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Biomedical subjects

F C Breedveld

Publications and source records attributed to F C Breedveld.

462 records · Page 26Linked to original sources
PubMedDate not supplied

Joint scintigraphy for quantification of synovitis with 99mTc-labelled human immunoglobulin G compared to histological examination.

OBJECTIVE: This study addressed the following questions: How does 99mTc-IgG scintigraphy compare to physical examination in the detection of synovitis as determined histologically, and is 99mTc-IgG scintigraphy a sensitive detector of histologically documented synovitis activity in the absence of clinically detectable knee joint swelling? METHODS: The results of measuring synovitis activity by physical examination and by scintigraphy with technetium-99m labelled polyclonal human immunoglobulin G (99mTc-IgG) were compared with the results of histological examination of synovial biopsies taken from the knee joints of patients with rheumatoid arthritis (n = 21), osteoarthritis (n = 9) and various other rheumatic diseases (n = 10). RESULTS: The sensitivity of 99mTc-IgG scintigraphy in detecting synovitis activity, as determined histologically (85%), was higher than the sensitivity of joint swelling (65%). In the absence of clinically detectable knee joint swelling the sensitivity of 99mTc-IgG scintigraphy was 83%. CONCLUSION: This study shows that 99mTc-IgG scintigraphy is a more sensitive method than physical examination in detecting histologically documented synovitis activity.

Adult↗
PubMedDate not supplied

Autoantibodies to neutrophil cytoplasmic enzymes in Felty's syndrome.

In this study we determined the occurrence of anti-neutrophil cytoplasmic antibodies (ANCA) and the specificity of these antibodies (Ab) in the serum of patients with Felty's syndrome (FS) and in serum of patients with uncomplicated rheumatoid arthritis (RA). ANCA, detected by indirect immunofluorescence on ethanol-fixed neutrophils, was found in 77% of 30 patients with FS and in 36% of 50 RA patients. Ab against lactoferrin (LF) occurred more frequently in FS patients (50%) than in RA patients (4%), whereas reactivity against the other cytoplasmic antigens tested (proteinase-3, myeloperoxidase and elastase) did not differ significantly between these patient groups. The specific reactivity of FS sera with LF was established by demonstrating that the Ab reactivity resided in IgG, was located in the F(ab')2 fragments and could be inhibited from binding to the ELISA plate-bound LF by purified LF in the fluid phase. These results demonstrate that anti-LF Ab occur in FS and suggest that the detection of anti-LF Ab in patients with FS may be useful in the diagnosis of FS.

Adult↗
PubMedDate not supplied

Antibiotics as disease modifiers in arthritis.

The tetracyclines, especially minocycline, are supposed to have antiarthritic properties. Their efficacy has been tested in open clinical studies on RA patients. Recently a double-blind placebo-controlled trial was performed which revealed the antirheumatic properties of minocycline. The mode of action of the tetracyclines in arthritis is unknown, but could be linked to the immunosuppressive activity seen in vitro. The antiproliferative effect of minocycline in cloned synovial T-cells is demonstrated; moreover IFN-gamma production in cloned synovial T-cells is inhibited by minocycline.

Adolescent↗
PubMedDate not supplied

T cell vaccination in humans: the experience in rheumatoid arthritis.

To determine the effects of T cell vaccination (TCV) in patients with rheumatoid arthritis (RA), thirteen RA patients were inoculated with attenuated synovial T lymphocytes which contain the putatively pathogenic cells. The procedure was technically feasible and free from toxicity. Variable clinical and immunological responses were found. However, in one patient with recent onset disease and treated with a defined T cell clone, a temporary beneficial response coincided with depressed mitogen reactivity and a decrease of rheumatoid factors. This study may serve as a lead for future research on TCV in humans.

Animals↗
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T cell receptor rearrangements in juvenile rheumatoid arthritis: a search for oligoclonality.

Southern blot analysis of DNA from paired samples of synovial compartment (membrane and/or fluid) and peripheral blood T cells from nine children with juvenile rheumatoid arthritis (JRA) was carried out. Using a T cell receptor C beta probe, dominant TCR rearrangements were discovered in specimens from three patients: synovial fluid T cells from one, synovial fluid and synovial membrane cells from a second, and synovial membrane and peripheral blood cells from a third. The patient showing dominant bands in peripheral blood as well as in synovium was the only child in the series with systemic disease. Since non-specific T cell recruitment is likely to dilute antigen specific clones to low levels, the finding of dominant rearrangements in three of nine patients may indicate that oligoclonality is indeed a feature of JRA.

Arthritis, Juvenile↗
PubMedDate not supplied

Bone mineral density in ambulant, non-steroid treated female patients with rheumatoid arthritis.

Bone mass measurements were performed in a group of 30 ambulant, non-steroid treated female patients with rheumatoid arthritis (RA) of relatively short duration (mean 4.9 years). The bone mineral density (BMD) of the lumbar spine and femoral neck was assessed by dual-energy x-ray absorptiometry (DEXA), and related to parameters of disease activity and severity. Lumbar BMD was within the range of normal while femoral BMD was decreased compared to age-matched controls. BMD values, expressed as the percentage of age-matched healthy controls (BMD%), were positively related to the body mass index and negatively related to the number of swollen joints, the erythrocyte sedimentation rate and the platelet count. No relation was found between the lumbar and femoral bone mass on the one hand and disease duration, number of disease modifying anti-rheumatic drugs ever used, Ritchie articular index, C-reactive protein, functional ability or radiological scores on the other. It is concluded that in ambulant non-steroid treated female RA patients lumbar bone mass as measured with DEXA is within the range of normal, while femoral bone mass is slightly reduced. Both lumbar and femoral bone mass are related to the body mass index and parameters of disease activity.

Absorptiometry, Photon↗
PubMedDate not supplied

Relevance of the tumor necrosis factor alpha (TNF alpha) -308 promoter polymorphism in TNF alpha gene regulation.

Tumor necrosis factor alpha (TNF alpha) is a central mediator of the immunological response and the location of the gene within the major histocompatibility complex (MHC) has prompted much speculation about the role of TNF alpha alleles in inflammatory and MHC-associated autoimmune diseases. A G to A transition polymorphism at position -308 of the TNF alpha promoter/enhancer region has been described. The uncommon -308A allele was shown to be strongly associated with human leukocyte antigen (HLA)-DR3, known to be related to a TNF alpha "high producer" phenotype. In support for a clinical relevance, the -308A allele is implicated in susceptibility for cerebral malaria. In this study, we determined the junctional consequences of the TNF -308 polymorphism. Therefore, we analyzed both allelic forms (TNF alpha(-308G) and TNF alpha(-3O8A)) of the TNF alpha enhancer/promoter region (-598/+108) in a transient transfection system, using chloramphenicol acetyltransferase (CAT) as reporter gene. The T cell line Jurkat and the B cell line Raji served as hosts in these experiments. The results showed no differences in the level of inducible reporter gene expression between the TNF(-3O8G)/CAT and the TNF(-308A)/CAT constructs. These data were confirmed by allele specific TNF alpha transcript quantification (ASTQ) analysis, which demonstrated that both TNF alleles contribute equally to the total amount of mRNA in peripheral blood mononuclear cells (PBMCs) stimulated with phorbol 12-myristate 13-acetate (PMA)/anti-CD3. In analogy, no difference between the level of transcription of the -308A and -308G alleles was observed in lipopolysaccharide (LPS)-stimulated peripheral blood monocytes. This study indicates that the TNF alpha -308 G to A transition is not responsible for differential TNF alpha production induced by standard in vitro stimuli.

Alleles↗
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Variations in the monitoring and management of the side effects of antirheumatic drugs by means of laboratory tests.

OBJECTIVE: To ascertain the strategies Dutch rheumatologists would employ in the monitoring of side effects of non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs (DMARDs) by means of laboratory tests, and in the management of detected toxicity. METHODS: A questionnaire was sent to all practicing Dutch rheumatologists concerning NSAIDs and the following DMARDs: antimalarials (AMALs), intramuscular gold (Au), d-penicillamine (DPEN), sulfasalazine (SASP), methotrexate (MTX) and azathioprine (AZA). RESULTS: The response rate was 72% (83/114). Except for AMALs, at least 90% of rheumatologists determined the haemoglobin concentration during NSAID or DMARD therapy, the white blood cell (WBC) and platelet count during DMARD, serum creatinine and transaminases during MTX, and proteinuria during Au and DPEN therapy. At least 88% did not request a urinalysis when prescribing AMALs, and serum bilirubin and albumin when prescribing all drugs. The majority used monitoring intervals of < 3 months when prescribing DMARDs (except for AMALs) during the induction phase of therapy and during the maintenance phase in the case of Au and MTX treatment. For all DMARDs except AMALs, 65% to 75% would change the treatment when the WBC count was 2.5-3.4 x 10(9)/l. When the platelet count was 100-150 x 10(9)/l, 67% to 85% would not. The percentage of rheumatologists that would change the medication when the transaminase levels were 2 to 3 times the upper limit of normal or when proteinuria was 0.5-1.0 g/l varied considerably irrespective of the drug involved. CONCLUSIONS: The strategies that Dutch rheumatologists would employ showed uniformity in the choice for some laboratory tests, but also showed considerable variation in the case of other tests, the monitoring intervals, and treatment interventions.

Adverse Drug Reaction Reporting Systems↗
PubMedDate not supplied

Levels of circulating cellular fibronectin are increased in patients with rheumatoid vasculitis.

OBJECTIVE: To investigate whether serum levels of circulating cellular fibronectin (cFN) are increased in patients with rheumatoid arthritis (RA) complicated by vasculitis. METHODS: Levels of serum cFN were determined by an enzyme-linked immunosorbent assay (ELISA) in 26 RA patients with histologically proven vasculitis of recent onset (RV) and were compared to the levels in 47 RA patients with extraarticular manifestations of recent onset but no histological evidence of vasculitis (RA+), 43 patients with uncomplicated RA (RA-), 16 patients with systemic lupus erythematosus and active disease (SLE), 30 patients with active Crohn's disease (CD), 21 young healthy controls (yHC) and 17 elderly healthy controls (eHC). Plasma levels of cFN and von Willebrand factor antigen were also determined in the RA patients. RESULTS: In RV patients, the median cFN level was significantly (P = 0.01) higher compared to that of RA+ patients, and was also significantly (P < 0.0000) higher compared to the cFN level in the RA-, SLE, CD, yHC and eHC groups. When compared to eHC, the cFN level was significantly higher in RA+ (P = 0.008); it was also higher in RA-, although not significantly (P = 0.42). 77% of the RV patients, 55% of the RA+ patients, and 37% of the RA-patients had a cFN level > 2 SD above the mean level for eHC. At an optimal cut-off titre the sensitivity of the cFN ELISA in discriminating RV patients from RA+ patients was 90%, the specificity was 46% and the accuracy was 68%. Plasma levels of cFN correlated significantly (r = 0.62; P < 0.001) with the von Willebrand factor antigen levels. CONCLUSIONS: Increased levels of serum cFN are present in patients with RA, and are frequently found in RA patients with extraarticular manifestations, particularly in those with vasculitis.

Adolescent↗
PubMedDate not supplied

Human parvovirus B19 infection is not followed by inflammatory joint disease during long term follow-up. A retrospective study of 54 patients.

OBJECTIVE: To investigate whether recent human parvovirus B19 (B19) infection provokes inflammatory arthritis, we assessed the outcome of 54 patients with recent B19 infection who were referred to the Department of Rheumatology. METHODS: Consecutive patients referred between 1985 and 1995 and found to have a recent B19 infection were studied retrospectively by sending a questionnaire and, if necessary, by physical examination. RESULTS: In the acute phase of B19 infection, all patients had arthralgia and many also complained of myalgia and malaise. Arthritis was found in 61% of the patients, skin rash in 72% and fever in 64%. Except for the arthralgia and malaise, most of the symptoms resolved rapidly. After a mean followup of 5 years (SD 2.9 yrs.) none of the patients reported persistence of joint swelling or restricted motion. CONCLUSION: None of the 54 patients with recent B19 infection developed chronic arthritis.

Acute Disease↗
PubMedDate not supplied

Rheumatoid vasculitis presenting as appendicitis.

Appendicitis was diagnosed in a 38-year-old patient with seropositive rheumatoid arthritis. Despite appendectomy the patient's clinical condition deteriorated. Thorough microscopical evaluation of the pathological anatomical specimens from the appendix made possible a diagnosis of necrotizing vasculitis. The systemic nature of the vasculitis was confirmed with a muscle biopsy. A complete remission was induced with immunosuppressive treatment. The case exemplifies a rare but serious manifestation of rheumatoid vasculitis.

Adult↗