Punched-card aid in rheumatological diagnosis.

A punched-card diagnostic system is described for use in rheumatological practice. The system is based on pattern recognition and provides a list of both common and rare possible diseases. The system is simple and can be manufactured cheaply, and may be of particular use to family doctors in remote areas of practice. The system has also potential as an educational tool for both undergraduate and postgraduate students of medicine.

Clinical and histological evaluation of synovial needle-biopsies in patients suffering from rheumatoid arthritis. I. Relationship between clinical activity and histological pattern.

In 50 patients suffering for 1-15 years from rheumatoid arthritis, needle-biopsy of the synovial membrane was carried out. The finding correlated with the general clinical activity of the disease. Each type of histological change was evaluated with regard to its diagnostic value in assessing clinical activity. Among the histological changes, oedema, synovial cell proliferation, lymphocyte-plasma cell proliferation and necrotic vasculitis showed a negative correlation with clinical activity, while a positive correlation was observed between clinical activity and the presence of fibrin (fresh and old), fibrinoid, fibrinoid basophilia, fibroblast proliferation, synovial cell desquamation, concentric perivascular sclerosis, fibrosis and hyalinosis. Vascular changes of the synovial membrane such as oedema, fresh fibrin exudate, necrotic vasculitis showed a negative correlation with clinical activity while hyalinization and concentric sclerosis and clinical activity were found to be in positive correlation. It is concluded that in the course of rheumatoid arthritis the histological changes do not necessarily run parallel with the clinical activity of the disease.

Clinical and histological evaluation of synovial needle-biopsies in rheumatoid arthritis. II. Relationship between local clinical activity and histological pattern.

The histological pattern of synovial needle-biopsies of 50 patients suffering from classical or definitive rheumatoid arthritis has been compared with the clinical activity of the disease. Each histological change was evaluated in terms of its value in characterizing local clinical activity. It was shown that most changes of the synovial ground tissue are in a positive correlation with local clinical activity. Among the vascular changes of the synovial membrane, oedema of vascular walls, exudation of fresh fibrin, leukocyte infiltration and thickening of vascular walls were in negative correlation, while chronic fibrin, lymphocytic or plasma cell infiltration and hyalinosis were in positive correlation with local clinical activity.

Maintenance therapy of rheumatoid arthritis and of osteoarthrosis with proglumetacin.

Maintenance therapy with proglumetacin was studied in an open investigation in 25 patients with classical or definite rheumatoid arthritis and in 34 patients with osteoarthrosis. Proglumetacin (150 mg) was administered twice daily, at meals, and therapy was continued without interruption for 12 months. Patients with rheumatoid arthritis showed a progressive improvement in objective parameters (erythrocyte sedimentation rate, haemoglobin) and in semi-objective parameters (pain, articular tenderness, number of painful joints, morning stiffness, grip strength, Ritchie articular index). Patients with osteoarthrosis also showed a progressive improvement in objective parameters (movement angles of the affected joints) and in subjective parameters (pain, mobility, response to therapy). During the study, 4 patients reported occasional nausea (3 with vomiting), and 3 reported episodes of slight headache. These symptoms did not require interruption of treatment. Haematology, blood chemistry and urinalysis were not adversely affected by the treatment. Five drop-outs were recorded in the rheumatoid arthritis group: 2 because patients failed to report, 2 because of severe relapses which required a radical change in the therapeutic programme and 1 for incorrect enrollment. Fourteen drop-outs were recorded in the osteoarthrosis group: 6 because the patients failed to report, 4 because of orthopaedic surgery and 4 because it was necessary to change the therapeutic programme. No drop-out was due to an intolerance to proglumetacin. It is concluded that proglumetacin appears to have the effectiveness of tolerability features required for a first-choice medicament for long-term maintenance treatment of patients with rheumatoid arthritis or with osteoarthrosis.

Polarization optical investigation by topo-optical reactions of various blood platelet aggregates.

Phases I and II (early and advanced) of platelet aggregation could readily be followed and studied by various topo-optical reactions. Our studies indicate that in the early stage (monitored by an aggregometer) aggregates show no alteration in membrane structure of platelet. In the advanced stage (phase II), in addition to membrane alteration, platelets 2-3 times larger than in the control were observed. These were stained selectively in the pH 1-2 range with thiazine dyes. After hyaluronidase digestion they lost the ability to stain and became birefringent. The elucidation of this phenomenon requires further study.

Topo-optical reactions of the human blood platelet membrane.

The polarization optical analysis of human blood platelets was carried out by means of topo-optical staining reactions. Similar studies have not been performed so far. With this approach we were able to demonstrate the spatially oriented nature of glycoprotein components in the platelet membrane. Using a sialic acid specific topo-optical reaction the sialic acid component of human platelet membrane was selectively demonstrated and the even distribution of sialic acid residues on the membrane surface was also suggested. Polarization optical analysis has shown a membrane-parallel orientation of oligosaccharide chains carrying sialic acids.

HLA-DR antigens in juvenile chronic arthritis.

Twenty-five patients with juvenile chronic arthritis (JCA) were typed for HLA-A,-G,-C and -DR antigens to establish significant differences between normal controls and patients with adult rheumatoid arthritis (RA). HLA-DR antigens were correlated with subgroups of disease, and with several clinical features and immunological parameters of JCA. The frequency of DRW8 antigen was significantly higher in JCA than in normal adult controls or patients with RA. This significance was even higher in the persistent pauciarticular subgroup. Connections were found between DR antigens and clinical, immunological parameters, and some of them proved to be statistically significant. Results are presented and discussed in detail.

Beta-2-microglobulin-specific autoantibodies cause platelet aggregation and interfere with ADP-induced aggregation.

The anti-platelet activity of beta-2-microglobulin (beta 2m) specific autoantibodies isolated from sera of patients with autoimmune diseases was tested in direct and ADP-induced aggregation assays. It was established that human anti-beta 2m autoantibodies and heterologous rabbit anti-beta 2m antibodies evoke a dose-dependent aggregation of human platelets. Anti-beta 2m autoantibodies also impaired ADP-induced platelet aggregation. Antibodies with anti-beta 2m activity could be desorbed from the platelets and lymphocytes of a patients with systemic lupus erythematosus who was not thrombocytopenic. The possibility that such autoantibodies may alter platelet function is considered.

A 3-month, double-blind study of proglumetacin and naproxen in the treatment of rheumatoid arthritis.

A double-blind clinical trial was carried out on 2 parallel groups each of 20 in-and out-patients with classical or definite rheumatoid arthritis, to compare the efficacy and tolerance of proglumetacin, a new non-steroidal anti-inflammatory drug, with naproxen. Each patient received daily either 300 mg proglumetacin or 500 mg naproxen in two divided doses, at meals, over a period of 3 months. The whilst both drugs were effective in the long-term treatment of chronic rheumatoid arthritis, proglumetacin appeared to be somewhat more effective than naproxen in reducing the duration of morning stiffness, the articular inflammation score index, erythrocyte sedimentation rate and the dosage of concomitant basic medication. Few side-effects were reported but 1 of the 2 patients in the naproxen group who developed allergic reactions had to be withdrawn during the first few days of treatment.

Prevalence of anti-beta-2 microglobulin autoantibodies in sera of rheumatoid arthritis patients with extra-articular manifestations.

The frequency and concentration of specific factors binding beta 2 microglobulin were investigated in sera and synovial fluids of patients and in sera of normal controls. High anti-beta 2 m activity was detected in the sera of adult RA patients, particularly in those of with extra-articular disease. Similarly, anti-beta 2 m was present in the synovial fluids of RA but not of osteoarthrosis patients. Both the binding of anti-beta 2 m activity to the Sepharose staphylococcal protein A and its elution position in the second 'IgG' peak after Sephadex G-200 gel filtration suggest the antibody nature of the activity. The possibility of differences not only in titre but also in the specificity of heterologous and homologous anti-beta 2 m antibodies are discussed.

[Functional analysis of immune complex-rich serum fractions in autoimmune diseases by in vitro C3 activation of fresh blood]. / Funktionale Analyse immunkomplexreicher Serumfraktionen bei Autoimmunerkrankungen durch in vitro C3 Aktivation des frischen Plasmas.

A method, measuring the activity of circulating immune complexes, based on C3 conversion of fresh human plasma by means of 3 per cent PEG precipitable immune complex-rich sera fractions is reported. Sera of patients suffering from autoimmune diseases of the connective tissue as well as of healthy controls were investigated. In case of standardised protein concentration of immune complexes, significantly low C3 conversion frequency of the isolated fractions has been observed in the control group as compared to the examined patients (rheumatoid arthritis with and without extraarticular manifestations, or juvenile chronic arthritis, or systemic lupus erythematosus). PEG fractions of RA with extraarticular manifestations induced the significantly highest C3 splitting. It is assumed that immune complexes will show a distinct interaction with the complement system also in vivo, and are therefore directly implicated in the systemic course of the disease process.

Autoantibodies specific to beta-2-microglobulin inhibit the Fc receptor-dependent phagocytosis of human monocytes.

Effect of anti-beta2-microglobulin (beta2m) antibodies was investigated on the in vitro Fc and C3 receptor dependent phagocytic capacity of human peripheral monocytes. Both rabbit and human anti-beta2m antibodies inhibit the Fc receptor-mediated phagocytosis. Anti-beta2m antibodies do not influence the spontaneous or C3b receptor-mediated ingestion. The inhibitory activity by human autoantibodies but not by rabbit anti-human beta2m antibodies was diminished when incubation was performed at 37 degrees C instead of 20 degrees C.

Levamisole-induced neutropenia and agranulocytosis: association with HLA B27 leukocyte agglutinating and lymphocytotoxic antibodies.

Among 37 patients treated with levamisole for rheumatoid arthritis (n = 19), for Reiter's disease (n = 4) and for chronic articular brucellosis (n = 14) followed up during 6-12 months, 3 developed agranulocytosis and 3 severe neutropenia. Serum samples drawn before and during treatment were tested for leukocyte agglutinating and lymphocytotoxic antibodies. Leukocyte agglutinating antibodies were induced in 8 patients, in 5 of them in association with agranulocytosis or neutropenia. In 1 patient with agranulocytosis and in another one with neutropenia lymphocytotoxic antibodies were also induced. Two agranulocytotic and one neutropenic patient possessed HLA B27 antigen. In altogether 11 HLA B27 carriers the number of circulating neutrophils were significantly reduced during levamisole treatment when compared with those of patients lacking HLA B27 antigen.

Beta2-microglobulin-containing IgG complexes in sera and synovial fluids of rheumatoid arthritis and systemic lupus erythematosus patients.

The occurrence and composition of complexed beta2-microglobulin (beta2m) in sera and synovial fluids of rheumatoid arthritis and systemic lupus erythematosus patients and control persons was investigated. Beta2m-containing complexes were detected in immune complex (IC)-enriched fractions isolated by precipitation with 3% polyethylene glycol 6000, in the macromolecular peaks after Sephadex G-200 gel filtration, and in IC desorbed from solid-phase Clq. Beta2m complexes were demonstrated also after precipitation of redissolved PEG-insoluble material by anti-human beta2m serum or isolation of the complexes by use of Sephadex-anti-beta2m. IgG was co-isolated with beta2m on Sephadex-anti-beta2m and free beta2m inhibited the binding of IgG to Sephadex anti-beta2m, indicating that IgG was present in the complexed beta2m. Analysis by SDS-polyacrylamide gradient electrophoresis under reducing conditions indicated that the purified beta2m complexes contained IgG and beta2m.

Serological abnormalities in juvenile chronic arthritis: a review of 46 cases.

Data of 46 patients with juvenile chronic arthritis were evaluated. All of them were under the age of 16 at the time of study. Patients with juvenile ankylosing spondylitis, psoriatic arthritis, and arthritis associated with inflammatory bowel disease were excluded from this series. Twenty-six patients had pauciarticular, 9 had systemic, 8 had polyarticular, and 3 patients had seropositive 'adult type' JCA. In all patient groups IgG, IgM, IgA, and C3 levels were significantly higher than in the control group. None of the controls but 13 of 46 patients had high IgE levels. IgA and IgG values were significantly higher in the seropositive subgroup than in the pauciarticular subgroup. There was no other positive correlation between levels of immunoglobulins, C3, and clinical features of disease. Platelet counts were significantly higher in patients with active disease. In the control group 4 out of 10 children had 'hidden' rheumatoid factor. All these children with positive findings were young.