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Biomedical subjects

E Munthe

Publications and source records attributed to E Munthe.

At least 55 records · Page 3Linked to original sources

Capillary column gas chromatography--mass spectrometry in studies on rheumatoid arthritis.

A method is described for determining the organic acid profile of synovial fluid. The method requires 50--100 microgram of sample and involves ion exchange for isolation of the acids followed by combined capillary column gas chromatography--mass spectrometry. Normal synovial fluid and synovial fluid from patients with rheumatoid arthritis show a similar qualitative pattern of acids (mainly fatty acids) resembling the pattern found in serum. The concentrations of the organic acids in the abnormal synovial fluids are 5--10 times higher than those in the fluid from the normal joints. In patients receiving treatment with gold thiomalate, free thiomalate was excreted in the urine. The release of this thiol upon gold therapy is of consequence for the further understanding of the mechanism of action of certain drugs against rheumatoid arthritis.

Arthritis, Rheumatoid↗

Do penicillamine and Myocrisin act the same way in rheumatoid arthritis?

Our observations, as well as similarities between penicillamine and Myocrisin in clinical action and side effects in RA make it not unreasonable to think that thiomalate may have a penicillamine-like effect. Only a controlled clinical trial with thiomalate in RA can provide an answer to this question.

Animals↗

No effect of transfer factor in juvenile rheumatoid arthritis by double-blind trial.

A previously pilot study of treatment with transfer factor in 3 patients with juvenile rheumatoid arthritis (JRA) gave promising results. However, in this small and open study no definite conclusions could be drawn. Therefore, a double-blind group trial was performed in 12 JRA patients treated with transfer factor, and in 12 placebo-treated control patients. The patients were evaluated clinically, by laboratory tests, and by estimation of different lymphocyte populations and cell-mediated immunity in vitro and in vivo. Transfer factor was not found to be of significant therapeutic value in patients with JRA. The only statistically significant difference between the two groups was a greater reduction in the percentage of T lymphocytes in transfer factor-treated patients than in control patients. The significance of this is difficult to explain and could have appeared by chance. No side effects of treatment with transfer factor were noted.

Adolescent↗

Studies on cold insoluble globulin. I Concentrations in citrated plasma in rheumatic disorders.

Cold insoluble globulin (CIG) is a normal glycoprotein of human serum and plasma. The physiological significance of this protein is unknown, but is shows a temperature-dependent relation to fibrinogen and fibrin. It is possible that it represents a substrate for activated fibrin-stabilising factor in the polymerisation of fibrin. CIG is found on the surface of fibroblasts. In the present study CIG was estimated in citrated plasma in 115 patients with rheumatic diseases. Increased amounts were found in patients with systemic lupus erythematosus, secondary amyloidosis in classical and definite rheumatoid arthritis, and in male patients with juvenile rheumatoid arthritis.

Adolescent↗

Trace elements in serum and urine of patients with rheumatoid arthritis.

Patients with rheumatoid arthritis were found to have elevated urinary copper excretion rates. They also had increased serum levels of coeruloplasmin and presumably also of a non-coeruloplasmin copper fraction. The zinc levels in serum and urine did not differ significantly from control values. Serum selenium and serum iron were decreased as compared with those of the healthy controls. It is suggested that an increased copper-to-selenium ratio may be of pathogenetic signficance. Biochemical changes induced by copper may be antagonized (at least partly) by the treatment with gold thiomalate and D-penicillamine. If serum selenium deficiency in RA can be confirmed in larger materials, selenium supplementation as a therapeutic measure should be considered.

Arthritis, Rheumatoid↗

Transitory IgA-deficiency, persistent IgE deficiency and recurrent respiratory tract infectious disease after splenectomy.

In a 14 year old boy, a ruptured spleen was removed. Two months after the splenectomy he developed recurrent infections of the respiratory tract. A deficiency of IgA and IgE in his blood serum was found. His impaired resistance to respiratory tract infections responded well to substitution therapy with IgA. Spontaneous clinical recovery occurred during 3 years after the splenectomy, and was parallelled by a slow return of IgA to normal levels, whereas the absence of IgE persisted. The identical twin brother of the patient, who had his spleen intact, had normal levels of serum IgA and did not suffer from frequent respiratory tract inflammations.

Adolescent↗

[Indomethacin].

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Chemical Phenomena↗

Effect of penicillamine on complement in vitro and in vivo.

In most normal human sera the addition of penicillamine to a final concentration of 0-2 mmol/l and subsequent dialysis caused a slight reduction in serum haemolytic complement (CH50). At 200 mmol/l, CH50 activity was no longer demonstrable. Even high concentrations of penicillamine were needed to inhibit the ability of immunoglobulin to fix complement to preformed or forming immune complexes. This indicated that the reduction of CH50 observed in serum was due to an effect on the complement factors. In vivo, a dose of 240 mg penicillamine caused a slight transient reduction in CH50 in rabbit serum, while 1000 mg penicillamine had no effect on serum CH50 in patients with rheumatoid arthritis. In arthritis patients there was, however, some evidence for removal of complement deposits in synovial tissue during penicillamine treatment. Since it is theoretically possible that concentrations high enough to cause reduction of complement activity can be achieved locally in synovial tissue, the effect on complement may be one of the mechanisms by which penicillamine exerts its effect in rheumatoid arthritis.

Animals↗

Complement and immunoglobulins in synovial fluid from synovectomized patients with rheumatoid arthritis.

In order to see if the complement (C) consumption and conversion, which are typical of rheumatoid joints, continue after synovectomy, 23 knee joints in which synovectomy had been performed from 4-5 to 6-5 years previously, were studied. The mean ratio of the concentration of C3, C4, and C5 in synovial fluid to that in palsma of the same patient was significantly lower than the corresponding ratio for the total protein content. This was found both in joints with active arthritis and in joints without clinical signs of arthritis, and in both seropositive and seronegative patients. Conversion products of C3 were found in 7 of the synovial fluids. The study thus indicated that the complement alterations in synovectomized joints are very similar to those in nonsynovectomized rheumatoid joints. In one synovial fluid agarose electrophoresis showed multiple sharp bands in the gamma region. By crossed immunoelectrophoresis some bands seemed to contain IgG with one type of light chains only. In plasma of the same patients the bands were much weaker, indicating local production of oligoclonal IgG in the joint.

Arthritis, Rheumatoid↗

Different lymphocyte populations in rheumatoid arthritis and their relationship to anti-Ig activities.

The anti-immunoglobulin activities of rheumatoid arthritis appear to be related not only to plasma cells and their precursors, the B-lymphocytes. Evidence for interaction of IgG with T-lymphocytes and with Fc-bearing lymphocyte-like cells has now appeared. Both these cell types can mediate cytotoxicity which may also induce inflammation in addition to that provoked by rheumatoid factors and immune complexes. Rheumatoid factors and immune complexes may act primarily through the complement system. However, active inflammation in rheumatoid patients can occur without abundant immune complexes, e.g. in B-cell-deficient patients (31). In some cases this may be due to activation of the alternate complement pathway. However, the T-cell system with its series of lymphokines may also play an active part-in the inflammatory process. And both T-lymphocytes and Fc-bearing lymphocyte-like cells, the K-cells, can mediate cytotoxicity. Also in such patients further studies are needed to work out the complex interactions between these cell types and to discover the underlying cause or agent in the chronic destructive rheumatoid inflammation.

Antibodies, Anti-Idiotypic↗

Evidence for complement activation by the alternate pathway in the arthritis of hypogammaglobulinemic patients.

The chronic, rheumatoid synovitis in four patients (two children and two adults) with immunodeficiency was studied by means of immunopathological examination of synovial tissues and fluids. Their immunodeficiencies were extensively studied, with various tests for humoral and cell-mediated immunity. The two children were boys with Bruton's disease. One adult, female, had common variable immunodeficiency. One adult male had severe hypogammaglobulinemia. All patients had isolated deposits of complement component C3 in their synovial membranes, usually without traces of immunoglobulins. Depressed levels of complement component C3 were found in the joint fluid, in contrast to high levels in the corresponding serum in one patient. Components of the alternate pathway, properdin and C3A, were found in the tissues, but not components of the classic pathway, C1q and C4. The findings suggest that chronic, rheumatoid arthritis in hypogammaglobulinemic patients may be related to activation of C3 by the alternate pathway.

Agammaglobulinemia↗