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ID PMID Title PublicationDate abstract
1329775 Localization of tumor necrosis factor receptors in the synovial tissue and cartilage-pannu 1992 Oct OBJECTIVE: We have previously described the location of tumor necrosis factor alpha (TNF alpha)-producing cells in synovial tissue and cartilage-pannus junction in rheumatoid arthritis (RA). To further understand the local actions of TNF alpha, we investigated the expression of TNF receptors (TNF-R) on cells in the same compartments in patients with RA. METHODS: The expression of both p55 TNF-R and p75 TNF-R was determined using alkaline phosphatase-conjugated mouse anti-alkaline phosphatase (APAAP) and double immunofluorescence staining techniques with monoclonal antibodies. RESULTS: In RA synovial membrane, both p55 TNF-R and p75 TNF-R were detectable in up to 90% of the cells in the lining layer, and were demonstrated on cells in deeper layers of the membrane, including vascular endothelial cells. Cells in lymphoid aggregates expressed both TNF-R, but with a predominant expression of p75 receptor. At the cartilage-pannus junction, the majority of pannus cells, especially those invading cartilage, expressed both the p55 and the p75 TNF-R. Sequential section and double immunofluorescence staining showed that the TNF-R-expressing cells were in the vicinity of TNF alpha-containing cells, and some TNF alpha-containing cells also expressed TNF-R. TNF-R-expressing cells were also detected in osteoarthritic and normal synovial tissue, but in smaller numbers and at a lower intensity. CONCLUSION: These results provide histologic evidence that both p55 TNF-R and p75 TNF-R are expressed by a variety of cell types in RA synovial tissue, reflecting the fact that a wide range of cells are potential targets for TNF alpha in this tissue. This study further supports the hypothesis that TNF alpha plays a major role in the pathogenesis of RA.
8254100 Rheumatoid arthritis and B cell lymphoma with pathological changes of reactive histiocytos 1993 Nov A 67 year old woman with rheumatoid arthritis was admitted to hospital in acute renal failure. Her clinical features included increasing dyspnoea and oedema, and a computed tomogram of the abdomen showed a large mass in the retroperitoneum. Twenty six days later, she died, and a post mortem examination was carried out. The histological changes of the mass indicated B cell lymphoma of diffuse large cell type, with a reactive proliferation of erythrophagocytosing histiocytes. Immunocytochemical studies showed that the histiocytes were positive for CD-68 and lysozyme, but negative for S-100 protein. Such neoplastic B cell proliferation accompanied by activation of benign looking histiocytes with erythrophagocytosis is very rare.
1625388 [A case of gold-induced pneumonitis showing a positive reaction in the drug lymphocyte sti 1992 Jan A case of acute interstitial pneumonia developing during gold therapy is reported. A 67-year-old female with rheumatoid arthritis for about twenty years who received a total dose of 80 mg of gold thiomalate (Shiosol) for about two months, developed high fever and dry cough. Exertional dyspnea developed and chest roentgenogram showed diffuse small nodular and reticular shadows. RA and RAPA tests were positive. Drug lymphocyte stimulation test (DLST) for Shiosol was positive. The dyspnea resolved on administration of methylprednisolone. Chest roentgenogram and CT-scan showed improvement. A total dose of 80 mg of gold thiomalate, as administered in this case, is the minimum dose previously reported in Japan. It has been recently reported that allergic reaction is the mechanism of gold lung. In the present case, positive DLST indicated the existence of many activated lymphocytes, and was very useful in the diagnosis of gold lung.
1522089 The use of computerized tomography in the measurement of glenoid version. 1992 Aug Computerized tomography was done preoperatively on twenty shoulders (thirteen patients) in which there were severe arthritic changes, to measure glenoid version. Ten of the twenty shoulders had osteoarthrosis; eight, rheumatoid arthritis; and two, gouty arthritis. To help determine normal values, computerized tomographic scans of the chest of sixty-three patients who did not have roentgenographic evidence of disease of the shoulder were studied retrospectively for comparison as a control group. In the group of patients who had severe arthritis, the mean glenoid orientation was 11 degrees of retroversion (range, 2 degrees of anteversion to 32 degrees of retroversion). The computerized tomographic scans showed uneven wear of the glenoid surface, osteophytes, large cysts, and posterior displacement of the humeral head. In the control group, the mean orientation of the glenoid was 2 degrees of anteversion (range, 14 degrees of anteversion to 12 degrees of retroversion). The difference between the groups was significant (p less than 0.0001). Glenoid retroversion was increased in the patients who had severe arthritis, and the computerized tomographic scans accurately revealed the extent and pattern of erosion of the bone.
8651965 N-[4-hydroxyphenyl] retinamide in rheumatoid arthritis: a pilot study. 1996 Jun OBJECTIVE: To evaluate the efficacy and tolerability of N-[4 hydroxyphenyl] retinamide (4-HPR), a synthetic retinoid, in the treatment of rheumatoid arthritis (RA). METHODS: An uncontrolled, open clinical trial with synovial biopsy pre- and postmedication to evaluate the clinical effects of 4-HPR as well as its effects on metalloproteinase gene expression. RESULTS: Twelve patients with severe, longstanding RA were enrolled in this study. Six patients withdrew before study completion, 2 because of drug toxicity, 2 because of a flare of RA, and 2 because of intercurrent medical problems. No patient met predetermined Paulus criteria treatment response, and there was no improvement in the laboratory parameters, except for a modest decrease in C-reactive protein. No decrease in messenger RNA for the metalloproteinases collagenase and stromelysin was seen in the 2 patients in whom paired synovial biopsies were obtained. CONCLUSION: No beneficial clinical effect was observed with the retinoid 4-HPR in the treatment of severe, longstanding RA at the 300 mg/day dosage studied. The use of higher dosages is precluded by the observed toxicities. The effect of this drug in patients with early or mild disease was not studied. Although this particular retinoid was not effective in this pilot study, the use of other retinoids in RA should still be considered.
1589613 [The hormonal changes in postmenopausal women with rheumatoid arthritis]. 1992 Mar We have studied the levels of sexual hormones in 45 female patients suffering seropositive rheumatoid arthritis (RA). Patients were classified in two groups. Group 1 (premenopausal), was formed by 26 women and group 11 (postmenopausal) by 19 women. They were compared to 40 control women (20 premenopausal and 20 postmenopausal). Age and body surface as similar in both groups. Mean estradiol, progesterone and androgen plasma levels in group 1 were similar to the premenopausal control group. On the contrary, group 11 patients presented a statistically significant increase in plasma androgen levels when compared to the postmenopausal control group. This seems to indicate that postmenopausal women suffering rheumatoid arthritis present a hyperandrogenic situation, which could have a beneficial effect on the clinical expression of the disease.
7677444 Intra-articular pressure changes in rheumatoid and normal peripheral joints. 1995 Aug OBJECTIVE: To investigate the intraarticular pressure (IAP) dynamics of a spectrum of joints in rheumatoid and normal subjects in order to determine whether a reperfusion event is likely to occur at these sites. METHODS: IAP was measured in the metacarpophalangeal (MCP) (n = 8), wrist (n = 8), ankle (n = 4), and elbow joints (n = 4) of rheumatoid subjects, in addition to the MCP (n = 8), wrist (n = 6), and ankle joints (n = 1) of normal healthy controls, using the hand held portable 295-1 Intra-Compartmental Pressure Monitor System (Stryker, UK). RESULTS: Resting IAP was positive in all rheumatoid joints, and subatmospheric or weakly atmospheric in normal subjects (p < 0.01). Exercise produced an increase in IAP in rheumatoid subjects only (p < 0.01). The addition of saline to normal joints mimicked the IAP changes seen in the rheumatoid group. CONCLUSION: These observations suggest that increased resting IAP is a marker for chronic joint inflammation. The IAP increase seen in the rheumatoid group during exercise supports the concept of hypoxic reperfusion mediated joint injury.
7979582 Bone mineral density in nonsteroid treated early rheumatoid arthritis. 1994 Oct OBJECTIVES: To determine whether significant reduction in bone mass is detectable in early disease in patients with rheumatoid arthritis (RA) and to examine the possible influences of disease activity and physical disability on bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN). METHODS: LS and FN BMD values were measured and Z scores determined in a cross-sectional study of 104 patients with RA of less than five years duration. BMD values were also compared between a subgroup of 64 patients and a normal control group matched for age, sex, menopausal status and body mass. BMD values and Z scores were correlated with disease activity, measured by the Stoke Index, disability, measured by HAQ score, and disease duration. RESULTS: Premenopausal female patients with RA had significantly reduced mean FN Z scores (-0.62, 95% CI -0.30 to -0.94) which correlated with HAQ scores (Rs 0.358, p = 0.05) and age (Rs 0.397, p = 0.03). There were no significant changes of BMD in males or postmenopausal females. Disease duration and disease activity did not correlate with BMD changes. CONCLUSION: BMD is reduced in premenopausal female patients with early RA possibly related to the attainment of peak bone mass. No significant reduction of BMD was found in males or postmenopausal females with early disease. Physical disability but not disease activity appears to play a role in the reduction of FN bone mass.
8911649 Hormones and autoimmunity: animal models of arthritis. 1996 May Hormones, particularly those involved in the hypothalamic-pituitary-gonadal and -adrenal axes (HPG and HPA), play important roles in various animal models of autoimmunity such as systemic lupus erythematosus in mice and collagen-induced arthritis (CIA) in mice and rats, and the streptococcal cell wall, adjuvant and avridine arthritis models in rats. Intimately linked to the subject of hormones and autoimmunity are gender, sex chromosomes and age. The importance of these factors in the various animal models is emphasized in this chapter. Several major themes are apparent. First, oestrogens promote B-cell dependent immune-complex mediated disease (e.g. lupus nephritis) but suppress T-cell dependent pathology (CIA in mice and rats), and vice versa. Second, testosterone's effects are complicated and depend on species and disease model. In rats, testosterone suppresses both T-cell and B-cell immunity. In mice, the effects are complex and difficult to interpret, e.g. they tend to enhance CIA arthritis and suppress lupus. Sex chromosome/sex hormone interactions are clearly involved in generating these complicated effects. Third, studies in Lewis and Fischer F344 rats exemplify the importance of corticosteroids, corticotrophin releasing hormone and the HPA axis in the regulation of inflammation and the predisposition to autoimmune diseases. Fourth, the HPA axis is intimately linked to the HPG axis and is sexually dimorphic. Oestrogens stimulate higher corticosteroid responses in females. The animal model data have major implications for understanding autoimmunity in humans. In particular, adrenal and gonadal hormone deficiency is likely to facilitate T-cell dependent diseases like rheumatoid arthritis, while high oestrogen levels or effects, relative to testosterone, are likely to promote B-cell dependent immune-complex-mediated diseases such as lupus nephritis.
1578466 Rheumatoid pleural effusion: response to intrapleural corticosteroid. 1992 Mar The management of a patient with a large symptomatic rheumatoid pleural effusion is described. Thoracentesis and bed rest gave only short term modest benefit. A more lasting and beneficial response was obtained with an intrapleural injection of (120 mg) depomethylprednisolone acetate. This treatment is a useful interim measure until disease suppressive therapy gives systemic control.
1358078 Use of short-term efficacy/toxicity tradeoffs to select second-line drugs in rheumatoid ar 1992 Oct OBJECTIVE: Preferred drugs for rheumatoid arthritis (RA) should be those that have maximal efficacy with the least toxicity. We evaluated the efficacy and toxicity tradeoffs for drugs frequently used in the treatment of RA. METHODS: We updated 2 metaanalyses of published clinical trials, by adding trials published through 1990 and trials of azathioprine (AZA). We tested 3 different definitions of efficacy, each plotted against 3 different toxicity measures, for antimalarial drugs, methotrexate (MTX), auranofin, injectable gold, D-penicillamine, sulfasalazine (SSZ), AZA, and placebo. Efficacy measures included composite efficacy (a combination of joint count, grip strength, and erythrocyte sedimentation rate), tender joint count alone, and a measure based on how many patients dropped out due to inefficacy. Toxicity measures were the proportion dropping out due to toxicity, the same dropouts with side effects weighted for severity using a modification of a published toxicity index, and the proportion with severe toxicities (defined as a score of at least 7 of 10 on the toxicity index). The latter were usually organ toxicities (e.g., cytopenias and renal involvement). RESULTS: All 9 efficacy/toxicity tradeoff plots suggested that MTX and antimalarial drugs had the highest efficacy relative to toxicity. MTX scored among the most efficacious of the drugs and, of these, had the least toxicity. Antimalarial drugs, though showing only moderate efficacy, had the lowest toxicity rate of all the drugs. SSZ scored close to MTX but was, in general, slightly more toxic. CONCLUSION: In the short-term context of clinical trials, antimalarial drugs and MTX have the best efficacy/toxicity tradeoffs and may, therefore, be the preferred drugs.
8185692 Interleukin-1 beta induces cytosolic phospholipase A2 and prostaglandin H synthase in rheu 1994 May OBJECTIVE: In order to investigate potential regulatory mechanisms for the increased production of prostaglandin E2 (PGE2) in interleukin-1 beta (IL-1 beta)-stimulated rheumatoid synovial fibroblasts (RSF), this study examined the induction of phospholipase A2 (PLA2) and prostaglandin H synthase (PGHS) enzymes and the correlation of these events with PGE2 production in IL-1 beta-stimulated RSF. METHODS: Protein and messenger RNA (mRNA) levels of cytosolic PLA2 (cPLA2) and PGHS-2 enzymes in IL-1 beta-stimulated RSF were measured by Western and Northern blotting, respectively, using specific antisera and complementary DNA probes. Enzymatic activity of cPLA2 was determined in cell-free reaction mixtures utilizing mixed micelles of 14C-phosphatidylcholine and Triton X-100 as the substrate. PGE2 levels were quantitated using a commercial enzyme immunoassay kit. RESULTS: Incubation of RSF with IL-1 beta increased the mRNA and protein levels for the high molecular weight cPLA2 as well as for the mitogen/growth factor-responsive PGHS (PGHS-2). The IL-1 receptor antagonist completely abolished the induction of these two enzymes and the stimulation of PGE2 production by IL-1 beta in RSF. In contrast, levels of the other known forms of these enzymes, i.e., the 14-kd secretory group II PLA2 (sPLA2) and the constitutive form of PGHS (PGHS-1), were unaffected by IL-1 beta treatment. CONCLUSION: These are the first data to demonstrate the coordinate induction by IL-1 of cPLA2 and PGHS-2 in RSF. The time-course for the induction of these enzymes suggests that their increase contributes to the increased production of PGE2 in IL-1-treated RSF, and may help explain the capacity of RSF to produce large amounts of PGE2.
8204235 Spontaneous orbital hemorrhage during general anesthesia and arthroplasty. 1994 Mar A 72-year-old woman who had a history of arthritis and cerebral vascular accident 4 years earlier underwent hand surgery. Because regional anesthesia was not successful, general anesthesia was administered. Shortly before extubation, proptosis developed in her left eye, and she was unable to open it. The condition was due to spontaneous orbital hemorrhage and resolved with conservative treatment.
9013382 Reevaluation of some double-blind, randomized studies of dexibuprofen (Seractil): a state- 1996 Dec This article presents a reevaluation of studies previously performed regarding the efficacy and safety of dexibuprofen (Seractil; S(+)-ibuprofen) for use in patients with inflammatory or degenerative diseases. Using appropriate standardized measures (univariate and multivariate analysis with the Mann-Whitney statistic with confidence intervals), the authors were able to compare the effects of treatment in different diseases. For the primary criterion and for the combined analysis of all efficacy criteria, one-sided equivalence was proved in all six studies reviewed.
8356391 Differential expression of gelatinase B (MMP-9) and stromelysin-1 (MMP-3) by rheumatoid sy 1993 Primary cultures of adherent rheumatoid synovial cells (ASC) are comprised of variable proportions of fibroblasts, macrophages and stellate cells (activated fibroblasts). These cultures were shown to produce the metalloproteinases stromelysin-1 (MMP-3), gelatinase A (MMP-2) and gelatinase B (MMP-9) by Western blotting and zymography techniques. Immunolocalisation studies showed that MMP-3 was mainly produced by the fibroblastic cells whereas MMP-9 was restricted to macrophages (CD68 positive). Subcultured synovial fibroblasts, devoid of macrophages, did not produce MMP-9 as judged by zymography and immunolocalisation; but when stimulated with phorbol myristate acetate and interleukin-1 alpha both MMP-9 and MMP-3 were co-expressed. These 'activated' fibroblasts assumed a dendritic or stellate morphology, which in localisation studies was usually associated with enhanced enzyme production. Immunolocalisation studies of rheumatoid synovial tissue showed that relatively few cells were positive for MMP-3 and MMP-9. Localisation of MMP-9 corresponded to a proportion of macrophages positive for the CD68 marker throughout the synovial tissue. MMP-3 localisation was not associated with the macrophage marker, but was observed in both the synovial lining layer and deeper stromal locations. Widespread distribution of both enzymes was not observed in fresh tissues, but this increased in tissues subjected to short-term explant cultures. Thus, both in vitro and in vivo studies indicated that synovial fibroblasts or B-cells are effective producers of MMP-3 whereas macrophages elaborate MMP-9, observations that demonstrated different metalloproteinase phenotypes under similar environmental conditions.
7858000 Anatomical urinary stress incontinence in women with rheumatoid arthritis: its frequency a 1994 Jun OBJECTIVE: The objectives of this study were to develop a valid screening tool for anatomical urinary stress incontinence (AUSI), to use it to determine the frequency of AUSI in women with RA, and to identify the cognitive, behavioral, and psychological coping strategies used by these women to deal with incontinence. METHODS: A screening tool concerning AUSI was validated by comparing self-reported incidences of AUSI with clinical evaluation. Questionnaires regarding presence of AUSI and cognitive, behavioral, and psychological coping strategies were sent to 750 women clinically diagnosed with RA. RESULTS: Of the 262 respondents (35% response rate), 21% had characteristics of AUSI, a rate similar to general population studies. Coping strategies varied depending on whether the women were at home or away from home and whether the women were alone or with others. CONCLUSIONS: There is a need for women with incontinence and the health care workers who serve them to be educated about AUSI and its treatments.
7915222 A possible linkage of HLA-DRB haplotypes with Tiopronin intolerance in rheumatoid arthriti 1994 May To investigate the relationship between HLA class II genotypes and toxic intolerance during treatment with Tiopronin, a slow-acting drug used in the treatment of rheumatoid arthritis (RA), we studied 40 patients who were divided into two groups: a group of 22 patients without side effects and a group of 18 patients with intolerance to Tiopronin. The PCR-RFLP method was used to determine the HLA-DR, DQ and DP genotypes. The patients in the two groups had similar genetic backgrounds with an expected high frequency of DRI and DR4 alleles. However, DR1/DR4 heterozygosity was significantly increased in patients with intolerance (p = 0.03, Odds Ratio = 10.5). In addition, one intolerant patient had a DR1/DR7 genotype which shared DRw53 (DRB4*0101) with DR1/DR4. Furthermore, two subtypes of DR5, DRB1*1102 and DRB1*1201, were increased among intolerant patients (11.1% vs 0%, p = 0.03, OR = 13.97). In total, DR1/DRw53 heterozygotes, DRB1*1102 and DRB1*1201 represented 61.1% of intolerant patients. Therefore, a detailed HLA class II typing might be useful before RA treatment by Tiopronin to predict and avoid toxic side effects in the patients with increased risk. Further investigation is currently underway.
9010084 Microfocal techniques in quantitative radiography: measurement of cancellous bone organiza 1996 Dec Microfocal radiography records, with unusually good resolution, the detailed structural organization of cancellous bone. A textural imaging method, fractal signature analysis (FSA), was used to quantify the horizontal and vertical trabecular organization recorded within macroradiographic images of the spine of post-menopausal women and the tibia in osteoarthritic knees, and the analysis of variance method was applied to the wrist and hand of rheumatoid patients. Changes in trabecular structure were found to correlate with (i) body weight, age and bone mineral density in the lumbar spine of post-menopausal women; (ii) the degree of cartilage loss and age in the tibia of patients with knee OA; and (iii) analysis of variance quantified the extent of 'normal', osteopaenic and eroded bone in rheumatoid joints. Quantitation of cancellous bone organization can add significantly to our understanding of disease processes and effect of therapy in diseased joints.
8099860 Soluble intercellular adhesion molecule-1 (sICAM-1) in patients with rheumatoid arthritis 1993 Jul Serum levels of the soluble form of the intercellular adhesion molecule-1 (sICAM-1) have been advocated as a parameter of clinical relevance in determining the activation of the immune system in inflammatory disease(s). We have determined sICAM-1 levels in 46 patients with rheumatoid arthritis (RA), in 53 patients with systemic lupus erythematosus (SLE), and in 82 healthy controls using a commercially available ELISA system. When compared to the healthy controls, sICAM-1 levels of the patients did not differ statistically significantly nor was there any difference between the patient groups. However, there was a strong correlation within the patient groups between sICAM-1 levels and conventional measures of disease activity. Thus, although sICAM-1 may be of theoretical interest with regard to immune activation, our results do not support the view of sICAM-1 providing additional information to the clinical rheumatologist when it is compared to more conventional measures such as acute-phase proteins or clinical activity scores.
1402151 The transoral approach to the cervical spine. 1992 Oct The transoral surgical approach is useful for operating on structures at the base of the brain and the upper cervical spinal cord. For example, this route has been used for resecting spinal tumors and clipping vertebrobasilar aneurysms. In the past, this surgical approach was not advocated due to concerns about exposure and infection. However, the availability of the microscope, computed tomography, computed myelotomography, magnetic resonance imaging and intraoperative radiography as well as more effective techniques have improved the diagnosis of pathology of the craniovertebral junction and surgical performance. An understanding of the operative procedures involved with this approach assists the neuro-science nurse in preoperative teaching and anticipating potential postoperative complications.