[Löfgren syndrome]. / Löfgren-Syndrom.

A short review on incidence, prevalence, possible causes and pathologic findings in sarcoidosis is given. Especially the symptomatology, differential diagnosis and therapy will be described. Finally some data on 10 patients with this syndrome will be presented.

[Drug therapy of arthrosis]. / Medikamentöse Therapie der Arthrose.

The drug therapy of osteoarthritis and mainly of the large joints consists in less severe cases in analgesic drugs. Nonsteroidal antirtheumatic drugs with their analgesic and antiinflammatory action are used in more severe cases. In elderly persons their side effects are more serious, therefore strict controls are important. Therapy with so-called chondroprotective substances is not yet established but the glycosaminoglycan-peptid and also the glucosaminosulfate may be able to slow down the arthrotic process. An additional therapeutic possibility are intraarticular injections of hyaluronic acid and the knee-lavage. A drug therapy in osteoarthritis should never be given as a single measure, but always in combination with physiotherapy and general measures like weight reduction or using a cane, etc.

[Function of cytokines in cartilage degradation]. / Bedeutung der Zytokine beim Knorpelabbau.

Growth-hormones like Insulin-Like-Growth-Hormone-1 (IGF-1) and Tissue-Growth-Factor-beta (TGF-beta) and Cytokines IL-1, IL-6 and TGF-alpha play an important part in the homeostasis and also degradation of the articular cartilage. IL-1 stimulates the production of proteolytic enzymes and inhibits the synthesis of aggrecan and leads therefore to a degradation of the cartilage. TNF-alpha acts in a similar way, whereas the significance of IL-6 for chondrocytes is not yet fully understood. TGF-beta and IGF-1 in contrast have a positive influence on cartilage metabolism, f. ex. TGF-beta stimulates the synthesis of the natural occurring metalloproteinase-inhibitor (TIMP).

Bronchoalveolar lavage in rheumatoid arthritis.

Bronchoalveolar lavage (BAL) was performed on 70 RA patients, 28 without extra-articular manifestations, nine with pulmonary involvement, 13 with sicca-syndrome, 20 with other extra-articular manifestations such as renal involvement, cutaneous vasculitis and rheumatoid nodules. Fifteen patients without rheumatic or pulmonary disease served as the control group. Compared with the control group RA patients showed a statistically significant increase of lymphocytes, especially of activated (DR+)T(CD3+)-helper (CD4+) cells, resulting in a significantly diminished percentage of alveolar macrophages, B(CD21+)-lymphocytes, T-suppressor (CD8+) cells and an increased CD4/CD8 ratio. This cell distribution pattern was more pronounced in RA patients with lung involvement with significant differences to the other RA patients with regard to lymphocytes, DR positive cells and CD4 positive/DR positive cells. It is concluded that these results indicate an altered balance of immunocompetent cells not only in the joints but also in the lung. The changes are more distinct if local manifestations can be diagnosed clinically.

[Helicobacter pylori and nonsteroidal antirheumatics]. / Helicobacter pylori und nicht-steroidale Antirheumatika.

The frequency of occurrence of Helicobacter pylori in the antral mucosa was investigated prospectively in a group of 66 patients (17 men, 49 women, mean age 58 +/- 8.4 years) who had been treated with nonsteroidal anti-rheumatic drugs and 33 controls (14 men, 19 women, mean age 60.7 +/- 6.6 years) who had not received these drugs. In the first group the indication for gastroscopy was ingestion of nonsteroidal antirheumatic drugs for at least 8 weeks, irrespective of dyspeptic symptoms (present in 25 patients), while in the second group the reason for endoscopy was either clinical symptoms (n = 18) or the presence of blood in the faeces. Helicobacter pylori was demonstrated by culture in 36 out of the 66 patients who had received nonsteroidal antirheumatics (54.5%); these comprised 24 out of 46 patients (52.2%) with chronic inactive gastritis and 12 out of 15 patients (80%) with chronic active gastritis. In the control group H. pylori was detected by culture in 22 out of 33 patients (66.7%); these included 11 out of 19 patients (57.9%) with chronic inactive gastritis and 11 out of 12 patients (91.7%) with chronic active gastritis. H. pylori was not demonstrated in any of the seven patients who had histologically normal gastric mucosa. In both groups there was significant correlation between demonstration of the microorganism and severity of inflammation. There is hence no evidence that nonsteroidal antirheumatic drugs have any influence on the colonisation of the antral mucosa by Helicobacter pylori.

Demonstration of a new antinuclear antibody (anti-RA33) that is highly specific for rheumatoid arthritis.

Using immunoblot analysis with soluble nuclear extracts from HeLa cells, we identified autoantibodies to an antigen with a molecular weight of approximately 33,000 in 36% of 95 sera from rheumatoid arthritis patients, but in only 1 of 170 controls. The antigen, termed RA33, was resistant to DNase and RNase digestion but sensitive to proteinase K treatment. There was no discernible relation to other autoantibodies. Thus, this newly described autoantibody appears to be highly specific for rheumatoid arthritis.

[Clinical effectiveness and tolerance of auranofin in patients with chronic polyarthritis. Results of a multicenter long-term study]. / Klinische Wirksamkeit und Verträglichkeit von Auranofin bei Patienten mit chronischer Polyarthritis. Ergebnisse einer multizentrischen Langzeitstudie.

In an open multicenter trial, 90 patients with rheumatoid arthritis were treated with a daily dose of 6 mg auranofin. The duration of the treatment was 12 months. A significant improvement in the following parameters was observed: grip strength, number of swollen and painful joints after the 4th month, blood erythrocyte sedimentation rate decreased significantly after the 2nd month. Of the 90 patients, 56 (62.3%) completed the therapy, in 14 (15.5%) it was discontinued because of side effects and in 8 (8.9%) because of inefficacy. 12 patients (13.3%) stated other reasons for discontinuing the therapy (non compliance). The reported side-effects were mostly gastrointestinal, especially diarrhoea and loose stools. The evaluation of results referring to the duration of the disease shows that patients with a duration of less than 2 years reacted better to the improvement with auranofin therapy than patients with a longer sickness history.

[Chronic polyarthritis in advanced age]. / Die chronische Polyarthritis im höheren Lebensalter.

Approximately a quarter of polyarthritis in the elderly is beginning with a single- or oligo-articular attack of big joints. The first attack of the shoulder joints is noticed especially in men. Most of the patients with rheumatoid arthritis in the elderly have a gradually progressive course. There is often showed a very high blood sedimentation rate (BSR); rheumatoid factor is rare. Generally there is a strongly marked osteoporosis. The success of therapy with disease modifying agents is comparable with that of younger patients with rheumatoid arthritis, but there is a smaller tolerance to gold and D-penicillamine. In some non-steroidal anti-rheumatic drugs a lower dosage is recommended.

The efficacy and safety of fentiazac and diclofenac sodium in peri-arthritis of the shoulder: a multi-centre, double-blind comparison.

In a double-blind parallel group comparison of efficacy and safety, 19 patients with peri-arthritis of the shoulder received 200 mg fentiazac twice daily and 19 received 50 mg diclofenac sodium twice daily, with both drugs given orally for 3 weeks. In both groups, observers' verbal rating scales of pain severity at rest and on movement showed decreases that were significant by week 1. Both groups also had significant improvement in abduction, external rotation, retroversion and anteversion. At week 1, the patients reported improvement, on a verbal rating scale, of global effectiveness, but there were no subsequent changes. There were no statistically significant differences between the treatments in any of these variables. Five (26%) fentiazac-treated patients and four (21%) diclofenac sodium-treated patients reported adverse effects, mostly gastro-intestinal. One case of rash in each group and one case of pruritus in a diclofenac sodium-treated patient were severe enough for the patients to be withdrawn from therapy. There were no clinically significant changes in laboratory values. It was concluded that fentiazac (400 mg/day) and diclofenac sodium (100 mg/day) were equally effective within 1 week in decreasing pain severity and improving shoulder mobility.

[Differential diagnostic value of nephelometrically determined protein fractions in the synovial fluid]. / Zur differentialdiagnostischen Wertigkeit von nephelometrisch bestimmten Proteinfraktionen in der Synovialflüssigkeit.

Synovial fluids of patients suffering from rheumatoid arthritis and osteoarthritis with effusions of the knees were examined. Different parameters were evaluated out of the synovial fluid (immunglobulins, Complement-1Q,-3,-4, haptoglobins, alpha-1-anti-trypsin, alpha-2-macroglobulin, transferrin, ceruloplasmin, rheumatoid factors, total count of cells, and ragocytes) and out of the plasma (blood sedimentation rate). The proteins were analysed by a nephelometricturbidimetric automatic centrifugal analyser. All parameters have been tested by valuable statistical methods and correlated to each other. The results worked out proved the reliability of the used test kits and apparative systems. Correlations within groups of parameters according to their formations (intra-and/or extraarticular) could not have been worked out in a way as it may be supposed. In contrast some parameters themselves are statistically different comparing rheumatoid arthritis and osteoarthritis. In general the results are on a higher level in the rheumatoid arthritis group. Using all parameters mentioned above the statistical differential diagnostic level is based on about 94%. If only blood sedimentation rate, total cell count and ragocytes are evaluated the level is based on 68%.

[Clinical diagnostic strategy in rheumatology]. / Klinische Diagnosestrategie in der Rheumatologie.

The diagnosis of rheumatic diseases should follow a pattern of stages, the first comprising family case history, the case history of the patient and basic physical examinations. The second stage should include X-ray examination and basic or, if necessary, more extensive laboratory tests and simple synovia analysis. The third stage would then incorporate articular biopsy, arthroscopy, different biopsies outside the joint, isotope examination, electromyography, thermography, arthrosonography, computed tomography etc. Allowance should be made in this connection for the diagnostic criteria established by different specialist bodies and the different degrees of diagnostic safety involved. While computerized diagnostic systems for rheumatic diseases can be of great help to the GP, they will never be as successful as the experienced rheumatologist.

[Local and systemic parameters in the synovial milieu]. / Lokale und systemische Parameter im synovialen Milieu.

Our own results as well as recent data from the literature confirm the already long known fact, that synovial fluid analysis allows only in very few diseases as for example a crystal synovitis a definite diagnosis in the individual case. In the majority of the patients this technique permits only to differentiate between inflammatory and non-inflammatory joint disease as well as an estimation of the local inflammatory activity of joint. The simultaneous histologic examination of synovial membrane according to our experience seems to bring no major additional information which exceeds the information given by each technique alone.

HLA antigens and toxicity to gold and penicillamine in rheumatoid arthritis.

One hundred sixty-eight patients with rheumatoid arthritis treated with chloroquine (n = 87), gold salts (n = 133) and/or penicillamine (n = 77) were investigated for possible associations between HLA antigens and toxic reactions. Patients with 2 or more side effects to gold and/or penicillamine had a significantly increased frequency of antigens HLA-B8 and DR3 compared to patients with one or without adverse reactions. Proteinuria to gold or penicillamine was significantly associated with HLA-B8 (relative risk [RR] 4.2) and DR3 (RR 14.0) whereas nonnephrologic side effects to gold or penicillamine were associated with B7 and DR2 (RR 3.5 and 2.8). Patients with skin reactions to gold had a significantly greater frequency of HLA-B7. We found no correlation between chloroquine side effects and any HLA antigen. The results suggest a genetic predisposition to toxic reactions to gold or penicillamine based on an immunologic dysregulation.

Concentrations of lonazolac in serum and synovial fluid of patients with inflammatory or degenerate joint disease.

In 15 patients with inflammatory and degenerative joint disease the concentrations of lonazolac were measured in serum and synovial fluid at steady state conditions. The mean concentration in the synovial fluid in 14 patients was 0.275 microgram/ml, which was 48% of that in the serum. For the patients with inflammatory joint disease, the synovial fluid concentration of lonazolac was 61% of that in the serum whereas in degenerative joint disease it reached only 39%.

[Comparison of oral and parenteral gold therapy--review of the literature]. / Vergleich oraler und parenteraler Goldtherapie--Literaturübersicht.

Numerous open and placebo-controlled trials have shown Auranofin, an oral gold salt, to be effective in the base-line treatment of rheumatoid arthritis. In comparative trials the drug was found to be somewhat less potent than sodium aurothiomalate. Whether it is equal or superior to other base-line antirheumatoids like D-penicillamine or antimalarials, can as yet not be established because of the small patient groups involved in the published trials. While adequately effective clinically, oral gold salts, like their parenteral counterparts, do not halt the radiological progression of rheumatoid lesions. Overall, Auranofin is much better tolerated than the parenteral gold salts, although soft feces are more commonly seen and diarrhea may occur occasionally. Skin rashes as well as proteinuria and thrombocytopenia have been reported in some instances so that, as during parenteral treatment, laboratory studies at regular intervals are mandatory. On account of its oral dosage form and its low side-effect rate Auranofin is a true alternative to conventional parenteral gold salt therapy.

Double-blind, multi-centre trial to compare a once-daily combination of trimethoprim and sulfamethopyrazine with ampicillin 4-times daily in patients with urinary infections.

Sixty-eight patients with urinary infection were allocated at random to receive treatment with either 500 mg ampicillin 4-times daily or a trimethoprim (250 mg)/sulfamethopyrazine (200 mg) combination given once daily after a double, loading dose on the first day. All patients complained of urinary symptoms and showed significant bacteriuria, E. coli being the pathogen most frequently recovered. Clinical and microbiological assessments were carried out on entry and, as a rule, after 3 to 4 days and 1 to 2 weeks of treatment. In the 35 patients receiving trimethoprim/sulfamethopyrazine, 40 (95%) of the 42 original infecting organisms were eradicated. In the 33 patients on ampicillin, the eradication rate was 32 (89%) out of 36 organisms. The course of urinary symptoms was similarly favourable in the two groups. Overall response was considered as 'excellent' or 'good' in 89% of the patients receiving the combination preparation and in 82% of those given ampicillin. Clinical and biological tolerance was satisfactory under both regimens. A longer follow-up control should confirm the value of the new combination in the treatment of urinary infections.