed1998

Characteristic magnetic resonance imaging entheseal changes of knee synovitis in spondylarthropathy.

OBJECTIVE: To use magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and spondylarthropathy (SpA) to determine if the primary site of abnormality differs. METHODS: Twenty patients with recent-onset knee effusion (10 with SpA and 10 with RA) were evaluated using fat-suppressed MRI. Knee joint effusion and synovitis were confirmed using ultrasonography. MRI scans were independently scored by 2 observers who were blinded to the patient's diagnosis. RESULTS: All 10 of the SpA patients, but only 4 of the 10 RA patients, had focal peri-entheseal high signal (compatible with fluid or edema) outside the joint (P = 0.01). Six of the SpA patients had bone marrow edema that was maximal at entheseal insertions; in 4 cases this was multifocal. No RA patients showed such an abnormality (P = 0.01). CONCLUSION: Prominent entheseal abnormalities on MRI are a consistent feature of new-onset synovitis in SpA, but are a minor feature of RA. This finding has important implications for the diagnosis, classification, and mechanisms of synovitis in patients with SpA.

Adult↗
PubMed1998

Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist.

OBJECTIVE: To evaluate the efficacy and safety of interleukin-1 receptor antagonist (IL-1Ra) in patients with rheumatoid arthritis (RA). METHODS: Patients with active and severe RA (disease duration <8 years) were recruited into a 24-week, double-blind, randomized, placebo-controlled, multicenter study. Doses of nonsteroidal antiinflammatory drugs and/or oral corticosteroids (< or =10 mg prednisolone daily) remained constant throughout the study. Any disease-modifying antirheumatic drugs that were being administered were discontinued at least 6 weeks prior to enrollment. Patients were randomized to 1 of 4 treatment groups: placebo or a single, self-administered subcutaneous injection of IL-1Ra at a daily dose of 30 mg, 75 mg, or 150 mg. RESULTS: A total of 472 patients were recruited. At enrollment, the mean age, sex ratio, disease duration, and percentage of patients with rheumatoid factor and erosions were similar in the 4 treatment groups. The clinical parameters of disease activity were similar in each treatment group and were consistent with active and severe RA. At 24 weeks, of the patients who received 150 mg/day IL-1Ra, 43% met the American College of Rheumatology criteria for response (the primary efficacy measure), 44% met the Paulus criteria, and statistically significant improvements were seen in the number of swollen joints, number of tender joints, investigator's assessment of disease activity, patient's assessment of disease activity, pain score on a visual analog scale, duration of morning stiffness, Health Assessment Questionnaire score, C-reactive protein level, and erythrocyte sedimentation rate. In addition, the rate of radiologic progression in the patients receiving IL-1Ra was significantly less than in the placebo group at 24 weeks, as evidenced by the Larsen score and the erosive joint count. IL-1Ra was well tolerated and no serious adverse events were observed. An injection-site reaction was the most frequently observed adverse event, and this resulted in a 5% rate of withdrawal from the study among those receiving IL-1Ra at 150 mg/day. CONCLUSION: This study confirmed both the efficacy and the safety of IL-1Ra in a large cohort of patients with active and severe RA. IL-1Ra is the first biologic agent to demonstrate a beneficial effect on the rate of joint erosion.

Adolescent↗
PubMed1998

The assessment of knowledge in ankylosing spondylitis patients by a self-administered questionnaire.

The aim of the present study was to assess ankylosing spondylitis (AS) patients' level of knowledge, using a self-administered multiple-choice questionnaire. The questionnaire, based on the Arthritis and Rheumatism Council (ARC) leaflet on AS, examined four areas: (A) general knowledge; (B) immunogenetic tests and inheritance; (C) general management; (D) joint protection, pacing and priorities. Statistical analysis was used to validate the questionnaire and to examine correlations with gender, age, disease duration and level of general education. The questionnaire was consistent, reliable and easy to read. The results showed AS patients to have a high level of knowledge (mean = 19.4, maximum possible = 25), although some wrong beliefs about the role of blood tests, the HLA-B27 antigen and inheritance were discovered. No statistical correlation was found between gender, age, duration of the disease, level of general education and the level of knowledge. These data suggest that this questionnaire is a simple way to detect the level of knowledge of patients with AS. The average score achieved by AS patients was outstanding, possibly reflecting the good quality of previous educational programmes. Patients' confusion regarding blood tests, genetics and inheritance was highlighted and should be addressed.

Activities of Daily Living↗