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Biomedical subjects

R M Flipo

Publications and source records attributed to R M Flipo.

At least 91 records · Page 5Linked to original sources

[Treatment of refractory rheumatoid arthritis with cyclosporine].

The efficacy of low-dose cyclosporin-A (CyA) has been clearly demonstrated for rheumatoid arthritis. However, the long-term benefit-risk ratio remains to be investigated in patients with refractory RA. Thirty one patients were included in a prospective open study (24 females, seven males, mean age = 55 years). The mean duration of RA was 11 years and refractory RA was defined by the need of corticosteroid treatment in 26 patients and the previous failure of at least five second line drugs including methotrexate in 27 patients. Initial dosage of CyA was 3 mg/kg/d and could be progressively increased up to 5 mg/kg/d. The mean duration of the study was one year (3-39 months). At 3 months, clinically relevant improvement occurred in 22 patients (71%). Seven were withdrawn due to inefficacy. The main side-effects were hypertension (22 cases) and nephrotoxicity (18 cases) requiring the withdrawal from the study, respectively in one case and in four cases. Raised serum creatinine level had required reduction of the dosage with loss of efficacy in four cases. CyA appears to be an effective therapy for severe treatment refractory RA. Despite a high incidence of side-effects, the efficacy and the monthly management of the patients lead to a good benefit/risk ratio with a percentage of continuation of treatment of 42% at one year.

Administration, Oral↗

Labial salivary gland biopsy assessment in rheumatoid vasculitis.

OBJECTIVES: To assess the vascular involvement in labial salivary gland (LSG) from patients with rheumatoid vasculitis (RV). METHODS: Forty seven patients with rheumatoid arthritis (RA) took part in a prospective study. Among them, 12 had proven RV. LSG biopsy was performed after local anaesthesia. RESULTS: Histological appearance of inflammatory vascular damage was observed in all but one patient with proven RV (92%). Inflammatory vascular involvement was also identified in LSG biopsy of seven patients with RA (20%) and only one patient in the control group (8%). A second specimen of LSG was studied after a mean treatment period of six months and failed to show any feature of inflammatory vascular involvement in three of the five cases that were analysed. CONCLUSIONS: The study emphasises the high incidence of immunopathological features of microvascular damage in patients with RV. LSG biopsy is minimally invasive and may be a potential useful tool for the diagnosis of RV especially when skin lesions are absent or impossible to biopsy. The assessment of the predictive value of positive LSG biopsy in RA requires a long term prospective study.

Aged↗

[The risk/benefit ratio of low-dose cyclosporin in the treatment of severe rheumatoid arthritis].

Although the efficacy of cyclosporine therapy in rheumatoid arthritis has been established, there have been no long term studies of the risk/benefit ratio of cyclosporine A in severe rheumatoid arthritis. A prospective, open-label one-year study included 106 patients (83 women and 23 men; mean age 53 years; mean disease duration, 11 years) with rheumatoid arthritis. Mean number of previous second-line treatments was four and 69% of patients had failed methotrexate therapy. The initial dosage of cyclosporine was 3 mg/kg/d and was increased if needed up to 5 mg/kg/d. The dosage was reduced in the event of serum creatinine elevation (by more than 30% versus baseline) or diastolic blood pressure elevation (above 95 mmHg). The statistical analysis was performed on an intention-to-treat basis. In the 45 patients who completed the one-year study period, the mean dosage was 3.6 +/- 1 mg after six months and 3.3 +/- 1 mg/kg/d after one year. Significant improvements were seen in all the clinical efficacy parameters. The mean reduction in corticosteroid dosage was 0.5 mg/d. The study drug was discontinued prematurely in 61 patients (36 because of adverse events and 21 because of inefficacy). Twelve of the 56 patients with serum creatinine level elevation on at least one occasion and seven of the 35 patients with diastolic blood pressure elevation were taken off the study drug.

Adult↗

[Hip diseases in hemorrhagic rectocolitis. Apropos of 4 cases].

Erosive hip lesions are uncommon in patients with ulcerative colitis. We analyzed features of chronic hip lesions in four ulcerative colitis patients seen over the last 30 years. Two patients also had axial disease. Both hips were involved in all four cases. Roentgenographic features resembled those seen in ankylosing spondylitis in two cases. Severe destruction occurred in two patients. Two patients developed acetabular protrusion. All four patients rapidly required total hip arthroplasty, illustrating the poor prognosis of hip lesions associated with ulcerative colitis.

Adolescent↗

[Pigmented villonodular synovitis of the hip. Results of a national survey apropos of 58 cases].

Pigmented villonodular synovitis is an uncommon synovial disease which only rarely involves the hip. In a multicenter retrospective study, we identified 58 histologically-proven cases. There were 33 females and 25 males. Mean age at diagnosis was 38 years. In all but two cases, only one hip was involved; the right hip was affected somewhat more often (33 cases) than the left. Two patients probably had bilateral hip disease. Mean delay to diagnosis was four years. Pain was the presenting symptom in most cases. A palpable mass in the groin was found in six patients. Plain roentgenograms were considered normal in only three patients. Bony cysts were seen in 39 patients and kissing cysts in 19. Joint space narrowing was found in 40 patients and was diffuse in half the cases. Roentgenograms suggested pigmented villonodular synovitis in 63% of cases, osteoarthritis of the hip in 16%, and inflammatory hip disease in 14%. Additional imaging studies included opaque arthrography in 21 subjects, computed tomography in 23, magnetic resonance imaging in 11, and arthroscopy in 9. Initial treatment was osmic acid synoviorthesis in 14 patients, partial synovectomy in 9, and total synovectomy in 21; in addition, eight patients had insertion of a cup prosthesis and 13 had total arthroplasty of the hip. Treatment was successful in 65% of cases after a mean follow-up of three years; among the 35% of failures, there were seven recurrences (14%). Total hip arthroplasty was performed secondarily in nine patients. This study illustrates the diversity of roentgenological changes in pigmented villonodular synovitis of the hip and the high frequency of osteoarticular lesions precluding conservative treatment. Magnetic resonance imaging and/or arthroscopy should be used to establish the diagnosis at an early stage when conservative treatment with total synovectomy and synoviorthesis is most likely to be successful.

Adolescent↗

Increased capillary permeability in systemic rheumatoid vasculitis: detection by dynamic fluorescence nailfold videomicroscopy.

OBJECTIVE: Several histological studies suggest a vascular involvement in rheumatoid arthritis (RA). We evaluated morphological and functional changes of skin capillaries in patients with RA. METHODS: We studied capillary permeability by nailfold fluorescence videomicroscopy in patients with RA with and without systemic vasculitis to establish the sensitivity, specificity, and the prognostic value of the technique for the diagnosis of systemic rheumatoid vasculitis (SRV). Nine patients with SRV, 22 patients with active RA without signs of vasculitis, and 16 controls were evaluated. RESULTS: No difference in conventional capillaroscopy was observed when we compared patients with SRV and RA. Using fluorescence videomicroscopy after intravenous injection of fluorescein sodium, we observed an increase of transcapillary dye diffusion in 9/9 patients with SRV, in 13/22 patients with RA without vasculitis and in 4/16 control patients. Our results give a sensitivity of 100% in SRV, a specificity of 44%, a positive predictive value of 34% and a negative predictive value of 100%. CONCLUSION: Our present study points out the functional alteration of the capillary wall in patients with RA with or without vasculitis and suggests the usefulness of dynamic fluorescence nailfold capillaroscopy in patients with RA when systemic vasculitis is suspected, not as a diagnostic tool, but because of the high negative predictive value of the technique.

Aged↗

Aspergillus spondylodiscitis: successful conservative treatment in 9 cases.

OBJECTIVE: To assess the effectiveness of medical treatment by clinical, radiological, and biological analysis of outcome in 9 patients with aspergillus spondylodiscitis. METHODS: Retrospective study including 9 patients with aspergillus discitis, in which 7 were immunosuppressed; 3 were heart transplant patients, 2 had acute lymphoblastic leukemia, 1 hairy cell leukemia and one was receiving prednisone for bronchial asthma. Four patients had isolated spinal aspergillosis infection. In 4 cases, disc space infection occurred after pulmonary aspergillosis. In the last case the spondylodiscitis occurred after aspergillus endocarditis and mycotic limb embolism. In all cases a percutaneous needle biopsy of the intervertebral disc was performed; the subsequent culture produced Aspergillus fumigatus in 8 cases and Aspergillus flavus in 1. Itraconazole was given to all patients (mean dose: 350 mg/day); it was given alone in 2 cases, in addition to 5 flucytosine and amphotericin B in 6 cases, and in addition to amphotericin B in the last case. RESULTS: Improvement was obtained in the 9 cases, with full recovery in the absence of any surgical debridement after a mean treatment duration of 5.5 months and a mean followup delay of 16 months. CONCLUSION: Early recognition of aspergillus spondylodiscitis in immunocompromised hosts is important. Itraconazole alone or in combination is an effective therapy. There may be an increased incidence of aspergillus discitis due to the increasing frequency of immunosuppression associated conditions including organ transplantation, chemotherapy, or acquired immune deficiency syndrome.

Adult↗

Synovial fibroblast-like cell transfection with the SV40 large T antigen induces a transformed phenotype and permits transient tumor formation in immunodeficient mice.

OBJECTIVE: To understand the intracellular signals leading to transformed-like growth of synovial fibroblast-like cells from patients with rheumatoid arthritis (RA). METHODS: Cell lines stably transfected with one or both of 2 complementary oncogenes, the SV40 large T antigen and the ras oncogene, were studied for phenotypic changes. RESULTS: Synovial fibroblast-like cells stably transfected with the SV40 large T antigen, but not the ras oncogene, showed high levels of growth factor independent proliferation, grew under anchorage independent conditions, expressed cathepsin L mRNA, and formed transient tumors in immunodeficient mice. Synovial fibroblast-like cells stably transfected with both oncogenes appeared phenotypically similar to synovial fibroblast-like cells transfected with the large T antigen alone. CONCLUSION: The SV40 large T antigen confers a phenotype on synovial fibroblast-like cells similar to that stimulated by growth factors, suggesting that it stimulates the same intracellular signalling pathway leading to cytokine induced, transformed synovial fibroblast-like cell growth. When injected into immunodeficient mice these transfected cells formed tumors characterized by rapid, transient growth, central necrosis, and neutrophil infiltration.

Animals↗

[Value of the assay of protein SAA and urinary antitrypsin activity in osteoarticular infections].

Erythrocyte sedimentation rate is normal in 20% to 25% of patients with discitis due to common pathogens. We evaluated serum amyloid A (SAA) protein and urinary trypsin inhibitory activity in osteoarticular infections comparatively with erythrocyte sedimentation rate and serum C-reactive protein in 20 patients including 14 with discitis due to common pathogens and 6 with septic arthritis. Assays were performed on D0, D8, D15, D30, and D60 after initiation of antimicrobial therapy. On D0, all four markers were significantly higher in patients with septic arthritis than in patients with discitis. C-reactive protein levels exhibited the fastest kinetics with a return to normal values within 15 days in both conditions. Urinary trypsin inhibitory activity was only slightly elevated in patients with discitis and returned to normal within 30 days in both conditions. Serum amyloid A levels required 30 to 60 days to return to normal. Erythrocyte sedimentation rate exhibited the slowest kinetics, with normal values being achieved only after 60 days. Although simple, rapid, and inexpensive, urinary trypsin inhibitory activity determination exhibits poor sensitivity. Serum amyloid A assay is not routinely available but may be a valuable parameter for monitoring patients whose erythrocyte sedimentation rate and C-reactive protein level are normal (as in 2 of our patients with discitis).

Arthritis, Infectious↗

[Imaging of pigmented villonodular synovitis].

Pigmented villonodular synovitis is a rare disease which is usually benign but sometimes causes wide articular destruction. Since its clinical signs and symptoms are not specific, the disease may remain undiagnosed, sometimes for long periods. The diagnosis is generally confirmed at pathology, but it can now be strongly suggested by modern imaging methods. Standard radiography may be normal, with a variety of images. Arthrography with an opaque material points to the diagnosis in only two-third of the cases. Ultrasonography is non-specific. Computed tomography may be strongly suggestive of pigmented villonodular synovitis in cases with high density synovia; when coupled with arthrography, it provides detailed information on lesions of the cartilage and on extension of the synovial process. The most sensitive and specific method is magnetic resonance imaging, the most characteristic sign being low-intensity signal areas on T1- and T2-weighted sequences, corresponding to haemosiderin-loaded nodules. Performed after standard radiography, magnetic resonance imaging is the best examination method for the diagnosis and pretherapeutic evaluation of suspected villonodular synovitis.

Humans↗

Labial salivary gland biopsy is a reliable test for the diagnosis of primary and secondary amyloidosis. A prospective clinical and immunohistologic study in 59 patients.

OBJECTIVE: Reports of the detection of amyloidosis by labial salivary gland (LSG) biopsy have been mostly anecdotal. The aim of this study was to assess the value of this method in the diagnosis of amyloidosis. METHODS: LSG biopsy tissues were studied with a combination method using Congo red stain and immunohistologic characterization using an antibody directed against the serum amyloid P (SAP) component. Electron microscopy was performed in all cases. In a prospective study, we evaluated 30 patients with biopsy-proven AA or AL amyloidosis. We compared these patients with a control group of 29 age-matched patients without clinical or biologic evidence of amyloid disease (14 had rheumatoid arthritis and 15 had plasma cell dyscrasia). RESULTS: In 26 of the 30 patients with known systemic amyloidosis, amyloid deposits were identified on LSG biopsy (sensitivity of 86%). In 1 of the remaining patients, amyloid deposits were identified on LSG biopsy and systemic amyloidosis was confirmed by abdominal fat biopsy and 123I-labeled SAP scintigraphy. CONCLUSION: This study emphasizes the high sensitivity of LSG biopsy in the diagnosis of amyloidosis, even in the absence of oral symptoms.

Adult↗

Stimulation of the secretion of latent cysteine proteinase activity by tumor necrosis factor alpha and interleukin-1.

OBJECTIVE: Cultured synovial fibroblast-like cells from 3 patients with rheumatoid arthritis (RA) and 3 patients with osteoarthritis (OA) were evaluated for their potential to secrete cysteine proteinases spontaneously and after stimulation by tumor necrosis factor alpha (TNF alpha) or interleukin-1 (IL-1). METHODS: Culture media and cell lysates were analyzed before and after high performance liquid chromatography (HPLC) using the enzymatic substrate, Z-Phe-Arg-AMC, and by immunoblotting with anti-cathepsin B antiserum. Immunolocalization of cathepsin B was studied on cell monolayers. RESULTS: Latent cysteine proteinase activity was found to be secreted spontaneously by cultured synovial fibroblast-like cells. This activity was increased after treatment with either TNF alpha or IL-1. Stimulated protease activity was eluted by HPLC at a peak coincident with that of purified cathepsin B. By immunoblot, cell supernatants contained a 43-kd form of cathepsin B, while cell lysates contained a 30-kd form, consistent, respectively, with cathepsin B before and after cleavage of its propeptide. An intracellular increase in cathepsin B after treatment with TNF alpha was also seen with immunohistochemical studies. CONCLUSION: TNF alpha (in the 6 cases studied) and IL-1 (in 4 cases) stimulated the secretion of a latent cysteine proteinase activity from synovial fibroblast-like cells, which appears to represent primarily cathepsin B.

Arthritis, Rheumatoid↗

[Rheumatoid polyarthritis in the elderly--rhizomelic pseudopolyarthritis: what differences?].

The authors have conducted a comparative retrospective study between polymyalgia rheumatic (N = 26) and rheumatoid arthritis in the elderly (N = 44), including HLA DRB1 genotype determination by PCR-RFLP analysis. No clinical nor biological differences were significant between the 2 groups of patients. However 70% of RA patients had one ore more susceptibility alleles (shared epitope hypothesis) and 50% in polymyalgia rheumatica.

Aged↗

[Systemic manifestations of rheumatoid arthritis: prognostic value of the HLA DRB1 0405 allele].

The aim of the present study was to determine HLA DRB1* genotype by PCR-RFLP analysis in patients with rheumatoid arthritis (N = 122) associated with extra-articular manifestations (N = 24). A significant increased of DRB1* 0405 was found in RA patients with extra-cellular involvement (odd-ratio = 8.33, confidence interval = 1.44 - 56.7). In patients with RA, HLA DRB1*0405 allele might constitute a susceptibility marker of extra-articular involvement such as vasulitis or cardio-pulmonary manifestations.

Alleles↗