I Watt

Leiden University Medical Centre, Leyden, South Holland, Netherlands

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Publications (147)629.75 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to identify risk factors for knee osteoarthritis (OA) development in a young to middle-aged population with sub-acute knee complaints. This, in order to define high risk patients who may benefit from early preventive or future disease modifying therapies. Knee OA development visible on radiographs and MR in 319 patients (mean age 41.5 years) 10 years after sub-acute knee complaints and subjective knee function (KOOS score) was studied. Associations between OA development and age, gender, activity level, BMI, meniscal or anterior cruciate ligament (ACL) lesions, OA in first-degree relatives and radiographic hand OA were determined using multivariable logistic regression analysis. OA on radiographs and MR in the TFC is associated with increased age (OR: 1.10, 95 % 1.04-1.16 and OR: 1.07, 95 % 1.02-1.13). TFC OA on radiographs only is associated with ACL and/or meniscal lesions (OR: 5.01, 95 % 2.14-11.73), presence of hand OA (OR: 4.69, 95 % 1.35-16.32) and higher Tegner activity scores at baseline before the complaints (OR: 1.20, 95 % 1.01-1.43). The presence of OA in the TFC diagnosed only on MRI is associated with a family history of OA (OR: 2.44, 95 % 1.18-5.06) and a higher BMI (OR: 1.13, 95 % 1.04-1.23). OA in the PFC diagnosed on both radiographs and MR is associated with an increased age (OR: 1.06, 95 % 1.02-1.12 and OR: 1.05, 95 % 1.00-1.09). PFC OA diagnosed on radiographs only is associated with a higher BMI (OR: 1.12, 95 % 1.02-1.22). The presence of OA in the PFC diagnosed on MR only is associated with the presence of hand OA (OR: 3.39, 95 % 1.10-10.50). Compared to normal reference values, the study population had significantly lower KOOS scores in the different subscales. These results show that knee OA development in young to middle aged patients with a history of sub-acute knee complaints is associated with the presence of known risk factors for knee OA. OA is already visible on radiographs and MRI after 10 years. These high risk patients may benefit from adequate OA management early in life.
    Clinical Rheumatology 09/2014; · 1.77 Impact Factor
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    ABSTRACT: OBJECTIVE: To investigate patterns of osteoarthritis (OA) progression within hand joints and the relationship between hand OA progression and progression of OA at the knee. METHODS: Radiographic progression over 6 years, defined as change in osteophytes or joint space narrowing above the smallest detectable change, was assessed on hand and knee radiographs of 236 hand OA patients participating in the Genetics, Arthrosis and Progression (GARP) sibling pair cohort study using OARSI atlas. Clustering of radiographic progression between hand joint groups (DIP, PIP, IP-1 and CMC-1) was assessed using χ(2) test. Symmetry, clustering by row and ray and familial aggregation in sibling pairs were also evaluated. The association between hand OA progression and progression of OA at the knee was assessed using generalised estimating equation analysis. RESULTS: There was clustering of OA progression between hand joint groups, the strongest relationship among DIP, PIP and IP-1 joints. Other patterns were symmetry (OR 4.7 (95% CI 3.3 to 6.5)) and clustering by row (OR 2.9 (95% CI 1.9 to 4.6)) but not by ray (OR 1.3 (95% CI 0.7 to 2.4)). There was familial aggregation of hand OA progression. Patients with progression of hand OA had a higher risk for radiographic change at the knee than those without hand OA progression (OR 2.3 (95% CI 1.3 to 4.0)). CONCLUSIONS: Progression of hand OA clusters between hand joint groups, especially between IP joints, and within sibling pairs. It is associated with OA change at the knee. These findings contribute to defining hand OA subsets and suggest a role for systemic factors.
    Annals of the rheumatic diseases 02/2013; · 9.27 Impact Factor
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    ABSTRACT: To study the association between metacarpal bone mineral density (BMD) loss and progressive hand osteoarthritis (OA) over 2 years. Using the Kellgren-Lawrence (KL) grading scale and the Osteoarthritis Research Society International Atlas, standardised hand radiographs of 181 patients with primary OA at multiple sites (mean age 60 years, 80% women, mean body mass index 27 kg/m(2)) were assessed for hand OA at baseline (KL ≥ 2 in two or more hand joints) and progressive hand OA over 2 years (≥ 1 point increase in total osteophyte and joint space narrowing score in patients with hand OA at baseline). Changes in BMD were measured over 2 years in metacarpals 2-4 by digital x-ray radiogrammetry. Accelerated BMD loss was defined as loss of >3 mg/cm(2)/year. Logistic regression analyses were performed to assess the associations between BMD loss and progressive hand OA. The baseline prevalence of hand OA was 68% and, after 2 years, 32% of these patients had progressive hand OA. Accelerated BMD loss was present in 79% of the patients with progressive hand OA compared with 60% and 57% of the patients with non-progressive hand OA and no hand OA, respectively. BMD loss was independently associated with progressive hand OA compared with non-progressive hand OA with a RR (95% CI) of 2.1 (1.1 to 4.3). Accelerated metacarpal BMD loss is associated with progressive hand OA over a period of 2 years; knowledge of common mechanisms may lead to development of therapeutic interventions for hand OA.
    Annals of the rheumatic diseases 05/2011; 70(9):1625-30. · 9.27 Impact Factor
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    ABSTRACT: To compare the reliability, sensitivity to change and feasibility of three radiographic scoring methods for hand osteoarthritis (OA). Baseline, 2-year and 6-year hand radiographs of 90 patients with hand OA were read in triplicate in chronological order by three readers from different European centres using the OARSI atlas (OARSI), Kellgren--Lawrence grading scale (KL) and Verbruggen--Veys anatomical phase score (VV). Reliability was determined using intraclass correlation coefficients and smallest detectable change (SDC). Sensitivity to change was assessed by the proportion of progression above the SDC. Feasibility was reflected by the mean performance time. Intra- and inter-reader reliability was similar across methods. Inter-reader SDCs (% maximum score) for KL, OARSI and VV were 2.9 (3.2), 4.1 (2.9) and 2.7 (1.8) over 2 years and 3.8 (4.1), 4.6 (3.3) and 4.0 (2.5) over 6 years, respectively. KL detected a slightly higher proportion of progression. There were differences between readers, despite methods to enhance consistency. The mean performance time (SD, minutes) for KL, OARSI and VV was 4.3 (2.5), 9.3 (6.0) and 2.8 (1.5), respectively. Methods had comparable reliability and sensitivity to change. Global methods were fastest to perform. For multicentre trials use of a central reading centre and multiple readers may minimise inter-reader variation.
    Annals of the rheumatic diseases 05/2011; 70(8):1465-7. · 9.27 Impact Factor
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    ABSTRACT: To agree terminology and to develop recommendations for the diagnosis of calcium pyrophosphate deposition (CPPD). The European League Against Rheumatism (EULAR) CPPD Task Force, comprising 15 experts from 10 countries, agreed the terms and recommendations for diagnosis of CPPD using a Delphi consensus approach. Evidence was systematically reviewed and presented in terms of sensitivity, specificity and positive likelihood ratio (LR) to support diagnosis; ORs were used for association. Strength of recommendation (SOR) was assessed by the EULAR visual analogue scale. It was agreed that 'CPPD' should be the umbrella term that includes acute calcium pyrophosphate (CPP) crystal arthritis, osteoarthritis (OA) with CPPD and chronic CPP crystal inflammatory arthritis. Chondrocalcinosis (CC) defines cartilage calcification, most commonly due to CPPD and detected by imaging or histological examination. A total of 11 key recommendations were generated on the topics of clinical features, synovial fluid (SF) examination, imaging, comorbidities and risk factors. Definitive diagnosis of CPPD relies on identification of SF CPP crystals. Rapid onset inflammatory symptoms and signs are suggestive but not definitive for acute CPP crystal arthritis. Radiographic CC is not highly sensitive or specific, whereas ultrasonography appears more useful (LR=24.2, 95% CI 3.51 to 168.01) for peripheral joints. Recognised risk factors for CPPD include ageing, OA and metabolic conditions such as primary hyperparathyroidism, haemochromatosis and hypomagnesaemia; familial forms are rare. SORs varied from 53 to 99 (maximum 100). New terms for CPPD were agreed and 11 key recommendations for diagnosis of CPPD were developed using research evidence and expert consensus.
    Annals of the rheumatic diseases 03/2011; 70(4):563-70. · 9.27 Impact Factor
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    ABSTRACT: To develop evidence-based recommendations for management of calcium pyrophosphate deposition (CPPD). A multidisciplinary guideline development group of 15 experts, representing 10 European countries, generated key propositions for management of CPPD using a Delphi consensus approach. For each recommendation research evidence was searched systematically. Whenever possible, the effect size and number needed to treat for efficacy and RR or OR for side effects were calculated for individual treatment modalities. Strength of recommendation was assessed by the European League Against Rheumatism visual analogue scale. Nine key recommendations were generated, including topics for general management, treatment of acute attacks, prophylaxis against recurrent acute attacks and management of chronic symptoms. It was recommended that optimal treatment requires both non-pharmacological and pharmacological treatments. For acute CPP crystal arthritis, cool packs, temporary rest and joint aspiration combined with steroid injection are often sufficient. For prophylaxis or chronic inflammatory arthritis with CPPD, oral non-steroidal anti-inflammatory drugs with gastroprotective treatment and/or low-dose colchicine 0.5-1.0 mg daily may be used. Other recommendations included parenteral or oral corticosteroid for acute CPP arthritis in those unresponsive or unsuited to other measures, and low-dose corticosteroid, methotrexate or hydroxychloroquine for chronic inflammatory arthritis with CPPD. Asymptomatic CPPD requires no treatment. Strength of recommendations varies from 79% to 95%. Nine key recommendations for management of CPP crystal associated arthritis were developed using both research evidence and expert consensus. Strength of recommendations was provided to assist the application of these recommendations.
    Annals of the rheumatic diseases 03/2011; 70(4):571-5. · 9.27 Impact Factor
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    ABSTRACT: In order to gain insight in the pathogenesis of erosive hand osteoarthritis (OA), the evolution of erosions in hand OA and risk factors involved were investigated. The 6-year evolution in radiographic Verbruggen-Veys anatomical phase was assessed in interphalangeal joints of 236 patients with hand OA (mean age 59 years, 83% women) from the GARP (for 'Genetics ARthrosis and Progression') sibling pair study. Erosive evolution comprised phase transitions from non-erosive to erosive phases and from active erosions to remodelling. Clustering of erosive evolution within patients was assessed using the χ² test. Familial aggregation was evaluated in sibling pairs by estimating ORs for siblings and probands sharing erosive evolution. Local baseline determinants and the effect of high sensitivity C reactive protein were assessed using generalised estimating equations. Erosive evolution took place in 181 of 4120 interphalangeal joints at risk (4.4%), corresponding to 60 patients (25.4% of study sample). Erosive evolution was found more often in multiple interphalangeal joints in one patient than would be expected by chance (χ² 373.0, p < 0.001). The adjusted OR (95% CI) for a sibling having erosive evolution if the proband had erosive evolution was 4.7 (1.4 to 15.8). Systemic inflammation was not associated with erosive activity. Independent local determinants were joint space narrowing (OR (95% CI) 8.9 (4.8 to 16.4)) and self-reported pain (OR (95%CI) 2.3 (1.1 to 4.7)). rosive evolution was clustered within patients and families. Local factors were also involved in the evolution. This increase in insight in the pathogenesis of erosive hand OA will contribute to the development of new treatments.
    Annals of the rheumatic diseases 02/2011; 70(2):326-30. · 9.27 Impact Factor
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    ABSTRACT: To validate a newly developed quantification method that automatically detects and quantifies the joint space width (JSW) in hand radiographs. Repeatability, accuracy and sensitivity to changes in JSW were determined. The influence of joint location and joint shape on the measurements was tested. A mechanical micrometer set-up was developed to define and adjust the true JSW in an acrylic phantom joint and in human cadaver-derived phalangeal joints. Radiographic measurements of the JSW were compared to the true JSW. Repeatability, systematic error (accuracy) and sensitivity (defined as the smallest detectable difference (SDD)) were determined. The influence of joint position on the JSW measurement was assessed by varying the location of the acrylic phantom on the X-ray detector with respect to the X-ray beam and the influence of joint shape was determined by using morphologically different human cadaver joints. The mean systematic error was 0.052 mm in the phantom joint and 0.210 mm in the cadaver experiment. In the phantom experiments, the repeatability was high (SDD = 0.028 mm), but differed slightly between joint locations (p = 0.046), and a change in JSW of 0.037 mm could be detected. Dependent of the joint shape in the cadaver hand, a change in JSW between 0.018 and 0.047 mm could be detected. The automatic quantification method is sensitive to small changes in JSW. Considering the published data of JSW decline in the normal and osteoarthritic population, the first signs of OA progression with this method can be detected within 1 or 2 years.
    Skeletal Radiology 02/2011; 41(1):41-9. · 1.74 Impact Factor
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    ABSTRACT: To investigate the long-term clinical and radiographic disease course of hand osteoarthritis (OA) and determinants of outcome. Clinical and radiographic measures were obtained at baseline and after 6 years in 289 patients with hand OA (mean age 59.5 years, 83.0% women). Clinical outcomes were self-reported pain and functional limitations assessed with the Australian/Canadian Osteoarthritis Hand Index (AUSCAN). Poor clinical outcome was defined as a follow-up score not fulfilling the Patient Acceptable Symptom State. Radiographic outcome was assessed by osteophytes and joint space narrowing (JSN) on standardised hand radiographs using the Osteoarthritis Research Society International (OARSI) atlas. Radiographic progression was defined as a change in osteophytes or JSN, above the smallest detectable change. Change in outcome measures was calculated and baseline determinants for poor clinical outcome and radiographic progression were assessed using logistic regression analysis. Clinical change showed great variation, with half of the population reporting deterioration. Poor outcome in pain was related to high levels of functional limitations and a high number of painful joints at baseline. Poor outcome on functional limitations was related to high baseline pain levels. Radiographic progression was present in 52.5% of patients and associated with high baseline levels of pain, nodes, osteophytes and the presence of erosive OA and nodal OA. Clinical change and radiographic progression were not related. This study gives insight in the clinical and radiographic course of hand OA as well as determinants of outcome. These findings enable better patient information on prognosis. The relationship between clinical and radiographic outcome needs further investigation.
    Annals of the rheumatic diseases 01/2011; 70(1):68-73. · 9.27 Impact Factor
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    ABSTRACT: To systematically evaluate the association between MRI findings (cartilage defects, bone marrow lesions (BML), osteophytes, meniscal lesion, effusion/synovitis, ligamentous abnormalities, subchondral cysts and bone attrition) and pain in patients with knee osteoarthritis (OA) in order to establish the relevance of such findings when assessing an individual patient. The Medline, Web of Science, Embase and Cumulative Index to Nursing & Allied Health Literature (CINAHL) databases up to March 2010 were searched without language restriction to find publications with data on the association between MRI findings of knee OA (exposure of interest) and knee pain (outcome). The quality of included papers was scored using a predefined criteria set. The levels of evidence were determined qualitatively using best evidence synthesis (based on guidelines on systematic review from the Cochrane Collaboration Back Review Group). Five levels of evidence were used: strong, moderate, limited, conflicting and no evidence. A total of 22 papers were included; 5 had longitudinal and 17 cross-sectional data. In all, 13 reported a single MRI finding and 9 multiple MRI findings. Moderate levels of evidence were found for BML and effusion/synovitis. The OR for BML ranged from 2.0 (no CI was given) to 5.0 (2.4 to 10.5). The OR of having pain when effusion/synovitis was present ranged between 3.2 (1.04 to 5.3) and 10.0 (1.1 to 149). The level of evidences between other MRI findings and pain were limited or conflicting. Knee pain in OA is associated with BML and effusion/synovitis suggesting that these features may indicate the origin of pain in knee OA. However, due to the moderate level of evidence these features need to be explored further.
    Annals of the rheumatic diseases 01/2011; 70(1):60-7. · 9.27 Impact Factor
  • Osteoarthritis and Cartilage 10/2010; 18. · 4.26 Impact Factor
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    ABSTRACT: To investigate the association between systemic and local inflammation and incident and progressive radiographic secondary osteoarthritis (OA) in interphalangeal joints (IPJs) over 3 years in rheumatoid arthritis (RA) patients and the effect of tumor necrosis factor alpha (TNF-α) inhibitor infliximab on secondary OA in IPJs. In the present observational longitudinal study baseline and 3-year hand X-rays of 416 recent-onset RA patients were scored for osteophytes and erosions in IPJs, blinded for time, using Osteoarthritis Research Society International atlas and Sharp-van der Heijde score. The associations between inflammatory factors and incident and progressive secondary OA in distal IPJs (DIPJs) and proximal IPJs (PIPJs) and the effect of infliximab compared to disease-modifying anti-rheumatic drug treatment on secondary OA were analyzed by multivariable regression and generalised estimating equations analyses. Sixty-seven percent of the patients were female with, at baseline, a mean age of 54 years and OA present in DIPJs and PIPJs in 37% and 13%. Three years later, new secondary OA in DIPJs and PIPJs was seen in 11% and 10%, and progressive secondary OA in 36% and 35%. High erythrocyte sedimentation rate over 3 years and progressive erosive damage were risk factors for incident secondary OA in DIPJs, but not in PIPJs. At joint level, progression of erosions was associated with both incident and progressive secondary OA, only in DIPJs. Infliximab treatment was associated with lower incident secondary OA in PIPJs [relative risk 0.5 (95% confidence interval 0.2, 1.0)], independent of decrease in inflammation. Incident and progressive secondary OA in DIPJs over 3 years was associated with high inflammatory activity in RA. Infliximab treatment reduced incident secondary OA in PIPJs independent of decrease in inflammation, suggesting that anti-TNF-α therapy might be effective against secondary hand OA via other pathways than suppression of inflammation. Further studies in populations of primary hand OA are necessary to determine the role of anti-TNF-α in treatment of primary hand OA.
    Osteoarthritis and Cartilage 10/2010; 18(10):1256-62. · 4.26 Impact Factor
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    ABSTRACT: To describe the clinical burden of erosive osteoarthritis (EOA) of the hand in terms of pain, functioning and health-related quality of life (HRQL) and its relationship to nodal osteoarthritis (OA). Patients with EOA (n=42) and non-EOA (n=194) of the hand were compared. Pain was assessed with the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Michigan Hand Outcome Questionnaire (MHQ) and pain intensity upon pressure. Functioning was evaluated with AUSCAN, MHQ, grip strength, pinch grip and hand mobility tests. HRQL was measured with the Short Form-36. Patient satisfaction with hand function and aesthetics were also evaluated. The presence of nodal OA as well as its extent (reflected by the number of nodes) was assessed. Mean differences between patient groups were estimated with linear mixed models. To determine whether differences were independent of the nodal character of the disease, adjustments were made for the number of nodes. Patients with EOA experienced more pain, more functional limitation, less satisfaction with hand function and aesthetics and worse hand mobility than patients with non-EOA. HRQL was similar for the two groups. Patients with EOA had more nodes. A higher number of nodes was associated with worse outcome. After correction for the number of nodes, only hand mobility and patient satisfaction remained different between the groups. Patients with EOA have a higher clinical burden than those with non-erosive disease. This higher burden is only partly attributed to the erosive disease itself, but mainly to the nodal character of the disease.
    Annals of the rheumatic diseases 10/2010; 69(10):1784-8. · 9.27 Impact Factor
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    ABSTRACT: To define localized development of knee osteoarthritis (OA) that arises from anterior cruciate ligament (ACL) and meniscal injuries identified at magnetic resonance (MR) imaging performed a decade ago and the subsequent management of those findings in patients with subacute knee symptoms. The present study was approved by local medical ethics review boards, and written informed consent was obtained. Three hundred twenty-six patients (mean age, 42 years; 108 female) from a previously reported series of 855 patients were followed up with regard to the effect of MR imaging-guided treatment for subacute knee problems. The mean follow-up period was 10 years. Initial findings and treatment were compared with the follow-up radiograph and 3.0-T MR image findings. Odds ratios (ORs), with corresponding 95% confidence intervals, were used to identify the effects between variables. Patients with ACL ruptures had an increased risk of developing joint space narrowing (JSN), cartilaginous defects, osteophytes, bone marrow lesions, and subchondral cysts medially or laterally (OR, 2.4-9.8). Patients with medial meniscal tears had an increased risk of developing JSN, cartilaginous defects, osteophytes, and bone marrow lesions medially (OR, 2.0-15.3). Patients with lateral meniscal tears had an increased risk of developing JSN, cartilaginous defects, osteophytes, bone marrow lesions, and subchondral cysts laterally (OR, 2.1-10.5). Meniscectomy had no effect on the risk of developing OA. Localized knee OA developed from risk factors identified from the findings of MR imaging performed a decade ago in patients with subacute knee symptoms and did not depend on the surgical treatment of those findings.
    Radiology 08/2010; 256(2):536-46. · 6.21 Impact Factor
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    ABSTRACT: To investigate the association of ultrasound (US) features-grey scale (GS) synovitis, synovial thickening, effusion and power Doppler signal (PDS)-with symptoms in hand osteoarthritis (HOA). Fifty-five consecutive patients (mean age 62 years, 87% women) with HOA, fulfilling the American College of Rheumatology criteria, were assessed for pain upon palpation and filled in Australian/Canadian Osteoarthritis Index (AUSCAN) scores, visual analogue scale pain and Short Form-36 (SF-36). US was performed in all metacarpophalangeal, proximal interphalangeal, distal interphalangeal, first interphalangeal and first carpometacarpal joints, and features were semiquantitatively scored (0-3). Generalised estimating equations were used to calculate OR (95% CI) for the association between US features and pain per joint adjusted for relevant confounders. The association between US features summated scores and self-reported outcomes was studied by linear regression analysis. GS synovitis, effusion, synovial thickening and PDS were shown in 96%, 91%, 73% and 86% of patients, respectively. US features were dose-dependently associated with pain upon palpation (OR 4.5 (95% CI 2.2 to 9.0), 4.4 (2.0 to 9.4), 4.9 (2.2 to 11.0) and 4.1 (2.2 to 7.9)). GS synovitis was associated with AUSCAN pain, stiffness and SF-36, and effusion with AUSCAN pain. GS synovitis, effusion, synovial thickening and PDS are associated with pain in HOA, suggesting a role for inflammation. Further follow-up studies are warranted.
    Annals of the rheumatic diseases 07/2010; 69(7):1367-9. · 9.27 Impact Factor
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    ABSTRACT: Objective. To assess whether genetic variation in the interleukin-1 (IL-1) gene cluster contributes to familial osteoarthritis (OA) by influencing innate ex vivo production of IL-1 or IL-1 receptor antagonist (IL-1Ra). Methods. Innate ex vivo IL-1 and IL-1Ra pro-duction upon lipopolysaccharide (LPS) stimulation of whole blood cells was measured in subjects from the Genetics, Osteoarthritis and Progression (GARP) Study, which includes sibling pairs in which at least one sibling has symptomatic OA at multiple sites. Radio-graphic OA (ROA) was assessed by Kellgren/Lawrence score. Subjects from the GARP Study and controls from the Rotterdam Study were genotyped for 7 single-nucleo-tide polymorphisms (SNPs) encompassing the IL-1 gene cluster on chromosome 2q13. Linkage disequilibrium analysis and genotype and haplotype association analy-sis were performed to assess the relationship between the IL-1 gene cluster SNPs, innate ex vivo cytokine production, and OA. Results. Among subjects in the GARP Study, the haplotype variable-number tandem repeat in intron 2/T8006C/T11100C 2/2/1 of the IL1RN gene was significantly associated with reduced innate ex vivo bioavailability of IL-1 upon LPS stimulation (P 0.026) and with ROA at the highest number of joint locations. Conclusion. These results show that genetic vari-ation at the IL-1 gene cluster is associated with lower IL-1 bioavailability and with OA at a large number of joint locations. The data further indicate that, among subjects with OA affecting the highest number of joints, the innate immune system may be activated, thereby obscuring possible underlying mechanisms. Osteoarthritis (OA) is a common joint disease and an important cause of pain and disability in the general population. Genetic factors play an important role in the etiology of various subtypes of OA (1–5). There has been a large amount of interest in the role of cytokines as mediators of joint damage and inflamma-tion in the pathogenesis of OA. Chondrocytes are known to respond to interleukin-1 (IL-1) by reducing the synthesis of matrix components and increasing the syn-thesis of matrix metalloproteinases (MMPs) (6). MMPs degrade extracellular matrix components in articular cartilage. IL-1 receptor antagonist (IL-1Ra) is the nat-ural competitive inhibitor of IL-1, occupying the cell surface IL-1 receptor without triggering signal transduc-tion, and its levels might be considered critical in determining IL-1 bioavailability (6).
    05/2010; 62:1119-1126.
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    ABSTRACT: Internal rotation contracture of the shoulder is common in children with neonatal brachial plexus palsy. A long-standing contracture may cause osseous deformities in the developing shoulder. The purpose of the study was to evaluate the relationship between osseous deformities of the glenohumeral joint and structural differences due to muscle denervation in the rotator cuff muscles. One hundred and two children with residual neonatal brachial plexus palsy underwent magnetic resonance imaging of both shoulders. The glenoid version and posterior, medial, and superior subluxation of the humeral head were measured. The shapes of the glenoid and the humeral head were categorized, and the infraspinatus, supraspinatus, subscapularis, and deltoid muscles were scored as being normal, atrophic, or atrophic with fatty degeneration. Muscle degeneration was most prominent in the subscapularis muscle. Glenoid version correlated with the structural differences in the subscapularis muscle. Posterior subluxation of the humeral head and the shape of the glenoid correlated with all abnormal rotator cuff muscles. Superior humeral subluxation correlated only with changes in the supraspinatus muscle. Medialization and the shape of the humeral head were not associated with atrophic changes of the rotator cuff. Regeneration of the rotator cuff muscles was not significantly different in patients with a C5-C6 (C7) or a complete brachial plexus lesion. However, the changes in glenoid version, the degree of posterior humeral subluxation, and the degree of medial humeral subluxation were significantly more severe in patients with a C5-C6 (C7) lesion compared with those in patients with a complete lesion of the brachial plexus. Structural differences in the rotator cuff muscles alter the direction of the humeral head forces on the developing glenoid fossa and can lead to osseous deformities. Glenohumeral deformities are significantly greater with a C5-C6 (C7) lesion than with a complete brachial plexus lesion in which the large internal rotators are also affected. Reducing the muscular imbalance that occurs with a C5-C6 (C7) lesion could diminish glenohumeral joint incongruency and may improve the outcome of subsequent soft-tissue release or tendon transfer surgery.
    The Journal of Bone and Joint Surgery 04/2010; 92(4):935-42. · 3.23 Impact Factor
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    ABSTRACT: To assess whether genetic variation in the interleukin-1 (IL-1) gene cluster contributes to familial osteoarthritis (OA) by influencing innate ex vivo production of IL-1beta or IL-1 receptor antagonist (IL-1Ra). Innate ex vivo IL-1beta and IL-1Ra production upon lipopolysaccharide (LPS) stimulation of whole blood cells was measured in subjects from the Genetics, Osteoarthritis and Progression (GARP) Study, which includes sibling pairs in which at least one sibling has symptomatic OA at multiple sites. Radiographic OA (ROA) was assessed by Kellgren/Lawrence score. Subjects from the GARP Study and controls from the Rotterdam Study were genotyped for 7 single-nucleotide polymorphisms (SNPs) encompassing the IL-1 gene cluster on chromosome 2q13. Linkage disequilibrium analysis and genotype and haplotype association analysis were performed to assess the relationship between the IL-1 gene cluster SNPs, innate ex vivo cytokine production, and OA. Among subjects in the GARP Study, the haplotype variable-number tandem repeat in intron 2/T+8006C/T+11100C 2/2/1 of the IL1RN gene was significantly associated with reduced innate ex vivo bioavailability of IL-1beta upon LPS stimulation (P = 0.026) and with ROA at the highest number of joint locations. These results show that genetic variation at the IL-1 gene cluster is associated with lower IL-1beta bioavailability and with OA at a large number of joint locations. The data further indicate that, among subjects with OA affecting the highest number of joints, the innate immune system may be activated, thereby obscuring possible underlying mechanisms.
    Arthritis & Rheumatology 04/2010; 62(4):1119-26. · 7.48 Impact Factor
  • Osteoarthritis and Cartilage 09/2009; 17. · 4.26 Impact Factor
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    ABSTRACT: To develop evidence-based recommendations for the diagnosis of knee osteoarthritis (OA). The multidisciplinary guideline development group, representing 12 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched systematically. Whenever possible, the sensitivity, specificity and likelihood ratio were calculated for individual diagnostic indicators and a diagnostic ladder was developed using Bayes' method. Secondary analyses were undertaken to test directly the recommendations using multiple predictive models in two populations from the UK and the Netherlands. Strength of recommendation was assessed by the EULAR visual analogue scale. Recommendations covered the definition of knee OA and its risk factors, subsets, typical symptoms and signs, the use of imaging and laboratory tests and differential diagnosis. Three symptoms (persistent knee pain, limited morning stiffness and reduced function) and three signs (crepitus, restricted movement and bony enlargement) appeared to be the most useful. Assuming a 12.5% background prevalence of knee OA in adults aged > or =45 years, the estimated probability of having radiographic knee OA increased with increasing number of positive features, to 99% when all six symptoms and signs were present. The performance of the recommendations in the study populations varied according to the definition of knee OA, background risk and number of tests applied. 10 key recommendations for diagnosis of knee OA were developed using both research evidence and expert consensus. Although there is no agreed reference standard, thorough clinical assessment alone can provide a confident rule-in diagnosis.
    Annals of the rheumatic diseases 09/2009; 69(3):483-9. · 9.27 Impact Factor

Publication Stats

3k Citations
629.75 Total Impact Points

Institutions

  • 2005–2013
    • Leiden University Medical Centre
      • • Department of Rheumatology
      • • Department of Radiology
      Leyden, South Holland, Netherlands
  • 1988–2001
    • University of Bristol
      • Medical School
      Bristol, England, United Kingdom
  • 1996
    • University of the West of England, Bristol
      Bristol, England, United Kingdom
  • 1993
    • Hospital Kuala Lumpur
      Kuala Lumpor, Kuala Lumpur, Malaysia
  • 1992
    • Bristol Hospital
      Bristol, Connecticut, United States
  • 1987
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom