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J Jespersen

Publications and source records attributed to J Jespersen.

At least 73 records · Page 4Linked to original sources
PubMed1997

A simplified statistical method for local INR using linear regression. European Concerted Action on Anticoagulation.

A simplified method of International Normalized Ratio (INR) derivation using linear regression of certified INR plotted against local prothrombin time (PT) results has been compared with INR from conventional orthogonal regression. Linear regression assumes error only with the local PT results whereas orthogonal regression assumes error with both reference and local results. The reliability of local INR derivation using lyophilized plasmas has been assessed in a collaborative study. INR from conventional fresh plasma International Sensitivity Index (ISI) calibrations have been compared with INR from calibrations with two types of lyophilized plasma, artificially depleted and coumarin. Although calibration slopes differed with the two types of analysis and the different lyophilized plasmas, both gave reasonable approximations to fresh plasma ISI calibrations. With orthogonal regression the overall percentage INR deviation was 5.25% with the artificially depleted plasmas and 6.85% for the results with lyophilized coumarins. With the linear regression, deviation was 8.40% for the artificially depleted plasmas and 5.05% for coumarin-treated patients' lyophilised-plasma. The simpler regression method appears to be worthy of further study as the present report has demonstrated that if the calibrant plasmas are accurately certified with the thromboplastin International Reference Plasma (IRP) results approximate to the conventionally determined INR using the manual PT technique. Coagulometers require further assessment.

Blood Coagulation Tests↗
PubMed1997

Lack of correlation between blood fibrinolysis and the immediate or post-operative blood loss in transurethral resection of the prostate.

OBJECTIVE: To evaluate whether the activation of the extrinsic tissue-type plasminogen activator-related fibrinolysis is implicated in the blood loss in patients with benign prostatic hyperplasia, undergoing transurethral prostatic resection (TURP). PATIENTS AND METHODS: TURP was performed in 24 men and the operative and post-operative blood loss determined. The activation of the tissue-type plasminogen activator-related fibrinolysis was followed using new sensitive and specific assays, and the changes related to the blood loss. Measurements of the plasma concentrations of free tissue-type plasminogen activator (t-PA) activity, tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) activity, plasminogen activator inhibitor 1 (PAI-1) antigen, plasminogen (Plg) activity, plasminogen (Plg) antigen, alpha 2-antiplasmin (alpha 2-AP), D-dimer and fibrin degradation products (FbDP) were all determined and the area under the curve (AUC) for each of these quantities correlated with the blood loss. RESULTS: TURP was followed by a marked activation of the fibrinolytic system. There was an immediate increase in systemic t-PA activity and t-PA antigen, coinciding with a significant drop in PAI activity. Post-operatively, PAI activity and PAI-1 antigen increased. The formation of plasmin was indicated by a fall in the plasma concentration of Plg activity and Plg-antigen and alpha 2-AP but which increased significantly at the end of the study period. Increased systemic fibrinolytic activity was further confirmed by a marked increase in fibrin D-dimer and FbDP. There was no correlation between the AUC in the operative period of any of the fibrinolytic variables and the measured blood loss. In the post-operative period, t-PA antigen (P = 0.004), PAI activity (P = 0.043), PAI-1 antigen (P = 0.016) and alpha 2-AP (P = 0.047) all correlated with the post-operative blood loss, while there was no correlation between fibrin D-dimer or FbDP and blood loss. CONCLUSION: The fibrinolytic system is activated during and after TURP, but the increased activity is not of pathophysiological importance for the blood loss.

Aged↗
PubMed1997

Post-operative blood loss after transurethral prostatectomy is dependent on in situ fibrinolysis.

OBJECTIVE: To evaluate whether post-operative blood loss in patients with benign prostatic hyperplasia, undergoing transurethral resection of the prostate (TURP), depends on in situ fibrinolysis in urine, and to determine the relative contributions of the urokinase and tissue-type plasminogen activator systems. PATIENTS AND METHODS: TURP was performed in 24 men (median age 68.5 years, range 52-78) and the weight of resected tissue, the operative and post-operative blood loss determined. The concentrations of the urokinase- (u-PA) and tissue-type plasminogen activator (t-PA)-related fibrinolysis in their urine was followed using sensitive and specific assays, and the changes related to post-operative blood loss. Measurements of the urinary concentrations of free t-PA activity, t-PA antigen, free u-PA activity, u-PA antigen and fibrin degradation products (FbDP) were determined and the area under the curve for each of these quantities correlated with the post-operative blood loss. RESULTS: The post-operative blood loss correlated significantly with the per-operative loss (P = 0.047) and the weight of resected tissue (P = 0.029). There was a highly significant correlation between the area under the curve of FbDP in the urine and the post-operative blood loss (P < 0.005), while there was no significant positive correlation between the PA concentration or activity in the urine and post-operative blood loss. There was a significant correlation between the urinary t-PA activity and the amount of FbDP in the urine (P = 0.047), and a significant correlation between the weight of resected tissue and the amount of FbDP in the urine (P = 0.014). CONCLUSION: The post-operative blood loss after TURP is significantly related to an increase of the urinary fibrinolytic activity and the enhanced fibrinolytic activity is probably caused by t-PA.

Aged↗
PubMed1997

Does long-term angiotensin converting enzyme inhibition affect the concentration of tissue-type plasminogen activator-plasminogen activator inhibitor-1 in the blood of patients with a previous myocardial infarction.

BACKGROUND: Large-scale studies have indicated that treatment with angiotensin converting enzyme (ACE) inhibitors reduces the incidence of myocardial infarction and unstable angina pectoris among patients with recent myocardial infarction and moderate left ventricular dysfunction. An improved endogenous fibrinolysis might be responsible for this effect. OBJECTIVES: To investigate the effect of trandolapril on the endogenous tissue-type plasminogen activator (t-PA) in patients with a recent myocardial infarction and moderate left ventricular dysfunction. METHODS: Fifty-six patients with acute myocardial infarction and a wall motion index < or = 1.2 were allocated randomly either to administration of trandolapril or to placebo. When possible, the study drug dose was increased gradually to 4 mg trandolapril or a corresponding amount of placebo during the first month after randomization. Blood samples for determination of the variables of the fibrinolytic system, ACE activity and ACE genotype were collected prior to randomization and during out-patient visits in months 1, 3, 6, 9 and 12. After the subject had fasted overnight, blood samples were collected in the morning (0800-1000 h) after the subject had rested supine for at least 15 min, from a venous cannula inserted into the forearm. The effect of trandolapril on the fibrinolytic variables was evaluated by calculating the area under the curve (AUC1-12) from month 1 to month 12. RESULTS: The trandolapril group and the placebo group were similar with respect to baseline clinical characteristics, baseline fibrinolytic variables and baseline plasma ACE activity. The trandolapril group did not differ significantly from the placebo group with respect to AUC1-12 t-PA antigen [11.67 (3.95-26.45) versus 10.34 ng/ml (3.71-19.62), P = 0.19] and AUC1-12 plasminogen activator inhibitor type-1 (PAI-1) antigen [27.57 (8.38-89.49) versus 24.40 ng/ml (7.94-90.62), P = 0.92]. A significant and clear trend in variation with time of t-PA antigen was observed for the trandolapril group, but not for the placebo group. The fibrinolytic variables were similar at baseline for the different ACE genotype insertion (I) and deletion (D) groups (II, ID and DD). Trandolapril treatment was associated with a significant (P < 0.04) increase in the AUC1-12 of t-PA antigen in the ID group compared with that of the placebo-treated ID group, whereas PAI-1 antigen concentration did not differ between the groups. Trandolapril treatment was not associated with any significant change in the fibrinolytic variables for the other genotype groups. CONCLUSIONS: Chronic ACE-inhibitor treatment with trandolapril was not associated with any significant difference in the blood concentrations of t-PA and PAI-1 compared with placebo. The suggested specific interaction between ACE inhibition and the increase in t-PA in patients with ACE genotype ID will require further confirmation.

Aged↗
PubMed1997

Plasma resistance to activated protein C regulates the activation of coagulation induced by thrombolysis in patients with ischaemic heart disease.

OBJECTIVE: To determine whether there was a relation between plasma resistance to activated protein C and the coagulation activation induced during thrombolysis with 100 mg alteplase in 25 patients with acute ischaemic heart disease. METHODS: Blood samples were collected before (t = 0 h), during (t = 2.25 h), and after (t = 4 h, t = 12 h, and t = 24 h) thrombolysis to examine the relation between baseline activated protein C resistance ratio and markers of coagulation activation-that is, thrombinantithrombin III-complexes and prothrombin fragment 1 + 2 generated during thrombolysis. RESULTS: There was a negative correlation between activated protein C resistance ratio and area under the curve of thrombin-antithrombin III-complexes (rs = - 0.60; P < 0.003) and there was a trend to a negative correlation between activated protein C resistance ratio and area under the curve of prothrombin fragment 1 + 2 (rs = - 0.37; P = 0.07). This accorded with the negative correlation between activated protein C resistance ratio and the peak value of thrombin-antithrombin III-complexes (rs = - 0.55; P < 0.005) and between activated protein C resistance ratio and the peak value of prothrombin fragment 1 + 2 (rs = - 0.42; P < 0.04). Components of the protein C/S system or known inhibitors of activated protein C may influence the activated protein C resistance ratio. There were no associations between the activated protein C resistance ratio and protein C, protein C inhibitor, or plasminogen activator inhibitor type-1, whereas there was a trend to a negative correlation between activated protein C resistance ratio and protein S. CONCLUSIONS: The results indicate that plasma resistance to activated protein C may be one of the main mechanisms regulating the activation of coagulation induced by thrombolysis. This study suggests that it may be possible to single out individuals with a high risk of reocclusion before the start of thrombolytic therapy.

Aged↗
PubMed1997

Factor VII polymorphisms in populations with different risks of cardiovascular disease.

Increased plasma factor VII coagulant activity (FVII:C) has been associated with the risk of ischemic heart disease (IHD). Differences in plasma FVII:C among individuals are associated with three common polymorphisms in the FVII gene. Therefore, we investigated FVII polymorphisms in four populations that differ in their risk of developing cardiovascular disease, namely, Europeans, Greenland Inuit, Gujarati Indians, and Afrocaribbeans. We studied (1) the promoter polymorphism, which is the result of a decanucleotide insertion in the FVII promoter at position -323 from the start of translation; (2) the hypervariable region 4 polymorphism (HVR4), which is the result of a variable number of tandem repeats in intron 7; and (3) the RQ353 polymorphism, a guanine-to-adenine substitution in the position of the codon for amino acid 353 resulting in an amino acid replacement of arginine (R) by glutamine (Q) in the FVII protein. The frequencies of these three polymorphisms and their linkage disequilibrium were different in the four populations studied. The frequencies of the alleles associated with higher plasma FVII:C were lower in the Europeans than in the Inuit, a population with a lower incidence of IHD. There was an association between both the promoter polymorphism and the RQ353 polymorphism and the plasma FVII:C in the Europeans, the Inuit, and the Gujarati Indians, and an association only between the RQ353 polymorphism and plasma FVII:C in the Afrocaribbeans. Only in the Inuit was the HVR4 polymorphism associated with plasma FVII:C. In multiple regression analysis, the additional information provided by the promoter polymorphism when the other polymorphisms were already included in the model was the most pronounced, suggesting that the promoter polymorphism may be the functional mutation having the greatest effect on determining plasma FVII:C.

Adult↗
PubMed1997

Effects of dietary fat quality and quantity on postprandial activation of blood coagulation factor VII.

Acute elevation of the coagulant activity of blood coagulation factor VII (FVIIc) is observed after consumption of high-fat meals. This elevation is caused by an increase in the concentration of activated FVII (FVIIa). In a randomized crossover study, we investigated whether saturated, monounsaturated, or polyunsaturated fats differed regarding postprandial activation of FVII. Eighteen healthy young men participated in the study. On 6 separate days each participant consumed two meals (times, 0 and 1 3/4 hours) enriched with 70 g (15 and 55 g) of either rapeseed oil, olive oil, sunflower oil, palm oil, or butter (42% of energy from fat) or isoenergetic low-fat meals (6% of energy from fat). Fasting and series of nonfasting blood samples (the last at time 8 1/2 hours) were collected. Plasma triglycerides, FVIIc, FVIIa, and free fatty acids were analyzed. There were marked effects of the fat quantity on postprandial responses of plasma triglycerides, FVII, and free fatty acids. The high-fat meals caused, in contrast to the low-fat meals, considerable increases in plasma triglycerides. Plasma levels of FVIIc and FVIIa peaks were 7% and 60% higher after consumption of high-fat meals than after consumption of low-fat meals. The five different fat qualities caused similar postprandial increases in plasma triglycerides, FVIIc, and FVIIa. These findings indicate that high-fat meals may be prothrombotic, irrespective of their fatty acid composition. The postprandial FVII activation was not associated with the plasma triglyceride or free fatty acid responses.

Adult↗
PubMed1997

Dietary fish oil (4 g daily) and cardiovascular risk markers in healthy men.

Some epidemiological observations indicate that 1 to 2 weekly servings of fish prevent ischemic heart disease (IHD). This might be explained by an effect of the very-long-chain n-3 polyunsaturated fatty acids (n-3 VLCPUFA) of fish oil on lipid metabolism and/or the hemostatic system, both involved in IHD development. We studied the effect of incorporating natural fish oil (4 g daily equivalent to 0.91 g n-3 VLCPUFA and corresponding to one to two weekly servings of fatty fish) into the diet in a 4-week parallel, randomized, and double-blind trial of 47 healthy males aged 29 to 60 years. Sunflower oil was used as placebo. The fish oil had no significant effect on plasma lipids, apolipoproteins, lipoprotein(a), blood coagulation FVII, fibrinogen, endogenous fibrinolysis, beta-thromboglobulin, von Willebrand factor, glucose, or insulin in fasting blood samples. In nonfasting samples (n = 19), fish oil was associated with an approximately 30% decline in plasma triglycerides (P < .02) and a 9% decline in FVII protein (P < .05), whereas FVII coagulant activity and fibrinolysis were unaffected. In conclusion, our findings indicate that lowering of postprandial triglycerides is the only n-3 VLCPUFA effect that could contribute to primary prevention of IHD in healthy middle-aged men as assessed by currently measurable lipid and hemostatic risk markers.

Adult↗
PubMed1997

No effect of unfractioned or low molecular weight heparin treatment on markers of vascular wall and hemostatic function in incipient diabetic nephropathy.

OBJECTIVE: The high risk for cardiovascular disease in IDDM patients with nephropathy may be mediated by abnormal function of the vascular wall. We investigated whether heparin was able to modulate markers of vascular wall and hemostatic function in patients with incipient nephropathy. RESEARCH DESIGN AND METHODS: Thirty-five IDDM patients with incipient nephropathy were randomized to treatment with placebo, unfractioned heparin, or low molecular weight heparin in a double-blind trial. The treatment was given as 1 h of conventional intravenous high-dose treatment and in a conventional subcutaneous low-dose regime for 3 months. Transcapillary escape rate of albumin and plasma levels of von Willebrand factor, fibrinogen, prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, tissue type plasminogen activator, tissue plasminogen activator inhibitor type 1, total cholesterol, HDL cholesterol, and triglycerides were measured before and after treatment. Of the patients, 31 completed the study. RESULTS: We found no significant effect of heparin on markers of vascular wall and hemostatic function by any of the treatments. CONCLUSIONS: Treatment with high- or low-dose heparin induced no modulation of markers of vascular wall or hemostatic function in IDDM patients with incipient diabetic nephropathy.

Adult↗
PubMed1997

Anticoagulant properties of rabbit lungs in tissue thromboplastin-induced intravascular coagulation.

This study was conducted in order to examine possible anticoagulant properties of the lungs during tissue thromboplastin-induced intravascular coagulation. Rabbit brain tissue thromboplastin (n = 17) or saline (n = 6 + 3) was infused above the right atrium (n = 11 + 3) of the heart or in the arcus aorta (n = 6) for a period of 120 min in non-pregnant New Zealand rabbits. Rabbits infused with tissue thromboplastin responded with significantly (p < 0.05) more excessive changes in a number of haemodynamic variables (heart rate, PaO2,PaCO2, blood pH etc.) compared with rabbits infused with saline. Similarly, the prothrombin time (p < 0.05) and the activated partial thromboplastin time (p < 0.05) were significantly more prolonged in rabbits receiving tissue thromboplastin compared with control animals. Also the concentration of blood platelets (p < 0.05), plasma fibrinogen (p < 0.05), antithrombin (p < 0.05), and protein C (p < 0.05) decreased significantly in thromboplastin-treated animals compared with control animals. In all these haemostatic variables there was a common trend that animals infused with tissue thromboplastin in the arcus aorta responded more excessively than animals infused in the right atrium of the heart, and these deviations were statistically significant for fibrinogen (p < 0.05) and prothrombin time (p < 0.05). Similarly, animals infused with tissue thromboplastin in the arcus aorta had an increased number of microthrombi in the lungs and kidneys compared with animals receiving tissue thromboplastin above the right atrium. As the lungs are the first pass organ when you infuse above the right atrium the results from this study suggest that the lungs play a key role in protecting the organism against excessive tissue thromboplastin-induced activation of coagulation.

Animals↗
PubMed1997

Plasminogen activators in human nasal polyps and mucosa.

Fibrinolysis is one of the processes that are involved in inflammation. In this study we have investigated if it is also involved in bilateral nasal polyposis, a disease with an inflammatory component. Fibrinolytic activity in the nasal mucosa and nasal polyps has been studied in 10 patients with bilateral nasal polyposis. Tissue-type plasminogen activator (t-PA) and urokinase-like plasminogen activator (u-PA) activities and antigen levels have been determined in polyp tissue and control nasal mucosa. t-PA activity is higher in nasal mucosa (median: 4.26 i.u./mg) as compared with nasal polyps (median: 0.65 i.u./mg; p = 0.03); u-PA activity is slightly lower in nasal mucosa (median: 0.040 i.u./mg) as compared to polyps (median: 0.065 i.u./mg; not significant). The percentage of u-PA to t-PA is 7.9% in nasal mucosa and 22.8% in nasal polyps (p < 0.01). The shift towards a higher u-PA/t-PA ratio in nasal polyps suggests an inflammatory process. Plasma levels of C-reactive protein are all within normal limits, which may suggest that PA activity is restricted to a local inflammatory reaction in the airway mucosa. The higher u-PA/t-PA ratio in nasal polyps and the higher levels of u-PA, when compared with the findings in other organs affected by inflammation, indicate that u-PA plays a part in the inflammatory events resulting in nasal polyps.

Adult↗
PubMed1996

Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities.

BACKGROUND: Disturbances of the fibrinolytic system that lead to decreased removal of fibrin deposits may be important risk factors for coronary thrombosis. There is as yet no consensus on the prognostic value of fibrinolytic parameters, which may be attributed in part to the choice of confounding variables controlled for. METHODS AND RESULTS: The ECAT study is a prospective multicenter study of 3043 patients with angina pectoris followed for 2 years. Baseline measurements included 10 fibrinolytic variables. The results were analyzed in relation to the subsequent incidence of myocardial infarction or sudden coronary death. They are presented before and after adjustment for clusters of confounding variables that are markers of different mechanisms: insulin resistance (body mass index, triglyceride, and HDL cholesterol), inflammation (fibrinogen and C-reactive protein), and endothelial cell damage (von Willebrand factor). An increased incidence of events was associated with higher baseline concentrations of tissue plasminogen activator (TPA) antigen (P = .0002), plasminogen activator inhibitor-1 (PAI-1) activity (P = .02), and PAI-1 antigen (P = .001). The associations of PAI-1 activity and PAI-1 antigen with risk of events disappeared after adjustment for parameters reflecting insulin resistance but were not affected by other adjustments. TPA antigen was affected to a similar extent by adjustment for parameters reflecting insulin resistance. Inflammation, or endothelial cell damage, but the risk association disappeared only after combined adjustments. CONCLUSIONS: The prognostic role of PAI-1 in predicting coronary events is related principally to insulin resistance, whereas that of TPA antigen could be explained only by its relationship with different mechanisms, including insulin resistance, inflammation and endothelial cell damage.

Adult↗
PubMed1996

Elevated fibrinogen and the relation to acute phase response in diabetic nephropathy.

Insulin-dependent diabetic patients with nephropathy have a high risk of cardiovascular disease. Chronic inflammation is a part of the pathogenesis of atherosclerosis, and presently we have studied the relation between the inflammatory state, measured as levels of interleukin-6 and C-reactive protein and fibrinogen in diabetic nephropathy. Thirty-three insulin-dependent diabetic patients with diabetic nephropathy (urinary albumin excretion rate (AER) > 300 mg/24-h) and 22 patients with incipient diabetic nephropathy (AER 30-300 mg/24-h) were compared with 14 non-diabetic controls and 17 diabetic patients with normal AER (<30 mg/24-h). Fibrinogen was significantly higher in diabetic nephropathy than in non-diabetic controls and diabetic patients with normal AER (median 8.1, range (5.4-15.6) mu mol/l vs. 6.6 (5.0-12.1) mu mol/l, p < 0.05, and 6.2 (5.0-9.0) mu mol/l, p < 0.005, respectively), while C-reactive protein did not deviate between groups. Interleukin-6 was significantly elevated in all insulin-dependent diabetic patients (diabetic nephropathy (3.2 (1.0-14.5) pg/ml, p < 0.005), incipient nephropathy (3.7 (1.0-22.9) pg/ml, p < 0.005) and diabetic patients with normal AER (2.7 (1.0-9.0) pg/ml, p < 0.05) compared with nondiabetic controls (1.2 (1.0-6.2) pg/ml)). When fibrinogen was adjusted for interleukin-6, C-reactive protein or both, the level of fibrinogen was still higher in patients with diabetic nephropathy than in patients without nephropathy (p < 0.05), which suggests that inflammation is not the only mechanism that increases fibrinogen levels in patients with diabetic nephropathy.

Acute-Phase Reaction↗
PubMed1996

No influence of proinsulin and insulin on plasma levels of plasminogen activator inhibitor type 1 and tissue plasminogen activator in young women before and during intake of contraceptive steroids.

Clinical observations in patients predisposed to cardiovascular disorders and recent experimental observations suggest that proinsulin and insulin participate in the regulation of fibrinolysis in vivo. In the present study, we examined if proinsulin and insulin affect the constitutive (fasting) secretion of plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) in young healthy women (N = 17). We also measured the antigen concentrations of PAI-1 and t-PA during slow and fast changes in proinsulin and insulin levels induced by oral (OGTT) and intravenous (IVGTT) glucose tolerance tests. The assessments were performed before and after 6 months of treatment with contraceptive steroids, which have a well-defined influence on the fibrinolytic variables. We observed no consistent correlations between fasting values of proinsulin, insulin, PAI-1, and t-PA either before or during hormonal treatment. Before hormonal treatment, PAI-1 and t-PA antigen levels decreased (P < .05) during the hyperproinsulinemia and hyperinsulinemia induced by the OGTT and IVGTT. After hormonal intake for 6 months, a decrease only in t-PA concentrations during the OGTT was observed despite similar proinsulin and insulin responses to the glucose loads. Our findings suggest that proinsulin and insulin have no influence on the regulation of plasma levels of PAI-1 and t-PA in young healthy women, irrespective of intake of contraceptive steroids.

Adult↗
PubMed1996

European Concerted Action on Anticoagulation (ECAA)-the multicentre calibration of rabbit and human ECAA reference thromboplastins. Steering Committee.

Two candidate ECAA reference preparations have been calibrated in a multicentre exercise at 14 representative national laboratories to provide reference thromboplastin for a large field study in 16 European countries. Two preparations were required because of the established differences in ISI arising from the two main routes of calibration via rabbit and human IRP. To be comparable with working reagents in everyday use a human plain recombinant reagent of low ISI and a rabbit plain preparation of moderately high ISI were selected. A precise calibration of the two candidate preparations has been achieved with the manual PT technique and an ISI of 0.95 (SE 0.0078) for the human reagent and 1.67 (SE 0.0322) for the rabbit reagent.

Animals↗