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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Total body bone mineral (TBBM) measured by dual photon absorptiometry and local bone mineral (BMC) measured by single photon absorptiometry were determined in 55 patients with definite or classical rheumatoid arthritis. All of them had been on a steady dose of anti-inflammatory drugs for at least 12 months, and furthermore, 13 patients were on glucocorticoids. The results were compared with 49 normal persons matched for sex, age and menopausal state. A highly significant correlation was found between BMC and TBBM in the patients (r = 0.84, SEE = 13.0%) as well as in the controls (r = 0.77, SEE 10.5%). Moreover, the intercepts and the slopes were virtually of the same order. Subdividing the patients according to glucocorticoid treatment the same high correlations were shown in the two subgroups. As a group the patients on glucocorticoids had a highly significant generalized osteopenia (a reduction of TBBM of 26% compared to normals). The patients on other anti-inflammatory drugs had a significant, but less pronounced generalized osteopenia (a reduction of TBBM by 11% compared to normals). It is concluded, that BMC of the forearm can be used as a valid estimate of total body calcium in groups of patients with rheumatoid arthritis and in normal subjects.
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PMID:Relationship between local and total bone mineral in patients with rheumatoid arthritis and normal subjects. 667

BACKGROUND: Radiosynovectomy is a type of radiotherapy used to relieve pain and inflammation from rheumatoid arthritis. In this study, 188-Rhenium (188Re) colloids were characterized by physical and biological methodologies. This was used to assess which parameters of the kit formulation would be the basis in the development of a more effective radiopharmaceutical for synovectomy. Intraarticular injection in knees of rabbits assessed cavity leakage of activity. METHODS: The physical characteristics of tin (Sn) and sulphur (S) colloids were determined to assess the formulation with suitable properties. Particles were grouped in three ranges for analyzing their distribution according to their number, volume and surface. The ideal particle size range was considered to be from 2 to 10 microns. Membrane filtration and laser diffraction characterization methodologies were used. RESULTS: While membrane filtration could give misleading data, laser diffraction proportions more reliable results. The Sn colloid showed a better distribution of particle volume and surface than S colloid, in the 2 to 10 microns range. The 188Re-Sn colloid was obtained with a radiochemical purity higher than 95% after 30 minutes of autoclaving. While Sn colloid kit stability was verified for 60 days, the 188Re-Sn preparation was stable in the first 24 hrs. No significant intrabatch variability (n = 3) was detected. Biodistribution and scintigraphic studies in rabbits after intraarticular injection showed relevant activity only in knee, being 90% at 48 hours. CONCLUSION: The 188Re-Sn colloid is easy to prepare, is stable for 24 hours and shows minimal cavity leakage after intraarticular injection into rabbit knees, suggesting this radiotherapeutical agent has suitable physical properties for evaluation for joint treatment in humans.
BMC Nucl Med 2002 Oct 14
PMID:Physico-chemical characterisation and biological evaluation of 188-Rhenium colloids for radiosynovectomy. 1237 58

BACKGROUND: Radiosynovectomy is a therapy used to relieve pain and inflammation from rheumatoid arthritis and related diseases. In this study three 188Re particulate compounds were characterized according to their physico-chemical properties and their biological behavior in rabbits. The results were compared in order to establish which was the radiopharmaceutical that better fits the requirements of this kind of radiotherapy. METHODS: Three radiopharmaceutical formulations, tin colloid, hydroxyapatite particles (HA) and ferric hydroxide macroaggregates coated with tin colloid (FHMA), were physically characterized (number, volume and surface of the particles). For this purpose laser diffraction methodology was used. To evaluate cavity leakage of activity the following studies in New Zealand rabbits were performed: scintigraphic images for 48 hr after intraarticular injection of each radiopharmaceutical, biodistribution at 48 hr and urine samples collection during the first 24 hr post-radiopharmaceutical administration. RESULTS: Labeling procedures for 188Re-HA and 188Re-Sn-FHMA were labour intensive while 188Re-Sn was easily prepared. Furthermore, 188Re-Sn colloid offered the greatest surface area in the 2-10 microm range and was obtained with a radiochemical purity over 95%, while percentage of bound activity for 188Re-HA and 188Re-Sn-FHMA were 55% and 92% respectively. Stability was verified for the three radiopharmaceuticals for 24 hr. Scintigraphic studies and biodistribution in rabbits after intraarticular administration of the radiopharmaceuticals showed relevant activity only in the knee, this being over 90% of the residual activity in the whole body at 48 hr in every case. Renal elimination of 188Re-Sn colloid and 188Re-Sn-FHMA was detected by activity measurements in urine samples, during the first 12 hr post-radiopharmaceutical injection.The percentage of activity retained in the knee was 69.1% for 188Re-Sn colloid, 55.1% for 188Re-Sn-FHMA and 33.6% for 188Re-HA. CONCLUSION: The 188Re-Sn colloid was easy to prepare, minimum facilities were required, was stable for 24 hr and showed minimal leakage from the joint after intraarticular injection into the rabbit's knee. Furthermore, 188Re-Sn colloid has greater retention in the knee when it is compared with the other radiopharmaceuticals, so it could provide the best therapeutic effect/absorbed dose ratio for the patient.
BMC Nucl Med 2004 Jan 30
PMID:188Re radiopharmaceuticals for radiosynovectomy: evaluation and comparison of tin colloid, hydroxyapatite and tin-ferric hydroxide macroaggregates. 1504 Aug 7

TNFalpha is known to stimulate the development and activity of osteoclasts and of bone resorption. The cytokine was found to mediate bone loss in conjunction with inflammatory diseases such as rheumatoid arthritis or chronic aseptic inflammation induced by wear particles from implants and was suggested to be a prerequisite for the loss of bone mass under estrogen deficiency. In the present study, the regulation of osteoclastogenesis by TNFalpha was investigated in co-cultures of osteoblasts and bone marrow or spleen cells and in cultures of bone marrow and spleen cells grown with CSF-1 and RANKL. Low concentrations of TNFalpha (1 ng/ml) caused a >90% decrease in the number of osteoclasts in co-cultures, but did not affect the development of osteoclasts from bone marrow cells. In cultures with p55TNFR(-/-) osteoblasts and wt BMC, the inhibitory effect was abrogated and TNFalpha induced an increase in the number of osteoclasts in a dose-dependent manner. Osteoblasts were found to release the inhibitory factor(s) into the culture supernatant after simultaneous treatment with 1,25(OH)(2)D(3) and TNFalpha, this activity, but not its release, being resistant to treatment with anti-TNFalpha antibodies. Dexamethasone blocked the secretion of the TNFalpha-dependent inhibitor by osteoblasts, while stimulating the development of osteoclasts. The data suggest that the effects of TNFalpha on the differentiation of osteoclast lineage cells and on bone metabolism may be more complex than hitherto assumed and that these effects may play a role in vivo during therapies for inflammatory diseases.
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PMID:Tumor necrosis factor-alpha: alternative role as an inhibitor of osteoclast formation in vitro. 1658 Aug 96

Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p << 0.001) and rheumatoid factor (RF) IgM (p << 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates.
BMC Proc 2007
PMID:Large-scale linkage analysis of 1302 affected relative pairs with rheumatoid arthritis. 1846 40

Rheumatoid arthritis (RA) is a chronic, complex autoimmune inflammatory disorder with poorly known etiology. Approximately 1% of the adult population is afflicted with RA. Linkage analysis of RA can be complicated by the presence of phenotypic and genetic heterogeneity. It is shown that the ordered-subset analysis (OSA) technique reduces heterogeneity, increases statistical power for detecting linkage and helps to define the most informative data set for follow-up analysis. We applied OSA to the family data from the North American Rheumatoid Arthritis Consortium study as part of the Genetic Analysis Workshop 15 (GAW15). We have incorporated two continuous covariates, 'age of onset' and 'anti-CCP level' (anti-cyclic citrinullated peptide), into our genome-wide ordered-subset linkage analysis using 809 Illumina SNP markers in 5713 individuals from 606 Caucasian RA families. A statistically significant increase in nonparametric linkage (NPL) scores was observed with covariate 'age of onset' in chromosomes 4 (p = 0.000003) and 9 (p = 0.002). With the covariate 'anti-CCP level', statistically significant increases in NPL scores were observed in chromosomes 2 (p = 0.0001), 18 (p = 0.00007), and 19 (p = 0.0003). Once we identified the linked genomic region, we then attempted to identify the best plausible parametric model at that linked locus. Our results show significant improvement in evidence for linkage and demonstrate that OSA is a useful technique to detect linkage under heterogeneity.
BMC Proc 2007
PMID:A genome-wide ordered-subset linkage analysis for rheumatoid arthritis. 1846 41

Three LOD score statistics are often used for genome-wide linkage analysis: the maximum LOD score, the LOD score statistic proposed by Kong and Cox, both based on the allele-sharing between affected sib pairs, and the maximization of the LOD score function of Morton on two genetic models and an heterogeneity parameter.Using only identity-by-descent sharing between affected sibs as linkage information, we studied the behavior of these three statistics under the null hypothesis in the rheumatoid arthritis simulated data (Genetic Analysis Workshop 15 Problem 3 - simulating model known). Distributions under the null hypothesis show that identical values of the statistics correspond to very different genome-wide p-values: comparison and interpretation of several linkage statistics cannot be done on the observed value. The Kong and Cox LOD score statistic had slightly better power to detect the HLA region involved in rheumatoid arthritis compared to the other methods. In a second step, we show that performing the analysis under a greater number of genetic models in the hope of better scanning the space of models, does not increase the power of detection.
BMC Proc 2007
PMID:On the choice of linkage statistics. 1846 42

To evaluate whether there is evidence for two rheumatoid arthritis (RA) susceptibility genes on chromosome 6, we applied new robust methods for two-locus multipoint identical-by-descent mapping to the rheumatoid arthritis data of the Genetic Analysis Workshop 15. The software GEEARP was used to estimate the locations and the corresponding genetic effects for one locus or two linked loci in a region on chromosome 6, on the basis of affected relative pairs. These methods were applied to the data sets from the North American Rheumatoid Arthritis Consortium, Canada, France, and the first screen of United Kingdom. From the resultant 95% confidence intervals given by a robust variance estimator, a linked region, other than the well-known HLA region, was at 54.7-69.6 cM, providing evidence for a second rheumatoid arthritis susceptibility locus on chromosome 6.
BMC Proc 2007
PMID:One- and two-locus models for mapping rheumatoid arthritis-susceptibility genes on chromosome 6. 1846 43

We have used the genome-wide marker genotypes from Genetic Analysis Workshop 15 Problem 2 to explore joint evidence for genetic linkage to rheumatoid arthritis across several samples. The data consisted of four high-density genome scans on samples selected for rheumatoid arthritis. We cleaned the data, removed intermarker linkage disequilibrium, and assembled the samples onto a common genetic map using genome sequence positions as a reference for map interpolation. The individual studies were combined first at the genotype level (mega-analysis) prior to a multipoint linkage analysis on the combined sample, and second using the genome scan meta-analysis method after linkage analysis of each sample. The two approaches were compared, and give strong support to the HLA locus on chromosome 6 as a susceptibility locus. Other regions of interest include loci on chromosomes 11, 2, and 12.
BMC Proc 2007
PMID:Combining linkage data sets for meta-analysis and mega-analysis: the GAW15 rheumatoid arthritis data set. 1846 44

We applied nonparametric quantitative trait linkage analysis to two rheumatoid arthritis quantitative phenotypes, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide autoantibody titer measurements, using 5700 genome-wide Illumina single-nucleotide polymorphism genotypes on 658 Caucasian North American Rheumatoid Arthritis Consortium families. Peak LOD scores for both quantitative traits were located in the human leukocyte antigen region 6p21 (15.8 and 13.8 for RF and anti-cyclic citrullinated peptide, respectively) followed by 11p12 (3.2 and 3.6). In addition, there were LOD scores of 3.2 on 2q32 for RF and 3.6 on 4q24 for anti-cyclic citrullinated peptide. The resulting linkage signals for both phenotypes are very similar to previous results for rheumatoid arthritis as a qualitative variable, with rheumatoid factor measurements being most closely aligned. Interestingly, anti-cyclic citrullinated peptide exhibits a stronger linkage peak on 2p14 than rheumatoid factor and rheumatoid arthritis, and stronger linkage on 4q24. Finally, we used ordered subset analyses to determine if sub-ranges of these two traits increased rheumatoid arthritis linkage signals; however, our analyses did not reveal significant effects of the quantitative traits on rheumatoid arthritis linkage signals in this population.
BMC Proc 2007
PMID:Genome-wide single-nucleotide polymorphism linkage analyses of quantitative rheumatoid arthritis phenotypes in Caucasian NARAC families. 1846 45


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