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PMID	Title	PublicationDate	abstract
2924460	Atlantoaxial instability and neurologic indicators in rheumatoid arthritis.	1989 Apr	Atlantoaxial subluxation in rheumatoid arthritis is characterized by pain, disability, and occasionally death. Surgical fusion of the offending vertebrae is the appropriate surgical remedy, but it is a procedure with a high failure and complication rate. Because cord compression and myelopathy are the main complications of this condition, it would be logical to use evidence of early neurologic deficit as an indicator for surgery. A group of 250 patients with rheumatoid arthritis were investigated to evaluate the neurologic status with respect to the degree of instability in the proximal cervical spine. Neurologic isolated signs such as hyperreflexia could not be correlated with the onset of cervical myelopathy or quadraparesis or to the radiographically measured degree of atlantoaxial instability. These signs should not be used as an indication for surgery. The positive indications are intractable pain, cervical myelopathy, and severe atlantoaxial instability.
1757929	Mortality predictors among 263 patients with rheumatoid arthritis.	1991 Sep	A cohort of 263 patients who completed Health Assessment Questionnaires (HAQ) each year from 1981 to 1989 is examined. Forty-three (43) possible covariates measured in 1981 are considered that might help predict mortality over the 8 years of the study. We use univariate correlation coefficients, stepwise regressions, and survival functions to identify a number of covariates that appear useful for predicting survival: age (-), prednisone use (-), disability index (-), male sex (-), never married (-), penicillamine use (+), divorced (+), and no occupation (-). Our results confirm studies suggesting that the HAQ disability index is a useful prognosticator of length of survival.
3814192	Cyclosporin A treatment of refractory rheumatoid arthritis.	1987 Jan	Ten patients with rheumatoid arthritis were entered into a 24-week pilot study of oral cyclosporin A at a starting dosage of 6 mg/kg/day, followed by a 12-week washout period. Significant improvement in clinical parameters was observed at 12 weeks and 24 weeks (P less than 0.02 versus baseline for joint pain and joint swelling indexes and patient and physician assessments; P less than 0.04 versus baseline in the numbers of painful/tender joints and swollen joints). Adverse reactions were varied: renal impairment occurred in all patients and hypertension occurred in 7. All patients demonstrated an increase in defined disease activity at cessation of treatment and through the washout period. Cyclosporin A is clinically effective in the treatment of patients with refractory rheumatoid arthritis, but its value as an intervention therapy is limited by its toxicity.
3101621	Evidence for oligoclonal B cell expansion in the peripheral blood of patients with rheumat	1986 Dec	Peripheral blood lymphocytes from patients with rheumatoid arthritis and osteoarthritis were examined for evidence of oligoclonal B cell expansion using the computer assisted flow cytometric technique of kappa-lambda (kappa-lambda) analysis. Eleven of 29 patients with rheumatoid arthritis but only one of 16 with osteoarthritis gave abnormal results (p less than 0.025). Abnormal kappa-lambda determinations did not correlate with age, duration of disease, presence of rheumatoid factor, or other clinical and laboratory parameters. Therapy with oral or intramuscular gold compounds appeared to diminish the incidence of kappa-lambda abnormality. These findings may indicate defective control of clonal B cell proliferation in rheumatoid arthritis.
1930911	Cytokines in rheumatoid arthritis.	1991 Aug	Joints with rheumatoid arthritis are a site for chronic inflammation involving T cells, B cells, macrophages and dendritic cells. When these cells interact cytokines are likely to be produced. The presence of different cytokines in the synovial fluid of patients with rheumatoid arthritis has been studied and the macrophage derived cytokines such as IL-1, IL-6, TNF-alpha, TGF-beta and PDGF have usually been detected in large quantities, whereas T cell produced cytokines (IL-2, IL-4, IFN-gamma) are absent or present in small quantities. IL-1, IL-6 and TNF-alpha have several functions which suggest that they participate in the chronic disease process of rheumatoid arthritis, such as increasing production of eicosanoid, collagenase and prostaglandin E2. Many synovial B cells are activated and produce large amounts of immunoglobulins. We searched for a B cell stimulatory activity in rheumatoid synovial fluid and found a B cell differentiation and helper activity. Cytokines in the joints of patients with rheumatoid arthritis seem central for the propagation of the disease process. Specific intervention in cytokine production or in its effects might help to relieve symptoms in rheumatoid patients.
2873247	Rheumatoid arthritis after Takayasu's arteritis.	1986 Apr	The association of Takayasu's arteritis with other rheumatic disease is rare. We report a 37-year-old female who developed Takayasu's arteritis in her 20s and subsequently developed rheumatoid arthritis.
3944948	Noncontraceptive hormones and rheumatoid arthritis in perimenopausal and postmenopausal wo	1986 Mar 14	The use of noncontraceptive hormones before onset of joint disease was compared between 490 perimenopausal and postmenopausal women with rheumatoid arthritis and a control group of 659 women with soft-tissue rheumatologic disorders and/or osteoarthritis. Both groups were sampled randomly from the attendees of five rheumatologic clinics. A negative association was found between the onset of rheumatoid arthritis and the previous use of noncontraceptive hormones (odds ratio, 0.32; 95% confidence interval, 0.16 to 0.64). This association persisted on univariate and multivariate control of potentially confounding variables and on subgroup analysis. The protective effect of oral contraceptives on the development of rheumatoid arthritis was confirmed.
1920330	Relationship of self-efficacy to pain behavior.	1991 Jul	Our purpose was to examine the effects of self-efficacy on the pain behaviors exhibited by patients with rheumatoid arthritis (RA). Seventy-two patients with RA were assessed using a standardized videotaping procedure for rating specific pain behaviors such as limps, facial grimaces, and guarded movements. Patients also completed questionnaires measuring self-efficacy and depression. Hierarchical regression was used to assess the relationship between self-efficacy and pain behavior after the effects of demographic characteristics and disease activity were statistically controlled. Higher self-efficacy was found to be related to fewer pain behaviors. In contrast, depression was found to be unrelated to pain behavior. Our results indicate that the pain behaviors that patients with RA exhibit are related to their self-efficacy, not solely to their disease activity.
2769668	Urinary hydroxy-pyridinium crosslinks provide indices of cartilage and bone involvement in	1989 Jul	The urinary concentrations relative to creatinine of the collagen crosslinks, pyridinoline (PYD) and an analogue derived specifically from bone collagen, deoxy-pyridinoline (DPD), were measured using a high performance liquid chromatography (HPLC) technique in 41 patients with rheumatoid arthritis (RA) and 45 patients with osteoarthritis (OA), and were compared with values of 118 healthy control individuals. The levels of DPD were increased significantly in both RA and OA suggesting accelerated bone degradation in both disease groups. PYD concentrations were also significantly increased in both diseases, but larger increases were detected in patients with RA, for which this index correlated with clinical measures of joint involvement and biochemical variables of inflammatory activity. Cross-sectional studies showed that treatment with disease modifying drugs (gold and D-penicillamine) led to decreased crosslink levels but longterm corticosteroids resulted in increased urinary crosslinks, probably due to the induction of bone resorption. Measurement of both pyridinium crosslinks in urine may therefore provide information on the stage, activity, level of bone involvement and efficacy of drug therapy in arthritic diseases.
2711138	Intra-articular temperature measurements after superficial heating.	1989	Superficial heating of the joint is widely used in various rheumatic conditions and is considered as decreasing the intra-articular temperature. This study shows that heating the joint with hot pack significantly increases the articular temperature from 35.2 +/- 1.5 degrees C (mean +/- SD) to 36.4 +/- 1.0 degrees C (p less than 0.001), while intra-cavity temperature of the contralateral unheated knee joint did not change significantly. Since such elevation of temperature of one degree C is liable to enhance the inflammatory process, the use of superficial heating has to be carefully reconsidered in acute and chronic inflammatory joint diseases.
1802490	Tumour necrosis factor alpha and interleukin-2 in plasma from rheumatoid arthritis patient	1991 Dec	Tumour necrosis factor alpha (TNF alpha) and interleukin-2 (IL-2) are potential immunological mediators of pathogenetic changes in rheumatoid arthritis. We measured the concentrations of TNF alpha and IL-2 in plasma from 2 groups of patients suffering from rheumatoid arthritis (RA). One group had high and one had low disease activity. In addition, in connection with steroid treatment in the high disease activity group, TNF alpha was significantly increased in plasma from RA patients with high disease activity compared with those of low disease activity (p = 0.0009). Furthermore, TNF alpha decreased significantly in relation to steroid medication, parallel to clinical improvement (p = 0.016). All IL-2 concentration measurements were within the estimated normal range. The increased TNF alpha plasma levels in patients with rheumatoid arthritis with high disease activity, might result from activated white mononuclear cells in the inflamed joints. This might, in part, support the theory that TNF alpha is a possible mediator of pathogenetic changes known to occur in rheumatoid arthritis.
1884588	MRI of the cervical spine: rheumatoid arthritis compared with cervical spondylosis.	1991 Aug	This study is a comparison of the cervical spine MR images from 26 patients with rheumatoid arthritis of the cervical spine with those from an age and sex matched group suffering from cervical spondylosis. Erosion of bone and major atlanto-axial subluxation were confined to rheumatoid arthritis. Soft tissue changes revealed by MRI included distortion of normal ligaments and bursae around the dens, particularly in rheumatoid arthritis. Abnormal masses of soft tissue were found in both groups, but those suggesting acute inflammation were much more frequent in rheumatoid arthritis than in cervical spondylosis. Neural compression was well demonstrated, and in rheumatoid arthritis was usually caused by bony structures whereas in cervical spondylosis it was usually due to disc material. It is concluded that MRI should be used as the first investigation to follow plain films in rheumatoid arthritis of the cervical spine. Bone and soft tissue changes are clearly shown, but interpretation of the images requires the recognition that some observed abnormalities may be due to coincidental cervical spondylosis.
3401054	Phytohaemagglutinin induced proliferation of lymphocytes from patients with rheumatoid art	1988 Jul	The response of peripheral blood lymphocytes to stimulation by mitogens such as phytohaemagglutinin (PHA) is commonly depressed in both rheumatoid arthritis and iron deficiency, and as many rheumatoid patients are anaemic with evidence of abnormal iron metabolism it is possible that the same mechanism underlies the observed suppression in both conditions. In the present study the mitogenic response to PHA of lymphocytes from three rheumatoid patients, who were also iron deficient, and two healthy controls has been shown to be significantly less in iron deficient than iron containing media (p less than 0.001). In addition, iron deficient sera from these patients reduced the PHA induced proliferation of lymphocytes from a normal subject (p less than 0.01), an effect which was prevented by prior addition of iron to these serum samples. In iron containing media lymphocytes from five patients and two controls showed no difference in their response to PHA for both the minimum mitogen concentration which enhanced transformation and the peak [3H]thymidine uptake; but patients' lymphocytes showed significantly less response to PHA concentrations of 5 and 10 mg/l (p less than 0.02), resulting in a reduction in the area under the dose response curves up to 20 mg/l (p less than 0.05). These findings show both that iron deficient sera can impair PHA induced lymphocyte transformation and that lymphocytes from iron deficient rheumatoid patients have impaired responsiveness to PHA. Iron is known to be required intracellularly for the enzyme ribonucleotide reductase, which is important for DNA synthesis, and reduced activity of this enzyme could explain these observed effects.
2920048	Lack of correlation between the Steinbrocker staging of hand radiographs and the functiona	1989 Feb	We evaluated the correlation between destructive changes seen on hand radiographs and disability in 54 patients with definite or classic rheumatoid arthritis. No statistically significant correlation was found between radiographic findings and patient disability as determined by patient and physician assessment or by the patient's score on the Arthritis Impact Measurement Scales questionnaire. These findings call into question the appropriateness of using hand radiographs as a determinant of disability or as a criterion for disability insurance benefits.
1920305	Are the results of controlled clinical trials and observational studies of second line the	1991 Jul	We studied 122 controlled clinical trials and observational studies of second line therapy that involved 16,071 patients. The mean disease duration was 7.61 years at study entry. Controlled clinical trials were inherently short term, and 90.5% of patients were followed for 1 year or less (mean 8.8 months). The mean followup of observational studies was 31 months. Outcome assessments that included functional measurements were rare in either study type, as were considerations of socioeconomic factors. Except for methotrexate, which was used longer, half of the studies indicated discontinuation of therapy after 1.5 years. Good retention rates in studies of 3 to 12 months were not representative of longterm results, but controlled clinical trials and observational studies were similar as to retention during the first treatment year. Observational studies following controlled clinical trials can yield important information about RA treatment effectiveness not available from controlled clinical trials alone.
2182168	Comparison and evaluation of a disease activity index for use in patients with rheumatoid	1990 Apr	An algorithm (Stoke index) has been designed to give a global measure of disease activity in rheumatoid arthritis. This algorithm has been created as an easy to use flow diagram based on two objective laboratory measures (C-reactive protein and erythrocyte sedimentation rate), one subjective and two semi-objective clinical measures (morning stiffness, synovitis score and Ritchie articular index). Results of six clinical markers and seven laboratory markers of disease activity on a cohort of 371 rheumatoid patients have been used to evaluate the algorithm and compare it with a previously described index of disease activity (Mallya-Mace index). Principal component analysis validates its ability to measure disease activity. Sensitivity is described by the distribution of patients between the two index scores. Change in index score by patients over a 6-month period indicates reversibility. The Stoke index demonstrates greater sensitivity and reversibility than the Mallya-Mace index. These findings indicate that the algorithm described provides a useful index of global disease activity for use in the assessment of rheumatoid arthritis.
1883694	The immunopathogenesis of rheumatoid arthritis.	1991 Jun	There is little doubt that the immune system plays an integral role in the pathogenesis of rheumatoid arthritis. However, the contributions of various cell types, including lymphocytes, antigen-presenting cells, and mesenchymal cells and their mechanisms of participation, are debatable. Basic research has focused on these questions over the last decade, with particular attention to soluble mediators of inflammation (eg, cytokines) and the activation states of T lymphocytes and synovial lining cells. A brief overview is presented in the context of studies published during the last year.
2427090	Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients. Asso	1986 Jul	Serum and red blood cell methotrexate (MTX) levels, as well as hepatic levels of MTX and folate, were analyzed in 24 patients who had received long-term oral MTX weekly for the treatment of rheumatoid arthritis. The serum MTX level peaked rapidly and was insignificant after 24 hours. The red blood cell MTX level was not related to the interval from the last MTX dose. In hepatic tissue obtained by liver biopsy, MTX was found in a predominantly polyglutamated form with depleted hepatic folate stores when compared with baseline specimens. A brief period of therapy with oral folinic acid repleted hepatic folate. It is possible that MTX hepatotoxicity is related to reduced hepatic folate levels and formation of MTX polyglutamates.
2155914	Localization of collagenase mRNA in rheumatoid arthritis synovium by in situ hybridization	1990 Jan	Collagenase has been implicated as playing an important role in the connective tissue destruction that is a major feature of rheumatoid arthritis. Numerous cell types in the hyperplastic rheumatoid synovium are capable of synthesizing collagenase. Past studies have used predominantly synovial fibroblasts in culture as a model system for the regulation of collagenase production, but the major cellular source of the enzyme in vivo has not been determined. Using the techniques of in situ hybridization histochemistry and indirect immunofluorescence, we determined the cellular source of collagenase in frozen sections of human synovium. Collagenase mRNA production was localized to cells along the synovial lining layer in rheumatoid arthritis. These were identified as the macrophage-like Type A synovial lining cells by immunofluorescence with antibody LeuM3. Endothelial cells, fibroblasts, and T and B lymphocytes were devoid of detectable collagenase mRNA. Synovial tissue sections from patients with osteoarthritis and trauma did not contain detectable collagenase mRNA. These data identify the Type A macrophage-like synovial lining cell as the primary source of collagenase mRNA in vivo in the rheumatoid arthritis synovium and, potentially, as a major effector cell in the tissue destruction of the disease.
3588907	Cervical rheumatoid arthritis: value of flexion and extension views in imaging.	1987 Jul	The magnetic resonance (MR) imaging findings in the cervical spines of eight patients with long-standing polyarticular rheumatoid arthritis were reviewed. Three pathologic conditions were readily demonstrated: anterior atlantoaxial subluxation (n = 6), atlantoaxial impaction (n = 6), and subaxial subluxation (n = 6). An abnormal soft-tissue signal was noted in the preodontoid space in six patients; this signal was thought to represent the associated inflammatory mass. MR imaging was useful not only for depicting the bony abnormalities in the cervical spine that are associated with rheumatoid arthritis, but also can directly show the effect of the disease process on the spinal cord and brain stem.