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Biomedical subjects

U Abildgaard

Publications and source records attributed to U Abildgaard.

At least 109 records · Page 6Linked to original sources
PubMed1989

[Treatment of iliofemoral venous thrombosis].

In a series of 41 patients with iliofemoral venous thrombosis, 23 were treated with heparin only. Five patients received ultra high dose streptokinase without any detectable thrombolysis. 11 patients were treated according to the conventional dose regimen for streptokinase. Three of these obtained complete thrombolysis, and two partial thrombolysis. Two patients were treated primarily with thrombectomy, whereas five patients were referred to thrombectomy after streptokinase had failed. Operation resulted in complete recanalization in four cases, and partial recanalization in two cases. We recommend the conventional dose regimen for streptokinase as first-line therapy for iliofemoral venous thrombosis. Thrombectomy should be considered if phlegmasia cerulea dolens is present, or when streptokinase is contraindicated. Thrombectomy can be carried out equally well after streptokinase failure, if major symptoms last less than a week.

Adult↗
PubMed1989

Heparin cofactor IIOslo. Mutation of Arg-189 to His decreases the affinity for dermatan sulfate.

Heparin and dermatan sulfate increase the rate of inhibition of thrombin by heparin cofactor II (HCII) approximately 1000-fold by providing a catalytic template to which both the inhibitor and the proteinase bind. A variant form of HCII that binds heparin but not dermatan sulfate has been described recently in two heterozygous individuals (Andersson, T.R., Larsen, M.L., and Abildgaard, U. (1987) Thromb. Res. 47, 243-248). We have now purified the variant HCII (designated HCIIOslo) from the plasma of ne of these individuals. HCIIOslo or normal HCII (11 nM) was incubated with thrombin (9 nM) for 1 min in the presence of heparin or dermatan sulfate. Fifty percent inhibition of thrombin occurred at 26 micrograms/ml dermatan sulfate with normal HCII and greater than 1600 micrograms/ml dermatan sulfate with HCIIOslo. In contrast, inhibition of thrombin occurred at a similar concentration of heparin (1.0-1.5 micrograms/ml) with both inhibitors. To identify the mutation in HCIIOslo, DNA fragments encoding the N-terminal 220 amino acid residues of HCII were amplified from leukocyte DNA by the Taq DNA polymerase chain reaction and both alleles were cloned. A point mutation (G----A) resulting in substitution of His for Arg-189 was found in one allele. The same mutation was constructed in the cDNA of native HCII by oligonucleotide-directed mutagenesis and expressed in Escherichia coli. The recombinant HCIIHis-189 reacted with thrombin in the presence of heparin but not dermatan sulfate, confirming that this mutation is responsible for the functional abnormality in HCIIOslo.

Amino Acid Sequence↗
PubMed1989

Efficacy of controlled-release isosorbide-5-mononitrate as adjunctive treatment to beta-blocking agents in patients with stable angina pectoris.

Twenty-four patients with severe stable angina pectoris were included in a randomized, double-blind, placebo-controlled, cross-over study to assess the efficacy of a controlled-release preparation of isosorbide-5-mononitrate (ISMN-CR) 60 mg once daily or twice daily as adjunctive treatment to a beta blocker. In bicycle ergometer exercise tests performed 4 h after study drug intake, total exercise time and time until 1-mm ST-depression increased significantly during both regimens as compared with placebo (p less than 0.05). However, only the 60-mg once-daily regimen was significantly better than placebo with regard to time until angina pectoris. The results indicate that ISMN-CR 60 mg once daily is effective as adjunctive to beta-blocker treatment, and nitrate tolerance appeared to develop during the twice-daily regimen. In 10 of the patients, the effect of additional sublingual nitroglycerin (NTG) was studied. Exercise time after NTG remained remarkably constant throughout all study periods. Exercise time was significantly prolonged after additional NTG and independent of the dose level of ISMN-CR. This indicates that cross-tolerance to NTG was not induced during sustained treatment with ISMN-CR.

Adrenergic beta-Antagonists↗
PubMed1989

Factor VII and extrinsic pathway inhibitor in acute coronary disease.

This report describes studies on the activation of coagulation factor VII (FVII) and the inhibition of the extrinsic coagulation pathway in acute ischaemic heart disease. FVII and the inhibitor of the tissue thromboplastin-FVII complex, called extrinsic pathway inhibitor (EPI), were determined in plasma from 68 patients and compared to findings in 37 normal individuals. The mean FVII amidolytic activity, the mean FVII clotting activity, as well as the FVII clotting/FVII amidolytic ratio were not significantly different in the patient groups as compared to the controls. The fraction of FVII clotting activity that is sensitive to phospholipase C, 'the FVII-phospholipid complex', was 8% in controls, 19% (P less than 0.05) in patients with acute myocardial infarction, 15% (n.s.) in angina pectoris and 13% (n.s.) in heart failure/arrhythmia patients. The 'FVII-phospholipid complex' was highly significantly correlated to triglycerides in plasma in patients with acute myocardial infarction (r = 0.88, P less than 0.001) and angina pectoris (r = 0.89, P less than 0.001). The mean EPI levels were significantly increased in patients with acute myocardial infarction (132%), angina pectoris (134%), and heart failure (150%) as compared to the control population (110%). The FVII clotting/EPI ratio was significantly decreased both in patients with acute myocardial infarction and heart failure, whereas the FVII amidolytic/EPI ratio was significantly decreased only in the heart failure group. Apparently, in patients with acute ischaemic heart disease, a moderate increase in the procoagulant activity is accompanied by a marked increase in the anticoagulant activity of the extrinsic coagulation pathway, suggesting a balanced activation system.

Acute Disease↗
PubMed1989

Extrinsic pathway inhibitor in postoperative/posttraumatic septicemia: increased levels in fatal cases.

The activity of the extrinsic pathway inhibitor (EPI), which is the factor-Xa-dependent inhibitor of the factor VIIa-tissue thromboplastin complex, was serially determined in 13 patients with postoperative/posttraumatic septicemia, and compared to the activity of antithrombin (AT), heparin cofactor II and protein C (PC). In the survivors (n = 8), initial low values for all the inhibitors normalized during recovery. In the demises (n = 5), a progressive increase in EPI activity was observed until death, whereas progressive decreases were observed for the other inhibitors. No correlation was found between the inhibitor values and the endotoxin concentration. We conclude that EPI activities are increased in the late course of fatal septicemia. Apparently, a large EPI-AT gap is a severe prognostic indicator in such patients.

Adolescent↗
PubMed1989

High plasma levels of extrinsic pathway inhibitor and low levels of other coagulation inhibitors in advanced cancer.

Serial determinations of plasma coagulation inhibitor levels were performed with chromogenic substrate activity assays in 7 patients with cancer. At time of diagnosis normal median activities of Antithrombin, Protein C, Heparin Cofactor II and Extrinsic Pathway Inhibitor were found. The inhibitor activities changed significantly with the progress of malignant disease; Antithrombin, Protein C and Heparin Cofactor II decreased whereas Extrinsic Pathway Inhibitor increased. Determinations in 13 additional patients in the terminal phase of cancer confirmed this finding. The inhibitor activities were expressed in per cent of a pooled reference plasma. In the total series of 20 patients studied, median activity of Extrinsic Pathway Inhibitor was 183% (range 61-378%) and significantly (p less than 0.005) above age-adjusted normal reference 10 days (range 1-20 days) prior to death. Median activities of Antithrombin was 59% (range 20-109%), of Protein C 54% (range 24-130%) and Heparin Cofactor II 59% (range 33-110%), all significantly below age adjusted normal reference (p less than 0.001). The coagulation inhibitor levels seem related to the stage of disease in patients with cancer.

Aged↗
PubMed1989

Fatalities in a stroke unit.

During the first 4 years of the CV unit the mortality rate among 464 patients was 5.2 per cent. The records of the 24 fatalities were reviewed. In the 10 patients submitted to autopsy the clinician's opinion of the cause of death was confirmed in 6 cases. In 4 cases autopsy revealed brain abscess, pulmonary embolism, acute myocardial infarction and pneumonia, respectively. Other significant findings not registered clinically were made in 4 cases. Twenty-three patients underwent a cerebral CT scan which showed positive findings in 19 cases. In one patient a brain abscess was misinterpreted as a brain infarction and in 2 other patients with a negative CT scan, autopsy revealed a small pontine and hemispheric infarction, respectively. Apart from the misdiagnosis of the brain abscess the accuracy of the CT scan was acceptable. Extracranial complications as a cause of or contributing to death in stroke patients are common. Prevention, early detection and treatment of these complications are important. The findings underscore the importance of autopsy in the evaluation of stroke patients.

Aged↗
PubMed1989

Hemodynamic and functional changes during renal venous stasis in dog kidneys.

The effect of renal venous pressure (RVP) elevation on renal hemodynamics and tubular function was studied in neurolept anaesthetized dogs. Renal blood flow (RBF) was measured electromagnetically. Clearance of 51Cr-EDTA was used as a measure of the rate of glomerular filtration (GFR). GFR, urinary excretion rates of sodium and water, and lithium clearance (CLi) were used for assessing the absolute and fractional reabsorption rates of sodium and water in the proximal as well as in more distal segments of the nephron. The vasoconstrictor response to RVP elevation was partly abolished by acute surgical denervation or by local application of lidocain on the renal capsule, suggesting that RVP elevation activates an adrenergic vasoconstrictor reflex comprising the spinal cord, and elicited from stretch receptors located in the renal capsule. Further studies in alpha-adrenoceptor blocked or chronic denervated kidneys and in decapsulated kidneys favour the view, that neurogenic and myogenic mechanisms significantly influence the vasoconstrictor response to RVP elevation: The neurogenic contribution to the vasoconstrictor response comprising intrarenal and extrarenal vasoconstrictor mechanisms evoked reflexly by RVP elevation; the myogenic contribution to the vasoconstrictor response comprising opposing vasodilator mechanisms due to increase in renal interstitial tissue pressure during RVP elevation. Studies carried out in intact kidneys, acutely surgically or chronically denervated kidneys or alpha-adrenoceptor blocked kidneys indicate that the increase in proximal reabsorption rates during moderate RVP elevation is due mainly to local intrarenal alpha-adrenergic reflex mechanisms, since the decrease in CLi (during constant filtered load) induced by RVP elevation was unaffected by acute surgical denervation, but completely abolished by chronic denervation of the kidney, or by local alpha-adrenoceptor blockade of the kidney.

Animals↗
PubMed1988

Antithrombin Oslo: type Ib classification of the first reported antithrombin-deficient family, with a review of hereditary antithrombin variants.

Patients with classical antithrombin deficiency (Type I) from seven unrelated kindreds were studied by crossed immunoelectrophoresis of plasma in the presence and absence of heparin. The only abnormal pattern was found in the kindred first reported by Egeberg in 1965. An abnormal cathodal peak of antithrombin antigen was found in the presence, but not the absence, of heparin in the first dimension gel. We have named this variant antithrombin Oslo. Such evidence of an abnormal protein, despite equivalent low levels of antithrombin antigen and activity, has been denoted previously by Sas as Type Ib deficiency. In the context of this new report, we review the literature to date on 33 other variants of the Types Ib, II and III subclassifications with a discussion of the value of the classification scheme.

Antithrombins↗
PubMed1988

Heparin induces release of extrinsic coagulation pathway inhibitor (EPI).

Extrinsic pathway inhibitor (EPI) is a potent inhibitor of the factor VIIa-tissue thromboplastin complex. The effect of heparin on EPI activity was studied using a chromogenic substrate assay. Addition of heparin to test plasma or whole blood in vitro increased EPI activity. This increase in EPI activity was reduced by the addition of polybrene and/or antibodies to antithrombin (anti-AT). Polybrene was therefore added to the assay system. However, part of this effect (up to 20% of baseline value) was not abolished. After intravenous injection, EPI activity increased dose-dependently. The increase was about 200% of baseline value after 7500 U heparin, and was not reduced by the addition of polybrene and/or anti-AT. A slower and prolonged increase in EPI activity occurred after subcutaneous injections of unfractionated heparin and low molecular weight heparin (LMWH). Venous occlusion failed to increase EPI activity levels. Normal EPI values were observed in patients with severe liver cirrhosis and during warfarin treatment. Gel filtration of human endothelial cell culture supernatant revealed one inhibitory fraction with molecular weight about 43.000. We conclude that EPI probably is produced in endothelial cells and may be released by heparin.

Antithrombins↗
PubMed1988

Renal tubular function in patients treated with high-dose cisplatin.

The effect of three cycles of high-dose cisplatin (40 mg/m2 day for 5 days) on renal tubular function was evaluated in 30 patients. A significant impairment of proximal tubular salt and water reabsorption rates was observed, but also distal tubular function seemed to be affected. These changes were also present 6 months after termination of treatment. Sodium and magnesium clearance increased significantly during treatment. Magnesium clearance normalized shortly after treatment but sodium clearance was significantly elevated 6 months after treatment. Proteinuria, albuminuria, and amino aciduria, together with an increase of beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) excretion rates, were observed during each treatment cycle. A good correlation was registered between the increase in urinary excretion rates of protein, NAG, and magnesium and the decrease in proximal tubular salt and water reabsorption during cisplatin administration.

Acetylglucosaminidase↗
PubMed1988

Effect of renal venous pressure elevation on tubular sodium and water reabsorption in the dog kidney.

This study was performed in order to quantify the effects of renal venous pressure (RVP) elevation on absolute and fractional reabsorption rates of sodium and water in proximal and distal segments of the nephron in dog kidneys. Renal blood flow (RBF) was measured electromagnetically. Clearance of [51Cr]EDTA was used as a measure of the rate of glomerular filtration (GFR). GFR, urinary excretion rates of sodium and water, and lithium clearance were used for assessing the absolute and fractional reabsorption rates of sodium and water in the proximal as well as in more distal segments of the nephron. In the kidneys with intact innervation RVP elevation to 19.9 +/- 0.1 mmHg caused significant increases in both absolute (APR) and fractional (FPR) proximal reabsorption rates from 33.4 +/- 4.2 to 38.7 +/- 2.0 ml min-1 and from 0.62 +/- 0.04 to 0.71 +/- 0.04, respectively. These responses were unaffected by acute surgical denervation of the kidneys. In contrast, chronic renal denervation or infusion of phentolamine (5 micrograms kg-1 min-1) into the renal artery eliminated the increase in APR and FPR during RVP elevation to 20 mmHg. Chronic, but not acute renal denervation depleted renal tissue content of adrenaline and noradrenaline. The results suggest that the increase in APR and FPR during RVP elevation is due mainly to local sympathetic reflex mechanisms.

Adrenergic alpha-Antagonists↗
PubMed1988

Intrarenal blood flow distribution in dog kidney determined by 99mTc microaggregates and 201Tl.

Intrarenal distribution of blood flow was assessed with radioactive albumin microaggregates (MA) in three cortical zones of the dog kidney. The experimentally obtained zonal fractions of total renal blood flow were compared with predicted zonal blood flow fractions obtained in a mathematical model. The maximal degree of skimming that could possibly occur in a single experiment was estimated. The analysis showed that local blood flow in the inner cortical zone was maximally underestimated by 17% because of skimming of MA, and in the outer cortical zone the blood flow was maximally overestimated by 13% with the method of radioactive MA uptake. Renal uptake of 201Tl was measured simultaneously in exactly the same locations. Paired measurements of intrarenal blood flow distribution by MA and Tl uptake methodologies showed that local blood flow assessed with MA in the inner cortical zone was significantly lower than that obtained with 201Tl and that a higher blood flow rate was obtained in the outer cortical zone with MA compared with 201Tl. This disparity could be accounted for by the effect of skimming of MA as predicted by the model.

Animals↗
PubMed1988

Comparison of low molecular weight heparin vs. unfractionated heparin in gynecological surgery.

In a double-blind, randomized trial, the antithrombotic effect and haemorrhagic complications of low molecular weight heparin (LMWH) (Heparin fragment 2165, KabiVitrum) and unfractionated heparin (UH) were compared. LMWH (5000 anti-XaU) was injected every 24 h, UH (5000 IU) every 12 h; both drugs by subcutaneous injection. During 1984-85, 215 patients were examined clinically and by plethysmography. Venography was performed whenever DVT was suspected. None of the patients proved to have DVT. Bleeding complications were found in 54% of the cases. The LMWH group had a statistically significant predominance of bleeding complications as reflected by wound haematomas (p = 0.02) and the number of blood transfusions (p = 0.02). The heparin concentration was higher in the LMWH group (mean 0.13 IU/ml) than in the UH group (mean 0.13 IU/ml) measured 2 h after the injection. In the doses administered, LMWH and UH seem effective in the prevention of thrombosis. The increased bleeding tendency in the LMWH group probably was a consequence of the to high dosage.

Adult↗
PubMed1988

The inhibitor of F VIIa in plasma measured with a sensitive chromogenic substrate assay: comparison with antithrombin, protein C and heparin cofactor II in a clinical material.

The plasma inhibitor(s) of factor VIIa-tissue thromboplastin cooperates with factor Xa. This "Extrinsic Pathway Inhibitor" has been quantitated with a sensitive chromogenic substrate assay. Gel filtration of plasma separates 3 EPI peaks. Postoperatively, both EPI and the other coagulation inhibitors decrease. Unlike the other inhibitors, EPI is usually normal in severe liver cirrhosis. In disseminated intravascular coagulation, EPI levels vary considerably.

Antithrombins↗
PubMed1987

A sensitive assay of extrinsic coagulation pathway inhibitor (EPI) in plasma and plasma fractions.

We have previously shown that addition of adsorbed plasma to a mixture of TP and FVII reduces the amount of subsequently added FX that can be activated. We now report that this inhibitory effect of plasma is increased dramatically by first incubating TP and FVII with a minor amount of FX. This results in a progressive loss in the ability of TP-FVIIa to convert subsequently added FX to FXa. An assay system quantitating the inhibitory effect of 1 microliter of heated, citrated plasma is described. Optimal inhibition is obtained when the initial amount of FX added is about 0.00125 U, which is 1/16 of the amount used as reagent to measure remaining TP-FVIIa. FVII and FX must be removed from test plasma prior to assay. The inhibitory activity is reduced more by BaSO4 adsorption than by heating plasma to 56 degrees C for 15 minutes. Gel filtration of plasma separates three distinct fractions with inhibitory activity.

Blood Coagulation↗