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H Zeidler

Publications and source records attributed to H Zeidler.

At least 127 records · Page 7Linked to original sources
PubMed1997

Anti-CD2 (OX34) MoAb treatment of adjuvant arthritic rats: attenuation of established arthritis, selective depletion of CD4+ T cells, and CD2 down-modulation.

Anti-CD2 MoAbs have previously been shown to induce tolerance and to block B cell differentiation, T cell and monocyte activation. Since these immune functions are important in joint inflammation, we asked whether administration of the anti-CD2 MoAb OX34 has a beneficial effect on established rat adjuvant arthritis, a model of human rheumatoid arthritis, and how it affects CD2-bearing leucocyte subsets. Female Lewis rats with established adjuvant arthritis received a total of 5 mg OX34 or isotype-matched control MoAb starting on day 15 after adjuvant injection. Weight and arthritis score (AS) were measured in a blinded fashion. Peripheral blood cells were analysed for numbers of leucocyte subsets at various time points. Animals were killed on day 30 and lymphatic organs were processed for immunohistology. Clinically, OX34 treatment led to increased body weight and reduced AS. Although OX34 binds to CD4+ and CD8+ T cells in a comparable fashion, OX34 treatment reduced CD4+ T cells, but not CD8+ T cells. Among CD4+ T cells CD45RC+ ('naive') T cells virtually disappeared; CD45RC- ('recently activated') T cells were slightly reduced. A reduction of CD4+ T cells was also found in the lung, liver, bone marrow, spleen and lymph nodes. Down-modulation of the CD2 molecule by OX34, again, affected CD4+ T cells, suggesting a specific signal for CD4+ but not CD8+ T cells. In conclusion, the anti-CD2 MoAb OX34 attenuates established rat adjuvant arthritis. In spite of similar binding to CD4+ and CD8+ T cells, OX34 depletes only CD4+ T cells and down-modulates the CD2 molecule on these cells. These results suggest a therapeutic benefit from CD2-directed therapy for chronic types of arthritis.

Animals↗
PubMed1997

Initiation and perpetuation of rat adjuvant arthritis is inhibited by the anti-CD2 monoclonal antibody (mAb) OX34.

OBJECTIVE: The purpose of this study was to investigate the therapeutic potential of the anti-CD2 mAb OX34 first with regard to bone protection in established rat adjuvant arthritis (AA) and secondly with regard to prevention of AA induction. METHODS: Established AA was treated with dexamethasone (1 mg/kg body weight) for two days plus OX34 mAb or control mAb over three days (2 mg and then 1 mg) starting at different time points of the disease. For prevention studies animals were injected as above with mAb before induction of AA. Arthritis score (AS), hindpaw thickness, and body weight were blindly measured three times per week. Flow cytometry and hindpaw radiography were performed at the end of the study (day 29). RESULTS: Treatment of early AA with OX34 mAb combined with dexamethasone but not dexamethasone plus control mAb dramatically suppressed established AA as assessed by AS and hind paw thickness (> 65% and > 80% reduction, respectively; p < 0.05). Most importantly, early treatment in the course of AA almost completely prevented bone destruction in established AA. When given before AA induction OX34 alone prevented the initiation of arthritis compared with controls (AS reduction 83-95%, p < 0.05). In addition, OX34 plus dexamethasone treatment resulted in depletion of CD4+ T cells but not CD8+ T cells. IL2R+ and CD45RC- ('memory') T cells were significantly reduced. CONCLUSIONS: Anti-CD2 mAb treatment prevents AA induction confirming the role of CD4+ T cells in the induction phase of AA. In addition, early OX34 plus dexamethasone treatment resulted in pronounced clinical improvement and joint protection. OX34 treatment therefore inhibits the initiation and the perpetuation of rat AA.

Animals↗
PubMed1996

Specificities of human TAP alleles for HLA-B27 binding peptides.

OBJECTIVE: Allelic TAP polymorphism has been linked to susceptibility to Reiter's syndrome and was suggested to influence disease phenotype in HLA-B27 positive patients with ankylosing spondylitis. In the present study, we examined whether the human TAP alleles functionally differ in their translocation specificity for HLA-B27-binding nonamers. METHODS: TAP translocation of a panel of HLA-B27-binding peptides was measured with a labeled reporter peptide containing an N-linked glycosylation acceptor site in streptolysin O-permeabilized cells with different TAP alleles. RESULTS: The different human TAP alleles tested did not measurably differ in their peptide specificity. CONCLUSION: The polymorphism of human TAP does not affect the translocated repertoire of HLA-B27 ligands and is therefore unlikely to play a decisive role in the development of HLA-B27-associated disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Characterization of a soluble form of CD58 in synovial fluid of patients with rheumatoid arthritis (RA).

Reduced levels of a soluble form of the adhesion receptor and CD2 ligand CD58 (sCD58) were previously described in RA patients. In order to understand the biological significance of this finding we biochemically characterized sCD58 in RA and asked how well sCD58 binds to CD2. sCD58 concentrations were measured in serum and synovial fluid (SF) samples of RA patients by two ELISAs, one detecting domain 1 of CD58 (CD58-D1), and the other one the complete molecule (CD58-D1 + D2). Small amounts of split sCD58-D1 were found in most RA sera, but not SF. In addition, split sCD58-D2 was detected in SF by affinity chromatography, SDS-PAGE, and Western blotting. Gel filtration gave similar peaks at 95-125 kD for RA sera, SF, and normal serum. Binding of SF-sCD58 to the CD2+ Jurkat variant JBB1 or recombinant CD2 was stronger than urinary sCD58 and reached binding of oligomeric recombinant CD58 at low concentrations. In conclusion, sCD58-split products were found in RA sera and SF. At concentrations as they occur in vivo, SF-sCD58 binds to CD2 much more strongly than urinary sCD58. It is conceivable that locally released sCD58 blocks the CD2/CD58 interaction under physiological conditions. Insufficient release of sCD58, e.g. in synovitis, might result in T cell accumulation and perpetuation of inflammation.

Adult↗
PubMed1996

Diclofenac combined with cyclosporine in treatment refractory rheumatoid arthritis: longitudinal safety assessment and evidence of a pharmacokinetic/dynamic interaction.

OBJECTIVE: (1) To characterize potential changes in diclofenac pharmacokinetics and renal function in patients with rheumatoid arthritis (RA) treated with diclofenac and cyclosporine; (2) to prospectively collect longitudinal safety data during use of this drug combination. METHODS: Twenty patients with severe, treatment refractory RA were sequentially treated with stable doses of diclofenac (100-200 mg/day) for one month followed by diclofenac combined with cyclosporine (3 mg/kg/day) for one month. Pharmacokinetic profiles of diclofenac were obtained at the end of each treatment period. Combined therapy was continued for an additional 5 months, during which doses of both drugs could be individually titrated and safety data collected. RESULTS: During co-administration, diclofenac exposure doubled, as shown by an average 104% increase in the area-under-the-curve. Diclofenac half-life was not altered. Serum creatinine was significantly elevated from a baseline value of 0.8 +/- 0.1 mg/dl on diclofenac alone to 1.0 +/- 0.3 mg/dl after one month co-administration with cyclosporine. The magnitude of creatinine elevation was not correlated with that of change in diclofenac exposure, suggesting the pharmacokinetic interaction per se may not additionally contribute to the effect on renal function resulting from this drug combination. During longterm treatment with both medications, prospectively collected safety data indicated that renal function could be stabilized when drug doses were individually titrated in response to serial clinical and laboratory evaluations. The overall pattern of adverse events and laboratory abnormalities in the study population were similar to those reported in patients with RA treated with other nonsteroidal antiinflammatory agents and concomitant cyclosporine. CONCLUSION: Diclofenac can be safely combined with cyclosporine in the management of RA when appropriate clinical monitoring and dose titrations are performed. Due to the pharmacokinetic interaction that increases diclofenac systemic exposure, it would be prudent to start combination therapy with diclofenac doses at the lower end of the therapeutic dose range.

Adult↗
PubMed1995

Sulfasalazine in the treatment of spondylarthropathy. A randomized, multicenter, double-blind, placebo-controlled study.

OBJECTIVE: To assess the efficacy and tolerability of sulfasalazine (SSZ) in the treatment of spondylarthropathy. METHODS: We conducted a 6-month randomized, placebo-controlled, double-blind, multicenter study of patients with spondylarthropathy whose disease had remained active despite treatment with nonsteroidal antiinflammatory drugs. Patients were treated with SSZ (3 gm/day) or placebo. The primary efficacy variables were the physician's and patient's overall assessments, pain, and morning stiffness. End points were analyzed in the intent-to-treat and completer patient populations; the time course of effect was analyzed in the completer patient population. RESULTS: Of the 351 patients enrolled, 263 (75%) completed the 6-month treatment period. The withdrawal rates were 35 (20%) and 53 (30%) in the placebo and SSZ groups, respectively. In the intent-to-treat analysis of end point efficacy, the between-treatment difference reached statistical significance only for 1 of the 4 primary outcome variables, the patient's overall assessment of disease activity, for which 60% of the patients taking SSZ improved by at least 1 point on a 5-point scale, in contrast to 44% of the patients taking placebo. Laboratory markers of inflammation also showed statistically significant change in favor of SSZ. In subgroup analysis, the most impressive effects were seen in patients with psoriatic arthritis, both for the 4 primary efficacy variables and for secondary efficacy variables such as the number of inflamed joints. Adverse events were more frequent in the SSZ group than the placebo group, but all were transient or reversible after cessation of treatment. CONCLUSION: The results of this study show that SSZ had greater efficacy than placebo in the treatment of active spondylarthropathy, notably in patients with psoriatic arthritis.

Adult↗
PubMed1995

Lyme disease in a 74-year-old forest owner with symptoms of dermatomyositis.

We describe a 73-year-old forest owner with widespread erythema, myalgia, and proximal muscle weakness. The clinical signs and the results of electromyography, magnetic resonance imaging, and a muscle biopsy were consistent with dermatomyositis. However, serology was positive for Borrelia burgdorferi. More importantly, B burgdorferi DNA was detected in skin by polymerase chain reaction techniques, and spirochete-like organisms were detected in the muscle by silver staining. Lyme disease with muscle involvement can mimic or trigger dermatomyositis and should be considered in the differential diagnosis of dermatomyositis.

Aged↗
PubMed1995

Elevated serum nitrate concentrations in active spondyloarthropathies.

We determined the concentrations of nitrate, reflecting endogenous nitric oxide (NO) production, by gas chromatography in the sera of patients with spondyloarthropathy. In those patients with active disease, as indicated by elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) serum nitrate levels (n = 7; mean 73.2 +/- s.d. 21.7 mumol/l) were significantly (P < 0.001) increased in comparison to patients with inactive spondyloarthropathy (n = 7; 31.7 +/- 9.5 mumol/l) and healthy volunteers (n = 10; 33.4 +/- 15.9 mumol/l). The nitrate serum levels correlated closely with CRP and ESR (r = 0.8, P < 0.001, each). There were no major differences in dietary nitrate intake between the study groups. The increased concentrations of serum nitrate in patients with active spondyloarthropathy indicate that NO production is enhanced in these patients.

Adult↗
PubMed1995

Sensitivities of PCR, MicroTrak, ChlamydiaEIA, IDEIA, and PACE 2 for purified Chlamydia trachomatis elementary bodies in urine, peripheral blood, peripheral blood leukocytes, and synovial fluid.

Routine microbiological diagnosis of Chlamydia-induced reactive arthritis is based mainly on the detection of Chlamydia trachomatis with urogenital swabs or in urine. Because chlamydial antigen, rRNA, and DNA are present in low quantities in the inflamed joint, highly sensitive assays are needed to detect C. trachomatis not only at the primary site of infection but also in peripheral blood and peripheral blood leukocytes, which are suspected carriers for dissemination, and in synovial fluid. To evaluate possible tools for this purpose, the sensitivities of PCR, MicroTrak, Chlamydia EIA, IDEIA, and PACE 2 for the detection of defined numbers of purified C. trachomatis elementary bodies (EB) in urine, peripheral blood, peripheral blood leukocytes, and synovial fluid were determined. In urine, PCR detected 2, MicroTrak and ChlamydiaEIA detected 2 x 10(3), and PACE 2 and IDEIA detected 2 x 10(4) EB per ml. In peripheral blood, only PCR and MicroTrak detected C. trachomatis, with detection limits of 100 and 2 x 10(7) EB per ml, respectively. For peripheral blood leukocytes, the detection limits were 2 EB per ml for PCR and 2 x 10(4) EB per ml for MicroTrak, ChlamydiaEIA, IDEIA, and PACE 2. In synovial fluid, PCR detected 200, MicroTrak and IDEIA detected 2 x 10(5), and PACE 2 detected 10(6) EB per ml. ChlamydiaEIA was unable to detect 2 x 10(6) EB per ml in synovial fluid. In summary, PCR was found to be the most sensitive method. The sensitivities of the other methods tested were at least 1,000 times lower than that of PCR. PCR should therefore be considered a most promising tool for routine diagnosis of Chlamydia-induced arthritis.

Antigens, Bacterial↗
PubMed1995

Urinary nitrate excretion is increased in patients with rheumatoid arthritis and reduced by prednisolone.

OBJECTIVES: To determine daily production of nitric oxide (NO) measured as urinary nitrate excretion, and the effect of prednisolone in patients with rheumatoid arthritis (RA). METHODS: Twenty four hour urinary nitrate was measured by gas chromatography in 10 patients with RA, before and two to four weeks after commencement of prednisolone 0.5 mg/kg body weight, and in 18 healthy controls. RESULTS: Before the start of prednisolone treatment the urinary nitrate excretion in patients with RA was 2.7-fold greater (p < 0.001) than that in healthy volunteers. After prednisolone it decreased significantly, by 28%, at which time inflammatory activity (as indicated by C reactive protein, erythrocyte sedimentation rate, joint count, and early morning stiffness) was also reduced considerably. Despite this decrease, the urinary nitrate excretion in patients with RA remained twice that in the control group (p < 0.05). CONCLUSIONS: Our data suggest that the endogenous production of NO is enhanced in patients with RA. Furthermore, the results indicate that, in parallel with suppression of inflammation, this increased NO synthesis could be reduced by prednisolone treatment.

Adult↗
PubMed1994

TCR1+ large granular lymphocyte proliferation in rheumatoid arthritis.

The T gamma-lymphoproliferative syndrome is characterized by a proliferation of large granular lymphocytes (LGL). It is often associated with neutropenia, and in 30% of cases with rheumatoid arthritis (RA). Phenotypic analysis has demonstrated that in most cases of RA with T gamma-proliferative disease, the LGL represent T cells with a clonal rearrangement of the alpha/beta T cell receptor (TCR2). Here, three patients with gamma/delta TCR1+ LGL proliferation suffering from long-standing arthritis and neutropenia are described. The first patient with RA showed an expansion of a heterogeneous CD2+ CD16+ CD56- LGL population, of which 30% coexpressed TCR1 with V delta 1 rearrangement. The second patient with ankylosing spondylitis and RA was suffering from proliferation of TCR1+ (V gamma 9-, V delta 1-), CD2+ CD16- CD56- LGL with low coexpression of CD8. The third patient with RA was suffering from a proliferation of TCR1+ (V delta 1+, V gamma 9-) CD4- CD8- CD16- CD56- lymphocytes. On the basis of these unusual findings, the pathogenetic role of TCR1+ T cells in RA is discussed.

Aged↗
PubMed1994

Epidemiology of musculoskeletal conditions in the geriatric population.

Geriatric rheumatology and the epidemiology of musculoskeletal diseases in elderly persons constitute a new field. Although difficult to estimate, the prevalence rate of disabling joint diseases increases as people age. Osteoarthritis (OA) is the most common type of joint disease in geriatric patients. Symptomatic OA has a much lower prevalence rate than does radiographic OA. However, symptomatic disease is important in that it may motivate a patient to seek medical attention. The prevalence of rheumatoid arthritis (RA) also increases with advancing age. The onset of RA in both large and small joints in patients older than 60 years is more frequent and begins with greater disease activity as compared to patients younger than 60. Moreover, RA runs a more severe course in older than in younger patients. Thus, epidemiologic data suggest that elderly individuals could be major consumers of nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used in the management of musculoskeletal disorders. The prevalence of these disorders increases with advancing age and, coupled with increasing longevity, poses a growing challenge to practicing physicians in their treatment of these patients.

Adult↗