PubMed Health⌕ Search

Biomedical subjects

S B Abramson

Publications and source records attributed to S B Abramson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Nitric oxide stimulates ADP ribosylation of actin in association with the inhibition of actin polymerization in human neutrophils.

In these studies we provide conclusive evidence that (beta/gamma) actin present in human neutrophils is a substrate for nitric oxide (NO)-dependent ADP ribosylation and that this modification is associated with the inhibition of actin polymerization. A 43-kDa substrate for NO-dependent ADP ribosylation was identified as actin by four methods: (1) comigration with the botulinum C2 toxin substrate by two-dimensional gel electrophoresis (pI 5.2), (2) identity between the peptide map generated by V8 protease digestion of the NO and botulinum C2 substrates, (3) immunoprecipitation with antiactin antibodies, and (4) the ability of NO to ADP ribosylate purified neutrophil G-actin in the presence of plasma membrane cofactors. Because the ADP ribosylation of actin by the botulinum C2 toxin is known to inhibit F-actin polymerization, we examined the effect of NO on actin assembly. Flow cytometry revealed that NO inhibited formyl-methionine-leucine-phenylalanine (fMLP)-dependent (30 s at 37 degrees C) F-actin formation (108 +/- 8 vs. 89 +/- 6 relative fluorescence units, P < .02). These results were confirmed by quantification of F-actin formation by gel scanning (10% sodium dodecyl sulfate gel, Coomassie, and densitometry): pretreatment of polymorphonuclear leukocytes with NO resulted in a reduction of fMLP-induced, cytoskeletal-associated F-actin, which was accompanied by an increase of Triton-soluble G-actin. NO also inhibited F-actin formation, as observed by means of rhodamine phalloidin staining of neutrophils adherent to a fibronectin-coated surface. This effect was accompanied by a dose-dependent inhibition of neutrophil adherence in NO-treated cells. The data indicate that NO inhibits cytoskeletal assembly and adherence in human neutrophils in association with the ADP ribosylation of actin.

Actins↗
PubMed1995

False positive seroreactivity to Borrelia burgdorferi in systemic lupus erythematosus: the value of immunoblot analysis.

UNLABELLED: The object of this study was to determine the incidence of seropositivity to B. burgdorferi by the commonly available enzyme-linked immunosorbent assay (ELISA) in patients with SLE and other rheumatic diseases and to evaluate immunoblot analysis as a tool to differentiate true from false positive ELISA. Sera were obtained from patients with SLE (n = 35), rheumatoid arthritis (n = 26), seronegative arthritis (n = 28) and Lyme disease (n = 18). Reactivity to B. burgdorferi antigens was analysed by two available diagnostic techniques: ELISA and immunoblot. Correlations were made between seroreactivity to B. burgdorferi and standard serological tests of autoimmunity: antibodies to nuclear antigens, dsDNA, cardiolipin, SSA and SSB. Seroreactivity to B. burgdorferi antigens by the ELISA system was detected in 40% of patients with SLE, 8% of patients with rheumatoid arthritis and 4% with seronegative arthritis. Among patients seropositive by ELISA, immunoblots were negative in all cases. However, eight of 14 patients with rheumatoid arthritis (57%) showed cross-reactivity to multiple borreli antigens. No significant correlations were found between Lyme seropositivity by ELISA and other autoantibodies except IgM rheumatoid factor (r = 0.61, P < 0.01) in patients with rheumatoid arthritis. IN CONCLUSION: a positive ELISA for Lyme disease was found in up to 40% of patients with established SLE and also in other rheumatic diseases. However, specific serum antibodies to Borrelia were not confirmed by the more specific immunoblot technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗
PubMed1995

The neutrophil in rheumatoid arthritis.

The destructive capacity of the neutrophil has long been appreciated, and the presence of extraordinary numbers of neutrophils in the synovial fluid of patients with RA supports a role for these cells in the pathogenesis of joint destruction. In this article, we reviewed the current state of knowledge of neutrophil function in the inflammatory response, and emphasized the subjects of neutrophil/endothelial adhesion and the role of chemoattractants and cytokines in neutrophil mobilization. We also discussed the mechanisms of action of neutrophil destruction of cartilage and the interplay of signals between the neutrophil and the chondrocyte. The capacity of many of the drugs used to treat RA to interfere with one or several of these processes underscores the importance of the neutrophil in RA and suggests that future therapeutic strategies could target neutrophil activation within the synovial space.

Antirheumatic Agents↗
PubMed1994

Nitric oxide reacts with intracellular glutathione and activates the hexose monophosphate shunt in human neutrophils: evidence for S-nitrosoglutathione as a bioactive intermediary.

We performed experiments to determine whether nitric oxide promoted the formation of intracellular S-nitrosothiol adducts in human neutrophils. At concentrations sufficient to inhibit chemoattractant-induced superoxide anion production, nitric oxide caused a depletion of measurable intracellular glutathione as determined by both the monobromobimane HPLC method and the glutathione reductase recycling assay. The depletion of glutathione could be shown to be due to the formation of intracellular S-nitrosoglutathione as indicated by the ability of sodium borohydride treatment of cytosol to result in the complete recovery of measurable glutathione. The formation of intracellular S-nitrosylated compounds was confirmed by the capacity of cytosol derived from nitric oxide-treated cells to ADP-ribosylate glyceraldehyde-3-phosphate dehydrogenase. Depletion of intracellular glutathione was accompanied by a rapid and concomitant activation of the hexose monophosphate shunt (HMPS) following exposure to nitric oxide. Kinetic studies demonstrated that nitric oxide-dependent activation of the HMPS was reversible and paralleled nitric oxide-induced glutathione depletion. Synthetic preparations of S-nitrosoglutathione shared with nitric oxide the capacity to inhibit superoxide anion production and activate the HMPS. These data suggest that nitric oxide may regulate cellular functions via the formation of intracellular S-nitrosothiol adducts and the activation of the HMPS.

Adenosine Diphosphate Ribose↗
PubMed1994

Inhibition of neutrophil function by aspirin-like drugs (NSAIDS): requirement for assembly of heterotrimeric G proteins in bilayer phospholipid.

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit neutrophil functions via mechanisms that are independent of their effects on prostaglandin biosynthesis. We examined the effects of sodium salicylate and piroxicam on GTP/GDP exchange by a regulatory G protein (G alpha i). Plasma membrane and cytosol of human neutrophils were prepared by nitrogen cavitation and discontinuous sucrose density centrifugation. Salicylate (3 mM) and piroxicam (50 microM) reduced [35S]GTP gamma S binding to purified plasma membranes [65 +/- 3.7 and 75 +/- 5.3% (P < 0.003) of control, respectively]. Membrane-associated G alpha/beta gamma was solubilized by treatment of plasma membranes with sodium cholate. NSAIDs did not inhibit binding of GTP to solubilized G alpha/beta gamma derived from detergent-treated plasma membranes. Lipid reconstitution was achieved by detergent dialysis followed by the addition of bilayer liposomes (phosphatidylcholine). Salicylate and piroxicam inhibited GTP gamma S binding to G alpha/beta gamma derived from solubilized plasma membranes reconstituted in phosphatidylcholine vesicles (bilayer structures) but had no effect when phosphatidylethanolamine (hexagonal phase II structure) was used for reconstitution. Salicylate and piroxicam had no effect on GTP binding to cytosolic fractions in which soluble G alpha i exists as a free subunit, suggesting that the effect required either assembly of G alpha i/beta gamma heterotrimer or the presence of a lipid bilayer. Although the addition of purified bovine beta gamma subunits to dialyzed cytosol increased both the total GIP binding capacity and the pertussis toxin-dependent ADP-ribosylation of G alpha i, consistent with assembly of a G protein heterotrimer, NSAIDs had no effect on GTP binding. In contrast, NSAIDs inhibited GTP binding to heterotrimeric G alpha cytosol/beta gamma bovine when the complex was inserted into bilayer liposomes. The data indicate that salicylate and piroxicam disrupt neutrophil function via their capacity to interfere with GTP/GDP exchange at an alpha subunit of a regulatory G protein, an effect which requires assembly of the active heterotrimer G alpha i/beta gamma in a phospholipid bilayer.

Animals↗
PubMed1994

Intravascular neutrophil activation in systemic lupus erythematosus (SLE): dissociation between increased expression of CD11b/CD18 and diminished expression of L-selectin on neutrophils from patients with active SLE.

Previous studies have shown that neutrophils in the circulation of patients with active systemic lupus erythematosus (SLE) are activated as judged by their increased surface expression of the beta 2-integrin CD11b/CD18. Since activation of neutrophils leads to altered expression of another adhesion molecule, L-selectin (LS), we examined neutrophils from patients with SLE for changes in the expression of CD11b/CD18 and LS by cytofluorographic analysis of immunofluorescent-labeled cells. Overall there was no difference between surface expression of CD11b/CD18 on neutrophils from SLE patients or controls [mean fluorescence 225 +/- 26 vs 225 +/- 13 relative fluorescence units (RFU), respectively]. However, as previously reported, neutrophils from patients with more active disease (activity score > or = 3, UCH Middlesex activity score) expressed greater CD11b/CD18 than neutrophils from controls (319 +/- 40 RFU, P < 0.03, n = 9) or from patients with less active disease (193 +/- 10 RFU, P < 0.006). Indeed, CD11b/CD18 expression correlated directly with disease activity (r = 0.54, P < 0.02). Stimulation of neutrophils ex vivo with the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (100 nM) induced up-regulation of CD11b/CD18 in cells from both SLE patients and controls (205 +/- 12% vs 239 +/- 15% of basal, respectively), but neutrophils from the most active patients (score > or = 3) increased CD11b/CD18 expression less than controls (175 +/- 12% of basal, P < 0.003, n = 9). The magnitude of the stimulated increment in expression of CD11b/CD18 on neutrophils correlated inversely with SLE activity (r = -0.64, P < 0.003, n = 20). Surprisingly, we observed no change in LS expression on neutrophils from SLE patients compared to controls (143 +/- 14 vs 141 +/- 16 RFU, respectively) even in patients with the highest activity indices (154 +/- 21 RFU). In contrast to CD11b/CD18, there was no correlation between LS expression and disease activity (r = 0.12, P = NS). Stimulation of neutrophils reduced the expression of LS similarly in both controls and SLE patients (67 +/- 3% vs 58 +/- 4% reduction, respectively) and did not correlate with disease activity (r = 0.07, P = NS, n = 20). These results show, for the first time, that changes in CD11b/CD18 expression do not correlate with LS expression on neutrophils from patients with active SLE.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, CD↗
PubMed1994

The role of nitric oxide in the pathogenesis of preeclampsia.

OBJECTIVE: Nitric oxide, a potent vasodilator released by endothelial cells, inhibits platelet aggregation and adhesion to vascular endothelial surfaces. Because endothelial cell damage is considered pivotal in the pathogenesis of preeclampsia, this study was initiated to determine whether nitric oxide production is decreased in patients with preeclampsia. STUDY DESIGN: Twenty-six patients with preeclampsia (as defined by a blood pressure > or = 140 mm Hg systolic or 90 mm Hg diastolic plus proteinuria, > or = 300 mg per 24 hours or > or = 2+ by dipstick, both occurring on two occasions > or = 4 hours apart) and 26 normotensive women with singleton gestations in the third trimester were studied. Because nitric oxide is spontaneously oxidized to both nitrite and nitrate, two analytic assays were used serially. Serum nitrite levels were initially determined with the Greiss reagent and subsequently analyzed with Escherichia coli nitrate reductase. RESULTS: With the Greiss reagent alone the mean +/- SEM of serum nitrite level in 26 patients with preeclampsia was significantly decreased compared with 26 normotensive patients (3.46 +/- 1.43 mumol/L vs 4.65 +/- 0.85 mumol/L, p = 0.02). With the addition of the nitrate reductase enzyme of Escherichia coli the mean +/- SEM of serum nitrite level in 26 preeclamptic patients was again significantly decreased compared with 26 normotensive patients (20.04 +/- 1.25 mumol/L vs 27.38 +/- 2.23 mumol/L, p = 0.02). One patient with the syndrome of hemolysis, elevated liver enzymes, and low platelets demonstrated a concurrent decrease in serum nitrite over a 2-week period, emphasizing the relationship of nitric oxide to the pathophysiologic features of the syndrome. CONCLUSIONS: Circulating levels of nitrite are decreased in patients with preeclampsia. These data support the concept that diminished nitric oxide synthesis contributes to the pathophysiologic changes seen in preeclampsia.

Adult↗
PubMed1993

Nitric oxide stimulates the ADP-ribosylation of actin in human neutrophils.

ADP-ribosylation is an important post-translational protein modification; however, endogenous substrates are poorly characterized. In these studies we examined the effects of nitric oxide on the ADP-ribosylation of neutrophil proteins. Purified cytosol and plasma membrane were incubated with 32P-NAD (5 microM, 1 microCi, 30 min) in the presence or absence of nitric oxide. Nitric oxide induced the ADP-ribosylation of the 37 kD substrate present only in cytosol. Nitric oxide treatment of plasma membrane plus cytosol revealed the ADP-ribosylation of an additional 43 kD protein. This 43 kD substrate was identified as actin by both phalloidin precipitation and immunoblot (2-D) gel using specific anti-actin antibodies. The data indicate that nitric oxide stimulates the ADP-ribosylation of two discrete substrates in fractionated PMN, one of which can be identified as actin. NO-induced ADP-ribosylation may contribute to the modulatory effect of nitric oxide on neutrophil functions, including F-actin assembly.

Actins↗
PubMed1993

Modulation of human T cell responses by nitric oxide and its derivative, S-nitrosoglutathione.

OBJECTIVE: To examine the effects of nitric oxide (NO) and its more stable derivative, S-nitrosoglutathione (SNO-GSH), on the response of activated T lymphocytes. METHODS: The effects of NO and SNO-GSH on DNA synthesis, interleukin-2 (IL-2) production, IL-2 receptor expression, and cGMP accumulation were determined in phytohemagglutinin-activated peripheral blood mononuclear cells (PBMC) and spleen T cells. RESULTS: Nitric oxide (half-life [T1/2] < 15 seconds) did not inhibit T cell proliferation. However, the derivative SNO-GSH (25 microM) (T1/2 > 2 hours) inhibited DNA synthesis by a mean +/- SD of 65 +/- 19.6% (P < 0.001) in PBMC and 75 +/- 15% (P < 0.001) in spleen cells. Macrophage depletion of PBMC did not abrogate the inhibition. SNO-GSH had no effect on IL-2 production or IL-2 receptor expression. NO (25 microM) increased the cGMP content of PBMC (0.65 +/- 0.15 pmoles/10(6) cells; P < 0.04), as did SNO-GSH (25 microM) in both PBMC (3.8 +/- 1; P < 0.001) and spleen T cells (5.2 +/- 1.2; P < 0.001). Methylene blue and hemoglobin, which are NO inhibitors, inhibited SNO-GSH-induced cGMP accumulation (P < 0.001). CONCLUSION: SNO-GSH inhibits T cell DNA synthesis independently of IL-2 production and in association with cGMP accumulation via a NO-dependent mechanism. We suggest that NO and its S-nitrosothiol derivatives may act as endogenous inhibitors of T cell-mediated inflammation.

Cyclic GMP↗
PubMed1992

Novel synthesis of S-nitrosoglutathione and degradation by human neutrophils.

S-nitrosoglutathione (SNO-GSH), a stable derivative of nitric oxide, is an endothelium-derived relaxation factor, which provokes vasodilation, inhibits platelet aggregation, and inhibits neutrophil (PMN) superoxide anion (O2+) generation. We have established a novel method for synthesis of S-nitrosoglutathione using a column containing S-nitrosothiol covalently attached to agarose. S-nitrosoglutathione was a product as assessed after separation using C-18 reverse-phase HPLC and absorption spectroscopy. We examined the stability of SNO-GSH in the presence or absence of PMN. The half-life (mercuric acid diazotization) of SNO-GSH in Hepes was greater than 60 min. The addition of resting PMN did not affect the T1/2 of SNO-GSH. PMN exposed to N-fMet-Leu-Phe (FMLP, 10(-7) M) reduced measurable SNO-GSH (15 microM) at 5 min (48 +/- 5.0% control, P less than 0.05). Incubation (5 min, 37 degrees C) of PMN with 10 microM tenidap (an anti-inflammatory drug which inhibits PMN activation) before addition of FMLP blocked the PMN-dependent degradation of SNO-GSH (42 +/- 3 vs 78 +/- 1.3% control, P = 0.01). We confirmed the recovery of SNO-GSH through measurements by bioassay (platelet aggregation) and HPLC analysis. The degradation of S-nitrosothiols by activated neutrophils may reverse the inhibitory effect of S-nitrosothiols on PMN functions and contribute to tissue injury at sites of inflammation.

Cysteine↗
PubMed1992

Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors.

We have recently demonstrated that human neutrophils (PMN) possess two different classes of adenosine receptors (A1 and A2) that, when occupied, promote chemotaxis and inhibit the generation of reactive oxygen species (e.g., O2- and H2O2), respectively. We have previously demonstrated that adenosine protects endothelial cells (EC) from injury by stimulated neutrophils (PMN) both by diminishing generation of H2O2 and inhibiting adherence of PMN to EC. We therefore determined whether occupancy of A1 or A2 adenosine receptors regulated adherence of PMN to EC. At concentrations similar to those required to inhibit release of O2- by ligation of A2 receptors, both adenosine (IC50 = 56 nM) and 5'N-ethylcarboxamidoadenosine (NECA, IC50 = 8 nM), the most potent A2 agonist, inhibited adherence to EC by stimulated PMN (FMLP, 0.1 microM). In direct contrast, the specific A1 agonists N6-phenylisopropyladenosine and N6-cyclopentyladenosine (CPA) promoted PMN adherence to EC at concentrations of 1-100 nM. To further investigate the mechanisms by which adenosine receptor agonists affected the adherence of stimulated PMN we examined the effect of NECA (A2) and CPA (A1) on the adherence of PMN to fibrinogen (a ligand for the beta 2 integrin CD11b/CD18) and to gelatin. In a dose-dependent manner (IC50 = 2 nM), NECA inhibited the adherence of FMLP-treated PMN to fibrinogen- but not gelatin-coated plates. In contrast, CPA (A1) promoted adherence of stimulated PMN to gelatin-(EC50 = 13 pM) but not fibrinogen-coated plates. Theophylline (10 microM), an adenosine receptor antagonist, reversed the inhibition by NECA (0.3 microM) of stimulated neutrophil adherence to fibrinogen. These observations not only confirm the presence of A1 and A2 receptors on PMN but also suggest two opposing roles for adenosine in inflammation. Occupancy of A1 receptors promotes neutrophil adherence to endothelium and chemotaxis (a proinflammatory role) whereas occupancy of A2 receptors inhibits adherence and generation of toxic oxygen metabolites (an antiinflammatory role).

Adenosine↗
PubMed1992

Activation of the alternative complement pathway accompanies disease flares in systemic lupus erythematosus during pregnancy.

OBJECTIVE: To assess the activity of systemic lupus erythematosus (SLE) during pregnancy and to distinguish it from preeclampsia. METHODS: We prospectively measured the complement activation products Ba, Bb, SC5b-9, and C4d, as well as the conventional complement determinants C3, C4, and CH50, during pregnancy in 14 patients with SLE and 10 women with preeclampsia. RESULTS: Four of the 14 SLE patients were considered to have disease flares, 3 occurring in the second trimester and 1 postpartum. In these patients, significant abnormalities of Ba, Bb, SC5b-9, and CH50 were noted. In contrast, measures of C4d did not distinguish between pregnant patients who had flares and those whose SLE remained stable. Although decreased values of C3 were rarely seen in the patients with stable disease, normal values of C3 during lupus pregnancy were not reliably associated with stable disease. Three of 10 non-SLE patients with preeclampsia had elevated levels of Ba; however, in each case, the CH50 level was close to or within the normal range. This was in sharp contrast to the findings observed in the 4 patients with active SLE, in whom high levels of plasma Ba were always associated with low CH50 values. Moreover, the ratio of CH50 to Ba was significantly lower in the patients with lupus flares than in the non-SLE patients with preeclampsia. CONCLUSION: While a decline in the CH50 level alone could otherwise be attributed to decreased synthesis of complement components, these data demonstrate that ongoing activation of the alternative complement pathway can accompany disease flares in pregnant women with SLE.

Complement Activation↗
PubMed1992

Neuropeptides and inflammation. A somatostatin analog as a selective antagonist of neutrophil activation by substance P.

OBJECTIVE: Substance P and somatostatin are neuropeptides found in peripheral sensory nerves. In vitro, these have opposing effects on inflammatory cells. We compared the effects of these peptides on the activation of neutrophils. METHODS: Neutrophils were isolated from healthy volunteers, and chemotaxis, superoxide anion generation, aggregation, and changes in cytosolic calcium and GTPase activity were measured in the presence of substance P, somatostatin, and the chemoattractant FMLP. RESULTS: Substance P was an effective chemoattractant, 20% as potent as FMLP at equimolar concentrations. Substance P also stimulated GTPase activity in neutrophil plasma membranes. Somatostatin did not activate neutrophils; however, it effectively inhibited neutrophil chemotaxis and GTPase activity provoked by substance P, but not by FMLP. CONCLUSIONS: These studies demonstrate that substance P can effectively stimulate chemotaxis, possibly via effects on a GTP-binding protein distinct from that triggered by FMLP, and that somatostatin is a selective antagonist of substance P. The biochemical specificities of these peptides on cells may modulate neurogenic inflammation at the local level.

Anions↗
PubMed1992

Assessment of disease activity and impending flare in patients with systemic lupus erythematosus. Comparison of the use of complement split products and conventional measurements of complement.

OBJECTIVE: To determine whether increased levels of the complement split products generated in the activation of the alternative or classical pathway accompany more severe disease activity in patients with systemic lupus erythematosus (SLE) and whether these measurements are useful in predicting flares of disease. METHODS: Levels of Ba, Bb, SC5b-9, and C4d were measured in 380 plasma samples obtained from 86 SLE patients who were prospectively followed up for 15 months. RESULTS: In the 20 patients who had inactive disease at the initiation of the study, the mean values of all of the complement split products at entry were within the normal range. In the 47 patients with stable or moderate disease activity, levels of Ba were significantly increased, while the mean values for Bb, SC5b-9, and C4d did not differ significantly from those in patients with inactive disease. The mean entry value of each analyte was highest in the group of 19 patients who had the most severe disease activity at initial evaluation. Traditional measurements of complement, i.e., C3, C4, and CH50, followed similar trends, but did not discriminate between the 3 groups of patients as well as did measurements of the split products. Analysis of the disease course in the patients with inactive or stable/moderate disease revealed that an elevated level of C4d had the most sensitivity with regard to subsequent flare, while an elevated Bb level had the highest specificity and the greatest predictive value. CONCLUSION: These data suggest that elevated levels of complement split products, particularly products of alternative and terminal pathway activation, more accurately reflect disease activity than do conventional measurements of complement in SLE and may be useful in the prediction of impending disease flares.

Complement C3 Convertase, Alternative Pathway↗
PubMed1992

Quantitative electroencephalography. A new approach to the diagnosis of cerebral dysfunction in systemic lupus erythematosus.

OBJECTIVE: Neuropsychiatric manifestations are common in patients with systemic lupus erythematosus (SLE), but accurate diagnosis is often difficult. We conducted a prospective study to determine the utility of neurometric quantitative electroencephalography (QEEG) as an indicator of cerebral dysfunction in SLE patients. METHODS: Fifty-two SLE patients were divided into 4 groups based on the results of neuropsychiatric evaluations. These included patients with objective evidence of neuropsychiatric SLE (NPSLE), patients with neuropsychiatric symptoms, patients with no evidence of NPSLE, and patients with a prior history of NPSLE: All QEEG findings were compared with data in an age-regressed normative database and with findings in an independent sample of normal subjects. RESULTS: QEEG sensitivity was 87%, and specificity was 75%. QEEG results were abnormal in 74% of the SLE patients with neuropsychiatric symptoms and in 28% of the patients with no evidence of active NPSLE: QEEG profiles varied as a function of the severity and type of neuropsychiatric manifestation present. Within this patient population, QEEG was more sensitive than magnetic resonance imaging, computed tomography scanning, or conventional EEG. CONCLUSION: Neurometric QEEG may be a sensitive indicator of cerebral dysfunction in patients with NPSLE and can differentiate patients with diverse neuropsychiatric manifestations. When combined with a careful clinical history and evaluation, QEEG provides information that may be useful for the early detection of NPSLE and for serial evaluation of disease activity and treatment efficacy.

Adult↗
PubMed1992

Treatment of gout and crystal arthropathies and uses and mechanisms of action of nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory agents have anti-inflammatory, analgesic, and antipyretic actions. Nonsteroidal anti-inflammatory drugs are the preferred class of agents for the treatment of gout and other crystal-induced arthropathies. The use of colchicine for other than the prophylaxis of acute attacks is discouraged owing to side effects, which include death. The inhibition of the enzyme prostaglandin H synthase by most nonsteroidal anti-inflammatory drugs explains many of their effects and toxicities. However, it is likely that additional biologic actions are important. These include the inhibition of the transcription of the gene for prostaglandin H synthase, a direct central effect on peripheral inflammation, and the modulation of the functions of a variety of cells (eg, neutrophils, lymphocytes, and chondrocytes). This review focuses on the current controversy in the treatment of gout and discusses the recent literature on the actions of nonsteroidal anti-inflammatory drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

The effect of macrophage colony-stimulating factor on haemopoietic recovery after autologous bone marrow transplantation.

Macrophage colony-stimulating factor (M-CSF) is active in the late stages of monocyte maturation, activates mature monocyte-macrophages and enhances their production of various other cytokines. We have examined the effects of a 21 d course of escalating doses of M-CSF purified from human urine (hM-CSF) on recovery following autologous bone marrow transplantation (ABMT) in 20 patients with malignant lymphomas. Four patients were treated at each dose level of 4, 8, 16, 32 and 64 x 10(6) U/m2/d and results compared to 46 concurrent controls. There was no significant difference in recovery to an absolute neutrophil count (ANC) of 0.5 x 10(9)/l (median 20 d in hM-CSF group versus 22 in controls) or in recovery of platelets to 50 x 10(9)/l (32 d versus 39 d, 0.05 less than P less than 0.1); hM-CSF patients received a median of 81 platelet units following ABMT (controls 112 units, P = NS). hM-CSF patients had a median of 5.5 d with fever greater than 37.5 degrees C (control 8, P = NS), received parenteral antibiotics for 14.5 d (control 17, P = NS) and had a 50% incidence of bacteraemia (control 48%). hM-CSF treated patients were discharged by a median of day 29 following transplantation (control 33, P less than 0.05). Platelet and neutrophil recovery correlated significantly with the number of marrow mononuclear cells (MNC) reinfused in the hM-CSF group (P = 0.05 and P = 0.014 respectively) but not in controls. Subgroup analysis showed that hM-CSF patients receiving greater than 2 x 10(8) MNC/kg body weight reached an ANC of 0.5 x 10(9)/l by a median of day 16.5 (control 18.5, NS), became platelet transfusion independent by day 17 (control 29, P less than 0.05) and reached a platelet count of 50 x 10(9)/l by day 21 (control 40, P less than 0.05). No significant toxicity attributable to hM-CSF treatment was seen. These results suggest that hM-CSF accelerates platelet recovery following ABMT and that relatively large marrow innocula are required to see this effect.

Adult↗