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Biomedical subjects

R M Flipo

Publications and source records attributed to R M Flipo.

At least 19 recordsLinked to original sources
PubMed2000

Microemulsion formulation of cyclosporin (Sandimmun Neoral) vs Sandimmun: comparative safety, tolerability and efficacy in severe active rheumatoid arthritis. On behalf of the OLR 302 Study Group.

OBJECTIVE: To compare the safety, tolerability and efficacy of the new oral microemulsion formulation of cyclosporin A (CyA; Sandimmun Neoral) and the original CyA formulation (Sandimmun), in patients with severe active rheumatoid arthritis (RA), over a 12-month period. METHODS: In this double-blind, multicentre study, patients were randomized to treatment with Neoral or Sandimmun, starting with 2.5 mg/kg/day, with dose adjustments after 4 weeks. Primary efficacy criteria included patients' assessment of disease activity. Pharmacokinetic and safety assessments were performed at regular intervals. RESULTS: Compared with Sandimmun, Neoral showed a consistent trend towards greater clinical efficacy from week 12 onwards, including a significant difference in patients' assessment of disease activity at the study end-points. A significantly lower increase in dose from baseline was observed with Neoral at week 24. Pharmacokinetic assessments at week 24 showed increased absorption and decreased variability with Neoral. No differences in safety were found between treatment groups. CONCLUSION: These observations indicate that Neoral is as safe and at least as effective as Sandimmun and have important implications for patient management given the increasing role for CyA in the treatment of severe, active RA.

Antirheumatic Agents↗
PubMed2000

Arthritis, tenosynovitis, fasciitis, and bursitis due to sea urchin spines. A series of 12 cases in Réunion Island.

UNLABELLED: Arthritis, tenosynovitis, and bursitis due to sea urchin spine injuries have unique pathological features and run a chronic course until the spines are removed. Of the 40 cases of sea urchin spine-related clinical symptoms published to date, only 12 had osteoarticular symptoms. PATIENTS AND METHODS: We studied 12 cases with osteoarticular symptoms seen in Réunion Island from 1994 to 1998. There were nine cases of arthritis and one case each of tenosynovitis, fasciitis, and bursitis. The nine males and three females had an age range of 9 to 50 years. RESULTS: The injury was at the knee in six cases, the foot in three, and the hand in three. The time from injury to lesion development ranged from two days to two and a half months. Laboratory tests were normal apart from evidence of mild inflammation in three of the arthritis cases. The spine was visible on plain radiographs in eight cases. Histology was done in seven patients and consistently showed a typical foreign body granuloma. Removal of the spine with synovectomy was performed in 11 cases and consistently ensured a full recovery. DISCUSSION: The clinical manifestations and management in our patients were compared to those in earlier reports. The differential diagnosis of laboratory test, radiographic, and histologic findings is reviewed. Pathogenic hypotheses and the immunogenic effect of the protein sheath that surrounds sea urchin spines are discussed. CONCLUSION: The diagnosis of these frequently under-recognized lesions rests on a careful history and on converging histologic, radiologic, and clinical findings.

Adolescent↗
PubMed2000

Rheumatologic manifestations of pachydermoperiostosis and preliminary experience with bisphosphonates.

OBJECTIVE: Pachydermoperiostosis is manifested by finger clubbing, hypertrophic skin changes, and periosteal bone formation. We describe 5 cases revealed primarily by their rheumatologic manifestations. Also reported are preliminary experiences on the use of intravenous pamidronate as a treatment. METHODS: This is a retrospective study including the analysis of clinical manifestations, laboratory results and morphological examinations gathered from patients' medical records. We evaluated efficacy of treatment with 1 mg/kg iv pamidronate in the 3 new cases. RESULTS: Before treatment with iv pamidronate, the patients' global assessment was poor (twice) and very poor (once). The physician's global assessment was poor in 3 patients. After treatment with iv pamidronate, 2 patients had significant improvement. Physician and patient global assessments were very good, good, and moderate. No side effects were observed. All biological variables were within normal ranges at 12 month followup visit. CONCLUSION: Pachydermoperiostosis must be recognized by the rheumatologist, since it can present symptomatically through articular manifestations. When conventional treatment modalities fail, iv pamidronate might be useful.

Adult↗
PubMed1999

Ultrasound velocity through the phalanges in normal and osteoporotic patients.

Quantitative ultrasound (US) measurements have been shown to be a new technique assessing bone status. This study aimed to assess a new US instrument, the DBM Sonic 1200(R) (IGEA) which permits the measurement of the speed of sound in the proximal phalanges (SOSp) of the hand. The results obtained were compared with DXA (SOPHOS) and US measurements at the calcaneus (Achilles(R) LUNAR). The in vivo precision expressed by coefficient of variation was 0.91%. Ultrasound measurements of phalanges were significantly correlated with BMD in the entire group of 90 subjects: osteoporotic patients (n = 47) and controls (n = 43) (r = 0.44, femoral neck and 0.45, lumbar spine, P < 0.01). A significant correlation was also found in the control group (r = 0.33, lumbar spine and 0.38, femoral neck, P < 0.05) but not in the osteoporotic group (r = 0.3, lumbar spine and 0.17, femoral neck, P > 0.05). Mean values for 31 postmenopausal, osteoporotic women and age-matched controls showed a significant decrease in US measurements at the phalanges (P < 0.05) and the calcaneus (P < 0.01) as well as bone mineral density (BMD) at the spine and femoral neck (P < 0.01) in the osteoporotic group. A decision threshold for a sensitivity of 80% for osteoporotic fractures resulted in a specificity value of only 37% for SOSp, between 53 to 65% for calcaneus US measurements and 45 to 56% for BMD. The Z score, the odds ratio, the ROC curves, and areas under the curves plotted for the subgroup of 31 fractures and their healthy controls showed poorer values for SOSp than BMD and calcaneus US measurements. In conclusion, US measurements of phalanges seem to be less efficient than calcaneus US and BMD measurements to distinguish osteoporotic from healthy women. Other studies and also prospective studies are required to assess the interest in fracture risk assessment.

Aged↗
PubMed1999

[Prevalence of antiphospholipid antibodies in Horton's disease and in polymyalgia rheumatica].

PURPOSE: Antiphospholipid antibodies (APL) are frequently observed in the course of giant cell arteritis and polymyalgia rheumatica. However, their role and relationships with potential ischemic events are still debated. METHODS: To determine the prevalence of APL in relation with ischemic events, 62 patients with giant cell arteritis and/or polymyalgia rheumatica were retrospectively studied. RESULTS: Before corticosteroid treatment 41% of the 51 patients with giant cell arteritis and 64% of the 11 patients with isolated polymyalgic rheumatica had high IgG ACL levels, with a frequency significantly higher than that (15.6%) of the control group which was composed of healthy elderly. IgM ACL were found in only two patients with giant cell arteritis. There was no correlation between the occurrence of an ischemic event (22 ischemic events in the 51 patients with giant cell arteritis) and the presence of ACL, even though the latter were more frequently observed in the giant cell arteritis group (52% versus 41% in non ischemic patients). The prevalence of ACL increased, reaching 59% if lupus anticoagulant was associated, but the difference was not significant. ACL disappeared soon after corticosteroid therapy had been initiated. CONCLUSION: Though ACL are frequently seen in giant cell arteritis and/or polymyalgia rheumatica, they are not related to ischemic events and disappear rapidly after corticosteroid treatment.

Adrenal Cortex Hormones↗
PubMed1999

Synovectomy combined with the Sauvé-Kapandji procedure for the rheumatoid wrist.

The aim of synovectomy-stabilization (synovectomy combined with the Sauvé-Kapandji procedure) of the rheumatoid wrist is to obtain a stable painless wrist, retaining enough mobility for function. Thirty-nine wrists were retrospectively examined, at a mean follow up of 64.8 months. The improvement in pain was very significant. We noticed a decrease in wrist motion affecting both flexion and radial deviation. The arthritic change in the wrist continued to increase. We noticed a mean ulnar shift of 2.2 mm and a mean increase in the radial deviation of the wrist of 7 degrees. Only transfer of the extensor carpi radialis longus tendon to the extensor carpi radialis brevis tendon was effective in correcting radial deviation of the carpus. Ninety-seven per cent of patients were very satisfied or satisfied. These encouraging results, even at advanced stages of wrist arthritis, have prompted us to lessen the indications for wrist arthrodesis.

Adult↗
PubMed1999

Percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fractures: an open prospective study.

OBJECTIVE: To assess the efficacy and safety of percutaneous vertebroplasty in osteoporotic vertebral compression fractures responsible for severe and persistent pain. METHODS: Sixteen patients were included in this open prospective study. Inclusion criteria were: one or 2 vertebral fractures responsible for severe pain, i.e., higher than 50 mm on a visual analog scale (VAS: 0-100 mm), scores 3, 4 or 5 according to the McGill-Melzack scoring system, and evolving for more than 3 months. Assessment criteria were the changes over time (Days 3, 30, 90, 180) in VAS and McGill-Melzack scoring system. The changes over time in a generic health status instrument score [the Nottingham Health Profile (NHP)] were also assessed. Statistical comparisons were performed using the Wilcoxon T test. RESULTS: There were 9 women and 7 men: postmenopausal osteoporosis (n = 7), corticosteroid induced osteoporosis (n = 2), and male osteoporosis (n = 7). Vertebroplasty was performed in 20 vertebrae. A statistically significant decrease of both VAS (-53%, p < 0.0005) and McGill-Melzack scoring system (p < 0.005) was observed at Day 3. The results were also significant at Days 30, 90, and 180 for both scales (p < 0.005 and p < 0.01, respectively). A significant decrease over time for 5/6 dimensions of the NHP score was also noted: pain (p < 0.01), physical mobility (p < 0.05), emotional reactions (p < 0.05), social isolation (p < 0.05), and energy (p < 0.05). We observed no adverse event, and no vertebral fracture has occurred after 6 months of followup. CONCLUSION: Percutaneous vertebroplasty is a useful and safe procedure for treating persistent painful osteoporotic fractures. Controlled studies with longterm followup are required.

Aged↗
PubMed1999

Contribution of magnetic resonance imaging to the diagnosis of extraskeletal Ewing's sarcoma.

A case of extraskeletal Ewing's sarcoma presenting as a large gluteal mass is reported. This is a rare tumor with a frequently grim prognosis. Although the definitive diagnosis requires histological examination, magnetic resonance imaging is useful for determining the location of the tumor, evaluating its spread, and eliminating skeletal Ewing's sarcoma by establishing the integrity of the neighboring bone marrow. The tumor is seen on T1-weighted images as low signal with heterogeneous postgadolinium enhancement. Signal intensity on T2-weighted images is variable. In the case reported here, combination chemotherapy with external beam radiation therapy was ineffective, and the patient died 12 months after the diagnosis.

Adult↗
PubMed1998

Genotypic and phenotypic analysis of the polymorphic thiopurine S-methyltransferase gene (TPMT) in a European population.

1. Characterization of allelic variants of the TPMT gene (TPMT) responsible for changes in TPMT activity, and elucidation of the mechanism by which these alleles act, are required because of the clinical importance of this polymorphism for patients receiving thiopurine drugs. 2. We defined the mutational and allelic spectrum of TPMT in a group of 191 Europeans. Using PCR-SSCP, we screened for mutation the entire coding sequence, the exon-intron boundaries, the promoter region and the 3'-flanking region of the gene. Six mutations were detected throughout the ten exons and seven TPMT alleles were characterized. Four of them, TPMT*2, *3A, *3C and *7, harbouring the known mutations, G238C, G460A, A719G or T681G, were nonfunctional and accounted for 0.5, 5.7, 0.8 and 0.3% of the allele totality, respectively. 3. Within the promoter region, six alleles corresponding to a variable number of tandem repeats (VNTR), were identified. VNTR*V4 and *V5a which harbour four or five repeats of a 17-18 bp unit, were the most frequent (55% and 34%, respectively). The other VNTR alleles, having from five to eight repeats, were rarer. 4. The TPMT phenotype was correctly predicted by genotyping for 87% of individuals. A clear negative correlation between the total number of repeats from both alleles and the TPMT activity level was observed, indicating that VNTRs contribute to interindividual variations of TPMT activity. Therefore, additional analysis of the promoter region of TPMT can improve the phenotype prediction rate by genotyping.

Alleles↗
PubMed1998

Diagnostic value for rheumatoid arthritis of antiperinuclear factor at the 1:100 threshold. Study of 600 patients and meta-analysis of the literature.

Six hundred sera from patients with chronic rheumatic diseases including 429 with rheumatoid arthritis were tested in a blind fashion for IgG antiperinuclear factor using an indirect fluorescent antibody assay on buccal cells. Using the dilution of 1:100 found to be optimal in an earlier study, 283 of the 429 (66%) rheumatoid arthritis sera and 22 of the 171 (13%) control sera were positive for antiperinuclear factor. Titers were higher in the rheumatoid arthritis group than in the control group. A meta-analysis of studies that used sera diluted 1:80 or 1:100 (2853 sera including 939 from patients with rheumatoid arthritis, 1539 from patients with other rheumatic diseases and 375 from healthy controls or patients with unclassified rheumatic diseases) yielded a sensitivity of 0.75, a specificity of 0.93, and a positive predictive value of 0.87. These data demonstrate that antiperinuclear factor testing contributes usefully to the diagnosis of rheumatoid arthritis.

Adolescent↗
PubMed1998

Safety and tolerability of conversion from stable Sandimmun maintenance treatment to Sandimmun Neoral in patients with rheumatoid arthritis.

OBJECTIVE: To assess the safety and tolerability of converting patients with rheumatoid arthritis (RA) taking a stable dose of cyclosporin A (CyA) maintenance treatment (Sandimmun, SIM) to a new microemulsion capsule formulation, Sandimmun Neoral (Neoral), at an initial dose of 2.5 mg/kg/day. METHODS: In this single arm, open multicenter study, 28 patients were recruited to enter a 6 week pre-conversion period; of these, 22 patients completed 12 weeks' treatment with Neoral. RESULTS: During the 12 week post-conversion period, 11 patients experienced adverse events considered to be drug related; most were mild to moderate in severity and reflected the known safety profile for CyA. Only slight differences in efficacy variables were observed after conversion. The mean Neoral dose at Week 12 (2.84 mg/kg/day) was lower than the mean SIM pre-conversion dose (3.38 mg/kg/day). The study showed that, in patients with RA undergoing stable SIM maintenance treatment, conversion to an initial Neoral dose of 2.5 mg/kg/day did not give rise to any clinically relevant safety and tolerability concerns, and efficacy of the treatment was maintained compared with SIM. CONCLUSION: This conversion strategy constitutes a clinically acceptable alternative to a 1:1 dose conversion.

Adult↗
PubMed1998

A randomized, double blind, placebo controlled multicenter trial of murine anti-CD4 monoclonal antibody therapy in rheumatoid arthritis.

OBJECTIVE: To assess safety and efficacy of a murine anti-CD4 monoclonal antibody (Mab) in a population of patients with rheumatoid arthritis (RA) compared to treatment with placebo. METHODS: Fifty-eight patients with defined RA were included in this placebo controlled, randomized, double blind, multicenter study. Of the 48 women and 10 men (mean age 54.5 years), 25 were functional class II and 31 were class III, with 9 years' disease duration; the mean of previous disease modifying antirheumatic drugs was 4; 49 were taking steroids (mean dosage 11 mg/day of prednisone). Eighty percent were rheumatoid factor positive. All were in an active state of the disease with: pain > 4 (mean at inclusion 6.6), tender joints > 4 (mean 12), swollen joint count > 3 (mean 9), morning stiffness > 45 min (mean 185), erythrocyte sedimentation rate > 30 mm (mean 59) or C-reactive protein (CRP) > 30 mg/l (mean 63). Treatment was randomized between murine anti-CD4 Mab (B-F5, Diaclone, 20 mg/day) or placebo intravenously for 10 consecutive days. Efficacy was assessed with a composite index (Paulus), with evaluation of number of patients with 20 or 50% improvement in each group. Changes in measures of single clinical or biological variables were also evaluated. RESULTS: The 2 groups were comparable at inclusion. Treatment was well tolerated. Mild side effects (chills, fever, rash) were seen in both groups. Percentage of patients with global 20 or 50% response did not differ between placebo and Mab groups at Day 10 or at Day 30. Evaluation of single variables showed reduced CRP, swollen joint count, and Ritchie index in some B-F5 patients at Day 10, although in the B-F5 group as a whole only CRP was significant. CONCLUSION: No significant improvement in RA after murine anti-CD4 Mab was observed.

Adult↗
PubMed1998

Factors linked to disease activity in a French cohort of patients with spondyloarthropathy.

OBJECTIVE: To identify risk factors associated with disease activity, in a group of patients with spondyloarthropathy (SpA) living in France. METHODS: Patients fulfilling the ESSG or Amor criteria for SpA were enrolled in a cross sectional multicenter study. Disease activity was assessed using a French version of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Univariate and multivariate analyses were used to identify a link between BASDAI and disease characteristics, genetic factors, and environmental factors such as infectious events, mental stress, working conditions, and dietary factors. RESULTS: We studied 293 patients. On multivariate analysis, BASDAI appeared to be mainly linked to disease duration (negative correlation), the absence of sacroiliitis, and the "frequency of meals taken out of home" (negative correlation). CONCLUSION: Disease activity in a French population of patients with SpA appeared to be linked mainly to a shorter disease duration and a peripheral pattern of arthritis, as well as to dietary habits. The underlying links between this last environmental factor and disease activity remained hypothetical and could only reflect a nontested social factor.

Adult↗
PubMed1998

Is bone turnover a determinant of bone mass in rheumatoid arthritis?

OBJECTIVE: To study the relationship between bone turnover markers and bone mineral density in patients with rheumatoid arthritis. METHODS: We studied 54 patients, 24 of whom were receiving low dose steroids, and compared them to 54 age and sex matched controls. RESULTS: An 8.2% decrease of femoral neck bone mineral density (BMD) was found in patients not taking steroids compared with controls (confidence interval 1.2-15.3%). Serum markers of bone turnover -- namely, procollagen type I C-terminal propeptide (PICP) and procollagen type I N-terminal propeptide (PINP), which reflect bone formation, and procollagen type I C-terminal telopeptide, which reflects bone resorption -- were significantly increased compared with controls (p < 0.05, p < 0.01, p < 0.01, respectively). Both PINP levels and PICP levels were correlated with the femoral neck BMD as well as osteocalcin levels: R = -0.32 (p < 0.05), R = -0.29 (p < 0.05), and R = -0.42 (p < 0.01), respectively. The best independent predictors of bone mass (stepwise multiple regression analysis) at the femoral neck were steroid use, osteocalcin levels, age, height, the presence of rheumatoid factor, and the Health Assessment Questionnaire score, which explained 61.6% of the variance in femoral neck BMD. CONCLUSION: Elderly patients with RA using steroids with severe disease and high levels of osteocalcin have marked osteoporosis at the hip.

Adult↗
PubMed1997

Association of rheumatoid arthritis with an amino acid allelic variation of the T cell receptor.

OBJECTIVE: To investigate allelic variations of T cell receptor residues for a contribution to rheumatoid arthritis (RA) susceptibility. METHODS: We conducted an RA case-control study involving 1,579 northwest Europeans: 766 patients with erosive and rheumatoid factor-positive disease and 813 control subjects. Productive changes of segments TCRAV6S1, TCRAV7S1, TCRAV8S1, TCRAV10S2, and TCRBV6S1, TCRBV6S7 were investigated by single-strand conformation polymorphisms. The TCRAV8S1 association was confirmed by restriction fragment length polymorphism. RESULTS: In the systematic study (77 patients and 119 controls), an increase in 1 TCRAV8S1 genotype was found in the RA patients (P = 0.0004). This finding was replicated in 2 further populations, one from France (212 patients and 254 controls) and the other from Britain (477 patients and 440 controls), with a similar odds ratio (OR), which allowed pooling of the data and confirmation of the association (OR 1.3 [95% confidence interval 1.1-1.7], P = 0.008). CONCLUSION: These findings show evidence that TCRA is an RA susceptibility locus.

Alleles↗