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Biomedical subjects

T Vischer

Publications and source records attributed to T Vischer.

At least 19 recordsLinked to original sources
PubMed2004

Three month treatment of reactive arthritis with azithromycin: a EULAR double blind, placebo controlled study.

OBJECTIVE: To determine the efficacy of weekly treatment with oral azithromycin for 13 weeks on the severity and resolution of reactive arthritis (ReA). METHODS: 186 patients from 12 countries were enrolled in a randomised, double blind, placebo controlled trial. Inclusion criteria were inflammatory arthritis of < or =6 swollen joints, and disease duration of < or =2 months. All patients received a single azithromycin dose (1 g) as conventional treatment for possible Chlamydia infection, and were then randomly allocated to receive weekly azithromycin or placebo. Clinical assessments were made at 4 week intervals for 24 weeks. RESULTS: 152 patients were analysable (34 failed entry criteria), with a mean (SD) age of 33.8 (9.4) and duration of symptoms 30.7 (17.5) days. Mean C reactive protein (CRP) was 48 mg/l, and approximately 50% of those typed were HLA-B27+, suggesting that the inclusion criteria successfully recruited patients with acute ReA. Treatment and placebo groups were well matched for baseline characteristics. There were no statistical differences for changes in any end point (swollen and tender joint count, joint pain, back pain, heel pain, physician and patient global assessments, and CRP) between the active treatment and placebo groups, analysed on an intention to treat basis or according to protocol completion. The time to resolution of arthritis and other symptoms or signs by life table analyses was also not significantly different. Adverse events were generally mild, but were more commonly reported in the azithromycin group. CONCLUSIONS: This large trial has demonstrated that prolonged treatment with azithromycin is ineffective in ReA.

Adolescent↗
PubMed2002

Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology.

In rheumatology and other medical specialties there is a discrepancy between the widespread use and the imprecise designation of glucocorticoid treatment regimens. Verbal descriptions of glucocorticoid treatment regimens used in various phases of diseases vary between countries and institutions. Given this background, a workshop under the auspices of the EULAR Standing Committee on International Clinical Studies including Therapeutic Trials was held to discuss this issue and to seek a consensus on nomenclature for glucocorticoid treatment. This report summarises the panel's discussion and recognises that answers derived from consensus conferences are not definitive. Nevertheless, recommendations on glucocorticoid treatment are presented that (1) reflect current and best knowledge available and (2) take into account current clinical practice. A question-answer rationale presentation style has been chosen to convey the messages, to summarise the meeting in a readable format, and to avoid dogmatism.

Drug Administration Schedule↗
PubMed1998

Validation of questionnaire-based response criteria of treatment efficacy in the fibromyalgia syndrome.

OBJECTIVE: To compare the validity of self-reported questionnaires as response criteria of treatment efficacy in patients with fibromyalgia syndrome. METHOD: At the beginning of the treatment period, 70 fibromyalgia patients, randomly allocated to electro-acupuncture or placebo, underwent a clinical evaluation by rheumatologists and answered 1) a generic quality of life questionnaire--the Psychological General Well-Being Index (PGWB), 2) a specific function and symptom questionnaire, and 3) a pain questionnaire--the Regional Pain Score (RPS). The same evaluation was repeated at the end of the treatment period. Severity of the condition was assessed by a composite outcome score, a combination of different clinical outcome measures forming a clinical severity index. The variations between these questionnaire scores before and after treatment and the variations between the clinical severity indices estimated by clinicians were used as measures of the treatment impact. The first rationale for the validation was a positive correlation between clinical and questionnaire score changes. Another rationale for validation of the new instruments was the ability to identify the different treatment interventions. RESULTS: The correlation between the clinical severity index and the RPS was good (r = 0.62). Moreover, the RPS demonstrated a good discriminant power in detecting patients with effective treatment: it showed a specificity of 74% and a sensitivity of 75%. The PGWB correlated less well with the clinical score and was less discriminant. The specific function and symptom questionnaire showed little additional validity. CONCLUSIONS: Outcomes of syndrome severity such as pain and subjective well-being, as measured by self-reported questionnaires, can be valid instruments to evaluate treatment efficacy in short-term clinical trials. In the current study, the RPS proved to be particularly useful to assess the widespread tenderness of fibromyalgia and demonstrated high discriminative power.

Activities of Daily Living↗
PubMed1998

Relation between the heavy chain complementarity region 3 characteristics and rheumatoid factor binding properties.

Among the rheumatoid factors (RFs), monospecific and polyspecific types can be distinguished. However the molecular basis responsible for their different specificity is not well understood. In a previous report, we have shown that the binding of the majority of the polyspecific antibodies is salt-sensitive. No binding to IgG was observed under high ionic strength (0.3-0.5 M NaCl). This salt-sensitivity was only observed for 18% of the monospecific RFs. Here, we have analyzed 14 RFs representing the 3 different groups (6 salt-insensitive monospecific, 4 salt-sensitive monospecific and 4 salt-sensitive polyspecific RFs). By analysis of the amino acid composition and the distribution of polar and non-polar residues of their heavy chain complementarity-determining region 3 (H-CDR3) in relation to mono/polyspecificity, salt-sensitivity and reactivity against human IgG subclasses, we have identified common structural features responsible for their different binding properties. Salt-sensitive RFs (mono as well as polyspecific antibodies) were characterized by long H-CDR3's (15.3+/-2.7) that contained large numbers of hydrophilic residues such as arginine and serine, while salt-insensitive RFs had more hydrophobic H-CDR3's of smaller length (11.3+/-2.4). In addition, for the monospecific RFs, remarkably similar hydrophilicity H-CDR3 profiles were found that were correlated with their specificity for IgG subclasses. These observations confirm the importance of the H-CDR3 for the binding of RFs to IgG. Furthermore, on the basis of their shorter H-CDR3's and their rather unique H-CDR3 hydrophilicity profiles, it is likely that the majority of the monospecific RFs should be considered as a group of RFs that is independent of the polyspecific RF repertoire.

Amino Acid Sequence↗
PubMed1997

Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythematosus are significantly higher than in other rheumatic diseases and correlate with disease activity.

OBJECTIVE: To investigate the difference in acute phase protein responses between patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and spondyloarthropathies (SpA). METHODS: Circulating levels of cytokines inducing the production of acute phase proteins such as interleukin (IL)-6, IL-1 beta, and tumor necrosis factor (TNF)-alpha, and of cytokine inhibitors such as TNF soluble receptors (TNF-sR55 and TNF-sR75) and IL-1 receptor antagonist (IL-1ra), were measured in 2 cohorts of patients. The first cohort included 52 patients with SLE and 22 with RA, and the second included 21 with SLE, 20 with RA, and 18 with SpA. An examination at the time of blood collection and the Systemic Lupus Activity Measure (SLAM) index were used to assess disease activity in patients with SLE. Serum levels of IL-6 were measured using a biological assay, and concentrations of IL-1 beta, TNF-alpha, TNF-sR55, TNF-sR75, and IL-1ra were assessed by immunoassays. RESULTS: Although C-reactive protein (CRP) levels were significantly lower in SLE than in RA or SpA, the concentrations of circulating IL-6 or TNF-alpha were higher in SLE. The most striking observation was that TNF-sR levels were significantly higher in SLE than in RA or SpA. The TNF-alpha: TNF-sR ratio was also significantly lower in SLE than in RA. TNF-sR55 and TNF-sR75 levels correlated with disease activity in SLE. CONCLUSION: The weak acute phase protein response in SLE may be explained by a decreased ratio between inducing cytokines and their inhibitors. In addition, TNF-sR may prove a useful biological marker for the followup of SLE, where acute phase protein response is generally low during disease exacerbations.

Acute-Phase Proteins↗
PubMed1997

Concentrations and origins of soluble interleukin 6 receptor-alpha in serum and synovial fluid.

OBJECTIVE: To determine levels of soluble interleukin 6 receptor-alpha (sIL-6R alpha) in synovial fluid (SF) and serum from patients with different rheumatic diseases, and to analyze its cellular origin compared to IL-6. METHODS: IL-6 and sIL-6R alpha concentrations were measured in sera, SF, and culture supernatants of different cells types using specific sandwich ELISA. RESULTS: IL-6 levels were significantly higher (30 to 1000-fold) in SF than in sera, and higher in inflammatory arthropathies such as rheumatoid arthritis (RA), chondrocalcinosis, and gout than in osteoarthritis (OA). sIL-6R alpha levels in SF from patients with RA, gout, and chondrocalcinosis were also higher (24.7 +/- 7.5, 23.2 +/- 9.1, and 19.5 +/- 7.4 ng/ml, respectively) than in patients with OA (10.1 +/- 5 ng/ml), although the difference was distinctly smaller. In contrast, sIL-6R alpha concentrations did not differ significantly between the sera of healthy donors and patients. sIL-6R alpha levels were similar in SF and sera from inflammatory arthropathies, but lower in all osteoarthritic SF, compared to their corresponding serum. In contrast to IL-6, sIL-6R alpha was produced in high amounts by hepatocytes but not by structural cells of the joint (chondrocytes, synoviocytes, fibroblasts, and endothelial cells). Polymorphonuclear cells and mononuclear cells released intermediate levels. A significant correlation between sIL-6R alpha concentration and total number of leukocytes was observed in SF. CONCLUSION: Elevated levels of sIL-6R alpha were found in serum, likely to result from a marked release by hepatocytes in vitro. That levels are higher in inflammatory SF may be due in part to release by inflammatory cells in situ.

Antigens, CD↗
PubMed1996

[Current didactic concepts--243 participants evaluate Rheuma 2000].

The Swiss League against Rheumatic diseases in collaboration with rheumatologists organized a special educational program for general practitioners. An evaluation questionnaire was filled in by 238 of the 243 participants. With an average value of 4.57 points out of possible 5.0 the new educational concept was very successful. The interactive learning process in small groups seems to be a good alternative to formal lectures.

Education, Medical, Continuing↗
PubMed1996

Comparison of rheumatoid factors of rheumatoid arthritis patients, of individuals with mycobacterial infections and of normal controls: evidence for maturation in the absence of an autoimmune response.

We analyzed the rheumatoid factors (RF) produced by Epstein-Barr virus-transformed monoclonal B cells established from four patients with rheumatoid arthritis (RA), three individuals with a history of Mycobacterium tuberculosis (TB) and four normal controls (NI). Fifty-eight RF were analyzed for specific activity (international units-RF/microgram) for the Fc part of IgG and their interaction with tetanus toxoid (TT) and DNA (polyspecificity). Furthermore, we sequenced the V-D-J heavy chain region of 16 (9TB-/7RA-) RF. Significant differences were observed between the NI-RF and the TB- and RA-RF. While the RF repertoire of normal individuals comprised of low-avidity RF of which the majority (15/17) were polyspecific, more than half of the TB- and RA-RF were monoreactive. Furthermore, the monospecific TB- and RA-RF were of significantly higher avidity than the NI-RF (RA > TB > > NI). With respect to polyspecificity specificity, the RF in the three groups were comparable: the interaction with DNA, TT as well as with Fc was inhibited either by an increase of the ionic strength to 0.3-0.5 M NaCl or by addition of the polyanion dextran sulfate, indicating that the antibodies interacted with similar anionic epitopes shared by the three antigens. Analysis of the V-D-J heavy chain regions showed significant differences between the respective RF. The salt-sensitive binding was highly correlated with the presence of arginine in the complementarity-determining region 3 (CDR3). Furthermore, whereas the polyspecific RF consisted predominantly of germ-line encoded antibodies, the genes of the monospecific RA/TB-RF were somatically mutated (RA > TB). It is therefore likely that maturation of RF can be initiated by chronic infections and that monospecific, somatically mutated RF are not a unique characteristic of autoimmune diseases.

Adolescent↗
PubMed1996

Circulating levels of IL-11 and leukaemia inhibitory factor (LIF) do not significantly participate in the production of acute-phase proteins by the liver.

To investigate the contribution of IL-11 and LIF to acute-phase protein (APP) production, we first analysed the effects of IL-11 and LIF on production of C-reactive protein (CRP), fibrinogen, and haptoglobin by human primary hepatocytes. We also measured the serum levels of IL-11, LIF, and CRP in serum from patients with inflammatory rheumatic diseases to assess the role of these cytokines in the APP response in vivo. We included patients with conditions associated with a high APP response such as rheumatoid arthritis (RA) or spondylarthropathy (SpA), and others usually associated with a weak APP response such as systemic lupus erythematosus (SLE), in order to investigate whether these cytokines could account for the differences in APP responses. Our results showed that IL-11 and LIF induced only minimal stimulation on production of APP by human primary hepatocytes compared with IL-6, known as the major inducer. Serum levels of CRP were elevated in RA and SpA, and significantly higher than in SLE patients. Despite the presence of a high APP response in some of our patients and despite the fact that we used sensitive assays to measure IL-11 and LIF, serum levels of both cytokines were not detected in any of the tested sera. In conclusion, our results show that circulating levels of IL-11 or LIF do not contribute significantly to the production of APP in vivo, and that they do not account for the difference in APP response between SLE and other inflammatory rheumatic diseases.

Acute-Phase Proteins↗
PubMed1995

Lipopolysaccharide binding protein as a marker of inflammation in synovial fluid of patients with arthritis: correlation with interleukin 6 and C-reactive protein.

OBJECTIVE: To determine levels of lipopolysaccharide binding protein (LBP) in serum and in synovial fluid (SF) of patients presenting with various articular disorders [degenerative arthritis, rheumatoid arthritis (RA), reactive arthritis (ReA)] and to correlate these levels with C-reactive protein (CRP) and interleukin 6 (IL-6), 2 markers of the acute phase response. METHODS: LBP was measured by a radioimmunoassay made up of lipopolysaccharide (LPS) to capture LBP and radiolabelled anti-LBP antibodies to detect LBP. LBP was also measured for its ability to present fluorescein isothiocyanate LPS (FITC-LPS) to human monocytes. CRP was measured by nephelometry and IL-6 bioassay. RESULTS: Levels of LBP in serum and in SF were significantly higher in patients with RA and ReA than in the control group of degenerative arthropathies. In the latter group, LBP values were similar to those found in controls. Serum LBP values correlated positively with SF LBP values. LBP values also correlated with CRP and IL-6 levels measured in SF. Functionally, LBP was found to be active and able to present LPS to monocytes, resulting in tumor necrosis factor-alpha (TNF-alpha) release upon LPS challenge. CONCLUSION: These in vitro data support the observation that LBP could play a major role in local joint disorders. Our results also strengthen the view that LBP may be a new marker of synovial inflammation.

Acute-Phase Proteins↗
PubMed1994

Elevated serum levels of interleukin-1 receptor antagonist in polymyositis/dermatomyositis. A biologic marker of disease activity with a possible role in the lack of acute-phase protein response.

OBJECTIVE: To determine whether the lack of acute-phase protein (APP) response in numerous patients with polymyositis/dermatomyositis (PM/DM) is related to an imbalance between cytokines and cytokine inhibitors. METHODS: Levels of C-reactive protein (CRP), interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), IL-6, IL-1 receptor antagonist (IL-1ra), TNF soluble receptor 55 kd (sTNFR 55 kd), and sTNFR 75 kd were tested in the serum of 15 patients with PM/DM, 14 patients with spondylarthropathies (SPA), and 12 healthy blood donors. Serum IL-1 beta, TNF alpha, IL-6, IL-1ra, sTNFR were measured by specific immunoassays. RESULTS: Serum levels of CRP were lower in PM/DM patients than in SPA patients. Normal or slightly elevated CRP values were found in 10 of the 15 PM/DM patients, 7 of whom had active myositis. Serum IL-6 levels were significantly higher in SPA patients than in PM/DM patients, whereas serum IL-1ra and sTNFR levels were significantly higher in PM/DM than in SPA patients. IL-1ra levels were particularly elevated in patients with active myositis and decreased in response to treatment. CONCLUSION: These differences in cytokine levels, particularly IL-1ra, between PM/DM and SPA patients are indicative of distinct pathogenic mechanisms. High levels of IL-1ra may account for the weak APP response in some PM/DM patients. Our results suggest that measurement of IL-1ra, together with clinical examination, may provide useful information for the followup of PM/DM patients.

Adult↗
PubMed1993

Absence of correlation between interleukin 6 and C-reactive protein blood levels in systemic lupus erythematosus compared with rheumatoid arthritis.

To investigate if the low C-reactive protein (CRP) response frequently observed in systemic lupus erythematosus (SLE) is related to an impaired expression of interleukin 6 (IL-6), considered its main inducer, we studied serum IL-6 and CRP levels in 37 patients with SLE and 22 with rheumatoid arthritis (RA). Results show that in contrast to CRP, IL-6 levels are significantly higher in SLE than in RA. A linear regression analysis shows a positive correlation between levels of these 2 molecules in RA but not in SLE. Similarly, levels of fibrinogen, another acute phase protein mainly induced by IL-6, did not correlate with IL-6 in SLE. Our results suggest an impairment of part of the acute phase response to IL-6 that might play a role in the pathogenesis of SLE.

Antibodies↗
PubMed1992

Inhibitors of interleukin 1 activity in synovial fluids and in cultured synovial fluid mononuclear cells.

Measurement of interleukin 1 (IL-1) in synovial fluids (SF) yielded variable results and implied the presence of an inhibitory activity. As peripheral blood monocytes produce an IL-1 receptor antagonist (IL-1ra), we investigated whether SF mononuclear cells (SFMC) also secreted such inhibitory activity. MC isolated from inflammatory SF produced, in addition to variable levels of IL-1, a specific IL-1 inhibitor of approximately 23 kDa which blocked both IL-1 biological activity and binding to its receptor. Western blot, using a polyclonal antibody to rhIL-1ra, indicated that SFMC secreted material that shared immunological crossreactivity with the cloned IL-1ra. IL-1 inhibitory activity was also detected in SF but not formally demonstrated to be related to IL-1ra. In conclusion, SFMC could produce IL-1ra and an imbalance between IL-1 and its specific antagonist may be relevant to the severity of joint destruction.

Blotting, Western↗
PubMed1989

Molecular interactions of Leishmania promastigote surface protease with human alpha 2-macroglobulin.

The interaction of Leishmania promastigote surface protease (PSP) with the plasmatic protease inhibitor alpha 2-macroglobulin (alpha 2M) was investigated. In plasma, solubilized PSP forms covalent complexes only with alpha 2M, at the exclusion of other protease inhibitors. The formation of complexes is accompanied by the proteolytic cleavage of the alpha 2M subunit and by the transition from the 'slow' to the 'fast' form of alpha 2M. The proteolytic activity of solubilized PSP on azocasein is inhibited by alpha 2M. In contrast, we found no evidence for a specific interaction of alpha 2M with the surface of promastigotes and PSP proteolytic activity on intact cells was not inhibited by alpha 2M.

Animals↗