Cerebral stroke treated in a general medical department.
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Biomedical subjects
Publications and source records attributed to U Abildgaard.
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A simplified method for the assay of antithrombin III (AT) with the highly reactive thrombin substrate 2AcOH X H-D-CHG-Ala-Arg-pNA (substrate Th-1) is described. The assay may be performed at either 30 degrees C or 37 degrees C, and alternatively with the substrate H-D-Phe-Pip-Arg-pNA (S-2238). The standard curve is linear in the 12.5-150% range. For routine assays, 3 standard dilutions of plasma are sufficient, and these may be stored at -20 degrees C for 3 weeks. As only the test plasma must be diluted prior to the assay procedure, the test is more rapidly performed than previous manual assays. In 80 patients plasma samples, with AT in the 19-108% range, there was a high correlation with the results of immunoquantification (r = 0.96). There was also a high correlation between the results obtained with the manual method and the automated version described using the Cobas-Bio Centrifugal Analyser and substrate Th-1 (r = 0.96). Low AT levels in hereditary deficiency (particularly during heparin treatment), in liver cirrhosis, in disseminated intravascular coagulation (DIC), and heparin-treated thrombosis were confirmed.
Crude, commercial thrombin preparations and purified bovine thrombin were incubated with normal human reference plasma and the amount of thrombin inactivated was calculated. 1 ml of human plasma inactivated 140-193 NIH U of the various crude thrombin preparations. In the presence of heparin, a lower thrombin-inactivating capacity of plasma was confirmed using crude thrombin, but this phenomenon was less pronounced with the purified thrombin preparation. The molar concentration of the purified bovine thrombin was determined by active site titration. Comparing with protein concentration (A280), this preparation was 92% pure. 1 ml of human plasma inactivated 2.57 mumol of thrombin in the absence of heparin, and 2.50 mumol with heparin. Assuming 1:1 stoichiometry in the thrombin-antithrombin reaction, these results suggest that the concentration of antithrombin in the pooled reference plasma is approximately 2.57 mumol/l or 0.15 g/l.
Possible sequelae to genital trauma were investigated in ten male victims of torture. Two of the victims examined showed testicular atrophy. No significant difference was found in the serum concentrations of follicle-stimulating hormone, luteinizing hormone, testosterone, and prolactin in those subjected to genital torture, when compared with a control group. Serum spermatocoagglutinins were not found to be increased in either of the two groups.
An amidolytic assay system with tissue thromboplastin (Tpl), purified coagulation factors VII and X, and the chromogenic substrate S-2222 was developed. Antithrombin III (AT) accounts for about one third of the total inhibition exerted by normal plasma in this test system. This effect of AT was prevented by adding purified AT blocking antibodies. Normal plasma and serum showed approximately similar inhibitory effects. The inhibition was probably directed against activated factor VII (F VIIa). Gel filtration of adsorbed normal plasma on Ultrogel AcA 34 showed three inhibitory peaks which were different from AT.
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The incidence of thromboembolic complications (TE) during pregnancy in women with congenital antithrombin III (AT) deficiency has retrospectively been estimated to be about 70%. 8 women with congenital AT deficiency were studied during 9 pregnancies. Subcutaneous or intravenous heparin in doses to prolong the activated partial thromboplastin time (APTT) was given during pregnancy as prophylaxis or therapeutic treatment. During delivery and abortion the AT level was brought to normal by infusion of AT concentrate and the heparin was reduced or withdrawn. Four pregnancies were uncomplicated with regard to TE and resulted in 4 healthy children. Five pregnancies were terminated by induced or spontaneous abortion. 1 woman had TE during heparin prophylaxis and 2 women had TE before the prophylaxis was started. 1 of the latter suffered from a new TE during continued heparing treatment. Insufficient prolongation of APTT was registered at the time of TE in both women with TE during heparin treatment.
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Polysaccharide was isolated from human spleen mastocytoma by proteolytic digestion, precipitation with cetylpyridinium chloride, digestion with chondroitinase ABC, and ion-exchange chromatography on DEAE-cellulose. The final product (0.7 mg per g of starting material, MW 8000) behaved like standard heparin on ion-exchange chromatography and on electrophoresis, and contained D-glucuronic acid, L-iduronic acid, D-glucosamine and sulfate in the proportions expected for heparin. Affinity chromatography on antithrombin-Sepharose separated a distinct high-affinity fraction (4-5% of the total material). Structural analysis of this fraction showed that about 10% of the D-glucosamine residues were N-acetylated, the remainder N-sulfated. The anticoagulant activity of the isolated heparin was 71 B.P. units per mg (whole-blood system), or 30 units per mg (anti-thrombin and chromogenic substrate). 205 and 10-15 units per mg (chromogenic assay) were found for high and low affinity fractions, respectively. These results demonstrate conclusively the occurrence of heparin in a human tissue.
Fourteen patients with jejunoileal bypass for obesity were treated for one week with a calcium supplement of 3g daily. During this period diarrhoea was significantly (P < 0.005) reduced by 23 per cent (97 per cent confidence limits: 7-46 per cent). Ten of the patients had hyperoxaluria (median value 961 mumol/24 h; range 633-2742 mumol/24 h). The treatment with calcium significantly (P < 0.005) decreased the concentration of oxalate in urine by 23 per cent (98 per cent confidence limits: -5-+54 per cent). The calcium supplement did not increase urinary calcium-excretion rate or albumin-corrected serum calcium.
The influence on the metabolism of phenytoin of some sulfonamides given in common clinical doses has been studied. In single dose experiments sulfaphenazole increased phenytoin half-life (T/2) by 237% and decreased phenytoin metabolic clearance rate (MCR) by 67%. Sulfadiazine, sulfamethiazole, sulfamethoxazole + trimethoprim and trimethoprim increased phenytoin T/2 by 80, 66, 39 and 51% respectively, and decreased phenytoin MCR by 45, 36, 27 and 30% respectively. Sulfamethoxazole gave a small but significant increase in phenytoin T/2 but not a corresponding fall in phenytoin MCR. No changes were found in phenytoin T/2 and MCR after treatment with sulfamethoxypyridazine, sulfadimethoxine and sulfamethoxydiazine. Steady state experiments confirmed the findings of the single dose experiments. It is suggested that sulfaphenazole, sulfadiazine, sulfamethizole, sulfamethoxazole + trimethoprim and trimethoprim inhibit hepatic metabolism of phenytoin.
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