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Biomedical subjects

T W Huizinga

Publications and source records attributed to T W Huizinga.

At least 37 records · Page 2Linked to original sources
PubMed2001

Delayed referral of female patients with rheumatoid arthritis.

OBJECTIVE: To analyze whether sex differences in referral exist in patients with rheumatoid arthritis (RA). METHODS: At the Department of Rheumatology of the Leiden University Medical Center, a special early arthritis clinic (EAC) was established. General practitioners (GPs) were encouraged to refer patients with joint complaints to the EAC. Subsequently, the diagnosis RA was made by a rheumatologist. RESULTS: In this report, 142 women and 82 men were included. The delays in patient's first encounter with a GP for both sexes were comparable. However, a significant difference in the GP's delay in referring female patients with RA to the EAC in comparison with male patients was observed (median of 93 days vs 58 days; p = 0.008). CONCLUSION: This report determined GP referral delay of female patients to a rheumatologist. GPs should be made aware that early detection and early referral of patients with RA are crucial for early treatment.

Academic Medical Centers↗
PubMed2000

TNF-308A and HLA-DR3 alleles contribute independently to susceptibility to systemic lupus erythematosus.

OBJECTIVE: To evaluate the respective contributions of tumor necrosis factor (TNF) promoter polymorphisms and HLA-DR alleles to susceptibility to systemic lupus erythematosus (SLE). METHODS: TNF-238G/A and 308G/A promoter polymorphisms and HLA-DRB1 alleles were determined in 99 consecutive Caucasian SLE patients and 177 Caucasian controls. Standard and Mantel-Haenszel odds ratios were calculated to assess the magnitude of the susceptibility factors. The presence or absence of the SLE classification criteria was determined and correlated with the TNF promoter and HLA-DRB1 genotypes. RESULTS: The frequency of the TNF-308A/A and 308G/A genotypes was significantly higher in SLE patients (odds ratio 5.0). Conversely, TNF-238G/A and 238A/A genotypes were equally prevalent in SLE patients and controls. The HLA-DR3 specificity (DRBI*0301 allele) was significantly more prevalent in the SLE population (odds ratio 4.4). Stratification to correct for interdependence of the 2 loci confirmed the association of both TNF-308A and HLA-DR3 with SLE (Mantel-Haenszel odds ratio 3.2 and 2.4, respectively). No correlation was found between TNF promoter and HLA-DRB1 genotypes and any SLE classification criterion or disease manifestation. CONCLUSION: TNF-308A and HLA-DR3 alleles are independent susceptibility factors for SLE.

Adult↗
PubMed2000

Evidence of central nervous system damage in patients with neuropsychiatric systemic lupus erythematosus, demonstrated by magnetization transfer imaging.

OBJECTIVE: The clinical symptoms of neuropsychiatric systemic lupus erythematosus (NPSLE) are usually reversible, but whether the associated brain damage is also reversible is still a matter of debate. Since magnetization transfer imaging (MTI) is more sensitive than conventional magnetic resonance imaging (MRI) in demonstrating brain damage, it has become a useful tool in the detection and quantification of diffuse brain disorders such as multiple sclerosis. In this study, MTI was applied to investigate whether central nervous system (CNS) damage is present in patients with a history of NPSLE. METHODS: Eleven female patients with a history of NPSLE and no previous or concurrent primary neurologic or psychiatric disease (ages 17-49 years), 11 female patients with SLE without a history of NPSLE (non-NPSLE; ages 15-51 years), and 10 healthy female controls (ages 17-47 years) underwent MTI. From these MTI scans, quantitative data on the uniformity of the brain parenchyma and atrophy were derived. RESULTS: One NPSLE and 1 non-NPSLE patient were excluded from this study due to infarctions detected with conventional MRI. MTI measures normalized for intracranial volume, reflecting abnormalities of the brain parenchyma as well as atrophy, were lower (P < 0.001) in the NPSLE group than in both control groups. A higher (P < 0.005) mean ratio of cerebrospinal fluid to intracranial volume, indicative of atrophy, was present in the NPSLE group compared with either the non-NPSLE patients or healthy controls. Still, the MTI measures solely reflecting uniformity of the brain parenchyma (normalized for brain volume) were also significantly (P < 0.001) lower in the NPSLE patients than in both control groups. CONCLUSION: This study demonstrates that using MTI, CNS damage can be demonstrated in patients with a history of NPSLE. MTI might, therefore, be an alternative and sensitive tool to detect brain injury in NPSLE, and might also be useful in studying the natural history of the disease.

Adolescent↗
PubMed2000

Cartilage degradation and invasion by rheumatoid synovial fibroblasts is inhibited by gene transfer of a cell surface-targeted plasmin inhibitor.

OBJECTIVE: Joint destruction in rheumatoid arthritis (RA) is a result of degradation and invasion of the articular cartilage by the pannus tissue. The present study was undertaken to examine the role of the plasminogen activation system in cartilage degradation and invasion by synovial fibroblasts and investigate a novel gene therapeutic approach using a cell surface-targeted plasmin inhibitor (ATF.BPTI). METHODS: Adenoviral vectors were used for gene transfer. The effects of ATF.BPTI gene transfer on RA synovial fibroblast-dependent cartilage degradation were studied in vitro, and cartilage invasion was studied in vivo in the SCID mouse coimplantation model. RESULTS: The results indicate that cartilage matrix degradation by rheumatoid synovial fibroblasts is plasmin mediated and depends on urokinase-type plasminogen activator for activation. Targeting plasmin inhibition to the cell surface of the fibroblasts by gene transfer of a cell surface-binding plasmin inhibitor resulted in a significant reduction of cartilage matrix degradation in vitro and of cartilage invasion in vivo. Compared with uninfected rheumatoid synovial fibroblasts, the mean +/-SEM cartilage degradation in vitro was reduced to 87.9+/-0.9% after LacZ gene transfer versus a reduction to 24.0+/-1.6% after ATF.BPTI gene transfer (P<0.0001). The mean +/- SEM in vivo cartilage invasion score was 3.1+/-0.4 in the control-transduced fibroblasts and 1.8+/-0.4 in the ATF.BPTI-transduced fibroblasts (P<0.05). CONCLUSION: These results indicate a role of the plasminogen activation system in synovial fibroblast-dependent cartilage degradation and invasion in RA, and demonstrate an effective way to inhibit this by gene transfer of a cell surface-targeted plasmin inhibitor.

Activating Transcription Factors↗
PubMed2000

Detection of cerebral involvement in patients with active neuropsychiatric systemic lupus erythematosus by the use of volumetric magnetization transfer imaging.

OBJECTIVE: To determine whether volumetric magnetization transfer imaging (MTI) histogram analysis can detect abnormalities in patients with active neuropsychiatric systemic lupus erythematosus (NPSLE) and to compare the MTI findings in patients with active NPSLE, chronic NPSLE, and multiple sclerosis (MS), as well as in normal control subjects. METHODS: Eight female and 1 male patient with active nonthromboembolic NPSLE (mean +/- SD age 39 +/- 9 years), 10 female patients with chronic NPSLE (age 33 +/- 11 years), 10 female patients with SLE and no history of NPSLE (non-NPSLE; age 34 +/- 11 years), 10 female patients with inactive MS (age 41 +/- 6 years), and 10 healthy control subjects (age 33 +/- 11 years) underwent MTL. Using the MTI scans, histograms were composed from which we derived a variety of parameters that quantitatively reflect the uniformity of the brain parenchyma as well as the ratio of cerebrospinal fluid to intracranial volume, which reflects atrophy. RESULTS: The magnetization transfer ratio (MTR) histograms in the non-NPSLE group and the healthy control group were similar, whereas those in the chronic NPSLE and MS groups were flatter. There was also flattening of the histograms in the active NPSLE group, but with a shift toward higher MTRs. CONCLUSION: Our results indicate that volumetric MTI analysis detects cerebral changes in the active phase of NPSLE. The abnormalities in the brain parenchyma of patients with chronic NPSLE produced MTI values that were the same as those in patients with inactive MS. MTI values in the active phase of NPSLE differed from those in the chronic phase, which might reflect the presence of inflammation. These preliminary results suggest that MTI might provide evidence for the presence of active NPSLE. MTI might also prove to be a valuable technique for monitoring treatment trials.

Acute Disease↗
PubMed2000

Innate production of interleukin-10 and tumor necrosis factor affects the risk of multiple sclerosis.

Multiple sclerosis (MS) typically presents with a relapsing-remitting onset. This can be distinguished from primary progressive MS. Typical MS is characterized by a profound inflammatory reaction in which anti-inflammatory cytokine interleukin-10 (IL-10) and pro-inflammatory cytokine tumor necrosis factor (TNF) may play a pivotal role. We tested the hypothesis that patients with MS have a distinct innate cytokine production that contributes to the susceptibility for and outcome of MS. The innate cytokine production of patients was estimated as the average production of cytokines in lipopolysaccharide -stimulated whole-blood cultures of 2 to 5 first-degree healthy family members. A total of 126 family members of 50 patients with typical MS, 61 family members of 25 patients with primary progressive MS, and 129 control subjects of 54 families were enrolled in this study. We found that members of families with low IL-10 and high TNF production had a fourfold increased risk of developing typical MS compared with members of families with high IL-10 and low TNF production. Patients with MS were eightfold more likely to develop typical MS than primary progressive MS when they belonged to families with low IL-10 and high TNF production. The presence of human leukocyte antigen-DR2 was associated with MS but not with TNF production. This study shows that typical MS is associated with an innate pro-inflammatory cytokine profile in contrast to primary progressive MS.

Adult↗
PubMed2000

Are differences in interleukin 10 production associated with joint damage?

OBJECTIVE: Constitutive differences between individuals in cytokine production may determine the variation in the course of inflammatory arthritis. METHODS: The association between interleukin 10 (IL-10) production and joint destruction was studied by comparing IL-10 mRNA content in synovial biopsies from seven patients with destructive joint disease and six patients with non-destructive joint disease. The IL-10 mRNA content was 0.4 +/- 0.6 arbitrary units in erosive joints compared with 2.3 +/- 1.2 arbitrary units in non-erosive joints (P: < 0.03, Mann-Whitney U:-test). As this difference suggested that IL-10 production was associated with joint destruction, we tested whether the IL-10 locus determined the extent of joint damage. RESULTS: Innate differences in IL-10 production are locus-dependent. In line with these data, we showed that innate differences in IL-10 protein production were also present as differences in IL-10 mRNA levels. We tested if polymorphisms in the promoter of IL-10 were associated with the extent of joint damage. DISCUSSION: In a cohort study of female rheumatoid arthritis patients followed for 12 yr, the extent of joint destruction differed significantly between patients with different IL-10 genotypes. In patients with the -1082AA genotype who were studied prospectively, the mean increase in radiographic damage score (modified Sharp score of X-rays of hands and feet) during the first 6 yr was 9 +/- 9 per yr vs 19 +/- 16 per yr for patients with the genotype -1082GG (P: < 0.02). In line with these data, cultures of endotoxin-stimulated whole blood from 158 donors showed that the presence of the allele associated with less joint destruction correlated with slightly higher IL-10 production. CONCLUSIONS: Both the immunogenetic and the synovial biopsies suggest that a variation in IL-10 production is associated with joint destruction.

Adult↗
PubMed2000

Reliability and sensitivity to change of various measures of hand function in relation to treatment of synovitis of the metacarpophalangeal joint in rheumatoid arthritis.

OBJECTIVES: The reliability and discriminative capacity of hand function tests were studied in order to obtain tests suitable for the evaluation of local treatment of an arthritic metacarpophalangeal (MCP) joint. METHODS: To assess reliability, hand function tests were measured twice without local treatment of the MCP in 25 patients with rheumatoid arthritis (RA). The discriminative capacity of the hand function tests with respect to the results of intra-articular corticosteroid injection was assessed in 28 RA patients with synovitis of an MCP joint. Thereafter, a randomized, observer-blind treatment study was performed in 21 RA patients with synovitis of an MCP joint; 10 of the patients were treated. Results/Conclusions. This study showed that the efficacy of treatment of an MCP joint can be measured by several reliable and discriminative parameters: passive flexion, the Ritchie pain score, swelling, the Arthritis Impact Measurements Scales question about buttoning clothes, and visual analogue scale questions about the activity of the disease and swelling of the joint.

Adult↗
PubMed2000

High interleukin-10 production in first-degree relatives of patients with generalized but not cutaneous lupus erythematosus.

BACKGROUND: Preclinical research suggests that interleukin-10 (IL-10) is associated with susceptibility to and severity of systemic lupus erythematosus. Chronic cutaneous lupus erythematosus is thought to be immunogenetically different from systemic lupus erythematosus. We hypothesized that high innate production of IL-10 underlies systemic but not chronic cutaneous lupus erythematosus. METHODS: IL-10 production was determined after endotoxin stimulation of whole-blood samples. In whole-blood samples, disease activity and medication influence the IL-10 production in patients. Therefore, healthy first-degree relatives of patients were evaluated. One hundred sixty-six first-degree relatives of patients with systemic lupus, 50 first-degree relatives of patients with chronic cutaneous lupus, and 133 control persons were studied. Innate IL-10 production of the patient was estimated as the mean IL-10 production of the unaffected relatives. Polymorphisms located -1082, -819, and -592 base pairs relative to the IL-10 gene were typed by allele-specific oligohybridization of polymerase chain reaction-amplified DNA fragments. RESULTS: IL-10 production was higher in the families of patients with systemic lupus than in the control families (1517 +/- 94 vs 1180 +/- 59 pg/mL; P = 0.003). IL-10 production in the families of patients with chronic cutaneous lupus was similar to that in control families (1216 +/- 82 vs 1180 +/- 59 pg/ml; P = 0.74). IL-10 production was also similar in families of patients with severe compared with nonsevere systemic lupus (P = 1.0). The frequency of -1082/-819/-592 haplotypes GCC, ACC, and ATA was similar among patients and compared with the control persons (P = 0.29). CONCLUSIONS: High innate IL-10 production underlies susceptibility for systemic lupus erythematosus but not the severity of the disease. It is not related to chronic cutaneous lupus erythematosus.

Adult↗
PubMed1999

Feasibility of adenovirus-mediated nonsurgical synovectomy in collagen-induced arthritis-affected rhesus monkeys.

Gene transfer to synovial tissue by adenoviral vectors (Ad) was studied in vitro in cultured human synoviocytes and in vivo in seven primates with arthritis. Hyperplastic synovium was efficiently transduced with Ad.lacZ in vitro and in vivo in rhesus monkeys with collagen-induced arthritis, whereas chondrocytes were not transduced. Intraarticular injection of recombinant Ad harboring the luciferase gene showed the presence of reporter gene products only in Ad-injected joints. In addition, the feasibility of synovectomy by Ad harboring the herpes simplex virus thymidine kinase gene (tk) was studied. In vitro infection of synovium from rheumatoid arthritis patients with Ad.TK, followed by administration of ganciclovir, resulted in death of >90% of the synoviocytes. By mixing Ad.TK-infected with noninfected cells, it appeared that the presence of 10% infected synoviocytes resulted in the killing of more than 85% of the synoviocytes, demonstrating a substantial bystander effect. Intraarticular injection of Ad.TK in the knees of rhesus monkeys with arthritis, followed by treatment with ganciclovir for 14 days, resulted in increased apoptotic cell death in the synovium of Ad.TK-injected as compared with noninjected joints and ablation of the synovial lining layer. The procedure revealed no toxic side effects. These data suggest that nonsurgical synovectomy by tK gene therapy is feasible.

Adenoviridae↗
PubMed1999

Polymorphism within the tumor necrosis factor alpha (TNF) promoter region in patients with ankylosing spondylitis.

In addition to HLA-B27, other genetic factors are thought to be involved in the pathogenesis of ankylosing spondylitis (AS). Because of the location of the TNF gene in the vicinity of the HLA-B locus, and the prominent role in inflammation of its product, we investigated the association between AS and two G to A transition polymorphisms located at position -238 and -376 in the promoter region of the TNF gene. The distribution of the TNF alleles was determined in 86 HLA-B27+ AS patients and 163 healthy controls. From the 86 AS patients, 33 suffered from acute anterior uveitis (AAU). No significant difference for the TNF-376 polymorphism in AS and healthy controls was observed. The frequency of the TNF-238A allele in HLA-B27+ AS patients was significantly decreased compared to random controls (p = 0.021). However, the frequency of the TNF-238A allele in HLA-B27+ AS patients was not significantly different from that observed in HLA-B27+ healthy individuals (p = 0.6). Assessment of association showed that the TNF-238G allele is in linkage disequilibrium with the HLA-B27 allele (delta = 0.053; P = 0.008). Therefore, we conclude that the association between TNF-238G and AS is secondary to the HLA-B27 gene and that TNF-238 and-TNF-376 alleles are not likely to be involved in the susceptibility to AS.

Alleles↗
PubMed1999

Association of the TNF +489 polymorphism with susceptibility and radiographic damage in rheumatoid arthritis.

Multiple genetic factors contribute to susceptibility to rheumatoid arthritis (RA). The extent of variability in disease presentation in RA may be related to genetic heterogeneity. In this study we investigated the association of the TNF gene polymorphism at position +489 with susceptibility to and severity of RA. Analysis of the frequency of the +489 A and G alleles in a group of 293 consecutive RA patients and 138 healthy controls revealed a significant decrease of the A allele. The +489 GA patients had a 3.9 times decreased chance of having erosive disease than +489 GG patients. These results were confirmed in a prospective study using a cohort of 112 patients who were followed for 12 years. The progression rate of the erosion score over 12 years expressed as Sharp score for X-rays of hands and feet was 3.4 per year for the GA-genotyped patients and 12.1 for the GG-genotyped patients. These associations were independent of rheumatoid factor and HLA-shared epitope positivity. In conclusion, these data suggest that the intron TNF +489 polymorphism is associated with susceptibility to and disease severity of RA independently of HLA-shared epitope-positive alleles.

Adult↗
PubMed1999

Childhood-onset Systemic Lupus Erythematosus: clinical presentation and prognosis in 31 patients.

OBJECTIVE: To determine the clinical features at onset, the disease course, and prognostic factors in children with SLE. METHODS: The medical records of 31 patients with childhood-onset SLE were reviewed. Signs and symptoms at onset and during the course of the disease were documented as well as survival and SLICC/ACR damage index. The disease course was compared to 135 consecutive adult-onset SLE patients. RESULTS: Childhood-onset SLE most frequently presented with fatigue, arthritis, fever, weight loss, and malar rash. During follow-up, the frequency of the presence of malar rash, anemia, leukocytopenia, and anti-dsDNA antibodies was significantly higher in childhood-onset than in adult-onset patients. Mean SLICC/ACR damage index was 2.6 after 4.7 years of follow-up. The presence of arthritis, anemia, and seizures at the onset of disease resulted in a 2.6 to 3.9 times higher chance of a severe disease course. CONCLUSION: Patients with childhood-onset SLE suffer from substantial morbidity. Arthritis, anemia, and seizures at onset may be indicators of poor prognosis.

Adolescent↗
PubMed1999

The influence of a partially HLA-matched blood transfusion on the disease activity of rheumatoid arthritis.

OBJECTIVE: Based on the immunosuppressive effects of blood transfusions in organ transplantation, we determined the effect of a blood transfusion on disease activity of rheumatoid arthritis (RA). METHOD: In this double-blind pilot study, 40 patients with active RA were randomly assigned to receive a HLA-DRB1-matched blood transfusion (n = 30) or placebo (n = 10). Disease activity was scored according to the American College of Rheumatology response criteria during 6 months of follow-up. RESULTS: After 1 month and 6 months, respectively, 6 and 16% of patients fulfilled the response criteria in the blood transfusion group compared to none and 30%, respectively, in the placebo group. Following correction for the increase in haemoglobin levels, a majority of the response parameters in the blood transfusion group showed significant improvement compared to the placebo group. CONCLUSION: A DRB1-matched blood transfusion shows improvement of symptoms in several RA patients. Additional studies are required to identify blood transfusion regimens that enhance the potential for therapeutic responses.

Adult↗