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J Jespersen

Publications and source records attributed to J Jespersen.

At least 145 records · Page 8Linked to original sources
PubMed1991

Chronobiology of coronary risk markers in Greenland Eskimos: a comparative study with Caucasians residing in the same Arctic area.

We report a comparison of fibrinolytic variables between 10 Caucasians on a predominantly European diet and 10 Greenland Eskimos on a traditional Inuit diet containing a substantial amount of fish and sea animals. We studied the diurnal variation in tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) antigens and activities during a 24-h period. Blood samples were taken every 4 h. The variations of the sinusoidal curves were evaluated by the Friedman chi 2 test. t-PA and PAI-1 antigen in plasma fluctuated significantly during the 24 h (Eskimos p less than 0.00007 and p less than 0.0007; Caucasians p less than 0.00003 and p less than 0.02), with a peak in the early morning and a nadir in the afternoon. This also held true for PAI activity (Eskimos p less than 0.0008; Caucasians p less than 0.01), whereas t-PA activity showed an inverse but still significant pattern (Eskimos p less than 0.006; Caucasians p less than 0.0008). Amplitudes, areas underneath, and overall medians of the sinusoidal curves did not deviate between the two groups with respect to t-PA and PAI. In contrast to the significant variation of t-PA and PAI, the plasma concentrations of fibrin degradation products (D-Dimer), a measure of effective fibrinolysis, remained constant during the 24 h, and the absolute differences between groups did not reach statistical significance. These findings suggest that circadian variation of fibrinolytic activators and inhibitors is a basic biologic phenomenon, which is not affected by life-style, dietary habits, or ethnic differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Interleukin-1 and tumor necrosis factor-alpha in plasma of patients with acute ischemic heart disease who undergo thrombolytic therapy: a randomized, placebo-controlled study.

In patients with acute ischemic heart disease who undergo thrombolytic therapy we have previously observed a marked endothelium-dependent activation of the coagulation system. Concomitantly the concentrations of the fast acting plasminogen activator inhibitor type 1 (PAI-1) in plasma increased. The results of recent in vitro studies would suggest that these in vivo phenomena could be associated with the procoagulant effects of the cytokines interleukin-1 (IL-1) and/or tumor necrosis factor-alpha (TNF). In the present placebo-controlled study on patients with acute ischemic heart disease treated with thrombolytic agents we observe low or undetectable concentrations, and insignificant deviations during the study periods, of IL-1 and TNF in plasma. We conclude that IL-1 and TNF play a minor role for generation of coagulant activity and systemic deviations of PAI-1 in patients who undergo coronary thrombolysis.

Acute Disease↗
PubMed1990

Enhanced effective fibrinolysis following the neutralization of heparin in open heart surgery increases the risk of post-surgical bleeding.

The tissue-type plasminogen activator related fibrinolytic system was studied in 24 patients undergoing cardiopulmonary bypass surgery. The degradation of fibrinogen and fibrin was followed during and after surgery by means of new sensitive and specific assays and the changes were related to the blood loss measured in the chest tube drain during the first 24 postoperative hours. Although tissue-type plasminogen activator was significantly released into the circulation during the period of extracorporeal circulation (p less than 0.01), constantly low levels of fibrinogen degradation products indicated that a systemic generation of plasmin could be controlled by the naturally occurring inhibitors. Following extracorporeal circulation heparin was neutralized by protamine chloride, and in relation to the subsequent generation of fibrin, there was a short period with increased concentrations of fibrinogen degradation products (p less than 0.01) and a prolonged period of degradation of cross-linked fibrin, as detected by increased concentrations of D-Dimer until 24 h after surgery (p less than 0.01). Patients with a higher than the median blood loss (520 ml) in the chest tube drain had a significantly higher increase of D-Dimer than patients with a lower than the median blood loss (p less than 0.05). We conclude that the incorporation of tissue-type plasminogen activator into fibrin and the in situ activation of plasminogen enhance local fibrinolysis, thereby increasing the risk of bleeding in patients undergoing open heart surgery.

Adult↗
PubMed1990

Effects of newer oral contraceptives on the inhibition of coagulation and fibrinolysis in relation to dosage and type of steroid.

Oral contraceptives influence plasma proteins, causing changes in plasma procoagulants and fibrinolytic effectors. Estrogen is thought to be responsible for these changes, whereas progestogens, in particular those with an androgenic effect, may influence the magnitude of the changes. This concept is consistent with epidemiologic studies, suggesting a correlation between estrogen dose and cardiovascular episodes in oral contraceptive users. A delayed resolution of fibrin might contribute to an increased risk caused by decreased coagulation inhibition or fibrinolytic efficacy. Estrogen (30 micrograms or more) has a dose-dependent effect on clotting factors, including antithrombin III and proteins C and S. The effect of high- and low-dose oral contraceptives containing various progestogens on the fibrinolytic system is less clear. We have found that low-dose oral contraceptives containing levonorgestrel or lynestrenol enhance fibrinolysis, as revealed by an increase in plasminogen (30% to 40%), a decrease in histidine-rich glycoprotein (15% to 26%), an increase in tissue plasminogen activator activity (greater than 150%), and a decrease in tissue plasminogen activator inhibition (30% to 40%), concomitant with a slight decrease in tissue plasminogen activator antigen level (15% to 20%). New oral contraceptives contain less androgenic progestogens. Preliminary results of an ongoing study of women receiving either 20 micrograms of ethinyl estradiol with 150 micrograms of desogestrel or 30 micrograms of ethinyl estradiol plus 75 micrograms of gestodene revealed no change or changes similar to the older low-dose preparations after 6 months of treatment. Of particular importance was the finding that coagulation activation, expressed by the levels of thrombin-antithrombin III-complexes, fibrin formation, and the efficacy of fibrinolysis, expressed by the levels of fibrin degradation products, was identical in the two groups.

Blood Coagulation↗
PubMed1990

Studies on the mechanism of action of oral contraceptives with regard to fibrinolytic variables.

Evidence is provided that the fibrinolytic capacity in plasma is strongly dependent on circulating concentrations of tissue plasminogen activator rather than on concentrations of plasminogen activator inhibitor. Thus a decrease in plasma tissue plasminogen activator concentrations, as is the case in oral contraceptive users, may result in a decrease in plasma fibrinolytic capacity despite a parallel decrease in plasminogen activator inhibitor levels. It is now clear that the presence of specific intracellular receptors and a given motif in the genome are essential to mediate hormone-dependent regulation of gene expression. A computer search revealed potential estrogen and glucocorticoid-progesterone-responsive elements in the genes coding for tissue plasminogen activator, plasminogen activator inhibitor, and some other fibrinolytic variables. No convincing evidence for the presence of sex steroid receptors in endothelial cells was found, but liver cells clearly contain estrogen and androgen receptors. However, neither endothelial cells nor hepatocytes cultured in vitro showed a change in tissue plasminogen activator or plasminogen activator inhibitor synthesis on incubation with sex steroids (10(-9) to 10(-6) mol/L) for 3 days. An alternative explanation for the observed decreases in tissue plasminogen activator and plasminogen activator inhibitor concentrations in the plasma of oral contraceptive users is discussed.

Contraceptives, Oral, Combined↗
PubMed1990

Enhanced generation and resolution of fibrin in women above the age of 30 years using oral contraceptives low in estrogen.

Epidemiologic studies have suggested a relationship between the use of oral contraceptives and mortality from cardiovascular diseases in older women. Therefore we studied generation and resolution of fibrin in 28 healthy women above age 30 years, using oral contraceptives containing 30 to 50 micrograms of ethinyl estradiol. Thirty healthy nonusers served as control subjects. The oral contraceptive group had increased plasma concentration of thrombin-antithrombin III complexes (p less than 0.01), which indicated an enhanced generation of thrombin, increased plasma activity of tissue-type plasminogen activator (p less than 0.01), decreased plasma activity of plasminogen activator inhibition (p less than 0.01), and increased plasma concentration of fibrin degradation products (p less than 0.04). Interestingly, the ratio of thrombin-antithrombin III complexes/fibrin degradation products did not deviate significantly between groups. Twelve of the 28 women using oral contraceptives were light smokers, that is, less than 15 cigarettes per day. There were no differences in the determined variables between smokers and nonsmokers. Our study suggests that healthy women older than 30 years who use oral contraceptives containing 30 to 50 micrograms of ethinyl estradiol have an enhanced generation and resolution of fibrin, while the hemostatic balance is unaltered. These findings are unaffected by moderate cigarette smoking.

Adult↗
PubMed1990

Effects of total fat content and fatty acid composition in diet on factor VII coagulant activity and blood lipids.

In a strictly controlled cross-over study (twice 2 weeks) of 11 healthy adults, the effects of a low-fat diet (32% of total energy from fat) with a low or a high ratio of polyunsaturated to saturated fatty acids (0.28 and 0.89, respectively) were observed. Factor VII activity and antigen levels, serum cholesterol, HDL-cholesterol and triglycerides were measured. Factor VII activity was determined in clotting assays using human and bovine thromboplastin (interacting primarily with activated factor VII, F VIIa), allowing differentiation between F VIIc and F VIIa. A significant decrease of F VII levels (median 11.0-14.5%, P less than 0.05) and triglycerides (median 0.22-0.27 mmol/l, P less than 0.05) was observed on both diets, while only the highly unsaturated diet reduced serum cholesterol levels (median 0.65 mmol/l, P less than 0.001). There were no significant correlations between changes in blood lipids and F VIIc. Low fat diets may reduce the risk for ischemic heart disease without lowering of cholesterol levels by eliminating states of hypercoagulability such as elevated factor VII coagulant activity.

Adult↗
PubMed1990

A depression of active tissue plasminogen activator in plasma characterizes patients with unstable angina pectoris who develop myocardial infarction.

The balance between the coagulation system generating fibrin and its subsequent removal by the fibrinolytic system determines the fate of fibrin deposited in the vascular system. In a prospective study, selected haemostatic variables assessing this balance were determined in plasma samples from 20 consecutive patients admitted with unstable angina pectoris. Over a follow-up period of 6 years, eight patients developed myocardial infarction, whereas 12 patients did not. There was no significant difference between the two groups in the median plasma concentrations of thrombin-antithrombin III complexes reflecting the coagulant activity. The infarction group was characterized by a significantly lower median activity of tissue plasminogen activator in plasma euglobulins (P less than 0.05), a higher median concentration of tissue plasminogen activator antigen in plasma (P less than 0.05) and a tendency to higher plasma levels of antigenic and functional plasminogen activator inhibition. In all patients, the activities of tissue plasminogen activator inhibitor and of tissue plasminogen activator were significantly associated (rs = -0.4811, P less than 0.05). We conclude that a depressed fibrinolytic capacity attributable to a low tissue plasminogen activator activity is of pathogenetic importance for the development of myocardial infarction in patients with unstable angina pectoris.

Aged↗
PubMed1990

Interrelationship between coagulant activity and tissue-type plasminogen activator (t-PA) system in acute ischaemic heart disease. Possible role of the endothelium.

Patients with unstable angina pectoris (UAP; n = 20) and acute myocardial infarction (AMI; n = 34) were studied in the acute phase of ischaemic heart disease. We found significantly higher levels of thrombin-antithrombin-III (TAT) complexes, lower levels of systemic tissue plasminogen activator (t-PA) activity, and higher levels of plasminogen activator inhibitor (PAI) activity in the AMI patients compared to the UAP patients. In contrast to these specific changes, general acute phase reactants such as C-reactive protein, fibrinogen and von Willebrand factor did not differ significantly between the two groups. Studies of the relationship between coagulation (TAT-complexes) and fibrinolysis data revealed a significant positive correlation between plasma antigen concentrations of TAT-complexes and t-PA (P less than 0.02), and between TAT-complexes and PAI-I (P less than 0.002). These observations indicate a common pathophysiological mechanism underlying the changes in coagulation and fibrinolysis, suggesting that coagulation activity and t-PA-related fibrinolysis are interrelated processes in vivo, and probably take place at the level of the endothelial cell.

Acute-Phase Proteins↗
PubMed1990

The possible role of oral epithelial cells in tissue-type plasminogen activator-related fibrinolysis in human saliva.

We studied the fibrinolytic activities of the following subfractions of unstimulated human whole saliva on plasminogen-rich fibrin plates: (1) submandibular saliva, (2) parotid saliva, and (3) smears of buccal epithelial cells from ten healthy males. A cell-bound plasminogen activator could be demonstrated in the sediments of all three subfractions of whole saliva. The incorporation of antibodies (goat IgG) against human two-chain tissue-type plasminogen activator (t-PA) could quench the assessed fibrinolytic activities, whereas additional experiments suggested the absence of urokinase-like and F XII-dependent activators of fibrinolysis. The determinations in growth medium from buccal-epithelial cell culture of t-PA antigen by means of enzyme-linked immunosorbent assay showed the presence of t-PA. These clinical and experimental findings suggest that buccal-epithelial cells produce t-PA, while the activity of t-PA in parotid and submandibular saliva is very low.

Cells, Cultured↗
PubMed1990

Plasma HMW fibrinogen in patients with ischaemic heart disease.

Fibrinogen has been reported to be a risk factor for development of myocardial infarction in patients with ischaemic heart disease. The functional properties of plasma high molecular weight (HMW) fibrinogen would suggest that this fibrinogen species is responsible for the association. In a prospective study with a follow-up period of 6 years the plasma concentrations of clottable fibrinogen and of HMW fibrinogen were related to the subsequent development of myocardial infarction in 53 patients admitted with ischaemic heart disease. Neither the concentrations of clottable fibrinogen nor of HMW fibrinogen in the 25 patients developing myocardial infarction deviated from the concentrations in the 28 patients with an uncomplicated course. A significant positive correlation between the concentrations of clottable fibrinogen and of HMW fibrinogen (rs = 0.58, p less than 0.001) suggests that HMW fibrinogen represents a major fraction of the clottable fibrinogen concentration in patients with ischaemic heart disease.

Aged↗
PubMed1990

Metabolic aspects of oral contraceptives of relevance for cardiovascular disease. First European conference on sex steroids and metabolism.

The use of estrogens and progestogens in oral contraceptives has caused increased awareness of the metabolic effects of gonadal steroids. The interpretation of the accumulating number of scientific reports is, however, difficult. In particular, the overall picture of metabolic changes and their relation to the risk of cardiovascular diseases is confusing. Multiple risk factors may influence the development of cardiovascular diseases, which might have their origins in both the arterial and venous systems. Oral contraceptives may influence various of these risk factors, including changes in lipid, carbohydrate and hemostasis variables, and these risk factors in turn show clear inter-relationships. The First European Conference on Sex Steroids and Metabolism took place in May 1989. The Conference provided a platform for the Consensus Development Meeting which followed it. Based on questions formulated by the Consensus Committee which considered epidemiologic, carbohydrate, lipid and hemostasis aspects of relevance for the development of cardiovascular diseases, consensus statements were prepared in closed sessions by a panel of invited experts. The Consensus Report provides pertinent clinical guidelines for future contraceptive practice. A synopsis of the discussion and the concluding remarks will be presented regarding the influence of new low-dose oral contraceptives on hemostasis variables and on glucose and lipid metabolism.

Carbohydrate Metabolism↗
PubMed1990

Effects of methylamine and heparin on a rapid chromogenic assay of C1-esterase inhibitor in plasma.

We describe a rapid assay of C1-esterase inhibitor (C1-inh) activity in plasma. After adding purified C1s serine protease (EC 3.4.21.42) in excess to plasma, we determine the residual C1s activity towards a new chromogenic tripeptide, CH3CO-Lys(CbO)-Gly-Arg-pNA. Optimal conditions include the addition of methylamine (final concentration 0.12 mol/L) to reduce the potential inhibitory capacity of alpha 2-macroglobulin towards C1s and the addition of heparin (final concentration 3000 int. units/L) to enhance the reaction of C1s with C1-inh. The correlation with C1-inh antigen concentrations in plasma was excellent. The estimated interassay CV was 4.3%, whereas the intra-assay CV was 2.0% for activity concentrations within the range of normal individuals (means +/- 2 SD: 70-124%), 1.3% at lower concentrations. The method is more convenient, rapid, and precise than previous methods, and C1-inh activity in plasma can be assessed within 30 min. We found that concentrations of C1-inh in plasma were low during open-heart bypass surgery.

Antigens↗
PubMed1990

Specific, sensitive, precise, and rapid functional chromogenic assay of activated first complement component (C1) in plasma.

We present a new functional assay for the first complement component (C1) in plasma, based on its activation by inhibition of the C1-esterase inhibitor (C1-inh) when monospecific antiserum to C1-inh is added to the plasma. After maximal activation, we can determine the concentration of activated C1 by using an amidolytic rate assay with a chromogenic substrate. We have optimized the assay conditions with respect to incubation time, concentration of antiserum to C1-inh, ionic strength, and pH. Our method determines specifically the concentration in plasma of free activated C1, not complexes of activated C1 with C1-inh, and is not influenced by the concentration of C1-inh in the test sample. Concentrations of C1 correlated significantly with activities determined by a hemolytic assay (r = 0.55, t = 4.09, P less than 0.001). The estimated interassay CV was 5% and the intra-assay CV was 1%. The sensitivity, imprecision, and practical test performance of our assay are superior to those of conventionally used hemolytic assays.

Adult↗
PubMed1989

Rise of plasma t-PA fibrinolytic activity in a group of maturity onset diabetic patients shifted from a first generation (tolbutamide) to a second generation sulphonylurea (gliclazide).

During treatment with tolbutamide 10 maturity onset diabetic patients had no detectable activity of tissue-type plasminogen activator (t-PA) determined on two occasions 3 months apart. All 10 patients responded on the change in treatment to gliclazide with an increase in activity of t-PA. However, after 12 months of treatment the t-PA activity in one of the 10 patients returned to the baseline level, whereas the remaining nine patients had a sustained increased t-PA activity compared to the period during treatment with tolbutamide. The concentration in plasma of t-PA antigen under basal conditions and after stimulation (venous occlusion) increased significantly during the period of treatment with gliclazide. The plasma concentrations of plasminogen activator inhibitor remained unchanged throughout the study. In contrast to these findings seven patients with marked activities of t-PA during treatment with tolbutamide retained unchanged levels of the variables reported above after a change in treatment to gliclazide. Serum glucose, HBA1c, apolipoproteins A and B, and triglycerides remained constant throughout the study, whereas serum cholesterol showed a decrease in both groups of patients after 3 months (P less than 0.05) as well as after 12 months (P less than 0.05) of treatment with gliclazide. There was no significant relationship between serum cholesterol concentrations and plasma concentrations of t-PA antigen indicating that the increase in t-PA antigen was independent of the metabolic state of the patients.

Aged↗
PubMed1989

Levels of protein S during the normal menstrual cycle and in women on oral contraceptives low in estrogen.

Total protein S, a coagulation regulating protein, was determined by an electroimmunoassay in samples of plasma collected during one menstrual or hormone-induced cycle in 15 young women and 11 women using oral contraceptives with 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel. Distinct individual levels caused the with-in-group variations of plasma total protein S to be larger than the individual variations. There was no statistically significant difference between the groups, but in the hormone group there was a slight but statistically significant decrease during the hormone-induced cycle.

Adult↗
PubMed1989

Depressed plasma fibrinolytic activity in a group of patients with connective tissue diseases.

In various connective tissue disorders, a depressed fibrinolytic activity of the blood, attributed a contributory role in the development of disease, has been reported. We have determined selected fibrinolysis variables of the blood in 16 patients (7 patients with mixed connective tissue disease, 4 with systemic lupus erythematosus, 3 with rheumatoid arthritis and 2 with systemic sclerosis) and in 16 apparently healthy, age- and sex-matched controls. A significantly reduced mean activity of the intrinsic derived, urokinase-like plasminogen activator was found in the patient group. None of the other variables, including the extrinsic plasminogen activator (t-PA), differed from the control group. Possible implications of our findings in relation to the patho-physiology of these connective tissue diseases are discussed.

Adolescent↗