Quantitative photometrical assessment of iron deposits in synovial membranes in different joint diseases.

We investigated 86 synovial membranes from patients suffering either from rheumatoid arthritis (RA) or osteoarthritis (OA). Iron deposits in the synovial membrane were stained by the Prussian blue reaction, and the amount of stained iron was quantitatively assessed by microscope photometry. We found a statistically significant increase in iron deposits in the synovial membrane of RA patients when compared to OA patients. The amount of iron deposits correlated with the histological subtype of synovitis, those presenting with more exudative and proliferative features showing greater amounts of iron deposits. We also observed an inverse correlation between the haemoglobin concentration and erythrocytes in the serum and the amount of iron in the synovial membrane. From our data we concluded that iron deposits in the synovial membrane can contribute by several mechanisms, including activation of oxygen radicals, to the chronic inflammatory reaction in RA synovitis.

[Development of a new quantitative rheumatoid factor test]. / Entwicklung eines neuen quantitativen Rheumafaktortests.

A new simple identification of rheumatoid factor on nitrocellulose was developed that allows quantitative detection. Verification of the results was done by comparison with the established Waaler-Rose-Test and Latextest: Correlation coefficient of linear regression for Latextest rLR = 0.717 and for Waaler-Rose-Test rLR = 0.665; Spearman rank correlation coefficient for Latextest rs = 0.798 and for Waaler-Rose-Test rs = 0.700. The interday and intraday variations showed good results. The histograms for different patient groups showed significant distributions. The nitrocellulose-test satisfies ARA-criterium No. 6.

[HLA-B27-negative sacroiliitis as a complication of inflammatory forms of acne: case reports and review of the literature]. / HLA-B27-negative Sacroiliitis als Komplikation entzündlicher Akneformen: Fallberichte und Literaturübersicht.

In this review, three patients with severe inflammatory acne accompanied by a distinct rheumatologic syndrome are discussed together with 44 similar cases reported in the literature. This syndrome, here referred to as "acne-associated arthritis (AAA)" usually involves male teenagers and twins. The most characteristic clinical findings relate to the axial skeleton as well as the sterno-costo-clavicular region. Although no association with HLA-B27 has been found, AAA shares a number of clinical, radiological and histomorphological features with seronegative spondylarthropathies. Furthermore, nosological connections seem to exist with a number of ill-defined "hyperostotic osteoarthropathies." Similar characteristics are known from other "pustulotic or neutrophilic dermatosis." The hypothesis of an infectious etiology of AAA has not been substantiated. Responses to systemic antibiotics are generally disappointing, whereas steroids have been shown to exhibit some therapeutic efficacy.

[Clinical value of histomorphologic studies of joint capsules]. / Klinische Wertigkeit der histomorphologischen Untersuchungen von Gelenkkapseln.

The clinical significance of the histomorphological evaluation of synovial tissue from 389 patients with joint diseases was studied. From these data we conclude: (1) the histomorphological diagnosis in joint diseases is rarely of decisive value (6.2%); (2) in 23.1% of cases the histomorphological diagnosis is judged to be of clinical assistance; (3) the histomorphological grading of the inflammatory reaction in the joint under study corresponds in approximately two out of three cases to the clinical judgement.

Immunophotometric quantification of extravascular immunoglobulin deposits in the synovial membrane of patients with osteoarthritis and rheumatoid arthritis.

The amount of extravascular immunoglobulin deposits in the synovial membrane of patients with osteoarthritis and rheumatoid arthritis was studied in comparison with that of patients suffering from non-joint diseases. Immunoglobulin deposits were immunostained using the three-layer immunoperoxidase method. The staining results were quantified with the help of a microscope photometer connected with a scanning stage. Several experiments involving artificial test substrates, diseases with allegedly increased extravascular deposits or diseases not exhibiting extravascular deposits of immunoglobulins are used to validate the described microspectrophotometrical approach for measuring extravascular immunoglobulin deposits. The scanning photometry demonstrates significantly higher amount of extravascular immunoglobulin deposits in rheumatoid arthritis as compared with osteoarthritis and non-joint diseases.

[Incomplete Felty syndrome with manifestation of arthritis following a long-standing course of the disease]. / Inkomplettes Felty-Syndrom mit Manifestation der Arthritis nach jahrelangem Krankheitsverlauf.

A 62-year-old female patient with splenomegaly, severe granulocytopenia, recurrent infections and negative rheumatoid factor test initially had no clinical evidence of rheumatoid arthritis. Leucopenia responded to splenectomy and did not recur during 7 years follow-up. Symmetrical metacarpophalangeal joint-swelling developed 9 months after 7 years of radiographic destruction. This case emphasizes that arthritis may occasionally be a late and minor manifestation of Felty's syndrome.

[Results of long-term D-penicillamine therapy in chronic polyarthritis]. / Ergebnisse der D-Penicillamin-Langzeittherapie bei chronischer Polyarthritis.

In 34 patients with severe rheumatoid arthritis the therapeutic efficacy of 600 mg/die of D-penicillamine was evaluated for five years. Patients were included in the study only if the duration of their disease exceeded 6 months (upper limit 12 months), and there was involvement of 6 or more joints and an elevated erythrocyte sedimentation rate (1 Hour values greater than or equal to 25 mm). In 9 patients (26%) a decline in the activity index could be observed, but 7 of these subjects had a deterioration of findings as assessed by x-ray. The increase of the activity index indicated no therapeutic benefit in 25 patients (74%), which could be confirmed in all subjects by x-ray.

[Effectiveness of D-penicillamine therapy in chronic polyarthritis]. / Untersuchungen über die Wirksamkeit der D-Penicillamintherapie bei chronischer Polyarthritis.

In 52 patients with severe rheumatoid arthritis the therapeutic efficacy of 600 mg/die of D-penicillamine was evaluated for two years in a prospective trial. Patients were included in the study only if the duration of their disease exceeded 6 months (upper limit 12 months), and there was involvement of 6 or more joints and an elevated erythrocyte sedimentation rate (1 hour values greater than or equal to 25 mm). In 26 patients (50%) a decline in the activity index could be observed, but 18 of these subjects had a deterioration of findings as assessed by X-ray. The increase of the activity index indicated no therapeutic benefit in 26 patients (50%), which could be confirmed in 23 subjects by X-rays.

[No correlation between suppressor cell function and disease activity in natural history studies of patients with systemic lupus erythematosus]. / Keine Korrelation von Suppressorzellaktivität und Krankheitsaktivität in Verlaufsuntersuchungen von Patienten mit systemischem Lupus erythematodes.

In ten patients with systemic lupus erythematosus lymphocyte suppressor cell function was repeatedly monitored over a period of nine months. The method used is based on the finding that in vitro addition of ConA to PWM-stimulated lymphocytes activates suppressor T cells which in turn inhibit immunoglobulin synthesis. Nine of ten SLE patients exhibited significant impairment of IgG suppression but no correlation was found between the outcome of the IgG suppressor cell assay and disease activity or the treatment protocol applied.

Distribution of mast cells in human synovial tissue of patients with osteoarthritis and rheumatoid arthritis.

Mast cells are demonstrated in synovial membranes of patients with osteo-arthritis and rheumatoid arthritis using a new staining principle based on interaction of heparin in mast cell granules with peroxidase labeled avidin. It was found that mast cell numbers in the subsynovial layer of patients with rheumatoid arthritis were significantly lower than those in patients suffering from osteo-arthritis. This decrease can be mainly attributed to patients with rheumatoid arthritis whose synovitis was characterized by a distinct histomorphological pattern consisting of lining cell ulcers and granulation tissue. However, when mast cell numbers in rheumatoid arthritis and osteo-arthritis patients were compared without respect to mast cell distribution in the subsynovial layer or the stratum fibrosum, no statistical differences between the diseases could be observed.

Effect of ASTA Z 7557 (INN mafosfamide) a precursor of 4-hydroxy-cyclophosphamide on human T-lymphocytes' Fc-receptors and immunoregulatory functions.

The precursor ASTA Z 7557 of the in vivo active metabolite 4-hydroxy-cyclophosphamide (4OH-Cy) of cyclophosphamide (Cy) was tested for selective effects on human T-lymphocytes' Fc gamma-receptor expression and certain immunoregulatory functions. It has been found that ASTA Z 7557 does not alter the expression of Fc gamma-F- or Fc gamma-I-receptors on the T-cell membrane nor does it exhibit differential toxicity for either T-cell subpopulation. PWM-induced B-cell proliferation is inhibited by ASTA Z 7557, whereas B-cells' Ig-synthesis as well as ConA-driven T-cell proliferation is only blocked with higher doses of the reagent. Final concentrations above 1 microgram/ml may therefore abrogate ConA-induction of suppressor T-lymphocytes. Already ConA-activated suppressor cells of PWM-driven B-cell cultures, however, are not inhibited even with high doses of ASTA Z 7557.

[Fc gamma receptor-bearing T lymphocytes in systemic lupus erythematosus in relation to disease activity and treatment]. / T-Lymphozyten mit FcG-Rezeptoren bei Systemischem Lupus erythematodes in Abhängigkeit von Krankheitsaktivität und Therapie.

In peripheral blood of SLE-patients fluctuating patterns of Fc-gamma-receptor bearing T-lymphocytes have been observed, when long term monitoring has been performed. No influence of disease activity and corticoid treatment on number of Fc-gamma-receptor bearing lymphocytes was seen.

[Isolation, structure elucidation and synthesis of a hexapeptide from the hemodialysate of uremic patients]. / Isolierung, Strukturaufklrung und Synthese eines Hexapeptids aus dem Hämodialysat urämischer Patienten.

Lyophilised hemodialysates of uremic patients were fractionated on Sephadex G-15 for investigation of potential uremic toxins. One of the oligopeptides found in the fraction of postulated toxins was purified to homogeneity by gel, reversed-phase and adsorption chromatography and by high-performance liquid chromatography. Dansyl Edman degradation revealed the sequence Ala-Phe-Phe-Gly-Glu, which was synthesized by the solid-phase method. The comparison of synthetic and natural hexapeptide by chromatographic methods, mass spectrometry, 1H- and 13C-nuclear magnetic resonance proved the correct sequence. The peptide showed only weak activity in immunological test systems and in the lymphocyte proliferation test.

Two distinct Fc receptors for IgG on human peripheral T lymphocytes.

The proportion of human peripheral T lymphocytes forming rosettes with IgG-coated ox erythrocytes (ORBC) is increased after controlled hypotonic treatment. This increment may be as high as 40% of total T cells, depending on the lymphocyte donor. Such treatment is shown not to result in selective cell loss. Induced rosetting is mediated by a receptor specific for the Fc portion of human IgG (Fc gamma R). Inhibition of induced Fc gamma R activity is equally well accomplished by monomeric and by aggregated IgG of defined size. This is in contrast to the Fc gamma R detected before hypotonic treatment, which is not significantly inhibited by monomeric IgG. Capping studies established the structural independence of these two types of Fc gamma R in the lymphocyte membrane by virtue of selective cross-linking of either receptor while leaving the respective counterpart unaffected. The biochemical basis of the hypotonic effect is not yet resolved. However, the data presented suggest that hypotonicity results in removal of Fc gamma R-bound cytophilic IgG. Operationally, we propose the term induced Fc gamma R (Fc gamma R-I) for the here-described new type of receptor with high affinity for monomeric IgG.Fc gamma R that are directly assayable without hypotonic induction and not inhibited by monomeric IgG are termed free Fc gamma R (Fc gamma R-F).

[The effect of basic therapeutic procedures on the immunoregulatory T-cell apparatus in patients with chronic polyarthritis]. / Der Einfluss von Basistherapieverfahren auf den immunregulatorischen T-Zellapparat bei Patienten mit chronischer Polyarthitis.

Five by five patients with rheumatoid arthritis were treated with gold salts, D-penicillamine and cyclophosphamide. The T-lymphocyte subpopulations were measured. In patients, treated with gold salts or D-penicillamine, we did not find alterations of the number of TG- and TM-lymphocytes. The daily treatment with 100 mg cyclophosphamide will result in a significant reduction of TG-lymphocytes.

Distribution of lysozyme in synovial tissue of patients with osteoarthritis and rheumatoid arthritis demonstrated by different enzyme histochemical methods.

Lysozyme-producing cells were analysed by enzyme histochemistry in paraffin sections of synovial tissue of 60 patients with rheumatoid arthritis (RA) and 20 patients with osteoarthritis (OA). For lysozyme detection three enzyme histochemical systems - peroxidase-anti-peroxidase, alkaline phosphatase and biotin-avidin - were used in parallel experiments. Lysozyme was found to be produced by polymorphonuclear cells, mononuclear phagocytes and part of synovial lining cells. All types of lysozyme-producing cells were increased in RA compared with OA. Subgrouping of RA synovitis according to histomorphological criteria allowed the demonstration of an inverse relationship between the number of lysozyme-producing cells and the grade of proliferation of fibroblasts, called mesenchymoid transformation by Fassbender [19]. The different methods of lysozyme detection differed in specificity and sensitivity. The immunoenzymatic staining of lysozyme allows specific and quantitative evaluation of phagocytizing cells in RA and OA.

Urinary excretion of N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase in patients receiving amikacin or cis-platinum.

Urinary excretion of alanine aminopeptidase (EC 3.4.11.2) and N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30) was determined for 25-70 days in five patients receiving cis-platinum and for 8-53 days in six patients receiving amikacin. This study was performed to investigate if the excretion of urinary enzymes represents a sensitive parameter for the early detection of toxic kidney damage. The determination of N-acetyl-beta-D-glucosaminidase was carried out by the method of Knoll et al. [13]. The procedure of Mondorf et al. [14] for the estimation of alanine aminopeptidase activity was adapted to the Gemsaec Fast-Analyzer. In both patient groups an increase in the excretion of the two enzyme activities could be demonstrated. In patients receiving amikacin, the excretion of alanine aminopeptidase was always higher than that of N-acetyl-beta-D-glucosaminidase, whereas in three patients receiving cis-platinum it was the opposite. In two cis-platinum patients the excretion of both enzymes was of the same size. The changes during amikacin therapy seem to be reversible, whereas in four cis-platinum patients these changes seemed to be partly irreversible. Serum creatinine concentration was less sensitive than the urinary enzyme excretion for detection of kidney damage.

[Comparative study of the diagnostic value of disc electrophoresis of urinary proteins and measurement of the excretion of N-acetylglucosaminidase for the detection of renal tubule damage in chronic polyarthritis (author's transl)]. / Vergleichende Untersuchung zur diagnostischen Wertigkeit von Diskelektrophorese der Urinoproteine und N-Acetylglucosaminidaseausscheidung zur Erkennung von tubulären Nierenschädigungen bei chronischer Polyarthritis.

A method is described for the determination of the enzyme N-acetyl-beta-D-glucosaminidase in gel-filtered urine. The individual reaction parameters were tested, and the reliability of the method was determined. The stability of the enzyme in urine was investigated at different temperatures over a 6 week period. The excretion of N-acetyl-beta-D-glucosaminidase, like the analysis of urinary proteins by disc electrophoresis, is a sensitive parameter for renal damage. The two methods were compared, using 50 random urine samples from patients with chronic polyarthritis; both methods were found to have equal diagnostic value.

[Tubular nephropathy in chronic polyarthritis]. / Tubuläre Nephropathie bei chronischer Polyarthritis.

Disc electrophoresis and N-acetyl-beta-D-glucosaminidase (NAG) of urine are sensitive indicators of renal damage. In 28 from 50 patients with definite rheumatoid arthritis, a tubular proteinuria and a high urinary NAG-excretion and in 10 other patients one of these pathological parameters were detected. A positive correlation with disease activity was noted. Both methods are able to demonstrate a rheumatoid involvement of renal function.