Biomedical subjects

R A Turner

Publications and source records attributed to R A Turner.

At least 37 records · Page 2Linked to original sources

PubMed1990

An unusual manifestation of Paget's disease of bone: spinal epidural hematoma presenting as acute cauda equina syndrome.

Neurologic sequelae of Paget's disease of bone include involvement of the spinal cord or cauda equina due to mechanical compression by enlarged vertebrae, ischemia caused by a spinal artery, steal syndrome or neoplasm. We describe a patient with Paget's disease of bone who presented with acute cauda equina syndrome due to a spinal epidural hematoma. Clinicians need to recognize this entity since surgical intervention may result in a favorable outcome.

Aged↗

PubMed1990

A double blind placebo controlled trial of low dose clotrimazole in rheumatoid arthritis.

Seventy-three patients with rheumatoid arthritis were randomized in a double blind study to receive either clotrimazole (20 mg/kg/day) 2 days a week for 12 weeks or matching placebo. Patients receiving clotrimazole had significant improvements (p less than 0.05) from baseline in measurements of grip strength, joint count, and patient assessment of pain, but did not show significant improvement over patients treated with placebo. More adverse experiences, predominantly gastrointestinal complaints, occurred in patients taking clotrimazole resulting in 9 patients discontinuing therapy.

Adult↗

PubMed1990

Identification and isolation of a phospholipase A2 activating protein in human rheumatoid arthritis synovial fluid: induction of eicosanoid synthesis and an inflammatory response in joints injected in vivo.

Eicosanoids are important mediators of the destructive arthropathy observed in rheumatoid arthritis. The rate-limiting step in the eicosanoid synthesis pathway is the availability of free arachidonic acid. The phospholipase enzymes release arachidonic acid from membrane phospholipids and thus play an important role in the regulation of eicosanoid production. We have previously demonstrated enhanced phospholipase A2 and C enzyme activities in cells from patients with rheumatoid arthritis and have also described a phospholipase A2 activating protein (PLAP) in mammalian cell lines. In an attempt to determine the biochemical basis of enhanced phospholipase A2 activity found in patients with inflammatory joint disease, we examined synovial fluid from patients with rheumatoid arthritis for PLAP. To determine whether PLAP was specific for rheumatoid disease, we assayed specimens from patients with other arthropathies. Histologic examination of rheumatoid joint tissue, with the use of immunohistochemical techniques, demonstrated high concentration of PLAP in monocytes, macrophages, chondrocytes, vascular smooth muscle, and endothelial cells. Human PLAP could be biochemically isolated from synovial fluid from patients with rheumatoid arthritis and was found to be similar to PLAP previously isolated from murine and bovine sources. To determine whether PLAP could directly mediate any aspect of inflammatory disease, purified PLAP was injected into rabbit knee joints. This resulted in an acute inflammatory arthritis with synovial cell proliferation and synovial fluid leukocytosis. Purified PLAP also induced eicosanoid formation both in vivo and in vitro. With enzyme-linked immunosorbent assays, we found more PLAP in synovial fluid specimens from patients with rheumatoid arthritis compared with samples from patients with other inflammatory arthropathies as well as osteoarthritis, a noninflammatory arthropathy. These data suggest that PLAP may be responsible, at least in part, for some aspects of the destructive inflammatory arthropathy that is observed in patients with rheumatoid arthritis.

Adult↗

PubMed1989

Functional and metabolic heterogeneity among normal neutrophil subpopulations.

In this study, normal human peripheral blood neutrophils were separated into subpopulations by centrifugation on discontinuous Percoll density gradients and further characterized according to various functional and metabolic capabilities. Chemotaxis was measured in response to optimal concentrations (20 nM) of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). According to a population ratio analysis, the majority of cells that contain the highest proportion of fast migrating cells are isolated between the densities of 1.093 and 1.096 gm/ml. Arachidonic acid (AA) metabolism was also determined in neutrophil subpopulations. On initial density gradients, cells isolated from 1.084-1.087 gm/ml and incubated in the presence of exogenous [3H]AA produce 50% of the total [3H]LTB4 produced in response to ionophore A23187 stimulation; whereas after prelabeling with [3H]AA for 2 hr at 37 degrees C, the cells between 1.087 and 1.093 gm/ml are the most active at both releasing [3H]AA from the cellular phospholipids and synthesizing [3H]LTB4 (dpm/cell). These studies demonstrate the significant functional and metabolic heterogeneity that exists among normal neutrophil subpopulations.

Arachidonic Acid↗

PubMed1989

Biochemical characterization of soluble phospholipase A2 from rheumatoid synovial fluid.

Radiolabeled E. coli, Phosphatidylethanolamine (PE) and Phosphatidylcholine (PC), were used to characterize the phospholipase A2 (PLA2) activity in synovial fluid (SF) from rheumatoid arthritis (RA) patients. Cell-free fractions of SF contain a PLA2 enzyme that preferentially releases [14C]oleic acid from E. coli, requires calcium and is optimally active at neutral pH. Purified PE, but not PC is also readily degraded by the soluble enzyme. A cell-associated PLA2 present in sonicates of SF mononuclear cells and neutrophils preferentially releases [3H]AA from E. coli. These studies suggest the presence of at least two different enzymes with activity of PLA2 in rheumatoid SF.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1989

Phospholipid metabolism in polymorphonuclear leukocytes from rheumatoid arthritis patients: effects of non-steroidal anti-inflammatory agents and clotrimazole.

Arachidonic acid (AA) metabolism and phospholipase A2 (PLA2) activity were measured in the peripheral blood polymorphonuclear leukocytes (PMNL) from ten patients with rheumatoid arthritis (RA) on treatment with various non-steroidal anti-inflammatory agents (NSAIA). AA metabolism and PLA2 activity were measured both initially and after treatment with either placebo or Clotrimazole, a broad spectrum anti-mycotic agent, as a possible anti-rheumatic drug. AA metabolism was also measured in PMNL from ten patients with active RA untreated with any NSAIA and ten normal volunteers. Using 3H-AA prelabeled cells, we show that there was a significantly higher (P less than 0.025) production of 3H-LTB4 in response to stimulation with the calcium ionophore A23187 in untreated RA patients than in normal volunteers (mean +/- S.D.:4.8 +/- 1.6% and 3.1 +/- 1.0%, respectively). The production of 3H-LTB4 by PMNL from patients on NSAIAs was less elevated (mean +/- S.D.:4.1 +/- 1.5%) and was not significantly different from normal controls. Concurrently we examined PLA2 activity in PMNL-sonicates from ten of our study patients using autoclaved [14C]oleate-labeled E. coli biomembranes as an exogenous substrate. Using linear regression analysis, we demonstrate a significant correlation between in vitro PLA2 activity and the release of 3H-AA from the cellular phospholipids (deacylation) in response to A23187 stimulation (r = -0.526, P less than 0.025). We also demonstrate significant correlations between the overall clinical state of the RA patient, as evaluated by a modified rheumatoid activity index (MRAI), and both the release of 3H-AA from the cellular phospholipids and its production of total [3H]eicosanoids (r = -0.557, P less than 0.025 and r = 0.644, P less than 0.005, respectively). This data suggests that: PLA2 activity may, in part, account for the higher generation of LTB4 by RA PMNL; NSAIAs may be capable of modulating this abnormality; and Clotrimazole may affect the clinical or laboratory data of RA patients already on treatment with NSAIA.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1989

Characterisation of soluble and cell associated phospholipase A2 from rheumatoid synovial fluid.

The hydrolysis of radiolabelled Escherichia coli phospholipids, and micellar dispersions of phosphatidylethanolamine and phosphatidylcholine, were used to characterise the phospholipase A2 activity in synovial fluid from patients with rheumatoid arthritis. Cell free fractions of synovial fluid contain a phospholipase A2 enzyme that preferentially releases [14C]oleic acid from E coli biomembranes (specific activity 291.3 (SEM 27.6) pmol/min/mg). This enzyme requires calcium and is optimally active at neutral pH. Purified dispersions of phosphatidylethanolamine are also readily degraded by the soluble enzyme, but it is not active against phosphatidylcholine. The substitution of [14C]oleic acid by [3H]arachidonic acid for the labelling of E coli allowed differentiation between the soluble phospholipase A2 and the cell associated phospholipase A2 present in sonicates of mononuclear cells and neutrophils from peripheral blood and synovial fluid. The cell associated phospholipase A2 preferentially releases [3H]arachidonic acid from E coli cardiolipin. In this paper the phospholipid substrate specificity of phospholipase A2 from rheumatoid synovial fluid, the optimal assay conditions for its detection, and a standardised expression of activity in terms of pmol per minute per mg of protein are established.

Arthritis, Rheumatoid↗

PubMed1987

Nabumetone: a single-center three-week comparison with placebo in the treatment of rheumatoid arthritis.

Forty-six patients with definite or classical rheumatoid arthritis were entered into a three-week, double-blind, randomized, parallel study of nabumetone, 1,000 mg at bedtime, compared with placebo. Fifteen nabumetone-treated and 12 placebo-treated patients were evaluated for efficacy variables including physician's opinion of rheumatoid arthritis activity, patient's opinion of rheumatoid arthritis activity, articular index, morning stiffness, 50-foot walking time, grip strength, and acetaminophen consumption. Between-group analysis of improvement over baseline was significantly (p less than 0.05) greater for nabumetone-treated patients for six of the seven variables. Nabumetone was significantly favored over placebo in three global evaluations and significantly more placebo-treated (75 percent) than nabumetone-treated (20 percent) patients withdrew from the study due to an unsatisfactory therapeutic response. Of the 38 patients receiving the study medication, 22 percent of nabumetone-treated and 5 percent of placebo-treated patients reported adverse experiences either related to treatment or for which the relationship to treatment was unknown. No patients were withdrawn from the study as a result of these experiences and no long-term sequelae or clinically significant laboratory abnormalities were reported.

Adult↗

PubMed1987

Evaluation of nabumetone in the treatment of active adult rheumatoid arthritis.

The safety and efficacy of nabumetone and placebo were compared in a three-week, multicenter, double-blind, randomized, parallel evaluation involving patients with class II or III definite or classical rheumatoid arthritis. No patient received concomitant treatment with other nonsteroidal anti-inflammatory agents; however, disease-modifying agents (gold, steroids) were permitted. Of the 139 patients who entered the double-blind phase of the study, all were evaluable for safety, and 113 were evaluable for efficacy. Sixty-one patients received 1,000 mg of nabumetone per day at bedtime, and 50 were given placebo tablets; patients in both groups were permitted up to 3,250 mg of acetaminophen per day as needed for pain. After three weeks, nabumetone-treated patients exhibited a greater degree of improvement from baseline than did the placebo-treated patients, and the degree of improvement was statistically significant for four of seven variables.

Adolescent↗

PubMed1987

The assessment of pain in rheumatoid arthritis. Validity of a behavioral observation method.

It is difficult to objectively measure pain in rheumatoid arthritis (RA). A behavioral observation method for the assessment of RA pain has been developed. In this study, videotapes were made of 53 RA patients while they performed standardized maneuvers. Trained raters viewed the videotapes and recorded the frequencies of 7 pain behaviors. Clinical and laboratory measures of rheumatoid disease activity also were recorded for each patient. Rheumatology fellows viewed 20 randomly chosen video recordings of the patients and made global estimates of the intensity and unpleasantness of pain. Significant positive correlations were found between total pain behavior scores and measures of disease activity. The fellows' estimates of the intensity and unpleasantness of the patients' pain also were significantly and positively correlated with the total pain behavior scores. The behavioral observation method may be useful in the assessment of RA pain and may be included as an objective outcome measure in clinical trials with RA patients.

Adult↗

PubMed1987

Effects of psychological therapy on pain behavior of rheumatoid arthritis patients. Treatment outcome and six-month followup.

A randomized clinical trial was performed to evaluate a psychological treatment intervention and a social support program, compared with a control program in which no adjunct treatment was rendered, and their effects upon pain behavior, affect, and disease activity of 53 patients with rheumatoid arthritis. The psychological intervention produced significant reductions in patients' pain behavior and disease activity at posttreatment. Significant reductions were also observed in trait anxiety at posttreatment and 6-month followup. Relaxation training may have been the most important component of the psychological intervention. The social support program produced a significant reduction in trait anxiety only at posttreatment. This is the first well-controlled study to demonstrate reduced pain behavior, disease activity, and trait anxiety following psychological treatment.

Adult↗

PubMed1987

Neutrophil responsiveness to chemoattractant tripeptide in rheumatoid arthritis.

Neutrophils isolated from medication-free rheumatoid arthritis (RA) patients were assayed for responsiveness to the bacterial chemoattractant tripeptide formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe). Rheumatoid arthritis neutrophil preparations contained significantly lower percentages of rapidly migrating cells. This relative hyporesponsiveness of RA neutrophils was related to impaired sensing of chemotactic gradients. Rheumatoid neutrophil abnormalities in sensing of and responding to chemotactic gradients were not associated with resting or f-Met-Leu-Phe-induced changes in arachidonic acid metabolism.

Arachidonic Acids↗

PubMed1987

The assessment of pain in rheumatoid arthritis: disease differentiation and temporal stability of a behavioral observation method.

An observation method for the assessment of pain behaviors in patients with rheumatoid arthritis (RA) has been developed. We investigated the extent to which the frequencies of pain behaviors differentiated patients with RA and patients with chronic low back pain from depressed and nondepressed, pain free, control subjects. The reliability of the pain behavior frequencies of patients with RA across 2 observation sessions also was determined. Total pain behavior scores clearly differentiated patients with RA and low back pain from depressed and nondepressed, pain free, control subjects. Pain behavior observed in patients with RA showed a high degree of stability over time. The results of our study suggest that the behavioral observation method will prove useful in the assessment of RA pain in clinical and research settings.

Adult↗

PubMed1987

Analysis of combined rheumatoid factor determinations by the rheumatoid arthritis latex and sheep cell agglutination tests and the American Rheumatism Association criteria for rheumatoid arthritis.

The clinical records of randomly selected patients receiving both the sheep cell agglutination test (SCAT) and the latex agglutination test (RA latex) for rheumatoid factor (RF) were analyzed for the presence of American Rheumatism Association (ARA) criteria for rheumatoid arthritis (RA). When both tests were positive there was a 3-fold increase compared to only one test positive in the relative risk that a patient met ARA criteria for RA, and there was a 2-fold increase in the probability that a patient with 2 positive tests had classical RA compared to only a positive RA latex. The occurrence of RF reactive with both human and rabbit IgG identifies a population of patients likely to have more ARA criteria for RA and classical disease.

Agglutination Tests↗

PubMed1987

Clinical and genetic characteristics of upper gastrointestinal disease in rheumatoid arthritis.

Clinical and genetic studies were analyzed in 47 patients with rheumatoid arthritis (RA) who had upper gastrointestinal (GI) endoscopies. Fifty-three percent of patients with RA had peptic ulcers and/or erosions. Sixty percent of patients with ulcers and/or erosions had a history of peptic ulcer disease. Although a greater number of patients with ulcers and/or erosions was taking regular aspirin or indomethacin, comparable numbers of patients with abnormal and normal endoscopies were using nonsteroidal antiinflammatory drugs. Nineteen of the 25 patients (76%) with ulcers and/or erosions had type O blood. Patients with abnormal and normal endoscopies had similar frequencies of GI complaints and fecal blood loss. GI symptoms and occult fecal blood loss, therefore, are not prominent features of upper GI disease in RA. ABO screening may be helpful in determining which patients with RA are at risk for developing peptic ulcers and/or erosions.

ABO Blood-Group System↗

PubMed1986

Suppression of a pokeweed mitogen-stimulated plaque-forming cell response by a human B lymphocyte-derived aggregated IgG-stimulated suppressor factor: suppressive B cell factor (SBF).

The mechanisms whereby formed immune complexes (IC) or immunoglobulin aggregates can suppress further antibody production were explored by culturing normal human peripheral blood mononuclear leukocytes (PBL) with heat-aggregated IgG (HAIgG) and collecting the culture supernatants at 24 hr. These supernatants were found to suppress a pokeweed mitogen (PWM)-induced rheumatoid factor plaque-forming cell (RF-PFC) response in normal individuals. PWM-induced anti-trinitrophenylated sheep red blood cell (TNP-SRBC) PFC were also inhibited by suppressor supernatants from HAIgG-stimulated PBL, suggesting that the polyclonal PFC response was inhibited by a suppressor factor. The suppressor factor inhibited PWM stimulated RF-PFC throughout the culture period, but suppression was maximal at the peak of the RF-PFC response. Suppressor factor was only effective at the initiation of cultures, suggesting that it inhibited early events in the PWM-stimulated RF-PFC response. Molecular weight determination of the suppressor factor by differential membrane fractionation suggested a m.w. range of 30,000 to 50,000, and chromatography on Sephadex G-100 showed a peak activity at an approximate m.w. of 32,000. Studies suggested the factor was not an interferon. Depletion of T lymphocytes by E rosetting and macrophages/monocytes by G-10 adherence did not affect the generation of suppressor factor. Depletion of T lymphocytes (OKT4, OKT8) and NK cells (Leu-11b) by antibody-dependent, complement-mediated cytotoxicity also did not affect the generation of suppressor factor. Depletion of B lymphocytes with OKB7 resulted in the generation of significantly less suppressor factor. Suppression produced by unstimulated purified B lymphocytes was approximately one-half that seen when B lymphocytes were stimulated with HAIgG. Differential membrane fractionation studies suggested that only HAIgG-stimulated B cell cultures contained peak activity in the 30,000 to 50,000 m.w. fraction. Supernatants from unstimulated purified T cells also generated suppression, which was approximately one-half of that seen with HAIgG-stimulated B cells, but no increase in suppressor activity was seen in T cell cultures after incubation with HAIgG. These studies demonstrate that HAIgG is capable of stimulating B lymphocytes to produce a lymphokine, suppressive B cell factor (SBF), which is capable of suppressing a polyclonal PFC response. SBF may be important in feedback control of human immunoglobulin production.

Antibody Formation↗

PubMed1986

Decreased suppressive B cell factor (SBF) in rheumatoid arthritis: evidence for a defect in B cell autoregulation.

Rheumatoid arthritis (RA) is a disorder characterized by defective immunoregulation. Hypergammaglobulinemia, circulating immune complexes (IC), and autoantibodies such as rheumatoid factor (RF) are common serum abnormalities. To assess IC-mediated feedback suppression in RA, we evaluated the ability of a suppressive B cell factor (SBF) generated by culturing heat-aggregated IgG (HAIgG) with peripheral blood mononuclear leukocytes (PBL) from patients with RA and normal controls to suppress the pokeweed mitogen (PWM)-induced RF plaque-forming cell (PFC) response of normal PBL. RA patients generated less SBF than age-matched controls. Background suppression (supernatants obtained from PBL cultured without HAIgG) was similar in the RA patients and age-matched controls. To determine the effects of nonsteroidal antiinflammatory drug (NSAID) therapy on suppression, RA patients and age-matched controls were studied before and after NSAID therapy. NSAID therapy significantly reduced background suppression in RA patients who were not on immunosuppressive drugs and in age-matched controls, but there was no effect on SBF in RA patients or controls. There was a small increase in background suppression when NSAID were administered to RA patients on immunosuppressives, suggesting an ameliorative effect of NSAID in this group of patients, which tended to increase their level of suppression when compared with RA patients only on NSAID. Spontaneous RF-PFC were measured in normal controls and RA patients and were compared with suppressor activity. There were increased numbers of spontaneous RF-PFC in RA patients. Total suppressor activity was greatest in young adult controls, who also had the least RF-PFC. The percentage of suppression correlated inversely with the number of RF-PFC in patients and controls. Additionally, disease activity in RA as measured by total joint count and erythrocyte sedimentation rate (ESR) was shown to correlate inversely with total suppressor activity. We conclude that the PBL from patients with RA produce decreased SBF after HAIgG stimulation and that loss of suppression is also associated with aging. This study suggests a defect in IC-stimulated B cell suppressor activity in RA leading to decreased ability to suppress antibody and further IC formation. The combination of increased RF-PFC and decreased SBF suggests that there is defective B cell autoregulation in RA, which may be involved in the pathogenesis and chronicity of this disease.

Anti-Inflammatory Agents↗

PubMed1986

Effects of heavy metal ions on phospholipid metabolism in human neutrophils: relationship to ionophore-mediated cytotoxicity.

This study examined the effects of 0.1mM heavy metal ions (Au3+, Zn2+, Cr3+, Mn2+, and Cu2+) on ionophore-treated human neutrophils. Treatment of human neutrophils with 5-10 microM ionophore A23187 resulted in phospholipid deacylation and eicosanoid release within 5 min. After approximately 20 min, viability decreased significantly with near total cell death by 50 min. Heavy metal ions altered phospholipid metabolism, eicosanoid synthesis, and cytotoxicity in parallel fashion. Radioimmunoassays for 5-HETE and LTB4 demonstrated that Au3+ and Zn2+ stimulated, Cr3+ had little effect on, and Mn2+ and Cu2+ inhibited eicosanoid release from ionophore-treated neutrophils. Cells prelabelled with [3H]arachidonic acid exhibited similar metal-mediated effects on lipid metabolism. Strong negative correlations between metal effects on viability and the metabolism of arachidonic acid suggest that eicosanoids participate in ionophore-induced cytotoxicity.

Arachidonic Acids↗