PubMed Health⌕ Search

Biomedical subjects

J Jespersen

Publications and source records attributed to J Jespersen.

At least 109 records · Page 6Linked to original sources
PubMed1994

[Plasmin-mediated activation of the coagulation system. A study of patients with acute ischemic heart disease treated with recombinant tissue-plasminogen activator].

We have studied the response of haemostatic reaction products in peripheral blood of patients with acute ischaemic heart disease receiving combined recombinant tissue type plasminogen activator/heparin therapy. We have found evidence that formation of excessive amounts of plasmin in vivo in relation to such therapy significantly enhances the degradation of fibrin, and of fibrinogen as well as the formation of thrombin. We conclude that excessive plasmin formation by thrombolytic therapy causes systemic effects including activation of coagulation.

Acute Disease↗
PubMed1994

[Hemostatic balance during treatment with the newest contraceptives].

Thirty-four healthy young women were allocated to 12 consecutive cycles of treatment with monophasic combinations of: 20 micrograms ethinyl estradiol and 150 micrograms desogestrel (n = 15) or 30 micrograms ethinyl estradiol and 75 micrograms gestodene (n = 19). In both groups plasma levels of fibrinogen and factor VII increased while the capacity of coagulation inhibition was affected by increased protein C and decreased protein S levels. Increased fibrinolytic capacity was indicated by elevated activity and reduced antigen levels of tissue plasminogen activator and reduced activity and concentration of tissue plasminogen activator inhibitor. The ratio between thrombin-antithrombin-III-complexes and fibrin degradation products were unchanged signifying no effect of hormonal intake on the balance between thrombin formation and fibrin resolution. In conclusion, the dynamic balance between generation and resolution of fibrin was undisturbed during treatment with both hormonal compounds and our findings do not provide evidence for increased risk of thrombosis in normal women.

Adult↗
PubMed1994

Assessment of endothelial function during oral contraception in women with insulin-dependent diabetes mellitus.

The effects of contraceptive steroids on the expression of endothelial homeostasis were examined by direct and indirect measures in women with insulin-dependent diabetes mellitus (IDDM) in a prospective nonrandomized controlled study. Study subjects were 13 women with uncomplicated IDDM treated with a monophasic combination of 30 micrograms ethinyl estradiol and 75 micrograms gestodene for 12 consecutive cycles and 13 women of comparable diabetic status as control. During the study period, none of the participants developed increased renal albumin excretion, which was used as a direct measure of endothelial function. In the indirect assessment of endothelial function, we found a proportionate increase in plasma levels of thrombin-antithrombin III (TAT) complexes and D-dimer during treatment. Hormonal intake was followed by decreased antigen concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (type 1 [PAI-1]), whereas the activities of t-PA and PAI-1 were unchanged. Plasma levels of plasminogen and histidine-rich glycoprotein (HRG) increased and decreased, respectively, whereas an increase in von Willebrand factor was observed in the treatment group. No significant changes in direct or indirect measures were observed in the control group during the observation period of 12 months. In conclusion, no adverse effect on endothelial function was demonstrated by direct measures, but our findings suggest that a procoagulant state, compensated by enhanced activity of the fibrinolytic system, is induced by hormonal treatment. Clinical and metabolic monitoring is recommended if the use of oral contraceptives in women with IDDM is extended.

Adult↗
PubMed1994

Effects of contraceptive steroids on cardiovascular risk factors in women with insulin-dependent diabetes mellitus.

OBJECTIVE: We evaluated established cardiovascular risk factors within lipoprotein metabolism, hemostasis, and endothelial function in women with insulin-dependent diabetes mellitus who were using oral contraceptives. STUDY DESIGN: Twenty-five women with uncomplicated insulin-dependent diabetes mellitus, allocated to treatment with a monophasic combination of 30 micrograms ethinyl estradiol and 75 micrograms gestodene (treatment group, n = 12) or with nonhormonal contraception (control group, n = 13), were prospectively followed up for 12 months. Nonparametric methods were used for statistical evaluation. RESULTS: No statistical differences in the biochemical risk markers were noted between the two groups at the start of the study. In the treatment group serum levels of low-density lipoprotein cholesterol decreased, whereas the concentrations of total cholesterol, high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglycerides were unchanged. Within the coagulation system factor VII coagulant activity increased, while fibrinogen levels were unchanged. In the fibrinolytic system we found unchanged activities but decreased antigen concentrations of tissue plasminogen activator and plasminogen activator inhibitor. The concentration of von Willebrand factor increased, but no change in albumin excretion rates were found. In the control group no changes in any of the variables were observed. CONCLUSION: Intake of modern oral contraceptives does not deteriorate the cardiovascular risk profile in women with insulin-dependent diabetes mellitus, but our study indicates a risk of disturbances of the endothelial integrity, which needs further investigation.

Adult↗
PubMed1994

Fat high in stearic acid favorably affects blood lipids and factor VII coagulant activity in comparison with fats high in palmitic acid or high in myristic and lauric acids.

The effect of fats high in individual, prevalent saturated dietary fatty acids on lipoproteins and hemostatic variables in young healthy subjects was evaluated in a randomized strictly controlled metabolic feeding study. Three experimental diets: shea butter (S; 42% stearic acid), palm oil (P; 43% palmitic palmitic acid), and palm-kernel oil with high-oleic sunflower oil (ML; 10% myristic acid, 30% lauric acid) were served to 15 men for 3 wk each, separated by washout periods. Diet S compared with diet P resulted in significant reduction in plasma cholesterol (22%) LDL cholesterol (26%), apolipoprotein B (18%), HDL cholesterol (12%), apolipoprotein A-I (13%), and a 13% lower factor VII coagulant activity (P = 0.001). Similar differences were observed between diets S and ML. In conclusion, intake of shea butter high in stearic acid favorably affects blood lipids and factor VII coagulant activity in young men, compared with fats high in saturated fatty acids with 12-16 carbons.

Adult↗
PubMed1994

Low-fat, high-fiber diet favorably affects several independent risk markers of ischemic heart disease: observations on blood lipids, coagulation, and fibrinolysis from a trial of middle-aged Danes.

We served a low-fat (28% of energy), high-fiber (3.3 g/MJ) diet according to Nordic nutrition recommendations (Rec diet), and a high-fat diet (39% of energy) corresponding to the average Danish diet (Dane diet) for periods of 2 wk in a randomized crossover study of 21 healthy middle-aged individuals. The Rec diet resulted in lower serum concentrations of low-density-lipoprotein (LDL) cholesterol (medians: 2.77 vs 3.04 mmol/L, P < 0.001) and high-density-lipoprotein (HDL) cholesterol (1.08 vs 1.24 mmol/L, P < 0.001), and higher fasting triglycerides (1.11 vs 0.86 mmol/L, P = 0.04) than did the Dane diet. Furthermore, the Rec diet lowered plasma factor VII coagulant activity (FVIIc) (88% vs 96%, P = 0.002) and raised plasma fibrinolytic activity. Our observations indicate that a low-fat, high-fiber diet may not only reduce the atherogenic but also the thrombogenic tendency of an individual compared with a diet corresponding to the average Danish diet.

Blood Coagulation↗
PubMed1994

Effect on blood lipids, coagulation, and fibrinolysis of a fat high in myristic acid and a fat high in palmitic acid.

The hypothesis that myristic acid (C14:0) has a stronger cholesterol-increasing potential than does palmitic acid is based on very few experimental observations. A randomized, strictly controlled dietary study was therefore designed to investigate the effect of a synthetic fat that was high in myristic acid, and palm oil, which is high in palmitic acid, on lipoproteins and hemostatic variables. Twelve men were served two diets (40% of energy as fat) with 41% of fat as myristic (diet M) or palmitic acid (diet P) for 3 wk with 1 mo between the two dietary schedules. Plasma HDL cholesterol was 8% higher with diet M than with diet P: 1.10 +/- 0.06 (mean +/- SEM) vs 1.01 +/- 0.05 mmol/L (P < 0.006). Diet M raised factor VII coagulant (F VIIc) activity to 98% (77-117%) vs 96% (71-109%) (medians and ranges) after diet P (P = 0.02). Total and LDL-cholesterol concentrations did not differ between the diets. In conclusion, the myristic acid test fat was not more cholesterolemic than was palm oil, but it did induce a minor rise in F VIIc activity.

Adult↗
PubMed1994

Regulation of tissue-type plasminogen activator-mediated fibrinolysis by plasminogen activator inhibitor type-1 in patients with ischaemic heart disease: possible unfavourable effect of diuretics.

BACKGROUND: Impaired endogenous tissue-type plasminogen activator (t-PA)-mediated fibrinolysis may be involved in the evolution of myocardial infarction. t-PA-mediated fibrinolysis is believed to depend on the amount of active t-PA present in the circulation. Accordingly, we investigated the possible mechanisms responsible for impaired t-PA-mediated fibrinolysis in patients with ischaemic heart disease. METHODS: Forty-five survivors of acute myocardial infarction were examined 8 weeks after discharge from hospital. Intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; 0.4 micrograms/kg bodyweight) was used to stimulate the endogenous fibrinolytic system, and blood samples were collected before and after infusion. We compared the response of the t-PA-plasminogen activator inhibitor type-1 (PAI-1) fibrinolytic system in patients with preinfusion levels of active t-PA below or at the detection limit of the assay with that in patients with higher preinfusion levels of active t-PA. RESULTS: All patients responded to DDAVP infusion with an increase in plasma concentration of t-PA antigen. This response did not differ between the two groups. In contrast, the preinfusion levels of PAI activity were significantly higher in patients with undetectable plasma levels of active t-PA compared with patients with higher levels of active t-PA (22.3 versus 12.8 IU/ml; P < 0.01). Subgroup analyses demonstrated that patients treated with diuretics had significantly higher plasma concentrations of PAI-1 antigen (28.5 versus 17.9 ng/ml; P < 0.03) and a trend towards higher PAI activity (24.0 versus 14.6 IU/ml; P = 0.07) compared with patients not receiving diuretics. CONCLUSION: Our study strongly suggests that a high plasma level of PAI-1, the main inhibitor of t-PA, is responsible for impaired t-PA-mediated fibrinolysis in patients with ischaemic heart disease, and that treatment with diuretics may be associated with an unfavourable effect on the fibrinolytic system.

Aged↗
PubMed1994

A new automated method for continuous registration of factor VII activation in vitro. Activation is accelerated by the concentration of factor VII and the activity state of the protein.

When a plasma sample is exposed to tissue factor, single-chain factor VII (FVII) is gradually converted to the active two-chain form (FVIIa). In the present study, we have constructed a measurement system, which allows continuous registration of the activation of FVII to FVIIa in vitro. In this system, FVII activation follows parabolic kinetic after an initial lag-phase. The slope of the linear phase is a measure of the protein concentration of factor VII (FVIItotal), while the length of the non-linear phase represents the velocity of FVII activation. The time required for complete activation of FVII is inversely related to both FVIItotal and the relative amount of FVIIa in the sample. In future studies, this new measurement system will make it possible to study the process of FVII activation in different samples, and to examine how varying concentrations of exogenous added components affect the activation process in vitro.

Amino Acid Sequence↗
PubMed1994

Non-fasting factor VII coagulant activity (FVII:C) increased by high-fat diet.

Preliminary observations have suggested that non-fasting factor VII coagulant activity (FVII:C) may be related to the dietary fat content. To confirm this, we performed a randomised cross-over study. Seventeen young volunteers were served 2 controlled isoenergetic diets differing in fat content (20% or 50% of energy). The 2 diets were served on 2 consecutive days. Blood samples were collected at 8.00 h, 16.30 h and 19.30 h, and analysed for triglycerides, FVII coagulant activity using human (FVII:C) or bovine thromboplastin (FVII:Bt), and FVII amidolytic activity (FVII:Am). The ratio FVII:Bt/FVII:Am (a measure of FVII activation) increased from fasting levels on both diets, but most markedly on the high-fat diet. In contrast, FVII:Am (a measure of FVII protein) tended to decrease from fasting levels on both diets. FVII:C rose from fasting levels on the high-fat diet, but not on the low-fat diet. The findings suggest that high-fat diets increase non-fasting FVII:C, and consequently may be associated with increased risk of thrombosis.

Adult↗
PubMed1993

Multicentre evaluation of commercial kit methods: plasminogen activator inhibitor activity.

In order to study the analytical performance of different commercial kits for determination of plasminogen activator inhibitor (PAI) activity we distributed eight selected split samples to 11 European laboratories experienced with haemostasis testing. Three different laboratories were involved in the production of data from each of the commercial kits tested. A considerable variation of PAI activity results reported from the laboratories testing the same commercial kits was observed. The range of reported results could in individual samples exceed the median value indicating an interlaboratory variation of more than 100%. When we harmonized the results reported from different kits in different laboratories by means of an international standard from National Institute for Biological Standards and Control (NIBSC) we still observed that the results produced by some kits deviated systematically from results produced by other kits. Also, the harmonized results were used to estimate the overall coefficient of variation (CV) of PAI activity determined in various laboratories by different kits. We observed an inverse correlation between the PAI activity level and the CV with a CV of about 100% for low PAI activity levels and a CV of about 16% for high PAI activity levels. The high imprecision of the kits in the low concentration range of PAI activity indicates that unspecific factors in plasma may interfere with determination of active PAI. This was confirmed by the evaluation of the results from one of the plasma samples, which was PAI-1 depleted. The laboratories involved in the testing reported for this sample a mean value of 6.1 IU/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Preservation↗
PubMed1993

Multicenter evaluation of commercially available methods for the immunological determination of plasminogen activator inhibitor-1 (PAI-1).

In order to evaluate the comparability of data obtained with various available kits for the immunological determination of PAI-1 antigen in plasma and in order to investigate the underlying cause of observed differences, e.g. problems of specificity or of proper calibration of the provided standard, a multicenter study was organised in the framework of the Subcommittee of Fibrinolysis of the Scientific and Standardization Committee. Eight different plasma samples were distributed among 16 laboratories: a pooled normal plasma, NIBSC 87/512, PAI-1 antigen depleted plasma, PAI-1 depleted plasma supplemented with 59 ng/ml active PAI-1 and four different individual plasma samples. A considerable variation in absolute values is observed between the various kits, e.g. in pooled normal plasma a value is found ranging between 7.4 and 28 ng/ml. Harmonization of all data relative to the PAI-1-depleted plasma supplemented with an exact amount of active PAI-1 (59 ng/ml), followed by a statistical analysis using a two way analysis of variance, revealed that 6 out of 7 kits yielded values that were not significantly different with coefficients of variation around 30%. Correlations between the values obtained with these kits yielded slopes between 0.75 and 1.44 with correlation coefficients between 0.973 and 0.999. Values obtained with one kit appeared to be significantly different (even after harmonization) from the other kits (p < 0.001 to p < 0.05). Comparison of PAI-1 antigen with the PAI activity values in the analysed samples suggests that one kit may deal with a problem of a difference in reactivity between active and latent PAI-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1993

Dietary effects on circadian fluctuation in human blood coagulation factor VII and fibrinolysis.

Six healthy male volunteers were served 4 strictly controlled isoenergetic diets differing in fat (20% or 50% of energy) and fiber contents (2 or 4 g/MJ) for periods of 2 days. The diets were served in random order with at least 5 days separating each diet period. Blood samples for determination of factor VII clotting activity using human (FVIIc) and bovine thromboplastin (FVIIbt), and for assessment of factor VII antigen (FVIIag), tissue-plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, PAI activity, t-PA and euglobulin fibrinolytic activity, and triglyceride and insulin levels were collected regularly on the second day of each diet period. The high-fat diets resulted in significantly increased postprandial FVIIbt levels (peak values: 131% vs. 95%, P < 0.01), and higher postprandial FVIIbt/FVIIag ratios (peak values: 1.42 vs. 1.16, P < 0.01) compared with the low-fat diets. Fibrinolytic variables were not affected by the dietary changes and consistently showed characteristic U-shaped (t-PA and PAI-1 antigen, PAI activity), or inverted U-shaped (t-PA and euglobulin fibrinolytic activity) circadian patterns with troughs and peaks, respectively, at 17:30-21:30 h. The dietary fiber content had no significant influence on any of the measured variables. Our findings indicate that high-fat diets may increase blood thrombogenicity by virtue of augmented postprandial activation of factor VII.

Adult↗
PubMed1993

Effects of monophasic low-dose oral contraceptives on fibrin formation and resolution in young women.

OBJECTIVE: The purpose of this study was to examine key variables in the regulation of coagulation and fibrinolysis during intake of low-dose oral contraceptives containing newly developed progestogens. STUDY DESIGN: Thirty-four healthy young women were allocated to 12 consecutive cycles of treatment with monophasic combinations of 20 micrograms ethinyl estradiol and 150 micrograms desogestrel (n = 15) or 30 micrograms ethinyl estradiol and 75 micrograms gestodene (n = 19). Nonparametric analysis of variance was used for statistical evaluation. RESULTS: In both groups plasma levels of fibrinogen and Factor VIIc increased, and the capacity of coagulation inhibition was affected by increased protein C and decreased protein S levels. Increased fibrinolytic capacity was indicated by elevated activity and reduced antigen levels of tissue plasminogen activator and by reduced activity and concentration of plasminogen activator inhibitor. Thrombin-antithrombin III complexes and fibrin degradation products were unchanged, signifying no effect of hormonal intake on the degree of activation of the coagulation system or the efficacy of fibrinolysis. CONCLUSION: The overall dynamic balance between generation and resolution of fibrin was maintained during treatment with both hormonal compounds. Our findings suggest that the risk of thrombosis in normal women should not be increased.

Adult↗
PubMed1993

Depression of factor XII-dependent fibrinolytic activity in survivors of acute myocardial infarction at risk of reinfarction.

Defective fibrinolysis may constitute a risk for the development of myocardial infarction in patients with ischaemic heart disease. We studied prospectively the factor XII-dependent plasminogen proactivator system in 49 survivors of an acute myocardial infarction. Blood samples were collected 8 weeks after hospital discharge. The factor XII-dependent fibrinolytic activity in the specimens was determined on fibrin plates after complete immuno-inhibition of the urokinase-like and the t-PA related fibrinolytic systems. During the subsequent follow-up period of 2.4 years, 10 patients developed recurrent myocardial infarction, whereas the remaining 39 patients did not. The reinfarction group of patients had a significantly lower median factor XII-dependent fibrinolytic activity (24.9 blood activating units (BAU).ml-1) than the patients without a relapse (41.9 BAU.ml-1, P < 0.02). Plasma concentrations of factor XII did not deviate significantly between the groups (P > 0.05), whereas the median plasma concentrations of prekallikrein was slightly lower in the reinfarction group (90%) than in the non-reinfarction group of patients (105%, P < 0.02). These observations point to an association between a depressed factor XII-dependent fibrinolytic activity and an enhanced risk of reinfarction in patients with a previous episode of acute myocardial infarction.

Cholesterol↗
PubMed1993

Reactive coagulation induced by plasmin in patients treated with recombinant tissue-type plasminogen activator.

BACKGROUND: We and others have demonstrated that administration of thrombolytic agents causes the generation of thrombosis-promoting agents. At present, we have studied whether formation in vivo of excessive amounts of plasmin is responsible for the activation of coagulation in patients treated with recombinant tissue-type plasminogen activator. METHODS: Modified crossed immunoelectrophoresis was used for determination of the plasminogen-binding form of alpha 2-antiplasmin. Enzyme-linked immunosorbent assay methods were used for determination of hemostatic reaction products. RESULTS: The association between the generation of hemostatic reaction products and the exhaustion of the plasminogen-binding form of alpha 2-antiplasmin (PB alpha 2AP) was studied in 21 patients with acute myocardial infarction and 11 patients with unstable angina pectoris who were given a 3-hour, 100-mg intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA). We observed in all patients a fall in blood concentrations of PB alpha 2AP (P < 0.01) after 2.25 hours of treatment and, simultaneously, a significant increase in fibrin degradation products (P < 0.01), D-dimer (P < 0.01), fibrinogen degradation products (P < 0.01), prothrombin fragment 1 + 2 (P < 0.01), and thrombin-antithrombin III complexes (P < 0.01). When we evaluated individual data, we observed high concentrations of the reaction products when the PB alpha 2AP concentration after 2.25 hours of treatment was lower than 25% of the pretreatment values. Also, we observed highly significant associations between the increase in the plasma concentrations of fibrin degradation products and thrombin-antithrombin III complexes (rs = 0.72; P < 0.01), the increase in plasma concentrations of fibrin degradation products and prothrombin fragment 1 + 2 (rs = 0.63; P < 0.01), the increase in plasma concentrations of D-dimer and thrombin-antithrombin III complexes (rs = 0.78; P < 0.01), and the increase in plasma concentrations of D-dimer and prothrombin fragment 1 + 2 (rs = 0.79; P < 0.01). CONCLUSIONS: Generation of excessive amounts of plasmin is the main factor in producing the procoagulant response in patients who receive thrombolytic therapy with rt-PA, and intravenous heparin does not abolish this response. Plasmin inhibitors might be used in relation to thrombolytic therapy as indirect "antithrombotics."

Aged↗