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Paul Emery

Publications and source records attributed to Paul Emery.

108 records · Page 6Linked to original sources
PubMed2002

Comparative assessment of leflunomide and methotrexate for the treatment of rheumatoid arthritis, by dynamic enhanced magnetic resonance imaging.

OBJECTIVE: Ethical constraints on the conduct of placebo-controlled trials evaluating new therapies for serious chronic diseases, such as rheumatoid arthritis (RA), indicate the need for discerning methods to assess treatment effect in active-controlled clinical trials. Dynamic gadolinium-enhanced magnetic resonance imaging (DEMRI) is a sensitive technique for the detection of synovial inflammation in RA. Therefore, this investigation was undertaken to evaluate DEMRI as an efficacy assessment tool for differentiating treatment effect in a randomized, active-controlled trial comparing leflunomide and methotrexate. METHODS: Patients with active RA (n = 39) were randomized in a 2-center, prospective, double-blind clinical trial to receive either leflunomide (n = 18) or methotrexate (n = 21) therapy for 4 months. DEMRI scans were obtained at baseline and at 4 months, and the initial rate of enhancement (IRE) and the maximal signal intensity (SI) enhancement (ME) were calculated from the SI curves. Clinical improvement was assessed by conventional outcome measures. RESULTS: Thirty-four patients (17 treated with leflunomide and 17 with methotrexate) had usable baseline and end point DEMRI scans. Leflunomide treatment was associated with a significantly greater improvement in IRE compared with methotrexate treatment (P < 0.05). Average values of ME indicated reduction of inflammation with both leflunomide and methotrexate. The improvement in clinical signs and symptoms, as measured by traditional assessments, was comparable for both active treatments. CONCLUSION: Results of this study validate the sensitivity of DEMRI in detecting inflammatory changes in active RA in response to treatment. Improvement in synovial inflammation as measured by IRE was significantly better with leflunomide than with methotrexate over 4 months of therapy.

Adult↗
PubMed2002

The role of biomechanical factors and HLA-B27 in magnetic resonance imaging-determined bone changes in plantar fascia enthesopathy.

OBJECTIVE: To study the role of biomechanical factors and HLA-B27 in plantar fasciitis. METHODS: T1-weighted and T2 spectral presaturation with inversion recovery (fat suppressed) magnetic resonance imaging (MRI) sequences of the plantar fascia insertion and adjacent bone were performed on 28 patients with plantar fasciitis; 17 had spondylarthropathy (SpA)-associated disease, and 11 had mechanically induced disease. The relationship between the degree of bone edema, scored on a semiquantitative scale (from absent to severe), and the patient's HLA-B27 status was determined. RESULTS: On MRI, edema within the soft tissue at the enthesis was evident in both groups. Bone edema in the adjacent calcaneum was evident in 64.7% (11 of 17) of patients with SpA and in 45% (5 of 11) of those with mechanically induced disease (P = 0.441). HLA-B27 was identified in 9 (53%) of the patients with SpA but in none (0%) of those with mechanically induced disease. All 6 of the SpA patients with extensive bone edema but none of the 5 SpA patients with mild bone edema were HLA-B27 positive (P = 0.002). CONCLUSION: The association of HLA-B27 with bone pathology in early enthesitis may have implications for a better understanding of the pathogenesis of SpA.

Achilles Tendon↗
PubMed2002

Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion.

OBJECTIVE: T cells are involved in the pathogenesis of rheumatoid arthritis (RA). In animal models of autoimmune diseases, blockade of costimulatory molecules on antigen-presenting cells has been demonstrated to be effective in preventing or treating this disease by preventing T cell activation. To date, the effect of costimulatory blockade in patients with RA is unknown. The goal of this multicenter, multinational study was to determine the safety and preliminary efficacy of costimulatory blockade using CTLA-4Ig and LEA29Y in RA patients who have been treated unsuccessfully with at least 1 disease-modifying agent. METHODS: CTLA-4Ig, LEA29Y (0.5, 2, or 10 mg/kg), or placebo was administered intravenously to 214 patients with RA. Patients received 4 infusions of study medication, on days 1, 15, 29, and 57, and were evaluated on day 85. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (ACR20). All patients were monitored for treatment safety and tolerability. RESULTS: CTLA-4Ig and LEA29Y infusions were well tolerated at all dose levels. Peri-infusional adverse events were carefully monitored, and showed similar incidence across all dose groups with the exception of headaches, which were slightly more frequent in the 2 treatment groups. The incidence of discontinuations due to worsening of RA was 19%, 12%, and 9% at 0.5, 2, and 10 mg/kg, respectively, in the CTLA-4Ig-treated patients and 3%, 3%, and 6% at 0.5, 2, and 10 mg/kg, respectively, in the LEA29Y-treated patients (versus 31% in the placebo group). ACR20 responses on day 85 had increased in a dose-dependent manner (23%, 44%, and 53% of CTLA-4Ig-treated patients and 34%, 45%, and 61% of LEA29Y-treated patients at 0.5, 2.0, and 10 mg/kg, respectively, versus 31% of placebo-treated patients). CONCLUSION: Both of the costimulatory blocking molecules studied were generally safe and well tolerated. As compared with placebo, both CTLA-4Ig and LEA29Y demonstrated efficacy in the treatment of RA.

Abatacept↗
PubMed2002

Comparison of synovial tissues from the knee joints and the small joints of rheumatoid arthritis patients: Implications for pathogenesis and evaluation of treatment.

OBJECTIVE: Serial synovial biopsy samples are increasingly being used for the evaluation of novel therapies for rheumatoid arthritis (RA). Most studies have used tissues from knee biopsies, but technical improvements have made serial small joint arthroscopy feasible as well. Theoretically, there could be differences in the features of synovial inflammation between various joints as a result of mechanical factors, differences in innervation, and other factors. We therefore undertook this study to compare the cell infiltrate in paired synovial biopsy samples from inflamed knee joints and paired inflamed small joints of patients with RA. METHODS: Nine RA patients with both an inflamed knee joint and an inflamed small joint (wrist or metacarpophalangeal joint) underwent an arthroscopic synovial biopsy of both joints on the same day. Multiple biopsy specimens were collected and stained for macrophages, T cells, plasma cells, fibroblast-like synoviocytes, and interleukin-6 (IL-6) by immunohistochemistry. Sections were evaluated by digital image analysis. RESULTS: There were no significant differences in mean cell numbers for all markers investigated in samples from the knee joint compared with samples from the small joints. We detected statistically significant correlations for the numbers of sublining macrophages, T cells, and plasma cells, as well as for IL-6 expression, between the knee joint and the small joints. However, there was no significant correlation between different joints for the numbers of intimal macrophages or fibroblast-like synoviocytes. CONCLUSION: The results of this study show that the inflammation in one inflamed joint is generally representative of that in other inflamed joints. Therefore, it is possible to use serial samples from the same joint, selecting either large or small joints, for the evaluation of antirheumatic therapies.

Adult↗
PubMed2002

The geometric architecture of the subtalar and midtarsal joints in rheumatoid arthritis based on magnetic resonance imaging.

OBJECTIVE: To compare in vivo the 3-dimensional (3-D) geometric architecture of the subtalar and midtarsal joints in normal and rheumatoid arthritic (RA) feet, using magnetic resonance imaging (MRI) analysis. METHODS: MRI was performed on 23 patients with RA, all of whom had disease activity in the subtalar and/or midtarsal joints. Image processing techniques were used to create 3-D reconstructions of the calcaneus (C), cuboid (c), navicular (N), and talus (T) bones. Twenty-four standard architectural parameters were measured from the reconstructions and were compared with data from 10 normal subjects. These parameters defined both 3-D distance and angular relationships among the 4 bones studied. Pattern classification techniques were used to establish a geometric architecture foot profile for the RA patients. The degree of individual patient fit to the new RA foot profile and to profiles for normal, pes planus, and pes cavus foot types was derived. Logistic regression was used to examine the relationship of foot architecture to inflammatory disease characteristics and physical examination variables. RESULTS: Subtalar or midtarsal pain was reported by all 23 patients, and 22 of the 23 patients presented with >/=1 clinical feature of pes planovalgus deformity. In 21 patients, ultrasonography revealed synovitis at >/=1 tarsal joint or surrounding tendon. In the RA group, the normalized distances between the geometric centroids were significantly closer for bone pairs Cc and cT and significantly distracted for bone pair CN compared with the distances in normal subjects. In RA patients (versus normal subjects), the angles subtended at the bone centroids were significantly decreased in 3 bone groups (CNc, TCN, and TNc) and significantly increased in 3 bone groups (CcN, CcT, NTc). The angles formed between the major principal axes of bone pairs CT and cT were significantly increased in RA patients compared with those in normal subjects. Pattern classification defined 11 RA feet as having normal structure and 12 as having abnormal structure. However, the abnormal feet did not fit consistently with structures defined for RA, pes planus, or pes cavus foot types. Logistic regression demonstrated that subtalar joint synovitis was the only predictive factor for abnormal subtalar and midtarsal architecture (odds ratio 19.2, 95% confidence interval 1.77-200.0). CONCLUSION: This unique 3-D MRI-based technique successfully quantified the effects of RA on the geometric architecture of the foot and the patient-specific nature of these changes. This technique can be used to provide logical therapy for correction.

Adult↗
PubMed2002

Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells.

OBJECTIVE: There is an increased interest in rheumatology in mesenchymal progenitor/stem cells (MPCs) and their roles in rheumatic diseases, but little is known about the phenotype of these cells in vivo. The aim of this study was to isolate and characterize human bone marrow (BM) MPCs. METHODS: Fluorescence microscopy was used to identify putative MPCs among adherent BM cells. To purify them, a positive selection with antifibroblast microbeads was used, combined with fluorescence-activated cell sorting (FACS) for microbead+,CD45(low) cells. A more detailed phenotype of these cells was determined using 4-color flow cytometry, and standard chondrogenic, osteogenic, and adipogenic assays were used to investigate their differentiation potentials. RESULTS: Putative MPCs microscopically identified as large, fibroblast-like, D7-FIB+ cells were purified using positive selection with D7-FIB-conjugated (antifibroblast) microbeads followed by FACS for specifically bound microbead+,CD45(low) cells. These cells represented 0.01% of mononuclear cells in the BM. They were uniformly positive for CD105, LNGFR, HLA-DR, CD10, CD13, CD90, STRO-1, and bone morphogenetic protein receptor type IA (BMPRIA) and were negative for CD14, CD34, CD117, and CD133. Only cells with this phenotype could proliferate and produce adherent cell monolayers capable of chondrogenic, osteogenic, and adipogenic differentiation. D7-FIB- cells in the BM lacked any MPC activity. Uncultured skin fibroblasts had a phenotype similar to that of BM MPCs, but were negative for LNGFR, STRO-1, HLA-DR, and BMPRIA. CONCLUSION: This study shows the distinct phenotype, morphology, and method of isolation of BM MPCs. The findings may have implications for defining the physiologic roles of MPCs in arthritis, bone diseases, and joint regeneration.

Adolescent↗
PubMed2002

Advances in the understanding of entheseal inflammation.

The importance of enthesitis in the pathogenesis of spondyloarthropathy (SpA) is now well recognized. Several entheses comprise more than simply the insertion site, and they are part of a complex biomechanical organ to resist shear and compression. It is also evident that tendons that wrap around bony pulleys form an integral part of joint capsules, and share, along with imaging abnormalities and histopathologic changes, common anatomic, histologic, and biomechanical features with classically defined entheses. Researchers have called these regions of tendons functional entheses. Furthermore, certain synovial joints have much in common with classic entheses--most notably those lined with fibrocartilage rather than hyaline cartilage. These observations provide a unifying anatomic basis for SpA. Enthesitis is associated with underlying osteitis, whether mechanically induced or inflammatory-related--with the extent of osteitis determined by the human leukocyte antigen-B27 gene. Until recently, there was no effective therapy for resistant enthesitis, but it is now evident that enthesitis responds well to biologic blockade with anti-tumor necrosis factor. Unraveling the pathogenic basis of enthesitis will have important implications for understanding and defining therapies in SpA.

Antibodies, Monoclonal↗
PubMed2002

Dose-effect relationships of nonsteroidal anti-inflammatory drugs: a literature review.

BACKGROUND: Many clinicians believe that higher doses of nonsteroidal anti-inflammatory drugs (NSAIDs) are more effective than lower doses for the treatment of rheumatoid arthritis (RA) and osteoarthritis (OA) but are associated with higher rates of adverse events (AEs). However, there is a lack of consensus on dose-effect relationships with the NSAIDs. OBJECTIVE: The purpose of this review was to investigate evidence for the relationship between NSAID dose, efficacy, and the occurrence of AEs from clinical trials of RA and OA of the hip and knee. METHODS: Relevant English-language publications were identified through a search of EMBASE, MEDLINE, and REFLINE using the terms aceclofenac, diclofenac, etodolac, ibuprofen, isoxicam, lornoxicam, meloxicam, nabumetone, naproxen, piroxicam, tenidap, tenoxicam, arthritis, OA (hip and knee), RA, rheumatic disorders, and musculoskeletal disorders for the period January 1970 to December 1997 (this review was conducted in 1998). Bibliographies of retrieved publications were reviewed for other potentially relevant articles. Selected publications were evaluated for quality (likelihood of bias) based on 4 factors (randomization procedure; completeness of patient and treatment information; standardization and completeness of outcome data; and reporting of attrition data). RESULTS: This review included 99 publications concerning clinical trials conducted in 24 countries and enrolling 28,239 patients. The majority of reports were published in the 1990s, particularly in the latter half of that decade. The average quality of the publications improved over time, with a significant increase in mean quality score from 5.43 in the 1970s to 9.21 during the last half of the 1990s (P < 0.05). Only 8 reports directly compared high and low doses of the same drug in relation to efficacy. CONCLUSIONS: Data on the relationship of NSAID dose to efficacy and the incidence of AEs were limited. There is a need for clinical trials directly addressing dose-effect relationships of NSAIDs, as well as reviews of more current literature and reports in languages other than English.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Systemic sclerosis and interstitial lung disease: a pilot study using pulse intravenous methylprednisolone and cyclophosphamide to assess the effect on high resolution computed tomography scan and lung function.

OBJECTIVE: To document the effectiveness, including the longterm effect, of a course of intravenous (IV) pulses of methylprednisolone (MP) and cyclophosphamide (CYC) in patients with scleroderma (SSc) who had evidence of lung inflammation on high resolution computer tomographic (HRCT) scan of the chest. METHODS: Fourteen consecutive patients with SSc and lung involvement were treated with 6 pulses of IV MP (10 mg/kg) and IV CYC (15 mg/kg) given at 3-4 weekly intervals. HRCT scans and lung function tests were performed at baseline and after the 6th pulse. Further lung function tests were repeated at 12 months and annually thereafter. RESULTS: Modified Rodnan skin scores improved significantly by 35% from a median baseline score of 17 (IQR 14-26.5) to a posttreatment score of 13 (IQR 10.5-18.5; p = 0.0058). HRCT scan scores improved significantly (p = 0.04). Twelve of 13 patients experienced either improvement or stabilization of the HRCT score. Median DLCO and lung volumes remained stable during the first 12 months. After a median followup of 26 months (IQR 19-43), 67% of patients experienced deterioration in DLCO. Median deterioration was 23% (IQR 44-0.6), with the median rate of deterioration of the predicted value of the DLCO/month being 0.87% (IQR 1.24-0.02). The treatment was safe and well tolerated. CONCLUSION: This IV regimen stabilized lung disease in patients with SSc. When treatment was stopped, or reduced in intensity, a deterioration in lung function occurred in the majority of patients. Rate of deterioration of DLCO may be a useful marker for determining the intensity of treatment. These findings have implications for treating lung disease and designing clinical trials in patients with SSc.

Adult↗
PubMed2002

Evidence supporting the benefit of early intervention in rheumatoid arthritis.

Numerous challenges confront the rheumatologist in identifying the earliest possible time during which the patient will have persistent rheumatoid arthritis (RA) or risk factors for severe RA. The first challenge is that of accurate diagnosis: clinical assessments are nonspecific and current diagnostic criteria lack sensitivity. Further compounding the problem, the patient may not seek medical attention, or may not be referred to a rheumatologist, until symptoms have been present for some time. Studies indicate that initiating treatment with disease modifying antirheumatic drugs (DMARD) as soon as possible after diagnosis produces significant clinical and functional benefit and appears to retard the rate of radiographic progression of erosions. Delaying treatment by as little as 8 or 9 months sets the stage for damage that cannot be reversed.

Antirheumatic Agents↗