HLA-DR/DQ interaction in patients with erosive rheumatoid arthritis presenting articular and extraarticular disease manifestations.

In the present study we have analysed the effect of HLA-DRB1 and -DQB1 alleles on disease progression and genetic predisposition among 201 RA patients. We clearly confirm the association of RA with HLA class II alleles sharing the (Q)R/KRAA amino acid (AA) cassette in the third hypervariable region (HVR3) of the DR beta-chain. The HVR3 (Q)R/KRAA motif was significantly overrepresented among RA patients (79% vs. 40%, P < 0.001), with one third of the patients homozygous (28% vs. 6.7%, P < 10(-9)) and the number of rheumatoid factor positive (RF+) patients was significantly increased among HVR3 (Q)R/KRAA homozygous in comparison to HVR3 (Q)R/KRAA negative individuals. Erosive disease defined by the Larsen Score and personal disability determined using the Health Assessment Questionnaire (HAQ) was significantly increased among patients positive for the HVR3 motif with the worst outcome among HVR3 (Q)R/KRAA homozygous patients. In contrast, there was no association of the shared HVR3 AA cassette and disease severity in the majority of patients presenting systemic (extraarticular) disease. Homozygosity for the shared HVR3 motif was only marginally increased among patients presenting 'severe' extraarticular disease in comparison to patients with articular disease (33% vs. 43%, P = ns). Similarly, patients with nodular disease were not more often homozygous for the HVR3 (Q)R/KRAA motif. Furthermore, we observed no HLA-DR independent association of DQB1 alleles among HVR3 (Q)R/KRAA positive patients and controls. Our analysis supports the predominant role of HLA-DR for genetic susceptibility to RA. In the clinical setting, however, HLA-DR typing may be limited to assess the individual risk of patients for disease progression.

Magnetic resonance imaging of the craniocervical junction in rheumatoid arthritis: value, limitations, indications.

The cervical spine is the second most common location for manifestation of rheumatoid arthritis (RA). Symptoms are typically related to involvement of the craniocervical junction. Unfortunately, conventional radiographic examination is often unable to demonstrate that RA is the cause of such symptoms. Magnetic resonance imaging (MRI) provides an unique opportunity to visualize nerves, connective tissue, and bone in all planes without the use of contrast agents. These features suggest that MRI could provide important information related to RA of the cervical spine. The possibilities and limitations of MRI were therefore evaluated in 60 patients with cervical RA. The main objective of this study was to correlate symptoms and clinical findings with MRI results to establish indications for this imaging procedure.

[Effect of gold on lymphocyte stimulation by influenza A in chronic polyarthritis]. / Goldwirkung auf die Lymphozytenstimulation durch Influenza A bei chronischer Polyarthritis.

In vitro stimulation with influenza-A antigens of the peripheral lymphocytes from patients with rheumatoid arthritis is significantly higher than that in those from healthy controls. Stimulation was performed without autologous serum, is dependent on the monocyte function and correlates with disease activity. Gold compounds can inhibit monocyte function and so the lymphocyte stimulation by influenza-A antigens. Cortico-steroids do not do this. Under gold compound treatment, lymphocyte stimulation was markedly reduced in about 70% of cases and was correlated with clinical success.

[Demonstration of increased influenza-A-antibody levels in the serum of patients with chronic polyarthritis]. / Nachweis von erhöhten Influenza-A-Antikörperspiegeln im Serum von Patienten mit chronischer Polyarthritis.

Patients with rheumatoid arthritis show increased levels of anti-influenza-A antibodies in their sera compared to healthy controls and patients with other inflammatory rheumatic diseases (systemic lupus erythematosus, ankylosing spondylitis and psoriatic arthritis). These antibody levels are dependent on the activity of rheumatoid arthritis.

[Interaction of isoxicam and digoxin]. / Untersuchungen zur Wechselwirkung von Isoxicam und Digoxin.

The influence of maintenance therapy with Isoxicam, 200 mg daily, on digoxin steady-state plasma levels was studied on 12 healthy volunteers. One person dropped out from the investigation program on account of cardiac sensations following the invasion phase with digoxin. No statistically significant differences could be shown during concomitant therapy or after withdrawal of Isoxicam. Neither were toxic glycoside plasma concentrations observed. There were no pathological clinicochemical parameters, in particular no changes in renal function values.

[Indomethacin kinetics in synovia and plasma following administration of indomethacin Gits 7/85 in patients with chronic polyarthritis]. / Indomethacin-Kinetik in Synovia und Plasma nach Gabe von Indomethacin Gits 7/85 bei Patienten mit chronischer Polyarthritis.

Patients suffering from rheumatoid arthritis received a single dose of the new therapeutic system of indomethacin (Gits 7/85). Samples of plasma and synovial fluid were taken after 1, 2, 4, 6, 8, 10, 12, and 24 h. Concentration peaks could not be observed. After 2-3 h plasma levels were achieved which remained constant over the investigational period. Indomethacin concentrations in synovial fluid were seen with some delay. All synovial fluid levels after single application were lower than the plasma concentrations. The kinetics of elimination showed no difference between the two compartments. The above findings confirm the expectations regarding the new therapeutic system of indomethacin (Gits 7/85), i.e., the maintenance of a nearly constant plasma and synovia level for at least 10 h. The avoidance of peaks is seen as an additional advantage.

An interaction study between benoxaprofen and digoxin.

The influence of maintenance therapy with benoxaprofen, 600 mg daily, on digoxin steady-state plasma levels was studied in 12 patients with rheumatic disease. No difference could be shown during concomitant therapy or after withdrawal of benoxaprofen (p greater than 0.10 and p greater than 0.90, respectively). Toxic concentrations were not observed. There were no changes in renal function values.

[Comparison of bumadizone-, phenylbutazone- and oxyphenbutazone-plasma levels after a single oral dose of phenylbutazone and of bumadizone, respectively (author's transl)]. / Vergleichende Untersuchung der Bumadizon-, Phenylbutazon- und Oxyphenbutazon-Plasmaspiegel nach einmaliger Gabe von Phenylbutazon und von Bumadizon.

Bumadizone-calcium-semihydrate and phenylbutazone were given orally to two groups (I and II) consisting of 6 persons each; plasma levels of bumadizone, phenylbutazone and oxyphenbutazone were determined over a period of 384 h. For bumadizone a plasma half-life of 6.9 h was found, maximum plasma levels were reached after 1-6 h varying from 27 to 46 microgram/ml. Phenylbutazone- and oxyphenbutazone-AUC-values were compared between the two groups.

[Muscle blood flow and capillary diffusion capacity in patients with rheumatoid arthritis (author's transl)]. / Das Verhalten von Kapillarer Muskeldurchblutung und von kapillarer Transportkapazität (PS-Produkt) bei Patienten mit chronisch-progredienter Polyarthritis.

Capillary blood flow (Xenon-133) and diffusion capacity for Chrom-51-EDTA (PS-Product of Renkin) of striated muscle tissue were examined by double isotope method in patients with rheumatoid arthritis. Xenon-Clearance and PS-Product were studied under normal conditions and following hyperemisation. There existed no significant difference between rheumatoid patients and normal subjects and there was no evidence of increased capillary permeability. Apparently, derangement of muscle capillaries is rare in rheumatoid arthritis.

[Determination of azapropazone and 8-hydroxyazapropazone in urine by direct quantitative thin-layer chromatography (author's transl)]. / Die Bestimmung von Azapropazon und 8-Hydroxyazapropazon im Harn durch direkte quantitative Dünnschichtchromatographie.

A method for quantitative determination of 5-dimethyl amino-9-methyl-2-propyl-1H-pyrazolo[1,2-a] [1,2,4]benzotriazine-1,3-(2H)-dione (azapropazone) and 8-hydroxyazapropazone in urine has been described. The analysis is performed by quantitatively thin-layer chromatography. The method is selective with a standard deviation of about 5%. After daily oral administration of 3 x 300 mg azapropazone-dihydrate a mean excretion of azapropazone of 62% and a mean excretion of 8-hydroxyazapropazone of 14% was determined.

[Kinetics of digitoxin during antirheumatic therapy with azapropazone (author's transl)]. / Digitoxin-Kinetik unter antirheumatischer Therapie mit Azapropazon.

The effect of chronic therapy with 5-dimethylamino-9-methylamino-9-methyl-2-propyl-1H-pyrazolo[1,2-a] [1,2,4] benzotriazine-1,3-(2H)-dione-dihydrate (azapropazone-dihydrate; Prolixan 300) on the elimination of a single i.v. dose of digitoxin was studied in 8 patients with rheumatoid arthritis and osteoarthritis using a crossover design. 0.5 mg digitoxin were injected i.v. alone and together with a chronic oral therapy of azapropazone starting 3 weeks before digitoxin was given. Digitoxin plasma levels were determined by radioimmunoassay over a period of 19 days. The half-life for plasma digitoxin was 6.4 +/- 0.5 days after digitoxin alone and 7.0 +/- 0.6 days during azapropazone treatment. In two patients the half-life of digitoxin was increased by about one-third during azapropazone therapy. The areas under the plasma digitoxin curve were 2592 +/- 262 ng/ml X h and 2615 +/- 273 ng/ml X h, respectively. None of the differences were statistically significant. It was concluded that there was no clinically significant interaction between azapropazone and a single dose of digitoxin.

[On the determination of azapropazone from plasma by direct quantitative thin-layer chromatography (author's transl)]. / Uber die Bestimmung von Azapropazon aus Plasma durch direkte quantitative Dünnschichtchromatographie.

For the purpose of investigating drug interactions, a new selective method for determination of 5-dimethylamino-9-methyl-2-propyl-1H-pyrazolo[1,2-a] [1,2,4]benzotriazine-1,3(2H)-dione-dihydrate (azapropazone, Prolixan 300) was developed. The method is based upon the direct quantitation of the drug by thin-layer chromatography using remission measurement. The method is well suited for routine analysis of numerous samples, because of its simplicity and rapidity. The standar deviation of the method is about +/-4% at therapeutic plasma concentrations.