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Biomedical subjects

R Westhovens

Publications and source records attributed to R Westhovens.

At least 19 recordsLinked to original sources
PubMed2000

Noninherited maternal antigens do not play a role in rheumatoid arthritis susceptibility in Europe. European Consortium on Rheumatoid Arthritis Families.

OBJECTIVE: It has been proposed that noninherited maternal antigens (NIMA) (HLA-DR antigens) might play a role in susceptibility to rheumatoid arthritis (RA), especially in patients who are not genetically predisposed, such as those who are HLA-DR4 and/or shared epitope (SE) negative. The present study was undertaken to test the NIMA hypothesis in a large cohort of European RA patients assembled by the European Consortium on RA Families (ECRAF). METHODS: HLA-DRB1 oligotyping was performed in families of European RA patients for whom both parents were alive. These families were consecutively recruited by the ECRAF between 1996 and 1998, for association studies. The frequencies of HLA-DR NIMA were compared with those of the noninherited paternal antigens (NIPA) after stratification for HLA-DR*04, *0401 and/or *0404, and SE status. NIMA or NIPA that coincided with inherited HLA-DR antigens were considered redundant and excluded from analysis. Calculations concerning the whole group and restricted to patients lacking parental RA were performed. RESULTS: One hundred seventy families from France (n = 81), Belgium (n = 23), Spain (n = 24), Italy (n = 19), Portugal (n = 14), and The Netherlands (n = 9) were oligotyped. The group of probands was predominantly female (88%), positive for rheumatoid factor, DR*04, and SE (71%, 58%, and 75%, respectively), and had erosive disease (75%). Parental RA was reported in 21 families. Using the NIPA as control, the frequency of HLA-DRB1*04, *0401 and/or *0404-, or SE-positive NIMA was not found to be increased in patients lacking these susceptibility alleles. The same was true when the 21 probands with parental RA were excluded from analysis. In DRB1*04-positive patients, we found no evidence of a relevant effect of HLA-DR3 or DR6 in the NIMA. CONCLUSION: Our results do not support the notion that noninherited maternal antigens have a role in susceptibility to RA in the offspring.

Adult↗
PubMed2000

Rheumatoid arthritis and osteoporosis.

Some controversial issues in the current literature in relation to osteoporosis and rheumatoid arthritis are updated and discussed. Because most studies agree that osteoporosis in postmenopausal women and in men with RA is more evident at the hip and radius than at the spine, and that the most important determinants of bone loss are disability, local disease activity, and cumulative corticosteroid dose, osteoporosis is not a common systemic extra-articular manifestation of RA. In early arthritis, periarticular osteoporosis does indeed reflect disease activity because it is closely related to the acute phase reactants, but once periarticular osteoporosis is established it is no longer a marker of disease severity. The threshold dose for corticosteroid-induced osteoporotic fractures is the cumulative rather than the actual dose. Statements based on quantitative tomography concerning the acute effects (and their reversal) of corticosteroids on bone have to be interpreted with care because of important body composition changes, in particular in bone marrow fat, during corticosteroid treatment. At present there is no evidence that anti-resorbing drugs can change the progress of RA erosions, probably because erosions are the result of non-osteoclast mediated mechanisms. Stress fractures in RA are underdiagnosed and are often confused with synovitis, and therefore it is likely that they are more frequent than commonly thought, especially in the lower limbs. Methotrexate osteopathy is known in oncological practice. Whether low dose methotrexate is toxic for bone is not clear, but a number of clinical observations suggest that the occurrence of spontaneous fractures and lower extremity pain is more frequent in methotrexate treated patients than expected. Prospective studies are necessary to confirm these impressions.

Adrenal Cortex Hormones↗
PubMed1999

Reference curve and diagnostic sensitivity for a new ultrasound device for the phalanges [correction of phalanages], the DBMsonic 1200, in Belgian women.

Quantitative ultrasound (US) applied in bone mass measurements is promising because it is a radiation-free and cheap technique that may provide information on bone quality. The DBMsonic 1200 (IGEA, Carpi) is such a new ultrasound device that measures mean amplitude-dependent speed of sound through the distal metaphyses of the four proximal phalanges (nondominant hand). We determined the standarded precision and constructed a reference curve for Belgian women. The diagnostic sensitivity was tested in established osteoporotic patients with at least one vertebral fracture, expressed as area under the curve (ROC) and compared with other bone mass measurement techniques such as dual-energy X-ray absorptiometry (DXA) and US of the heel. For a group of 93 women with different pathologies, the standardized precision obtained was 4.2 +/- 4.3%. Within this group, the standardized precision was 3.7 +/- 3.1% for 28 normals and 5.8 +/- 4.9% for 12 osteoporotic patients. The reference curve was constructed in 310 normal women (age range 21-84 years). The diagnostic sensitivity of this ultrasound device was compared with that obtained with spinal DXA and proximal femur results of the same individuals, as well as with ultrasound measurements of the calcaneus, and investigated in the osteoporotic patients older than 50 years and in age-matched controls. The area under the curve was 80.3% (SE 3.9%) for the DBMsonic 1200, 77.4% (SE 1.4%) for DXA of the spine, 79.5% (SE 3.9%) for DXA of the femoral neck and 70.1% (SE 4.9%) for US of the heel. Our data show an acceptable and comparable standardized precision in relation to other available data for the same device. In the group of osteoporotic women over 50 years of age we have found similar diagnostic sensitivity for the US measurements of the phalanges as for DXA of the lumbar spine and femoral neck. There is a minor, but no significantly higher diagnostic sensitivity than for ultrasound of the calcaneus. We conclude that this tool is promising for discriminating normal and osteoporotic female patients.

Absorptiometry, Photon↗
PubMed1999

Systemic lupus erythematosus, eosinophilia and Löffler's endocarditis. An unusual association.

A 24-yr-old male, known since the age of 11 to have a nonerosive arthritis and later diagnosed as having systemic lupus erythematosus (SLE), developed subacute heart failure with diffuse lung infiltrates and died suddenly after having presented a moderate hypereosinophilia for 6 months for which no other causes besides the SLE were found. A post mortem examination revealed Löffler's endocarditis (endocarditis parietalis fibroplastica) with acute pulmonary capillaritis. This represents Löffler's endocarditis in the setting of SLE. To the best of the authors' knowledge, this association has not been reported before.

Adult↗
PubMed1999

Sensitivity to change of generic quality of life instruments in patients with rheumatoid arthritis: preliminary findings in the generic health OMERACT study. OMERACT/ILAR Task Force on Generic Quality of Life. Life Outcome Measures in Rheumatology. International League of Associations for Rheumatology.

This is the initial report of the generic health OMERACT study concerned with the sensitivity to change of generic quality of life (QOL) measures. Our objective was to determine which QOL instrument is best able to show a statistically significant improvement in patients with rheumatoid arthritis (RA) demonstrating relevant improvement in a core set of disease activity and disease-specific disability measures. A multicenter controlled trial of a single group with repeated measurements at 0 (baseline), 3, and 6 months was conducted. All participating centers recruited 10 patients with RA who were about to start methotrexate therapy for the first time because of active disease. Assessments included disease activity measures, disease-specific disability measures, and generic QOL measures. To date, 40 patients have been recruited from 4 centers for the study. After 6 months of treatment many of the generic QOL measures showed a 20% improvement from baseline and medium standardized response means around 0.5. In particular, the Nottingham Health Profile (NHP) and the Rheumatoid Arthritis Quality of Life (RAQOL) measures had the largest percentage improvement (22 and 29%, respectively) and standardized response means (both with 0.54). Early results on the sensitivity of generic health QOL measures are promising, in particular for the NHP and RAQOL measures.

Antirheumatic Agents↗
PubMed1998

New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study.

Rheumatoid arthritis (RA), the most common autoimmune disease, is associated in families with other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM). Its genetic component has been suggested by familial aggregation (lambdas = 5), twin studies, and segregation analysis. HLA, which is the only susceptibility locus known, has been estimated to account for one-third of this component. The aim of this paper was to identify new RA loci. A genome scan was performed with 114 European Caucasian RA sib pairs from 97 nuclear families. Linkage was significant only for HLA (P < 2.5.10(-5)) and nominal for 19 markers in 14 other regions (P < 0.05). Four of the loci implicated in IDDM potentially overlap with these regions: the putative IDDM6, IDDM9, IDDM13, and DXS998 loci. The first two of these candidate regions, defined in the RA genome scan by the markers D18S68-D18S61-D18S469 (18q22-23) and D3S1267 (3q13), respectively, were studied in 194 additional RA sib pairs from 164 nuclear families. Support for linkage to chromosome 3 only was extended significantly (P = 0.002). The analysis of all 261 families provided a linkage evidence of P = 0. 001 and suggested an interaction between this putative RA locus and HLA. This locus could account for 16% of the genetic component of RA. Candidate genes include those coding for CD80 and CD86, molecules involved in antigen-specific T cell recognition. In conclusion, this first genome scan in RA Caucasian families revealed 14 candidate regions, one of which was supported further by the study of a second set of families.

Arthritis, Rheumatoid↗
PubMed1998

Results of the Kudo elbow prosthesis in patients with rheumatoid arthritis: a preliminary report.

Sixteen elbows in 15 rheumatoid arthritis patients had a total elbow replacement with insertion of a non-constrained surface-replacement prosthesis. One patient died of an unrelated cause, but all the others were available for follow-up (mean follow-up period: 35.4 months). The results were graded according to a modified version of the Morrey elbow score. A good result was seen in 13 elbows and a fair result in two. One infection occurred, which was cured with intravenous antibiotics and maintenance of the prosthesis in place; however, recurrent dislocation persisted. Another patient had postoperative instability with recurrent subluxations. Eleven patients were very satisfied and one was satisfied. The total active range of motion increased significantly from 70.3 degrees (SD 29.6) to 97.0 degrees (SD 15.4), mainly by increased flexion. The modified Morrey score increased significantly from 32.7 (SD 13.1) to 89.3 (SD 10.3). Pain decreased from severe (n = 12) and moderate (n = 3) preoperatively to mild (n = 5) and absent (n = 10) postoperatively.

Adult↗
PubMed1998

Diagnostic sensitivity of peripheral quantitative computed tomography measurements at ultradistal and proximal radius in postmenopausal women.

Peripheral quantitative computed tomography (pQCT) is a bone densitometry technique that is able to provide real volumetric bone density values not only of the total but also of trabecular and cortical bone separately. Normal reference curves were constructed with cross-sectional data obtained in 275 postmenopausal women (50-85 years), measured at 4% of the ulnar length (ultradistal region), and data for total, trabecular, and cortical bone density were obtained. In these postmenopausal subjects, continuously significant (p < 0.0001) age-dependent declines in bone density of 1.14%, 1.1%, and 0.57% for total, trabecular, and cortical bone, respectively, were observed while similar declines of 0.9%, 0.9%, and 0.4% per year since menopause, respectively, were found. The estimated mechanical stability index also showed linear dependencies with decreases of 0.84%/year and 0.6%/year since menopause (p < 0.0001). A more proximal acquisition at 15% of the ulnar length, an almost pure cortical region, resulted in linear declines of 0.41%/year and 0.27%/year (p < 0.0001) for the cortical bone and the mechanical stability index with significant changes of -0.27% and -0.23% per year, respectively, since menopause. Covariance analysis showed similar age dependencies of the different bone indices obtained in both regions of interest except for the stability index. A significant size adaptation of the bone with age was also observed, which was seen in the relationships of the trabecular and cortical bone areas to age and to bone density. Diagnostic sensitivity of all parameters for established osteoporosis was assessed by receiver operating characteristic (ROC) curves, comparing 99 patients with at least one fracture to the reference population. The area under these curves was highest in the ultradistal pure trabecular density of the radius (75%), followed by stability index (72%) and the area of cortical bone (65%) of the proximal site. No distinguishing power was seen for the cortical bone density values obtained in either the ultradistal (51%) or proximal radius (52%).

Age Factors↗
PubMed1998

Severe knee pain as the single symptom of CMV infection in acute ulcerative colitis treated with cyclosporine.

We describe a case of systemic cytomegalovirus (CMV) infection in an ulcerative colitis patient admitted to the hospital for an acute flare-up of his colitis. He was treated with combination immunosuppressive therapy including i.v. cyclosporine and corticosteroids and PO azathioprine. Severe bilateral stabbing knee pain was the only manifestation of CMV disease, which quickly responded to adequate antiviral therapy.

Acute Disease↗
PubMed1997

Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis.

BACKGROUND: The value of intensive combination therapy in early rheumatoid arthritis is unproven. In a multicentre, double-blind, randomised trial (COBRA), we compared the combination of sulphasalazine (2 g/day), methotrexate (7.5 mg/week), and prednisolone (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day) with sulphasalazine alone. METHODS: 155 patients with early rheumatoid arthritis (median duration 4 months) were randomly assigned combined treatment (76) or sulphasalazine alone (79). Prednisolone and methotrexate were tapered and stopped after 28 and 40 weeks, respectively. The main outcomes were the pooled index (a weighted change score of five disease activity measures) and the Sharp/Van der Heijde radiographic damage score in hands and feet. Independent health-care professionals assessed the main outcomes without knowledge of treatment allocation. FINDINGS: At week 28, the mean pooled index was 1.4 (95% CI 1.2-1.6) in the combined treatment group and 0.8 (0.6-1.0) in the sulphasalazine group (p < 0.0001). At this time, 55 (72%) and 39 (49%) patients, respectively, were improved according to American College of Rheumatology criteria. The clinical difference between the groups decreased and was no longer significant after prednisolone was stopped, and there were no further changes after methotrexate was stopped. At 28 weeks, the radiographic damage score had increased by a median of 1 (range 0-28) in the combined-therapy group and 4 (0-44) in the sulphasalazine group (p < 0.0001). The increases at week 56 (2 [0-43] vs 6 [0-54], p = 0.004), and at week 80 (4 [0-80] vs 12 [0-72], p = 0.01) were also significant. Further analysis suggests that combined therapy immediately suppressed damage progression, whereas sulphasalazine did so less effectively and with a lag of 6 to 12 months. There were fewer withdrawals in the combined therapy than the sulphasalazine group (6 [8%] vs 23 [29%]), and they occurred later. INTERPRETATION: This combined-therapy regimen offers additional disease control over and above that of sulphasalazine alone that persists for up to a year after corticosteroids are stopped. Although confirmatory studies and long-term follow-up are needed, this approach may prove useful in the treatment of early rheumatoid arthritis.

Adult↗
PubMed1997

Total lymphoid irradiation in rheumatoid arthritis. A ten-year followup.

OBJECTIVE: To report the findings of a 10-year followup of patients enrolled in a randomized trial of total lymphoid irradiation (TLI) versus chemotherapy for rheumatoid arthritis (RA). METHODS: A retrospective analysis of the charts of 19 patients who had been included in a randomized trial comparing TLI and chemotherapy for the treatment of RA. RESULTS: Ten years after the start of the trial, a higher number of TLI-treated patients had died (7 of 10), compared with patients who had received chemotherapy (2 of 9). In addition, 3 of the TLI-treated patients developed B cell-related malignancies, whereas no such malignancies developed in the control group. CONCLUSION: TLI was associated with a less-favorable long-term outcome than chemotherapy. These data stress the importance of careful long-term followup in experimental trials of immunosuppressive agents.

Aged↗
PubMed1997

Body composition in rheumatoid arthritis.

The objectives were to assess bone mineral density (BMD) at different body sites in rheumatoid arthritis (RA) patients related to disease severity parameters, disease duration and corticosteroid intake, and to look for body composition measurements as lean body mass (LBM) and per cent fat as possible prognostic factors in RA. Body composition values were measured cross-sectionally in 89 RA patients and compared with 157 controls. Patients were divided into males and postmenopausal females, ever steroid treated and never steroid treated. BMD values of all body sites were significantly lower compared to normals in all subgroups, except for the lumbar spine (L2 L4) in all postmenopausal women and males never treated with steroids. There was also no clear BMD decrease in the arms of male RA patients. LBM was significantly lower in all body parts compared to controls, whereas the fat distribution ratio (FDR) showed a clear shift to abdominal in all patients. These are parameters of chronic illness and a predictor of cardiovascular disease, respectively. BMD data confirm our previous data in different patient groups (low at appendicular sites, normal lumbar BMD), but no clear influence of disease severity and steroid intake could be found. Body composition data, as LBM and FDR, are also altered in RA patients: decreased LMB and more central FDR. Their usefulness as prognostic markers in early RA patients needs to be clarified prospectively in these patient groups.

Adrenal Cortex Hormones↗
PubMed1997

HLA typing in a large family with multiple cases of different autoimmune diseases.

OBJECTIVE: Because of the concurrence, in members of one family, of different autoimmune disorders [rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis (PS), and inflammatory bowel disease (IBD)], we investigated the genotypes of each member and compared the results with current knowledge of genetic inheritance of rheumatic and other autoimmune diseases. METHODS: Sera and peripheral blood lymphocytes of 16 family members were collected for HLA typing and investigation. RESULTS: All patients with RA were DR4 positive ad 4 of 5 showed the maternal A2B51DR4 haplotype. Two of 3 siblings with the genotype HLA-A2/3, B8/35, DR2/3 had SLE. Patients with IBD and psoriasis shared the haplotype HLA-A3, B35 CW4 DR2. CONCLUSION: The results show that the important role of patients, sex and confirm the association between HLA haplotype and RA or SLE. They support the hypothesis that autoimmunity is a mendelian dominant trait, and that secondary genes, including these of the major histocompatibility complex, confer phenotypic specificity.

Arthritis, Rheumatoid↗
PubMed1997

Total knee arthroplasty in the young rheumatoid patient.

Thirty-four total knee arthroplasties were performed for severe rheumatoid arthritis in 25 patients younger than 45 years. All patients were available for follow-up evaluation at an average of 7.2 years. According to the Knee Society scoring system, the knee score improved from an average of 21 points preoperatively to 85 points at follow-up (p < 0.001). The average functional score improved from 23 points to 87 points (p < 0.001). Average range of motion improved from 71 degrees to 93 degrees (p < 0.001). Nonprogressive radiolucencies less than 1-mm thick were observed in 6 knees. One knee was revised for severe polyethylene wear; another case was revised for chronic patellar dislocation. Actuarial survivorship analysis estimates a 97% survivorship after 5 years and 90% after after 10 years. In young rheumatoid patients, total knee arthroplasty can therefore be considered as a reliable procedure, with satisfactory results during at least the first 5 to 10 postoperative years.

Actuarial Analysis↗