Search PubMed⌕ Search

Biomedical subjects

A Sturk

Publications and source records attributed to A Sturk.

At least 109 records · Page 6Linked to original sources
PubMed1990

Protein C activity and antigen levels in childhood.

Hereditary protein C deficiency is an important risk factor for thrombosis. To enable its diagnosis shortly after birth, we determined reference values of protein C antigen and activity levels for the first 3 months of life. To establish an age-related range of protein C levels we also determined median values for individuals up to 18 years of age. A good correlation between the two levels was seen from the 3rd/4th month of life onwards, whereas in the first 2 months the activity levels were significantly lower than the antigen levels. This was not due to interference by the increased plasma citrate concentration at high haematocrit values, and may suggest a dysfunctional protein C molecule in the neonatal period. We found a rapid rise in protein C activity and antigen levels until the age of 7-9 months, followed by a slower progression toward adolescence. In contrast to previous reports, our results indicate that adult values are probably not achieved until sometime during the 2nd decade of life.

Adolescent↗
PubMed1990

Effect on thrombus growth and thrombolysis of two types of osmolar contrast media in rabbits.

Thromboembolic complications have been reported after diagnostic or interventional radiological procedures. However, contrast media inhibit platelet function and blood coagulation in vitro. To investigate these characteristics in vivo, we determined the effect of nonionic and ionic low osmolar contrast media on thrombus growth and thrombolysis in rabbits in a randomized study design. Rabbits received either ionic low osmolar contrast medium (ioxaglate), nonionic low osmolar contrast medium (iohexol) or saline. Thrombus growth was determined by the accretion of 125I-labeled fibrinogen on to autologous, nonradioactive, preformed thrombi in rabbit jugular veins. Thrombolysis was assessed by measurement of the decrease in radioactivity of standard sized preformed 125I-fibrinogen labeled thrombi. Ioxaglate significantly inhibited thrombus growth (60% inhibition, P less than 0.005 vs. saline), in contrast to iohexol, which had no significant effect (33% inhibition, P less than 0.2 vs. saline). Neither ioxaglate nor iohexol affected thrombolysis.

Animals↗
PubMed1990

Macro enzymes: prevalence, composition, detection and clinical relevance.

The presence of a macro enzyme, i.e. an enzyme with an abnormally high molecular weight, frequently leads to a genuinely increased serum activity or an interference in laboratory assays. This may thereby result in false positive diagnoses, such as acute myocardial infarction or pancreatitis. The various forms of macro enzymes are reviewed. In the case of immune complexes the immunoglobulins and (iso)-enzymes involved are discussed, as well as the specificity of the interaction, the prevalence and clinical relevance, associations with autoimmune or other diseases, and their behaviour in laboratory assays.

Adult↗
PubMed1990

Detection and clinical relevance of human endotoxemia.

An optimized chromogenic assay for the detection of endotoxins in human blood is described. The assay comprises the removal of the inhibitory activity of plasma components by a dilution plus heating procedure, endotoxin-dependent activation of Limulus amebocyte lysate, and chromogenic measurement of the activated lysate. The assay has a detection limit of 3 ng endotoxin/L plasma. At the 10 ng/L level within-assay CV and between-assay CV of 14 and 21% were obtained respectively. In a prospective clinical trial including 473 consecutive febrile patients the assay has previously been demonstrated to have positive and negative predictive values of 48% and 99% for impending Gram-negative sepsis, respectively. In a similar study in 76 consecutive patients with Gram-negative infection of the urinary tract, these values were 73% and 95%, respectively. We conclude that this assay may provide the means to select those patients who are most likely to benefit from anti-endotoxin treatment. To facilitate endotoxin testing in other laboratories, a preliminary evaluation of a commercial endotoxin assay versus our own method was performed with 108 duplicate blood samples obtained from septic patients. With this assay detection limits of 2-3 ng endotoxin/L plasma could be obtained, as well as a good correlation (r = 0.94) and level of consensus to establish endotoxemia (93%) as compared to the house method. The commercial assay may therefore facilitate the introduction of endotoxin testing in other laboratories.

Bacterial Infections↗
PubMed1989

Thrombin-antithrombin III complexes in the prediction of deep vein thrombosis following total hip replacement.

In 196 consecutive patients who underwent elective total hip surgery we investigated the diagnostic accuracy of the thrombin-antithrombin III complex immunoassay, as assessed on the first, fourth and tenth postoperative day, for the development of deep vein thrombosis (DVT). Patients received either LMW-heparinoid (n = 97) or placebo (n = 99) and underwent contrast venography on the tenth postoperative day. Thrombin-antithrombin III (T-AT) plasma levels were raised in all patients on the first postoperative day and gradually decreased during the study period. T-AT plasma levels were significantly higher in patients developing DVT when compared to patients without DVT and remained so until day 10. This difference was apparent both in the LMW-heparinoid group as well as in the placebo-treated patients. ROC-curve analysis revealed no satisfactory discriminative power for the diagnosis of developing DVT at any of the studied cut-off values for T-AT. We conclude that the postoperative determination of T-AT complex plasma concentrations in hip surgery patients has no clinical utility in the prediction of postoperative DVT.

Antithrombin III↗
PubMed1989

Synthesis of platelet-activating factor by human blood platelets and leucocytes. Evidence against selective utilization of cellular ether-linked phospholipids.

Synthesis of platelet activating factor (PAF) in blood platelet suspensions may be due to leucocyte contamination. We therefore investigated PAF synthesis in human blood platelet suspensions and granulocyte- (PMN)-enriched leucocyte suspensions upon stimulation by thrombin and Ca2+-ionophore A23187, both in the presence and absence of the presumed PAF catabolism inhibitor phenylmethylsulfonyl fluoride (PMSF). PAF synthesis was measured by aggregation of washed rabbit platelets and by [3H]acetate incorporation. In contrast to A23187, thrombin was unable to stimulate PAF synthesis by leucocytes. As thrombin did induce PAF synthesis by platelet suspensions, this was evidently not due to leucocyte contamination. A23187 also induced PAF synthesis by platelets, but this was dependent upon the platelet isolation method and possibly associated activation. The ratio of [3H]acetate incorporation into 1-alkyl- versus 1-acyl-2-acetylglycerophosphocholine upon stimulation of non-PMSF-treated leucocytes and platelets amounted to 12.8 and 1.2, respectively. These values are at least 10-fold higher than the ratio of 1-alkyl versus 1-acyl species in the cellular phosphatidylcholine precursor for PAF. By PMSF pretreatment, the distribution of incorporated [3H]acetate between 1-ether- and 1-ester-linked species became similar to that in the precursor phosphatidylcholines of the respective cell type, due to increased recovery of [3H]acetate in the acyl compounds. Both leucocyte and platelet homogenates rapidly degraded acylacetylglycerophosphocholine to (acetyl)glycerophosphocholine, and this deacylation was inhibited by PMSF pretreatment of the cells. We conclude that upon cell stimulation a phospholipase A2 converts both alkylacylglycerophosphocholine and diacylglycerophosphocholine to the 2-lysoanalogs in a ratio similar to the occurrence of the parent compounds. The acetyltransferase subsequently acetylates both compounds to acylacetylglycerophosphocholine and alkylacetylglycerophosphocholine (PAF), respectively. Deacylation of the 1-ester-linked species, either before or after acetylation, gives the impression of selective utilization of 1-ether-linked species for PAF production. It is only after inhibition of the deacylation by pretreatment of the cells with PMSF that a mainly nondiscriminative use of 1-ether- and 1-ester-linked species by both phospholipase A2 and acetyltransferase becomes evident.

Acetates↗
PubMed1989

DDAVP induces systemic release of urokinase-type plasminogen activator.

The desamino-d-arginine vasopressin (DDAVP) induced enhancement of endogenous fibrinolysis is generally attributed to the release of tissue-type plasminogen activator (t-PA) from the vessel wall. The observation of concurrent release of urokinase-type plasminogen activator (u-PA), which eventually might cooperate in the enhanced fibrinolytic activity, has not been reported thus far. In a preliminary study in two healthy human volunteers we found a 1.8-fold increase of urokinase-antigen (UK-antigen) and a 1.7-fold increase of plasmin-activatable pro-urokinase (pro-UK) activity to DDAVP intravenously. The plasma-peak levels coincided with the maximal t-PA level. These responses following infusion of DDAVP were subsequently confirmed in a randomized double blind cross-over study in six human volunteers. We conclude that u-PA is released by DDAVP concurrently with t-PA and that it is presumably from the same origin as t-PA i.e. endothelial cells. u-PA and t-PA may therefore cooperate in the enhanced fibrinolytic activity upon DDAVP infusion.

Deamino Arginine Vasopressin↗
PubMed1989

Enhanced thrombin generation in normal and hypertensive pregnancy.

We investigated the plasma levels of thrombin-antithrombin III complexes in women with uncomplicated pregnancy, patients with preeclampsia, gestational hypertension, and nonpregnant control subjects. In addition, we measured the coagulation inhibitors antithrombin III, protein C, and protein S. In normal pregnancy we observed a progressive increase in plasma thrombin-antithrombin III levels, and a decrease in protein S levels. In preeclampsia we observed increased thrombin-antithrombin III levels, reduced antithrombin III and protein C levels, and no further reduction of protein S compared with normal pregnancy. These new methods provide solid evidence for a prethrombotic state in normal pregnancy, especially in preeclampsia.

Adult↗
PubMed1989

The effects of bupivacaine and pipecoloxylidide on platelet function in vitro.

The influence of bupivacaine and its major metabolite, pipecoloxylidide, on human platelet function was studied in vitro. Significant inhibition of ADP and collagen-induced platelet aggregation occurred only with concentrations of bupivacaine above 10 micrograms.ml-1. This concentration (10-25 micrograms.ml-1) is much higher than would be expected in routine clinical use of bupivacaine for epidural analgesia. The inhibition of platelet aggregation was associated with a significant decrease in beta-thromboglobulin secretion. In contrast, pipecoloxylidide had no effect on platelet aggregation or the beta-thromboglobulin release. We conclude that the previously reported 30-min time-lag between the maximal plasma concentration of bupivacaine and the inhibition of platelet aggregation is unlikely to be due to a metabolism of bupivacaine to pipecoloxylidide.

Adult↗
PubMed1988

Platelet vinculin: a substrate of activated factor XIII.

In addition to plasma, Factor XIII of blood coagulation (FXIII) is also present in the cytosol of platelets, monocytes and macrophages. However, its intracellular function has not yet been revealed. Activated Factor XIII (FXIIIa) is a transglutaminase (protein-glutamine: amine gamma-glutamyltransferase, EC 2.3.2.13) of highly restricted substrate specificity with only a few known protein substrates. In this report, we showed that FXIIIa can link dansylcadaverine, radiolabelled histamine and putrescine to vinculin. Quantitative determinations revealed that in the vinculin molecule a single glutamine residue can serve as acyl donor for the incorporation of small-molecular-weight amines. Vinculin could not be crosslinked to another vinculin molecule. It could be covalently bound, however, to fibrinogen, which indicates that the acyl donor glutamine residue can be engaged in an epsilon-(gamma-glutamyl)lysyl crosslink formation. Since it has been shown that platelet actin and myosin, two main components of cytoskeleton, are also substrates for FXIIIa, and that vinculin is associated to the cytoskeleton during platelet activation, the involvement of FXIII in the stabilization of cytoskeleton at certain phases of cellular function is a likely possibility.

Animals↗
PubMed1988

Endotoxaemia: an early predictor of septicaemia in febrile patients.

In 473 consecutive febrile patients a sensitive and rapid chromogenic limulus assay was used to assess the value of endotoxaemia versus bacteraemia for predicting development of the syndrome of septicaemia. In each patient three blood specimens for culture and endotoxin testing were obtained at the onset of fever. Blood pressure, urinary output, and the occurrence of thrombocytopenia and metabolic acidosis were recorded prospectively during three days of follow-up. Septicaemia developed in 19 patients (4%). The sensitivity, specificity, and likelihood ratio for a positive result with the endotoxin assay were 79%, 96%, and 20, respectively. The corresponding indices for bacteraemia were 89%, 78%, and only 4. The results suggest that endotoxaemia is a clinically valid indicator for impending gram-negative septicaemia (positive predictive value 48%) and that the absence of endotoxaemia virtually rules out the risk that septicaemia will ensue (negative predictive value 99%).

Adolescent↗
PubMed1988

Acquired alpha-2-antiplasmin deficiency in acute promyelocytic leukaemia.

We report a prospective study in nine consecutive adult patients with acute promyelocytic leukaemia (APL). The study objective was to assess the prevalence of activation of blood coagulation and/or activation of fibrinolysis in APL. Coagulation and fibrinolytic parameters relevant to the objective included antithrombin III, plasminogen, fibrin/fibrinogen degradation products and alpha-2 antiplasmin activity and antigen levels. The results of this study revealed consistently normal antithrombin III levels, both before and in the course of antileukaemic treatment. Plasminogen levels were slightly decreased or normal. However, a distinct alpha-2 antiplasmin activity deficiency in all patients was observed with levels even reaching zero in three patients, during chemotherapy. Alpha-2 antiplasmin activity levels were consistently lower than the alpha-2 antiplasmin antigen levels. The in vitro binding of alpha-2 antiplasmin activity to fibrin clots was severely reduced which appeared to be due to the reduced alpha-2 antiplasmin plasma levels. Upon crossed-immunoelectrophoresis against alpha-2 antiplasmin antiserum two alpha-2 antiplasmin antigen peaks were observed in the plasma of all nine patients. All abnormalities were reversible 4 d after completion of chemotherapy. In a second series of 12 consecutive APL patients we confirmed the consistency of the alpha-2 antiplasmin activity deficiency and normal antithrombin III plasma levels. In addition Protein C activity and antigen levels were normal or near normal in 10 and reduced in two patients. Thrombin-antithrombin III complexes were increased in 10 and normal in two patients. We conclude that some activation of blood coagulation is present in APL (increased thrombin-antithrombin III complex levels) but its contribution to the coagulopathy seems to be minor (normal antithrombin III and only slightly reduced protein C levels). The observed reduced alpha-2 antiplasmin content of the fibrin clot in vitro may result in vivo in a fibrin clot that is highly susceptible to fibrin degradation, thus aggravating the coagulopathy in APL.

Blood Coagulation↗
PubMed1988

Laboratory and clinical evaluation of an assay of thrombin-antithrombin III complexes in plasma.

We evaluated a recently developed commercial assay for quantifying thrombin-antithrombin III (TAT) complexes in human plasma. The assay is precise (within-assay CV less than 10%, between-assay CV less than 13%), and sensitive (detection limit 0.7 micrograms of TAT per liter of plasma). Measurements for healthy volunteers yielded a normal reference (95 percentile) interval of 0.8 to 5.0 micrograms/L (n = 50, mean 2.1 micrograms/L, range 1.1 to 7.5 micrograms/L). TAT concentrations were increased in 25 of the 41 patients who fulfilled the clinical criteria of disseminated intravascular coagulation (DIC, overall mean 15.8 micrograms/L) and in 30 of the 35 patients with deep-vein thrombosis of the leg (overall mean 9.4 micrograms/L). We assessed the accuracy of the TAT assay by comparison with established criteria for the laboratory diagnosis of DIC involving various cutoff values for antithrombin III, factor V, fibrinogen, platelet count, fibrin/fibrinogen degradation products, and activated partial thromboplastin time. The low specificity of the TAT assay with regard to some of these criteria indicates that the latter are probably insensitive.

Antithrombin III↗
PubMed1988

The influence of epidural analgesia on platelet function and correlation with plasma bupivacaine concentrations.

The effect of epidural anaesthesia with bupivacaine 0.5% on platelet aggregation was studied in seven patients undergoing transurethral resection of the prostate. Peak plasma concentrations of bupivacaine 470 +/- 270 ng ml-1 occurred at 30 min after administration. At that time there were no significant changes in platelet aggregation. However, the maximum rate of the primary- and secondary-aggregation velocities induced by 1.0 microM ADP were significantly decreased at 1 h and 3 h after bupivacaine administration. The maximum percentage ADP-induced platelet aggregation was also decreased significantly at 1 h and 3 h. The minimum concentration of ADP required to induce secondary-phase platelet aggregation was significantly increased at 1 h but not at 3 h. There was a significant correlation between bupivacaine concentrations and all platelet aggregation parameters except the maximum ADP-induced aggregation. Platelet inhibition occurred at plasma bupivacaine concentrations that were considerably lower than those needed to produce similar inhibition in vitro.

Adenosine Diphosphate↗
PubMed1988

Endotoxins in portal blood.

Endotoxemia may complicate diseases of the bowel and liver, and is associated with the occurrence of renal failure, coagulation disorders and death. The bowel contains a large quantity of endotoxins. According to the classical hypothesis, endotoxins continuously transmigrate through the bowel mucosa, thereby entering the portal circulation. However, previous studies on portal endotoxemia were contradictory. We studied the presence of endotoxins in the portal vein in 21 consecutive patients with no diseases of the liver or the bowel, using a sensitive chromogenic endotoxin assay. In only two patients was low level portal endotoxemia detected after cross-clamping of the aorta, and subsequent reperfusion. We conclude that the normal bowel mucosa is an efficient barrier for endotoxins. Therefore, intestinal endotoxemia complicating liver disease is likely to result from enhanced permeability of the bowel mucosa.

Aorta, Abdominal↗