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Biomedical subjects

A E Voskuyl

Publications and source records attributed to A E Voskuyl.

At least 19 recordsLinked to original sources
PubMed2007

Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients.

BACKGROUND: Rheumatoid arthritis (RA) is a heterogeneous disease with unknown cause. AIM: To identify peripheral blood (PB) gene expression profiles that may distinguish RA subtypes. METHODS: Large-scale expression profiling by cDNA microarrays was performed on PB from 35 patients and 15 healthy individuals. Differential gene expression was analysed by significance analysis of microarrays (SAM), followed by gene ontology analysis of the significant genes. Gene set enrichment analysis was applied to identify pathways relevant to disease. RESULTS: A substantially raised expression of a spectrum of genes involved in immune defence was found in the PB of patients with RA compared with healthy individuals. SAM analysis revealed a highly significant elevated expression of interferon (IFN) type I regulated genes in patients with RA compared with healthy individuals, which was confirmed by gene ontology and pathway analysis, suggesting that this pathway was activated systemically in RA. A quantitative analysis revealed that increased expression of IFN-response genes was characteristic of approximately half of the patients (IFN(high) patients). Application of pathway analysis revealed that the IFN(high) group was largely different from the controls, with evidence for upregulated pathways involved in coagulation and complement cascades, and fatty acid metabolism, while the IFN(low) group was similar to the controls. CONCLUSION: The IFN type I signature defines a subgroup of patients with RA, with a distinct biomolecular phenotype, characterised by increased activity of the innate defence system, coagulation and complement cascades, and fatty acid metabolism.

Adult↗
PubMed2006

[Rheumatic diseases as risk factors for cardiovascular disease].

Cardiovascular disease is the leading cause of death in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE). In addition to mortality, cardiovascular morbidity is also markedly increased in these patients, compared with the general population. The increased cardiovascular risk can be explained only partially by an increased prevalence of classical risk factors for cardiovascular disease; it also appears to be related to inflammation. Prospective intervention trials aimed at the modification of cardiovascular risk factors are needed to determine the impact of cardiovascular risk reduction in patients with rheumatic disease. In addition to SLE, RA and AS should be acknowledged as new risk factors for cardiovascular disease.

Arthritis, Rheumatoid↗
PubMed2006

Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis.

BACKGROUND: Many patients with rheumatoid arthritis are currently successfully treated with infliximab (anti-tumour necrosis factor); however, about 30% of the patients do not respond to infliximab. One of the postulated hypotheses of not responding is the fast clearance of infliximab due to the development of infliximab-anti-infliximab complexes. OBJECTIVE: To investigate the in vivo mechanism of not responding and the role of human anti-chimeric antibodies (HACAs) by using radiolabelled infliximab. METHODS: Two responding and two non-responding patients with rheumatoid arthritis, infused with radiolabelled infliximab, were investigated by both imaging and serum analysis. RESULTS: Images showed predominant presence of infliximab in blood up to 24 h, with a trend of faster blood clearance and of higher liver/spleen uptake in a non-responding patient. Clinically inflamed joints showed uptake of the drug. The HACA level in the non-responders was high (1641 and 1008 U/ml), but low or not detectable in responders. Sucrose gradients of serum showed antibody complexes in both non-responders. Various sizes of antibody complexes, including very large ones, were observed in a non-responder who developed a serious infusion reaction. CONCLUSION: Formation of infliximab-anti-infliximab complexes were found in non-responders due to the presence of large amounts of HACA. This finding, supported by both imaging and serum analysis data, may explain failure of infliximab treatment.

Adult↗
PubMed2006

Lipids and inflammation: serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is characterised by inflammation and an increased cardiovascular risk. It was recently shown that active early rheumatoid arthritis is associated with dyslipidaemia, which may partially explain the enhanced cardiovascular risk. However, it is unknown when this dyslipidaemia starts. OBJECTIVE: To investigate the progression of the lipid profile over time and the influence of inflammatory parameters on this lipid profile, in people who later developed rheumatoid arthritis. METHODS: Levels of total cholesterol, high-density lipoprotein cholesterol (HDLc), triglycerides, apolipoprotein AI (apo AI), apolipoprotein B (apo B) and lipoprotein(a) (Lp(a)) were determined in 1078 stored, deep-frozen, serial blood bank samples, collected between 1984 and 1999, of 79 blood donors who later developed rheumatoid arthritis. These samples were compared with 1071 control samples of unselected blood donors, matched for age, sex and storage time. RESULTS: Samples of patients who later developed rheumatoid arthritis showed, on average, 4% higher total cholesterol, 9% lower HDLc, 17% higher triglyceride and 6% higher apo B levels than matched controls (p< or =0.05). The magnitude of the differences in lipid levels between groups, explained by C reactive protein (CRP), was limited. For example, only 3.6% of the difference in HDLc levels between the groups was explained by the CRP concentrations. CONCLUSION: Patients who later develop rheumatoid arthritis have a considerably more atherogenic lipid profile than matched blood donors at least 10 years before onset of symptoms. As inflammation only marginally explains the differences between the two groups, a modulating effect of lipids on inflammatory processes is hypothesised.

Adult↗
PubMed2006

Evaluation of bone mineral density, bone metabolism, osteoprotegerin and receptor activator of the NFkappaB ligand serum levels during treatment with infliximab in patients with rheumatoid arthritis.

OBJECTIVES: To examine whether treatment with anti-tumour necrosis factor (TNF) alpha prevents loss of bone mineral density (BMD) at the spine and hip (generalised) and in the hands (local) of patients with rheumatoid arthritis, and to study the changes in markers of bone metabolism, including receptor activator of the NFkappaB ligand (RANKL) and osteoprotegerin (OPG), during anti-TNF treatment. PATIENTS AND METHODS: 102 patients with active rheumatoid arthritis, who were treated with infliximab during 1 year, were included in this open cohort study. The BMD of the spine and hip (dual x ray absorptiometry) and hands dual x ray radiogrammetry was measured before the start of treatment and after 1 year. Changes in osteocalcin formation, beta-isomerised carboxy terminal telopeptide of type 1 collagen (beta-CTx, resorption), RANKL and OPG were determined at 0, 14, 30 and 46 weeks. RESULTS: The BMD of the spine and hip was unchanged during treatment with infliximab, whereas BMD of the hand decreased significantly by 0.8% (p<0.01). The BMD of the hip in patients with a good European League Against Rheumatism response showed a favourable change compared with patients not achieving such a response. Serum beta-CTx and RANKL were both considerably decreased compared with baseline at all time points. The decrease in beta-CTx was associated with the decrease in Disease Activity Score of 28 joints and C reactive protein during the 0-14 weeks interval. CONCLUSION: In patients with rheumatoid arthritis treated with infliximab, spine and hip bone loss is arrested, whereas metacarpal cortical hand bone loss is not stopped. The outcome of the study also supports a relationship between clinical response, in terms of reduced inflammatory activity, and changes in bone loss of the spine, hip and hands.

Adult↗
PubMed2006

Long-term outcome in polymyositis and dermatomyositis.

BACKGROUND: Although polymyositis and dermatomyositis are regarded as treatable disorders, prognosis is not well known, as in the literature long-term outcome and prognostic factors vary widely. AIM: To analyse the prognostic outcome factors in polymyositis and adult dermatomyositis. METHODS: We determined mortality, clinical outcome (muscle strength, disability, persistent use of drugs and quality of life) and disease course and analysed prognostic outcome factors. RESULTS: Disease-related death occurred in at least 10% of the patients, mainly because of associated cancer and pulmonary complications. Re-examination of 110 patients after a median follow-up of 5 years showed that 20% remained in remission and were off drugs, whereas 80% had a polycyclic or chronic continuous course. The cumulative risk of incident connective tissue disorder in patients with myositis was significantly increased. 65% of the patients had normal strength at follow-up, 34% had no or slight disability, and 16% had normal physical sickness impact profile scores. Muscle weakness was associated with higher age (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3 to 10.3). Disability was associated with male sex (OR 3.1; 95% CI 1.2 to 7.9). 41% of the patients with a favourable clinical outcome were still using drugs. Jo-1 antibodies predicted the persistent use of drugs (OR 4.4, 95% CI 1.3 to 15.0). CONCLUSIONS: Dermatomyositis and polymyositis are serious diseases with a disease-related mortality of at least 10%. In the long term, myositis has a major effect on perceived disability and quality of life, despite the regained muscle strength.

Adolescent↗
PubMed2006

The heart and cardiovascular manifestations in rheumatoid arthritis.

Cardiovascular features in rheumatoid arthritis (RA) are common. Among those are the classical extra-articular features that not only include pericarditis, cardiomyopathy/myocarditis, cardiac amyloidosis, coronary vasculitis, arrhythmia and valve diseases, but also congestive heart failure and ischaemic heart disease which are found more frequently and are associated with an increased mortality compared with the general population. This overview discusses the epidemiological aspects of these cardiovascular diseases and their relevance for diagnosis and treatment of RA.

Arthritis, Rheumatoid↗
PubMed2005

Antibodies against human 60 kDa heat shock protein are not associated with cardiovascular disease in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is associated with an unexplained increased risk of cardiovascular disease (CVD). Antibodies against human 60 kDa heat shock protein (anti-HSP60) are associated with the presence and severity of CVD. OBJECTIVES: To investigate whether anti-HSP60 antibodies are associated with prevalent CVD in patients with rheumatoid arthritis. METHODS: In a nested case-control design, anti-HSP60 antibody levels were measured in the serum samples of 192 rheumatoid patients. In a regression analysis the association between prevalent CVD and anti-HSP60 antibodies was examined, along with the possible influence on this association of several demographic, rheumatoid arthritis, and CVD related variables. RESULTS: In a random sample of 326 patients with rheumatoid arthritis, 48 cases were identified who also suffered from CVD. Three controls per case with rheumatoid arthritis but without CVD (n = 144) were matched for sex, age, disease duration, and smoking habits. A regression analysis showed no significant association between prevalent CVD and anti-HSP60 antibodies (odds ratio = 1.00 (95% confidence interval, 0.997 to 1.004)). After correcting for possible confounding variables, still no association was found. CONCLUSIONS: In contrast to the general population, anti-HSP60 antibody titres are not associated with prevalent CVD in patients with rheumatoid arthritis. These findings could be the result of an altered immune response to HSP60 in rheumatoid arthritis.

Aged↗
PubMed2005

[Persistent fever in a patient with Salmonella typhimurium gonarthritis].

A 65-year-old patient with systemic lupus erythematodes (SLE) developed fever and gonarthritis whilst taking prednisone and hydrochloroquine. Salmonella typhimurium, sensitive to amoxicillin, was grown in cultures of synovial fluid, blood and urine. After high dosages of intravenous amoxicillin, blood cultures and knee punctate became negative, but fever seemingly without a clinical focus persisted. By means of a fluoro-18-deoxyglucose positron emission tomography (FDG-PET) scan, an abscess was located in the left upper leg and successfully treated. In patients with impaired cell-mediated immunity, an extra-intestinal manifestation of Salmonella should be taken into consideration particularly if there appears to be no clinical focus. This may be detected by FDG-PET.

Aged↗
PubMed2005

Infliximab treatment reduces complement activation in patients with rheumatoid arthritis.

BACKGROUND: Tumour necrosis factor (TNF) blocking agents decrease C reactive protein (CRP) levels in rheumatoid arthritis (RA). It has been shown that CRP may contribute to complement activation in RA. OBJECTIVE: To assess the effect of intravenous infliximab treatment on complement activation, especially that mediated by CRP, in RA. METHODS: 35 patients with active RA (28 joint count Disease Activity Score (DAS28) >4.4) were treated with intravenous injections of infliximab (3 mg/kg, at weeks 0, 2, 6, 14, and 22). Clinical response and plasma levels of complement activation products, of CRP and of CRP-complement complexes, which are specific markers for CRP mediated complement activation, were assessed at the indicated time points up to 22 weeks. The relationship between CRP and CRP-complement complexes was analysed by paired t test between two time points and by generalised estimated equation, to test differences of variables over time. RESULTS: At 2 weeks after the first dose, infliximab significantly reduced overall C3 and C4 activation and plasma levels of CRP and CRP-complement complexes were also significantly reduced at this time point. The effects of infliximab on CRP and complement continued throughout the observation period and were more pronounced in patients with a good response to infliximab treatment. CONCLUSION: Treatment with infliximab decreases plasma levels of CRP and CRP dependent complement activation products and concomitantly may reduce complement activation in RA. Complement activation may be among the effector mechanisms of TNF in RA.

Adult↗
PubMed2005

Raised plasma levels of asymmetric dimethylarginine are associated with cardiovascular events, disease activity, and organ damage in patients with systemic lupus erythematosus.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide inhibitor and a new independent risk factor for endothelial dysfunction and cardiovascular disease. OBJECTIVE: To investigate the relationship between plasma ADMA levels and cardiovascular events (CVEs) and disease characteristics in patients with systemic lupus erythematosus (SLE). METHODS: Demographic and clinical data were collected and plasma ADMA levels were measured in 107 patients with SLE. A modified organ damage index was calculated as defined by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), excluding CVE as an item. RESULTS: Cardiovascular disease, defined as > or =1 previous arterial CVE, was recorded in 16/107 (15%) patients with SLE and increased across tertiles of ADMA levels (p = 0.023 for trend). Mean plasma ADMA levels were significantly higher in patients with SLE with a history of CVEs than in patients without a CVE history (p = 0.018). In multiple regression analysis a high SLEDAI score, high modified SDI, high titre of anti-dsDNA antibodies, and low serum HDL were significantly associated with high plasma ADMA levels. CONCLUSION: In patients with SLE, plasma ADMA levels are significantly associated with CVEs, measures of disease activity, and organ damage, independently of an unfavourable lipid profile.

Adult↗
PubMed2004

Relationship between serum trough infliximab levels, pretreatment C reactive protein levels, and clinical response to infliximab treatment in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the relationship between serum trough infliximab levels and clinical response to infliximab treatment in patients with rheumatoid arthritis (RA). METHODS: Disease activity and serum trough infliximab levels before and 2, 6, and 14 weeks after initiation of infliximab treatment at a dose of 3 mg/kg in a cohort of 105 patients with RA were assessed. Serum trough infliximab levels in responders and non-responders were compared. Additionally, the clinical responses of patients with high, intermediate, and low serum trough infliximab levels at 14 weeks were compared. RESULTS: After 14 weeks of treatment non-responders had lower serum trough levels of infliximab than responders (median (interquartile range) 0.5 (0.2-2.2) v 3.6 (1.4-8.2) mg/l; p<0.01)). Patients with low serum trough infliximab levels at 14 weeks had significantly less improvement in the 28 joint count Disease Activity Score (DAS28) score than patients with intermediate or high serum trough infliximab levels at 14 weeks. Pretreatment C reactive protein (CRP) levels correlated negatively with serum trough infliximab levels at 14 weeks after the start of treatment (Spearman rank correlation r(s) = -0.43, p<0.001). CONCLUSION: Serum trough levels of infliximab correlate with the clinical response to treatment with infliximab and pretreatment CRP levels. This study indicates that patients with high pretreatment CRP levels might benefit from higher dosages of infliximab or shorter dosing intervals.

Adult↗
PubMed2004

[Diagnosis of pulmonary hypertension: experiences with 187 patients referred to the VU Medical Center].

OBJECTIVE: To describe the results of a multidisciplinary diagnostic protocol in patients referred due to suspected pulmonary hypertension. DESIGN: Descriptive. METHOD: In 187 patients who were referred to the VU Medical Centre, Amsterdam, the Netherlands, between May 1998 and February 2003, due to suspected pulmonary hypertension, the diagnosis was established by means of a multidisciplinary diagnostic protocol. The referral and final diagnoses were analysed, as well as the treatment the patients had received. RESULTS: In 56 patients (30%), the application of the protocol lead to a modification of the diagnosis; 16 patients (9%) were found not to have pulmonary hypertension; in 20 of the 89 patients referred with 'primary pulmonary hypertension' (48% of all referrals), an underlying disease was still identified: 6 cases of a connective tissue disease, 5 cases of a chronic thromboembolic process, 5 cases of a condition of the left heart, and 4 cases of an atrial septal defect. CONCLUSION: The diagnosis 'primary pulmonary hypertension' can only be made once all secondary types of the disease have been ruled out. The application of a multidisciplinary diagnostic protocol together with a contribution of specialists with specific expertise can help to adjust the initial diagnosis and sometimes even reject it.

Adolescent↗
PubMed2004

Bone mineral density in patients with rheumatoid arthritis: relation between disease severity and low bone mineral density.

OBJECTIVE: To examine variables associated with bone mineral density (BMD) in patients with rheumatoid arthritis (RA). METHODS: We investigated 373 patients with low to moderately active RA. Patients with low disease activity were recruited from a cohort of patients in clinical remission. Patients with moderately active disease were included in a trial comparing the effects of long term high intensity exercise programme and conventional physical therapy. Demographic and clinical data were collected. Bone mineral density (BMD) was measured by means of dual x ray absorptiometry (DXA). Associations between demographic and clinical measurements on the one hand and BMD on the other were investigated in regression analyses. RESULTS: The patient group consisted of middle aged, mainly female, patients. The median (interquartile range) disease duration was 7 (4 to 13) years, the mean disease activity score (standard deviation) was 3.2 (1.4). Of the group, 66% was rheumatoid factor positive, and 83% (n = 304) had never used corticosteroids. The median Larsen score of hands and feet was 27 (5 to 61). Greater age and low body mass index were related to low BMD at the hip and spine. High Larsen score for hands and feet was significantly associated with low BMD at the hip. The use of corticosteroids was not independently associated with BMD. The results of the multiple regression analyses also applied to the subgroup of corticosteroid naive patients. CONCLUSION: BMD data of patients with low to moderately active RA demonstrated an association between high radiological RA damage and low BMD at the hip, which suggests an association between the severity of RA and the risk of generalised bone loss, which also occurred in corticosteroid naive patients.

Adrenal Cortex Hormones↗
PubMed2004

Symmetrical, painful ulceration of the lower limbs in a vascular surgery ward: a diagnostic challenge. Pyoderma gangrenosum associated with IgG-kappa paraproteinaemia.

We describe a 61-year-old patient who had been suffering from chronic ulcers of both legs for 18 months. Initially, his condition was diagnosed as ischaemic because of an ankle-brachial index of 0.6, as confirmed by additional angiography. A successful femoro-infragenual bypass procedure was performed, but the ulcers increased in size and number. He was then extensively analysed for a possible (macro)vascular origin of his symptoms. Angiographic analysis of both legs showed no arterial stenosis or occlusion. Despite the extensive experience of the vascular surgeons with leg ulcers, consultations by internal medicine, vascular medicine and dermatology, and tissue examination by our pathologists, pyoderma gangrenosum was not recognised. During a multidisciplinary meeting one of the specialists, to whom the lesions were shown, immediately considered the diagnosis on clinical grounds. The additional finding of IgG-kappa paraproteinaemia and improvement of the ulcers on treatment with corticosteroids were consistent with the diagnosis. Although the majority of patients on the vascular surgery ward have ulcers caused by ischaemia or a combined arterial/venous origin, another (rare) cause, namely pyoderma gangrenosum in association with IgG-kappa paraproteinaemia without the presence of multiple myeloma, should be taken into account.

Chronic Disease↗
PubMed2003

Polymyositis: an overdiagnosed entity.

BACKGROUND: According to widely used criteria (Bohan and Peter criteria, 1975), dermatomyositis (DM) is differentiated from polymyositis (PM) only by skin changes. More recent criteria also include histopathologic characteristics enabling the distinction between PM and DM and the differentiation of sporadic inclusion body myositis (s-IBM) from PM. The authors investigated the applicability of diagnostic features for diagnosing PM and DM. METHODS: The authors performed a retrospective follow-up study of 165 patients with 1) a previous diagnosis of myositis; 2) subacute onset of symmetric, proximal weakness; and 3) an evaluation between 1977 and 1998 excluding other neuromuscular disorders. RESULTS: The diagnoses at initial evaluation based on clinical, laboratory, and histopathologic criteria were PM, 9 (5%); DM, 59 (36%; 54 isolated, 3 with associated connective tissue disease [CTD], 2 with associated malignancy); unspecified myositis (perimysial/perivascular infiltrates, no PM or DM), 65 (39%; 38 isolated myositis, 26 with associated CTD, 1 with malignancy); and possible myositis (necrotizing myopathy, no inflammatory infiltrates), 32 (19%; 29 isolated myositis, 3 with associated CTD). At follow-up evaluation, five of the nine patients with PM had typical s-IBM features. None of the remaining four patients complied with the assumed typical signs of PM. Ten of the 38 patients with isolated unspecified myositis had been diagnosed with a CTD. CONCLUSIONS: Polymyositis is an overdiagnosed entity. At evaluation, more than half the patients with autoimmune myositis cannot be specifically diagnosed with polymyositis or dermatomyositis. A quarter of patients with isolated unspecified myositis subsequently developed connective tissue disease.

Adult↗