A double-blind clinical comparison of proquazone and naproxen in the treatment of patients with symptoms of lumbar nerve root compression syndrome.
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Biomedical subjects
Publications and source records attributed to R B Andersen.
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Fibrin deposits on rheumatoid synovial membranes and fibrinogen-antigenic material in rheumatoid synovial fluid were found to be identical by crossed immunoelectrophoresis into immunoglobulin against fibrinogen, by SDS-polyacrylamide gel electrophoresis, and by gel filtration on Sepharose CL 6B. The material was found to be neither fibrinogen nor fibrin, but degradation products. One of the fragments was purified by preparative agarose electrophoresis, and the physicochemical properties of this fragment were found to be different from those obtained by plasmin digestion of fibrinogen or fibrin. This indicates that other proteases than plasmin are responsible for the degradation products. The material was easily degraded by plasmin to D- and E-antigenic end products, identical to those obtained by plasmin digest of fibrinogen. The solubility of the material was poor in synovial fluid compared to serum and buffer. On the basis of these results, it is suggested that the fibrinlike material on the synovial membrane represents fibrinogen degradation products from the inflamed tissue. These products are likely released into the synovial fluid, and when their concentration here exceeds their solubility, they precipitate on the synovial membrane.
About 30% of patients with clinical osteoporosis had histological signs of osteomalacia, in spite of normal serum 25-hydroxyvitamin D3 (25-OHD3). The excess osteoid disappeared during treatment with 1alpha-hydroxyvitamin D3 (1alpha-OHD3). These patients might have reduced ability to convert 25-OHD3 to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). The intestinal calcium absorption increased during treatment with 1alpha-OHD3, but this was accompanied by a rise in urinary calcium excretion. Photon absorptiometry of the forearm indicated increased bone mineral content during treatment with a daily dose of 2 microgram 1alpha-OHD3 and a supplement of 1 g of calcium. This therapeutic combination, however, caused frequent episodes of hypercalcaemia, so further studies are necessary to evaluate an appropriate dose of 1alpha-OHD3 with or without a calcium supplement.
The effect of 1alpha-hydroxyvitamin D3 (1alpha-OHD3) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on the intestinal calcium absorption was studied in twenty patients with rheumatoid arthritis treated with prednisone at daily doses of 5--15 mg for 1/2--20 years. The fractional calcium absorption, measured before and after the treatment with the vitamin D compounds, increased in nineteen of the twenty patients. This was, however, accompanied by marked rises in the urinary calcium excretion. There was no correlation between the fractional calcium absorption and the duration of the prednisone treatment or the doses given.
Skin biopsies from forty patients with rheumatoid arthritis were studied for presence of immune deposits in the dermo-epidermal junction zone. In about half of these unselected patients with classical and definite rheumatoid arthritis, IgM, complement components and fibrinogen antigenic material were found. A positive correlation is demonstrated between immune deposits and the presence of cryoglobulins in serum. The presence of complement components in the skin deposits was found to be clearly related to the clinical activity of the disease, as judged by Lansbury's index.
Synthetic 1alpha-hydroxycholecalciferol, a potent vitamin D analogue, was given daily together with calcium to seven patients with senile osteoporosis and to three patients with prednisone-induced bone loss. Quantitative bone histology indicated increased formation and mineralization after three months of treatment. The bone resorption was reduced, a finding supported by a decrease in the urinary hydroxyproline excretion. Photon absorptiometry of the forearm showed a significant rise in the bone mineral content, in accordance with the histological findings. Serum calcium rose in all patients and severe hypercalcemia developed in one case. Urinary excretion of calcium and magnesium increased significantly. The findings indicate that treatment with 1alpha-hydroxycholecalciferol may be useful in osteoporosis due to aging or following corticosteroid administration. The patients must be carefully followed up because of the risk of hypercalcemia.
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Seven patients with osteoporosis of ageing were treated with synthetic 1alpha-hydroxycholecalciferol (1alpha-H.C.C.) for 3-4 months. The compound was given at a daily oral dose of 2 mug together with an oral supplement of 1 g of calcium. Clinically there was a striking improvement in the patients' physical fitness. Increased bone formation and mineralisation were seen on iliac-crest bone biopsy, and this was supported by an increased osteoblastic activity demonstrated by histochemical measurement of alkaline-phosphatase activity. Bone histology furthermore showed a reduced bone resorption, which was supported by a reduced urinary excretion of total hydroxyproline. Photon absorptiometry of the forearm accorded with the histological findings, showing a significant increase in the bone mineral content. Serum-calcium rose in all patients, one developing a severe transitory hypercalcaemia. The urinary excretion of calcium and magnesium increased significantly. The serum concentrations of 25-hydroxycholecalciferol and parathyroid hormone were not significantly affected by the treatment. It is concluded that 1alpha-H.C.C. is an effective tool in the treatment of senile osteoporosis.
Fibrin/fibrinogen degradation products observed in rheumatoid synovial fluid exhibit resistance to plasmin proteolysis. In the present study, the influence of the common bile acids on the plasmin digestion of these degradation products in 16 rheumatoid synovial fluids were quantitated immunologically by radial immunodiffusion, and qualitatively estimated by crossed immunoelectrophoresis. Addition of chenodeoxycholic acid, deoxycholic acid, and their taurine and glycine conjugates in concentrations of 3.33 mumole/ml of a mixture of rheumatoid synovial fluid and plasmin resulted in complete plasmin degradation. Cholic acid and its taurine and glycine conjugates were effective only in concentrations of 4.44 mumole/ml. A detergent, such as Triton X-100, had little or no effect on the plasmin digestion. Other proteins capable of influencing fibrinolytic activity, such as plasminogen and the inhibitors alpha1-antitrypsin and alpha2-macroglobulin, were not affected by the two detergents. The bile acids are thought to influence the fibrin/fibrinogen degradation products by unfolding the protein at a molecular level, by virtue of their properties as steroid detergents, leaving the fibrin/fibrinogen degradation products susceptible to plasmin digestion.
On the basis of the earlier observations of an ameliorating effect of jaundice on rheumatoid arthritis, the purpose of the present study was to confirm the influence of bile acids on rheumatoid arthritis. Ten patients were treated with intravenous infusions of chenodeoxycholic acid in single doses of 1-2 g, given over 5-8 hours on 1-4 consecutive days. The concentration of serum bile acids during the infusions were determined. The effect of the treatment was evaluated by means of the subjective experience of the patients, together with the ESR and Lansbury's clinical index. In 6 of the patients, pain relief was obtained for periods of up to 14 days after the last infusion, whereas the symptoms in the remaining 4 patients were unchanged. Where the ESR and the clinical index were concerned, it was characteristic that the course rose and fell, most often with an increase in initial values followed by a cecrease to below the pre-treatment level. In relation to the bile acid infusions, a brief rise, in most cases marked, was observed in the rheuma factors (Waaler-Rose). The serum bile acid concentrations registered during the infusions varied widely. However, no relation was observed between the concentrations and the effect. In all patients, phlebitis occurred in conjunction with each of the infusions. Transient, slight signs of liver injury were recorded in 3 patients, and, in 1 further patient, these signs were more pronounced and accompanied by fever together with deterioration of the joint condition. In all cases, the symptoms had disappeared within 1 week. It is concluded that a certain effect of the bile acid infusions on the clinical condition of rheumatoid arthritis and its related parameters was established. However, the effect was both temporary and inadequate, and especially because of the inevitable occurrence of phlebitis treatment cannot be recommended in tis present form.
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