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Biomedical subjects

A Sturk

Publications and source records attributed to A Sturk.

At least 73 records · Page 4Linked to original sources
PubMed1996

Intestinal permeability, circulating endotoxin, and postoperative systemic responses in cardiac surgery patients.

OBJECTIVES: To determine whether intestinal permeability increases during cardiac operations, and whether the degree of endotoxemia is related to this increase. Furthermore, to determine whether intestinal permeability is related to the hemodynamic state during operation and to postoperative systemic responses. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Twenty-three male patients undergoing elective coronary artery bypass surgery. INTERVENTIONS: Before surgery and during the fifth postoperative day, 100 mL of a solution containing L-rhamnose and cellobiose were administered orally. MEASUREMENTS AND MAIN RESULTS: Intestinal permeability was assessed by measuring the urinary excretion of L-rhamnose and cellobiose. Endotoxin concentrations in blood and prime fluid, hemodynamics, oxygen consumption, gas exchange, fluid balance, and the dose of vasoactive drugs were measured. Systemic responses were assessed by measuring hypermetabolism, circulatory support, and gas exchange. Intestinal permeation of cellobiose, reflecting paracellular transport, significantly increased during operation (p < 0.01), and correlated with the amount of circulating endotoxin (r2 = 0.46; p < 0.01). A high dose of ephedrine administered during operation, low baseline central venous pressure, and a less positive fluid balance during operation were associated with high intestinal permeability (r2 = 0.7; p < 0.01). Intestinal permeability was related to postoperative systemic responses (r2 = 0.49; p < 0.01). CONCLUSIONS: This study shows that during elective coronary artery bypass operations intestinal permeability between cells may increase. The degree of endotoxemia is related to this increase. Increased intestinal permeability is related to the use of ephedrine, especially during hypovolemia, and to postoperative systemic responses. Although a causative relation is not shown, these results might indicate that hypovolemia and vasoconstriction should be avoided during the operation.

Aged↗
PubMed1996

Cardiopulmonary bypass with modified fluid gelatin and heparin-coated circuits.

We have assessed the efficacy of cardiopulmonary bypass (CPB) using normal colloid oncotic pressure (COP) in a randomized, controlled study of 20 patients undergoing elective coronary artery surgery using heparin-coated circuits. For CPB, we used either crystalloid priming 1650 ml (n = 10) or colloid priming 1650 ml (2.4% modified fluid gelatin, n = 10). While COP did not change during bypass in the colloid group, a decline was observed in the crystalloid group (P = 0.005). By the end of bypass, the decrease in COP compared with baseline (delta COP) was 8.5 (S.D. 1.1) mm Hg in the crystalloid group compared with 1.5 (2.1) mm Hg in the colloid group (P = 0.0001). delta COP correlated positively with fluid balance during bypass (r2 = 0.41, P = 0.002). Similar increments in complement factors C3b/c and C4b/c, tumour necrosis factor-alpha and neutrophil elastase, but not endotoxins, were found in both groups as indicators of a systemic inflammatory response. A clinical performance score composed of fluid balance, postoperative duration of intubation and the difference between rectal temperature and skin temperature was more favourable in patients treated with colloid priming (P = 0.03). Median postoperative hospital stay was 7 (range 5-16) days in the crystalloid group compared with 5 (4-8) days in the colloid group (P = 0.016). Regression analysis indicated that CPB time, fluid balance during operation and postoperative PO2/FlO2 ratio were independent factors that predicted postoperative hospital stay. From these preliminary results we conclude that in the absence of endotoxaemia, use of a normal COP during CPB with modified fluid gelatin in heparin-coated circuits resulted in an improved postoperative course an a reduction in hospital stay.

Aged↗
PubMed1996

Endotoxaemia and postoperative hypermetabolism in coronary artery bypass surgery: the role of ketanserin.

In a randomized, double-blind clinical study in 29 patients undergoing elective coronary artery surgery, we assessed the role of ketanserin, an inhibitor of serotonin-induced vasoconstriction and weak alpha 1 sympathetic blocker, in reducing endotoxaemia and postoperative hypermetabolism. Male patients without major organ dysfunction were allocated randomly to receive either ketanserin or placebo. Hypermetabolism was defined as an increase in oxygen consumption in the early postoperative hours (delta Vo2). Circulating endotoxin (P = 0.04) and postoperative delta Vo2 (P = 0.03) were lower in the ketanserin patients. Endotoxaemia was associated also with low vascular filling. From these preliminary results we conclude that treatment with ketanserin during cardiac surgery may reduce but not abolish endotoxaemia and postoperative hypermetabolism.

Aged↗
PubMed1996

Prognostic value of troponin T, myoglobin, and CK-MB mass in patients presenting with chest pain without acute myocardial infarction.

OBJECTIVE: To assess the prognostic value of minor myocardial damage in patients presenting with chest pain without myocardial infarction. DESIGN: The relative risk of suffering a cardiac event in the next six months was assessed in patients with minor myocardial damage assessed by the cardiac markers CK-MB, myoglobin, and troponin T. SETTING: Emergency department of a large university hospital. PATIENTS: In 128 consecutive patients with chest pain, acute myocardial infarction (by WHO criteria) was ruled out; of these, 39 had a rise and fall of one or more markers, indicating minor myocardial damage. The presence of a documented history of coronary artery disease was assessed on admission. RESULTS: 24 patients had a subsequent event (cardiac death, acute myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting) in the next six months. An abnormal troponin T predicted a subsequent event while abnormal CK-MB or myoglobin did not. The relative risk for troponin T was 2.8 (95% confidence interval: 1.0 to 7.9), for myoglobin 1.0 (0.3 to 3.2), and for CK-MB 0.9 (0.2 to 3.4). A documented history of coronary artery disease predicted subsequent events with a relative risk of 3.9 (1.3 to 11.3). CONCLUSIONS: Troponin T was the only marker that predicted future events, but a documented history of coronary artery disease was the best predictor in patients in whom an acute myocardial infarction had been ruled out.

Aged↗
PubMed1996

Fetal and neonatal development of antithrombin III plasma activity and liver messenger RNA levels in sheep.

In healthy term human newborns a unique hemostatic balance exists with reduced plasma concentrations of several coagulant and anticoagulant proteins, including antithrombin III (AT III). In preterm newborns even lower AT III concentrations are observed, with an associated thromboembolic risk. As part of our study program on the gene regulation of AT III, we investigated whether the increase in plasma AT III activity during fetal and neonatal development is particularly controlled at the transcriptional level. Plasma AT III activity and liver AT III mRNA content between the 8th wk of gestation and the 4th wk after birth were determined in sheep. AT III activity gradually increased from 34% of the mean adult level at 8-10 wk of gestation to 86% (2.5-fold) at term (21 wk), and remained in the adult range after birth. The mean body weight, and thus plasma volume, increased 57-fold. Therefore, the total plasma AT III activity increased 140-fold. The total liver AT III mRNA content increased only 14-fold between these fetal stages, mainly due to increased liver weight. Therefore, the total plasma AT III activity increased 10-fold more than the liver AT III mRNA content. In the neonatal period between d 1-3 and 28, the total plasma AT III activity increased only 2-fold more than the liver AT III mRNA content. We conclude that the increase in plasma AT III activity during the fetal period, and similarly the neonatal period, is not regulated at the transcriptional level. Furthermore, a unique fetal isoform of AT III was detected in sheep. This isoform had a 2500-D higher molecular mass compared with the other fetal, neonatal, and adult AT III isoform, and disappeared from the circulation between d 2 and 7 after birth. These AT III isoforms differ in their carbohydrate moiety.

Animals↗
PubMed1995

Value of myoglobin, troponin T, and CK-MBmass in ruling out an acute myocardial infarction in the emergency room.

BACKGROUND: Ruling out acute myocardial infarction (AMI) on the basis of rapid assays for cardiac markers will allow early triage of patients and cost-effective use of available coronary care facilities. METHODS AND RESULTS: We studied the value of myoglobin, creatine kinase (CK)-MBmass, and troponin T in ruling out an AMI in the emergency room in 309 consecutive patients presenting with chest pain. The gold standard for AMI was the combination of history, ECG, and a typical curve of the CK-MB activity (CK-MBact). Myoglobin was the earliest marker, and its negative predictive value (NPV) was significantly higher than for CK-MBmass and troponin T from 3 to 6 hours after the onset of symptoms (myoglobin versus CK-MBmass, P < .03; myoglobin versus troponin T, P < .01). The NPV of myoglobin reached 89% 4 hours after the onset of symptoms. The NPV of CK-MBmass reached 95% 7 hours after the onset of symptoms. Troponin T was not an early marker for ruling out AMI, and NPV changed over time, together with CK-MBact. The early NPV was higher in a subgroup of patients with a low probability of the presence of AMI for the three markers. Cardiac markers rise earlier in patients with large infarcts than in patients with small infarcts as indicated by the cumulative proportion of the marker above the upper reference limit at each time point (myoglobin, P = .04; CK-MBmass, P = .013; troponin T, P = .016). CONCLUSIONS: For ruling out AMI in the emergency room, myoglobin is a better marker than CK-MBmass or troponin T from 3 until 6 hours after the onset of symptoms, but the maximal NPV reaches only 89%. At 7 hours, the NPV of CK-MBmass is 95%. The test characteristics are influenced by the probability of the presence of AMI in the patients studied and by the size of their AMI. Infarct size of AMI patients should be reported in studies evaluating cardiac markers.

Aged↗
PubMed1995

Myocardial performance in elderly patients after cardiopulmonary bypass is suppressed by tumor necrosis factor.

The aim of this study was to determine whether elderly patients (aged > or = 65 years, n = 20) in comparison with younger patients (aged < or = 55 years, n = 23) demonstrate a different biochemical and hemodynamic response to coronary artery bypass operations. In the elderly group, we calculated a smaller body surface area (p < 0.01) than that in the younger group, and more female patients were included in this group (p < 0.05). During cardiopulmonary bypass, the elderly had higher endotoxin plasma concentrations (p < 0.01) than the younger patients, and significantly more circulating tumor necrosis factor-alpha was found after operation (p < 0.04). In the intensive care unit, the elderly patients had a significantly higher pulmonary capillary wedge pressure (p < 0.001), a higher mean pulmonary artery pressure (p < 0.01), and a lower calculated left ventricular stroke work index (p < 0.05). Multivariate analysis for the postoperative outcome showed that the intergroup differences in tumor necrosis factor-alpha, mean pulmonary artery pressure, and pulmonary capillary wedge pressure could be explained mainly by the difference in age between the groups and that the calculated left ventricular stroke work index difference could be explained by the difference in circulating tumor necrosis factor-alpha levels. Thus in elderly patients higher circulating endotoxin and tumor necrosis factor-alpha concentrations were detected than in younger patients, which clinically resulted in a suppressed myocardial performance.

Age Factors↗
PubMed1995

Hemostatic function of aspirin-treated platelets vulnerable to cardiopulmonary bypass. Altered shear-induced pathway.

The impaired hemostasis of aspirin-treated patients is an annoying problem during and after cardiopulmonary bypass. The hemostatic function of platelets comprises two mechanisms: the shear-induced and the cyclooxygenase pathways. Because the latter is inhibited in aspirin-treated patients, the hemostatic function depends mainly on the former pathway. To investigate the effect of cardiopulmonary bypass on the shear-induced pathway, a double-blind study of preoperative aspirin treatment (325 mg) and placebo was conducted in 40 patients undergoing coronary artery bypass grafting. Postoperative blood loss was higher in the aspirin-treated patients than in the placebo-treated patients (p < 0.05). The shear-induced hemostasis was monitored by the in vitro bleeding test (Thrombostat), which mimics bleeding through an injured arteriole. The shear-induced pathway of aspirin-treated platelets was not affected before cardiopulmonary bypass, but it was impaired more during the operation (p < 0.01) and remained worse afterward (p < 0.05), compared with that of placebo-treated platelets. The inhibitory effects of aspirin on thromboxane production and on collagen-induced platelet aggregation remained throughout the operation. In aspirin-treated platelets, the aggregation capacity induced by adenosine diphosphate was inhibited before the operation (p < 0.05) and showed substantial recovery during the operation (p < 0.05). These results suggest that the shear-induced pathway of aspirin-treated platelets is more vulnerable to cardiopulmonary bypass than the pathway in normal platelets and causes severe impairment of hemostasis afterward.

Adenosine Diphosphate↗
PubMed1995

Early markers of blood coagulation and fibrinolysis activation in Argentine hemorrhagic fever.

Junin virus, an arenaviridae, is the etiological agent of Argentine hemorrhagic fever. In addition to thrombocytopenia, patients present several alterations in both the blood coagulation and the fibrinolytic system, but diffuse intravascular coagulation could not be demonstrated. To investigate further the activation status of the two systems, levels of thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2, protein C, total and free protein S, C4bBP, antithrombin III, t-PA, PAI-1 and D-dimer were measured. Fourteen patients with a confirmed diagnosis of Argentine hemorrhagic fever were included in the study, 2 were severe, 3 moderate and 9 mild clinical cases, but hemorrhages were slight throughout. Blood samples were collected for 6 consecutive days on admission and on remission. At admission TAT and F1 + 2 levels were increased in 13/14 patients, reaching 0.33 nM (0.06-0.87) and 2.16 nM (0.96-6.5), respectively. PC was low in 4 cases, fPS in 6 and tPS in 2, whereas C4bBP and ATIII values were within normal range. t-PA and D-dimer levels were high in 11/14 patients, reaching 20 ng/ml (2.7-106) and 1660 ng/ml (877-3780) respectively, while PAI-1 was considerably increased in the 2 severe cases and normal in the remainder. These results suggest low level though persistent process of blood coagulation and fibrinolysis activation in this viral hemorrhagic disease. We believe these abnormalities may lead to the well described bleeding manifestations in these patients.

Antithrombin III↗
PubMed1995

Coagulation activation and tissue necrosis in meningococcal septic shock: severely reduced protein C levels predict a high mortality.

In 35 consecutively admitted children (mean age: 4.3 years) with a clinical diagnosis of meningococcal septic shock (MSS), activation of the coagulation and fibrinolytic pathways was evaluated directly at admittance to the paediatric intensive care unit (ICU). The association of clinical signs and haemostatic abnormalities was assessed. All patients had signs of extensive activation of the coagulation system. The 28-day mortality was 26%. Protein C activity was strongly reduced, especially in non-survivors in whom it was significantly lower than in survivors (5% versus 23%; p < 0.0001). There was a strong negative correlation between protein C activity and the mean size of the skin lesions (r = -0.71, p < 0.001). These results suggest that an acquired protein C deficiency in MSS is related to the pathogenesis of purpura fulminans. Furthermore, no increase in C4b-binding protein (C4BP) and no decrease in the ratio free protein S/total protein S was observed, suggesting that a deficiency of free protein S as a result of increased C4BP does not play a pathogenetic role in meningococcal septic shock.

Adolescent↗
PubMed1995

A point mutation in an invariant splice acceptor site results in a decreased mRNA level in a patient with severe coagulation factor XIII subunit A deficiency.

Amplification and sequencing of exons I-XV of the gene encoding subunit A of coagulation factor XIII (FXIII) in a patient with severe subunit A deficiency revealed a single G-->A base substitution at the last position of intron E, mutating the invariant AG dinucleotide splice acceptor site to AA. Northern blot analysis of FXIII subunit A mRNA levels in peripheral mononuclear leukocytes showed that this mutation leads to an undetectable FXIII subunit A mRNA level, suggesting that the mutant transcript is either highly unstable or only spliced at low efficiency. Despite this low mRNA level we were able to amplify cDNA fragments containing the exonV-exonVI junction. Sequence analysis showed that the AA dinucleotide is not recognized by the splicing machinery. Instead, an AG dinucleotide located seven bases downstream of the mutated splice acceptor site is used as alternative acceptor. The resulting, alternatively spliced, FXIII subunit A transcript contains a deletion of the first seven bases of exon VI, while translation continues out of frame and leads to a premature stop codon 27 bases thereafter.

Base Sequence↗
PubMed1995

The influence of insulin, beta-estradiol, dexamethasone and thyroid hormone on the secretion of coagulant and anticoagulant proteins by HepG2 cells.

As a basis for regulatory studies on the influence of hormones on (anti)coagulant protein production by hepatocytes, we examined the amounts of the plasma proteins antithrombin III (AT III), protein C, protein S, factor II, factor X, fibrinogen, and prealbumin produced by the hepatoma cell line HepG2, into the culture medium, in the absence and presence of insulin, beta-estradiol, dexamethasone and thyroid hormone. Without hormones these cells produced large amounts of fibrinogen (2,452 +/- 501 ng/mg cell protein), AT III (447 +/- 16 ng/mg cell protein) and factor II (464 +/- 31 ng/mg cell protein) and only small amounts of protein C (50 +/- 7 ng/mg cell protein) and factor X (55 +/- 5 ng/mg cell protein). Thyroid hormone had a slight but significant effect on the enrichment in the culture medium of the anticoagulant protein AT III (1.34-fold) but not on protein C (0.96-fold) and protein S (0.91-fold). This hormone also significantly increased the amounts of the coagulant proteins factor II (1.28-fold), factor X (1.45-fold) and fibrinogen (2.17-fold). Insulin had an overall stimulating effect on the amounts of all the proteins that were investigated. Neither dexamethasone nor beta-estradiol administration did substantially change the amounts of these proteins. We conclude that the HepG2 cell is a useful tool to study the hormonal regulation of the production of (anti)coagulant proteins. We studied the overall process of protein production, i.e., the amounts of proteins produced into the culture medium. Detailed studies have to be performed to establish the specific hormonal effects on the underlying processes, e.g., transcription, translation, cellular processing and transport, and secretion.

Antithrombin III↗
PubMed1994

Aprotinin preserves hemostasis in aspirin-treated patients undergoing cardiopulmonary bypass.

Various clinical trials have shown that hemostasis is improved by the administration of aprotinin during cardiopulmonary bypass. However, this effect has not been proved for those patients treated preoperatively with aspirin. Therefore, a double-blind, placebo-controlled study was conducted to test the efficacy of low-dose aprotinin (2 x 10(6) KIU in the pump prime solution) in preserving hemostasis in 40 aspirin-treated (325 mg) patients undergoing coronary artery bypass grafting. Aprotinin brought about a decrease in the postoperative blood loss (p < 0.05). The in vitro bleeding test (Thrombostat) demonstrated that aprotinin preserved the platelet hemostatic function in aspirin-treated patients during cardiopulmonary bypass (p < 0.05). The inhibitory effects of aspirin on collagen-induced platelet aggregation and thromboxane production were not influenced by aprotinin treatment. The findings from the present study indicate that aprotinin preserves hemostasis in aspirin-treated patients during cardiopulmonary bypass, but aspirin's effect on platelets is maintained. Therefore, aprotinin seems to be a useful adjunct treatment in aspirin-treated patients undergoing coronary artery bypass grafting.

Aprotinin↗
PubMed1994

Perfusion-related factors of endotoxin release during cardiopulmonary bypass.

To investigate whether the release of endotoxin during cardiopulmonary bypass (CPB) is determined by perfusion-related factors, endotoxin concentrations were determined before, during, and after CPB in 21 male patients (age range 45-75 years) undergoing elective coronary artery bypass grafting. Hemodynamic parameters and oncotic pressure were also measured. Significant increases in endotoxin concentrations were observed after the start of CPB (P < 0.005), before aortic cross-clamp release (P < 0.05), and after aortic cross-clamp release (P < 0.05). The median endotoxin concentration after cessation of CPB was 0.264 EU/ml (range < 0.036-0.480 EU/ml). Endotoxin concentrations derived from the prime solutions were not contributory. Positive correlations were found between arterial pressure after the start of CPB and the endotoxin concentration 10 min after (r = 0.58, P < 0.01) and between the duration of aortic cross-clamping and the endotoxin concentration after the cessation of CPB (r = 0.64, P < 0.005). Arterial pressure after the start of CPB, the duration of aortic cross-clamping, and decrease in oncotic pressure appeared to be independent variables in a forward variable selection model that predicted endotoxin concentrations after CPB. We conclude that in patients undergoing elective coronary artery bypass grafting, an early phase of endotoxin release during CPB could be demonstrated, and that this is due to vasoconstriction. The endotoxin concentrations after the cessation of CPB were determined by early vasoconstriction, duration of aortic cross-clamping, and hypo-oncotic hemodilution.

Aged↗
PubMed1994

Activation of platelets by low-osmolar contrast media: differential effects of ionic and nonionic agents.

PURPOSE: To determine the effects of an ionic low-osmolar contrast medium (ioxaglate) and two nonionic low-osmolar contrast media (iohexol and iopamidol) on human platelet activation in vitro. MATERIALS AND METHODS: Flow cytometry analysis subsequent to reaction with fluorescence-labeled monoclonal antibodies was used to detect antigens that appear on the platelet surface on activation. RESULTS: Ioxaglate did not activate platelets, but evidence of platelet activation by iohexol and iopamidol was found in blood from two and three healthy volunteers, respectively, of the six volunteers studied. In addition, ioxaglate inhibited the thrombin-induced in vitro activation of platelets, whereas iohexol and iopamidol did not. CONCLUSION: These findings support a tendency toward a higher frequency of thromboembolic complications with nonionic low-osmolar contrast media, although clinical trials will be needed to confirm this possible trend.

Female↗
PubMed1994

Laboratory and clinical evaluation of a chromogenic endotoxin assay for horses with acute intestinal disorders.

In this study the laboratory and clinical performance of a chromogenic endotoxin assay for equine plasma was evaluated. The assay was sensitive (detection limit 3 ng LPS/L plasma), reproducible (within and between-assay CV at 50 ng LPS/L E. coli O111:B4 LPS standard addition was 5% and 7.5%, respectively), and not substantially affected by enhancement or inhibition phenomena (recovery of an in vitro spike was 75-125% in 80% of the samples). LPS added to whole blood was rapidly inactivated upon incubation at 37 degrees C but not at 0 degrees C. A recently developed blood collection tube for LPS testing was found suitable, i.e. LPS-free and providing non-contaminated samples. In 48 horses suffering from acute abdominal diseases requiring surgical treatment, LPS levels were significantly higher in platelet-rich plasma (PRP) than in platelet-poor plasma (PPP), and the proportional difference was related to the PRP platelet count (r = 0.52, p < 0.001, mean difference 48%, range 8-77%). LPS levels were also significantly higher in horses that died or were euthanized than in surviving horses (mean 16.5 and 7.1 ng/L PRP, respectively, p < 0.05). We conclude that LPS can be measured in equine plasma with picogram sensitivity and recommend the use of PRP instead of PPP for clinical LPS testing. For clinical use a decision limit for endotoxaemia of 5 ng LPS/L PRP appeared to be inadequate. Analysis at a higher cut-off level for endotoxaemia and the evaluation of clinical, pathological, and laboratory parameters would be more meaningful.

Acute Disease↗
PubMed1994

Monitoring anticoagulant therapy by activated partial thromboplastin time: hirudin assessment. An evaluation of native blood and plasma assays.

BACKGROUND: Recombinant hirudin (RH) is a new anticoagulant for prophylaxis and treatment of venous and arterial thrombosis. To which extent the activated partial thromboplastin time (APTT) is suitable for monitoring of RH has not been properly evaluated. Recently, a capillary whole blood device was developed for bed-side monitoring of the APTT and it was demonstrated that this device was suitable to monitor heparin therapy. However, monitoring of RH was not evaluated. STUDY OBJECTIVES: To evaluate in vitro and ex vivo the responsiveness and reproducibility for hirudin monitoring of the whole blood monitor and of plasma APTT assays, which were performed with several reagents and two conventional coagulometers. RESULTS: Large interindividual differences in hirudin responsiveness were noted in both the in vitro and the ex vivo experiments. The relationship between the APTT, expressed as clotting time or ratio of initial and prolonged APTT, and the hirudin concentration was nonlinear. A 1.5-fold increase of the clotting times was obtained at 150-200 ng/ml plasma. However, only a 2-fold increase was obtained at hirudin levels varying from 300 ng to more than 750 ng RH/ml plasma regardless of the assays. The relationship linearized upon logarithmic conversion of the ratio and the hirudin concentration. Disregarding the interindividual differences, and presuming full linearity of the relationship, all combinations were equally responsive to hirudin. CONCLUSIONS: All assays were equally responsive to hirudin. Levels up to 300 ng/ml plasma can be reliably estimated with each assay. The manual device may be preferable in situations where rapid availability of test results is necessary.

Adult↗