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Biomedical subjects

B Combe

Publications and source records attributed to B Combe.

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

[Course, follow-up and prognosis of rheumatoid polyarthritis].

Rheumatoid arthritis is the more frequent chronic inflammatory arthritis. It is a potentially severe disease which causes a functional handicap in nearly half the patients 10 years after the first clinical symptoms. However rheumatoid arthritis is a heterogenous disorder and no prognostic factors are universally accepted and validated. Clinical and biological data collected to date have provided a limited amount of information. Nevertheless, erythrocyte sedimentation rate, C reactive protein and rheumatoid factor titer appeared to be the more powerful available indicators or prognosis at the early stage of the disease. Recent studies strongly suggests that some autoantibodies and mainly genetic markers (HLA-DRB1 alleles) could be correlated with disease severity. Consequently, it would appear possible to distinguish immunogenetically homogeneous subpopulations of patients with rheumatoid arthritis. Serum concentrations of specific cartilage and bone molecules reflecting tissue turnover and metalloproteinases could correlate to rate of joint destruction. Finally a combination of the most pertinent markers could determine a "score of severity" of the disease.

Adult↗
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

Equivalence of nasal spray and subcutaneous formulations of salmon calcitonin.

The aim of this study was to assess the efficacy and safety of nasal spray and subcutaneous formulations of salmon calcitonin. Two-hundred-four patients, 27 males and 177 females, aged 72 years on average, with a recent, painful, vertebral crush fracture were given either 50 IU/day of subcutaneous salmon calcitonin (SCSCT, 102 patients) or 200 IU/day of intranasal salmon calcitonin (INSCT, 102 patients) for 30 consecutive days, according to a double-blind, double-placebo design. The two-sided 95% confidence interval of the difference between the two formulations for the pain on D30 assessed by Huskisson's Visual Analogue Scale (VAS) [-5.3 mm, 7.9 mm] was included in the [-10 mm, 10 mm] reference interval. Equivalence of the two formulations, was demonstrated. At the end of the study, the 95% confidence intervals of VAS of both treatment groups were included in the [0 mm, 30 mm] interval, which is considered to be clinically pertinent. Relief was obtained in less than 10 days for more than 50% of patients. The urinary hydroxyproline/creatinine and calcium/creatinine ratios remained constant between D1 and D30 with both formulations. General safety was comparable between the two formulations. Local safety of INSCT was similar to that of its placebo.

Administration, Intranasal↗
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

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↗
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

[Prognostic factors in early inflammatory arthritis].

Rheumatoid arthritis (RA) and spondylarthropathies are the most frequent chronic inflammatory arthritides. RA is a potentially severe disease which causes a functional handicap in nearly half the patients 10 years after the first clinical symptoms. However RA is a heterogenous disorder characterized by wide variations in clinical manifestations, disease course and response to therapy. No prognosis factor has been identified and universally accepted and validated. Markers of prognosis would be highly appreciated by clinicians who could then more closely adapt their management decisions to the disease potential. Clinical and biological data collected to date have provided a limited amount of information. Nevertheless, ESR, CRP and rheumatoid factor titer appeared to be the most powerful available indicators of prognosis at the early stage of the disease. Recent progress in molecular biology strongly suggests that genetic markers (HLA-DRB1 alleles) could be correlated with disease severity and it would appear possible to distinguish immunogenetically homogeneous subpopulations of patients with RA. Serum concentrations of specific cartilage and bone molecules reflecting tissue turnover could correlate to rate of joint destruction. Finally a combination of the most pertinent markers could determine a "score of severity" of the disease. In spondylarthropathies, limited information is available at present. The variables which were usually correlated with disease severity are: onset before 16 years of age, hip arthritis, ESR, limitation of lumbar spine, sausage-like finger or toe, oligoarthritis, poor efficacy of nonsteroidal antiinflammatory drugs and rapid evolution during the first 2 years. Genetic factors could also have prognosis value that should be clarified.

Arthritis↗
PubMed1996

Sulphasalazine in psoriatic arthritis: a randomized, multicentre, placebo-controlled study.

A prospective double-blind, placebo-controlled, randomized study of 24 weeks duration was carried out comparing the efficacy and tolerability of sulphasalazine (SSZ) versus placebo in patients with psoriatic arthritis. A total of 120 patients were included in nine centres. All patients had active disease and fulfilled the criteria of definite psoriatic arthritis of at least 3 months duration. They received either SSZ (2.0 g/day) or placebo. Efficacy variables included pain, patient's overall assessment of joint and skin improvement, morning stiffness, Ritchie articular index, ESR and CRP. An intention-to-treat (ITT) analysis was performed for the 117 patients who qualified (three patients did not qualify due to missing data after baseline). A per-protocol analysis was performed for the 81 patients who completed the 6 months study period (SSZ = 38, placebo = 43). Major reasons for withdrawal were inadequate response (SSZ = 4, placebo = 7) and adverse events (SSZ = 8, placebo = 12). Pain was the only statistically significantly different primary outcome variable at end point in favour of SSZ in the ITT analysis. No significant differences were present in other clinical or biological variables, although there was a trend in favour of SSZ for some variables. SSZ, at a dose of 2.0 g/day, appeared to be a safe treatment in patients with psoriatic arthritis. At this dosage, its efficacy was only demonstrated for the pain variable.

Adult↗
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↗
PubMed1995

[Can the prognosis of early rheumatoid arthritis be predicted?].

Rheumatoid arthritis is a frequently and potentially severe disease which causes a functional handicap in nearly half the patients 10 years after the identification of the first clinical manifestations. Some patients develop very severe forms with joint destruction and multiple organ involvement while in others the disease remains benign, even after a long clinical course of several years. Theoretically, the future intensity of rheumatoid arthritis in a given patient cannot be predicted at the time of early diagnosis. No prognosis factor has been identified and universally accepted and validated. A marker of prognosis would be highly appreciated by clinicians who could then more closely adapt their management decisions to the disease potential. Clinical and biological data collected to date have provided a limited amount of prognostic information but recent progress in molecular biology suggests that genetic markers could be correlated with disease severity. Several HLA-DRB1 alleles including DR1*0401, DRB1*0404, DRB1*0101 and sometimes DRB1/1001 and DRB1/1402 are potential markers. In France 85% of the patients with rheumatoid arthritis have one of these genes compared with 25% in the general population. In patients with a "high risk" alleles, the second haplotype could also have prognostic value. It would appear possible to distinguish immunogenetically homogeneous subpopulations corresponding to the more severe forms of the disease. It is still too early to propose therapeutic strategies based on current prognosis markers, but a combination of the most pertinent markers should be already used to select homogeneous subsets of patients in fundamental research and clinical trials.

Arthritis, Rheumatoid↗
PubMed1995

Total and free methotrexate pharmacokinetics, with and without piroxicam, in rheumatoid arthritis patients.

The pharmacokinetic profile of total and free methotrexate (MTX) and the effect of piroxicam on MTX pharmacokinetics was studied in 20 rheumatoid arthritis patients receiving a stable dosage of MTX (10 mg/week). Plasma protein binding ranged from 25 to 55%. To describe the variations with time of the unbound fractions a mathematical characterization relationship between the total and free MTX was used. Total and free MTX were correlated with the sigmoid maximum effect model. The slope factor (gamma) was proportional to the number of binding sites. The free fraction for a given patient can be evaluated from this relationship. Total clearance of MTX was not statistically different with piroxicam (8.0 l/h for total MTX, 13.7 l/h for free MTX) vs without piroxicam. Likewise, there were no significant difference in tmax, area under the plasma concentration vs time curve, distribution and elimination half-lives, mean resonance time, and volumes of distribution. Although the highest observed total MTX concentration was significantly lower with piroxicam, there were no significant pharmacokinetic interactions between low-dose MTX and piroxicam.

Adult↗
PubMed1995

Prognostic factors in rheumatoid arthritis. Comparative study of two subsets of patients according to severity of articular damage.

Clinical and biological profiles at the onset of the disease, obtained retrospectively, and human leucocyte antigen typing were studied in 47 rheumatoid arthritis (RA) patients with severe articular damage (group 1) and in 47 patients with limited radiological abnormalities (group 2). The two groups were matched according to disease duration (mean: 8.1 yr). Systemic manifestations were more frequent in group 1. Erythrocyte sedimentation rate (ESR), platelet counts, C-reactive protein (CRP), rheumatoid factor and IgG titres were higher and haemoglobin level lower in group 1. HLA class II genotyping demonstrated that 95.7% of patients in group 1 were Dw4, Dw14 or DR1 as compared to 55.3% in group 2 and 37.1% in normal controls. Two RA-linked DRB1 genes were detected in 34.1% of patients in group 1, vs 8.5% in group 2 and 7.9% in controls. Multiple logistic regression analysis demonstrated that ESR, CRP and genetic markers were the most relevant independent variables and when combined could indicate the outcome in early RA. These data confirmed that different RA subtypes with different prognoses could be associated with particular clinical, biological and genetic profiles. Moreover, some of these factors could serve as predictive markers for outcome at the onset of RA.

Adult↗
PubMed1995

A study of ovarian function in rheumatoid arthritis.

Ovarian function was evaluated prospectively in 16 female rheumatoid arthritis patients in the childbearing age. None of the patients was using oral contraceptives. The control group included 31 women with tubal sterility. Serum levels of estrone, 17 beta-estradiol and progesterone were assayed and used to determine an estrogen index and a luteal index. An ovulatory score was calculated as the sum of the estrogen and luteal indices. Estrogen levels were lower in the rheumatoid arthritis group than in the control group, but the difference was not significant. No statistically significant difference was found for progesterone levels, suggesting that luteal function was normal in the rheumatoid arthritis patients. The rheumatoid arthritis group had a significantly lower mean ovulatory score reflecting a decreased likelihood of ovulation as compared with the control group (p < 0.01). This abnormality may explain why fertility is reduced in women with rheumatoid arthritis.

Adult↗