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Biomedical subjects

F J van der Meer

Publications and source records attributed to F J van der Meer.

At least 19 recordsLinked to original sources
PubMed2005

Quantitative optical coherence tomography of arterial wall components.

Optical coherence tomography (OCT) can be used to visualize the arterial wall and atherosclerotic plaques with high resolution. In this study, we verified the application of OCT to the quantitative analysis of plaque structural dimensions and optical attenuation coefficients of the components. We assessed the effect of balloon dilation on the OCT signal from the medial layer of porcine carotid artery ex vivo. Imaging of human autopsy samples was performed from the luminal side with a high (3.5 microm axial and 7 microm lateral) resolution OCT system (approximately 800 nm) or a regular (15-20 microm axial and 20 microm lateral resolution) OCT system (approximately 1,300 nm). For each sample, dimensions were measured by histomorphometry and OCT, and the optical attenuation was measured. In a tissue culture set-up, porcine carotid arteries were dilated and the attenuation coefficients of the dilated segments were compared to a control segment for 4 h. Quantitative analysis showed a strong and significant correlation between OCT and histology cap thickness measurements for both OCT systems. For both systems, the measured attenuation coefficients for diffuse intimal thickening and lipid-rich regions differed significantly from that of calcified tissue. Balloon dilation induced a time-dependent increase in the attenuation coefficient, which may be attributed to the induction of apoptosis. In conclusion both the high and regular resolution OCT systems can image the atherosclerotic plaques precisely. Quantitative analysis of the OCT signals allowed in situ determination of the intrinsic optical attenuation coefficient for atherosclerotic tissue components within regions of interest, which can help to discriminate between plaque and arterial wall components.

Analysis of Variance↗
PubMed2002

Levels of vitamin K-dependent procoagulant and anticoagulant proteins in over-anticoagulated patients.

Coumarin anticoagulants impair the biological activity of the vitamin K-dependent procoagulant and anticoagulant proteins. There are no reports that focus on the levels of these proteins in over-anticoagulated patients. Therefore, we determined the levels of factor II, factor VII, factor IX and factor X, protein C and protein S in 25 randomly selected over-anticoagulated patients (International Normalized Ratio >/= 6.0) and in 25 matched, therapeutically anticoagulated patients with an International Normalized Ratio within the therapeutic zone. Furthermore, to study a possible effect of the cause of over-anticoagulation, coagulant levels were compared between 16 over-anticoagulated patients with fever in the preceding 2 weeks and 24 over-anticoagulated patients with stable congestive heart failure. The pattern of procoagulant level reductions in the three groups of over-anticoagulated patients was largely the same as in therapeutically anticoagulated patients: factor X was the lowest and factor IX the highest. The difference was that, in over-anticoagulated patients, factor VII was relatively low among the procoagulant factors compared with therapeutically anticoagulated patients. Protein C was lower than protein S in over-anticoagulated patients with congestive heart failure, but was similar to protein S in the other study groups. In over-anticoagulated patients with fever, the vitamin K-dependent coagulation proteins except factor X were significantly lower than in over-anticoagulated patients with congestive heart failure, especially factor VII and protein S.

Adult↗
PubMed2001

[Self-monitoring and self dosing of oral anticoagulant therapy with vitamin K antagonists].

Anticoagulant therapy with vitamin K antagonists is effective in the prevention and treatment of thrombotic disease. The variable effect of these agents and the relatively small therapeutic width necessitate frequent checks on the intensity of the anticoagulation therapy as well as frequent dose-adjustments. Recently, small and reliable portable machines have become available which enable patients themselves, by means of a drop of blood obtained from a finger prick, to measure the intensity of the anticoagulation therapy and if necessary to adjust the treatment dose. In studies within the Netherlands where (selected) patients determined the 'international normalised ratio' (INR) themselves and if necessary adjusted the dose of the anticoagulant medication, the INR was mostly within the therapeutic target area. Furthermore, the independence, the possibility for travelling and the time saved were experienced as positive aspects. Under certain conditions, allowing patients themselves to check the INR and if needs be to adjust the dose of the anticoagulation treatment, may be an acceptable alternative for anticoagulation therapy check-ups performed by the thrombosis service.

Administration, Oral↗
PubMed2000

Paraparesis after lumbar puncture in a male with leukemia.

A diagnostic lumbar puncture was performed in a 12-year-old male with acute lymphoblastic leukemia. Because of thrombocytopenia (platelet count 42,000/mm(3)), a platelet transfusion was given immediately before the lumbar puncture. However, the platelet count was not re-examined. The patient developed progressive paraparesis shortly after the lumbar puncture. Magnetic resonance imaging revealed an extensive spinal subdural hematoma from the T2 to S2 level. This case report illustrates the sometimes dramatic consequences of lumbar puncture in patients with childhood leukemia. Guidelines for the examination of the platelet count and correction of thrombocytopenia before lumbar puncture are discussed.

Child↗
PubMed2000

Disappearance of factor VIII autoantibodies preceding autoimmune haemolytic anaemia.

We describe a previously healthy woman who at the age of 44 years developed a factor VIII inhibitor, that over the years increased to a maximum level of 3600 Bethesda units (BU) mL(-1) in 1978. The epitope specificity of the factor VIII inhibitor was investigated and antibodies directed against the A2 and C2 domains of factor VIII were detected. The majority of these antibodies were of subclass IgG4. Over the years, the inhibitor titre gradually decreased and in 1989, the inhibitor could no longer be detected. Shortly after, the patient developed autoimmune haemolytic anaemia. A possible link between the disappearance of factor VIII inhibitors and the development of other autoantibodies may be explained by concomitant development of anti-idiotypic antibodies that neutralize the activity of factor VIII inhibitors. We were unable to detect anti-idiotypic antibodies, which could explain the decline in factor VIII inhibitor titre in this patient.

Aged↗
PubMed1999

Effect of danaparoid sodium on proteinuria, von Willebrand factor, and hard exudates in patients with diabetes mellitus type 2.

In diabetic nephropathy, heparan sulfate glycosaminoglycan side chains are reduced in glomerular basement membranes proportionally to the degree of proteinuria. Recently, it was demonstrated that additional therapy with danaparoid sodium, a mixture of sulfated glycosaminoglycans with mainly heparan sulfate, lowered proteinuria in type 1 diabetes patients with diabetic nephropathy. A randomized placebo-controlled parallel study was performed with 750 anti-Xa units of danaparoid sodium once daily in type 2 diabetes patients with severe proteinuria. The aim of the study was to evaluate the possible effects of danaparoid sodium on proteinuria, endothelial dysfunction, and hard exudates in the retina and to determine the safety/tolerability of this drug. Twenty-two patients completed the study, and one patient had to stop prematurely after 6 wk of danaparoid sodium treatment because of urticaria at the injection sites. Apart from a small decrease of hemoglobin and minor skin hematomas at the injection site in five patients in the danaparoid sodium group, no other safety parameters showed any clinically or statistically significant difference between and within groups. The relative change in time of both the urinary albumin and protein excretion rate corrected for creatinine did not differ between both treatment arms (P = 0.2 and 0.49, respectively). No retinal complications or changes of hard exudates occurred. von Willebrand factor was elevated in both groups, but was not influenced by either treatment modality. Contrary to the beneficial effects that occurred in type 1 diabetes patients with diabetic nephropathy, treatment for 8 wk with 750 anti-Xa units of danaparoid sodium gave no reduction of proteinuria, hard exudates, and von Willebrand factor.

Adult↗
PubMed1999

No indication for APTT screening in patients on oral anticoagulant therapy.

UNLABELLED: Patients on oral anticoagulant therapy (OAT) may bleed due to a very low factor IX level caused by a mutation at Ala-10 in the propeptide region of the factor IX gene. We evaluated screening of patients on OAT with an APTT to detect patients with this abnormality. In 734 patients an APTT was assessed. Twenty-three patients had a disproportionately prolonged APTT. In these patients the factor IX level, the mutation at Ala-10 and the frequency of bleeding complications were assessed. No severely lowered factor IX levels were found (1 patient with 5% factor IX). No mutations at Ala-10 were found and bleeding complications were not more frequent in these patients. CONCLUSION: Routine APTT screening of patients on OAT is not useful to detect patients with increased bleeding or with the Ala-10 mutation in the factor IX gene.

Administration, Oral↗
PubMed1998

Effect of plasma pooling on the International Sensitivity Index of prothrombin time systems.

Guidelines set by the World Health Organization (WHO) state that in order to calibrate a prothrombin time system for International Sensitivity Index (ISI), freshly prepared specimens from 20 normal individuals and 60 patients receiving coumarin are required. These numbers are required to obtain a precise value of the calibration line slope when there is considerable scatter of individual data about the regression line. The scatter can be reduced by pooling individual plasma samples. In the present study, four pooled plasmas were prepared, one from 20 normal individuals and three from three groups of 30 patients receiving treatment with long-term oral anticoagulants. Prothrombin times were determined with four thromboplastins, HepatoQuick (rabbit thromboplastin combined with adsorbed plasma), Recombiplastin (recombinant human thromboplastin), Thromborel-S (human placenta), and Thromboplastin-C Plus (rabbit brain). Calibration line slopes were calculated for the six possible combinations of thromboplastins using the set of all individual plasma samples and the set of four pooled plasmas. In most comparisons, the WHO calibration model was appropriate, i.e. the line calculated for the patients' samples passed through the mean of the normals. The calibration line slopes obtained with the set of four pooled plasmas did not differ by more than 5% from the corresponding slopes calculated with the original individual plasmas. For some combinations of thromboplastins non-linear relations were observed both with the individual plasmas and with the pooled plasmas. We conclude that pooling individual plasmas does not significantly change the calibration relation between prothrombin times determined with the original individual plasmas. Freshly pooled plasmas can be used to determine the ISI of prothrombin time systems with an acceptable degree of precision.

Anticoagulants↗
PubMed1997

[Acquired haemophilia A].

A 74-year-old man developed a severe bleeding disorder on the basis of acquired Factor VIII (F VIII) inhibitor. Coagulation assays showed a prolonged activated partial thromboplastin time (APTT) with a normal prothrombin time (PT);F VIII level was 0.07 IU and F VIII inhibitor level 8.8 Bethesda units (BU). At least half the cases of acquired haemophilia A are associated with pregnancy, the postpartum period or an underlying malignancy or autoimmune disease. Haemorrhagic diathesis can be severe and life-threatening. Treatment of acute haemorrhages consists of human or porcine factor VIII concentrate, activated prothrombin complex concentrate (FEIBA) or recombinant factor VIIa, depending on the antibody titre. Immunosuppressive therapy is successful in at least 60% of the patients in making the inhibitor disappear. In patients with a spontaneous haemorrhagic diathesis, a thorough medical history should be taken, coagulation assays should be performed and a specialist should be consulted.

Aged↗
PubMed1997

The role of compliance as a cause of instability in oral anticoagulant therapy.

To assess the role of non-compliance as a cause of instability in patients on oral anticoagulant therapy, a follow-up study of stably and instably anticoagulated patients and of patients beginning oral anticoagulant therapy was performed. Compliance was assessed by pill counting and with the use of pill bottles in the cap of which a microprocessor registered the exact date and time of opening of the bottle. (In)stability of oral anticoagulant therapy was expressed as the number of INRs and as the time spent within the target range and by squared sigma. Subsequently, as a pilot study, a randomized intervention study in instable, non-compliant patients was performed in which these patients were or were not informed about the real nature of the cap of the pill bottle. Nineteen stable and 19 unstable patients and 30 patients beginning therapy were followed for 3 months or less until therapy stopped. Compliance was better in the previously stably anticoagulated patients, although differences were small. Poor compliance was not a major cause of instability in patients starting therapy. Although the pilot intervention study was too small to assess the role of the special pill bottle, it was shown that compliance can be positively affected.

Administration, Oral↗
PubMed1997

Hemagglutinin-esterase, a novel structural protein of torovirus.

We have characterized the 3'-most 3 kb of the genome of bovine torovirus (BoTV) strain Breda. A novel 1.2-kb gene, located between the genes for the membrane and nucleocapsid proteins, was identified. This gene, the 3'-most 0.5 kb of which is also present in the genome of the equine torovirus isolate Berne virus (BEV), codes for a class I membrane protein displaying 30% sequence identity with the hemagglutinin-esterases (HEs) of coronaviruses and influenza C viruses. Heterologous expression of the BoTV HE gene yielded a 65,000-molecular weight N-glycosylated protein displaying acetylesterase activity. Serologic evidence indicates that the HE homolog is expressed during the natural infection and represents a prominent antigen. By using an antiserum raised against residues 13 to 130 of HE, the HE protein was detected in radioiodinated, sucrose gradient-purified BoTV preparations. Formal evidence that HE is a structural protein was provided by immunoelectron microscopy. In addition to the large, 17- to 20-nm spikes, BoTV virions possess shorter surface projections (6 nm on average). We postulate that these surface projections, which are absent from the BEV virion, are composed of the BoTV HE homolog. The HE gene, which has now been demonstrated in three different virus genera, is a showpiece example of modular evolution.

Amino Acid Sequence↗
PubMed1997

Danaparoid sodium lowers proteinuria in diabetic nephropathy.

Diabetic nephropathy is a progressive renal disease with thickening of the glomerular basement membrane and mesangial expansion and proliferation as histological hallmarks. The presence of the glycosaminoglycan side chains of heparan sulfate proteoglycan, an important constituent of the glomerular basement membrane, is decreased in diabetic nephropathy proportionally to the degree of proteinuria. Danaparoid sodium is a mixture of sulfated glycosaminoglycans consisting mainly of heparan sulfate. The study presented here involved performing a randomized placebo-controlled crossover study with danaparoid sodium in diabetic patients with overt proteinuria. The aim of the study was to evaluate the effect on proteinuria and safety/tolerability. Nine patients completed the study, without major side effects; the crossover study consisted of two 6-wk periods of treatment with 750 anti-Xa units danaparoid sodium subcutaneously once-daily or placebo. Following danaparoid sodium, significant declines of both albuminuria and proteinuria were found. After danaparoid sodium, the albumin excretion ratio standardized for urinary creatinine reduced with 17% in comparison with an increase of 23% after placebo (95% confidence interval of the difference,-75.9-3.9%; P = 0.03). The percentage change of the urinary protein excretion corrected for urinary creatinine differed at 8 wk significantly between both treatment arms (P = 0.001). Additional parameters for safety as hematological, hemostasis, biochemical parameters, and fundusphotography did not show any clinically significant difference for both groups. Only two patients had minor skin hematomas at the injection site while using danaparoid sodium. In conclusion, the supplementation was found to be feasible and was not associated with side effects. A significant decline of proteinuria was found. More prospective dose-finding and long-term studies must be performed to see whether danaparoid sodium could not only induce a reduction of proteinuria but also halt the progression of renal disease.

Adult↗