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Biomedical subjects

P Kierulf

Publications and source records attributed to P Kierulf.

At least 73 records · Page 4Linked to original sources
PubMed1994

Modulation of thrombotic responses in moderately stenosed arteries by cigarette smoking and aspirin ingestion.

Cigarette smoking is a known risk factor for cardiovascular disease in men and women, and it has been suggested that this risk is linked to enhanced formation of platelet thromboxane A2 (TxA2). This led us to investigate the effect of cigarette smoking and TxA2 formation on collagen-induced thrombogenesis in flowing nonanticoagulated human blood. Thrombus formation in blood from smokers and nonsmokers was compared before and 2 hours after ingestion of a single oral dose of 990 mg aspirin, which is sufficient to block platelet TxA2 formation. Nonanticogulated blood was drawn directly from an antecubital vein over collagen fibrils in a parallel-plate perfusion chamber by a peristaltic roller pump placed distally to the chamber. Wall shear rates at the collagen surface were characteristic for medium-sized (650 s-1) and moderately stenosed (2600 s-1) arteries. Blood-collagen interactions were morphologically quantified, and markers of platelet release, beta-thromboglobulin (beta-TG), and activation of coagulation, fibrinopeptide A (FPA), were measured immediately distal to the perfusion chamber. The thrombus volume in blood from cigarette-smoking individuals was nearly twofold larger than in blood from nonsmokers at 2600 s-1 (37.4 and 19.4 microns 3/microns 2; P < .03). However, ingestion of aspirin reduced the thrombus volume in blood from smokers by 61.8% (P < .01), which was substantially more than the 37.6% reduction in blood from nonsmokers (P < .03). Neither cigarette smoking nor aspirin ingestion affected thrombus formation at 650 s-1. The plasma levels of FPA and beta-TG were slightly lower in nonsmokers and after aspirin ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Clopidogrel--a platelet inhibitor which inhibits thrombogenesis in non-anticoagulated human blood independently of the blood flow conditions.

The goal of the present study was to investigate the effect of 7 and 14 days of daily oral administration of 75 mg clopidogrel on collagen-induced thrombogenesis in flowing non-anticoagulated human blood. Blood was drawn directly from an antecubital vein over immobilised collagen type III fibrils positioned in a parallel-plate perfusion chamber. The wall shear rates at the collagen surface were those characteristic for veins (100 s-1), and for medium sized (650 s-1) and moderately stenosed (2600 s-1) arteries. Clopidogrel ingestion reduced the thrombus volume significantly (p < 0.05) at 100 and 2600 s-1 (39 and 51% respectively). The beta-thromboglobulin plasma levels were reduced concomitantly. However, it was not possible to measure accurately the thrombus volume at 650 s-1, due to loose packing of the platelet thrombi. Transmission electron microscopy substantiated this observation and showed that clopidogrel profoundly reduced the platelet degranulation process (p < 0.005). The inhibitory effect of clopidogrel on platelet consumption by the growing thrombi resulted apparently in higher platelet concentration at the collagen surface, which enhanced the platelet-collagen adhesion at all three shear rates (p < 0.05). Despite the low deposition of fibrin on collagen, clopidogrel reduced significantly the fibrinopeptide A plasma levels and the fibrin deposition at shear rates below 650 s-1. This was apparently a consequence of the reduced platelet recruitment and the lower activation of platelets, since activated platelets in thrombi promote deposition of fibrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

HN-11500--a novel thromboxane A2 receptor antagonist with antithrombotic activity in humans at arterial blood flow conditions.

In the present study we have investigated the effect of a 100 mg single oral dose of a newly developed thromboxane A2 receptor antagonist on collagen-induced thrombogenesis in flowing human non-anticoagulated blood. Blood was drawn directly from an antecubital vein over immobilised collagen type III fibrils on a cover slip placed in a parallel-plate perfusion chamber. Shear rates at the collagen surface were characteristic for medium sized (650 s-1) and moderately stenosed (2,600 s-1) arteries. Blood-collagen interactions were morphologically quantified as platelet-collagen adhesion, fibrin deposition and thrombus volume. Activation peptides of coagulation, fibrinopeptide A (FPA), and of platelets, beta-thromboglobulin (beta-TG), were measured immediately distal to the perfusion chamber. HN-11500 ingestion reduced significantly the thrombus volume by 32% at 2,600 s-1, but not at 650 s-1. However, transmission electron microscopy revealed loosely packed and less degranulated platelets at 650 s-1. The beta-TG plasma levels were also reduced at both shear rates by the HN-11500 ingestion. The platelet-collagen adhesion was significantly enhanced at both shear rates. This was apparently a consequence of higher platelet concentrations at the collagen surface, because fewer platelets were consumed by the thrombi after the drug ingestion. In contrast, the coagulation, as measured by fibrin deposition and FPA plasma levels, was not significantly affected by HN-11500. Thus, it appears that the thromboxane A2 receptor antagonist HN-11500 reduces the thrombotic response by primarily impairing the platelet function at arterial blood flow conditions, and particularly at high wall shear rates.

Acetates↗
PubMed1993

Sequential intrapulmonary and systemic activation of coagulation and fibrinolysis during and after total hip replacement surgery.

Hip joint replacement surgery, using acrylic cement for prosthesis fixation, is associated with intraoperative cardiorespiratory dysfunction, and a high frequency of postoperative proximal deep vein thrombosis (DVT). Levels of prothrombin fragments 1+2 (F1+2), tissue plasminogen activator antigen (t-PA), plasminogen activator inhibitor 1 activity (PAI-1), D-dimer and interleukin 6 (IL-6) were measured in arterial (AB) and mixed venous blood (MVB) in five patients during and after total hip replacement operation with acrylic cement prosthesis fixation. Sequential peaks of F1+2, t-PA, PAI-1 and IL-6 appeared, starting with activation of coagulation during preparation of bone, closely followed by activation of fibrinolysis. Later, this was counteracted by an antifibrinolytic response and increase of IL-6. After a fibrinolytic shutdown on the third postoperative day as evidenced by a drop in t-PA and D-dimer concentrations, a second wave of coagulation was seen at the end of the first week. The present model, with frequent sampling of blood entering and leaving the lungs, confirms our earlier findings of the lung as a key organ in promoting coagulation following traumatic activation.

Aged↗
PubMed1993

Lipopolysaccharide-induced monocyte procoagulant activity, fibrinopeptide A, and PAI-I levels in persons with high or low levels of HDL-lipoprotein.

We have examined basal and stimulated monocyte procoagulant activity (PCA) in 10 persons with high HDL (1.62-2.47 mmol/L) and 10 persons with low HDL (0.43-1.29 mmol/L). Heparinized whole blood was incubated at 37 degrees C for 2 hours with 100 ng/ml of E. Coli lipopolysaccharide (LPS). Monocytes were isolated by density gradient centrifugation (purity > 70%), and PCA measured with a chromogenic peptide substrate assay. LPS-induced PCA was significantly higher in the high HDL group (p = 0.02), whereas basal levels were similar. Furthermore, the levels of total HDL, HDL2, as well as apo-A1 were all significantly correlated with LPS-induced monocyte PCA (p < 0.01, p < 0.01, and p = 0.03), whereas VLDL was inversely correlated (p = 0.02). PAI-I activity was significantly lower in the high HDL group (p < 0.01). LPS recovery in plasma after incubation, by LAL test, was significantly higher in the high HDL group (p = 0.02) and correlated to HDL2 (p = 0.04), and inversely correlated with triglycerides (p = 0.04). There was no significant difference between the two groups in plasma fibrinopeptide A (FPA) levels after LPS incubation.

Adult↗
PubMed1993

Cardiovascular risk factors: interactive effects of lipids, coagulation and fibrinolysis.

In western societies cardiovascular disease accounts for approximately one of every three deaths, and is a major contributor to chronic debiliation. During the last years our knowledge of factors that contribute to the development and progression of this disease has increased markedly. Elevated serum total cholesterol, hypertension and cigarette smoking are "traditional", well-known risk factors. In addition, low serum levels of high density lipoprotein (HDL) cholesterol predispose to development of disease, whereas in epidemiological studies the role of increased triglycerides is more controversial. During the last years derangements in several haemostatic components in persons who develop cardiovascular disease have been observed. Such alterations include increased plasma concentrations of fibrinogen, Factor VII coagulant activity and plasminogen activator inhibitor-1 (PAI-1). Furthermore, interactions between lipoproteins and haemostatic factors are gradually being disclosed. Serum triglycerides have been shown to correlate both to PAI-1 and to Factor VII. The lipoprotein (a), first described by Berg in 1963, also appears to be a link between lipoprotein metabolism and fibrinolytic function. In addition, linkages are observed between high triglycerides, low HDL cholesterol, reduced glucose tolerance, hyperinsulinemia, obesity, low physical activity, reduced fibrinolytic capacity and increased Factor VII. This clustering of risk factors has been suggested to be a coronary risk syndrome and has been called Reavens syndrome, syndrome X and insulin-resistance syndrome. A more descriptive name, athero-thrombogenic syndrome (ATS), has recently been suggested, thereby indicating that both atherosclerosis and thrombosis contribute to its development.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗
PubMed1993

Total protein in common duct bile measured by acetonitrile precipitation and a micro bicinchoninic acid (BCA) method.

Bile protein assays are complicated due to interference by other bile substances. In the present study we describe a microtiter plate method for the purification and quantification of bile proteins. The method is based on addition of acetonitrile in three steps to reconstituted freeze-dried bile, followed by ethanol washing of the precipitated proteins. Finally, protein in the precipitate is quantitated by two-point colour development using micro BCA reagents. Overall recoveries of protein in reconstituted bile spiked with exogenous protein (Seronorm) ranged from 91.0% (coefficient of variation; CV = 7.0%) to 97.1% (CV = 2.4%) by recoveries of 125I-Fibrinogen and 125I-Albumin. Bile pigments were largely removed during precipitation and washing, as verified by high pressure liquid chromatography (HPLC). Preferably the samples should be freeze-dried initially, as this lowered the blank readings. Two-point colour development with the BCA reagents were identical for standards assayed directly and standards added to protein depleted bile, and processed through all steps. Hence, no interference by either residual bile constituents nor the reagents upon the BCA protein assay could be detected. Standard curves ranged from 0.05 to 5.0 gl-1 (r > 0.98). Within day reproducibility (n = 15) was 7.8% (CV) and day to day (n = 10) was 12.1% (CV). Mean protein concentration in common duct bile from 30 patients was 1.20 gl-1 (range 0.34-3.87 gl-1). The method appears suitable for assay of bile protein, requires only limited sample volumes and allows processing of many samples within a short time.

Acetonitriles↗
PubMed1992

Long-term glycemic control and kidney function in insulin-dependent diabetes mellitus.

In this paper we examined the relationship between blood glucose control and initiation and progression of increased urinary albumin excretion. In this seven year Oslo study 45 insulin-dependent diabetes mellitus patients were initially randomized into three different modes of treatment: continuous subcutaneous insulin infusion (CSII), multiple injections, or two injections a day. After four years, the patients were free to choose their treatment, and therefore the data were analyzed according to mean HbA1 during seven years. The mean HbA1 was 11.2% (2.2) (SD) at start, and 9.5% (1.5) at seven years, which was a significant long-term improvement (P less than 0.001). Eight out of 10 patients with mean seven year HbA1 less than 8.5% improved their albumin excretion rate, and patients with mean HbA1 greater than 10% had an increased albumin excretion rate (from 26 mg/24 hr to 91 mg/24 hr, P less than 0.02). The glomerular filtration rate decreased slightly regardless of mean HbA1 level. Systolic blood pressure increased significantly regardless of mean HbA1. Diastolic blood pressure was unchanged in the patients with mean HbA1 less than 10%, but increased slightly (NS) in patients with HbA1 greater than 10%. We conclude that mean blood glucose as measured by glycosylated hemoglobin is a main determinant in the progression of urinary albumin excretion in insulin dependent diabetics, and near normoglycemia improves urinary albumin excretion.

Adolescent↗
PubMed1992

Compartmentalization of lipopolysaccharide production correlates with clinical presentation in meningococcal disease.

Lipopolysaccharide (LPS, endotoxin) was quantified in plasma and cerebrospinal fluid (CSF) collected simultaneously from patients with systemic meningococcal disease. High levels (median, 3800 ng/L; range, 750-14,000) were present in plasma and low levels (median, 40 ng/L; range, less than 25-165) in CSF of patients with fulminant septicemia. Conversely, high levels (median, 2500 ng/L; range, less than 25-500,000) in CSF and low or undetectable levels (median, less than 25 ng/L; range, less than 25-210) in plasma were associated with meningitis without septic shock. Levels of LPS were significantly correlated with protein levels in CSF (r = .50, P = .01) and inversely correlated with the ratio of glucose in CSF to that in blood (r = -.62, P = .0005). LPS level in CSF greater than 800 ng/L was significantly associated with greater than or equal to 10(9) leukocytes/L, protein levels greater than 0.5 g/L, and a glucose ratio less than 0.5. Thus, quantification of LPS levels in the plasma and CSF in systemic meningococcal disease is a better predictor of pathophysiologic events than is demonstrating the presence of live bacteria as in conventional culture.

Adolescent↗
PubMed1992

Population variation and genetics of plasma homocyst(e)ine level.

A high level of plasma homocyst(e)ine (H(e)) has been reported to be an independent risk factor for coronary heart disease (CHD), at least in some populations. We have determined the H(e) concentration in the plasma of two series of Norwegians in order to establish a baseline for future analysis of people with CHD. The mean sex- and age-adjusted homocyst(e)ine level was 10.6 (range 4.84-29.88) in one series and 10.5 (range 3.76-40.57) in the other. The H(e) level appeared to be independent of other proven or potential risk factors or protective factors with respect to CHD. The intraclass correlation coefficient in monozygotic (MZ) twins is a (possibly inflated) estimate of heritability. We have examined two series of MZ twins. The intraclass correlation coefficient was significant in both series. In one series, the Pearson correlation coefficient was 0.53 and the Kendall correlation coefficient 0.38. In the other, the values were 0.56 and 0.46, respectively. We conclude that in the population examined, H(e) levels exhibit significant heritability.

Adult↗
PubMed1992

Intrapulmonary thrombin generation and its relation to monomethylmethacrylate plasma levels during hip arthroplasty.

Frequent peroperative sampling of arterial and mixed venous blood was undertaken in eight consecutive patients during cemented hip arthroplasty to obtain a sequential picture of thrombin-antithrombin (TAT) and methylmethacrylate monomer (MMA) concentrations. TAT, detected neo-antigenically, reached its maximum levels after bone preparation, prior to introduction of cement and prosthesis. Furthermore, TAT values were higher in arterial than in mixed venous blood, indicating generation and inactivation of thrombin when blood is passing the lung. MMA concentration, measured by high pressure liquid chromatography, increased very rapidly and declined within 1 min following socket as well as shaft implantation, reaching the highest mean value of 3599 ng/ml only 30 s after femoral impaction of cement. MMA concentration was higher in mixed venous than in arterial blood, indicating elimination of the monomer during lung passage. This study confirms our previous observation that coagulation is activated prior to the implantation of bone cement and prosthesis into the femoral shaft; in addition, it provides further evidence of the thrombin-generating potential of the pulmonary capillary bed. Very frequent sampling was necessary to reveal the sharp rise in MMA levels following impaction of cement. Further investigations are needed to establish whether interaction between activated coagulation and MMA may predispose to cardiovascular complications.

Aged↗
PubMed1992

Meningococcal endotoxin in lethal septic shock plasma studied by gas chromatography, mass-spectrometry, ultracentrifugation, and electron microscopy.

We have compared gas chromatography and mass spectrometry (GC-MS) analysis with the Limulus amebocyte lysate (LAL) assay to quantify native meningococcal lipopolysaccharides (LPS) in five patient plasmas containing greater than 5 micrograms/liter by LAL. 3-Hydroxy lauric acid (3-OH-12:0) was used as a specific lipid A marker of neisserial LPS. The quantitative LAL results were confirmed by GC-MS (r = 0.98, P = 0.006). Seven patient plasmas were centrifuged at 103,000 g and the sedimentation behavior of native LPS compared with reference plasma proteins and with apo A1 and apo B100 representing high and low density lipoproteins. After 15 min of centrifugation, 84 +/- 2% (mean +/- SE) of the recovered LPS were found in the lower one-third of the centrifuged volume, whereas 6 +/- 1% remained in the upper one-third volume, indicating that meningococcal endotoxin circulates as complexes with high sedimentation coefficients. Bacterial outer membrane fragments were detected in the bottom fractions of three patient plasmas examined by means of electron microscopy. In three patient plasmas ultracentrifuged for 60 min at 103,000 g, the levels of apo A1 and apo B100 revealed minor changes, whereas only 1 +/- 1% of the recovered LPS remained in the upper one-third and 91 +/- 2% were found in the lower one-third volume. Few bioreactive LPS appear to be complexed with high and low density lipoproteins in meningococcal septic shock plasma.

Endotoxins↗
PubMed1992

Coronary risk factors in middle-aged men as related to smoking, coffee intake and physical activity.

The relationship between lifestyle and coronary risk factors in blood was investigated in 165 middle-aged men. Plasma fibrinogen, serum triacylglycerols (TG), and apolipoprotein B (apo B) were higher, and high density lipoprotein cholesterol (HDLc) lower in smokers (n = 69) than in non-smokers (n = 96). By linear regression analysis there was a significant positive association between degree of smoking and either total cholesterol (TC), apo B, or plasma fibrinogen, whereas smoking was inversely related to HDLc. Smoking and coffee intake were positively correlated with an atherogenic index, reflecting the balance between low and high density lipoproteins. Sedentary men (n = 59) had higher mean TC, apo B, and atherogenic index than physically active men (n = 104). Smokers used salt more often than non-smokers. Physically active men used vegetables more often than sedentary men. Combining several habits into a "bad habit" score gave a high level of significance for its association with TC, apo B, and the atherogenic index. The results indicate that lifestyle may influence several blood factors involved in atherosclerosis development.

Adult↗
PubMed1992

Quantification of lipopolysaccharides in human bile with or without gram-negative bacteria.

Lipopolysaccharide (LPS) was assayed in 78 samples of human common-duct bile, obtained at endoscopic retrograde cholangiography. The LPS was assayed by a chromogenic limulus amebocyte lysate (LAL) test, after dilution of bile samples in heparinized plasma and inactivation of inhibitors. The assay was not influenced by other biliary constituents, as demonstrated by the recovery of standards. Bile pigments did not influence the results. The LAL test was positive in 60 of the samples, 59 of which had a positive culture for gram-negative bacteria or Candida sp. The levels of LPS were significantly correlated to the total number of bacteria (n = 16, R = 0.55, p less than 0.05). The median LPS level was 35,250 ng/l and showed a very large variation (140 ng/l to 27.8 mg/l). In four of the samples gram-negative bacteria were present, but no LPS could be detected. The study demonstrates the presence of LPS in great quantities in human bile and supports the feasibility of using the LAL test on bile samples. The presence of LPS (within the detection limit) appears to be associated with local microbial colonization.

Adult↗
PubMed1991

Generation of procoagulant (thromboplastin) and plasminogen activator activities in peripheral blood monocytes after total hip replacement surgery. Effects of high doses of corticosteroids.

Development of thromboplastin (tpl) and plasminogen activator (PA) activity in monocytes and the effects of high doses of corticosteroids (HCD) on these activities were studied in patients undergoing a standardized surgical trauma. Twelve patients who received uncemented total hip prostheses were divided into a nonsteroid group (n = 6) and a steroid group (n = 6). We found no significant differences between the two patient groups regarding tpl or PA activities of peripheral blood mononuclear cells (PBM) isolated during the postoperative phase. However, in the nonsteroid group there was a tendency for increased expression of procoagulant activity and decreased fibrinolytic activity on the 1st postoperative day, favoring the formation of fibrin in the monocyte microenvironment. Further, PBM isolated on the 1st and 2nd day after surgery were significantly less capable of generating tpl activity on endotoxin stimulation than cells isolated preoperatively. This was not the case in the steroid group. These patients had also a tendency for decreased fibrinolysis at the end of the 1st postoperative week, indicating increased imbalance towards a more thrombotic stage after surgery.

Adrenal Cortex Hormones↗
PubMed1991

[The effect of doxazosin on blood pressure, lipids, fibrinogen and plasminogen activator inhibitor. A comparative study among smokers and non-smokers with essential hypertension].

Hypertensive cigarette smokers run particularly high risk of coronary heart disease. Doxazosin, which has beneficial effects on haemodynamic factors and lipid metabolism, may be a suitable agent for treating these patients. The effects on blood pressure and metabolic parameters were investigated in a 16-week, open, parallel, comparative study comprising 64 heavy cigarette smokers and 69 non-smokers who received doxazosin after four weeks on placebo. Eight patients (three smokers and five non-smokers) dropped out due to adverse effects. Blood pressure was significantly reduced in both groups, but there was no change in heart rate. Doxazosin induced a decrease in the triglyceride, total cholesterol and LDL-cholesterol levels, and an increase in HDL-cholesterol concentration. Thus, doxazosin has favourable effects on atherogenic factors in smoking hypertensive patients. There was also a significant lowering of plasma fibrinogen levels and plasminogen activator inhibitor (PAI-1) concentration in non-smokers.

Adult↗