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41.
Kreins Alexandra Y. Velasco Helena F. Cheong Kai-Ning Rao Kanchan Veys Paul Worth Austen Gaspar H. Bobby Booth Claire 《Journal of clinical immunology》2022,42(1):94-107
Journal of Clinical Immunology - Unconditioned hematopoietic stem cell transplantation (HSCT) is the recommended treatment for patients with adenosine deaminase (ADA)-deficient severe combined... 相似文献
42.
Comparison of Bilateral vs. Staged Unilateral Deep Brain Stimulation (DBS) in Parkinson's Disease in Patients Under 70 Years of Age
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43.
Durez P Van den Bosch F Corluy L Veys EM De Clerck L Peretz A Malaise M Devogelaer JP Vastesaeger N Geldhof A Westhovens R 《Rheumatology (Oxford, England)》2005,44(4):465-468
OBJECTIVES: To analyse the effect of a dose increase in patients with severe rheumatoid arthritis (RA) with insufficient clinical response to 3 mg/kg infliximab every 8 weeks. METHODS: Patients suffering from active refractory RA despite methotrexate, were treated with i.v. infusions of infliximab (3 mg/kg) on week 0, 2, 6 and every 8 weeks thereafter. Based on the clinical judgement at week 22, patients received a dose increase of 100 mg from week 30 on. The American College of Rheumatology (ACR) core set for disease activity measures was regularly assessed. RESULTS: Five hundred and eleven RA patients were included. At week 22, 61.4, 34 and 14.1% of all patients met ACR 20, ACR 50 and ACR 70 criteria, respectively, and 6.1% of patients were in remission. A low swollen joint count at baseline was correlated with improvement at week 22 for ACR 20 (P < 0.06), ACR 50 (P < 0.06) and ACR 70 (P < 0.005). The change in HAQ score between weeks 0 and 22 was predictive for response at week 54 (P < 0.01). The dose of infliximab was increased by 100 mg in 22% of the patients. Most baseline values of patients requiring dose increase were higher (P < or = 0.001) than the baseline values of the remaining patients. Increasing the dose of infliximab by one vial from week 30 on could circumvent the partial loss of response in these patients. CONCLUSION: Infliximab use in this large out-patient cohort resulted in a significant clinical improvement. A subgroup that partially lost response during the first 22 weeks could regain response by adding 100 mg of infliximab to the subsequent doses. Due to the current study design, however, a regression to the mean like effect could not be ruled out. 相似文献
44.
Expression of fibrinogen receptors during activation and subsequent desensitization of human platelets by epinephrine 总被引:2,自引:0,他引:2
Epinephrine causes platelet aggregation and secretion by interacting with alpha 2-adrenergic receptors on the platelet surface. Platelet aggregation requires the binding of fibrinogen to a specific receptor on the membrane glycoprotein IIb-IIIa complex. Although the IIb-IIIa complex is identifiable on the surface of resting platelets, the fibrinogen receptor is expressed only after platelet activation. The current studies were designed to examine the effect of occupancy of platelet alpha 2-adrenergic receptors by epinephrine on the expression of fibrinogen receptors and on the aggregation of platelets. The ability of epinephrine to induce the expression of fibrinogen receptors was studied under two different conditions: acute stimulation (less than 1 min) and prolonged stimulation (50 to 90 min), the latter of which is associated with a reduction or "desensitization" of the platelet aggregation response. Expression of the fibrinogen receptor was monitored with 125I-fibrinogen as well as with 125I-PAC-1 (PAC-1), a monoclonal antibody that binds to the glycoprotein IIb-IIIa complex only after platelets are activated. Epinephrine caused an immediate increase in PAC-1 and fibrinogen binding that was dependent on occupancy of the alpha 2-receptor by epinephrine and on the presence of extracellular free Ca (KCa = 30 mumol/L). By itself, 1 mmol/L Mg was unable to support induction of the fibrinogen receptor by epinephrine. However, it did decrease the Ca requirement by about two orders of magnitude. Prolonged stimulation of unstirred platelets by epinephrine led to a 70% decrease in the aggregation response when the platelets were subsequently stirred. Despite their decreased aggregation response, desensitized platelets bound PAC-1 and fibrinogen normally, indicating that the loss of aggregation was not due simply to a decrease in fibrinogen receptor expression. Although desensitization was not affected by pretreatment of the platelets with aspirin, it was partially prevented when extracellular Ca was chelated by EDTA during the long incubation with epinephrine. These studies demonstrate that once platelet alpha 2-adrenergic receptors are occupied by epinephrine, extracellular Ca is involved in initiating the aggregation response by supporting the induction of the fibrinogen receptor and the binding of fibrinogen. Furthermore. Ca-dependent reactions subsequent to fibrinogen binding may be necessary for maximal platelet aggregation and are impaired when platelets become desensitized to epinephrine. 相似文献
45.
Specific antinuclear antibodies are associated with clinical features in systemic lupus erythematosus 总被引:5,自引:0,他引:5
Hoffman IE Peene I Meheus L Huizinga TW Cebecauer L Isenberg D De Bosschere K Hulstaert F Veys EM De Keyser F 《Annals of the rheumatic diseases》2004,63(9):1155-1158
OBJECTIVES: To study associations between antinuclear antibodies (ANA) and signs/symptoms in patients with systemic lupus erythematosus (SLE). METHODS: A consecutive cohort of 289 patients with SLE was included; 235 fulfilled ACR criteria for SLE and were further analysed. ANA profiles were determined by line immunoassay and by indirect immunofluorescence on Crithidia luciliae. An extensive list of signs/symptoms was evaluated. RESULTS: Five clusters of antibodies were defined by cluster analysis: 1-antibodies to SmB, SmD, RNP-A, RNP-C, and RNP-70k; 2-antibodies to Ro52, Ro60, and SSB; 3, 4, and 5-antibodies to ribosomal P, histones and dsDNA, respectively. Significant associations (p< or =0.01) were found between anti-RNP-70k, anti-RNP-A, anti-RNP-C and Raynaud's phenomenon, between anti-RNP-A, anti-RNP-70k and leucopenia, and between anti-RNP-A, anti-RNP-C and a lower prevalence of urine cellular casts. Anti-SSA, anti-SSB were associated with xerostomia, and anti-SSB with pericarditis. Antibodies to ribosomal P were associated with haemolytic anaemia, leucopenia, and alopecia. Patients with anti-dsDNA antibodies had a higher risk for cellular casts and a lower risk for photosensitivity. Antihistone antibodies were associated with arthritis. CONCLUSIONS: In a large and consecutive cohort of patients with SLE, clusters of antibodies were identified. Previously reported associations of antibodies with symptoms were confirmed and new associations found. 相似文献
46.
Glycoprotein Ib and glycoprotein IX are fully complexed in the intact platelet membrane 总被引:3,自引:6,他引:3
Two new murine monoclonal antibodies, AK 1 and SZ 1, reactive with the human platelet glycoprotein (GP) Ib-IX complex have been produced by the hybridoma technique. Both AK 1 and SZ 1 immunoprecipitated the GP Ib-IX complex from Triton X-100-solubilized, periodate-labeled platelets. With trypsinized, labeled platelets, AK 1, SZ 1, and FMC 25 (epitope on GP IX) immunoprecipitated a membrane-bound proteolytic fragment of the GP Ib-IX complex consisting of GP IX and an congruent to 25,000 mol wt remnant of the alpha-chain of GP lb disulfide-linked to the beta-subunit. Unexpectedly, although AK 1 and SZ 1 immunoprecipitated purified GP Ib-IX complex, neither antibody immunoprecipitated the individual components of this complex, GP Ib or GP IX. When GP Ib and GP IX were recombined, however, AK 1 and SZ 1 again immunoprecipitated the reformed complex, strongly suggesting that both antibodies were recognizing an epitope present only on the intact complex. Cross-blocking studies indicated that AK 1 and SZ 1 recognized a very similar or identical epitope that was proximal to the epitope for FMC 25. Both AK 1 and SZ 1 bound to a similar number of binding sites (congruent to 25,000) on intact platelets as monoclonal antibodies directed against either GP lb or GP IX. The combined data suggests that GP lb and GP IX are fully complexed in the intact platelet membrane. 相似文献
47.
48.
AF Jorm H Christensen AS Henderson PA Jacomb AE Korten A Mackinnon 《Age and ageing》1996,25(2):126-129
Formal assessment of cognitive decline with cognitive tests can be difficult, requiring either two measurement points or a comparison of 'hold' with 'don't hold' tests. Informant-based assessment provides an alternative approach because informants can adopt a longitudinal perspective and directly rate cognitive change. A study was carried out to assess the validity of informant ratings collected by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A community sample of 500 subjects aged 74 or over underwent four cognitive tests on two occasions 3½ years apart. On the second occasion, informants filled out the IQCODE. Subjects rated as having moderate or severe decline were found to have greater change on the cognitive tests. These findings support the validity of informant ratings of cognitive decline. 相似文献
49.
Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis 总被引:5,自引:0,他引:5
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Calin A Dijkmans BA Emery P Hakala M Kalden J Leirisalo-Repo M Mola EM Salvarani C Sanmartí R Sany J Sibilia J Sieper J van der Linden S Veys E Appel AM Fatenejad S 《Annals of the rheumatic diseases》2004,63(12):1594-1600
OBJECTIVE: A double blind, randomised, placebo controlled study to evaluate the safety and efficacy of etanercept to treat adult patients with ankylosing spondylitis (AS). METHODS: Adult patients with AS at 14 European sites were randomly assigned to 25 mg injections of etanercept or placebo twice weekly for 12 weeks. The primary efficacy end point was an improvement of at least 20% in patient reported symptoms, based on the multicomponent Assessments in Ankylosing Spondylitis (ASAS) response criteria (ASAS 20). Secondary end points included ASAS 50 and ASAS 70 responses and improved scores on individual components of ASAS, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), acute phase reactants, and spinal mobility tests. Safety was evaluated during scheduled visits. RESULTS: Of 84 patients enrolled, 45 received etanercept and 39 received placebo. Significantly more etanercept patients than placebo patients responded at the ASAS 20 level as early as week 2, and sustained differences were evident up to week 12. Significantly more etanercept patients reported ASAS 50 responses at all times and ASAS 70 responses at weeks 2, 4, and 8; reported lower composite and fatigue BASDAI scores; had lower acute phase reactant levels; and had improved spinal flexion. Etanercept was well tolerated. Most adverse events were mild to moderate; the only between-group difference was injection site reactions, which occurred significantly more often in etanercept patients. CONCLUSIONS: Etanercept is a well tolerated and effective treatment for reducing clinical symptoms and signs of AS. 相似文献
50.
De Rycke L Baeten D Kruithof E Van den Bosch F Veys EM De Keyser F 《Arthritis and rheumatism》2005,52(7):2192-2201
OBJECTIVE: To analyze the clinical and biologic correlates of autoantibody induction during longer-term tumor necrosis factor alpha (TNFalpha) blockade with either the monoclonal antibody infliximab or the soluble receptor etanercept. METHODS: Thirty-four patients with spondylarthropathy (SpA) and 59 patients with rheumatoid arthritis (RA) were treated with infliximab for 2 years. Additionally, 20 patients with SpA were treated with etanercept for 1 year. Sera were blindly analyzed for antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen (anti-ENA) antibodies, and antihistone, anti-nucleosome, and anticardiolipin antibodies (aCL). The anti-dsDNA antibodies were isotyped. RESULTS: High numbers of infliximab-treated patients with SpA or RA had newly induced ANAs (61.8% and 40.7%, respectively) and anti-dsDNA antibodies (70.6% and 49.2%, respectively) after 1 year, but no further increase between year 1 and year 2 was observed. In contrast, induction of ANAs and anti-dsDNA antibodies was observed only occasionally in the etanercept-treated patients with SpA (10% of patients each). Isotyping revealed almost exclusively IgM or IgM/IgA anti-dsDNA antibodies, which disappeared upon interruption of treatment. Neither infliximab nor etanercept induced other lupus-related reactivities such as anti-ENA antibodies, antihistone antibodies, or anti-nucleosome antibodies, and no clinically relevant lupus-like symptoms were observed. Similarly, infliximab but not etanercept selectively increased IgM but not IgG aCL titers. CONCLUSION: The prominent ANA and anti-dsDNA autoantibody response is not a pure class effect of TNFalpha blockers, is largely restricted to short-term IgM responses, and is not associated with other serologic or clinical signs of lupus. Similar findings with aCL suggest that modulation of humoral immunity may be a more general feature of infliximab treatment. 相似文献