Jørgen Gram
University of Southern Denmark
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Featured researches published by Jørgen Gram.
Clinical Endocrinology | 2004
Jan Kvetny; P.E. Heldgaard; Else-Marie Bladbjerg; Jørgen Gram
objective Mild thyroid failure is associated with an increased risk for development of atherosclerosis, but whether subclinical hypothyroidism is related to risk for cardiovascular disease is controversial. The purpose of the present study was to examine a possible association between subclinical hypothyroidism and cardiovascular disease.
Thrombosis Research | 1996
Bjarne Myrup; Moniek P.M. de Maat; Peter Rossing; Jørgen Gram; Cornelis Kluft; Jørgen Jespersen
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.
American Journal of Obstetrics and Gynecology | 1999
Lars Franch Andersen; Jørgen Gram; Sven O. Skouby; Jørgen Jespersen
OBJECTIVES From observational studies, there is evidence that hormone replacement therapy in postmenopausal women causes a decrease in cardiovascular events. It remains unknown, however, precisely by which mechanisms this reduction is achieved. The primary aim of this work was to study the effects of hormone replacement therapy on established hemostatic risk factors during 1-year treatment of healthy postmenopausal women. The secondary aim was to investigate whether there was any significant difference in these risk factors between hormone replacement therapy administered as a cyclic estrogen/sequential progestogen or continuous estrogen/sequential progestogen regimen. STUDY DESIGN Sixty postmenopausal women were randomized to treatment with estradiol valerate 2 mg/day either continuously or cyclic (days 1 to 21; placebo on days 21 to 28). Both groups received cyproterone acetate 1 mg/day on days 12 to 21. Blood samples were collected before treatment and on cycle days 17 to 22 in cycles 3, 6, and 12. Thirty women with basic characteristics identical to the women included in the treatment group were included as a reference group. Blood samples were collected after 0, 6, and 12 months of observation. RESULTS Hormone replacement therapy during 1 year caused a marginal but significant increase in plasma concentration of factor VIIc after 12 months of treatment (P <.05), a significant decrease in fibrinogen, and a significant decrease in the protein concentrations of tissue-type plasminogen activator, plasminogen activator inhibitor-1, and lipoprotein(a) after 3, 6, and 12 months of treatment (P <.05). Possible differences in the integrated response between the reference group and the hormone replacement therapy group were evaluated by comparison of the area under the curve as estimated in each individual on the basis of each analyte in the sampling periods. The area under the curve of fibrinogen was significantly lower in the hormone replacement therapy group than in the reference group (P <.03), whereas other variables did not deviate significantly between the groups. The areas under the curve did not deviate significantly between the group that received cyclic estrogen/sequential progestogen and the group that received continuous estrogen/sequential progestogen. CONCLUSIONS One-year treatment with hormone replacement therapy influenced favorably a number of prognostic cardiovascular risk factors in healthy women. The most important effect was the lowering of fibrinogen. Furthermore, in this study the effect of hormone replacement therapy on hemostasis did not deviate between a cyclic estrogen/sequential progestogen regimen and a continuous estrogen/sequential progestogen regimen.
Thrombosis and Haemostasis | 2007
Jonas Angel Sjøland; Johannes Jakobsen Sidelmann; Mikkel Brabrand; R.S. Pedersen; Jørgen Houe Pedersen; Kim H. Esbensen; Kristina F. Standeven; Robert A. S. Ariëns; Jørgen Gram
Fibrin clots with reduced permeability, increased clot stiffness and reduced fibrinolysis susceptibility may predispose to cardiovascular disease (CVD). Little is known, however, about the structure of fibrin clots in patients with end-stage renal disease (ESRD). These patients suffer from a high risk of CVD in addition to their chronic low-grade inflammation. Using permeability, compaction and turbidity studies in 22 ESRD patients and 24 healthy controls, fibrin clots made from patient plasma were found to be less permeable (p < 0.001), less compactable (p < 0.001), and less susceptible to fibrinolysis (p < 0.001) than clots from controls. The maximum rate of turbidity increase was also higher for the patients than controls (p < 0.001), and scanning electron microscopy revealed higher clot density of fibrin fibers in clots from patients than clots from controls (p < 0.001). Patients had higher plasma concentrations of fibrinogen, C-reactive protein and interleukin 6 than controls. These plasma markers of inflammation correlated significantly with most of the fibrin structure characteristics observed in the patients. In contrast, plasma markers of azothemia showed no such correlations. The results suggest that in ESRD patients fibrin clots are significantly different from healthy controls, and that the fibrin structure characteristics in the patients are associated primarily with the inflammatory plasma milieu rather than with level of azothemia.
Fibrinolysis and Proteolysis | 1992
S. Munkvad; Jørgen Gram; J. Jespersen
Based on recent studies we hypothesised that the marked generation of thrombin in patients who undergo coronary thrombolysis was associated with substantial deviations of endogenous tissue-type plasminogen activator (t-PA) and the plasminogen activator inhibitor type 1 (PAI-1) in plasma. In the present placebo-controlled study we observe in 20 patients treated with recombinant t-PA (rt-PA) a marked increase (p<0.001) of antigen concentrations in plasma of endogenous t-PA and PAI-1 during the first 12h after initiation of treatment. The concentrations of endogenous t-PA and PAI-1 in plasma correlated significantly (p<0.05) with an estimate of generated thrombin in vivo, determined as plasma concentrations of thrombin-antithrombin III complexes. We conclude that the generation of coagulant activity following coronary thrombolysis is associated with an increased synthesis and/or release of endogenous t-PA and PAI-1, which suggests that the procoagulant condition involves an altered functional state of the vascular endothelium.
Thrombosis Research | 2008
Johannes Jakobsen Sidelmann; Frank Vitzthum; Eva Funding; Anna-Marie Bloch Münster; Jørgen Gram; Jørgen Jespersen
Factor VII-activating protease (FSAP) is involved in haemostasis and inflammation. FSAP cleaves single chain urokinase-type plasminogen activator (scu-PA). The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene leads to the expression of a FSAP variant with reduced ability to activate scu-PA, without affecting the ability to activate coagulation Factor VII (FVII). Previous studies have investigated the association of the 1601GA genotype with incidence and progression of carotid stenosis and deep venous thrombosis (DVT). The present study is the first to evaluate the potential association between the FSAP phenotype and DVT. We studied the association between the 1601G/A polymorphism, FSAP activity, FSAP antigen, Factor VIIa (FVIIa), prothrombin fragment 1+2 (F1+2), and C-reactive protein (CRP) in plasmas of 170 patients suspected for DVT. FSAP genotypes were equally distributed in patients with (n=64) and without DVT (n=106), (P=0.94). The 1601GA genotype was associated with significant reduction of FSAP activity (P<0.001) and FSAP antigen levels (P=0.04). Patients with DVT showed significantly higher FSAP activity (P=0.008), FSAP antigen (P=0.003), and F1+2 levels (P<0.001) than patients without DVT. The association between the FSAP measures and DVT disappeared when adjusted for CRP levels. F1+2 correlated positively to FSAP antigen (P=0.01), while FVIIa-levels were comparable in patients with and without DVT. We conclude that even though FSAP measures are significantly increased in patients with acute DVT, alterations in the scu-PA activating properties of FSAP are presumably not markedly involved in the development of acute DVT, and that the association between FSAP and DVT disappears after adjustment for CRP.
Metabolism-clinical and Experimental | 1988
Jørgen Gram; Jørgen Jespersen; Aage Kold
Selected variables of the fibrinolytic system were assessed in 23 men with insulin-treated diabetes with no measurable pancreatic beta-cell function. Gliclazide, a second-generation sulphonylurea drug, was administered to the patients over a period of 6 months in daily doses of 160 mg or 240 mg, and blood samples were obtained before, during, and after treatment. Determined by global assays, the drug did not significantly change plasminogen activator activities in euglobulins. Measurements of specific components of the system of fibrinolysis showed a marginal increase during administration of gliclazide of tissue-type plasminogen-activator antigen and prekallikrein activity in plasma, whereas the activities in euglobulins of the intrinsic plasminogen proactivators remained nearly the same during the study. Levels in plasma and euglobulin of C1-inactivator antigen and in plasma of factor XII antigen and t-PA inhibition capacity remained constant throughout the study. There were no changes of the increase in concentration of t-PA activity and t-PA antigen following venous occlusion. The metabolic state remained the same during the whole study. It is concluded that gliclazide induces small, but significant, non-insulin-dependent extrametabolic effects on the extrinsic (t-PA) and intrinsic (prekallikrein) system of fibrinolysis. Whether these changes are of physiological importance remains to be demonstrated.
Journal of the American College of Cardiology | 1991
Steffen Munkvad; Jørgen Jespersen; Jørgen Gram; Cornelis Kluft
In a randomized placebo-controlled study, seven patients with acute myocardial infarction allocated to intravenous treatment with 100 mg of recombinant tissue-type plasminogen activator (rt-PA) and seven patients allocated to placebo were studied during eight sampling periods before and after treatment. Seven patients with acute myocardial infarction treated intravenously with 1.5 million U of streptokinase were later studied during two sampling periods before and after treatment. The placebo group showed no significant deviations of endogenous factor XII-dependent fibrinolytic activity (p greater than 0.05). In the rt-PA group, this activity decreased significantly (p less than 0.001) after the infusion and remained depressed throughout the 1st 4 days. A significant decrease in activity (p less than 0.05) was also found in the streptokinase-treated patients. The depletion of factor XII-dependent fibrinolytic activity was not due to generation of inhibition or a depletion of factor XII, prekallikrein and plasminogen, but could be related to the proactivator of this system. It is concluded that rt-PA (and streptokinase) treatment in patients with acute myocardial infarction causes a prolonged depletion of factor XII-dependent fibrinolytic activity. This depression of endogenous fibrinolytic activity needs to be evaluated in relation to the enhanced risk of coronary reocclusion after thrombolytic therapy.
American Journal of Obstetrics and Gynecology | 1990
Jørgen Gram; Steffen Munkvad; Jørgen Jespersen
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.
Thrombosis Research | 1986
Jørgen Jespersen; Jørgen Gram; Tage Astrup
Plasmin is a labile enzyme destroyed by a process termed autodigestion. Studied by a kinetic assay on the substrate Tos-Gly-Pro-Lys-pNA this process is shown to follow a bimolecular mode of reaction, which is retarded by plasmin degradation products. Plasmin is protected by fibrinogen, by epsilon-aminocaproic acid (6-aminohexanoic acid), by increasing ionic strength, and by glycerol. CNBr fragments of fibrinogen did not protect. Lack of substrate protection of plasmin may give rise to errors in a two-stage plasminogen activator assay, while the presence of substrate in a one-stage method prevents degradation of the generated plasmin.