Using patients to teach functional assessment of patients with arthritis.
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Arthritis↗
Biomedical subjects
H B Lindsley
Publications and source records attributed to H B Lindsley.
Effects of exercise on fatigue, aerobic fitness, and disease activity measures in persons with rheumatoid arthritis.
The effects of 12 weeks of low-impact aerobic exercise on fatigue, aerobic fitness, and disease activity were examined in a quasi-experimental time series study of 25 adults with rheumatoid arthritis (RA). Measures were obtained preintervention, midtreatment (after 6 weeks of exercise), end of treatment (after 12 weeks of exercise), and at a 15-week follow-up. ANOVAS for repeated measures showed that those subjects who participated more frequently reported decreased fatigue, while those who participated less frequently reported an increase in fatigue. All subjects, on average, showed increased aerobic fitness and increased right and left hand grip strength, decreased pain, and decreased walk time. There were no significant increases in joint count or sedimentation rate. Significant improvements in measures at the 15-week follow-up also were found. Findings indicate that persons with RA who participate in appropriate exercises may lessen fatigue levels and experience other positive effects without worsening their arthritis.
Adult↗
Optimization of cellular ELISA for assay of surface antigens on human synoviocytes.
The cellular enzyme-linked immunosorbent assay (CELISA) permits assay of cell surface antigens on intact fixed cells. Using a monolayer of cells as the solid phase, the CELISA offers an inexpensive alternative to flow cytometry. In addition, this protocol has the decided advantages of miniaturization (small numbers of cells) and ease of replication (the 96-well cluster plate format). In efforts to optimize CELISA for detecting surface antigens on human fibroblastlike synoviocytes, the authors found that cell number, serum proteins, choice of culture plate, pipetting technique and fixatives may all impact the results of the CELISA.
Antigens, Surface↗
Mast cell granules potentiate endotoxin-induced interleukin-6 production by endothelial cells.
Mast cells are constituent cells of vascular tissue and their numbers are increased in atherosclerotic vessels. To gain insight into the role of mast cells in vascular inflammation, the effect of mast cell granules (MCG) on endothelial cell production of interleukin-6 (IL-6) was examined. Human umbilical vein endothelial cells (HUVEC) were cultured with lipopolysaccharide (LPS) in the presence or absence of rat peritoneal MCG and IL-6 production was assayed by enzyme-linked immunosorbent assay. The interaction of MCG with HUVEC in culture was examined by electron microscopy (EM). The EM studies revealed that MCG are internalized by HUVEC and appear intact even after 24 h in culture. Unactivated HUVEC produced little or no IL-6 either in the presence or absence of MCG. Treatment of HUVEC with LPS stimulated IL-6 production in a dose- and time-dependent fashion. Addition of MCG to LPS-activated HUVEC-resulted in the potentiation of IL-6 production at all LPS doses. MCG-induced enhancement of IL-6 production was evident even at a mast cell-to-endothelial cell ratio of 1:32. The enhancement of IL-6 production by MCG was also seen when tumor necrosis factor alpha was used as an activator. Although potentiation was evident when MCG were added 6 h before or after LPS stimulation, the maximum effect was noted when MCG and LPS were added simultaneously. MCG-mediated enhancement of IL-6 production was abrogated by pretreating MCG with protease inhibitors. Although MCG proteases potentiate IL-6 production by HUVEC, they do not degrade secreted IL-6. These results demonstrate that MCG interact with endothelial cells and modulate the production of an important inflammatory cytokine.
Animals↗
Analysis of elevated serum interleukin-6 levels in rheumatoid arthritis: correlation with erythrocyte sedimentation rate or C-reactive protein.
The purpose of this study was to determine whether selected antirheumatic drugs would suppress elevated circulating interleukin-6 (IL-6) levels in patients with rheumatoid arthritis (RA). The 267 patients who enrolled in a double-blind randomized protocol received placebo, naproxen (1500 mg/day), or prinomide (1500 mg/day) for up to 16 weeks. Serum samples from 143 of the patients completing the trial and from 135 normal donors were analyzed by quantitative sandwich enzyme-linked immunosorbent assay for IL-6 concentrations. A mean normal IL-6 value was determined to be 3 pg/ml (95th percentile value = 10 pg/ml). IL-6 levels at baseline for the patients with RA were significantly higher than those for control subjects (p < 0.0001). Elevated IL-6 levels (> 10 pg/ml) at baseline were found in 80% of subjects with RA (median = 36 pg/ml, range 12 to 403). For patients with elevated levels of either IL-6, C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR) at baseline, initial median values of IL-6, CRP, and ESR were compared with those from the final visit for each treatment group. There was no significant decrease in IL-6 levels with treatment. Median CRP levels decreased significantly, from 1.9 to 0.8 mg/dl (p = 0.002), as did median ESR (37 to 34 mm/hr, p = 0.013), only in the prinomide-treated group.
Adolescent↗
Increased levels of circulating intercellular adhesion molecule 1 in the sera of patients with rheumatoid arthritis.
OBJECTIVE: We sought to assess whether circulating levels of intercellular adhesion molecule 1 (ICAM-1) in patients with rheumatoid arthritis (RA) are elevated and correlate with clinical measures of disease activity and whether this ICAM-1 originates from the synovium. METHODS: Circulating ICAM-1 (cICAM-1) levels were determined by sandwich enzyme-linked immunosorbent assay of serum from 61 RA, 18 osteoarthritis (OA), and 11 inflammatory arthritis (IA) patients. In addition, paired serum and synovial fluid samples were collected from 17 RA, 9 OA, and 4 IA patients. The stability of cICAM-1 was assessed by overnight incubation at 37 degrees C. Finally, the potential degradative effects of synovial fluid proteases were assessed by incubation of recombinant soluble ICAM-1 with patient synovial fluid. RESULTS: RA sera contained significantly greater (P < 0.001) levels of cICAM-1 compared with RA synovial fluid and compared with sera or synovial fluid from the OA and IA patients. Circulating ICAM-1 levels were unaffected by overnight incubation at 37 degrees C and were unaffected by exposure to RA, OA, or IA synovial fluid. Serum levels of cICAM-1 demonstrated a weak, but significant (P < 0.05) correlation with the joint score and erythrocyte sedimentation rate in 25 RA patients treated with nonsteroidal antiinflammatory drugs. CONCLUSION: The greatest elevations of cICAM-1 were seen in RA patient sera. In both RA and OA, synovial fluid cICAM-1 levels were consistently lower than serum levels, suggesting that cICAM-1 did not originate in the synovium. Because the production of cICAM-1 can be increased by cytokines (e.g., interleukin-1, tumor necrosis factor alpha), elevated levels of circulating ICAM-1 in RA may be reflective of systemic exposure to elevated cytokine levels.
Aged↗
Proinflammatory cytokines enhance human synoviocyte expression of functional intercellular adhesion molecule-1 (ICAM-1).
We determined the ability of proinflammatory cytokines to enhance ICAM-1 (CD54) expression on, and PBMC adhesion to, human synoviocytes. Surface molecules were characterized by cell ELISA and by flow cytometry. Adhesion of PBMC to synoviocyte monolayers was measured by direct counting or by colorimetric staining. Most cytokines upregulated ICAM-1 expression (IL-1 beta > TNF alpha > IFN-gamma >> PDGF-bb, IL-6), but not GM-CSF or TGF beta. A similar concentration-dependent increase was observed for synoviocytes derived from patients with rheumatoid or osteoarthritis. Kinetic studies of ICAM-1 expression differed among several cytokines: an early rise with IL-1 beta or TNF alpha stimulation, a gradual increase with IFN-gamma, a transient increase with PDGF-bb, and a plateau with IL-6. Adhesion of PBMC to synoviocytes was increased by IL-1 beta or TNF alpha and reduced by MAb to CD54 or CD18. Increased synoviocyte adhesiveness may promote interactions with infiltrating inflammatory cells.
Arthritis, Rheumatoid↗
Regulation of the expression of adhesion molecules by human synoviocytes.
The capacity of synoviocytes to participate in inflammatory responses may be altered by the cytokine-enhanced expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). To examine this possibility, the ability of selected cytokines to enhance ICAM-1 expression was examined. The data indicated that each of these cytokines (interleukin-1 beta greater than tumor necrosis factor-alpha, interferon-gamma much greater than interleukin-6) can up-regulate synoviocyte ICAM-1 expression. This can potentially increase the ability of these cells to interact with infiltrating inflammatory cells, thereby propagating immunologically mediated inflammation such as occurs in rheumatoid synovitis.
Cell Adhesion Molecules↗
Low back pain evaluation and management.
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Back Pain↗
Sacroiliitis: MR imaging findings.
Magnetic resonance (MR) imaging was performed in seven asymptomatic volunteers and 17 patients with clinical and radiologic evidence of sacroiliitis. MR imaging findings were compared with those at computed tomography (CT) to determine the MR imaging appearance of the sacroiliac joint when normal and in sacroiliitis. The normal articulation was well depicted with MR imaging. Findings of sacroiliitis were identified in 20 sacroiliac joints (12 patients). MR imaging findings characteristic of sacroiliitis included abnormal cartilage signal intensity (95% of joints) and erosions (75% of joints) on T1-weighted images. Areas of increased intensity in the articulation (80% of joints) or in erosions (60% of joints) were seen on T2-weighted images. MR imaging was superior to CT for evaluation of cartilage and detection of erosions. Four sacroiliac joints (20%) and two patients (17%) with MR imaging findings of sacroiliitis were negative at CT. The authors conclude that MR imaging is a valuable method for detecting sacroiliitis, particularly when results of other imaging techniques are inconclusive.
Adolescent↗
Enhanced prostaglandin E2 secretion by cytokine-stimulated human synoviocytes in the presence of subtherapeutic concentrations of nonsteroidal antiinflammatory drugs.
Human synoviocytes were stimulated for 48 hours or 72 hours with cytokines (recombinant interleukin-1 beta and/or recombinant tumor necrosis factor alpha) in the presence or absence of selected nonsteroidal antiinflammatory drugs. The drugs were tested at subtherapeutic and clinically therapeutic levels, as follows: piroxicam 0.3 pM to 3 X 10(6) pM, sodium salicylate 30 nM to 3 X 10(6) nM, and indomethacin 3 pM to 3 X 10(6) pM. At low concentrations, all 3 drugs showed significant enhancement of prostaglandin E2 (PGE2) secretion (piroxicam, salicylate greater than indomethacin). At high, clinically therapeutic concentrations, all drugs showed suppression of PGE2 secretion (indomethacin greater than piroxicam greater than salicylate). The enhancement of PGE2 secretion may be partially responsible for the flare of arthralgia or arthritis frequently seen after termination of drug therapy.
Anti-Inflammatory Agents, Non-Steroidal↗
Takayasu arteritis presenting as retinal and vertebrobasilar ischemia.
A young woman presented with a 4-month history of retinal and vertebrobasilar ischemia. Angiography demonstrated narrowing of major branches of the aortic arch. Intractable, severe retroorbital pain of the right eye developed after a middle cerebral artery stroke. During 4 weeks of aggressive immunosuppressive therapy including IV high dose bolus corticosteroids and pulse cyclophosphamide, her neurologic deficit improved transiently, but her retroorbital pain persisted. She died of staphylococcal sepsis and pneumonia. An autopsy demonstrated thrombotic or fibrous occlusion, with minimal inflammation, of extracranial arteries.
Adult↗
Methotrexate-associated, early-onset pancytopenia in rheumatoid arthritis.
A patient with rheumatoid arthritis presented with pancytopenia 3 weeks after initiation of low-dose methotrexate administered orally. She had minimal renal insufficiency and hypoalbuminemia prior to initiation of methotrexate therapy, and had received a nonsteroidal anti-inflammatory drug concurrently. Bone marrow recovery occurred within 3 weeks. Patients receiving low-dose methotrexate therapy for rheumatoid arthritis require early monitoring for bone marrow injury, especially those who have risk factors for possible methotrexate toxicity.
Arthritis, Rheumatoid↗
Total lymphoid irradiation retards evolution of articular erosions in collagen induced arthritis.
Collagen induced arthritis was elicited in rats and monitored with serial magnification radiographs and serologic studies. Total lymphoid irradiation (TLI), 1050 rad in 3 fractions, was given at 1 of 2 days after primary immunization. Erosive arthritis and periostitis evolved more slowly in rats irradiated on Day 9 compared to nonirradiated control animals; in contrast, rats irradiated on Day 21 showed no significant differences. At Day 114 neither group receiving TLI differed from nonirradiated controls. Additional groups of rats were irradiated at varying times relative to collagen immunization. On Day 18 the mean IgM and IgG anticollagen antibody responses were transiently decreased in animals receiving TLI by Day 9, with no differences by Day 36.
Animals↗
Ankylosing spondylitis presenting as juxta-articular masses in females.
Juxta-articular inflammatory masses, sternomanubrial or sternoclavicular, were noted in two women who were subsequently found to have ankylosing spondylitis. The differential diagnosis of juxta-articular masses should include systemic rheumatic disorders as well as tumor or infection.
Adult↗
Elevated sacroiliac joint uptake ratios in systemic lupus erythematosus.
Sacroiliac joint radiographs and radionuclide sacroiliac joint uptake ratios were obtained on 14 patients with active systemic lupus erythematosus. Elevated joint ratios were found unilaterally in two patients and bilaterally in seven patients when their lupus was active. In patients whose disease became quiescent, the uptake ratios returned to normal. Two patients had persistently elevated ratios with continued clinical and laboratory evidence of active lupus. Mild sacroiliac joint sclerosis and erosions were detected on pelvic radiographs in these same two patients. There was no association between low back pain or HLA-B27 positivity and the radiographic or scintigraphic abnormalities. Elevated quantitative sacroiliac joint uptake ratios may occur as a manifestation of active systemic lupus erythematosus.
Adult↗
Ultrafiltration coefficient and glomerular capillary resistance a model of immune complex glomerulonephritis.
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Animals↗