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J Sany

Publications and source records attributed to J Sany.

At least 55 records · Page 3Linked to original sources
PubMed1997

The AIMS2-SF: a short form of the Arthritis Impact Measurement Scales 2. French Quality of Life in Rheumatology Group.

OBJECTIVE: To develop a short form of the Arthritis Impact Measurement Scales 2 (AIMS2) questionnaire, preserving content validity as the priority criterion. METHODS: A 2-step reduction procedure was used: 1) Delphi technique, with 1 panel of patients and 1 panel of experts each selecting 1 set of items independently; and 2) nominal group technique, where members of both panels reached consensus on the final selection of items, using information derived from item analysis. Psychometric properties of the AIMS2-Short Form (AIMS2-SF) and AIMS2 were compared using data from a cohort of 127 rheumatoid arthritis patients who completed the AIMS2 twice prior to the initiation of methotrexate (MTX) treatment and 3 months post-initiation of MTX treatment. RESULTS: The 2 panels reached consensus on a 26-item AIMS2-SF (54.4% reduction from the AIMS2). Factor analysis showed preservation of the 5-component structure. Convergent validity (Physical and Symptom components with clinical variables: r = 0.24-0.59), test-retest reproducibility (intraclass correlation coefficient >0.7), and sensitivity to change at 3 months (standardized response mean 0.36-0.8, except Social Interaction component [0.08]) were very close to the values for the original AIMS2. CONCLUSION: The AIMS2-SF is a shorter version of the AIMS2 (i.e., available in 2-page format) and has psychometric properties similar to those of the AIMS2.

Activities of Daily Living↗
PubMed1997

Polymorphism of the HLA-DMA and DMB genes in rheumatoid arthritis.

OBJECTIVE: To determine whether the HLA-DMA and DMB genes, whose encoded molecules are involved in HLA class II-restricted antigen presentation, contribute to the genetic susceptibility to rheumatoid arthritis (RA). METHODS: One hundred ninety-one RA patients, 147 control subjects, and 218 HLA-DRB1 genotype-matched control subjects were oligotyped for DMA and DMB genes. RESULTS: DMA*0103 and DMB*0104 were significantly increased in the RA patients compared with the randomly selected and the matched controls, thus indicating a direct influence of the DM genes. After stratification of the patients and matched controls according to DRB1 genotypes, only DMA*0103 was increased in the RA patients with DRB1*01, as well as in the patients negative for the RA-susceptibility DR alleles. CONCLUSION: Our results suggest that DMA*0103 could play an additional role in the genetic susceptibility to RA.

Alleles↗
PubMed1997

Long-term follow-up of 453 rheumatoid arthritis patients treated with methotrexate: an open, retrospective, observational study.

A total of 453 rheumatoid arthritis (RA) patients were followed up for 35.2 +/- 27.9 months (range 3-106). The clinical parameters decreased significantly after 6 months. Twenty-eight patients were in remission (6.4%). Rheumatoid factor (RF) positivity was less common in the group of patients in remission, with a higher frequency of visits and methotrexate (MTX) onset after 65 yr. There was a significant degradation of radiographic lesions (n = 60). A total of 101 patients (23.1%) stopped MTX, for toxicity (n = 61) and failure (n = 20). The onset of MTX after 65 yr, a low number of visits and the occurrence of side-effects were predictive of MTX withdrawal. A total of 259 patients (59.3%) had side-effects. A Ritchie's index < or = 10, a lower polymorphonuclear cell count and the absence of RF were predictive of side-effects. The probability of being on MTX at 5 yr was 73%. This study confirms the high efficacy of MTX in RA.

Adult↗
PubMed1997

Autoantibodies predicting the outcome of rheumatoid arthritis: evaluation in two subsets of patients according to severity of radiographic damage.

OBJECTIVE: Autoantibodies such as rheumatoid factor (RF), antikeratin antibodies (AKA), antiperinuclear factor (APF), and anti-RA 33 antibodies are considered of value for the diagnosis of RA. The purpose of this study was to evaluate these autoantibodies as predictors of severe radiographic damage in rheumatoid arthritis (RA). PATIENTS AND METHODS: Eighty six patients with RA (70 women, 16 men) fulfilling 1987 ACR criteria were selected from a cohort of 469 patients followed up since the first year of RA onset because they could be divided in two groups according to the severity of the radiographic damage. These 86 patients had a mean (SD) disease duration of eight (four) years: 43 patients had severe radiographic damage (Larsen score > or = 2) and 43 had limited radiographic damage (Larsen score < 2). The two groups were matched by disease duration and sex. The following autoantibodies were looked for: RF, ANA, AKA, APF, and anti-RA 33 antibodies. In addition, HLA class II DR beta alleles and standard inflammatory parameters (erythrocyte sedimentation rate, C reactive protein) were determined. RESULTS: Patients with severe radiographic damage differed from those with limited radiographic damage in that they had higher RF (p = 0.01), APF (p < 0.02), and AKA (p = 0.001) titres. Stepwise regression analysis was done to calculate the odds ratios (OR) for each clinical and laboratory variable; only presence of cutaneous nodules (OR: 14.9; 95% CI: 7, 128), HLA DRB1*04 or DRB1*01 (OR: 7.53; 95% CI: 1.32, 42.9), AKA (OR: 3.11; 95%, CI: 0.58, 16.8), a high erythrocyte sedimentation rate (OR: 2.66; 95% CI: 0.60, 11.9), and a high C reactive protein value (OR: 7.4; 95% CI: 1.43, 38.1) were predictive of severe radiographic damage. CONCLUSION: These data suggest that the risk of severe radiographic damage in RA patients is higher when cutaneous nodules, HLA DRB1*04 or DRB1*01, and/or AKA are present. The other autoantibodies of diagnostic significance are of little help for predicting joint destruction.

Adolescent↗
PubMed1997

Study of eight cases of cancer in 426 rheumatoid arthritis patients treated with methotrexate.

OBJECTIVE: To report cancer cases in 426 rheumatoid arthritis patients treated with methotrexate, and determine whether there was an increased incidence of cancer compared with patients never treated with methotrexate (rheumatoid controls) and to the whole regional population. METHODS: The duration of methotrexate treatment was 37.4 (SD 27.9) months. This population was compared with 420 rheumatoid arthritis controls and with a regional population of 812,344 people. Life table analysis was performed to compare the cancer incidence in the two rheumatoid populations. Adjustment for potentially confounding factors was done. The indirect standardisation methods was used to compare each rheumatoid population with the regional population. RESULTS: Eight cases of cancer (1.88%; 4.04 cases/1000 person years) were diagnosed in the methotrexate population v six (1.43%; 58.8 cases/1000 person years) in the rheumatoid controls. The life table method showed a higher incidence of cancer in the rheumatoid controls (P = 0.0001). In a multivariate analysis (Cox model), the only significant factor explaining this difference in the cancer incidence was age (P = 0.02). In the regional population there were 6418 new cases of cancer (0.79%; 2.85 cases/1000 person years). By the indirect standardisation method, the ratio of observed cases to expected cases of cancer in each of the rheumatoid populations was not significantly different from 1. CONCLUSIONS: In these eight cases, methotrexate was not found to be responsible for generating cancers. However, because of data regarding lymphomas and methotrexate, and because of the short follow up, especially in the control group, longer prospective studies are warranted.

Adult↗
PubMed1997

Inflammatory joint disease after immunizations. A report of two cases.

Serious adverse effects of immunizations are uncommon. The hepatitis B vaccine has been implicated in a few dozen cases of extraarticular, systemic, or inflammatory joint disorders. We report two cases in which hepatitis A vaccination (Havrix, Smith Kline Beecham) was followed by a connective tissue disorder or a spondylarthropathy in two healthy males aged 50 and 24 years, respectively. Both patients were HLA B27-negative but carried the HLA DR1 and/or DR4 antigen. The outcome was favorable after treatment with a corticosteroid or a nonsteroidal antiinflammatory agent. The pathophysiology of immunization-related rheumatic disorders may involve circulating immune complexes and/or a mechanism similar to that seen in reactive arthritis, i.e., a genetically-determined susceptibility to the bacterial or viral antigens contained in vaccines.

Adult↗
PubMed1997

Total and free methotrexate pharmacokinetics in elderly patients with rheumatoid arthritis. A comparison with young patients.

OBJECTIVE: To determine the pharmacokinetics of methotrexate (MTX) in a group of patients 65 to 83 years of age and to compare the pharmacokinetic data to those in patients 21 to 45 years of age. METHODS: Thirty-eight elderly patients (8 men, 30 women) and 24 young patients (6 men, 18 women) underwent this pharmacokinetic study. They received intramuscular administration of MTX each week, at a dose varying from 7.5 to 15 mg depending on the patient. MTX concentrations in plasma and ultrafiltrate samples were assayed by a fluorescence polarization immunoassay. Pharmacokinetic variables were estimated using a Bayesian approach with population parameters as a priori information together with 2 plasma MTX concentrations (2 and 8 h after injection). RESULTS: The extent of unbound fraction and the volume of distribution were not statistically significantly different between the 2 age groups. The elimination half-life measures of the free and total MTX were greatest in the elderly group (p < 0.001). The total clearances of free and total MTX were inversely proportional to age (p < 0.001). CONCLUSION: MTX clearance decreases with decreasing creatinine clearance and smaller doses may be chosen in this group. Thus, a dosage regimen should be adjusted in elderly patients or in those with renal impairment.

Adult↗
PubMed1997

Gene transfer to human rheumatoid synovial tissue engrafted in SCID mice.

OBJECTIVE: To assess the feasibility of gene therapy in rheumatoid arthritis (RA) and determine the appropriate vector. METHODS: Human rheumatoid synovial tissue from 6 patients with RA was transduced ex vivo with a recombinant retroviral vector (pMFG.nlsLacZ) containing the Escherichia coli beta-galactosidase (beta-gal) gene in a coculture assay in the presence of 20 ng/ml tumor necrosis factor alpha (TNF-alpha) for promoting cell division. We also conducted in vitro infection experiments using an adenoviral vector (AdCMVSpl.LacZ) containing the beta-gal gene. After gene transduction, the synovial tissue was engrafted subcutaneously in 8-week-old severe combined immunodeficiency (SCID) CB17 mice. Beta-gal expression was then monitored as a function of time (up to 21 days) and of virus dose [up to 50 colony forming units (cfu)/cell]. The efficacy of direct in vivo gene transfer was also tested by injection of 10(6) cfu of pMFG.nlsLacZ into rheumatoid synovial tissue engrafted in SCID mice. RESULTS: When recombinant retroviral vector was used, 30 +/- 5% of ex vivo infected synovial cells were positive for staining. In synovial tissue implanted in SCID mice, beta-gal expression declined to 5% after one week, but persisted for at least 21 days. Direct injection of pMFG.nlsLacZ vector into the rheumatoid synovial tissue implanted in SCID mice allowed efficient and stable in vivo infection of the synovial tissue. Ex vivo gene transfer with adenoviral vector resulted in a 98% infection rate of the synovial lining cells. However, beta-gal activity declined 7 days after subcutaneous implantation. CONCLUSION: Highly efficient gene transfer in rheumatoid synovial tissue is achievable with both adenoviral and retroviral vectors, but the results were transient. Exogenous gene transfer through retroviral vectors required stimulation with TNF-alpha for synovial cell division and proviral integration. Direct in vivo gene transfer with recombinant retrovirus was shown to be efficient. Transduction of human synovial tissue engrafted in SCID mice is a potent tool for developing preclinical models of gene therapy in RA.

Adenoviridae↗
PubMed1996

[Combination regimens in rheumatoid arthritis].

The objective of combination regimens in the treatment of rheumatoid arthritis is to improve effectiveness (additive or synergistic effect) and reduce the rate of side effects. Many combinations have been tried. In general, compared with single-drug regimens, combination therapy does not increase toxicity but clinical improvement has not been proven. In addition, there is no evidence concerning the long-term effects of combination regimens. Despite these drawbacks, combining drugs known to be effective in rheumatoid arthritis alone may be an interesting alternative for patients who have responded incompletely to single drugs, particularly methotrexate. However, for both single-drug and combination regimens we are still lacking proof of a real beneficial effect in terms of reducing functional impairment, improving quality of life, lengthening life expectancy, or reducing overmortality resulting from rheumatoid arthritis. Long-term outcome may provide some answers. Finally, there are still several combinations to be studied including methotrexate with "targeted" drugs such as anti-CD4 and anti-TNF alpha antibodies or the soluble TNF alpha receptor.

Arthritis, Rheumatoid↗
PubMed1996

Cryocrystalglobulinemia as a cause of systemic vasculopathy and widespread erosive arthropathy.

This report describes the case of woman who was admitted to the hospital for highly destructive axial and peripheral arthropathy in association with acute malignant hypertension and skin purpura. Type I IgGkappa serum cryoglobulinemia was identified and was classified as a monoclonal gammopathy of unknown significance. Cryoglobulin was shown to crystallize in the serum and synovium fluid and was responsible for both granulomatous microcrystalline synovial inflammation and occlusive vasculopathy in the kidneys and skin. Cryocrystalglobulinemia pathogenicity and therapeutic implications are discussed.

Arthrography↗
PubMed1996

Sicca syndrome associated with hepatitis C virus infection.

OBJECTIVE: To determine the prevalence of hepatitis C virus (HCV) infection in patients with sicca syndrome, and to determine the clinical, immunologic, and genetic characteristics of sicca syndrome associated with HCV. METHODS: We conducted a prospective study in a university hospital immunology-rheumatology department. Sixty-two consecutive patients with sicca syndrome according to the European criteria for Sjögren's syndrome were included. HCV infection was diagnosed in patients with positive recombinant immunoblot assay findings and the presence of viral RNA in serum and saliva. Rheumatoid factor (RF), cryoglobulins, antinuclear antibodies, and anti-SS-A/SS-B antibodies were sought. HLA typing was performed on all patients. RESULTS: The prevalence of HCV infection in patients with sicca syndrome was 19%. The incidence of neurologic involvement was significantly increased in patients with sicca syndrome associated with HCV infection (24% versus 4%; P < 0.03), as was elevations in transaminase levels (87.5% versus 16%; P < 0.0001). RF and cryoglobulins were more frequent in HCV-positive sicca syndrome patients (62% versus 30%; P < 0.03, and 56% versus 10%; P < 0.001, respectively). In contrast, anti-SS-A/SS-B antibodies were present in 38% of HCV-negative sicca syndrome patients, but in only 1 HCV-positive sicca syndrome patient (P < 0.01). No significant difference in HLA type was observed. Viral RNA was present in the saliva of 83% of HCV-positive sicca syndrome patients, but in none of the HCV-negative sicca syndrome patients. CONCLUSION: We observed a high prevalence of HCV infection in our patients with sicca syndrome. HCV-positive sicca syndrome patients had specific clinical characteristics and were seronegative for SS-A/SS-B antibodies. Moreover, HCV RNA was present in the saliva of patients with HCV-associated sicca syndrome.

Antibodies↗
PubMed1996

A limited sampling method to estimate methotrexate pharmacokinetics in patients with rheumatoid arthritis using a Bayesian approach and the population data modeling program P-PHARM.

This paper describes a methodology to calculate methotrexate (MTX) pharmacokinetic parameters after intramuscular administration using two samples and the population parameters. Total and free MTX were measured over a 36-h period in 56 rheumatoid arthritis patients; 14 patients were studied after a two-dose scheme at 15-day intervals. The Hill equation was used to relate the free MTX to the total MTX changes in plasma concentrations, and a two-compartment open model was used to fit the total MTX plasma concentrations. A non-linear mixed effect procedure was used to estimate the population parameters and to explore the interindividual variability in relation to the following covariables: age, weight, height, haemoglobin, erythrocyte sedimentation rate, platelet count, creatinine clearance, rheumatoid factor, C-reactive protein, swelling joint count, and Ritchie's articular index. Population parameters were evaluated for 40 patients using a three-step approach. The population average parameters and the interindividual variabilities expressed as coefficients of variation (CV%) were: CL, 6.94 l center dot h-1 (20.5%); V, 34.8 l (32.2%); k12, 0.0838 h-1 (47.7%); k21, 0.0769 h-1 (61.6%); ka, 4.31 h-1 (58%); Emax, 1.12 mu mol center dot l-1 (19.7%); gamma, 0.932 (12.3%); and EC50, 2.14 mu mol center dot l-1 (27.3%). Thirty additional data sets (16 new patients and 14 patients of the previous population but treated on a separate occasion) were used to evaluate the predictive performance of the population parameters. Twelve blood samples were collected from each individual in order to calculate individual parameters using standard fitting procedures. These values were compared to the ones estimated using a Bayesian approach with population parameters as a priori information together with two samples, selected from the individual observations. The results show that the bias was not statistically different from zero and the precision of these parameters was excellent.

Adult↗
PubMed1996

Prospects and advances in hormonal immunomodulatory therapy.

Modulation of the immune network through the hormonal system is an exciting emerging concept. It results from a decade of experimental research obtained on rodents. Unfortunately, the therapeutic response on NZB/NZW F1 mice with murine lupus or in adjuvant induced arthritis are not transferable to man. This new field opens new therapeutic perspectives with well known and relatively safe drugs (hormone agonists, antagonists or inhibitors of hormonal secretion). Today we lack controlled, randomized clinical studies, with long-term follow-up. We also need to identify the subgroup of patients who could benefit from hormonal immunomodulation (sex, basal hormonal status, menopausal status for women, disease activity).

Adjuvants, Immunologic↗
PubMed1996

Arthritis associated with monoclonal gammapathy: clinical characteristics.

We report nine cases of arthritis associated with a monoclonal gammapathy. Joint involvement was noted simultaneously or after the diagnosis of monoclonal gammapathy was made. The cases had oligoarthritis or polyarthritis mimicking rheumatoid arthritis. However, rheumatoid factor was absent in all patients, and distal interphalangeal joints were involved in two cases and sacroiliitis in one. The plasma cell dyscrasia was a multiple myeloma in two cases and monoclonal gammapathy of undetermined significance in the other patients. The light chain isotype was kappa in eight of our patients. A type I cryoglobulinaemia was associated in four cases; it was detected in the synovial fluid of two of them. We suggest that the occurrence of paraproteinaemia with chronic arthritis is more than a chance association. Moreover, a monoclonal gammapathy should be searched for in patients presenting with atypical seronegative arthritis.

Adult↗
PubMed1996

Effect of age on the efficacy and tolerance of methotrexate in rheumatoid arthritis.

The objective of this study was to assess the influence of age on the efficacy and toxicity of methotrexate in rheumatoid arthritis. Four hundred and sixty-nine patients were separated according to the age of onset of methotrexate treatment: before 65 yr (group 1, n = 416) and after 65 yr (group 2, n = 53). No difference was found in the evolution of clinical and biological parameters between the two groups. The number of patients in remission at the end of the study was equal. The frequency and type of side-effects were similar. No significant difference was found in the frequency and reasons for methotrexate withdrawal. We noted a trend towards lower therapeutic maintenance of methotrexate when prescribed after the age of 65 yr (P = 0.07, actuarial method). In conclusion, the age at initiation of methotrexate treatment probably did not influence its efficacy and toxicity in rheumatoid arthritis.

Actuarial Analysis↗
PubMed1996

Total and free methotrexate pharmacokinetics in rheumatoid arthritis patients.

The pharmacokinetics of total and free methotrexate (MTX) were investigated in 50 patients with rheumatoid arthritis. Each patient received 10 mg MTX intramuscularly. The free and total plasma concentrations of MTX were measured over a 36-h period after drug administration by using the Abbott TDx fluorescence polarization immunoassay. Plasma concentrations of MTX were described by a biexponential function. The mean terminal elimination half-lives of total and free MTX were 9.4 and 8.4 h, respectively, and the corresponding mean residence times, 8.5 and 9.2 h. No difference in these parameters was found by comparing total and free MTX. Total plasma clearance of the free fraction averaged 215 ml/min. The statistical comparison of the variations with time of the ratio of free to total MTX during the 36 h after the dose showed that the free fraction was significantly increased for 8 h after drug administration (p < 0.001). To describe these variations, the changes of the free MTX concentrations (unbound) were related to the changes of the total MTX concentrations by using the Hill equation. Mean plasma protein binding ranged from 20 to 57% for these patients.

Adult↗
PubMed1996

Oral contraception, parity, breast feeding, and severity of rheumatoid arthritis.

OBJECTIVE: To investigate the influence of breast feeding, use of the oral contraceptive pill (OCP), and parity on rheumatoid arthritis (RA). METHODS: One hundred and seventy six women with RA were compared with 145 control subjects; all had at least one child. RA patients were classified as having severe (n = 82) or mild disease (n = 89) according to clinical joint evaluation, radiological score, biological inflammation, and the presence of HLA-DR1 or -DR4 alleles. RESULTS: The mean age of RA patients was 58 years, and the mean age at the time of diagnosis of RA was 46 years. The mean time between onset of RA and the first birth was 23.6 (SD 3.8) years. The OCP user rates were 33% in the RA group and 47.6% in the control group (p < 0.02). OCP use was related to the mother's year of birth. The relative risk for developing RA was 0.598 (95% confidence interval (CI) 0.33 to 1.1) in women who had used OCP for more than five years compared with those who had never used OCPs. In contrast, the age at which the first pregnancy occurred, the number of children breast fed, and the duration of breast feeding were comparable in RA patients and healthy subjects. Among the RA patients, parity, duration of breast feeding, and the number of breast fed children were significantly increased in those with severe disease. Having more than three children increased the risk of developing severe disease 4.8-fold when adjusted for age and OCP use. Forty six percent of women with severe RA had a history of breast feeding duration greater than six months before disease onset, compared with 26% of patients with mild disease (p < 0.008). Having more than three breast fed children increased the risk of poor disease prognosis 3.7-fold. In contrast, OCP use had a protective role in the course of RA (44% of RA patients with mild disease were OCP users, compared with 21.7% of those with severe RA; p < 0.001). Among those using OCP for more than five years, the relative risk of developing severe disease was 0.1 (95% CI 0.01 to 0.6), after adjustment for age, parity, and breast feeding. CONCLUSION: Our results suggest that parity, and to a lesser extent breast feeding, before RA onset worsened RA prognosis, whereas OCP use had a protective role. Prolactin and oestrogen may have a role in these effects.

Adult↗