Detecting antithrombin deficiency may be a difficult task--more than one test is necessary.
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Antithrombins↗
Biomedical subjects
S R Kristensen
Publications and source records attributed to S R Kristensen.
Serial measurements of N-terminal pro-brain natriuretic peptide after acute ischemic stroke.
BACKGROUND: The exact time-course of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the prognostic importance in the immediate phase of ischemic stroke have not been established. METHODS: NT-proBNP was measured daily from admission to day 5 and again at 6-month follow-up in 250 consecutive patients with acute ischemic stroke. RESULTS: NT-proBNP peaked the day after onset of symptoms (p = 0.007) followed by a decrease until day 5 (p = 0.001, ANOVA). At 6-month follow-up the difference in the level of NT-proBNP was unchanged compared to day 5 (p = 0.42). NT-proBNP levels > or =615 pg/ml at day 2 after onset of symptoms was associated with 6-month mortality. CONCLUSION: NT-proBNP peaks the day after onset of symptoms in patients with acute ischemic stroke. A single measurement of NT-proBNP appears to be an indicator of 6-month mortality.
Acute Disease↗
Effect of long-term hormone replacement therapy on tissue factor pathway inhibitor and thrombin activatable fibrinolysis inhibitor in healthy postmenopausal women: a randomized controlled study.
It was recently reported from the Women's Health Initiative that healthy women using combined hormone replacement therapy (HRT) for 5 years have an increased cardiovascular risk. We hypothesize that the increased risk is confined to subgroups of atherosclerotic women. Such women may have higher arterial tissue factor expression and higher thrombin formation, and changes in tissue factor pathway coagulation inhibitor (TFPI) and thrombin activatable fibrinolysis inhibitor (TAFI) may be deleterious. Healthy postmenopausal women (n = 719) were randomized to hormone therapy [n = 357; opposed (n = 290) and unopposed (n = 67)] or no treatment (n = 362). Plasma TFPI and TAFI and the TFPI -287T/C and TAFI -438G/A polymorphisms were measured 5-6 years after randomization. Concentrations of TFPI were significantly lower in the hormone group than in the control group (P < 0.001) and in all genotypes of the TFPI polymorphism. Overall, concentrations of TAFI did not differ between the two groups but were reduced by hormone therapy in homozygotes for the rare TAFI -438 A allele (P < 0.05). The hormone effects on TFPI and TAFI were similar in smokers and non-smokers and in women using unopposed and opposed therapy. The observed decrease in TFPI may contribute to the increased cardiovascular risk associated with HRT.
Arteriosclerosis↗
Positive impact of hormone replacement therapy on the fibrinolytic system: a long-term randomized controlled study in healthy postmenopausal women.
BACKGROUND: The mechanisms by which postmenopausal hormone replacement therapy (HRT) may influence risk of cardiovascular disease are still unclear. Impaired fibrinolytic function is associated with an enhanced risk of cardiovascular disease and therefore the effect of HRT on fibrinolysis may be of importance. OBJECTIVES: To investigate the prolonged effect of HRT on the fibrinolytic system and to determine whether two common polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) genes modulate this effect. METHODS: Healthy postmenopausal women (n = 248) were randomized to HRT (n = 122) or no substitution (n = 126) 5 years prior to investigation. RESULTS: Significantly higher values of t-PA activity and lower values of PAI-1 activity and PAI-1 antigen were found in the HRT group compared with the control group. This effect was independent of smoking and without influence from the two common polymorphisms PAI-1 -675(4G/5G) and t-PA intron8ins311. Furthermore, no difference between opposed estrogen (with norethisterone acetate as the gestagen component) and unopposed estrogen therapy was found. Both an intention-to-treat and a per-protocol analysis were performed and similar results were obtained. CONCLUSIONS: Long-term treatment with HRT in healthy postmenopausal women was found to be associated with a beneficial fibrinolytic profile. This effect was found independent of smoking status, opposed and unopposed estrogen therapy had equal effect, and no influence of the two common polymorphisms PAI-1-675(4G/5G) and t-PA intron8ins311 was found. This effect of HRT on fibrinolytic capacity may be one of the beneficial effects of HRT in relation to cardiovascular diseases.
Drug Therapy, Combination↗
A cellular model system of differentiated human myotubes.
The aim of this study was to select an effective and stable protocol for the differentiation of human satellite cells (Sc) and to identify the optimal time period for the experimental use of differentiated human Sc-cultures. In order to identify the differentiation conditions which give a good survival of myotubes and a high grade of differentiation, Sc-cultures were induced to differentiate in media supplemented with either 2% fetal calf serum (FCS) 2% horse serum (HS) or 10% HS. Based on higher CK-activities in cultures differentiating in FCS-supplemented media compared to horse sera, fetal calf serum was chosen to induce differentiation. The ATP, DNA and protein content increased during the first 4 days after induction of differentiation and was followed by a period with minor changes. The maximal differences of ATP, DNA and protein between days 4-10 were evaluated and the differences in the three components were found to be less than 20% of the average value with a certainity of more than 0.9. Day 8-myotubes were investigated morphologically and were found immunoreactive for fast myosin, and expressed areas with clear cross striation. We recommend the use of differentiated Sc-cultures in the period from day 4 to 8 after induction of differentiation as only minor differentation-related changes will take place in the cells during this period of time.
Adenosine Triphosphate↗
[Macro creatine kinase as a pitfall in diagnosis of acute myocardial infarction].
Measurement of creatine kinase and the more heart-specific creatine kinase B has been a mainstay in the diagnosis of acute myocardial infarction in Denmark since the 1970's. However, an elevated creatine kinase B may reflect other conditions than myocardial damage, for example the presence of other isoenzymes or macro creatine kinase. A case is presented with a review of the literature.
Aged↗
Monitoring of free TRAM flaps with microdialysis.
The aim of this investigation was to follow the metabolism of free TRAM flaps using microdialysis. Microdialysis is a new sampling technique that provide opportunities to follow the biochemistry in specific organs or tissues. A double-lumen microdialysis catheter or probe, with a dialysis membrane at the end, is introduced into the specific tissue. Perfusion fluid is slowly pumped through the catheter and equilibrates across the membrane with surrounding extracellular concentrations of low molecular weight substances. The dialysate is collected in microvials and analyzed by an instrument using very small volumes. Glucose, glycerol, and lactate concentrations were measured in the flaps and compared with those in a reference catheter that was placed subcutaneously in the femur. The investigation continued 72 hr postoperatively. The study group consisted of 14 women who underwent reconstruction with a free TRAM flap, and one woman with a double TRAM flap. During flap ischemia, the concentration of glucose was reduced, while the lactate and glycerol levels increased. The differences between the flaps and controls were statistically highly significant. After reperfusion of the flaps, the concentrations of glucose, lactate, and glycerol approached normal. One flap failed because of an arterial anastomosis thrombosis. This was clearly demonstrated by the samples from the microdialysis: the concentration of glucose fell to an unmeasurable level; the concentration of lactate increased for a period before it stopped due to lack of glucose; and the concentration of glycerol increased to a very high level, probably because ischemia caused damage to the cell membranes of which glycerol is an important part. The authors concluded that microdialysis can detect ischemia in free flaps at an early stage, making early surgical intervention possible.
Breast Neoplasms↗
Biochemical markers of ischaemia for the early identification of acute myocardial infarction without St segment elevation.
Blood was collected on admission and after 1-2 h in 130 consecutive patients admitted with typical chest pain in order to assess the capacity of myoglobin, fatty-acid-binding protein (FABP), CK-MB mass, and troponin I (TnI) in the early identification of acute myocardial infarction (AMI) without ST elevation. Using the maximum value within 6 h of onset of symptoms, AMI was detected with a 90-95% sensitivity and a 81-94% specificity by FABP at a cut-off level 8-12 midrog/l, or 81-86% and 89-93%, respectively, by myoglobin at a cut-off level 70-90 microg/l. CK-MB mass and TnI had low sensitivity, albeit very high specificity. As almost all AMI patients were identified within 6 h, serial measurements of FABP or myoglobin ruled out AMI with a very high degree of certainty. Due to the low prevalence of AMI (16%), the positive predictive values were modest (47-73%), yet increasing the probability of AMI by a factor 3-4. Myoglobin and FABP are very useful markers in the early triage of chest pain patients.
Adult↗
[Biochemical diagnosis of acute coronary syndrome].
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Angina, Unstable↗
Longevity is independent of common variations in genes associated with cardiovascular risk.
Do extremely old persons have a genetically favourable profile which has protected them from cardiovascular death? We have tried to answer this question by measuring DNA polymorphisms of selected cardiovascular risk indicators [factor VII, FVII (R/Q353, intron 7 (37bp)n, and -323ins10), beta fibrinogen (-455G/A), plasminogen activator inhibitor type 1, PAI-1 (-675(4G/5G)), tissue plasminogen activator, t-PA (intron 8 ins311), platelet receptor glycoprotein IIb/IIIa, GPIIb/IIIa (L/P33), prothrombin (20210G/A), methylene tetrahydrofolate reductase, MTHFR (A/V114), angiotensin converting enzyme, ACE (intron 16 ins287), and angiotensinogen (M/T235)]. Blood was collected from 187 unselected Danish centenarians, and 201 healthy Danish blood donors, aged 20-64 years (mean age 42 years). Genomic DNA was amplified using PCR and the genotype was determined by RFLP methods or allele-specific amplification followed by agarose gel electrophoresis. The frequencies of the high-risk alleles in centenarians were: for FVII R/Q353 0.91; for FVII intron 7 (37bp)n 0.67; for FVII-323 ins10 0.90; for fibrinogen 0.16; for PAI-1 0.52; for t-PA 0.59; for GPIIb/IIIa 0.16; for prothrombin 0.008; for MTHFR 0.33; for ACE 0.52; and for angiotensinogen 0.36. Comparable frequencies were observed in the blood donors. Subgroup analysis of men and women separately gave similar results. The genotype frequencies in the centenarians and the blood donors were similar for all polymorphisms, and this study suggests that common variations in genes associated with cardiovascular risk do not contribute significantly to longevity.
Adult↗
Haemolysis following rapid experimental red blood cell transfusion--an evaluation of two infusion pumps.
BACKGROUND: The vast majority of infusion pumps used for rapid transfusion of large amounts of blood have never been properly examined regarding their influence on the quality of the red blood cells (RBCs) infused. In this study, we evaluated the effect of two different infusion pumps on the degree of RBC destruction following rapid experimental blood transfusion. METHODS: Divided into 2 groups according to age, 30 u of SAGM RBCs were infused through an experimental transfusion model by either a manual roller pump (MRP) or a pressure infusor pump (PIP). Fresh (i.e stored for 8-11 d) RBCs, 20 u, and 10 u of older (i.e. stored for 25-33 d) RBCs were randomly allocated to infusion with either of the two pumps. The rate of infusion was as fast as possible with the MRP, and with the PIP adjusted with an external applied pressure of 300 mm Hg. RBC samples collected before and after infusion were analyzed for total haemoglobin, free haemoglobin, haematocrit, total free potassium, lactate dehydrogenase (LDH) and the percentage of haemolysis. The time spent for each transfusion was measured by a stop watch. RESULTS: Following infusion, a marginal increase (i.e. considerably below 0.8%) in the percentage of haemolysis and LDH content was seen with both pumps. This increase was only statistically significant when RBCs stored for 8-11 d were used (P = 0.002 for both parameters). Irrespective of the age of the RBCs, no differences between the two pumps could be detected. Compared to the PIP, infusion with the MRP could be accomplished significantly faster, i.e. median 5.9 ml/s (5.2-6.4 ml/s) versus 2.9 ml/s (2.5-3.2 ml/s), (P < 0.0001). CONCLUSIONS: Both the pumps used in this study are safe alternatives for rapid transfusion of RBCs; however, with MRP this can be accomplished approximately twice as fast as with the PIP.
Adenine↗
Factor V Leiden and venous thrombosis in Danish centenarians.
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Aged↗
A fast and robust dual-label nonradioactive oligonucleotide ligation assay for detection of factor V Leiden.
Activated protein C resistance is in almost all cases caused by the factor V Leiden mutation (FV:R506Q). Due to the high prevalence and clinical significance of the mutation reliable methods suited for processing large sets of samples are in demand. We here present the oligonucleotide ligation assay (OLA) with lanthanide labeled oligonucleotides for the detection of FV Leiden. The assay is based on time resolved fluorescence measurement of lanthanide labeled oligonucleotides (DELFIA: Delayed Enhanced Lanthanide Fluorescence Immuno Assay) and on the specificity of T-4 DNA Ligase to join two adjacent oligonucleotides only when the two are complementary to the PCR template at the ligation junction. The Europium/Samarium fluorescence pattern is specific for each of the three genotypes (G/G, G/A, A/A) and clearly separates the three genotypes. By using a wildtype probe (Samarium labeled) and a mutant-specific probe (Europium labeled) simultaneously an internal control of the assay is included in each reaction. The assay is simple to perform, can be partly automated and is ideal for processing large sets of samples.
DNA Ligases↗
[Acute arsenic poisoning].
We report three cases of arsenic poisoning in a chemical factory. Three workers were exposed to vinyzene 10,10'-oxydephenarsine and developed mild symptoms of acute poisoning. All patients were treated with dimercaprol, and recovered after a few days. Urine analysis did not show increased arsenic excretion, but this could be due to the large urine samples taken. It is recommended that a urine sample is taken right after admission to hospital and new samples after eight and 16 hours.
Accidents, Occupational↗
Importance of various types of metabolic inhibition for cell damage caused by direct membrane damage.
Cell damage is caused by energy depletion or by direct membrane damage, or a combination when a direct membrane damage affects energy depleted cells. In this report it was investigated whether the extent of direct membrane damage induced by lysophosphatidyl choline (LPC) or phospholipase C (PhC) on quiescent fibroblasts depended on the metabolic state of the cells. When glycolysis was inhibited cell damage was always extensively increased, whereas cell damage was also increased to a minor degree when exposed to PhC during sole inhibition of oxidative phosphorylation. Acceleration of glycolysis in cells with a low rate of glycolysis resulted in a dramatic improvement of the membrane susceptibility within a few minutes. Thus, susceptibility of the cell membrane to direct membrane damage depends on the metabolic state. The results also emphasize previous findings that glycolysis has a special role in maintaining membrane function and integrity.
Antimycin A↗
Mechanisms of cell damage and enzyme release.
Release of intracellular enzymes to the extracellular space is a marker of cell damage in various diseases, e.g. liver, heart and muscle diseases. In the normal state the plasma membrane is impermeable to enzymes, and enzyme release, therefore, indicates a severe change of the membrane integrity. This review deals with the present knowledge about cellular changes leading to enzyme release, which may be caused either by energy depletion, e.g. in ischemia or shock, or by a direct membrane damage as caused by various toxins and inflammatory products. Inhibition of the energy metabolism results in ATP depletion leading to fluxes of Na+, K+ and Cl- down their gradients across the membrane and swelling of the cell. Subsequently Ca2+ leak into the cell activating phospholipases and the formation of eicosanoids, affecting the cytoskeleton and, perhaps, activating the formation of oxidants. The exact "point of no return" is not known but an uncontrolled Ca2+ activity in the cell probably has an important role in initiating the irreversible changes. The result of these reactions and probably other unknown reactions as well is damage to the membrane. This is evident morphologically at first by the formation of blebs that appears in the reversible phase, and later on by rupturing of the membrane, a sign of irreversible damage. A very small part of the enzyme release may occur in the reversible phase when blebs detach with resealing of the membrane, but the substantial part of enzyme release occurs as a result of irreversible cell damage when ATP has decreased to a low level and a serious disruption of the membrane integrity has taken place. All the secondary affections of the membrane during energy depletion may also occur as a primary direct membrane damage that more or less may affect the energy metabolism secondarily. The cell damage and enzyme release after some types of direct membrane damage is almost independent of the cellular energy metabolism whereas other types of direct membrane damage are counteracted by the cell by energy consuming reactions and, therefore, the final cell damage is a concerted action of the direct membrane damage and the energy depletion. This also means that a direct membrane damage may be more severe for the cell in energy depleted states than in the normal state. As in energy dependent cell damage the substantial part of enzyme release after a direct membrane damage is due to irreversible cellular changes. It appears that although the knowledge of the molecular basis of cell damage and enzyme release has grown there are still many questions to be answered about these complex processes.
Adenosine Triphosphate↗
Removal of calcium overload caused by A23187 is more dependent on glycolysis than oxidative phosphorylation.
An increase of cytosol Ca2+ may be the mediator of irreversible cell damage after ATP depletion. Ca2+ influx can also be induced by addition of the ionophore A23187. The extent of cell damage caused by A23187 during concomitant metabolic inhibition was investigated on quiescent fibroblasts. Inhibition of glycolysis resulted in increased cell damage compared to control, whereas an increased rate of glycolysis during inhibition of oxidative phosphorylation attenuated cell damage. These results indicate that glycolysis plays an important part in the removal of entering Ca2+.
Adenosine Triphosphate↗
Cytotoxicity testing of two CAPD dialysis fluids in a model system of quiescent fibroblasts.
Indications of some bio-incompatibility of fluids used for continuous ambulatory peritoneal dialysis (CAPD) have been found previously. We have tested cytotoxicity of an frequently used dialysis fluid, Dianeal, and a new bicarbonate-based dialysis fluid with a pH of 7.4, called 87b, in a model system of quiescent fibroblasts. The ATP level of the cells and release of lactate dehydrogenase was followed during incubation in the dialysis fluids. A marked cytotoxicity of Dianeal was found mainly due to a low pH (5.0-5.5) and to a minor degree because of the lack of potassium and glutamine. 87b was less cytotoxic but it also lacked potassium and glutamine.
Adenosine Triphosphate↗