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Biomedical subjects

K Söderberg

Publications and source records attributed to K Söderberg.

7 recordsLinked to original sources
PubMed1996

Once-daily subcutaneous dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis.

The aim of the study was to compare the efficacy and safety of once-daily subcutaneous injection of dalteparin, a low molecular weight heparin, with that of intravenous unfractionated heparin in the treatment of deep venous thrombosis (DVT). Patients were included if they had deep venous thrombosis distal to inguinal ligament and were randomised either before, if it was considered necessary, or after phlebographic verification of the diagnosis. There was no pre-inclusion treatment with unfractionated heparin. One hundred and twenty patients received dalteparin, administered subcutaneously once-daily at a fixed dose of 200 IU anti-factor Xa/kg, and 133 patients received a continuous intravenous infusion of unfractionated heparin (UFH). Oral anticoagulation was started on the first or second day, and initial treatment with dalteparin or UFH discontinued when the prothrombin time was in the therapeutic range (2 < INR < 3) on two consecutive days. Control phlebograms were taken within 4 days, thereafter. There were no significant differences between the two initial treatment groups in improvements in Marder score. Two major bleeding events occurred in the UFH group versus none in the dalteparin group. One patient in each group experienced clinically significant pulmonary embolism. During a mean follow-up period of 6.9 +/- 1.5 months, recurrent DVT occurred in four patients in the dalteparin group and in two of the UFH group. These results confirm those of a previous study on dalteparin in the initial treatment of DVT, and suggest that dalteparin administered once-daily at a fixed dose of 200 UI/kg is as effective and well-tolerated as UFH in patients with DVT below the inguinal ligament. The present study also demonstrates that dalteparin can be started as soon as the diagnosis of DVT is suspected and without pre-treatment with UFH. Given that the administration of once-daily subcutaneous injections needs not require a patient to be hospitalised, studies to investigate the possibility of using dalteparin for the initial treatment of DVT in the outpatient setting are warranted.

Acute Disease↗
PubMed1995

A comparative study of three low-molecular weight heparins (LMWH) and unfractionated heparin (UH) in healthy volunteers.

The levels of anti-IIa and anti-Xa activity, as reported in laboratory and clinical studies on low molecular weight heparin (LMWH) preparations, show a high degree of variability. This variation has been proposed as correlated to the variation in incidence of postoperative deep vein thrombosis (DVT) (8-30%) in different LMWH studies on comparable populations undergoing elective hip surgery. The aim of this study was to compare the ex vivo potency of Clexane (enoxaparin), Fragmin (dalteparin) and Logiparin (tinzaparin), applying the concept of bioequivalence, although unknown which activity/activities are best correlated to efficacy. Unfractionated heparin (UH) was included in the study as a reference drug. The drugs were studied with a cross-over technique in 12 healthy subjects and given subcutaneously in the doses recommended for orthopedic surgery. Blood samples were drawn each hour up to 10 h and at 12 h after administration. Anti-Xa and anti-IIa activities were measured using chromogenic substrate methods. The anti-Xa peak activity (Cmax) and the area under the curve (AUC) were highest for Clexane and Fragmin and lower for Logiparin and UH. Clexane and Fragmin were considered bioequivalent in anti-Xa activity. Regarding anti-IIa activity, no bioequivalence was found between the products. Fragmin was clearly different, with Cmax and AUC approximately twice as high as the other drugs. Whether the demonstrated differences in anti-Xa and anti-II activities are of any clinical significance remains unclear and can only be established by comparative clinical studies.

Adult↗
PubMed1991

The influence of surgical trauma on factor XaI and IIaI activity and heparin concentration after a single dose of low-molecular-weight heparin.

To study the influence of surgical trauma on the XaI and IIaI activity after injection of a low-molecular-weight heparin (LMWH) 24 patients undergoing elective cholecystectomy received one subcutaneous injection of the LMWH Fragmin. Each group of eight patients received either 2,500 or 5,000 XaI U 2 h before operation or 5,000 XaI U 10 h before surgery. For comparison an additional eight patients received 5,000 IU unfragmented heparin (UH) before operation. Laboratory analyses included amidolytically measured XaI- and IIaI-activities and direct measurements of heparin. Dose-dependent increase in the XaI- and IIaI-activity with maximal levels about 3-4 h after injection was seen. Patients given the LMWH 2 h before operation had lower levels of XaI-activity 2 h after injection than those receiving it 10 h before surgery, despite the same dose given. This correlated with the heparin concentrations, where the highest concentration was measured in patients given the LMWH 10 h before surgery. In conclusion, the surgical trauma of a cholecystectomy does not seem to have any major influence on the XaI- or IIaI-activity after administration of the studied LMWH. Alterations of the absorption and/or elimination rates cannot, however, be ruled out, but are related to factors other than the operative trauma per se, such as effects of premedication or circadian rhythmic variations.

Adult↗
PubMed1989

Antithrombotic effects of heparin oligosaccharides.

Size homogeneous heparin oligosaccharides were prepared from nitrous acid depolymerized heparin by means of repeated gel filtration chromatography. These oligosaccharides were then further separated with respect to affinity for antithrombin by means of affinity chromatography. All the high-affinity oligosaccharides thus obtained had a strong ability to potentiate factor Xa inhibition while their ability to inhibit factor IIa abruptly dropped below a chain length of 20 monosaccharides. In a rabbit stasis model, high-affinity oligosaccharides below a chain length of 20 units also showed a continuous decrease in antithrombotic effect with increasing degree of depolymerization. However, there was no distinct drop paralleling the thrombin inhibiting capacity. Low-affinity oligosaccharides also exhibited a weak antithrombotic effect, although they did not always contribute to an increased anti-factor Xa activity ex vivo. This was the case whether or not they were administered alone or in combination with high-affinity oligosaccharides. Low-affinity oligosaccharides may therefore exert an antithrombotic effect per se with a mechanism of action that is independent of antithrombin III.

Animals↗
PubMed1986

Heparin and its low molecular weight derivatives: anticoagulant and antithrombotic properties.

The anticoagulant and antithrombotic effect of heparin has been known for many decades. Nevertheless, the knowledge of structure-activity relationships and its mechanisms of action has been rather limited. However, in recent years important progress has been made and our understanding of how heparin works has increased significantly. Based on this information, attempts have been made to modify heparin to get improved pharmacological properties. The present communication summarizes the recent development. It is shown that certain heparin derivatives of low molecular weight are highly interesting compounds from a clinical point of view. Biochemical and pharmacological properties of such a preparation named Fragmin are presented.

Blood Coagulation↗
PubMed1982

Expression of the structural proteins of Semliki Forest virus from cloned cDNA microinjected into the nucleus of baby hamster kidney cells.

The three structural proteins of Semliki Forest virus--i.e., the capsid, p62, and E1 proteins--were expressed in baby hamster kidney cells from cloned DNA transcribed from the virus-specific 4.1-kilobase mRNA. The cDNA was engineered into an expression vector developed by others [Mulligan, R. C. & Berg, P. (1980) Science 209, 1422--1427] downstream from the simian virus 40 early promoter and was introduced into cell nuclei by microneedle injection. Immunofluorescence analysis of injected cells showed that the capsid protein was located in the cell cytoplasm, whereas the membrane proteins were associated with cellular membranes. The p62 protein was shown to be transported from the rough endoplasmic reticulum to the plasma membrane, whereas the E1 protein remained in the rough endoplasmic reticulum.

Animals↗