Biomedical subjects

C Beyeler

Publications and source records attributed to C Beyeler.

At least 19 recordsLinked to original sources

PubMed2004

Self assessment in continuous professional development: a valuable tool for individual physicians and scientific societies.

OBJECTIVES: To assess the appreciation of self assessment (SA) by multiple choice question (MCQ) tests during continuous professional development (CPD) meetings and to evaluate the attitude towards the option of recertification. METHODS: A questionnaire was completed at a meeting of the Swiss Societies of Rheumatology and Physical Medicine and Rehabilitation in 2003 (response rate 94.9% (223/235)). RESULTS: 60.9% of members found SA useful to assess rheumatological knowledge by MCQ tests; 71.3% thought it motivating to receive an anonymous feedback; 47.2% wanted an additional individualised feedback; 70.8% asked for SA to be continued every 2 years during CPD sessions; 26.3% favoured the option of recertification with identical standards to the Swiss certifying examination in rheumatology. Physicians in private practice less often chose the option of recertification than physicians employed by hospitals (OR = 2.09, 95% CI 1.03 to 4.18). No correlations between the type and duration of specialisation, personal reading time, frequency of attendance at CPD meetings, sex of the members, and the choices made were found. CONCLUSIONS: SA by MCQ tests during CPD meetings is highly accepted by Swiss rheumatologists. This reliable, valid, and economic method of learning needs assessment enables individual physicians and scientific societies to plan educational with specific goals in mind.

Attitude of Health Personnel↗

PubMed2000

Polymorphonuclear elastase-alpha1-proteinase inhibitor (elastase-alpha1 antitrypsin) in patients with rheumatic diseases: influence of disease activity.

OBJECTIVE: To determine whether elastase-alpha1-proteinase inhibitor (E-alpha1PI) complex behaves as an acute phase reactant in inflammatory arthritis. METHODS: E-alpha1PI complex was measured in the plasma of 89 patients with different rheumatic diseases and 28 healthy controls. Correlations were sought between standard indices of disease activity as patients went into remission with the use of disease modifying antirheumatic drugs (DMARD). RESULTS: Compared with levels in 28 healthy controls, E-alpha1PI was significantly higher in 58 patients with rheumatoid arthritis (RA), 14 with ankylosing spondylitis, and 17 with noninflammatory rheumatoid disease. No significant correlations were found between E-alpha1PI and various laboratory and clinical variables of disease activity in RA before introduction of a DMARD. There was a slight decrease in E-alpha1PI over 24 weeks of treatment as other acute phase reactants fell significantly, although this did not reach significant levels. No correlations were found between intra-individual change of E-alpha1PI and different indices of disease activity from Week 0 to Week 24. CONCLUSION: E-alpha1PI complex levels, measured as an index of neutrophil activation, did not correlate with improvement in disease activity in inflammatory arthritis afforded by DMARD.

Adult↗

PubMed1998

An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians.

The metabolism of the anticonvulsant drug mephenytoin exhibits a genetic polymorphism in humans. This polymorphism exhibits marked racial heterogeneity, with the poor metabolizer PM phenotype representing 13-23% of oriental populations, but only 2-5% of Caucasian populations. Two defective CYP2C19 alleles (CYP2C19*2 and CYP2C19*3) have been described, which account for more than 99% of Oriental poor metabolizer alleles but only approximately 87% of Caucasian poor metabolizer alleles. Therefore, additional defects presumably contribute to the poor metabolizer in Caucasians. Recent studies have found a third mutation CYP2C19*4, which accounts for approximately 3% of Caucasian poor metabolizer alleles. A fourth rare mutation (CYP2C19*5A) (C99,A991,Ile331;C1297T,Arg433-->Trp) resulting in an Arg433 to Trp substitution in the heme-binding region has been reported in a single Chinese poor metaboliser outlier belonging to the Bai ethnic group. The present study identifies a second variant allele CYP2C19*5B (C99-->T; A991-->G, Ile331-->Val; C1297-T, Arg433-->Trp in one of 37 Caucasian poor metabolizers. The frequency of the CYP2C19*5 alleles is low in Chinese (approximately 0.25% in the Bai ethnic group) and Caucasians (< 0.9%). However, these alleles contribute to the poor metabolizer phenotype in both ethnic groups and increases the sensitivity of the genetic tests for identifying defective alleles to approximately 100% in Chinese poor metabolizers and 92% in Caucasian poor metabolizers genotyped in our laboratory. The Arg433 to Trp mutation in the heme-binding region essentially abolishes activity of recombinant CYP2C19*5A toward S-mephenytoin and tolbutamide, which is consistent with the conclusion that CYP2C19*5 represents poor metabolizer alleles.

Alleles↗

PubMed1997

Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis.

The objective was to analyse whether the activity of the cytochrome P450 isoenzyme CYP3A4 is altered by disease activity of rheumatoid arthritis (RA). Urinary 6 beta-hydroxycortisol excretion, expressed as a fraction of the urinary creatinine output, was measured in 21 patients with RA treated with three different disease-modifying anti-rheumatic drugs (DMARDs) over 24 weeks. There were no correlations between urinary 6 beta-hydroxycortisol/creatinine (6 beta-OHC/Creat) ratio and measurements of disease activity such as plasma viscosity, Ritchie articular index and early morning stiffness. In addition, the three DMARDs sulphasalazine, sodium aurothiomalate and D-penicillamine, smoking and the intake of various CYP3A4 substrates had no consistent detectable effect on the 6 beta-OHC/Creat ratio. There is no evidence that the dosage of drugs metabolized by the CYP3A4 isoenzyme needs to be adjusted for disease activity in RA.

Adult↗

PubMed1997

Quantitative liver function in patients with rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study.

The objectives were to determine quantitative liver function prospectively in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX), to search for risk factors for a loss of quantitative liver function and to assess the relationship between quantitative liver function and histological staging. A total of 117 patients with RA (ACR criteria, 85 women, mean age 59 yr) had measurements of galactose elimination capacity (GEC), aminopyrine breath test (ABT) and liver enzymes [aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (AP), 7-glutamyl transferase (GGT), bile acids, bilirubin, albumin] before treatment with weekly i.m. MTX injections and every year thereafter. In 16 patients, liver biopsies were performed. Before the introduction of MTX, mean GEC was 6.6 mg/min/kg [5th to 95th percentile (5-95 PC) 5.1-8.5; reference range 6.0-9.1] and mean ABT was 0.80% kg/mmol (5-95 PC 0.42-1.30: reference range 0.6-1.0). During treatment with MTX [mean weekly dose 11.8 mg (5-95 PC 5.4-20.2), mean observation period 3.8 yr (5-95 PC 0.4-6.9)], significant declines of GEC (-0.12 mg/min/kg per year. t = 3.30, P < 0.002) and ABT (-0.06% kg/mmol per year, t = 4.81, P < 0.001) were observed. Negative correlations were found between the annual change in GEC and GEC at baseline (Rs = -0.40, P < 0.0001), and the annual change in ABT and ABT at baseline (Rs = -0.43, P < 0.0001). No correlations were found between the annual change in GEC or ABT and weekly MTX dose, age or percentage of increased liver enzymes, and no effect of a history of alcohol consumption > 30 g/week became evident. Two patients with Roenigk grade III had impaired quantitative liver function, while 14 patients with Roenigk grades I and II exhibited a high variability of GEC and ABT from normal to abnormal values. The continuous declines in GEC and ABT observed deserve attention in patients with prolonged treatment. Patients with a low GEC or ABT at baseline seem not to be at increased risk for a further loss of quantitative liver function. An impaired GEC or ABT does not necessarily concur with hepatic fibrosis on histological examination.

Alanine Transaminase↗

PubMed1996

[Methotrexate treatment of rheumatoid arthritis].

Weekly low dose methotrexate has a beneficial efficacy: toxicity ratio compared to other disease-modifying antirheumatic drugs. Methotrexate shows one of the most pronounced effects on disease activity, with improvement of functional status and slowing of radiological progression of joint destruction. In addition, the short- and medium-term withdrawal rate is low and due to usually minor side effects. However, major complications such as interstitial pneumonitis, hepatic fibrosis and osteopathy deserve special attention, in particular during long-term treatment. Careful patient selection and monitoring, in close cooperation between the rheumatologist and general practitioner, contribute to optimal security of methotrexate treatment. The present overview summarizes scientific data and makes practical recommendations.

Antirheumatic Agents↗

PubMed1996

Pulmonary function in rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study.

Lung volumes and gas exchange were investigated prospectively in 96 patients with rheumatoid arthritis selected without regard to pulmonary disorders and treated with i.m. methotrexate (MTX) injections [mean weekly dose 13.0 mg (5th-95th percentile (5-95 PC) 7.6-20.8)]. Individual changes over time during MTX treatment [mean duration 2.9 yr (5-95 PC 0.4-5.3)] were assessed by regression analyses in each individual. Forced vital capacity (FVC) remained stable in the majority of patients [mean annual change +0.8% (5-95 PC -8.1 to +14.0) of calculated normal value]. In addition, transfer factor using the indicator gas CO (TL,CO) was unaltered in most patients [mean annual change -2.1% (5-95 PC -16.2 to +11.8) of predicted value]. However, there were significant decreases in the forced expiratory volume in 1 s (FEV1) before and after inhalation of 0.2 mg salbutamol [mean annual change -0.8% (5-95 PC -8.4 to +3.2) and -1.3% (5-95 PC -7.8 to +3.9) of the FVC measured, respectively]. In addition, there were significant increases in alveolar-arterial Po2 gradients (P(A-a),O2) at rest and after exercise [mean annual change +1.7 mmHg (5-95 PC -5.2 to +12.2) and +1.8 mmHg (5-95 PC -3.5 to 9.0), respectively]. Nevertheless, the amounts were small in view of the reliability of the methods applied and reflect, at least in part, the normal process of ageing. The annual change in FEV1/FVC was negatively correlated with FEV1/FVC at baseline (Rs = -0.46, P < 0.001). The annual change in TL,CO was also negatively correlated with TL,CO at baseline (Rs = -0.31, P = 0.028). No other risk factors for deterioration of lung volumes or gas exchange were found, including mean weekly MTX dose, age, gender, smoking, presence of rheumatoid factor and pulmonary function at baseline. We conclude that MTX has no major effect on pulmonary function in the majority of patients and that there is no evidence that patients with pre-existing pulmonary disease are at increased risk for further deterioration of lung function.

Aged↗

PubMed1996

Severe osteoporosis due to systemic mast cell disease: successful treatment with interferon alpha-2B.

We describe a 33-year old man suffering from severe vertebral osteoporosis and urticaria pigmentosa due to systemic mast cell disease (SMCD). Because i.v. clodronate therapy could not prevent further vertebral fractures, an additional treatment with interferon alpha-2b was initiated. During 24 months of treatment, our patient had no further pain episodes, no new vertebral fractures were discovered, trabecular bone mineral density (BMD) increased significantly and urticarial symptoms improved. Nevertheless, the extent of skin lesions remained unchanged. On histological examination, a remarkable decrease of mast cells was observed in the bone marrow, but not in the skin. Five months after discontinuation of interferon alpha-2b, trabecular BMD decreased and urticarial symptoms deteriorated. These findings illustrate a beneficial effect of interferon alpha-2b on SMCD-induced osteoporosis as well as urticarial symptoms, and raise the question whether this treatment may have a diverse impact on mast cell population in different tissues.

Adult↗

PubMed1996

Relationship between genotype for the cytochrome P450 CYP2D6 and susceptibility to ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVES: To determine whether particular genotypes for the cytochrome P450 enzyme CYP2D6, a polymorphic enzyme, are associated with susceptibility to ankylosing spondylitis (AS) and rheumatoid arthritis (RA), or linked with any specific clinical or familial features of the two conditions. METHODS: CYP2D6 genotypes were determined in 54 patients with AS, 53 patients with RA, and 662 healthy controls. Leucocyte DNA was analysed for the presence of mutations by restriction fragment length polymorphism analysis with the restriction enzyme Xbal and by two separate polymerase chain reaction assays. RESULTS: On the basis of odds ratio (OR), individuals with two inactive CYP2D6 alleles were more susceptible to AS than controls (OR 2.71, 95% confidence interval (CI) 1.04 to 7.08), with a stronger effect for the CYP2D6B allele (OR 4.11, 95% CI 1.54 to 11.0). No significant differences in the distribution of overall genotypes and allele frequencies were observed between RA and controls. No significant relationships were found between the skeletal, extraskeletal or familial features of AS or RA (iritis, psoriasis, inflammatory enteropathy and rheumatoid nodules, kerato-conjunctivitis sicca, pleuritis, rheumatoid and antinuclear factors) and the overall genotype. CONCLUSIONS: Our findings suggest a modest association between homozygosity for inactive CYP2D6 alleles, particularly CYP2D6B alleles, and susceptibility to AS. However, our results fail to demonstrate a genetic link between CYP2D6 genotype and RA.

Aged↗

PubMed1996

Urinary glucaric acid excretion in rheumatoid arthritis: influence of disease activity and disease modifying drugs.

OBJECTIVE: To examine if a correlation exists between cytochrome P-450 enzyme induction and disease activity in patients with rheumatoid arthritis (RA), measuring urinary excretion of D-glucaric acid (GA) as an index of phase II drug metabolism. METHODS: Patients with RA were treated with sulphasalazine, sodium aurothiomalate, or D-penicillamine in standard dose regimens, for 24 weeks. Patients with ankylosing spondylitis (AS) or non-inflammatory arthritis (NIA) acted as controls. The urinary GA:creatinine ratio was measured at 0, 12, and 24 weeks of treatment. RESULTS: Patients with RA had a slightly greater urinary GA:creatinine ratio than patients with AS or NIA at baseline; this increased during treatment with disease modifying antirheumatic drugs (DMARDs). Sulphasalazine treatment had a greater effect on GA excretion than sodium aurothiomalate or D-penicillamine; this difference was statistically significant between weeks 0 and 12 (p = 0.01). Gamma glutamyltranspeptidase concentration showed a weak correlation with GA excretion between weeks 0 and 12 (p = 0.03), but all other measurements of changes in disease activity (plasma viscosity, C reactive protein, platelets, and articular index) were found not to correlate with GA excretion between weeks 0-12 or 0-24. CONCLUSION: The increased excretion of GA in patients with RA receiving DMARD treatment is probably the result of an indirect effect on hepatic metabolism bearing no relationship to disease activity.

Adult↗

PubMed1996

Bone alkaline phosphatase in rheumatoid arthritis: a longitudinal study.

OBJECTIVE: To determine whether the raised total alkaline phosphatase (TAP) found in patients with active rheumatoid arthritis (RA) is derived primarily from an increase of the bone or liver isoenzyme, and to evaluate the treatment effect of steroids and disease modifying antirheumatic drugs (DMARD) on bone alkaline phosphatase (BAP) in serial analyses. METHODS: 58 patients with RA were treated with the DMARD gold sodium thiomalate (n = 22), D-penicillamine (n = 18), or sulfasalazine (n = 18) over a 24 week period with regular assessment of disease activity and measurement of BAP using a newly developed specific double monoclonal radioimmunometric assay. RESULTS: In the RA group as a whole, BAP correlated with TAP at all time points (e.g., Week 0 rs = 0.50, p < 0.0001). In contrast, no correlation was found between the intraindividual change of BAP and TAP between Weeks 4 and 24. TAP was correlated with disease activity (assessed by plasma viscosity rs = 0.33, p < 0.02 for the whole RA group and rs = 0.48, p < 0.0002 for intraindividual change from Weeks 4 to 24). Similarly, gamma-glutamyltranspeptidase was correlated with disease activity (rs = 0.56, p < 0.0001, and rs = 0.50, p < 0.0001, respectively). In contrast, BAP was not correlated with disease activity. Low dose steroids and the 3 DMARD studied had no significant effect on the time course of BAP. CONCLUSION: In the majority of patients with active RA, any increase of TAP is not mirrored by an increase of BAP. This supports the hypothesis that inflammatory reactions result in an increase in the plasma concentration of the membrane bound enzymes of the hepatobiliary system, including gamma-glutamyltranspeptidase and the liver isoenzyme of alkaline phosphatase, which is likely to be responsible, at least in part, for the increase of TAP. Since BAP is not correlated with disease activity, BAP measurements are not useful in monitoring response to treatment.

Aged↗

PubMed1995

[Gluten-sensitive enteropathy with intestinal T-cell lymphoma: an unusual cause of in disabling osteomalacia].

We describe a 64-year-old woman with a malignant intestinal T-cell lymphoma who presented four years later with disabling osteomalacia and secondary hyperparathyroidism due to malabsorption. Only two years later, when the patient had developed fatty stools, flatulence and weight loss, diagnosis of gluten-sensitive enteropathy (GSE) was confirmed by small-intestine biopsy. This case report illustrates that in adults GSE can be oligosymptomatic for long periods. In cases of osteomalacia or rare intestinal T-cell lymphoma a detailed history of bowel movements, inspection of stools, quantification of fat excretion in stools and laboratory tests for malabsorption are recommended. Positive antibodies against gliadin, endomysium and reticulin may support the diagnosis of GSE. However, intestinal biopsy is necessary to verify the presence of GSE. In view of the unspecific histological changes, a follow-up biopsy is recommended in oligosymptomatic cases. Serial measurements of antibodies allow supervision of compliance for a diet strictly free of gluten. In addition, lactose containing milk products need to be restricted initially because of secondary lactase deficiency.

Celiac Disease↗

PubMed1995

Polymorphic acetylation: lack of influence of rheumatic disease activity and concomitant drug administration.

Acetylation polymorphisms have been linked with a tendency to develop rheumatic diseases. We investigated the effect of changes in the disease activity of patients with rheumatoid arthritis (RA) during disease-modifying antirheumatic drug (DMARD) treatment, and on the capacity of these patients to acetylate the sulphonamide sulphadimidine. Fifty-four patients with RA treated with gold, sulphasalazine or D-penicillamine, 12 patients with AS and 16 patients with non-inflammatory arthritis (NI) were investigated over a 24-week period. The capacity of these individuals to acetylate sulphadimidine was determined at baseline and after 12 and 24 weeks. Although there was a tendency for sulphadimidine acetylation to increase in patients with RA from a median of 84.5% [interquartile range (IQR) 77.0-95.0%] at baseline to 90.5% (IQR 77.5-96.0%) at week 24, this failed to reach statistical significance. In contrast, the trend in patients with AS or NI was towards a decrease in acetylation. There was no correlation between changes in disease activity and sulphadimidine acetylation during DMARD intervention.

Acetylation↗

PubMed1995

Diffuse idiopathic skeletal hyperostosis (DISH) of the shoulder. A controlled radiological study.

The prevalence of hyperostotic spurs (HS) in different areas of the shoulder was studied in 36 probands with and 58 probands without thoracospinal hyperostosis on lateral chest radiographs. Bilateral shoulder radiographs in three projections were analysed blindly, recording the presence of HS at six separate sites (glenoid, greater tuberculum, acromion, acromioclavicular joint, coracoid and humeral shaft) and applying defined grading criteria. The prevalence of HS ranged from 11.7% of the shoulders at the coracoid to 50.0% at the glenoid. The prevalence of HS was similar on both sides [right, 30.1% of the sites versus left, 27.0%, relative risk (RR) 1.12 (95% confidence interval [Cl] 0.93-1.35)] and was not related to sex and history of work. Classification for the presence of shoulder hyperostosis was identical on both sides with the exception of one individual. In probands with thoracospinal and shoulder hyperostosis all areas analysed contributed to the classification. However, this was particularly prominent at the humeral shaft [RR 5.3 (95% Cl 2.1-13.0)] and the coracoid [RR 8.4 (95% Cl 1.9-36.4)]. These results indicated that the prevalence of HS and the specificity for the presence of diffuse idiopathic skeletal hyperostosis (DISH) vary between different sites. We suggest that future grading criteria for shoulder hyperostosis take into account the localization of HS, in addition to their number and size.

Aged↗

PubMed1995

Bone alkaline phosphatase in rheumatic diseases.

A double monoclonal immunoradiometric assay specific for bone alkaline phosphatase (BAP) was used to determine whether the raised total alkaline phosphatase (TAP) often found in patients with active rheumatoid arthritis (RA) and ankylosing spondylitis (AS) is derived from bone or liver. Fifty-eight patients with RA were compared to 14 with AS and 14 with non-inflammatory rheumatic diseases (NI). None had clinical liver disease and only one had a slightly elevated aspartate transaminase activity. Elevated BAP concentrations were found in seven patients (5 RA, 1 AS, 1 NI), only two of whom also had abnormal TAP. Abnormal TAP activities were found in only three patients (all RA). BAP did not correlate with disease activity in RA or AS. In contrast, TAP correlated with disease activity (assessed by plasma viscosity) in RA (P < 0.002) and gamma-glutamyl transferase (GGT) also correlated with plasma viscosity in RA (P < 0.01). Both TAP and BAP were significantly correlated with GGT in RA (P < 0.001 and P < 0.02, respectively). These findings are discussed, together with possible reasons for the conflicting nature of some of the observations.

Adult↗

PubMed1994

Intraindividual variability of the bioavailability of low dose methotrexate after oral administration in rheumatoid arthritis.

OBJECTIVES: To analyse whether the intraindividual variability of the bioavailability of oral methotrexate in rheumatoid arthritis (RA) is as high as the interindividual variability and whether the bioavailability testing can be simplified. METHODS: Fifteen mg methotrexate was given orally after an overnight fast to 10 patients with RA on two occasions, one week (n = 4) or two years (n = 6) apart, respectively. Plasma samples were taken at specific time intervals and analysed by fluorescence polarisation immunoassay. The areas under the plasma concentration versus time curves from 0 to infinity (AUC) were calculated after fitting to a two-compartment extravascular model with lag time. RESULTS: The interindividual variability of the AUCs showed a more than five fold range from 77 to 471 min x mumol/l. In contrast, the intraindividual differences of AUCs between the two visits ranged from 3 to 100 min x mumol/l, reflecting a 3-30% change in nine of 10 patients. Close correlations were found between the AUCs and the plasma concentrations with a most pronounced correlation eight hours after methotrexate intake (r = 0.975; p < 0.001). CONCLUSIONS: The high interindividual variability of the AUCs was confirmed. Conversely, only a modest intraindividual variability was disclosed. Plasma sample analysis at a single time point four to eight hours after methotrexate application could simplify estimation of the bioavailability.

Administration, Oral↗

PubMed1994

Phenotype/genotype relationships for the cytochrome P450 enzyme CYP2D6 in rheumatoid arthritis: influence of drug therapy and disease activity.

OBJECTIVE: To determine whether particular genotypes for the cytochrome P450 enzyme CYP2D6, a polymorphic enzyme, are associated with susceptibility to rheumatoid arthritis (RA) and whether CYP2D6 enzyme activity is altered as a result of the disease or its treatment. METHODS: CYP2D6 genotypes and metabolic phenotypes were determined for 53 patients with RA and 73 healthy controls. Genotyping was carried out by restriction fragment length polymorphism analysis with the restriction enzyme XbaI and by 2 separate polymerase chain reaction assays; phenotyping was by analysis of in vivo metabolism of the probe drug debrisoquin. RESULTS: No significant difference in the distribution of overall genotypes between the 2 groups was observed. When the frequency of individual alleles was investigated, a significant difference in allele frequency for the CYP2D6D allele (p < 0.005) was observed with fewer patients with RA showing this mutation. Metabolic phenotypes were broadly similar between the patients and controls. However, a number of the patients with RA showed higher than expected metabolic ratios for their particular genotype due to interference by the analgesic dextropropoxyphene in the phenotyping procedure. CONCLUSION: Our findings demonstrate that CYP2D6 activity is not impaired in RA.

Adult↗

PubMed1994

[Spondylarthritis--a family of inflammatory-rheumatic diseases].

Spondyloarthritides are chronic inflammatory disorders, characterized by sacroiliitis, spondylitis, peripheral arthritis, extra-articular manifestations and association with HLA-B27. Specific clinical presentations allow to differentiate between different diseases such as ankylosing spondylitis, reactive arthritis, psoriasis arthritis and arthritis in inflammatory bowel disease. For therapy, regular physiotherapy, ergonomic counselling, anti-inflammatory drugs, disease-modifying drugs and antibiotics for chlamydia-induced reactive arthritis are used.

Combined Modality Therapy↗