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Biomedical subjects

E de Jonge

Publications and source records attributed to E de Jonge.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of different plasma substitutes on blood coagulation: a comparative review.

OBJECTIVE: To compare the effects of different colloid plasma substitutes on blood coagulation and postoperative blood loss. DATA SOURCES: Relevant studies were obtained from the medical literature. STUDY SELECTION: Articles were selected that provided data on the effects of colloids on hemostasis and postoperative blood loss in humans. Studies comparing different colloids were looked for using MEDLINE and by searching through the references of studies as they were collected. DATA SYNTHESIS: Articles were reviewed and relevant data were extracted and partly presented in comparative tables. CONCLUSIONS: Dextran, gelatin, and hydroxyethyl starch (HES) all can induce a specific decrease of von Willebrand factor and factor VIII:c. Blood coagulation is most impaired by dextran and high molecular weight HES, both associated with increased postoperative blood loss. The effects of HES on blood coagulation have been shown to depend on its molecular weight and rate of elimination. Detrimental effects have been shown for high molecular weight HES. Medium molecular weight (MMW)-HES with a high degree of substitution (HES 200/0.62) and MMW-HES with high C2/C6 hydroxyethylation ratio (HES 200/0.5/13) are slowly degradable and have been shown to impair blood coagulation after repeated administration. Rapidly degradable HES 200/0.5/6 and gelatin-based plasma expanders appear not to impair hemostasis. However, based on the reviewed literature, all artificial colloids could potentially induce increased bleeding tendency after infusion of very large volumes and especially when given to patients with even mild forms of von Willebrand disease. In those circumstances, crystalloid solutions or alternatives such as plasma or albumin, although associated with other serious complications, could be considered.

Blood Coagulation↗
PubMed2001

Rationale for restoration of physiological anticoagulant pathways in patients with sepsis and disseminated intravascular coagulation.

OBJECTIVE: In the pathogenesis of disseminated intravascular coagulation, dysfunctional natural anticoagulant pathways appear to play a pivotal role. In this article, we will address the mechanisms that contribute to this defect in the regulation of coagulation activation. Furthermore, we will explore the experimental and clinical evidence that restoration of these anticoagulant pathways results in clinical improvement. DATA SOURCES: We have searched and reviewed published articles on experimental studies of disseminated intravascular coagulation models in animals and clinical studies in patients with disseminated intravascular coagulation. DATA SYNTHESIS: All three major anticoagulant pathways, that is, the antithrombin pathway, the protein C system, and tissue factor pathway inhibitor, are defective in sepsis and disseminated intravascular coagulation. Several mechanisms contribute to this defect. Restoration of these pathways, in principle, by administration of coagulation inhibitor concentrates or recombinant anticoagulant factors, appears to ameliorate the coagulation disorder and, more important, result in improvement of clinically relevant outcomes, such as a reduction of organ failure and mortality. CONCLUSIONS: Restoration of disrupted physiologic anticoagulant pathways in disseminated intravascular coagulation is not only a logical point of impact in patients with sepsis and an activated coagulation system, but also is associated with an improved outcome in experimental and (initial) clinical studies.

Animals↗
PubMed2001

Uterine carcinosarcoma with melanocytic differentiation.

A 65-year-old black woman was found to have a 3.0 cm endometrial tumor that was a carcinosarcoma with a major epithelial and a less prominent mesenchymal component. The latter was undifferentiated but one focus of chondroid differentiation was noted. The former showed papillary serous differentiation. Melanin pigment was observed in both epithelial and mesenchymal components. Staining with antisera to S100 protein and HMB-45 confirmed the presence of melanocytes. An endocervical focus of tumor also contained melanin. Electron-microscopic studies showed large tumor cells with an irregularly indented nucleus and abnormal giant cytoplasmic melanosomes. Only one case of uterine carcinosarcoma with melanocytic differentiation has been previously reported.

Aged↗
PubMed2000

Up-regulation of HIV coreceptors CXCR4 and CCR5 on CD4(+) T cells during human endotoxemia and after stimulation with (myco)bacterial antigens: the role of cytokines.

Concurrent infections in patients with human immunodeficiency virus (HIV) infection stimulate HIV replication. Chemokine receptors CXCR4 and CCR5 can act as HIV coreceptors. The authors hypothesized that concurrent infection increases the HIV load through up-regulation of CXCR4 and CCR5. Using experimental endotoxemia as a model of infection, changes in HIV coreceptor expression were assessed in 8 subjects injected with lipopolysaccharide (LPS, 4 ng/kg). The expression of CXCR4 and CCR5 on CD4(+) T cells was increased 2- to 4-fold, 4 to 6 hours after LPS injection. In whole blood in vitro, LPS induced a time- and dose-dependent increase in the expression of CXCR4 and CCR5 on CD4(+) T cells. Similar changes were observed after stimulation with cell wall components of Mycobacterium tuberculosis (lipoarabinnomannan) or Staphylococcus aureus (lipoteichoic acid), or with staphylococcal enterotoxin B. LPS increased viral infectivity of CD4-enriched peripheral blood mononuclear cells (PBMCs) with a T-tropic HIV strain. In contrast, M-tropic virus infectivity was reduced, possibly because of elevated levels of the CCR5 ligand cytokines RANTES and MIP-1beta. LPS-stimulated up-regulation of CXCR4 and CCR5 in vitro was inhibited by anti-TNF and anti-IFN gamma. Incubation with recombinant TNF or IFN gamma mimicked the LPS effect. Anti-interleukin 10 (anti-IL-10) reduced CCR5 expression, without influencing CXCR4. In accordance, rIL-10 induced up-regulation of CCR5, but not of CXCR4. Intercurrent infections during HIV infection may up-regulate CXCR4 and CCR5 on CD4(+) T cells, at least in part via the action of cytokines. Such infections may favor selectivity of HIV for CD4(+) T cells expressing CXCR4. (Blood. 2000;96:2649-2654)

Adult↗
PubMed2000

Reduced ex vivo chemokine production by polymorphonuclear cells after in vivo exposure of normal humans to endotoxin.

Monocytes from patients with sepsis have a reduced capacity to produce cytokines, a state referred to as immunoparalysis. To determine whether polymorphonuclear leukocytes (PMNL) can be rendered hyporesponsive, PMNL from 6 healthy volunteers intravenously challenged with lipopolysaccharide (LPS; 4 ng/kg) were stimulated ex vivo with heat-killed bacteria or LPS, and the release of the CXC chemokines interleukin-8, epithelial-derived neutrophil attractant-78, and growth-related oncogen-alpha was measured. At 1 and 2 h after LPS administration in vivo, PMNL produced fewer CXC chemokines after stimulation with bacteria or LPS (all P<.05). Serum obtained 2 h after in vivo administration of LPS did not influence chemokine production by PMNL from 6 healthy volunteers not previously exposed to LPS. Thus, intravenous injection of LPS induces a refractory state of PMNL that is not caused by soluble factors produced in response to in vivo exposure to LPS.

Adult↗
PubMed2000

Current management of disseminated intravascular coagulation.

Both a bleeding and a thrombotic disorder, disseminated intravascular coagulation presents diagnostic and therapeutic challenges. At present, diagnosis requires a set of blood tests; therapy focuses on reversing the underlying disorder and providing supportive treatment. Clinical studies of specific tests and treatments are now under way.

Aged↗
PubMed2000

The in vivo kinetics of tissue factor messenger RNA expression during human endotoxemia: relationship with activation of coagulation.

Triggering of the tissue factor (TF)-dependent coagulation pathway is considered to underlie the generation of a procoagulant state during endotoxemia. To determine the in vivo pattern of monocytic TF messenger RNA (mRNA) expression during endotoxemia, 10 healthy volunteers were injected with lipopolysaccharide (LPS, 4 ng/kg) and blood was collected before and 0.5, 1, 2, 3, 4, 6, 8, and 24 hours after LPS administration. Total blood RNA was isolated and amplified by NASBA (nucleic acid sequence-based amplification), followed by quantitation of TF mRNA by an electrochemiluminescence (ECL) assay. To compare the pattern of coagulation activation with the kinetics of monocytic TF mRNA expression, we measured plasma levels of markers of thrombin generation, thrombin-antithrombin (TAT) complexes, and prothrombin fragment 1 + 2 (F1 + 2). Baseline value (mean +/- SEM) of the number of TF mRNA molecules per monocytic cell was 0.08 +/- 0.02. A progressive and significant (P <.0001) increase in TF expression was observed after LPS injection (+0.5 hour: 0.3 +/- 0.1, +1 hour: 1.3 +/- 0.9, +2 hours: 4.1 +/- 0.9), peaking at +3 hours (10 +/- 1.9 TF mRNA molecules per monocyte). As TF mRNA levels increased, thrombin generation was augmented. Peak levels of TAT and F1 + 2 were reached later (at t +4 hours) than those of TF mRNA. TF mRNA, TAT, and F1 + 2 levels returned to baseline after 24 hours. In conclusion, we used a NASBA/ECL-based technique to quantify TF mRNA in whole blood during human endotoxemia and observed a 125-fold increase in TF mRNA levels. Our data demonstrate a pivotal role for enhanced TF gene activity in the activation of coagulation after LPS challenge. (Blood. 2000;96:554-559)

Adult↗
PubMed2000

Granulocyte colony-stimulating factor receptors on granulocytes are down-regulated after endotoxin administration to healthy humans.

Granulocyte colony-stimulating factor (G-CSF) is considered an important mediator of host defense against infection, and recombinant G-CSF is administered to patients with various infections. G-CSF binds to a specific receptor that is expressed on granulocytes and monocytes. To obtain insight about the regulation of the G-CSF receptor after an acute infectious challenge, 8 healthy subjects received an intravenous injection of lipopolysaccharide (LPS; 4 ng/kg), and receptor expression was determined on blood leukocytes by fluorescence-activated cell sorter analysis, both by measurement of saturation binding of recombinant G-CSF and by use of an anti-G-CSF-receptor antibody. LPS induced a transient decrease in granulocyte, but not monocyte, G-CSF-receptor expression. In whole blood in vitro, not only LPS but also gram-positive stimuli and proinflammatory cytokines were capable of down-modulating the G-CSF receptor on granulocytes. Bacterial antigens down-regulate the G-CSF receptor at the surface of granulocytes, which may impair neutrophil functions important for antibacterial host defense.

Adult↗
PubMed2000

[Disseminated intravascular coagulation].

Disseminated intravascular coagulation is characterised by systemic activation of blood coagulation, resulting in formation of intravascular thrombi and impaired organ perfusion. Simultaneously, the ongoing consumption of platelets and coagulation factors may lead to bleeding. Disseminated intravascular coagulation is seen in septicaemic infections, trauma, malignancies, obstetrical complications, vascular diseases, toxic and immunological reactions. In summary, the systemic deposition of fibrin is caused by enhanced thrombin generation, simultaneous depression of physiological anticoagulant mechanisms and diminished fibrin degradation due to inhibition of fibrinolysis. The increased insight into the pathogenesis of disseminated intravascular coagulation provides a solid basis for development of improved management strategies for patients with this complication. Therapy may include anticoagulants, platelet and plasma transfusion, concentrates of coagulation inhibitors and antifibrinolytic agents.

Anticoagulants↗
PubMed2000

Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia.

Inhibition of the tissue factor pathway has been shown to attenuate the activation of coagulation and to prevent death in a gram-negative bacteremia primate model of sepsis. It has been suggested that tissue factor influences inflammatory cascades other than the coagulation system. The authors sought to determine the effects of 2 different doses of recombinant tissue factor pathway inhibitor (TFPI) on endotoxin-induced coagulant, fibrinolytic, and cytokine responses in healthy humans. Two groups, each consisting of 8 healthy men, were studied in a double-blind, randomized, placebo-controlled crossover study. Subjects were studied on 2 different occasions. They received a bolus intravenous injection of 4 ng/kg endotoxin, which was followed by a 6-hour continuous infusion of TFPI or placebo. Eight subjects received 0.05 mg/kg per hour TFPI after a bolus of 0.0125 mg/kg (low-dose group), and 8 subjects received 0.2 mg/kg per hour after a bolus of 0.05 mg/kg (high-dose group). Endotoxin injection induced the activation of coagulation, the activation and subsequent inhibition of fibrinolysis, and the release of proinflammatory and antiinflammatory cytokines. TFPI infusion induced a dose-dependent attenuation of thrombin generation, as measured by plasma F1 + 2 and thrombin-antithrombin complexes, with a complete blockade of coagulation activation after high-dose TFPI. Endotoxin-induced changes in the fibrinolytic system and cytokine levels were not altered by either low-dose or high-dose TFPI. The authors concluded that TFPI effectively and dose-dependently attenuates the endotoxin-induced coagulation activation in humans without influencing the fibrinolytic and cytokine response. (Blood. 2000;95:1124-1129)

Adult↗
PubMed2000

Endotoxin down-regulates monocyte and granulocyte interleukin-6 receptors without influencing gp130 expression in humans.

Interleukin (IL)-6 is important for host defense against various pathogens. The IL-6 receptor (IL-6R) complex consists of a ligand-binding component (IL-6R) and a signal-transducing component (gp130). In a study designed to obtain insight into the regulation of this receptor complex during inflammation, 8 healthy subjects received an intravenous injection of lipopolysaccharide (LPS; 4 ng/kg), and receptor expression was determined on blood leukocytes by use of fluorescence-activated cell cytometry. LPS induced a transient decrease in monocyte and granulocyte IL-6R expression but did not influence gp130. The plasma concentrations of soluble IL-6R and soluble gp130 did not change after LPS administration. Expression of the receptor for leukemia inhibitory factor, a member of the IL-6R family, remained unaltered after LPS injection. In whole blood in vitro, LPS and gram-positive stimuli and proinflammatory cytokines were capable of down-modulating the IL-6R. Monocytes and granulocytes may down-regulate IL-6R at their surface upon their first interaction with bacterial antigens.

Adult↗
PubMed2000

Novel approaches to the management of disseminated intravascular coagulation.

OBJECTIVE: Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to widespread deposition of fibrin in the circulation. We addressed the issue of whether there is evidence that this fibrin deposition contributes to multiple organ failure. We also explored the current knowledge on the pathogenesis of DIC and reviewed current and future treatment for DIC. DATA SOURCES: We searched and reviewed published articles on experimental studies of DIC models in animals and clinical studies in patients with DIC. DATA SYNTHESIS: There is ample experimental and clinical evidence that DIC contributes to morbidity and mortality. Recent knowledge on important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and therapeutic approaches to patients with DIC. Although the trigger for the activation of the coagulation system may vary depending on the underlying condition, it is usually mediated by several cytokines. Thrombin generation proceeds via the (extrinsic) tissue factor/factor VIIa route and simultaneously occurring depression of inhibitory mechanisms, such as antithrombin III and the protein C-protein S system. Also, impaired fibrin degradation, because of high circulating levels of plasminogen activator inhibitor, type 1, contributes to enhanced intravascular fibrin deposition. CONCLUSIONS: Although the cornerstone of DIC management is the specific and vigorous treatment of the underlying disorder, strategies aimed at inhibiting coagulation activation may theoretically be justified. Such strategies have been found to be beneficial in experimental and initial clinical studies. These strategies, which follow from our current understanding of the pathophysiology of DIC, involve inhibition of tissue factor-mediated activation of coagulation or restoration of physiologic anticoagulant pathways by means of the administration of antithrombin concentrate or (activated) protein C concentrate. Although no complete evidence from controlled clinical trials is available for most of the proposed therapeutic interventions, these novel strategies are being studied.

Animals↗
PubMed2000

Reduced Th1, but not Th2, cytokine production by lymphocytes after in vivo exposure of healthy subjects to endotoxin.

Endotoxin (lipopolysaccharide [LPS]) tolerance is characterized by a reduced capacity of monocytes to produce proinflammatory cytokines upon restimulation in vitro. To determine whether LPS exposure induces a change in lymphocyte cytokine production and whether this results in a shift in the T-helper 1 (Th1)/Th2 balance, whole blood obtained from seven healthy subjects before and after an intravenous injection of LPS (4 ng/kg) was stimulated in vitro with the T-cell stimulus anti-CD3/CD28 or staphylococcal enterotoxin B. Whole-blood production of the Th1 cytokines gamma interferon (IFN-gamma) and interleukin-2 (IL-2) was markedly reduced at 3 and 6 h, while the production of the Th2 cytokines IL-4 and IL-5 was not influenced or was slightly increased. The IFN-gamma/IL-4 ratio was strongly decreased at 6 h. Serum obtained after LPS exposure could slightly inhibit the release of IFN-gamma but increased IL-4 production during stimulation of blood drawn from subjects not previously exposed to LPS. Normal serum also inhibited IFN-gamma production, albeit to a lesser extent. LPS exposure influences lymphocyte cytokine production, resulting in a shift toward a Th2 cytokine response, an effect that may be mediated in part by soluble factors present in serum after LPS administration in vivo.

Adult↗
PubMed2000

Platelets release thrombopoietin (Tpo) upon activation: another regulatory loop in thrombocytopoiesis?

Thrombopoietin is produced at a constant rate by the liver and kidney and is removed from the circulation upon binding and subsequent uptake via the Tpo receptor, c-Mpl, expressed by platelets and mega-karyocytes. Apart from uptake, this study shows that platelets can also function as a storage pool for Tpo. Upon stimulation with various platelet agonists, full-length biologically active Tpo was released by platelets. Platelet fractionation experiments indicated that this Tpo most likely is contained in the granules. When platelets were preincubated with Tpo-peptide mimetic or truncated Tpo prior to maximal activation, a three- to fivefold increment in Tpo release was seen. whereas, the release of other granule proteins such as vWF-propeptide or serotonin remained unchanged. Therefore, the Mpl agonists might compete with Mpl-bound Tpo, thereby releasing Tpo into the platelet supernatant. Intravascular release of Tpo by platelets might occur in patients with massive platelet activation, as occurs in patients with disseminated intravascular coagulation. The Tpo concentration in these patients is elevated (p <0.01) and correlates with markers for thrombin generation, TAT complexes and F1+2(r(p)= 0.8 and 0.9; p <0.01). This suggests that the increment in Tpo concentration was attributed to Tpo release by activated platelets in vivo, which might be instrumental in subsequent stimulation of thrombocytopoiesis.

Adult↗
PubMed1999

Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints.

BACKGROUND: Excessive bleeding may complicate cardiac surgery, and is associated with increased morbidity and mortality. Pharmacological strategies to decrease perioperative bleeding have been investigated in a large number of controlled trials, most of which have shown a decrease in blood loss. However, most studies lacked sufficient power to detect a beneficial effect on clinically more relevant outcomes. We did a meta-analysis of all randomised, controlled trials of the three most frequently used pharmacological strategies to decrease perioperative blood loss (aprotinin, lysine analogues [aminocaproic acid and tranexamic acid], and desmopressin). METHODS: Studies were included if they reported at least one clinically relevant outcome (mortality, rethoracotomy, proportion of patients receiving a transfusion, or perioperative myocardial infarction) in addition to perioperative blood loss. In addition, a separate meta-analysis was done for studies concerning complicated cardiac surgery. FINDINGS: We identified 72 trials (8409 patients) that met the inclusion criteria. Treatment with aprotinin decreased mortality almost two-fold (odds ratio 0.55 [95% CI 0.34-0.90]) compared with placebo. Treatment with aprotinin and with lysine analogues decreased the frequency of surgical re-exploration (0.37 [0.25-0.55], and 0.44 [0.22-0.90], respectively). These two treatments also significantly decreased the proportion of patients receiving any allogeneic blood transfusion. By contrast, the use of desmopressin resulted in a small decrease in perioperative blood loss, but was not associated with a beneficial effect on other clinical outcomes. Aprotinin and lysine analogues did not increase the risk of perioperative myocardial infarction; however, desmopressin was associated with a 2.4-fold increase in the risk of this complication. Studies in patients undergoing complicated cardiac surgery showed similar results. INTERPRETATION: Pharmacological strategies that decrease perioperative blood loss in cardiac surgery, in particular aprotinin and lysine analogues, also decrease mortality, the need for rethoracotomy, and the proportion of patients receiving a blood transfusion.

Aminocaproates↗
PubMed1998

An evaluation of Patient Data Management Systems in Dutch intensive care.

OBJECTIVE: To assess the agreement between the functions of seven configurations of Patient Data Management Systems (PDMS) and the Dutch specifications prepared by the users prior to use. DESIGN: An observational descriptive study with hospital visits of seven configurations of five different PDMS systems including three commercial systems and two locally developed systems. SETTING: Seven Dutch level I intensive care units in university and teaching hospitals. MEASUREMENTS AND RESULTS: A substantial disagreement was found between the Dutch specifications and the actual functions of the PDMS configurations tested. Between the PDMS configurations, major differences in key features, including "automated charting", "information and care planning", and "management information", were observed. Automated charting is adequately supported by the three commercial systems. All configurations tested had limited functions supporting care planning. In none of the configurations tested was the required function present to support unit management with reports on resource utilisation and outcome performance. The automatic calculation of prognostic scores was either absent or incorrect. The implementation, the (continuous) configuration and the training required a substantial investment in costs and human resources. CONCLUSION: Today, none of the PDMSs tested satisfy the Dutch specifications. This can be explained by technical impossibilities of the systems and shortcomings in the actual configuration or in the unit organisation. The PDMS might become a valuable tool in improving the quality of ICU practice, but full implementation of these systems according to the specifications still has a long way to go.

Database Management Systems↗