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Biomedical subjects

R M Flipo

Publications and source records attributed to R M Flipo.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1997

Treatment of severe, recalcitrant reflex sympathetic dystrophy: assessment of efficacy and safety of the second generation bisphosphonate pamidronate.

The objective of the study was to assess the efficacy and the safety of pamidronate (APD) in recalcitrant reflex sympathetic dystrophy (RSD). Ten women and 13 men with a mean (+/-standard deviation, SD) age of 44 +/- 11 years were included. The involved sites were: the ankle (n = 10), the foot (n = 7), the hand (n = 3), the hip (n = 2), the knee (n = 2) and the shoulder (n = 1). Some patients had more than one site involved. Mean (+/-SD) duration of the disease was 15 +/- 13 months. RSD was in pseudo-inflammatory phase in 16 patients and in ischaemic phase in 7 patients. RSD was post-traumatic in 17 cases; 11 patients have been previously treated unsuccessfully by sympathetic blockades. APD was administered intravenously (perfusion) to a dose of 1 mg/kg/day during 3, 2 or one day. Fourteen patients received APD during 3 consecutive days whereas 7 patients have been treated during 2 consecutive days and 2 patients only during 1 day mainly due to adverse events. Efficacy was assessed by a decrease of pain = visual analogic scale (VAS, 0-100 mm) and verbal scale (PVS, range 0-3). Moreover, the patient and the observer have estimated the efficacy of the treatment on a verbal scale (EVS, range 0-3). Measurements of these parameters were performed immediately before the treatment and 7, 30, 60 and 90 days later. The maximum duration after treatment was 9 months. A significant decrease of VAS and PVS were observed between D0 and D30 (p = 0.0002 and p = 0.0002 respectively), D0 and D60 (p = 0.0004, p = 0.0004 respectively), and D0 and D90 (p = 0.00003, p = 0.0001 respectively). A significant increase of EVS was only observed between D0 and D90 (p = 0.03). Adverse events were noted in 14 patients: transient fever (n = 6), venous inflammation (n = 2), transient symptomless hypocalcaemia (n = 3), nausea (n = 1), lymphopenia (n = 1), transient hypertension (n = 1). These results suggest an efficacy of APD in recalcitrant RSD. Double-blind placebo controlled studies are required to back up these preliminary results.

Adult↗
PubMed1997

Natural course of erosive arthropathy of the hand in patients undergoing hemodialysis.

OBJECTIVE: To assess the radiographic features of erosive arthropathy of the hands occurring in patients undergoing hemodialysis, and its relationship with metabolic abnormalities. PATIENTS AND DESIGN: A retrospective study of hand radiographs of 80 patients on maintenance hemodialysis was performed with the aim of detecting erosive arthropathy. RESULTS AND CONCLUSIONS: Ten patients showed erosive arthropathy of the hands with a predilection for distal interphalangeal joints. The first joint abnormality was joint space narrowing with or without erosion. The mean duration of hemodialysis was 5 years (range 1-15 years). The development of arthropathy could not be related to a metabolic factor. The pathogenesis of arthropathy of the hands is possibly multifactorial, accounting for the disparate descriptions of the radiographic features in the literature.

Adult↗
PubMed1997

[Osteoporosis in pregnancy: apropos of 2 cases].

Two women, 31 and 19 years old, developed acute back pain with non-traumatic vertebral fractures one month after delivery in one case, and during the 9th month of gestation in the second case. For the first patient, the evolution was favorable with an increase of bone mineral density (15.2% over fourteen months under calcium and vitamin D). Ten years later, the osteoporosis of the second patient worsened without any new pregnancy. Our observations suggest the possibility of different pathogenies in pregnancy-associated osteoporosis.

Adult↗
PubMed1997

Selective induction of the secretion of cathepsins B and L by cytokines in synovial fibroblast-like cells.

We have investigated the potent influence of some cytokines, tumour necrosis factor-alpha (TNF-alpha), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and interferon-gamma (IFN-gamma), on the secretion of cysteine proteinases (cathepsins B and L) by cultured synovial fibroblast-like cells from patients with rheumatoid arthritis (RA). After treatment of synovial fibroblast-like cells with cytokines, culture media were evaluated for cathepsins B and L by enzyme immunoassays, and for cathepsin B and L activities using the enzymatic substrates. Z-Phe-Arg-AMC and Z-Arg-Arg-AMC, and specific inhibitors. Treatment of synovial fibroblast-like cells with TNF-alpha or PDGF resulted in a marked increase in cathepsin B secretion. Moreover, after prolonged PDGF treatment, the amount of secreted cathepsin B returned to the low control level. In contrast, bFGF led to increased cathepsin L secretion. IFN-gamma induced both cathepsin B and L secretion. Our results show that cytokines induce a selective secretion of cathepsins B and L by synovial fibroblast-like cells. This selective effect of cytokines on the secretion of cysteine proteinases suggests that synovial fibroblast-like cell-mediated articular degradation is a highly regulated process.

Arthritis, Rheumatoid↗
PubMed1997

ICAM-1, E-selectin, and TNF alpha expression in labial salivary glands of patients with rheumatoid vasculitis.

OBJECTIVE: To assess the expression of ICAM1, VCAM1, E-selectin, CD44, and TNF alpha in labial salivary glands of patients with rheumatoid vasculitis. METHODS: Labial salivary glands from six patients with rheumatoid vasculitis before and after treatment, six aged matched rheumatoid arthritis patients without clinical evidence of rheumatoid vasculitis, 10 patients with primary Sjögren syndrome, 10 patients with rheumatoid arthritis and proven secondary Sjögren syndrome, and six controls were tested with specific antibodies. RESULTS: ICAM1, E-selectin, and TNF alpha were significantly expressed in endothelial cells and perivascular cellular infiltrate only in rheumatoid vasculitis before treatment. CONCLUSIONS: The expression of ICAM1, E-selectin, and TNF alpha allows an assessment of the activity of the vasculitic process in rheumatoid vasculitis. Labial salivary gland biopsy findings in patients with rheumatoid arthritis and visceral vasculitis without purpura or neuropathy (that is, mesenteric, coronary, or cerebral vasculitis) would be of interest and are examples where labial salivary gland tissue is more accessible than the affected tissue.

Arthritis, Rheumatoid↗
PubMed1997

Pulmonary function tests and high resolution computed tomography of the lungs in patients with rheumatoid arthritis.

OBJECTIVE: To compare the results of pulmonary function tests (PFTs) and high resolution computed tomography (HRCT) of the lungs in rheumatoid arthritis (RA) patients. METHODS: Sixty eight patients (54 women, 14 men) fulfilling the revised criteria for RA were consecutively included in a transversal prospective study. Their mean age was 58.8 years (range: 35-82) and the mean duration of the disease was 12 years (range: 5-16). Rheumatoid factor was positive in 52 patients (76.5%). Fifty two patients (76.5%) were lifelong non-smokers. Detailed medical and drug histories were obtained. PFTs comprised spirometry and gas transfer measurements. Results for PFTs were expressed as percentage of predicted values for each individual adjusted for age, sex, and height. HRCT was undertaken with a Siemens Somatom Plus. RESULTS: A significant decrease of FEV1/ FVC, FEF25%, FEF50%, FEF75%, FEF25-75%, and TLCO was observed (p < 0.05) and 13.2% of the patients had a small airways involvement defined by a decrease of FEF25-75% below 1.64 SD. The most frequent HRCT findings were: bronchiectasis (30.5%), pulmonary nodules (28%), and air trapping (25%). The patients with small airways involvement had a high frequency of recurrent bronchitis (75% v 34%, p = 0.05) and bronchiectasis (71% v 23%, p = 0.019). The patients with bronchiectasis were characterised by low values of FEV1, FVC, FEF25-75%, and TLCO (p < 0.01), a high prevalence of small airways involvement (29% v 5%, p = 0.019), and a low prevalence of HLA DQA1 *0501 allele (14% v 33%, p < 0.05). CONCLUSION: This study suggests a significant association between small airways involvement on PFTs and bronchiectasis on HRCT in unselected RA patients.

Adult↗
PubMed1997

How useful are bone turnover markers in rheumatoid arthritis? Influence of disease activity and corticosteroid therapy.

UNLABELLED: Rheumatoid arthritis is associated with osteopenia possibly related to increased bone resorption. Until recently, the markers used to evaluate bone turnover lacked specificity, and as a result studies were difficult to interpret. OBJECTIVES: To study bone remodeling in patients with rheumatoid arthritis, with special attention to the effects of corticosteroid therapy. PATIENTS AND METHODS: Forty-eight patients (36 women and 12 men) with a mean age of 54.6 +/- 11.6 years and a mean disease duration of 11 +/- 9 years were studied. Thirty-nine patients (81%) had positive tests for rheumatoid factors, and 21 (43.7%) were under corticosteroid therapy, with a mean treatment duration of 4.5 +/- 2.9 years and a mean daily dosage of 9.4 +/- 2.5 mg prednisone. A group of age- and sex-matched controls was also studied. Serum levels of procollagen Type I C-terminal propeptide (PINP), procollagen Type I N-terminal propeptide (PINP), and procollagen type I C-terminal telopeptide (ICTP) were determined in all patients and controls. The first two markers reflect bone formation and the last bone resorption. Other tests performed in each patient were the erythrocyte sedimentation rate, serum C-reactive protein, serum total alkaline phosphatase, serum osteocalcin, 24-hour urinary hydroxyproline excretion, and calcium/creatinine ratio in a morning urine sample. Several clinical parameters were used to evaluate disease activity and severity in the rheumatoid arthritis patients. RESULTS: ICTP levels were significantly elevated in the patients as compared with the controls (6.6 +/- 3.9 ng/ml versus 3.1 +/- 1.2 ng/ml, P = 0.0001), whereas no significant differences were found for PICP or PINP. Similar results were found when the analysis was confined to nonsteroid-medicated patients. Conversely, PICP levels were higher in steroid-medicated patients than in controls (P = 0.0132) and were correlated with steroid therapy duration (r = 0.436). ICTP levels were correlated with age (r = 0.3), Lee's index (r = 0.585), the Health Assessment Questionnaire score (r = 0.391), and the erythrocyte sedimentation rate (r = 0.442). Urinary hydroxyproline excretion was elevated in 41.6% of the patients. CONCLUSION: Our data suggest that rheumatoid arthritis is associated with increased bone resorption, and that steroid therapy further accelerates bone remodeling in this disease.

Adrenal Cortex Hormones↗
PubMed1997

Percutaneous vertebroplasty in patients with osteolytic metastases or multiple myeloma.

UNLABELLED: Osteolytic metastases and spinal myeloma lesions are difficult to treat because they denote disseminated malignant disease. The pain-relieving and other effects of radiation therapy are delayed. We evaluated short- and medium-term outcomes of vertebroplasty in this indication, in patients with severe or excruciatingly severe pain (McGill-Melsack score 4 or 5) unresponsive to narcotics. PATIENTS AND METHODS: forty vertebras were treated in 37 patients including 29 with bone metastases and eight with multiple myeloma. Mean age was 58 years (range 36-83). The spinal segment involved was the cervical spine in five cases, the thoracic spine in 12 and the lumbar spine in 23. Vertebroplasty was done under fluoroscopy guidance after premedication and local anesthesia. RESULTS: thirty-six patients (97.3%) reported a decrease in their pain 48 hours after the procedure; five of these patients (13.5%) were completely free of pain, 20 (55%) were significantly improved and 11 (30%) were moderately improved. One patient failed to respond. The clinical results were not correlated to the extent of vertebral body filling. Beneficial effects were increased or unchanged in 100% of cases after one month, 88.9% after three months and 75% after six months. Leakage of the cement outside the vertebral body occurred in 29 cases (72.5%), usually into the paraspinal soft tissues (n = 21,52.5%). Leakage was usually clinically silent and only two patients developed severe nerve root pain due to leakage into a neural foramen, with in both instances a favorable outcome after surgery. CONCLUSION: Vertebro- plasty is simple and effective for the treatment of osteolytic metastases and multiple myeloma lesions, but should be performed only in centers with neurosurgical and/or orthopedic surgery units because of the possibility of severe complications.

Adult↗