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Biomedical subjects

F C Breedveld

Publications and source records attributed to F C Breedveld.

At least 217 records · Page 12Linked to original sources
PubMed1997

TNF-alpha promoter polymorphisms, production and susceptibility to multiple sclerosis in different groups of patients.

TNF-alpha production in whole blood cultures upon stimulation with LPS was determined in 179 individuals from 61 families in order to characterise the magnitude of inherited differences in TNF-alpha production. The three families characterised by highest TNF production showed 7.1 +/- 0.3 ng TNF/ml upon culture with 10 ng LPS and 10.2 +/- 0.2 ng TNF/ml upon culture with 1000 ng LPS. in contrast to the three families characterised by the lowest TNF production that showed a production of 1.6 +/- 0.1 ng TNF upon culture with 10 ng and 2.5 +/- 0.2 ng/ml upon culture with 1000 ng LPS/ml. This difference could not be attributed to the promoter polymorphisms -308 G to A. -238 G to A or -376 G to A, although the -238 GA donors produced 2.1 +/- 0.9 ng TNF upon culture with 10 ng endotoxin compared to 3.2 +/- 2.2 ng TNF for the -238 GG donors. In line with these results the frequency of the -238 GG genotype was increased in hospitalized MS patients in a nursing home (100% 238GG, n = 57) compared to MS patients in an outpatient's clinic (94% 238GG, n = 98) or Dutch controls (90% 238GG, n = 180). These results suggest that the -238 GG genotype is differently distributed in hospitalized MS patients in a nursing home.

Disease Susceptibility↗
PubMed1997

Rheumatic manifestations of hepatitis C virus infection.

Infection with hepatitis C virus (HCV) is a major cause of chronic hepatitis and has been associated with the occurrence of mixed cryoglobulinaemia. Treatment with interferon alpha can lower the titres of HCV, improve liver lesions and decrease cryoglobulins. In this report, a patient with HCV infection is described who developed arthritis, cutaneous vasculitis and sialoadenitis, together with hepatitis and cryoglobulinaemia. Clinical remission, particularly of the systemic symptoms, was achieved during treatment with interferon alpha.

Aged↗
PubMed1997

Measurement of morning stiffness in rheumatoid arthritis clinical trials.

OBJECTIVE: Morning stiffness (MS) is a common problem for patients with rheumatoid arthritis (RA). However the clinical evaluation of the symptom has proved to be difficult. The aim of the study was to determine the responsiveness of two methods for measuring MS. METHODS: Data from an uncontrolled (n = 63) and a controlled study (n = 80) of inpatient multidisciplinary team care for RA were analyzed. MS was measured by its duration to maximum improvement and by its severity on a visual analog scale (VAS). The responsiveness of both assessment methods was computed by calculating effect sizes and t-statistics, and by receiver operating characteristic (ROC) curves with clinical improvement according to the definition of the American College of Rheumatology as an external criterion. RESULTS: With respect to the ability to detect a clinical improvement between admission and discharge in the uncontrolled study, and a difference in improvement between the treatment and the control group in the controlled study, the effect sizes and t-values of the VAS for severity of MS were consistently higher than those of the duration of MS. In contrast to the duration, the responsiveness of the VAS for MS compared favorably with the responsiveness of other endpoint measures. The ROC surface area of the VAS was higher than that of the duration. CONCLUSION: For the evaluation of MS in RA clinical trials, the assessment of MS by a severity score is more responsive than one based on duration and compares favorably with the performance of other endpoint measures.

Aged↗
PubMed1997

Early rheumatoid arthritis. Future treatment.

As the pathophysiology of rheumatoid arthritis (RA) becomes more clearly defined there is the expectation that biotechnological advances may allow additional forms of therapeutic intervention that are specific for the disease process. The purpose of this review is to describe the use of biological agents in the treatment of RA. Encouraging results in animal models using vaccines based on the pathogenic T-cell or the autoantigen have prompted the design of selective immune-based therapies. Preliminary studies following this strategy have not yet shown clinical efficacy. The results of early studies with monoclonal antibodies against leukocyte surface antigen were promising but were not sustained in controlled studies. Exciting data have been collected from placebo-controlled studies of monoclonal antibodies against TNF alpha. The development of biological agents in RA may not be as quick as expected but the steady progress makes it likely that our weapons to combat unwanted autoimmune responses will become more accurate and effective.

Antirheumatic Agents↗
PubMed1997

Vasculitis associated with connective tissue disease.

Vasculitis, one of the clinical features shared by connective tissue diseases, should be considered when signs and symptoms are observed that may result from tissue ischaemia due to damaged vessels. The lesions seem to result from specific and non-specific immunopathogenic mechanisms targeted at the vascular endothelium. Because of the therapeutic implications it is the physician's responsibility to document its presence and the extent of organ involvement. Prompt institution of immunosuppressive drugs may be lifesaving. On the other hand there are some forms of vasculitis accompanying connective tissue disease which are entirely benign. Patients with infarctions of extremities and progressive functional disturbances of the central nervous system or internal organs because of vasculitis should be treated with high dosages of corticosteroids in combination with cytostatic drugs. Remissions are frequently obtained within three to six months of initiation of treatment and can be maintained with a less aggressive treatment regimen.

Connective Tissue Diseases↗
PubMed1997

Do synovial fluid acute phase proteins from patients with rheumatoid arthritis originate from serum?

This study was performed in order to gain insight into the occurrence, glycosylation and the possible origin of the acute-phase proteins alpha1-acid glycoprotein (AGP) and alpha1-protease inhibitor (PI) in sera and synovial fluid from patients with rheumatoid arthritis (RA). Therefore paired sera and synovial fluid samples from patients with RA, and paired synovial fluid samples from right and left knees of patients with varying degrees of arthritis were studied. Crossed affinity immunoelectrophoresis (CAIE) was used with concanavalin A and Aleuria aurantia lectin for the detection of the degree of branching and fucosylation, respectively, and the monoclonal CSLEX-1 for the detection of Sialyl Lewis(X) (SLe(X)) groups on AGP. For PI, not only CAIE, but also high-pressure-anion-exchange chromatography with pulsed amperometric detection was used to study the glycosylation. It was established that the concentrations of AGP and PI were increased in the serum of RA patients compared to normal healthy controls, but that the concentration of both proteins, as well as albumin, was significantly lower in synovial fluid than in serum. Furthermore, the type of glycosylation of both AGP and PI found in RA was significantly different from that found in normals, with increased fucosylation, but there were no major differences in the degree of branching of AGP- or PI-glycans in RA, compared to normals. No differences in glycosylation could be established between serum and synovial fluid in RA. For PI an increased fucosylation was found, both in serum and synovial fluid, using both methods of detection, and it could be established that only the alpha1-->3- and not the alpha1-->6-fucosylation of PI was affected by RA. The increased fucosylation of AGP resulted in an increased expression of SLe(X) on AGP-glycans. Since the alpha1-->3-fucosylation of AGP was significantly increased in both serum and synovial fluid from RA patients, and this correlated with systemic but not with local disease parameters, it can be suggested that acute phase proteins in synovial fluid are most probably of hepatic origin.

Adult↗
PubMed1997

Yersinia enterocolitica: a cause of chronic polyarthritis.

To investigate the role of Yersinia persistence in chronic undifferentiated arthritis, two patients who had chronic undifferentiated polyarthritis and circulating IgA and IgG antibodies to Yersinia outer proteins were studied. Immunofluorescence using antibodies directed against Yersinia adhesin A was performed on colonic and synovial tissue. Synovial tissue T cells were cloned aspecifically and screened for their proliferative responses to Yersinia enterocolitica. Furthermore, a Yersinia-specific polymerase chain reaction (PCR) was performed on synovial tissue. Both patients were found to have Yersinia antigens in colonic and synovial tissue. Y. enterocolitica-positive T-cell clones were grown from the synovial tissue: 4 CD4+ clones of 37 clones from patient 1 and 6 CD4+ clones of 53 clones from patient 2. Yersinia-specific PCR products were not detected in the synovial tissue specimens. The results support the hypothesis that an immune-mediated response to Yersinia antigens may play an important role in the pathogenesis of chronic undifferentiated arthritis.

Adhesins, Bacterial↗
PubMed1997

The two-year follow-up of a randomized comparison of in-patient multidisciplinary team care and routine out-patient care for active rheumatoid arthritis.

The long-term effects of a period of 11 days of in-patient multidisciplinary team care were compared with routine out-patient care in 80 patients with active rheumatoid arthritis (RA). Endpoint measures included swollen and tender joint counts, the patient's assessment of pain, the patient's and the physician's assessments of disease activity, the ESR and the Health Assessment Questionnaire (HAQ). Two years after hospitalization, all 39 patients randomized to the in-patient group and 39 out of 41 patients randomized to the out-patient group were evaluable. At 2 yr, in the in-patient group the improvement according to mean changes from baseline was greater than that in the out-patient group for all endpoint measures except for the HAQ score, the differences not reaching statistical significance. Averaged over the time points 2, 52 and 104 weeks, the improvement was significantly greater in the in-patient group than in the out-patient group, except for the ESR and HAQ score. In conclusion, a short period of in-patient multidisciplinary team care has a beneficial effect on disease activity over a period of 2 yr and should be considered as a useful treatment modality in patients with active RA.

Adult↗
PubMed1997

Bone matrix degradation by the plasminogen activation system. Possible mechanism of bone destruction in arthritis.

The observed increase in urokinase-type plasminogen activator (u-PA) and its receptor (u-PAR) in synovial tissue of patients with rheumatoid arthritis (RA) suggests pathophysiological involvement of the plasminogen activation (PA) system in inflammatory joint disease. In the present study, we investigated the capacity of the PA system to degrade non-mineralized and mineralized bone-like matrix in vitro as a model for bone destruction. Transfected mouse LB6 cell lines, that expressed either human u-PA or u-PAR, were cultured separately and simultaneously on radiolabelled bone matrix in the presence of plasminogen. Osteoblast-like murine calvarial MC3T3-E1 cells were used to produce a well-characterized, highly organized bone-like matrix, that could be mineralized in the presence of beta-glycerol phosphate. Bone matrix degradation was followed by the release of radioactivity in the culture medium. u-PA-producing cells, in contrast to u-PAR-producing cells, degraded both non-mineralized and mineralized bone matrix. This effect could be inhibited by anti-u-PA antibodies, as well as by tranexamic acid and by aprotinin, indicating that the degrading activity is u-PA mediated and plasmin dependent. Co-cultivation of a small portion of u-PA-producing cells with u-PAR-expressing cells resulted in a marked increase in degradation activity. Reduction of this potentiating effect by suramin or the amino-terminal fragment of u-PA, both competitive inhibitors of u-PA receptor binding, shows that this synergistic effect is due to binding of u-PA to u-PAR. u-PAR must be cell associated, as binding of u-PA to a soluble u-PAR prevented this enhancement. The capability of the PA system to degrade bone matrix in vitro, and the previously demonstrated increased expression of u-PA and u-PAR in synovial tissue of patients with RA, further support a role for the PA system in the development of bone erosions.

3T3 Cells↗
PubMed1997

Tumour necrosis factor alpha gene polymorphisms in rheumatoid arthritis: association with susceptibility to, or severity of, disease?

Genetic factors associated with rheumatoid arthritis (RA) might involve variant tumour necrosis factor (TNF)-alpha genes. Therefore, polymorphisms at positions -308, -238, -376, -163 and +70 relative to the transcription initiation site were studied with respect to the susceptibility to, or severity of, RA. TNF-alpha genotypes of 283 RA patients and 116 healthy individuals were determined. Clinical data were obtained from patient files and questionnaires. The distribution of TNF-alpha alleles was similar in RA patients and healthy controls. With respect to disease severity, the TNF-alpha -238GA genotype was found to be associated with the absence of erosions [odds ratio (OR) 4.1, confidence interval 1.0-17]. In addition, this genotype was associated with a lower number of hand joints affected by erosions within the first 3 yr of disease onset compared to -238GG. The association between the -238 polymorphism and radiographic progression was independent of the presence of HLA-DR4. In line with this observation, the OR for the presence of erosions in patients with both risk factors (DR4 and -238GG) compared to patients who lack these factors was 11.1 (1.8-6.8). No associations between the TNF-alpha -308, +70 and -376 alleles and susceptibility to, or severity of, RA could be demonstrated. Our data indicate that the TNF-alpha -238GA genotype is associated with decreased radiologically detectable progression of RA.

Adenine↗
PubMed1997

Do patients with systemic sclerosis have abnormal gallbladder function?

OBJECTIVE: To determine gallbladder motility in patients with systemic sclerosis. DESIGN: Case control study. SETTING: University hospital, out-patient department of rheumatology. PATIENTS: Ten patients with systemic sclerosis according to the criteria of the American Rheumatism Association with documented involvement of the gastrointestinal tract and 10 healthy controls matched for age, sex and body mass index. INTERVENTION: Cephalic vagal cholinergic simulation by modified sham feeding and hormonal stimulation by infusion of cholecystokinin. MEASUREMENTS: Gallbladder volume obtained by ultrasonography and determination of plasma cholecystokinin concentrations. RESULTS: Fasting gallbladder volumes were not significantly different between patients with systemic sclerosis and controls (19.6 +/- 1.9 cm3 and 23.3 +/- 2.9 cm3, respectively, mean plus or minus standard error of the mean). Neither were there significant differences in reduction of gallbladder volume in response to modified sham feeding (35 +/- 4% and 33 +/- 4%, respectively) nor during cholecystokinin infusion (56 +/- 4% and 60 +/- 6%, respectively). The increase in plasma cholecystokinin levels during infusion was not different in the two groups. CONCLUSION: Gallbladder motility in patients with systemic sclerosis is preserved in response to both cholinergic and hormonal stimulation, even when other gastrointestinal motor disturbances are present. These results suggest that patients with systemic sclerosis are not at increased risk for cholelithiasis because of gallbladder dysmotility.

Case-Control Studies↗
PubMed1997

Effect of resumption of second line drugs in patients with rheumatoid arthritis that flared up after treatment discontinuation.

OBJECTIVE: To assess the effect of resumption of second line drugs in patients with rheumatoid arthritis (RA) that flared after treatment discontinuation. METHODS: RA patients were studied whose RA flared up after discontinuation of second line treatment while being in remission and who received a second course of the drug. Disease activity parameters were prospectively assessed at the time of treatment discontinuation, during the period when the disease flared up, and three months thereafter. Furthermore the medical charts were reviewed at 12 months after treatment resumption. RESULTS: There were 51 patients included in the study: 25 patients treated with antimalarial drugs, 10 with parenteral gold, four with d-penicillamine, eight with sulphasalazine, two with azathioprine, and two with methotrexate. Disease activity parameters showed significant improvement within three months of treatment resumption, but remained significantly worse when compared with that measured before treatment discontinuation. Within three months 47% of the patients fulfilled 20% response criteria. Disease activity 12 months after treatment resumption was considered to be absent in 35%, mild in 43%, and moderate or active in 22% of the patients. In four (8%) patients the resumed treatment was stopped because of lack of efficacy. Side effects were recorded in four patients, which did not result in treatment discontinuation. CONCLUSIONS: Resumption of second line drugs in RA patients whose disease flared up after discontinuation of treatment is effective and safe in most patients. Half of the patients responded within three months after resumption of the second line drug.

Acute Disease↗
PubMed1997

Genetic linkage analysis of 14 candidate gene loci in a family with autosomal dominant osteoarthritis without dysplasia.

The role of various gene loci was investigated in a family in which familial osteoarthritis (FOA), with onset at an early age, is transmitted as an autosomal dominant mendelian trait. The absence of clinical and radiographic signs of dysplasia and calcium pyrophosphate deposition disease (CPDD) indicates that the basic disease process in this family is osteoarthritis (OA). Genetic linkage analysis of 14 candidate genes resulted in the exclusion of 10 important genes (COL2A1, COL9A1, COL9A2, COL11A1, COL11A2, COMP, the CPDD region, CRTL-1, CRTM, and MMP3). Other relevant genes were not informative in this family. The candidate loci previously identified in FOA and heritable skeletal disorders associated with OA are clearly not involved in the development of the primary FOA phenotype in the family investigated, indicating genetic heterogeneity.

Adult↗
PubMed1997

HLA-DRB1, DQA1, and DQB1 genotypes and risk of vasculitis in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the association of rheumatoid vasculitis (RV) with the expression of the shared epitope, HLA-DRB1*04, DQA1, and DQB1 alleles. METHODS: A case-control study was designed to compare the frequency of the shared epitope, DRB1*04 alleles, DQA1, and DQB1 alleles of 31 patients with RV with that of 76 patients with rheumatoid arthritis (RA) without vasculitis. RV cases were discerned in subgroups according to presence or absence of minor skin vasculitis and major organ lesions. HLA-DRB1, DQA1, and DQB1 typing was performed by a polymerase chain reaction amplification and oligonucleotide hybridization. RESULTS: Overall, no associations were found between RV and the shared epitope, the DRB1*04 alleles, DQA1, or DQB1 alleles. The risk of developing RV with minor skin vasculitis (i.e., purpura or petechiae) was 10-20-fold increased in patients with DRB1*04, in particular in those homozygous for DRB1*04, and also in those with DRB1*0401. No such association was found for patients with major organ lesions. CONCLUSION: The occurrence of vasculitis in RA is not associated with the shared epitope. DQA1, or DQB1 alleles. However, the risk of minor skin vasculitis is higher in patients carrying DRB1*04.

Adult↗
PubMed1997

Elevated levels of inflammatory cytokines in bone marrow of patients with rheumatoid arthritis and anemia of chronic disease.

OBJECTIVE: Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) play an important role in decreased erythropoiesis in patients with anemia of chronic disease (ACD) and rheumatoid arthritis (RA). Modulation of quantities of bone marrow erythroid progenitors during chronic inflammation may be one of the pathogenetic mechanisms leading to ACD. We studied bone marrow from patients with ACD with RA by investigating, first, local production of inflammatory cytokines in the bone marrow, and second, the relative fraction of late erythroid progenitors (erythropoietin and transferrin receptor positive cells; EpoR+ TrfR+) in bone marrow. In addition, the effects of TNF-alpha on EpoR+ TrfR+ cells were studied in vitro. METHODS: Levels of IL-6 and TNF-alpha were measured by EL ELISA in supernatant of bone marrow and peripheral blood cultures from 14 patients with RA and ACD and 14 patients with RA without anemia. The numbers of EpoR+ TrfR+ cells in bone marrow samples of both groups were assessed by 2 color fluorescence flow cytometry. RESULTS: Levels of IL-6 and TNF-alpha were significantly higher in the supernatant of bone marrow cultures of patients with ACD compared to controls. No significant differences in the fraction of EpoR+ TrfR+ cells in samples was observed between the 2 groups of patients. Incubation of the samples with TNF-alpha did not result in modulation of the number of EpoR+ TrfR+ cells. CONCLUSION: Local production of proinflammatory cytokines in the bone marrow may be associated with the development of ACD in RA.

Adolescent↗
PubMed1997

The limited value of the Health Assessment Questionnaire as an outcome measure in short term exercise trials.

OBJECTIVE: To examine the value of the Health Assessment Questionnaire (HAQ) as an outcome measure in short term exercise trials. We studied the association of the objectives of exercise, namely joint mobility, muscle strength, and physical condition, with the HAQ. METHODS: Data for 100 patients with rheumatoid arthritis (RA) included in a study to examine the effect of exercise therapy were used for secondary analysis. Disease activity was determined by the disease activity score (DAS3), pain was scored on a visual analog scale (VAS), and depression was measured by the Dutch Arthritis Impact Measurement Scale. Aerobic capacity (VO2max) estimated from a submaximal ergometer test, grip strength (kPa), isokinetic muscle strength of the knee (Nm/kg), and the Escola Paulista de Medicina range of motion (EPM-ROM) score, a measure of general flexibility, were used as indicators for physical impairments. All variables were entered in a forward multiple regression analysis with the HAQ as dependent variable. RESULTS: The HAQ was significantly correlated with the DAS3 score (r = 0.53), pain (r = 0.51), depression (r = 0.40), joint mobility (r = 0.27), quadriceps strength (r = -0.35), and grip strength (r = -0.50), but not with physical condition. The DAS3 score was first entered in the multiple regression analysis model, followed by pain, quadriceps strength, and grip strength (R2 = 0.45). After 12 weeks of exercise therapy changes in the HAQ were significantly correlated with changes in pain (r = 0.41), in depression (r = 0.33), and in quadriceps strength (r = -0.25), but not with changes in joint mobility or physical condition. CONCLUSION: Physical impairments are weakly associated with the HAQ. The HAQ is not an appropriate instrument to detect changes in physical impairments due to short term exercise therapy.

Adult↗