Biomedical subjects

J Sany

Publications and source records attributed to J Sany.

At least 19 recordsLinked to original sources

PubMed1999

Systemic viral interleukin-10 gene delivery prevents cartilage invasion by human rheumatoid synovial tissue engrafted in SCID mice.

OBJECTIVE: To assess the effects of viral interleukin-10 (vIL-10) gene delivery on human rheumatoid synovial tissue. METHODS: SCID mice were engrafted subcutaneously with human rheumatoid synovial tissue and homologous cartilage before systemic injection of 10(9) plaque-forming units of type 5 E1a Elb-deficient non-replicative adenovirus vector containing the vIL-10 gene under control of the cytomegalovirus promoter (AdvIL-10; n = 10) or a control gene (AdvIL-10mut; n = 7). Three weeks later, the graft was removed for histologic analysis of cartilage invasion by synovial tissue. The number of CD3-positive mononuclear cells was assessed in the synovial tissue by immunohistology. Messenger RNA (mRNA) expression of matrix metalloproteinase 3 (MMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1), and proinflammatory cytokines was determined by polymerase chain reaction. RESULTS: Systemic vIL-10 gene transfer resulted in high sustained production of vIL-10 protein in SCID mouse sera (mean +/- SD 25 +/- 5 ng/ml on day 40 post vector injection). Moreover, vIL-10 mRNA expression was detected in the synovial tissue 3 weeks after intravenous injection of AdvIL-10, reflecting the gene transfer in the human graft. In animals treated with AdvIL-10, cartilage invasion by rheumatoid synovial tissue was significantly inhibited compared with the control vector (mean +/- SD histologic score 2.5 +/- 0.52 versus 0.75 +/-0.8; P < 0.0001). The number of T cells infiltrating the synovium and perichondral resorption in the animals treated with AdvIL-10 gene were not significantly modified relative to the control vector. In animals treated with AdvIL-10, the MMP-3-TIMP-1 balance was partially restored, independent of the effect on mRNA expression of tumor necrosis factor a, IL-1, IL-6, or IL-8. CONCLUSION: Systemic vIL-10 gene transfer prevented cartilage invasion by synovial tissue engrafted in SCID mice. This model offers the opportunity to study the biologic effects of gene transfer in vivo in rheumatoid synovium.

Adenoviridae↗

PubMed1999

Anti-heat shock protein 70 kDa and 90 kDa antibodies in serum of patients with rheumatoid arthritis.

OBJECTIVES: Stress proteins (HSPs) are highly conserved immunodominant antigens found in various species. The purpose of this study was to assess the prevalence and prognostic significance of antibodies to HSC 70 kDa and HSP 90 kDa in three groups of patients with longstanding rheumatoid arthritis (RA) defined based on the severity of articular erosions. METHODS: 73 patients with longstanding (> 6 years) RA whose HLA-DR genotype was known were divided in three groups according to Larsen's score and compared with 47 recent onset (<1 year) RA patients and with control groups composed of patients with other inflammatory diseases (n=137) or of normal controls (n=48). IgGs and IgMs to HSC 70 kDa and HSP 90 kDa were determined using an ELISA with purified bovine HSC 70kDa or HSP 90 kDa. RESULTS: Concentrations of IgGs and IgMs to HSC 70 were significantly increased in 41.1% and 42.5% of longstanding RA patients, respectively. Corresponding figures for IgGs and IgMs to HSP 90 were 39.7% and 56%. IgMs to HSC 70 and HSP 90 were less frequent in recent onset RA (19% and 13% respectively). Among the groups with other inflammatory diseases, only the MCTD group exhibited high frequencies of IgGs to HSC 70 (80%) and HSP 90 (85%). DRB1*0401 positive RA patients (n=23) were not more likely to have increased concentrations of antibodies to HSC 70 kDa or HSP 90 kDa than other RA patients (DR4 positive but DRB1*0401 negative, or DR1 positive, n=31; or negative for both DR4 and DR1, n=14). IgGs to HSP 90 kDa were significantly more frequent (p<0.05) in longstanding RA patients whose Larsen's score was 4 or more (57%) than in those whose Larsen's score was 2 or 3 (39.4%) or less than 2 (16%). No associations were found between Larsen's score and IgGs or IgMs to HSC 70 kDa or IgMs to HSP 90 kDa. A significant correlation was demonstrated between IgGs to HSP 90 kDa and two other serological markers for RA, rheumatoid factor, and anti-Sa antibody; there were no correlations with antikeratin antibody, antiperinuclear factor, or anti-RA 33. CONCLUSION: IgGs to HSP 90 kDa are most common in longstanding RA patients with articular erosions, suggesting that they may be related to the articular prognosis in RA

Adolescent↗

PubMed1999

Anti-Sa antibody is an accurate diagnostic and prognostic marker in adult rheumatoid arthritis.

OBJECTIVES: To evaluate in various groups of patients with chronic joint disease the sensitivity and specificity of anti-Sa antibody, recently described in sera from adults with rheumatoid arthritis (RA); and to determine the prognostic significance of anti-Sa in initial sera from patients with long standing RA with or without severe joint destruction. METHODS: Serum samples from 489 patients were included. Of these, 154 were collected from patients with RA attending 2 rheumatology units. Controls were 335 patients with a variety of inflammatory joint diseases other than RA. IgG anti-Sa was detected using an immunoblotting method with purified Sa antigen from human placenta extracts. All patients were tested for the following antibodies: rheumatoid factor (RF), anti-keratin antibody (AKA), antiperinuclear factor (APF), and anti-RA 33. HLA class II DRB alleles were also determined. RESULTS: Anti-Sa was detected in 39.8% of RA sera overall, 46.7% of sera from the long standing RA group, and 23.5% of sera from the recent onset RA group (p<0.01). In patients with long standing RA, statistically significant associations were found between the presence of anti-Sa and the following variables: RF (p<0.0001), AKA (p<0.0001), APF (p<0.00001), and HLA DRB1*04 or 01 (p<0.01). In contrast, no association was found with anti-RA33. Anti-Sa was positive in 11 adult controls (7.8%) and in 26 pediatric patients with juvenile chronic arthritis (22%). The specificity of anti-Sa for RA was 92.1% in adults with well characterized rheumatic diseases and 85.9% in adults and children together. Among patients with long standing RA, those with destructive disease were more likely to test positive for anti-Sa (66.6%) than those with nondestructive disease (22.2%) (p<0.0001). Comparisons with other serologic markers for RA demonstrated that anti-Sa was sensitive (68.4%) and was also the test with the highest specificity (79%), positive predictive value (75%), and negative predictive value (71%) for discriminating between patients who do and those that do not develop late severe radiographic damage. CONCLUSION: Immunoblot-detected IgG anti-Sa is a sensitive serologic marker for RA patients with severe radiographic damage.

Adult↗

PubMed1999

Radiologic progression in early rheumatoid arthritis treated with methotrexate.

OBJECTIVE: To evaluate radiologic progression in patients with early rheumatoid arthritis (RA) receiving methotrexate (MTX) as the first slow acting drug. METHODS: An open, prospective study of 29 patients with RA (21 F, 8 M, mean age 48.5+/-15.4 yrs). The mean duration of RA was 6.6 (2-60) months; and rheumatoid factor was present in 11 cases. Clinical, biological, and radiographic evaluations were done before the start of MTX treatment and after 13+/-3.8 months. Radiographs of hands and wrists were blindly studied by 2 physicians, using Larsen's and modified Sharp's methods. There was a significant correlation for the scores of the 2 physicians evaluated by kappa coefficient. Radiographic evolution was defined as an increase of 15 points in the radiologic score by each method used. RESULTS: Patients showed significant clinical improvement after one year of MTX treatment. Despite clinical and biological improvement, significant mean radiographic progression was noted, with Larsen's method (p = 0.001) and Sharp's method (p = 0.034), without reaching the maximum score. However, using the definition of radiographic progression, the radiologic scores indicated stabilization in 23 patients with Larsen's method and in 24 patients with Sharp's method. CONCLUSION: This study revealed mild radiographic progression in early RA patients treated with MTX for one year. Further controlled studies are needed.

Antirheumatic Agents↗

PubMed1998

Adenovirus-mediated transfer of viral IL-10 gene inhibits murine collagen-induced arthritis.

IL-10 is a potent anti-inflammatory cytokine that has received growing attention for its therapeutic potential. We examined the efficiency of adenoviral-mediated gene transfer of IL-10 on the incidence and severity of murine collagen-induced arthritis (CIA). Male DBA1 mice immunized with collagen II were treated by systemic administration of 10(9) plaque-forming units of replication-defective adenoviral vector expressing viral IL-10 (vIL-10) on day 30, when clinical symptoms of arthritis start. The transgene was shown to inhibit the onset of CIA, to decrease severity, and profoundly suppress the overall joint histopathology of the experimental arthritis. Significant IL-10 concentrations were obtained in the serum of injected animals for 7 days. Inhibition of arthritis was enhanced by administration of increasing doses of adenovirus-vIL-10. In addition, the local immunosuppressive effect of gene-delivered vIL-10 could be neutralized by a monoclonal anti-vIL-10 Ab. The CIA symptoms in the group treated with the same construct expressing inactive vIL-10 (vIL-10 mut) were similar to those in untreated animals. Our data indicate that a single systemic administration of an adenoviral vector encoding vIL-10 may be a good candidate to suppress arthritis.

Adenoviridae↗

PubMed1998

Mutations of the p53 tumour suppressor gene in erosive rheumatoid synovial tissue.

Erosive rheumatoid arthritis (RA) is accompanied by synovial tissue hyperplasia associated with the proliferation of transformed-appearing synovial lining cells. In the present study we have analysed the expression of the p53 tumour suppressor gene in the synovial pannus tissue from patients at various stages of the disease. We used a combination of polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) on DNA and reverse transcription, PCR and sequencing on cDNAs from synovial tissues or purified synovial cell populations of 24 RA and three osteoarthritis (OA) patients. We also studied p53 expression by immunohistochemical analysis. Mutations suspected after SSCP were identified by systematic sequencing of the p53 exon 6, especially in the fibroblast-like, adherent synovial cell population, associated with an erosive disease. Some accumulation of the protein was detected in immunohistochemical analysis of the p53 tumour suppressor gene in the patients' synovial tissues. However, no sign of malignancy was seen in these patients after a 2-year survey. These results show some abnormalities in the p53 tumour suppressor gene in RA patients, but do not allow this to be related to characteristic proliferative features of the rheumatoid synovium.

Adolescent↗

PubMed1998

Interleukin-4 and interleukin-10 are chondroprotective and decrease mononuclear cell recruitment in human rheumatoid synovium in vivo.

We used the severe combined immunodeficient (SCID) mouse model to assess the effect of interleukin-4 (IL-4) or IL-10 injection on cartilage degradation and mononuclear cell (MNC) recruitment to human rheumatoid synovium in vivo. Human rheumatoid synovium and cartilage from five rheumatoid arthritis patients, obtained after joint replacement surgery, were engrafted subcutaneously to 6-8-week-old SCID CB17 mice. Synovial tissues were injected with recombinant human IL-4 (rhIL-4, 100 ng; rhIL-10, 100 ng), both cytokines, or tumour necrosis factor-alpha (TNF-alpha) (1000 U), or phosphate-buffered saline twice a week for 4 weeks. The graft was removed and immunochemical analysis was carried out to assess intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression. Moreover, cartilage degradation was assessed through the quantification of the erosion surface on a computerized image of the engrafted cartilage at high power view. MNC recruitment in the synovial tissue was determined by labelling blood MNC with indium-111 before their intraperitoneal injection. The activity obtained in the region of the graft were determined with a gamma camera 72 hr postinjection. The results are expressed as a percentage of initial injected activity. After 4 weeks we observed a decrease of cartilage area in controls (77 +/- 8%), inhibited after injection of IL-4, IL-10, or both cytokines (90 +/- 3%, 89.1 +/- 4%, 89.2 +/- 5% respectively), and 57 +/- 17% after TNF-alpha injection. The % MNC activity in the graft decreased to 77 +/- 81% (NS), 9 +/- 4% (P < 0.003) and 19 +/- 6% (P < 0.007) compared with untreated synovial tissue after treatment with IL-4, IL-10, or both cytokines, respectively. Moreover, IL-10 but not IL-4 decreased the expression of ICAM-1 but not VCAM-1 or E-selectin by synovial cells. These results suggest that IL-10 and IL-4 could have chondroprotective properties, and that IL-10 but not IL-4 inhibits MNC traffic towards the synovial tissue efficiently.

Animals↗

PubMed1998

Effects of moderate renal insufficiency on pharmacokinetics of methotrexate in rheumatoid arthritis patients.

OBJECTIVES: To determine the effects of impaired renal function on the pharmacokinetics of methotrexate (MTX) in rheumatoid arthritis (RA) patients. METHODS: 77 RA patients were included in this study. MTX was administered intramuscularly (7.5 to 15 mg). Subjects were divided into four groups, according to their creatinine clearance (CLCR); group 1: CLCR lower than 45 ml/min; group 2: CLCR between 45 and 60 ml/min, group 3: CLCR between 61 and 80 ml/min and group 4: CLCR higher than 80 ml/min. Blood samples were collected from each subject before drug administration and at two and eight hours after administration. Individual pharmacokinetic parameters were estimated using a Bayesian approach. RESULTS: MTX concentrations (total and free) were 1.3 to 1.6-times higher in group 1 than in groups 2, 3, and 4. For total and free MTX, t1/2 eliminations were 22.7 hours in group 1, 13.5 hours in group 2, 12 hours in group 3, and 11 hours in group 4. Clearance of total MTX was 64, 92, 96, 115 ml/min in groups 1 to 4, respectively, it was 118, 163, 171, 206 ml/min in groups 1 to 4 for the free MTX, respectively. Volume of distribution averaged 2.16 l/kg in group 1, 1.92 l/kg in group 2, 1.61 l/kg in group 3, and 1.56 l/kg in group 4. Elimination half life was significantly increased and total clearance was significantly reduced with the degree of renal impairment. Linear regression revealed good correlations between clearance values of MTX and creatinine clearance. CONCLUSION: Individual testing is required rather than a general decrease of the MTX dose based only on CLCR.

Aged↗

PubMed1998

Distribution of HLA-DRB1 alleles of patients with polymyalgia rheumatica and giant cell arteritis in a Mediterranean population.

OBJECTIVE: To evaluate HLA-DRB1 associations in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) compared to rheumatoid arthritis (RA). METHODS: One hundred twenty-one patients were included and oligotyped: 79 with PMR alone and 42 with GCA (14 also had PMR). We also genotyped 1609 healthy controls and 433 patients with RA. Statistical analysis included Fisher's exact test and calculation of the odds ratio (95% CI). RESULTS: Compared to controls, the DRB1*04 phenotype was increased in PMR (39.2%; OR = 2.4, p = 0.0005) and GCA (45.2%; OR = 3.1, p = 0.0005). This association was weaker than in RA (p = 0.01). DRB1*07 was more frequent in GCA (31.0%) than in PMR (13.4%; p = 0.03), but the difference was not significant in comparison to controls. The distribution of DRB1*04 subtypes was similar in PMR and GCA, but different from RA and controls. However, the frequency of 0402 and 0403 subtypes could not be distinguished from that in patients with RA. Double occurrence of RA associated alleles was less frequent in PMR and GCA (9.9%; p = 0.005) than in patients with RA (20.8%). There was no significant relationship between markers of disease activity/severity and HLA-DRB1 genes in PMR or GCA. CONCLUSION: PMR and GCA were associated with HLA-DRB1*04, but more weakly than RA. Nevertheless, these data suggest that HLA-DRB1* genes are closely related to susceptibility in PMR, GCA, and RA and do not support the hypothesis of a different linkage to the 3rd hypervariable region of DRB1 alleles. By contrast with RA, HLA-DRB1* genes do not appear to be indicators of disease severity in PMR and GCA.

Aged↗

PubMed1998

Gastric administration of recombinant 65 kDa heat shock protein delays the severity of type II collagen induced arthritis in mice.

OBJECTIVE: The 65 kDa heat shock protein (HSP) chaperonin is a highly conserved intracellular protein. HSP are involved in the pathogenesis of arthritis, but are not able to induce experimental arthritis. T cell clones recognizing the 180-188 amino acid sequence of 65 kDa HSP are present in inflamed synovium of both adjuvant arthritis and rheumatoid arthritis (RA). Oral administration of bovine collagen II or co-chaperonin 10 kDa HSP has been shown to induce an immune tolerance state to collagen induced arthritis (CIA). We investigate the effect of oral gavage with 65 kDa HSP on CIA. METHODS: We immunized 6-8-week-old DBA1 male mice with bovine type II collagen. A group of 25 mice were given oral recombinant mycobacterial 65 kDa HSP before immunization (30 microg in 200 microl phosphate buffered saline (PBS) at Days -7, -5, -2) while PBS alone was administered in 27 controls. A 3rd group was fed 65 kDa HSP according to the same protocol but was not immunized with collagen II (n = 8). The clinical arthritis score was recorded 3 times/week until Day 60. Antibodies to collagen II were determined by ELISA. RESULTS: The incidence of arthritis was comparable in the 2 groups (72 vs 70%). The onset of arthritis was not delayed in mice fed HSP. However, the severity of arthritis was lower 10 days after arthritis onset in animals fed 65 kDa HSP (clinical score 1.83 +/- 0.79 vs 2.74 +/- 1.1; p < 0.0001). No animals in Group 3 had arthritis. Serum IgG anti-type II collagen levels were decreased in HSP treated mice (optical density 0.33 +/- 0.21 vs 0.46 +/- 0.21; p < 0.0001). However, the ratio of IgG1/IgG2a antitype II collagen antibody response remained unchanged in the mice fed 65 kDa HSP. CONCLUSION: These results suggest that oral administration of 65 kDa HSP may diminish collagen induced arthritis.

Administration, Oral↗

PubMed1997

[Medical treatment of rheumatoid polyarthritis].

Treatment of rheumatoid arthritis must be instituted as early as possible when the diagnosis is established. In the severe forms, a treatment by a trained team allowing pluridisciplinar coping is needed. The general practitioner takes an important place in this team. The treatment of rheumatoid arthritis includes five points: information of patient, medico-psychological approach, local and general treatments, rehabilitation and sometimes surgery. Due to the heterogeneity of rheumatoid arthritis, the therapeutic strategy is adapted according to the evolution, the benefice/risk ratio and the prognostic factors.

Adult↗

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↗