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J van der Meer

Publications and source records attributed to J van der Meer.

At least 37 records · Page 2Linked to original sources

[Treatment and prevention of haemorrhage with recombinant activated factor VII, not only in hemophilia].

Based on the improved insight into the mechanism of blood coagulation in vivo, recombinant factor VIIa (rFVIIa) has been developed as a pro-haemostatic agent. It has been shown that this treatment is effective in patients with haemophilia and an inhibiting antibody against a coagulation factor. Administration of rFVIIa can be effective in the treatment of bleeding episodes and the prevention of perioperative blood loss in a number of other coagulation disorders as well. Initial clinical studies indicate that administration of rFVIIa may also reduce blood loss in patients with severe bleeding without pre-existent abnormalities in blood coagulation, but this requires confirmation in additional clinical trials.

Autoantibodies↗

Efficacy of recombinant factor VIIa administered by continuous infusion to haemophilia patients with inhibitors.

We have prospectively monitored treatment of haemophilia patients with inhibitors by recombinant factor VIIa (rFVIIa) administered by continuous infusion to obtain more insight in the underlying factors of the clinical efficacy of this administration method. At present, 43 treatment episodes of 14 different Dutch haemophilia inhibitor patients are included in the database. Analysis of the data showed a discrepancy between the efficacy of rFVIIa continuous infusion treatment of acute and surgical bleeds in the oral cavity [one (14%) effective, two (29%) partially effective, four (57%) not effective] and other parts of the body [29 (80%) effective, four (11%) partially effective, two (6%) not effective, one (3%) impossible to classify]. Patients who had acute or surgical oral cavity bleeds, uncontrolled by rFVIIa continuous infusion, reacted favourably to rFVIIa continuous infusion in other locations of the body. Acute bleeding episodes in the oral cavity, which could not be controlled by rFVIIa continuous infusion, stopped when the treatment regimen was switched to rFVIIa bolus injections. Finally, haemostatic control during dental extractions was excellent after the initial rFVIIa bolus injection preceding the continuous infusion, but rebleeds occurred in all patients within 48 h under rFVIIa continuous infusion coverage. These observations suggest that the efficacy of rFVIIa continuous infusion depends, at least in part, on the location of the body in which the bleeding occurs and that rFVIIa bolus injections are more effective than rFVIIa continuous infusion in the oral cavity. We hypothesize that the inability of rFVIIa continuous infusion treatment to sufficiently inhibit fibrinolysis is the underlying cause of the decreased efficacy of rFVIIa continuous infusion treatment in the oral cavity.

Acute Disease↗

Effects of recombinant activated factor VII on coagulation measured by thromboelastography in liver transplantation.

Besides the conventional laboratory tests, thromboelastography (TEG) is used to monitor hemostasis during liver transplantation. A previous pilot study suggested a beneficial effect of recombinant activated factor VII (rFVIIa) on transfusion requirements in liver transplantation. In the present study, we assess the effects of rFVIIa on coagulation variables and TEG. In six study patients, the prothrombin time (PT), the activated partial thromboplastin time (aPTT) and TEG variables [reaction time (r), kinetic time (k), or clot formation time, alpha angle (alpha), and maximal amplitude (MA)] were recorded before and after the administration of a bolus of 80 microg/kg rFVIIa. These patients were compared with six controls who did not receive rFVIIa. In contrast with the control group, a significant shortening of PT (P = 0.028) and aPTT (P = 0.028), r (P = 0.046) and k (P = 0.043) values, and a significant incline of the alpha angle (P = 0.028) were noticed after injection of rFVIIa, whereas MA increased not significantly (P = 0.075). rFVIIa rapidly improved coagulation variables in liver transplant patients including PT and aPTT. Of the TEG variables, r, k and alpha angle significantly improved, and MA showed a trend to increase. These data suggest that rFVIIa not only influences the speed of clot formation, but also the physical properties of the clot, which cannot be detected by routine coagulation tests.

Adult↗

Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation: a pilot study.

BACKGROUND: Large transfusion requirements, i.e., excessive blood loss, during orthotopic liver transplantation (OLT) are correlated with increased morbidity and mortality. Recombinant factor VIIa (rF-VIIa) has been shown to improve hemostasis in a variety of conditions, but has never been studied in liver transplantation. METHODS: We performed a single-center, open-label, pilot study in adult patients undergoing OLT for cirrhosis Child-Pugh B or C, to assess efficacy and safety of rFVIIa. rFVIIa (80 microg/kg) was administered at the start of the operation, to be repeated according to predefined criteria. Packed red blood cells (RBC), fresh-frozen plasma, and platelet concentrates were administered according to predefined criteria. Perioperative transfusion requirements in study patients were compared with matched controls. RESULTS: Six patients were enrolled in the study. All received a single dose of rFVIIa. Transfusion requirements (given as median, with range in parentheses) were lower in the study group than in matched controls: 1.5 (0-5) vs. 7 (2-18) units of allogeneic RBC (P=0.006), 0 (0-2) vs. 3.5 (0-23) units of autologous RBC (P=0.043), total amount of RBC 3 (0-5) vs. 9 (4-40) units (P=0.002). Transfused fresh-frozen plasma was 1 (0-7) vs. 8 (2-35) units (P=0.011). Blood loss was 3.5 L (1.4-5.3) vs. 9.8 L (3.7-35.0) (P=0.004). One study patient developed a hepatic artery thrombosis at day 1 postoperatively. CONCLUSIONS: A single dose of 80 microg/kg rFVIIa significantly reduced transfusion requirements during OLT. Further study is needed to establish the optimally effective and safe dose of rFVIIa in orthotopic liver transplantation.

Adult↗

Recurrent severe bleeding from gastrointestinal angiodysplasia in a patient with von Willebrand's disease, controlled with recombinant factor VIIa.

A patient with von Willebrand's disease had recurrent gastrointestinal bleeding from angiodysplasia, with inadequate response to von Willebrand factor substitution, medical and endoscopic treatment, and resection of affected bowel. Frequent blood transfusions were required. She started home treatment with recombinant activated factor VII (rFVIIa) at the onset of bleeding, in addition to her standard therapy. From then on, bleeds could be controlled rapidly and no more blood transfusions were needed. We conclude that rFVIIa is effective in this case of angiodysplasia and might be a therapeutic option in similar patients.

Angiodysplasia↗

Risk of venous thromboembolism in carriers of factor V Leiden with a concomitant inherited thrombophilic defect: a retrospective analysis.

Factor V Leiden is the most common genetic defect associated with venous thromboembolism. Its clinical expression is limited and shows a wide intrafamilial and interfamilial variation, which might be explained by the influence of other genetic risk factors. We retrospectively studied 226 patients with factor V Leiden and documented venous thromboembolism (probands) and 400 first-degree carrier relatives to assess the contribution of concomitant genetic risk factors to the occurrence of venous thromboembolism. The prothrombin G20210A mutation was found in 8.3%, homozygosity of factor V Leiden in 7.2%, and inherited deficiencies of antithrombin, protein C or protein S in 4.7% of symptomatic carriers (probands and relatives), as compared with 6.0, 3.4 and 0.9% of asymptomatic carriers, respectively. The total follow-up time in relatives was 11 049 years. Prevalences of venous thromboembolism were 10.8% in single heterozygous factor V Leiden carrier relatives, 16.0% in double-heterozygotes for factor V Leiden and the prothrombin mutation, 36.8% in homozygotes for factor V Leiden, and 40.0% in double-heterozygotes for factor V Leiden and an inherited deficiency of protein C or protein S. Annual incidences in these groups were 0.39, 0.57, 1.41, and 4.76%, respectively. Multivariate analysis showed a small, non-significant additional effect of the prothrombin mutation on the risk of venous thromboembolism in heterozygotes for factor V Leiden [adjusted hazard ratio, 1.3; 95% confidence interval (CI), 0.5-3.8]. This effect was more pronounced for homozygosity of factor V Leiden (adjusted hazard ratio, 3.9; 95% CI, 1.7-9.0) and inherited protein C or protein S deficiencies (adjusted hazard ratio, 17.5; 95% CI, 3.8-81.2). Our data provide evidence of clustering of the evaluated genetic thrombophilic defects in symptomatic factor V Leiden carriers and support the assumption that the clinical expression of factor V Leiden depends on clustering in a part of carriers.

Adult↗

Effects of acetone, methanol, or paraformaldehyde on cellular structure, visualized by reflection contrast microscopy and transmission and scanning electron microscopy.

The authors recently showed variable subcellular immunoreactivity of the Bcl-2 and Bax proteins after fixation of cell monolayers with acetone, methanol, or paraformaldehyde (PF) followed by methanol (PF/methanol). Here, the authors demonstrate by reflection contrast microscopy and transmission electron microscopy that acetone or methanol fixation result in complete loss of integrity of intracellular structures in contrast with PF or glutaraldehyde fixation. Scanning electron microscopy revealed poor preservation of plasma membrane integrity after fixation in acetone or methanol. Fixation with PF before methanol reduced damage to intracellular and plasma membranes. In addition, Western blot analysis demonstrated loss of Bcl-2 and Bax protein during acetone or methanol fixation, whereas PF fixation before methanol permeabilization markedly reduced this loss. For studies on the intracellular localization of soluble or unknown types of antigen, the authors discourage the use of acetone and methanol as single fixatives.

Acetone↗

Effect of a physical therapeutic intervention for balance problems in the elderly: a single-blind, randomized, controlled multicentre trial.

OBJECTIVE: To establish the effect of a short, individualized exercise programme on balance dysfunction in the elderly. DESIGN: A single-blind, randomized, controlled, multicentre trial. SETTING: Physical and recreational therapy departments from two rehabilitation centres. PARTICIPANTS: Ninety-four subjects of >75 years with functional balance problems living independently or in a residential care facility. Seventy-seven subjects completed the intervention period and four-week follow-up. At a one-year follow-up 49 subjects were evaluated on balance functioning. INTERVENTIONS: Twelve sessions of an individualized balance training programme (experimental group) or 12 sessions of an individualized extra attention programme (control group) given in 4-6 weeks. MAIN OUTCOME MEASURES: Berg Balance Scale and the Dynamic Gait Index to establish balance functioning, a visual analogue scale to establish fear of falling in daily life and the Hospital Anxiety Depression Scale to verify feelings of anxiety and depression. RESULTS: Subjects in the experimental group improved significantly more on the Berg Balance Scale and the Dynamic Gait Index than those in the control group (p f 0.001, p f 0.001, respectively). However the effect disappeared at a one-year follow-up on the Berg Balance Scale. No prognostic factors could be identified to determine who would benefit most from the individualized exercise programme. Results on the other response variables revealed no effect of the intervention. CONCLUSION: A short individualized exercise programme can improve functional balance in people aged 75 years and older. This improvement was maintained at least for one month but had worn off by one year.

Activities of Daily Living↗

Acting on an environmental health disaster: the case of the Aral Sea.

The Aral Sea area in Central Asia has been encountering one of the world's greatest environmental disasters for more than 15 years. During that time, despite many assessments and millions of dollars spent by large, multinational organizations, little has changed. The 5 million people living in this neglected and virtually unknown part of the world are suffering not only from an environmental catastrophe that has no easy solutions but also from a litany of health problems. The region is often dismissed as a chronic problem where nothing positive can be achieved. Within this complicated context, Medecins Sans Frontieres, winner of the Nobel Peace Prize in 1999, is actively trying to assess the impact of the environmental disaster on human health to help the people who live in the Aral Sea area cope with their environment. Medecins Sans Frontieres has combined a direct medical program to improve the health of the population while conducting operational research to gain a better understanding of the relationship between the environmental disaster and human health outcomes. In this paper we explore the health situation of the region and the broader policy context in which it is situated, and present some ideas that could potentially be applied to many other places in the world that are caught up in environmental and human health disasters.

Agriculture↗

[CBO guideline 'Deep venous thrombosis and pulmonary embolism; revision of the earlier guidelines. Dutch Organization for Quality Assurance in Hospitals].

Diagnosis of clinically suspected deep venous thrombosis is based on a clinical score, serial compression ultrasonography and D-dimer assay. For the diagnosis of pulmonary embolism perfusion scintigraphy, ventilation scintigraphy, echography of the leg veins and pulmonary angiography in that order lead to the lowest mortality, morbidity and costs. Diagnostics with spiral CT followed by pulmonary angiography leads to equal mortality and fewer angiography procedures. Decision rules based on anamnesis, physical examination, blood gas analysis and chest radiograph have proved to be insufficiently reliable. The present D-dimer assays have too little sensitivity and too much variability. Thrombo-prophylaxis with low-molecular-weight heparin is indicated for general surgery, joint replacement of the knee or hip, cranial and spinal surgery, subarachnoid haemorrhage after surgical treatment of an aneurysm, acute myocardial infarction, ischaemic stroke or spinal cord lesion, intensive care patients, patients with acute paralysis due to a neuromuscular disorder, and bedridden patients with a risk factor. Prophylaxis has to be continued as long as the indication exists. In the acute phase of deep venous thrombosis or pulmonary embolism treatment with (low-molecular-weight) heparin in an adequate dose is necessary. When started at the same time as coumarin derivatives the treatment with heparin has to be continued for at least 5 days. The risk of postthrombotic syndrome after deep venous thrombosis will be lowered by carrying compression stockings for at least 2 years after the event.

Anticoagulants↗

Scanning electron microscopic analysis of endothelial cell coverage and quality in large vessels from multi-organ donors: effects of preservation on endothelial cell integrity.

Endothelial cell integrity (coverage and quality) of large donor vessels is important because these vessels are used for vascular reconstructions in solid-organ transplantation. Disruption of the endothelial cell monolayer will initiate blood coagulation and may lead to thrombosis of large vessels, often resulting in the loss of the transplanted organ. Iliac arteries and veins, removed from 10 heart-beating multi-organ donors at the end of the donor procedure, were analyzed using scanning electron microscopy at three different time points of preservation. Endothelial cell coverage and quality were determined immediately after removal from the donor, after 10 h (time of transplantation) and 7 d storage in 'University of Wisconsin' cold preservation solution (UW). Endothelial cell coverage decreased during the preservation of arteries, but was maintained in veins. Storage of the veins for 7 d in plastic bags showed a decreased endothelial cell coverage compared to storage in glass vials. Early removal of the blood vessels and proper storage, free floating and in clean UW, may improve maintenance of the endothelial cell integrity. These findings may be important in order to reduce the risk of thrombosis and, consequently, organ failure after transplantation. Furthermore, vessels with maintained endothelial cell integrity after 7 d may be used for in vitro research.

Adenosine↗