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Biomedical subjects

Alain Saraux

Publications and source records attributed to Alain Saraux.

At least 37 records · Page 2Linked to original sources

Induction of endothelial cell apoptosis by the binding of anti-endothelial cell antibodies to Hsp60 in vasculitis-associated systemic autoimmune diseases.

OBJECTIVE: Anti-endothelial cell antibodies (AECAs), which recognize a number of endothelial antigens, are seen in patients with systemic autoimmune diseases, more often in the presence of vasculitis than in its absence. Some AECAs induce apoptosis of endothelial cells (ECs), but their target antigens remain unknown. The aim of this study was to determine whether Hsp60 is a target antigen and whether AECAs induce apoptosis in ECs. METHODS: Two-dimensional electrophoresis and conventional Western blotting techniques were used to characterize AECA targets. Hsp60 reactivity was determined by enzyme-linked immunosorbent assay. RESULTS: Hsp60 was shown to be targeted by a proportion of AECAs. The level of reactivity was higher in patients with systemic autoimmune disease and vasculitis than in those without vasculitis and in patients with systemic lupus erythematosus than in patients with other systemic autoimmune diseases. Hsp60 was expressed on the plasma membrane of heat-stressed ECs, and this followed Hsp60 messenger RNA transcription, confinement of the protein to the cytoplasm, and translocation of the protein to the surface. Shedding of Hsp60 from ECs was induced by stress and resulted in the binding of soluble Hsp60 to the surface of ECs, particularly stressed ECs. Apoptosis of ECs was triggered by anti-Hsp60-containing AECA-positive sera and was inhibited by preincubation of the ECs with recombinant Hsp60. CONCLUSION: Our data support the notion that Hsp60 is an important target for AECAs and that such an interaction contributes to pathogenic effects, especially in vasculitis-associated systemic autoimmune disease.

Adult↗

Rheumatoid factor on a daily basis.

Rheumatoid factors (RF), which are antibodies (Ab) with specificity directed against gamma (?) globulins, are the commonest auto-Ab ever described in man. Some of them are referred to as agglutinating RF, others designated non-agglutinating RF. Not only do these characterize rheumatoid arthritis (RA), but they are also encountered in a variety of disease conditions, as well as a proportion of healthy controls. Although non-specific for RA, the measurement of agglutinating IgM-RF remains the most useful serological test for the diagnosis of this disease. Demonstration of abnormal amount of serum RF by any method for which the result has been positive in less than 5% of normal subjects has indeed become one of the seven revised criteria, listed by the American College of Rheumatology (Arnett, FC, Edworthy, SM, Bloch, DA, McShane, DJ, Fries, JF, Cooper, NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum, 1988: 31: 315-24), for the classification of RA. Over the course of years, the relative importance of genetic (Carson, DA, Chen, PP, Kipps, TJ, Radoux, V, Jirik, FR, Goldfien, RD, et al. Idiotypic and genetic studies of human rheumatoid factors. Arthritis Rheum, 1987: 30: 1321-1325) and environmental (Nemazee, DA, Sato, VL. Enhancing antibody, a novel component of the immune response. Proc Natl Acad Sci USA, 1982: 79: 3828-3832) factors in the production of such intriguing auto-Ab has been delineated.

Animals↗

B lymphocytes are required for development and treatment of autoimmune diseases.

Recent studies have revealed that B cells serve extraordinarily diverse functions within the immune system in addition to antibody production. These functions contribute to autoimmunity. They initiate the development of lymphoid architecture and regulate dendritic and T-cell function through cytokine production. Receptor editing is also essential to prevent autoimmunity. Both abnormalities in the distribution of B-cell subsets and the benefits of ablative B-cell therapy of autoimmune states confirm their importance. Results from transgenic models have demonstrated that the sensitivity of B cells to antigen receptor cross-linking correlates to autoimmunity, with particular reference to negative signaling by CD5 and CD22. These mechanisms maintain tolerance by recruiting src-homology 2 domain-containing protein tyrosine phosphatase-1. These findings open new prospects for immunotherapy of autoimmune diseases.

Animals↗

BAFF overexpression is associated with autoantibody production in autoimmune diseases.

The B-cell activity factor (BAFF) acts as a positive regulator of B-cell function. To gain further insight into the understanding of B-cell hyperactivity in autoimmune diseases, the serum level of BAFF was determined in 43 systemic lupus erythematosus (SLE) patients, 58 primary Sjögren's syndrome (pSS) patients, 28 rheumatoid arthritis (RA) patients, and 68 normal control subjects using an in-house sandwich ELISA. A commercial kit was used to detect soluble CD23 (sCD23) reflecting B-cell activation. In-house assays for the detection of autoantibodies also were used. We found an increased level of BAFF in SLE, pSS, and RA sera compared with normal subjects (respectively, 10.6 +/- 8.5, 15.8 +/- 12.9, 9.7 +/- 1.5 ng/mL vs. 4.6 +/- 2.9 ng/mL, P < .001). sCD23 released on B-cell activation also was found to be elevated in SLE, pSS, and RA compared with normal sera. However, no correlation was found between the circulating BAFF and the level of sCD23. By contrast, we observed that high levels of BAFF were associated with the presence of autoantibodies (anti-double-stranded DNA antibodies in SLE, anti-SSA antibodies in pSS, and rheumatoid factors in RA). Our data suggest that BAFF is influential in driving antibody production rather than activation of the B lymphocytes in autoimmune diseases.

Arthritis, Rheumatoid↗

Costs of workups for the diagnosis of early arthritis: results of a nationwide survey.

OBJECTIVE: To evaluate the costs of workups to diagnose early arthritis. METHODS: In 2000, the French Society for Rheumatology conducted a survey of a representative sample of French and Belgian rheumatologists (n = 239). The respondents were asked to consider 2 hypothetical scenarios, 1 describing undifferentiated arthritis and the other more suggestive of rheumatoid arthritis. They were then asked what diagnostic workup they would order. Costs for each study were determined in 2001 euros, according to the French public health system fee schedules. RESULTS: In total, 151 rheumatologists participated in the study (63%). The mean +/- SD diagnostic costs were 406.5 +/- 194.3 euro for the case with no diagnostic clues, and 280.7 +/- 154.3 euro for the case suggestive of early RA. Responses were very heterogeneous. The 2 main sources of expenditure were immunology tests and imaging. Hospital staff physicians tended to order more expensive workups, and costs tended to vary inversely with physician experience. The most important predictor of cost was diagnostic doubt, as estimated by the number of diagnoses proposed by respondents in each case; each additional diagnosis cost an additional 19.1-26.1 euro. CONCLUSION: Diagnostic workups after a first medical visit for early polyarthritis result in substantial direct costs. This observation and the great variability observed in physicians' practices point out the need for consensus on the appropriate workups for these patients.

Adult↗

Management of primary hyperthyroidism: toward minimal access surgery.

Fifteen years ago, bilateral exploration of the neck was dogma in parathyroid surgery. Now, less invasive procedures can be used to target lesions identified by new tests such as dual-phase Sestamibi scanning or intraoperative documentation of parathyroid hormone (PTH) level changes after removal of a parathyroid gland. A hand-held gamma probe can be used for intraoperative detection of high-uptake lesions, and video-assisted endoscopic surgery has been used successfully. With these new techniques, surgical exploration can be confined to one side of the neck through smaller incisions associated with better cosmetic results. The operating time is reduced, and in some cases the procedure can be done under local anesthesia. The objective of this article is to describe recent changes in the management of parathyroid adenoma requiring surgery.

Female↗

Post-fracture osteolysis of the pubic bone simulating a malignancy: report of a case.

Post-fracture osteolysis of the pubic bone is rare. We report a case of a 70-year-old woman with osteoporosis and a history of radiation therapy 2 years earlier. At presentation, she was found to have a bilateral sacral fracture and fractures of both pubic rami on one side. The pain persisted, and follow-up radiographs showed osteolysis of the pubic rami suggestive of metastatic disease. The development of a bony callus within 8 months established the diagnosis of benign osteolysis. About 50 cases of osteolysis at fracture sites have been reported to date, of which about a dozen occurred after radiation therapy. All the patients were elderly women with post-menopausal osteoporosis. Radiation therapy probably further increases the risk in this setting. The possibility of osteolysis at fracture sites in patients with osteoporosis should be borne in mind to avoid unnecessary and burdensome investigations that are costly and cause undue anxiety to the patients. Rest is the only effective treatment.

Aged↗

Agreement between rheumatologist visit and lay interviewer telephone survey for screening for rheumatoid arthritis and spondyloarthropathy.

OBJECTIVE: To evaluate agreement between a rheumatologist visit and a telephone interview by a patient organization member, regarding the diagnosis of rheumatoid arthritis (RA) or spondyloarthropathy (SpA) and the classification criteria for these two conditions. METHOD: Patients underwent a standardized interview and physical examination by hospital-based rheumatologists, who diagnosed RA in 230 cases, SpA in 175, and other conditions (controls) in 195. Members of patient organizations then used a standardized questionnaire to interview the patients by telephone about their diagnosis and about 1987 ACR classification criteria for RA and the ESSG criteria for SpA. RESULTS: Agreement between the two sources of data was poor for the classification criteria but satisfactory for the diagnosis (kappa, 0.84 (0.81-0.87) for RA and 0.78 (0.75-0.81) for SpA). CONCLUSION: Standardized telephone interviews conducted by patient organization members accurately identify the diagnosis made by rheumatologists based on a physical examination and medical record review, whereas agreement is poor regarding classification criteria for RA and SpA.

Arthritis, Rheumatoid↗

Ability of foot radiographs to predict rheumatoid arthritis in patients with early arthritis.

OBJECTIVE: In a cohort of patients with early arthritis, to evaluate how well foot radiographs at study inclusion predicted a diagnosis of rheumatoid arthritis (RA) 2 years later. METHODS: A cohort of patients with arthritis of less than one year duration was evaluated in a multicenter study and followed for 30 +/- 11 months. An observer blinded to patient data read all 149 hand and foot radiographs done at study inclusion, using item 7 of the 1987 American College of Rheumatology (ACR) criteria for RA and Sharp's method to score erosions and joint space narrowing. RESULTS: The kappa coefficient for the 1987 ACR item 7 was 0.52 for bony decalcification and 0.87 for erosions. Intra and interobserver correlation coefficients for Sharp's scores ranged from 0.90 to 0.98. Erosions at the feet were significantly associated with RA. The item 7 erosion component at the feet was more specific than the full item 7 (97.5% vs 94%; p = 0.01). Sharp's erosion score at the feet was not better than the erosion component of item 7 (sensitivity 18%; specificity 97.5%). Combined use of radiographs of the hands and feet improved the diagnostic performance of the item 7 erosion component; (sensitivity and specificity of item 7 erosions at the hands combined with the feet were 32.5% and 94.5%, respectively). CONCLUSION: The "erosion" criterion at the feet had the best diagnostic performance and was significantly associated with a diagnosis of RA. Combining hand and foot radiographs improved diagnostic performance.

Adult↗

Costs of rheumatoid arthritis in France: a multicenter study of 1109 patients managed by hospital-based rheumatologists.

OBJECTIVE: The economic impact of rheumatoid arthritis (RA) is substantial, but most studies provide cost estimates specific to a US population. We performed a cost-of-illness analysis of patients with RA for French society. METHODS: A cross-sectional study among rheumatologists in 148 hospitals in France was conducted between November and December 2000. Data were collected on health resource consumption associated with RA (treatments, medical devices, physician visits, examinations, hospitalization, other health professional care) during the previous 12 months. Direct costs and social costs were evaluated for 1109 RA patients. The relation of costs to disease activity and severity was analyzed. RESULTS: The annual direct cost of RA per patient was over euro4000. The costs due to hospitalizations represented around 60% of the costs. The major reason for hospitalization was acute care for RA in a rheumatic disease ward. Patients visited a physician an average of 13 times during the 12 months, 7.7 +/- 8.6 visits to an office-based physician and 5.1 +/- 4.4 visits to a hospital-based physician. Among them, 37% of patients were receiving at least one disability pension (16.7%) or sick-leave allowance (11.9%), with an estimated cost of euro7328 per patient. The mean annual budget per patient was euro2742. Medical and social costs increased in patients with severe disease (2 times), longer disease duration since diagnosis (more than double for patients with a history longer than 10 yrs vs patients with less than 2 yrs), active disease (1.4 times), and functional status (4 times more for American College of Rheumatology class IV than for class I). CONCLUSION: Direct costs represented 59% of the total costs for patients with active RA and 57% for patients with severe RA. Social costs represented 41% of the total costs on average.

Aged↗

A case of cutaneous sensory neuropathy associated with Churg-Strauss syndrome.

Cutaneous sensory neuropathy manifests as multiple, sharply demarcated areas of hypoesthesia with a variable degree of pain. This rare neuropathy is caused by a multifocal infection or inflammation of the small sensory nerves of the skin. We report a case in a patient with febrile arthritis and eosinophilia. Her chronic cough and the presence of extravascular infiltrates of eosinophils in a neuromuscular biopsy specimen suggested Churg-Strauss syndrome. The course was favorable under corticosteroid therapy.

Adult↗

Musculoskeletal manifestations in cystic fibrosis.

Although bone and joint manifestations are common in children with cystic fibrosis (CF), they have received little attention in adults. As compared to healthy individuals, bone mineral density is low, even with calcium intakes greater than 1500 mg/d. Nevertheless, calcium and phosphate levels in blood and urine are often normal, and vitamin D levels vary. Short stature with a low body mass index and central hypogonadism are the rule in these patients. Fractures and kyphosis are often reported. CF arthropathy occurs in 2-8.5% of patients. Arthritis develops, and there may be skin eruptions. Non-steroidal antiinflammatory drug therapy is effective. Hypertrophic osteoarthropathy associated with respiratory failure is present in 2-7% of patients. Rheumatoid arthritis, spondyloarthropathies, sarcoidosis, and amyloidosis have been reported in association with CF. Knee pain due to patellofemoral syndrome, quinolone-induced arthropathy, and mechanical back pain have been described. Rheumatoid factor titers are higher than in healthy controls, particularly in patients with episodic arthritis. No data are available on antiperinuclear factor or antikeratin antibody titers. Tests for antinuclear antibody are usually negative. Circulating immune complex levels and antibodies to heat shock proteins may be elevated. Antineutrophil cytoplasmic antibody of the bactericidal/permeability-increasing protein (BPI) or azurocidin (AZ) type has been reported, often in high titers (up to 40%).

Adolescent↗

Value of antibodies to citrulline-containing peptides for diagnosing early rheumatoid arthritis.

OBJECTIVE: To compare the diagnostic values of antiperinuclear factor (APF), antikeratin antibody (AKA), and anti-cyclic citrullinated peptides (anti-CCP) to discriminate between patients with and without rheumatoid arthritis (RA) and to determine the diagnostic value of anti-CCP used alone or with other tests. METHODS: Two hundred and seventy patients with early arthritis underwent standardized investigations in 1995-1997. The clinical utility of APF, AKA, and anti-CCP in first-visit sera was evaluated using receiver-operating characteristic curves. Combinations of anti-CCP with other laboratory tests were assessed by multiple logistic regression. RESULTS: Anti-CCP, APF, and AKA were not perfectly correlated with one another. Anti-CCP with 53 UI as the cutoff was 47% sensitive and 93% specific, versus 52% and 79%, and 47% and 94%, for APF and AKA, respectively. Multiple logistic regression selected anti-CCP, AKA, IgM-rheumatoid factor (RF) ELISA, and the latex test. CONCLUSION: Rheumatologists can routinely use 2 or 3 tests for diagnosing RA (latex and/or IgM RF ELISA, and either AKA or anti-CCP ELISA) and can add a third or fourth test when the diagnosis remains in doubt.

Adult↗

Value of laboratory tests in early prediction of rheumatoid arthritis.

OBJECTIVE: To determine which laboratory test or tests at presentation best predicted a diagnosis of rheumatoid arthritis (RA) 2 years later. METHODS: Two hundred seventy patients with early arthritis seen in 7 hospitals underwent comprehensive evaluations at 6-month intervals for 2 years, when the diagnosis of RA was assessed by 5 rheumatologists. The sensitivity and specificity of each test at the first visit for discriminating between RA (38%, n = 98) and non-RA patients were determined. Optimal cutoffs for continuous tests were derived from receiver operating characteristic curves. Sensitivity and specificity of test combinations selected by multiple logistic regression were determined. RESULTS: IgM rheumatoid factor (RF) by enzyme-linked immunosorbent assay, IgG-antikeratin antibody (AKA), and latex test had the strongest associations with RA. These 3 tests formed the most powerful combination for distinguishing RA from non-RA. CONCLUSION: IgM-RF, IgG-AKA, and the latex test are the best laboratory tests for discriminating between patients with and without RA. Combining these tests slightly improves diagnostic value.

Arthritis, Rheumatoid↗

Second-line drugs used in recent-onset rheumatoid arthritis in Brittany (France).

OBJECTIVE: The management of recent-onset rheumatoid arthritis (RA) is not well standardized. We conducted a survey of drugs prescribed to RA patients in Brittany at presentation and during the first 1 to 3 years of follow-up. METHODS: A cohort of 270 patients with recent-onset inflammatory joint disease was recruited between 1995 and 1997. The evaluation at presentation included a medical history, a thorough physical examination, and a standard battery of investigations. Follow-up at 6-month intervals was offered. At the last visit, between June and December 1999, a panel of five rheumatologists established that 98 patients had RA. RESULTS: At presentation, hydroxychloroquine and injectable gold were the most widely used second-line drugs, and only two patients were offered a combination of second-line drugs. At the last visit, the most commonly used drugs were methotrexate, injectable gold, and hydroxychloroquine (23, 23, and 21 patients, respectively); only three patients were on more than one second-line drug and 38 (38/98, 39%) patients were on glucocorticoid therapy. CONCLUSION: Rheumatologists in Brittany prefer monotherapy with hydroxychloroquine or injectable gold as the initial treatment. Later, they rely mainly on methotrexate, injectable gold, and hydroxychloroquine, often in combination with glucocorticoid therapy.

Antirheumatic Agents↗

Diagnostic value of radiographs of the hands and feet in early rheumatoid arthritis.

The extent to which radiographs of the hands and feet can contribute to the diagnosis of early rheumatoid arthritis (RA) has received little research attention. Yet, the workup for recent-onset inflammatory joint disease usually includes radiographs of the hands and feet. We reviewed the literature for data on the value of these radiographs for diagnosing early RA. We sought to determine whether radiographic changes in the hands and feet constitute a valid diagnostic criterion, i.e., show good discrimination, good reproducibility, and an ability to detect early disease. Furthermore, we evaluated whether the sensitivity, specificity, and positive and negative predictive values of these changes could be calculated from published data. Few cohort studies of early inflammatory joint disease have been published, and the data come mainly from studies in early RA. Among radiographic alterations described to date, erosions seem associated with the best reliability and discriminating power. Radiographic alterations are of limited sensitivity for early rheumatoid arthritis because they occur only after some time. Radiographs of the hands and feet are far easier to obtain than magnetic resonance imaging and ultrasonography, which seem promising but are still undergoing validation.

Arthritis, Rheumatoid↗