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ID PMID Title PublicationDate abstract
9632063 Salivary testosterone in postmenopausal women with rheumatoid arthritis. 1998 Jun OBJECTIVE: To study changes in testosterone concentrations in saliva and total testosterone, free testosterone, and sex hormone binding globulin (SHBG) concentrations in serum in 2 groups of postmenopausal women with rheumatoid arthritis (RA), one group with glucocorticoid treatment and the other without it. METHODS: The above mentioned hormonal levels were measured in 20 postmenopausal women with RA undergoing glucocorticoid treatment, in 24 postmenopausal women with RA without treatment, and in 36 postmenopausal women without RA. RESULTS: We observed significantly lower levels of total testosterone in serum, SHBG in serum, testosterone in saliva, and the free testosterone index in the group of patients with RA undergoing glucocorticoid treatment compared to the group without treatment. We did not observe changes in free testosterone concentrations in serum of the groups studied, which is believed due to its lower specificity. CONCLUSION: Testosterone in saliva is a useful indicator for monitoring androgenic status in women with RA.
11130855 Immunochemical and enzymatic study of ceruloplasmin in rheumatoid arthritis. 2000 Oct Forty adult patients (30 women and 10 men) with rheumatoid arthritis (RA), treated with nonsteroidal anti-inflammatory drugs, were studied. Serum levels of immunoreactive ceruloplasmin, oxidase activity of the ceruloplasmin and total copper, as well as the specific oxidase activity (enzyme activity per unit of mass) and the copper/immunoreactive ceruloplasmin relationship were significantly higher in the group of patients than in the healthy control group (p < 0.001). However, no significant difference was found for the concentration of non-ceruloplasmin copper between both groups. A statistically significant negative correlation was obtained for the concentration of serum thiobarbituric acid-reacting substances with the immunoreactive ceruloplasmin and its oxidase activity in the group of patients (p < 0.005). These results suggest that in RA increases of serum copper are produced at the expense of the fraction linked to the ceruloplasmin, diminishing the proportion of apoceruloplasmin and other forms poor in copper. Although the increase in the serum concentration of ceruloplasmin might offer an additional safeguard against oxidative stress. it does not appear to have a beneficial effect upon the activity of the illness as evaluated by means the biological inflammation markers C-reactive protein, erythrocyte sedimentation rate and sialic acid.
11293246 The effective of methotrexate on immune response cells in rheumatoid arthritis. 2000 Nov Methotrexate (MTX) is one of the most used medicines in rheumatoid arthritis [r. a.] treatment. There are many scientific reports which present influence of MTX on inflammatory process. In many centers influence of MTX on cytokines level have been investigated. Thanks to clinical studies it has been performed that MTX holds up activity and productions of Il-8, releasing of TNF-alpha and reduction of concentration Il-6. MTX holds up proliferation of monocytes, macrophages and synoviocytes. It has been indicated that MTX decreases synthesis of B-4 leucotrien in neutrophils, decreases level of neutral proteases, holds up cellular immunity and has antiproliferative influence on endothelial cells. There are reports, that MTX reduces expression of endothelial cells adhesive proteins and synthesis of chemotactic factors, stopping migration of leucocytes to tissues.
11727845 Serum YKL-40 concentrations in patients with early rheumatoid arthritis: relation to joint 2001 OBJECTIVE: YKL-40 is a secretory glycoprotein of chondrocytes, synovial cells, macrophages, and neutrophils. The aims were to determine serum YKL-40 in patients with early rheumatoid arthritis (RA) and seek associations with early joint erosions. METHODS: YKL-40 was measured by ELISA in serum samples collected every three month for 36 months from patients with early RA. The patients were treated with DMARDs and some were allocated to additional prednisolone. RESULTS: Serum YKL-40 was higher in RA patients compared with controls (98 vs. 42 microg/l, p<0.001). The mean serum YKL-40 during the study correlated with the progression in Larsen score (Pearson's test: p=0.004). Patients with a persistently high serum YKL-40 had larger progression in Larsen score compared with patients with normal serum YKL-40 (median progression: 7 vs. 0, p=0.003). CONCLUSION: These data suggest that elevated serum YKL-40 is related to progression in joint destruction in early RA patients.
10648020 Hemostatic factors and cardiovascular disease in active rheumatoid arthritis: an 8 year fo 2000 Jan OBJECTIVE: To investigate the prospective effect of hemostatic factors and inflammatory variables on the progression of cardiovascular disease in rheumatoid arthritis (RA). METHODS: Von Willebrand factor (vWF) and the fibrinolytic factors tissue plasminogen activator (tPA), measured as tPA capacity, and plasminogen activator inhibitor 1 (PAI-1), platelets, fibrinogen, and inflammatory markers were measured in 74 patients with active seropositive RA. Lipid levels, lipoprotein(a), and cardiolipin antibodies were also analyzed. Cardiovascular disease, measured by past cardiovascular events including thrombotic events, was registered in an 8 year followup. RESULTS: Patients with a cardiovascular event during the followup period (n = 26) had significantly higher levels of vWF, PAI-1, erythrocyte sedimentation rate (ESR), and haptoglobin at entry to the study. In a multiple logistic regression model controlling for several conventional cardiovascular risk factors and pharmacological treatment at sampling, PAI-1 and tPA were significantly associated with cardiovascular disease progression. CONCLUSION: The altered levels of vWF, PAI-1, and, in logistic regression, tPA in RA patients with cardiovascular disease progression indicates a status of hypofibrinolysis in these patients. Higher levels of ESR and haptoglobin may reflect the importance of the inflammatory process for the development of cardiovascular disease in RA.
10589354 Pharmacotherapeutic strategies for disease-modifying antirheumatic drug (DMARD) combinatio 1999 Nov OBJECTIVE: To provide a rational model for the use of disease-modifying antirheumatic drug (DMARD) combinations in the treatment of rheumatoid arthritis. METHODS: The DMARDs used today were examined for their mechanisms of action, kinetics, and toxicity, and collected into tabular formats for easier comparison. From these tables, matrices of potential positive or negative interfaces among combinations were constructed. Finally, these matrices were used to examine the usefulness of DMARD combinations by comparing them with published data. RESULTS: When clearly overlapping cells were found with respect to mechanisms of action, kinetics, or toxicity (e.g., methotrexate [MTX] plus azathioprine or MTX plus auranofin) predictions were good. When knowledge in these areas of kinetics and/or mechanisms of action were inadequate, predictions and results were not always consonant (e.g. MTX plus sulfasalazine; D-penicillamine plus hydroxychloroquine). CONCLUSIONS: The approach demonstrated in this paper toward rational combination therapy is logical and can be successful, although its success is circumscribed by our knowledge about the drugs we use. The rational approach to combination therapy demonstrated in this article can: 1) help prevent the use of combinations unlikely to be effective; 2) can point toward directions for useful research; and 3) can even be used when physicians are faced with patients whose needs have exceeded our present scientific knowledge.
11426020 Cardiovascular risk factors, including thrombotic variables, in a population with rheumato 2001 Jun OBJECTIVE: To compare prevalent cardiovascular disease, conventional cardiovascular risk factors and thrombotic variables in a cohort with well-controlled rheumatoid arthritis (RA) and in population controls. METHODS: Seventy-six RA patients and 641 controls, randomly sampled from the local population in the North Glasgow MONICA study. Conventional cardiovascular risk factors (blood pressure, smoking, cholesterol) and thrombotic variables [fibrinogen, von Willebrand factor (vWF), tissue plasminogen activator antigen (t-PA), fibrin D-dimer, plasminogen activator inhibitor (PAI-1), plasma viscosity] were measured by standard procedures. RESULTS: RA patients had a significantly higher prevalence of angina pectoris (P=0.03). Stroke also tended to be more common in the RA group, but the difference did not reach statistical significance (P=0.08). Diastolic blood pressure was significantly higher and serum cholesterol significantly lower in the RA group than in controls. Current smoking habits and exercise history were similar in the two groups, although RA patients were more likely to have previously smoked. Significant elevations in several thrombotic predictors of cardiovascular disease (fibrinogen, vWF, t-PA antigen and fibrin D-dimer) were found in the RA group. CONCLUSIONS: In this RA patient population, diastolic blood pressure was higher than in controls and thrombotic variables were elevated compared with controls. These features are identified as potential additional cardiovascular risk factors in the RA patients studied. Prospective studies of risk modification may permit the identification of factors which could lead to a reduction in the known increased cardiovascular risk in RA.
10505742 Long-term follow-up of cytokines and soluble cytokine receptors in peripheral blood of pat 1999 Sep Plasma levels of interleukin-1beta (IL-1beta), IL-2, soluble IL-2 receptor (sIL-2R), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and the p60 soluble TNF receptor (sTNFR) were repeatedly determined by enzyme-linked immunosorbent assays (ELISA) in 35 patients with different subtypes of juvenile rheumatoid arthritis (JRA) during an observation period of up to 36 months. The data were related to conventional inflammatory parameters and disease activity. Patients with systemic disease showed the most pronounced elevations of plasma cytokines, followed by polyarticular and pauciarticular JRA. Soluble receptors sIL-2R and sTNFR were consistently elevated in patients of all JRA subtypes and indicated disease activity even in patients with normal C-reactive protein (CRP). In contrast, the determination of IL-1beta, IL-2, IL-8, and TNF-alpha revealed strikingly different individual profiles in patients of the same clinical subtype of JRA and irrespective of disease activity. It is concluded that the determination of sIL-2R and sTNFR may be relevant for monitoring JRA, as they indicate disease activity also in cases with unaltered conventional inflammatory parameters. The different individual cytokine profiles of patients within identical subtypes of disease suggest JRA to be even more heterogeneous than hitherto assumed. The data should be considered in attempts to develop anticytokine strategies in the therapy of JRA.
10415637 Rheumatoid arthritis, personality, stress response style, and coping with illness. A preli 1999 Jun 22 Rheumatoid arthritis (RA) is an inflammatory chronic disease with an autoimmune pathogenesis and a complex multifactorial etiology. Various factors such as immunogenetic determinants, sex, age, and stress play an important role. The relationship between stress and RA is still unclear and undefined; however, various lines of research are developing in order to evaluate environmental, psychologic, and biologic stressors as predisposing factors. The aim of our study was to evaluate whether stress-related psychologic factors and personality disorders might be involved in the development of RA, by using a psychometric investigation-methodology in a series of patients. Fifteen in- and outpatients underwent a clinical interview and other specific psychometric tests. Macro- and microstressful life-events preceded RA onset in 86% of the cases. Sixty percent of the patients showed a correlation between flare-ups of the disease and appearance of microevents. Forty percent of the patients showed an obsessive-compulsive personality disorder (OCPD), 40% showed a borderline personality disorder (BPD), 7% showed a schizoid and a dependent disorder. Only 13% of the patients showed no personality disorders. Among the BPD group we also detected alexithymia. Our results should be considered as preliminary; on the other hand, the high prevalence of major life-events preceding the onset of RA and the presence of personality disorders support the role of the altered stress response system as an important pathogenetic factor and will be a matter of further studies.
11907701 Forearm bone mineral density in postmenopausal women with rheumatoid arthritis. 2002 Jan Osteoporosis in cases of rheumatoid arthritis (RA) is multifactorial, and the pathogenesis of bone loss induced by RA in postmenopausal women is not fully understood. The purpose of the present study was to determine the factors that affect forearm bone mineral density (BMD) in postmenopausal women with RA. In total, 839 postmenopausal women aged 46-90 years, were enrolled in the study; 470 patients with RA and 369 healthy controls (CON). Forearm (distal radius) BMD, measured by DXA using a DTX-200 (Osteometer, MediTech, CA, USA), was significantly lower in the RA group than in the CON group (P < 0.0001), even when adjusted for age, height, body weight, body mass index, and years since menopause (YSM) (P < 0.01). On multiple regression analysis, in the CON group, age and YSM were significantly correlated with BMD (P < 0.01 and P < 0.05, respectively). On the other hand, in the RA group, in addition to YSM, anatomic grade in the wrist, modified health assessment questionnaire (HAQ) score for the upper extremities, and erythrocyte sedimentation rate were each significantly correlated with BMD (P < 0.0001, P < 0.001, P < 0.0001, and P < 0.001, respectively), whereas functional class, duration of disease, dose of prednisolone used, modified HAQ score for the lower extremities, and the levels of c-reactive protein and rheumatoid factor were not. The present study with a large number of subjects shows that in addition to YSM, disuse (anatomic grade) of the wrist, arm function, and disease activity appear to be significant determinants of forearm BMD in postmenopausal women with RA.
11712766 Successful ovulation induction, conception, and normal delivery after chronic therapy with 2001 Nov Etanercept (Enbrel; Wyeth-Ayerst/Immunex Inc, Seattle, WA, USA) is a subcutaneously administered novel fusion protein consisting of the extracellular ligand-binding domain of the 75 kD receptor for tumor necrosis factor-alpha (anti-TNFalpha) and the Fc portion of human IgG1. The agent is synthesized by plasmid transfection of a Chinese hamster ovary cell line, utilizing recombinant DNA technology. Etanercept was approved by the US FDA for treatment of multi-drug resistant rheumatoid arthritis in 1998, but no human data exist regarding the impact of anti-TNFalpha therapy on human reproductive function or its use before ovulation induction. As TNFalpha potentiates collagenolysis via matrix metalloproteinase gene expression (thereby facilitating ovulation), there exists a theoretical risk that TNFalpha-inhibition could exert an undesirable effect on ovulation and pregnancy. In this report, we describe the first case of ovulation induction, intrauterine insemination, normal pregnancy and singleton delivery of a healthy infant following chronic ( > 1 year) pre-ovulatory TNFalpha-inhibitor therapy for rheumatoid arthritis. Reproductive endocrinologists and obstetrician-gynecologists should be familiar with etanercept therapy in the context of severe rheumatic disease, and offer appropriate reassurance regarding its safe use for infertility patients planning ovulation induction.
9035004 Pseudo-synovial cyst arising at the pubic bone region and forming a large femoral-inguinal 1997 Feb We describe a patient with rheumatoid arthritis who presented a large femoral-inguinal mass. The mass proved to be a synovial cyst-like structure communicating with rigid cystic lesions at the pubic bone. No obvious communication between the cystic lesions and the hip joint or bursae was seen by hip arthrogram or in surgery. Pathological examination of the cystic lesion at the pubic bone revealed infiltration of multiple rheumatoid nodules with marked fibrinoid necrosis into the bone, with synovium-like tissue on it. However, no synovial tissue was observed in the femoral-inguinal mass. These findings suggest that the femoral-inguinal mass was not a true synovial cyst but can be called a pseudo-synovial cyst arising at the pubic bone region.
10958875 Cystatin C, an early indicator for incipient renal disease in rheumatoid arthritis. 2000 Oct Rheumatoid arthritis (RA) is a chronic disease requiring potential nephrotoxic therapy with nonsteroidal antiinflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs (DMARDs). The rationale of our study was to examine the renal status of patients suffering from prolonged RA by means of plasma cystatin C, a new parameter of renal function. Fifty-six patients affected with RA for more than 5 years, and treated with NSAIDs for more than 50 months, were included in the study. Besides conventional markers of renal function (i.e. plasma creatinine, estimated glomerular filtration rate, creatinine clearance), we analysed plasma cystatin C by an automated, nephelometric immunoassay on a Behring nephelometer. Sixty percent of the RA patients exhibited elevated levels of plasma cystatin C, whereas only three out of 56 patients showed an elevated plasma creatinine, even though the creatinine clearance was decreased in 57% of these patients. Cystatin C exhibited a by far better correlation with creatinine clearance than plasma creatinine. In conclusion, patients with prolonged RA for more than 50 months, show a disturbed renal function despite normal plasma creatinine. Elevated cystatin C indicates such incipient renal disease, and is, not least because of a simple, well reproducible technique, more recommendable for screening purposes than tedious clearance determinations.
10219658 Biochemical effect of intra-articular injections of high molecular weight hyaluronate in r 1999 Mar OBJECTIVE: The purpose of this study was to analyze the biochemical characteristics of synovial fluids after treatment of patients with rheumatoid arthritis (RA) with intra-articularly injected hyaluronate (HA). TREATMENT: In a double-blind study, 13 patients received intra-articular injections of 1% HA in phosphate buffered saline (PBS) while 13 other patients were injected 0.01% HA in PBS, as the control group. Injections were administered once a week for five weeks. METHODS: Clinical efficacy and characteristics of synovial fluid were compared between groups. RESULTS: Significant clinical improvement was observed in the HA-treated group compared to the control group. The viscosity of retained synovial fluid increased. Stringing and HA concentration increased significantly whereas the concentrations of protein and chondroitin sulfate 4 and 6 decreased significantly. The HA molecular weight remained the same in both groups. CONCLUSION: Intra-articular HA injection altered the properties of synovial fluid and proved efficacious for patients with RA.
11791620 Apolipoprotein E phenotypes in rheumatoid arthritis with or without amyloidosis. 2001 Dec The role of apolipoprotein (apo) E in the pathogenesis of reactive amyloidosis is unclear. Here we evaluated the apoE phenotype distribution and apolipoprotein e allele frequencies in 55 adult patients with seropositive, erosive RA with amyloid and compared them with 55 matched RA patients without amyloid The apoE isotypes were determined by isoelectric focusing and immunoblotting. RA patients without amyloid had more often the apoE 3/3 phenotype (71%) than the RA+A patients (49%, P<0.05) or Finnish control subjects (47%, P<0.01) and the frequency of the apo epsilon3 allele was significantly higher among the RA patients without amyloid than among RA+A patients (P<0.05) or control subjects (P<0.01). The prevalence of the apoE3/4 phenotype among the RA+A patients, although higher, did not significantly differ from the RA patients without amyloid (40% and 26%, respectively, NS) or Finnish control subjects (40% and 35%, respectively, NS). The frequency of the apo epsilon4 allele among the RA+A patients did not signficantly differ from that of RA patients without amyloid (0.23 and 0.13, respectively, NS) or Finnish control subjects (both 0.23). However, the apo epsilon4 frequency of 0.13 among the RA patients without amyloid was significantly lower than that of Finnish control subjects (0.23, P<0.05). We conclude that the prevalence of the apoE4 isotype is not increased in patients with RA complicated by amyloidosis when compared with Finnish control subjects. Since the frequency of the apo epsilon4 allele is significantly decreased in RA patients without amyloid when compared with Finnish control subjects, the presence of the apoE4 in a patient with RA could, though, represent a relative risk factor for developing reactive amyloidosis.
10361385 Effects of gammalinolenic acid on interleukin-1 beta and tumor necrosis factor-alpha secre 1999 May BACKGROUND: Oils enriched in gammalinolenic acid, an unsaturated fatty acid, reduce joint pain and swelling in patients with rheumatoid arthritis. The cytokines interleukin-1 beta and tumor necrosis factor-alpha appear to contribute directly to joint tissue damage in patients with rheumatoid arthritis. Agents designed to interfere with the actions of interleukin-1 beta and tumor necrosis factor-alpha are being used to treat rheumatoid arthritis. METHODS: We examined the influence of gammalinolenic acid added to cells in vitro and administered orally in vivo on interleukin-1 beta and tumor necrosis factor-alpha secretion from activated human peripheral blood monocytes. Secretion of both cytokines was reduced by gammalinolenic acid. Administration of safflower oil as a polyunsaturated fatty acid control devoid of gammalinolenic acid did not change secretion of either cytokine. CONCLUSION: Suppression of IL-beta and TNF-alpha secretion by activated cells may be one mechanism whereby gammalinolenic acid suppresses synovitis in patients with rheumatoid arthritis.
10765920 Noninherited maternal antigens do not play a role in rheumatoid arthritis susceptibility i 2000 Apr 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.
9855217 Cortical photostimulation with filtered visible light as a treatment for rheumatoid arthri 1998 Not all extraocular photoreceptors in the human brain have been identified or their functions determined. The efferent and afferent fibres between the orbital frontal cortex and the hypothalamus cannot be overlooked in the context of the neuro-endocrine-immune feedback loop. It is suggested here that there are extraocular photoreceptors in the orbital frontal cortex, conceivably crucial for immunoregulation. The orbital frontal cortex of 7 volunteers with rheumatoid arthritis (RA) was photostimulated through the roof of the orbits with filtered visible light in sessions of 12, 14 and 16 minutes for a period of 6 weeks. Within 5 weeks, a significant decrease in the rheumatoid factor titres of 6 subjects was observed together with marked clinical improvement in 4 cases.
10332214 [A case of secondary systemic amyloidosis associated with rheumatoid arthritis after 3-yea 1999 Feb A 63-year-old woman who started to have polyarthralgia in December 1993 has been diagnosed as rheumatoid arthritis (RA) and treated with muscular injection of gold sodium thiomalate. She began to have nausea, vomiting, anorexia and watery diarrhea in October 1995. A year later, she had to receive intravenous infusion on admission since more frequent watery diarrhea occurred more than ten times within a day. On admission in our hospital in December 1996, she had proteinuria in addition to gastrointestinal symptoms. The biopsy specimen from stomach, duodenum and kidney proved systemic amyloidosis associated with RA. In spite of steroid-pulse, dimethyl sulfoxide (DMSO) and colchicine therapy, profound proteinuria in nephrotic syndrome was continued in association with hypoproteinemia, anasarca and renal failure. She was treated on hemodialysis and intravenous hyperalimentation (IVH) until November 1997 when A-V shunt operation on left forearm was performed. However, the shunt was not available for HD and she suffered from septicemia and died on December 1997. This patient was a rare case of secondary systemic amyloidosis associated with RA in early clinical course.
11361225 Lessons from an international survey of paper cases of 10 real patients from an early arth 2001 May OBJECTIVE: To determine how experts would classify 10 early-arthritis cases (7 atypical) and to study discrepancies in diagnoses relative to ACR criteria for rheumatoid arthritis (RA) or ESSG criteria for spondyloarthropathy (SpA). METHODS: Ten real cases (5 met ACR criteria for RA, 6 ESSG criteria for SpA, 3 both and 2 neither) followed for 28.5 +/- 4.8 months were sent as paper cases to 20 international and 12 French experts. Each expert selected a diagnosis among 8 possible choices and rated it on a 0-10 confidence scale. For each case, 3 analog scales (0-100 mm) were used to indicate the probability of RA, SpA or undifferentiated arthritis (UA). RESULTS: Experts often disagreed about diagnoses (up to 5 different diagnoses for a given case, with a mean of 3.9 per case). Similarly, expert opinions on probabilities for RA and SpA differed widely, with great overlap between confidence for RA, SpA and UA. Fulfilment of ACR or ESSG criteria was poorly related to the experts' diagnosis and evaluation of probabilities for RA and SpA. However, UA was a relatively infrequent choice (19%). CONCLUSIONS: There was no general consensus about the nosology of early RA and SpA. Classification of atypical early arthritis was not resolved by currently available criteria for RA and SpA. This may have implications for therapy in early disease.