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A Daragon

Publications and source records attributed to A Daragon.

At least 19 recordsLinked to original sources

Autoantibodies, metalloproteinases and bone markers in rheumatoid arthritis patients are unable to predict their responses to infliximab.

OBJECTIVES: To identify biochemical, immunological and bone markers as predictors of rheumatoid arthritis (RA) patients' responses to infliximab. METHODS: A total of 76 patients with active RA (American College of Rheumatology criteria), refractory to disease-modifying anti-rheumatic drugs, including methotrexate, received infliximab (3 mg/kg) infusions at weeks 0, 2, 6, and then every 8 weeks in combination with methotrexate or leflunomide. At week 14, infliximab efficacy was evaluated using disease activity score (DAS)28. A serum sample, collected just before starting infliximab, was tested by ELISA (unless stated otherwise) for the following immunological markers: rheumatoid factor by agglutination and ELISA (IgA, IgG and IgM isotypes); anti-cyclic citrullinated protein; autoantibodies recognizing calpastatin domain I and its 27 C-terminal fragment, glucose-6-phosphate isomerase, alpha-enolase; anti-keratin and anti-perinuclear factor antibodies (immunofluorescence); biochemical markers: C-reactive protein (nephelometry), metalloproteinase-1 and -3, tissue inhibitors of metalloproteinases-1 and -2, antioxidants (vitamins A and E; selenium); bone resorption markers: pyridinoline, deoxypyridinoline, osteoprotegerin, soluble receptor activator of nuclear factor-kappaB ligand, cartilage oligomeric matrix protein. Each parameter's predictive value of the response to infliximab was analysed using Fisher's exact, Mann-Whitney and chi-square tests. Hierarchical clustering was performed with The Institute for Genomic Research (TIGR) multiple experiment viewer software. RESULTS: Good, moderate and non-responder rates were 6.5, 61.8 and 31.5%, respectively. No significant difference was observed between responders and non-responders, regardless of the serum parameters considered. Analysis of dichotomous or continuous variables failed to identify markers predictive of a good or poor response to infliximab. CONCLUSION: The search for soluble markers in RA patients' sera likely to predict response to infliximab because of their involvement in RA pathogenesis seems disappointing. However, because of the limited power to detect smaller differences in biomarkers, the present study is a preliminary exploratory analysis.

Adult↗

Autoantibodies recognizing citrullinated rat filaggrin in an ELISA using citrullinated and non-citrullinated recombinant proteins as antigens are highly diagnostic for rheumatoid arthritis.

The objective of the study was to determine the diagnostic value for rheumatoid arthritis (RA) of anti-filaggrin autoantibodies (autoAb) recognizing citrullinated recombinant rat filaggrin (ACRF) in community cases of very early arthritis. To evaluate the diagnostic value of ACRF, were studied sera from patients with different classified rheumatic diseases and healthy subjects (group 1, n= 422) and 314 community cases of very early arthritis (group 2) that were classified as RA (n = 176), non-RA (n = 63) and undifferentiated (n = 75) arthritides after 1 years of follow-up. ACRF were measured using a new ELISA, with results expressed as the difference between the OD value obtained on citrullinated minus that on noncitrullinated rat filaggrin (differential ACRF; dACRF). For both groups, rheumatoid factors (RF), anti-keratin autoAb (AKA) and anti-perinuclear factor (APF) were tested; for group 2, anti-CCP autoAb were also tested. Different reactivity patterns against citrullinated and noncitrullinated filaggrin were observed. Almost all sera reacting with citrullinated but not noncitrullinated filaggrin were from RA patients. Among RA and non-RA sera that recognized both forms of filaggrin, a positive result was obtained only with RA sera. For groups 1 and 2, dACRF sensitivity was 58.4% and 30.7%, and specificity for RA was 99.5% and 98.4%, respectively. In group 2, dACRF specificity for RA was better than that of RF (92.1%), APF (95.2%), AKA (96.8%) and anti-CCP (95.2%). dACRF positive predictive value was high (98.2) and close to that given by the concomitant positivity of RF and anti-CCP autoAb. Despite a high positive correlation between AKA, APF, anti-CCP and dACRF test results, they were complementary since some sera were positive for only one test. Thus, in a community setting, anti-citrullinated rat filaggrin reactivity detected by a new ELISA, whose originality is based on the difference between serum's reactivities on the citrullinated and native forms of filaggrin, had a higher diagnostic value for RA than other autoAb.

Adult↗

Rheumatoid factor is the strongest predictor of radiological progression of rheumatoid arthritis in a three-year prospective study in community-recruited patients.

OBJECTIVE: To evaluate the predictive value of clinical, biological and radiological parameters for the prognosis of rheumatoid arthritis (RA) in a community-recruited cohort. METHODS: Ninety-one patients (mean age 49 yr, female/male ratio 2.9) with RA of limited duration (median 2 yr), 80% recruited from the community, were prospectively enrolled in 1996 (T1) and followed until 1999 (T2). Data collected at T1 were demographic characteristics, Ritchie articular index (RAI), extra-articular manifestations, Health Assessment Questionnaire (HAQ) score, C-reactive protein (CRP) and autoantibodies (autoAbs) [rheumatoid factors (RF), detected by latex fixation test and ELISA (IgM, IgA and IgG isotypes), anti-filaggrin, detected by immunofluorescence (anti-keratin antibodies, AKA; anti-perinuclear factor antibodies, APF) and ELISA (anti-citrullinated rat filaggrin antibodies, ACRFA), anti-Sa, anti-calpastatin recognizing the 27 C-terminal fragment (ACAST-C27) and domain I (ACAST-DI), anti-cardiolipin (ACL), antineutrophil cytoplasmic antibodies (ANCA), anti-annexin V (aANX V) and anti-Ro]. Hands were radiographed at T1 and T2, and read using the Sharp method as modified by van der Heijde. The main assessment criterion was progression of radiologically detected damage between T1 and T2. RESULTS: At T1, RA activity was mild (RAI 11/78; mean CRP 14 mg/ml), with minor functional disability (HAQ 0.8/3) and mild X-ray destruction (mean total Sharp score 9.2/280). At T1, 96% of the patients were on treatment (prednisone 72%, DMARDs 95%). The latex test detected autoAb in 46% of patients, RF-IgM was detected in 51%, RF-IgA in 36%, RF-IgG in 32%, AKA in 33%, APF in 45%, ACRFA in 45%, ACAST-C27 in 14%, ACAST-DI in 5%, anti-Sa in 22%, ACL in 3%, ANCA in 28%, aANX V in 9% and anti-Ro in 2%. At T2, the mean total Sharp score was 22.9. According to univariate analysis, T1 parameters associated with the independent variable were RAI, HAQ, CRP, latex test positivity and T1 Sharp scores. Multivariate analysis retained only latex test positivity and, to a lesser degree, joint-space narrowing score as independent predictors of radiological progression. CONCLUSION: RF is the main factor that can predict radiological progression in community cases of RA of limited duration.

Adult↗

[Osteoporosis in the elderly. Practical prevention and treatment].

A MAJOR PUBLIC HEALTH ISSUE: Osteoporosis in the elderly limits independence and quality of life. Preventive and curative treatment should be adapted to the patient's age. THERAPEUTIC OBJECTIVES: The goal of preventive like curative treatment is to reduce the risk of fracture. Risk can best be assessed from personal history of fracture or with bone densitometry. THERAPEUTIC METHODS: Non-drug methods are based on physical activity, diet, reduction of alcohol intake or smoking, and limiting the risk of falls. Drugs used include calcium, vitamin D, hormone replacement therapy and bisphosphonates. THERAPEUTIC STRATEGY: Prevention programs should focus first on non-drug methods, adapted to the patient's age. For drug regimens, hormone replacement therapy is rarely used after 70 years of age while calcium and vitamin D are widely used. Drugs inhibiting bone resorption, e.g. bisphosphonates, are added on for curative treatment. After the age of 80 years, the calcium vitamin D combination alone is useful. FOLLOW-UP: A simple surveillance scheme should include a check-up of renal function every year in patients taking bisphosphonates. It is most difficult to assess treatment efficacy on an individual basis.

Age Factors↗

Prospective X-ray densitometry and ultrasonography study of the hand bones of patients with rheumatoid arthritis of recent onset.

OBJECTIVE: Bone demineralization observed in early rheumatoid arthritis is not easily measured. To measure bone loss and to discriminate between rheumatoid arthritis and other rheumatic diseases, we used two methods: dual-energy X-ray absorptiometry and ultrasonography. METHODS: From a population-based recruitment, 32 patients with early peripheral polyarthritis (median disease duration: 4 months) were studied. Clinical, laboratory, functional, hand-bone assessments were made at the entry an at months 6 and 12. Bone X-ray densitometry measurements were made on 16 areas of the hand. Speed of sound was measured across the proximal phalanges of the four fingers. X-rays of both hands were scored according to the modified Sharp's score. At 12 months, patients were classified as rheumatoid arthritis (N = 15; 9 F) or as other rheumatic diseases. RESULTS: We found: 1) significantly decreased bone mineral density (BMD) of the whole hand, in the rheumatoid arthritis group versus the other rheumatic diseases group, at 6 and 12 months (P < 0.05); 2) no significant decrease of bone mineral density (BMD) in other areas in the rheumatoid arthritis group; 3) no significant change of ultrasounds in either group; and 4) no significant correlation between the decrease of BMD in the rheumatoid arthritis group and clinical, biological or radiologic parameters, except for IFNgamma, whose production in whole blood cell culture was lower at entry in the rheumatoid arthritis group. CONCLUSION: DEXA bone assessment in rheumatoid arthritis was able t detect bone loss in the whole hand at 6 months.

Absorptiometry, Photon↗

Rheumatoid factors, anti-filaggrin antibodies and low in vitro interleukin-2 and interferon-gamma production are useful immunological markers for early diagnosis of community cases of rheumatoid arthritis. A preliminary study.

OBJECTIVE: To determine whether measurements of different autoantibodies (Ab) and cytokines are useful to distinguish very early rheumatoid arthritis (RA) from other inflammatory rheumatisms. METHODS: From a population-based recruitment, 32 patients with very early polyarthritis (median duration: 4 months) were studied. Evaluations at entry (M0), and at 6 (M6) and 12 months (M12). Ab tested: rheumatoid factors (RF) by agglutination methods and ELISA, antiperinuclear factor (APF), antikeratin Ab (AKA), anti-Sa and antinuclear Ab. Cytokine production (TNFalpha, IL2, IFNgamma, IL1beta, IL10) in whole blood cell culture (WBCC) was determined at M0. At M12, patients were classified as having RA (N = 15) or other rheumatic diseases. RESULTS: At M0, AKA/APF and anti-Sa Ab frequencies were low, 13% and 7%, respectively. While most Ab detected at M0 persisted, others appeared during follow-up, particularly APF, which rose from 13 to 40% at M12. At M6, IgM-RF was detected in two RA patients exclusively by ELISA. AKA/APF were found to be highly specific markers for RA (100% specificity). At some time during follow-up, two RF-negative RA patients were AKA-positive. In two patients, AKA and APF were present at M0 before they satisfied ACR criteria. IL2 and IFNgamma production was significantly lower (P < 0.05) for RA patients. CONCLUSION: AKA/APF and anti-Sa Ab were detected in community cases of very early RA. AKA/APF and RF detected by ELISA might contribute to an earlier diagnosis of RA. Low production of IFNgamma and IL2 in WBCC constituted a distinct immunopathological feature in very early RA patients.

Antibodies, Antinuclear↗

Prospective evaluation of the frequency and clinical significance of antineutrophil cytoplasmic and anticardiolipin antibodies in community cases of patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the frequencies of antineutrophil cytoplasmic (ANCA), anticardiolipin (aCLA) and anti-beta(2)-glycoprotein 1 antibodies (abeta(2)-GP1A) in rheumatoid arthritis (RA) of limited duration in patients recruited primarily from private practitioners (80%), and to attempt to correlate the presence of these antibodies with certain clinical and/or biological criteria. Patients and methods. Patients (n = 102) with RA evolving for <5 yr (mean 2.2 yr) were recruited. A home evaluation collected clinical data [Ritchie articular index, Health Assessment Questionnaire (HAQ) index, extra-articular manifestations] and blood for biological analyses [C-reactive protein (CRP), rheumatoid factor, ANCA, aCLA, abeta(2)-GP1A]. ANCA were detected by indirect immunofluorescence on neutrophils and their specificity was determined by enzyme-linked immunosorbent assay (ELISA) and confirmed by immunoblotting; aCLA and abeta(2)-GP1A were detected by ELISA. RESULTS: Patients had mild RA (Ritchie = 11/78 +/- 9.6; HAQ = 0.79/3 +/- 0.7), probably due to the recruitment procedure. ANCA, aCLA and abeta(2)-GP1A frequencies were 18.5, 7 and 0%, respectively. Titres of ANCA and aCLA were low. A perinuclear ANCA staining pattern was exclusively observed and lactoferrin was shown to be the major antigen recognized. No relationship was found between ANCA and aCLA and/or rheumatoid factor, or any clinical manifestations. ANCA were more common in RA of longer duration (cut-off: 4 yr; P = 0.05) and aCLA were correlated with the CRP level (P = 0.05). CONCLUSIONS: In RA of recent onset, ANCA and aCLA were detected at low titres and frequencies, and were not associated with any clinical manifestations. A longitudinal study is needed to determine whether their early appearance is predictive of subsequent disease severity.

Adult↗

[Postpartum septic arthritis. Two case reports].

Nongonococcal septic arthritis can occur during the postpartum period. We report two cases, one involving the wrist and the sacroiliac joints and the other the pubic symphysis. The difficulty of initial diagnosis in the postpartum period is emphasized. This pathology is uncommon and may begin insidiously. The sacroiliac joint is particularly at risk for postnatal sepsis, but its deep localization hinders investigations. Besides the classical obstetrical infectious assessment (blood cultures, urine culture, vaginal sample, white blood cell count and CRP) and radiological investigations, joint puncture is needed to isolate the causal infectious agent. Joint immobilization in combination with major 3-month antibiotic therapy is usually successful, generally with no sequellae.

Adult↗

Molecular diagnosis of Ureaplasma urealyticum in an immunocompetent patient with destructive reactive polyarthritis.

Polymerase chain reaction (PCR) amplification, which is a useful method for detecting infectious agents in joints, has potential utility in the molecular diagnosis of venereal-associated arthritis. Among pathogens detected by this technique, Ureaplasma urealyticum, which is primarily associated with reactive arthritis (ReA), is also implicated in septic arthritis in immunocompromised patients. We report here a case of destructive polyarthritis, initially suggestive of septic arthritis, in an immunocompetent patient whose PCR positivity for U. urealyticum DNA in one joint, in conjunction with the disease outcome and histologic findings, led to the diagnosis of destructive ReA.

Adult↗

Leiomyosarcoma of the tibia. Report of a case.

A 48-year-old man with an unremarkable medical history was admitted for a painful swelling over the anteromedial aspect of his right leg. Radiographs disclosed heterogeneity of the proximal tibia, with increased uptake on the bone scan. Computed tomography findings consisted of heterogeneity of the proximal tibial metaphysis and diaphysis with subtle cortical osteolysis, periosteal appositions and soft tissue involvement. Magnetic resonance images showed low signal from the metaphysis, diaphysis and soft tissues on T1 sections that enhanced after gadolinium and converted to high signal on T2 images. Lung metastases were also found. Histologic features were consistent with leiomyosarcoma, which was considered to have originated in the tibia since no other primary localization was found. Combination chemotherapy was successful in eliminating the clinical manifestations and clearing the lung metastases. Six months later, the same chemotherapy regimen failed to improve a local and pulmonary recurrence and the patient died a few months later. Primary leiomyosarcoma of bone is a rare tumor, of which one of the most characteristic locations is the proximal third of the tibia. Magnetic resonance imaging with both T1- and T2-weighted sequences is essential to evaluate intramedullary and soft tissue tumor spread. To our knowledge, there are no characteristic signal patterns allowing to differentiate leiomyosarcoma from other primary malignancies of bone. Immunohistochemical and electron microscope studies are useful diagnostic tools.

Basement Membrane↗

Computed tomography of the normal sternoclavicular joint.

OBJECTIVE: The objective of this work was to establish a reference population for the study of the sternoclavicular joint (SCJ). DESIGN: A prospective study of the SCJ was carried out by high-resolution computed tomography (CT). CT images were read by two radiologists and two rheumatologists using a pre-established grid (27 elementary signs). PATIENTS: Sixty healthy subjects, homogeneously distributed by sex and decade of life, from 20 to 80 years old, were studied. RESULTS AND CONCLUSIONS: The main results were the following: 98% of healthy subjects presented at least one sign; mean number of signs per subject was 2.4 +/- 1.9; mean number of signs was higher ( P < 0.005) in men (mean = 3.1 +/- 2.1) than in women (mean = 1.7 +/- 1.3); number of signs increased with age (P < 0.001). Some signs were very frequent: "ossification of the first costal cartilage" (88%), "Surrounded subchondral clavicular erosion" (27%). Some signs were significantly more frequent in the elderly: "sternal osteophyte" after the age of 70 (P < 0.01) and "meniscal calcification" (P < 0.01) and "sternal subchondral sclerosis" (P < 0.05) after the age of 60. The number of clavicular signs was greater than that of sternal signs (P < 0.001). These results can be used as references for the study of the SCJ.

Adult↗

Osteoarticular manifestations of pustulosis palmaris et plantaris and of psoriasis: two distinct entities.

OBJECTIVE: To test the hypothesis that pustulosis palmaris et plantaris and psoriatic arthritis (PsA) are two distinct diseases, and that the associated dermatoses are therefore also distinct diseases. METHODS: We prospectively performed clinical, radiological, biological, and bone scan investigations in 23 outpatients with pustolotic arthritis and 23 outpatients with PsA, matched by gender, age (+/- one year) and duration of arthritis (+/- two years). RESULTS: The anterior chest wall, especially the sternocostoclavicular joints, was more frequently involved in pustulotic arthritis than in PsA, both clinically (82% v 43%; p < 0.001) and radiologically (47% v 17%; p < 0.05). Sternocostoclavicular joints generally presented with erosive lesions in PsA, and with large ossifications in pustulotic arthritis. Peripheral joint involvement was mono- or oligoarticular, affecting proximal joints, in pustulotic arthritis (74% v 21%; p < 0.01), and polyarticular, involving small distal joints, in PsA (60% v 0%; p < 10(-4)), in which condition it was also more often erosive (43% v 8%; p < 0.01). The frequency of sacroiliitis and of spine involvement was similar in pustulotic arthritis and PsA. Biology and bone scan did not help distinguish between the two groups. CONCLUSIONS: Pustulotic arthritis and PsA are clinically and radiologically different, therefore pustulosis palmaris et plantaris and psoriasis are most probably distinct dermatological diseases.

Arthritis, Psoriatic↗

[Experimental study of the stabilization capability of upper metaphyseal tibial fractures by different types of external fixators].

PURPOSE OF THE STUDY: The major problem in external fixation of upper metaphyseal tibial fractures with a double-frame Hoffmann device is poor healing. With a dynamic fixation, it would be possible, with no change in technique, to compress the fracture site in a second phase, and therefore to facilitate the healing process. However, a new fixation device should not compromise the primary stability of the fixation. The aim of this experimental study on cadavers was to compare, in conditions very close to a clinical situation, the initial stabilization capability of five types of external fixation. MATERIAL: Five types of external fixators were tested on cadavers specimens: 1. a standard double-frame Hoffmann device; 2. a double-frame Hoffmann's device sagittaly reinforced with two additional anterior-posterior half-pins; 3. a type-1 axial dynamic fixation device using 6-mm conical pins; 4.a type-2 dynamic axial fixation device with 5-mm cylindrical pins; and 5. a mixed device including an lizarov-type epiphyseal fixation and a monoplane diaphyseal fixation. METHODS: The metaphyseal fracture was simulated by a transversal resection of a 20-mm segment. Specimens received by increments a load of up to 310 N, with which it was possible to determine stiffness components in valgus/varus, flexion/extension, rotation around the vertical axis and axial vertical displacement. The bone mineral content of the specimens was measured by Di Energy X-ray Absorptiometry. RESULTS: The stabilization characteristics of type-1 axial dynamic fixation were identical to those of the standard Hofmann's device in flexion/extension and in rotation as well as axially, but a greater mobility in valgus/varus was observed. The sagittal reinforcement of Hoffmann's device increased its rigidity in flexion/extension. The mixed lizarov fixation was stiffer than the standard Hoffmann's device in rotation; it was equivalent in valgus/varus and flexion/extension and less stiff in axial vertical displacement. In this study it was showed that the individual variability of bone mineral content is a negligible parameter. DISCUSSION: The experimental behaviour of the mixed Ilizarov device gives to assume that it may facilitate the healing process without endangering the primary stability of the fixation. However, this theoretical advantage should be validated in a randomized prospective clinical study.

Aged↗

Prognostic factors in low tumour mass asymptomatic multiple myeloma: a report on 91 patients. The Groupe d'Etudes et de Recherche sur le Myélome (GERM).

Between January 1985 and July 1989 we diagnosed asymptomatic stage I multiple myeloma according to Durie and Salmon [Durie and Salmon: Cancer 36:842, 1975] in 91 patients. All patients were followed without chemotherapy. Disease progression occurred in 41 patients and the median time to progression for all patients was 48 months. In the Cox multivariate regression analysis, hemoglobin levels < 12 g/dl (P < .01), bone marrow plasmacytosis > 25% (P < .01), and M-component size > or = 30 g/l for Ig G or > or = 25 g/l for Ig A (P < .01) were the only significant prognostic factors for progression. The 38 patients without any harmful factor remained free of progression for a median of more than 50 months. The 18 patients with two or three of these characteristics (high-risk group) had the shortest median time to progression of 6 months. Despite different times to progression, the response rate and survival after chemotherapy were similar for all groups of patients. Patients in the high-risk group for progression have to be frequently monitored for disease progression and might benefit from early treatment.

Adult↗