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Biomedical subjects

E C van Pampus

Publications and source records attributed to E C van Pampus.

17 recordsLinked to original sources
PubMed2001

A prospective study of asymptomatic carriers of the factor V Leiden mutation to determine the incidence of venous thromboembolism.

BACKGROUND: The factor V Leiden mutation is a common genetic defect associated with an increased risk for venous thromboembolism. The clinical implications for asymptomatic carriers of this mutation and, consequently, the usefulness of screening families in which a proband has both the mutation and venous thromboembolism are unclear. OBJECTIVE: To determine the incidence of venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation. DESIGN: Prospective cohort study. SETTING: University hospitals in the Netherlands. PARTICIPANTS: 470 asymptomatic carriers of the factor V Leiden mutation (234 men, 236 women; mean age, 43 years [range, 15 to 88 years]), 12 of whom were homozygous. Carriers were identified by screening the first-degree relatives (>15 years of age) of 247 symptomatic probands. MEASUREMENTS: Objectively diagnosed episodes of venous thromboembolism and the relationship between incidence and exposure to high-risk situations. RESULTS: Nine venous thromboembolic events were observed in 1564 observation-years, resulting in an annual incidence of 0.58% (95% CI, 0.26% to 1.10%). The incidence of spontaneous venous thromboembolism was 0.26% (CI, 0.07% to 0.65%) per year; 3.5% (CI, 0.1% to 17.8%) per episode of surgery, trauma, or immobilization; 0.0% (CI, 0.0% to 19.5%) per pregnancy; 1.8% (CI, 0.4% to 5.2%) per year of oral contraceptive use; and 2.9% (CI, 0.8% to 15.3%) per year of use of hormone replacement therapy. CONCLUSIONS: The absolute annual incidence of spontaneous venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation is low and does not justify routine screening of the families of symptomatic patients.

Adolescent↗
PubMed2001

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↗
PubMed2000

Increased D-dimer levels correlate with binding of activated protein C, but not tissue factor expression, on peripheral blood monocytes in cancer patients.

Monocyte tissue factor expression is supposed to play an important role in the hypercoagulability of blood in cancer patients. The relation between coagulation parameters and the expression of monocyte membrane proteins involved in hemostasis or monocyte activation was studied in 21 patients with a disseminated malignancy and 21 age- and sex-matched healthy controls. In the cancer patient group no increase of monocyte tissue factor expression was found (8. 4% vs. 7.8%; P = 0.83), but a significant increase of monocyte-bound activated protein C (APC) (28.8% vs. 13.4%; P = 0.009) and monocyte CD16 expression (34.5% vs. 27.0%; P = 0.007) was observed. There was also a significant increase of D-dimers (2.0 vs. 0.2 microg/ml; P = 0.001), a decrease of antithrombin (83.5% vs. 102.0%; P = 0.004), but no increase of TAT complexes (1.7 vs. 1.5 microg/l; P = 0.38) or factor VII(a) (68.5% vs. 75.0%; P = 0.52). The increase of D-dimers was significantly correlated with the monocyte APC (R = 0.60; P = 0. 005), but not with monocyte tissue factor levels (R = -0.22; P = 0. 35) or TAT complexes (R = 0.12; P = 0.60). These results reflect a local rather than systemic thrombin and fibrin formation. It is suggested that the APC formed locally enters the circulation and binds to peripheral blood monocytes. APC bound on monocytes is known to inhibit monocyte cytokine production and might therefore be involved in regulatory responses of monocytes in cancer patients.

Adolescent↗
PubMed2000

Factor XIII Val34Leu and the risk of venous thromboembolism in factor V Leiden carriers.

A mutation in factor XIII (Val34Leu) was reported to protect against venous thromboembolism. We evaluated the effect of Val34Leu on thrombotic risk in 352 factor V Leiden carriers who were first-degree relatives of 132 thrombotic propositi carrying factor V Leiden. The total observation period was 2,594 years in 92 Val34Leu carriers and 7,444 years in 260 non-carriers. The annual incidence of a first episode of venous thromboembolism was 0.31% in Val34Leu carriers and 0.44% in non-carriers [relative risk (RR) for venous thromboembolism: 0.7, 95% CI 0.3-1.5]. Age-specific RR for venous thromboembolism were (for Val34Leu carriers and non-carriers respectively): 1.0 (95% CI 0.3-3.2) in the age group of 15-30 years, 0.4 (95%, CI 0.05-3.0) in the age group of 30-45 years, 0.6 (95% CI 0.1-2.9) in the group aged 45-60 years and 0.5 (95% CI 0.06-4.5) in relatives older than 60 years. In conclusion, the impact of FXIII Val34Leu on the venous thromboembolic risk is modest, suggesting that screening for this mutation in factor V Leiden carriers is not justified.

Adolescent↗
PubMed1999

Increased risk for fetal loss in carriers of the factor V Leiden mutation.

BACKGROUND: An increased risk for fetal loss caused by placental thrombosis is probable in carriers of the factor V Leiden mutation but has not been demonstrated consistently in previous studies. OBJECTIVE: To determine the overall risk for fetal loss and the separate risks for miscarriage and stillbirth in carriers of the factor V Leiden mutation. DESIGN: Retrospective cohort study. SETTING: Three university hospitals. PARTICIPANTS: 228 carriers of the factor V Leiden mutation (77 propositi, 151 relatives) and 121 noncarrier relatives (controls). All participants had been pregnant at least once. MEASUREMENTS: Risks for fetal loss, miscarriage (defined as fetal loss within 20 weeks of gestation), and stillbirth (defined as fetal loss after >20 weeks of gestation) in women and in pregnancies were estimated and compared in carriers and noncarriers. Adjusted odds ratios were calculated by using multiple regression analysis. A random-effects model was used for comparisons of pregnancies. RESULTS: Fetal loss occurred in 31.6% of carriers and 22.3% of noncarriers, miscarriage occurred in 29.4% of carriers and 17.4% of noncarriers, and stillbirth occurred in 5.7% of carriers and 5.0% of noncarriers. Fetal loss recurred in 10.1% of carriers and 4.1% of noncarriers (odds ratio, 2.60 [95% CI, 0.96 to 7.03]). Adjusted odds ratios were 2.12 (CI, 1.35 to 3.33) for fetal loss, 2.08 (CI, 1.33 to 3.25) for miscarriage, and 1.60 (CI, 0.58 to 4.43) for still-birth when pregnancies in carriers and noncarriers were compared. Homozygous carriers had a greater risk for fetal loss (odds ratio, 2.01 [CI, 0.94 to 4.32]) and stillbirth (odds ratio, 4.85 [CI, 0.82 to 25.58]) than heterozygous carriers. CONCLUSIONS: Carriers of the factor V Leiden mutation have a greater risk for fetal loss (particularly miscarriage) than noncarriers. These data further suggest a greater risk for recurrence of fetal loss in carriers than in noncarriers and a greater risk for fetal loss and stillbirth in homozygous carriers than in heterozygous carriers.

Abortion, Habitual↗
PubMed1998

The incidence of venous thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis.

BACKGROUND: The factor V Leiden mutation is a genetic defect associated with an increased incidence of venous thromboembolism. When the incidence of venous thromboembolism in relatives of patients known to have the mutation outweighs the disadvantages of prophylactic strategies, family screening may be necessary. OBJECTIVE: To determine the incidence of venous thromboembolism in first-degree relatives of symptomatic carriers of the factor V Leiden mutation. DESIGN: Retrospective blinded study. SETTING: University hospitals. PARTICIPANTS: 437 first-degree relatives of 112 heterozygous propositi and 30 relatives of 6 homozygous propositi. MEASUREMENTS: Before DNA testing, information on previous venous thromboembolism and concomitant risk factors was obtained. Relatives with and without the FV: Q506 mutation were compared. RESULTS: The annual incidence of thromboembolism in relatives of heterozygous propositi was 0.45% (95% CI, 0.28% to 0.61%) in those with the mutation and 0.10% (CI, 0.02% to 0.19%) in those without the mutation (relative risk, 4.2 [CI, 1.8 to 9.9]). Among carriers, the incidence increased from 0.25% (CI, 0.12% to 0.49%) in the 15- to 30-year-old age group to 1.1% (CI, 0.24% to 3.33%) in persons older than 60 years of age. Half of the episodes of venous thromboembolism occurred spontaneously, 20% were related to surgery, and 30% were associated with pregnancy or use of oral contraceptives. CONCLUSIONS: The observed low annual risk for venous thromboembolism in persons carrying the factor V Leiden mutation does not seem to outweigh the risks for bleeding associated with coumarin prophylaxis or justify discouragement of the use of oral contraceptives. A general policy of screening the families of all patients with the factor V Leiden mutation does not seem to be indicated. The observations in this moderate-size, retrospective study need to be confirmed by prospective follow-up studies.

Adolescent↗
PubMed1998

Myelodysplasia presenting with pulmonary manifestations associated with neutrophilic dermatosis.

We present the case of a patient who suffered from severe pneumonia. Extensive diagnostic procedures revealed negative cultures and a severe neutrophilia in the bronchoalveolar lavage fluid suggestive of Sweet's syndrome. The persistent toxic leukocyte differentiation (not induced by infection) suggested an underlying hematologic disorder. One week later, she developed cutaneous lesions indicative of neutrophilic dermatosis. Bone marrow investigation showed refractory anemia with excess of blasts (RAEB). Both the pulmonary and cutaneous infiltrates improved after treatment with chemotherapy.

Female↗
PubMed1998

Inter-individual variability in Ca2+ signalling in platelets from healthy volunteers: effects of aspirin and relationship with expression of endomembrane Ca2+-ATPases.

Increased Ca2+ signal generation may lead to hyperactivity of platelets and contribute to thrombotic complications. Using fura-2-loaded platelets from 51 healthy volunteers, high variability was detected in the Ca2+ responses evoked by the receptor agonists, thrombin and collagen, and the inhibitor of sarco/endoplasmic reticulum Ca2+-ATPases (SERCA), thapsigargin (Tg). Oral intake of 500mg aspirin reduced the magnitude of the Ca2+ responses, and lowered the intra-individual coefficients of variance of the responses by 50%. However, the corresponding inter-individual variance coefficients were only a little influenced by aspirin intake, pointing to subject-dependent factors in Ca2+ handling that are unrelated to thromboxane formation. With each agonist, 6-9% of the subjects had platelets with relatively high Ca2+ responses (> mean + SD) both before and after aspirin intake. In 90% (9/10) of these cases the high responsiveness was confirmed in platelets obtained 6-12 months later. The Tg- but not thrombin-induced Ca2+ responses correlated inversely with the expression levels of SERCA PL/IM 430 (SERCA-3b) in platelets. After aspirin intake, the Ca2+ responses with collagen but not thrombin correlated inversely with SERCA-2b expression. These results suggest that, in the absence of potentiating effects of thromboxane, (i) the amount of PL/IM 430-recognizable SERCA may control the Ca2+ signal when SERCA-2b is specifically inhibited (with Tg), and (ii) the expression of SERCA-2b determine the collagen- but not the thrombin-evoked Ca2+ signal. Accordingly, limited Ca2+-pumping activity by low expression of one of the SERCA isoforms is likely to be one of the factors resulting in increased platelet activity towards collagen or thapsigargin but not thrombin.

Aspirin↗
PubMed1998

Contribution of thromboxane and endomembrane Ca2+-ATPases to variability in Ca2+ signalling of platelets from healthy volunteers.

Inter-individual variability in Ca2+ signal generation was studied in platelets from 15 healthy volunteers. The possible involvement of variation in thromboxane A production and variation in sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) was investigated by using platelets isolated before and after intake of 500 mg aspirin, and by measuring the expression levels of two main SERCA isoforms (SERCA-2b and PL/IM 430-recognizable SERCA). Considerable difference in Ca2+ responses were detected after platelet stimulation with thrombin, collagen or the SERCA-2b inhibitor, thapsigargin (TG), with inter-individual coefficients of variance of 22-43% in the absence and 15-41% in the presence of aspirin. Differences in thromboxane A2 generation and SERCA expression contributed to this variability in various ways. In the absence of aspirin, the amount of formed thromboxane A2 partially explains the level of the Ca2+ response induced by TG. On the other hand, in the absence of thromboxane-dependent effects, the expression levels of SERCA-2b and SERCA PL/IM 430 were inversely related to the responses evoked by collagen and TG, respectively. None of these factors were related to the level of the thrombin-evoked Ca2+ signal.

Journal Article↗
PubMed1993

Influence of aspirin on human megakaryocyte prostaglandin synthesis.

To evaluate whether currently popular aspirin regimens have an effect on the prostaglandin synthesis in human megakaryocytes we measured thromboxane B2 (TXB2) synthesis in response to thrombin stimulation in human megakaryocytes ex vivo. Human megakaryocytes were purified by Counterflow Centrifugal Elutriation from bone marrow punctures, taken from volunteers before and 2 hours after ingestion of one dose of 500 mg (n = 4), 80 mg (n = 4) or 40 mg (n = 2) aspirin. Subsequently, megakaryocytes were purified before and 12 h after ingestion of 80 mg (n = 3) aspirin twice daily for 1 week and 12 h after 500 mg (n = 3) aspirin. On average, 140 +/- 102 x 10(3) (mean +/- 1 SD) megakaryocytes were recovered. We found that aspirin inhibits megakaryocyte cyclooxygenase in a dose-dependent manner. Two hours after 500 mg of aspirin, TXB2 synthesis in megakaryocytes was inhibited by 96.8 +/- 2%, whereas one dose of 80 and 40 mg aspirin showed an inhibition of 79.4 +/- 13.7% and 80 +/- 6.2% respectively. However, the inhibition of TXB2 synthesis seems not to be long-lasting since, 12 h after the ingestion of aspirin, an increase of megakaryocyte TXB2 production could be observed which reached significance after the 500 mg aspirin dosage (p < 0.048). We conclude that human megakaryocyte cyclooxygenase is sensitive to aspirin inhibition and that low doses of aspirin (40 and 80 mg) enter the systemic circulation and are able to inhibit megakaryocyte cyclooxygenase, but this inhibition is incomplete and megakaryocyte cyclooxygenase seems to recover within 12 h after ingestion of aspirin.

Aspirin↗
PubMed1992

Expression of adhesion antigens of human bone marrow megakaryocytes, circulating megakaryocytes and blood platelets.

There is evidence that mature megakaryocytes migrate into sinusoids, enter the blood and fragment in the vascular bed. We wondered whether differences in expression of adhesion antigens could be associated with the egress of megakaryocytes from bone marrow into the peripheral blood or the fragmentation into platelets. Megakaryocytes from human marrow were purified by counterflow centrifugal elutriation followed by a glycoprotein Ib-dependent agglutination procedure. Megakaryocytes from central venous blood and pulmonary arteries were purified by counterflow centrifugal elutriation alone. Adhesion antigens were labelled in an immunohistochemical assay. Both bone marrow megakaryocytes and platelets from healthy volunteers stained > 75% positive for CD36, CD41, CD42, Cdw49b (alpha subunit VLA2), Cdw49e (alpha subunit VLA5), Cdw49f (alpha subunit VLA6) and CD62. Circulating megakaryocytes, although > 75% positive for CD41, had, unlike platelets and bone marrow megakaryocytes, a reduced and remarkable heterogeneous (5-100% positive) labelling with antibodies against Cdw49b, Cdw49e, Cdw49f. These results could be confirmed by comparing the bone marrow megakaryocytes, circulating megakaryocytes and platelets from 7 patients that were recovered and processed at the same time. Morphologically mature, circulating megakaryocytes have, unlike bone marrow megakaryocytes, a heterogeneous expression of adhesion antigens, especially of Cdw49b, Cdw49e, and Cdw49f.

Antigens, CD↗
PubMed1991

Imipenem-cilastatin for empirical therapy in neutropenic patients with fever: an open study in patients with hematologic malignancies.

In adult neutropenic patients with hematological malignancies, we explored imipenem-cilastatin as empirical antibiotic therapy in a dose of 500 mg four times daily. Changing to second-line treatment was only resorted to if clinical deterioration, new infections or recurrence of fever occurred. A clinically or microbiologically documented infection was apparent in 115 of 150 episodes studied (76.7%). Imipenem-cilastatin was successful in 70.7% of all episodes and in 67.8% of all proven infections. Modification was necessary and successful in 22.0% of all episodes. 11 patients died while still febrile, 6 of them by infection (4%) and 5 because of progressive disease (3.3%). Imipenem-cilastatin is safe initial therapy in neutropenic febrile patients.

Antibiotics, Antineoplastic↗
PubMed1991

Combining counterflow centrifugal elutriation and glycoprotein Ib-dependent purification of human megakaryocytes: efficacy and selectivity.

To estimate the efficacy of human megakaryocyte purification techniques, mixtures of known numbers of megakaryocytes with a known ploidy range and of bone marrow or peripheral blood mononuclear cells were made. These artificial bone marrow samples were submitted to either a counterflow centrifugal elutriation or Percoll density separation followed by the glycoprotein Ib-dependent agglutination procedure. Also crude bone marrow samples were submitted to counterflow centrifugal elutriation directly followed by a glycoprotein Ib-dependent agglutination. The counterflow centrifugal elutriation resulted in a mean megakaryocyte recovery of 81% (mean 81% +/- 2.3). Purification by glycoprotein Ib-dependent agglutination after either a Percoll density separation or counterflow centrifugal elutriation resulted in a recovery of 61% (mean 61% +/- 15%) and 81% (mean 81% +/- 6) respectively. Purity of the resulting material was 87% (mean 87% +/- 11) and 83% (mean 83% +/- 5) respectively. The various isolation procedures did not affect the ploidy distribution of megakaryocytes greater than or equal to 8N. Counterflow centrifugal elutriation was preferred as the preparing step before glycoprotein Ib-dependent agglutination because of the lower variability in recovery and purity of megakaryocyte populations. When large numbers of rather pure and mature megakaryocytes are required, counterflow centrifugal elutriation followed by the glycoprotein Ib-dependent agglutination is a relatively simple method to purify human megakaryocytes without an appreciable loss in ploidy class greater than or equal to 8N.

Bone Marrow Cells↗
PubMed1990

Purification of human megakaryocytes using a glycoprotein Ib dependent agglutination technique.

In order to study normal and abnormal human megakaryocytopoiesis we modified a glycoprotein Ib dependent megakaryocyte purification technique originally described in guinea pigs. After Percoll density centrifugation, 2 ml bone marrow aspirates were subjected to 3 steps of bovine plasma induced cell clumping, which should selectively agglutinate glycoprotein Ib positive cells. In 13 experiments the resulting samples contained 28-102 x 10(3) megakaryocytes (median 70) with a median purity of 79%. Megakaryocyte recovery ranged from 30-86% (median 51%). The DNA profile showed median values of 10% for 8 N, 44% for 16 N and 43% for 32 N megakaryocytes. The described method is relatively simple, inexpensive and gives results comparable with more elaborate techniques.

Agglutination↗
PubMed1988

Cardiac tamponade from misplaced central venous line in pericardiophrenic vein.

A patient in whom a left internal jugular vein catheter had first migrated into the left pericardiophrenic vein, and subsequently had perforated into the pericardium leading to a cardiac tamponade is described. Although this malposition has rarely been reported, it does not seem to be so infrequent, as three other similar misplacements have occurred in our institution. This malposition can be prevented by a high degree of suspicion, preferential use of the right internal jugular vein for catheterization, routine use of a J-tipped guidewire, limiting the depth of insertion of the guidewire during cannulation, routine roentgenographic control of radiopaque catheters, and (slow) injection of a small volume of radiopaque dye through the central venous catheter.

Adult↗
PubMed1985

[Corneal opacity].

A case with bilateral corneal opacification in the form of a half-ring is described. Routine laboratory tests revealed no abnormalities, and serum lipoprotein composition was normal. The authors suspect that this was a case of primary lipoidal keratopathy.

Adult↗