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Biomedical subjects

T L Vischer

Publications and source records attributed to T L Vischer.

At least 55 records · Page 3Linked to original sources

Follow-up with OM-8980 after a double-blind study of OM-8980 and auranofin in rheumatoid arthritis.

A 6-month double-blind study of OM-8980 and auranofin in 145 patients with rheumatoid arthritis was followed by an open observation period of 6 months for which 100 OM-8980-treated patients could be assessed. At the end of this second phase, the Ritchie index, number of swollen joints, pain scale, morning stiffness, grip strength and ESR had all improved further with respect to the significant improvements already recorded under OM-8980 and auranofin in the double-blind phase. The statistical analysis of the Ritchie index, pain scale and ESR showed significant changes in these 3 parameters during both the 6-month follow-up phase and the entire 12-month period. As regards the tolerance, 2 patients reported gastrointestinal disorders during the follow-up. The investigators' final assessment of efficacy indicated an improvement in 76% of the patients during the follow-up phase and in 95% during the entire 12-month period.

Adjuvants, Immunologic↗

Human alpha 2-macroglobulin as an inhibitor of insoluble trypsin.

alpha 2-Macroglobulin binds to insoluble trypsin bound on agarose beads inducing a reduction of proteolytic activity of the enzyme towards large substrates such as azocasein. When trypsin was bound on other matrices like sheep red blood cells or latex beads, the inhibition of proteolytic activity by alpha 2-macroglobulin was complete. These results show that alpha 2-macroglobulin inhibits similarly both soluble and insoluble proteinases.

Enzymes, Immobilized↗

[Rheumatologic complications in patients treated with intermittent hemodialysis].

Long-term hemodialysis is complicated by rheumatological problems. They can vary from pain syndromes without clinical signs to severe destructive arthritis. The latter is often associated with severe disability. Its origin can be related to deposition of amyloid or synovial overloading with aluminium or iron. Different factors influence its occurrence, such as the type of dialysis membrane used or the quantity of aluminium consumed by these hemodialysed patients. The authors evaluated the frequency and the type of rheumatic disorders in the hemodialysis center of the HCU in Geneva. A comparison of these findings with previous reports is presented and the etiopathogenesis is discussed.

Adult↗

[Superior gluteal nerve entrapment neuropathy].

We observed two female patients suffering from chronic gluteal pain of mechanical origin, without paresthesia. In the first case, the muscular pain was associated with weakness of hip abduction and with tenderness of the middle gluteal muscle. An electromyography, a principal examination, confirmed a diagnosis of entrapment of the superior gluteal nerve in one case and of the distal branch in the other. The proposed treatment, as in the case of neuropathic entrapment of the median nerve at the wrist, consists of a local infiltration of corticosteroids. If the symptoms persist, surgical intervention to free the nerve is indicated. For our first patient the clinical and electromyography cure has been completed. The neuropathy by chronic compression of a nerve in the gluteal area seems to be rare, but one has to consider further investigations in the case of chronic gluteal pain.

Adrenal Cortex Hormones↗

Cell surface antigen CD5 is a marker for activated human B cells.

A minor subset of B cells which in vivo express the surface antigen CD5, has attracted much attention because of its involvement in autoimmune responses. On the basis of observations showing self-renewal capacity of such cells in mice and also the absence of a substantial change of CD5 phenotype during B cell activation in vitro, the CD5+ B cells are now generally considered to represent a separate cell lineage. In the present study, CD5- B cells were isolated by cell sorter and then stimulated in vitro with mutagenized EL4 thymoma cells in the presence of T cell supernatant. About 70% of the B cells were CD5+ after 3 days. Thus, the CD5 antigen behaves as a B cell activation marker. In our system we found that the frequency of rheumatoid factor-producing B cells was on average three times higher in CD5+ than in CD5- B cells isolated ex vivo from human peripheral blood. Most likely this reflects frequent activation of such autoreactive B cells in vivo.

Antibody Formation↗

Detection of parvovirus in a patient with "reactive arthritis" by in situ hybridization.

We used in situ hybridization to search for the presence of viruses in synovial fluid cell preparations obtained from patients with various forms of knee arthropathies. One patient, presenting with acute reactive arthritis, was found to replicate parvovirus DNA in cells from synovial fluid whereas six other patients with various other forms of arthritis were negative for parvovirus infection. Five patients with osteoarthritis, constituting a control group in which an infectious etiology would not be expected, were consistently negative. In addition, no hybridization was found when synovial cell preparations of all patients were hybridized in situ with DNA probes specific for Epstein-Barr virus, cytomegalovirus, or enteroviruses.

Adult↗

Synovial fluid hydroxyapatite crystals: detection thresholds of two methods.

A method of synovial fluid preparation giving optimal hydroxyapatite detection as well as definitions of the threshold masses of hydroxyapatite in viscous synovial fluid detectable by x ray diffraction and scanning electron microscopy with energy dispersive analysis is reported. Use of an equal volume of 100% hydrazine with the synovial fluid optimised detection of hydroxyapatite. By x ray diffraction the threshold mass of hydroxyapatite was 500 micrograms and by scanning electron microscopy with associated energy dispersive analysis 5 micrograms.

Centrifugation↗

OM-8980 in rheumatoid arthritis: a 6-month double blind placebo controlled multicenter study.

A new immunomodulating drug, OM-8980, was compared to placebo in a 6-month double blind multicenter trial including 107 patients with active rheumatoid arthritis. Ritchie index, number of swollen joints and the pain scale improved significantly more with OM-8980 than with placebo. Grip strength, duration of morning stiffness and erythrocyte sedimentation rate improved more markedly with OM-8980 than with placebo, but the difference did not reach statistical significance. The use of analgesic and antiinflammatory drugs diminished significantly more with OM-8980 than with placebo. Clinical tolerance was good with 7 side effects reported in 3 of the 52 patients included in the OM-8980 group and 11 in 8 patients of the 55 in the placebo group (mostly gastrointestinal troubles and skin reactions). In the overall evaluation by both patients and physicians OM-8980 was significantly superior to placebo.

Arthritis, Rheumatoid↗

[The study of intra-articular infectious agents in reactive arthritis].

Reactive arthritis is differentiated from infectious arthritis by the lack of intraarticular infectious agents. Recently 2 groups, using different techniques have demonstrated intra-articular antigens in cases of reactive arthritis associated with Chlamydia and Yersinia infections. In this article we report the preliminary results of screening cells from synovial fluid for DNA of certain microorganisms by in situ hybridization. Our findings provide complementary evidence of the intra-articular presence of at least parts of microbes.

Antigens, Bacterial↗

[Rheumatic disorders and AIDS].

Various rheumatologic diseases were reported in patients infected by the HIV (human immunodeficiency virus); in most cases, they are related to Reiter's syndrome, reactive arthritis and opportunistic germs arthritis. Based on three cases we summarize the present knowledge in this field.

Acquired Immunodeficiency Syndrome↗

[Treatment of lumbar sciatica with or without neurological deficit using mechanical traction. A double-blind study].

Traction therapy for low back pain with sciatica has been evaluated in a double blind study. 60 patients hospitalized for sciatica with or without signs of sensory or motor deficiency were randomized to 3 treatment groups: "placebo traction" (5 kg), "light traction" (15 kg) and "normal traction" (50 kg). Clinical evaluation after 4, 8 and 12 traction sessions showed no difference between the three groups.

Adult↗

Immunomodulation by alpha 2-macroglobulin and alpha 2-macroglobulin-proteinase complexes: the effect on the human T lymphocyte response.

Alpha 2-macroglobulin (alpha 2M), various alpha 2M-proteinase complexes and methylamine-treated alpha 2M were added to human lymphocyte cultures stimulated with the specific antigen purified protein derivative of tuberculin (PPD), pokeweed mitogen (PWM) and anti-CD3. alpha 2M-trypsin diminished all reactions in a dose-dependent way. In the PPD-induced stimulation of peripheral blood mononuclear cells, both change of configuration and remaining proteinase activity contributed to the suppressive activity. Separate exposure of adherent cells or the highly purified T lymphocytes to alpha 2M-trypsin complexes indicated that the effect was mediated through adherent cells. Addition of indomethacin did not modify the results. In the interleukin 2 (IL2)-dependent stimulation of purified T lymphocytes by anti-CD3 the effect of alpha 2M-proteinase complexes was probably due to the digestion of IL 2 through remaining proteinase activity. As alpha 2M-proteinase complexes are formed at sites of inflammation, the multiple immunomodulatory effects of alpha 2M-proteinase complexes might contribute to the dysregulation of the immune system in inflammatory diseases.

Antigens, Differentiation, T-Lymphocyte↗

A double blind multicentre study of OM-8980 and auranofin in rheumatoid arthritis.

The therapeutic efficacy of the immunomodulator OM-8980 in rheumatoid arthritis was compared with that of auranofin, an oral gold salt, in a double blind, randomised multicentre study lasting six months. Seventy patients were treated with auranofin and 75 with OM-8980. The patients of both groups improved significantly at three and six months for all the clinical parameters observed: Ritchie index, number of swollen joints, morning stiffness, pain, grip strength, intake of non-steroidal anti-inflammatory drugs, and erythrocyte sedimentation rate. No serious side effects were observed in either group. The patients receiving auranofin had more adverse reactions, mainly affecting the gastrointestinal system.

Adjuvants, Immunologic↗

Quantitative analysis of precursors frequency of rheumatoid factor (RF) producing human B cells.

Recently, a new culture system has been devised which leads to activation, proliferation and differentiation into antibody secreting cells of at least 90% of human peripheral blood B-lymphocytes. The system uses mutant EL-4 thymoma cells of mouse origin for B cell activation and T cell/macrophage supernatant as source of cytokines (L. Wen et al., Eur. J. Immunol. 17, 887, 1987). By an ELISA system with Fc fragments as antigen and the F(ab)2 fragment of antibodies against human IgM labelled with alkaline phosphatase, we analysed the frequencies of B cells producing IgM-RFs. The mean frequency of IgM-RF producing cells in normal controls was 1/3100 (s.d. = 0.2 log; n = 5) of circulating B cells. In 2 patients with seropositive rheumatoid arthritis (RA) the frequencies were higher (1/492; 1/262), but in 2 other seropositive patients a normal (1/5540) or even a decreased (1/20000) frequency was observed. The possible relation between circulating and synovial RF producing B cells is currently being investigated.

B-Lymphocytes↗

Activation of resting T lymphocytes by cross-linked anti-CD3 (T3).

In this study we have examined the role of small numbers of adherent cells in the stimulation of highly purified resting T lymphocytes by cross-linked monoclonal anti-CD3 antibodies (T3). T cells were obtained by 3 cycles of purification, using adherence to plastic surface, nylon wool column separation and rosetting with 2-aminoethyl isothiouronium bromide-treated sheep red blood cells. They were stimulated either with T3 antibodies or with solid-phase rabbit anti-mouse IgG-T3 complexes. In standard high density cultures (1 X 10(5)-2 X 10(5) cells), soluble T3, interleukin (IL) 1 and IL 2, used separately, did not induce proliferation of T cells. Soluble T3 together with IL 2 slightly activated T cells to proliferate. Rabbit anti-mouse IgG-T3 complexes attached to the plastic wells induced stimulation in some cultures. The response was markedly increased after addition of IL 2, but not IL 1. The irregular response of these cultures suggested the presence of another variable signal. When cell numbers were reduced (12 X 10(3) cells), neither cross-linking of the CD3-Ti complex nor addition of exogenous IL 1 or IL 2, alone or in combination, stimulated the T cells to increase DNA synthesis. A positive response, comparable to complete peripheral blood mononuclear cells, was restored with 0.5% supplemented adherent cells, provided that IL 2 was present.

Antibodies, Monoclonal↗

Efficacy and tolerability of tenoxicam--an overview.

One-hundred and thirty-three clinical studies have been conducted with tenoxicam in patients with rheumatoid arthritis, osteoarthrosis, extra-articular rheumatism, ankylosing spondylitis and acute gouty arthritis. Its efficacy has been demonstrated in double-blind comparative studies against placebo, and dose-finding studies have found the optimal dose to be 20 mg. Most trials comparing tenoxicam with another NSAID have used piroxicam, an earlier oxicam derivative which also has a long half-life. In general, efficacy was similar in both drugs with a trend in favour of tenoxicam. The tolerability of tenoxicam has also been studied in detail. In short-term studies 11% of patients receiving 20 mg tenoxicam and 18% on 40 mg tenoxicam experienced side-effects (p less than 0.01), as did 20% treated with 20 mg piroxicam (p less than 0.01 against 20 mg tenoxicam). In long-term studies clinical tolerability of 20 mg tenoxicam was found to be superior to that of 20 mg piroxicam. The types of side-effects encountered were mainly gastrointestinal disturbances, followed in frequency by skin rashes. However, all side-effects were generally mild and reversible. The efficacy of tenoxicam is clearly established and its tolerability is acceptable with a 20 mg dose. Tenoxicam thus seems a promising drug and a useful addition to the therapeutic armamentarium.

Anti-Inflammatory Agents, Non-Steroidal↗