Loss of functional capacity caused by a delayed onset of DMARD therapy in rheumatoid arthritis. Long-term follow-up results of the Keitel function test. Brief definite report.

The aim of this analysis was to investigate the impact of the postponement of DMARD therapy on the functional outcome of rheumatoid arthritis after 10 years of disease. 321 individuals with a disease duration of at least ten years were selected out of a cohort of more than 1800 patients. Two groups were analysed separately: patients who started DMARD therapy within the first year of their disease, and patients who received their first DMARD not earlier than five years after the onset of RA.

Long-term application of disease modifying antirheumatic drugs (DMARD). A single-center, observational study of 1681 patients with rheumatoid arthritis (RA).

Objective: To study the long-term efficacy and safety of methotrexate (MTX), intramuscular gold, azathioprine (AZA), chloroquine (CQ), sulphasalazine (SASP), and D-penicillamine (DPA) in rheumatoid arthritis (RA) patients.

Methods: Between 1979 and 1994, clinical data were prospectively gathered in a single center. 1681 patients were followed-up for at least 4 years.

Efficacy and safety of a combination therapy of methotrexate, chloroquine and cyclophosphamide in patients with refractory rheumatoid arthritis: results of an observational study with matched-pair analysis.

The efficacy and safety of a combination of methotrexate (MTX), chloroquine (CQ) and cyclophosphamide (CYC) were studied in patients with refractory rheumatoid arthritis. A single-centre, matched-pair observational study with prospectively gathered data was performed. Fifty-six patients who had previously failed with MTX were treated with 15 mg MTX per week, 50 mg CYC three times a week and 250 mg CQ per day (group A).

Matrix metalloproteinases, but not cathepsins B, H, and L or their inhibitors in peripheral blood of patients with rheumatoid arthritis are potentially useful markers of disease activity.

Objective: The clinical activity of rheumatoid arthritis (RA) is not reliably reflected by laboratory measures. Proteolytic enzymes involved in the cascade of joint destruction are potentially useful parameters to monitor the extent of joint inflammation in RA. This study compares the validity of two classes of proteolytic enzymes, matrix metalloproteinases (MMP) and lysosomal cysteine proteinases (cathepsin B, H, and L) as well as their respective inhibitors to serve as parameters of RA disease activity.

Circulating levels of matrix metalloproteinases MMP-3 and MMP-1, tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP-1/TIMP-1 complex in rheumatic disease. Correlation with clinical activity of rheumatoid arthritis versus other surrogate markers.

Objective: To investigate whether plasma levels of matrix metalloproteinases 3 (MMP-3, stromelysin), MMP-1 (collagenase), tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP1/TIMP-1 complex (MT complex) are specifically elevated in erosive joint diseases compared to nonerosive rheumatic diseases, and to assess how these markers reflect the clinical activity of rheumatoid arthritis (RA) compared to circulating cytokines and markers of connective tissue turnover as well as established variables [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor titer].

Methods: Plasma levels of MMP-3, MMP-1, TIMP- 1, and MT complex were determined by ELISA. One hundred fifteen patients with RA, 20 with osteoarthritis (OA), 28 with psoriasis arthritis (PsA), 24 with ankylosing spondylitis (AS), 3 groups with systemic autoimmune diseases, and 30 healthy controls were analyzed.

Treatment of refractory rheumatoid arthritis with low-dose cyclophosphamide. Long-term follow-up of 108 patients.

Although cyclophosphamide (CYC) is an effective drug in the treatment of refractory rheumatoid arthritis (RA), the application of this drug in RA has largely been abandoned, due to potentially life-threatening adverse events such as myelosuppression and cancer development. However, the question remains open, whether it is possible to balance the toxicity and the efficacy of CYC with low-dose therapy. 108 patients with refractory RA or with vasculitic organ involvement were treated with 50 mg CYC per day.

Detection of insulin-like growth factor I and II in synovial tissue specimens of patients with rheumatoid arthritis and osteoarthritis by in situ hybridization.

Objective: To study the expression of insulin-like growth factor I and II (IGF I and II) in synovial tissue specimen of patients with rheumatoid arthritis (RA) and osteoarthritis (OA).

Methods: Synovial tissue sections were examined for the expression of IGF I and II by in situ hybridization using digoxigenin labeled antisense and sense RNA probes.

Results: The antisense probe of IGF I reacted with all specimens.

[Wound infection following surgical intervention for rheumatism and its relationship to preoperative basic therapy].

Theoretically, slow acting antirheumatic drugs are capable of affecting the body's infection resistance. We have therefore analyzed the records of all 558 RA-patients hospitalized and operated on at our department from 1985-1987 with respect to the incidence of post-surgical wound infections and possible links to previous treatment with slow acting antirheumatic drugs. A total of 2456 operations were performed, or 4.

Carcinogenicity of the antischistosomal nitrofuran trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-1,2,4-oxadiazole.

The antischistosomal and antitrypanosomal drug trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-1,2,4-oxadiazole [(SQ18506) CAS: 28754-68-9; (E)-amino-3-(2-(5-nitro-2-furyl)-vinyl)-1,2,4-oxadiazole] was carcinogenic for both male and female CD-1 mice when it was administered either in the diet or by gastric intubation. Dose-dependent increases in tumors of the forestomach and lymphatic tissues were observed in all groups receiving SQ18506 including mice infected with Schistosoma mansoni. The predominant tumor observed was squamous cell carcinoma of the forestomach.

Preclinical safety evaluation of the nadolol/bendroflumethiazide combination in mice, rats, and dogs.

Nadolol, a beta-adrenergic antagonist, and bendroflumethiazide, a thiazide diuretic, were administered orally alone and in combination to animals in acute and 6-month toxicity studies and in a rat teratology study. The two drugs in combination showed no evidence of potentiation of acute toxicity in mice. Nadolol and/or bendroflumethiazide were administered orally to rats at daily doses of 1000 or 160 mg/kg of nadolol and 125 or 20 mg/kg of bendroflumethiazide and to dogs at daily doses of 160 or 40 mg/kg of nadolol and 20 or 5 mg/kg of bendroflumethiazide for 6 months.

Preclinical safety testing of new drugs.

Preclinical safety testing is one important step in the development of new medicines. The requirements of such testing are the subject of government regulations and may vary in details, but not in general principles, in different countries around the world. The approach to preclinical safety testing of new drugs is multidisciplinary and requires the expertise of members from many different fields of science.

Amphotericin B methyl ester hydrochloride and amphotericin B: comparative acute toxicity.

In single-dose parenteral studies with mice and dogs, the methyl ester hydrochloride of amphotericin B proved to be significantly less toxic than the parent compound, especially to the kidney.