Search PubMed⌕ Search

Biomedical subjects

J van der Meer

Publications and source records attributed to J van der Meer.

At least 55 records · Page 3Linked to original sources

Blood loss in orthotopic liver transplantation: a retrospective analysis of transfusion requirements and the effects of autotransfusion of cell saver blood in 164 consecutive patients.

Liver transplantation is associated with excessive blood loss. In order to identify factors influencing blood loss and to provide a basis for a pilot study to evaluate recombinant activated factor VII as a haemostatic agent, a retrospective study was performed in 164 consecutive patients with cholestatic or noncholestatic liver disease, who underwent orthotopic liver transplantation at a single centre between 1989 and 1996. Transfusion of allogeneic and autologous (cell saver) blood was used as a measurement of blood loss. Transfusion requirements were associated with age, gender, primary disease, Child-Pugh classification, serum levels of activated partial thromboplastin time, antithrombin III, urea and creatinine, platelet number, year of transplantation, length of cold ischaemia time and autologous blood transfusion. Of these variables, Child-Pugh classification (P = 0.001), urea (P = 0.0007), year of transplantation (P = 0.002), cold ischaemia time (P = 0.01) and autologous blood transfusion (P < 0.0001) were independent predictors of transfusion requirements by multivariate analysis. Thus, blood loss and transfusion requirements depend primarily on the severity of liver disease, quality of the donor liver, experience of the transplantation team and use of autologous (cell saver) blood transfusion. These findings emphasize the need for appropriate drug therapy and a critical reappraisal of current transfusion policy.

Adult↗

Characterization of immortalized human umbilical and iliac vein endothelial cell lines after transfection with SV40 large T-antigen.

Most in vitro studies of human endothelial cells have relied on cells derived from human umbilical veins (HUVEC); however, heterogeneity of primary cultured endothelial cells can make critical interpretation of results difficult. Several endothelial cell lines have been produced to serve as a more constant source of endothelial cells. In this study, we characterized the endothelial cell lines EVLB3 and EVLC2 derived from HUVEC, and EVLK1 and EVLK2 derived from human iliac vein endothelial cells (HIVEC). These cell lines maintained the typical endothelial cell cobblestone morphology and appeared to be growth factor independent. They lost PECAM-1 and von Willebrand factor, GP96 was reduced to the level of vascular smooth muscle cells (SMC), but aSMC-actin was far less than in vascular SMC. Antigen levels of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) were comparable with young endothelial cells, and mRNA was present for tPA, PAI-1, tissue factor (TF), tissue factor pathway inhibitor and thrombomodulin. This study revealed that mRNA and protein expression of coagulation and fibrinolytic factors was influenced by the stage of cell confluence. No differences could be detected between the endothelial cell lines derived from HUVEC and HIVEC. These cell lines may be a useful tool for studies on cellular interactions of fibrinolytic components or exploring the regulation of TF expression.

Antigens, Polyomavirus Transforming↗

Worse clinical outcome but similar graft patency in women versus men one year after coronary artery bypass graft surgery owing to an excess of exposed risk factors in women. CABADAS. Research Group of the Interuniversity Cardiology Institute of The Netherlands. Coronary Artery Bypass graft occlusion by Aspirin, Dipyridamole and Acenocoumarol/phenoprocoumon Study.

OBJECTIVES: This retrospective study sought to assess differences in graft patency and clinical outcome between women and men after coronary artery bypass graft surgery (CABG). BACKGROUND: A less favorable clinical outcome has been reported in women as compared with men. Its relation to graft patency has not been studied. METHODS: We analyzed one-year follow-up data of 912 patients (120 women) who entered a randomized clinical drug trial. All patients received vein grafts; in 494 patients (56 women) internal mammary artery (IMA) grafts were also used. Graft patency was assessed by coronary angiography at one year. Primary clinical end points were myocardial infarction, revascularization procedures and death; secondary clinical end points included recurrent angina, heart failure and arrhythmias. RESULTS: Occlusion rates of vein grafts were 16.7% in women and 12.4% in men (odds ratio [OR] 1.62, 95% confidence interval [CI] 0.88 to 3.00, p = 0.12); occlusion rates of IMA grafts were 3.4% and 5.7% in women and men, respectively (OR 0.56, 95% CI 0.08 to 3.96, p = 0.56). Primary clinical end points were observed in 16.7% of women and 9.2% of men (OR 1.97, 95% CI 1.10 to 3.34, p = 0.022), and any clinical end point in 41.7% of women and 25.8% of men (OR 2.06, 95% CI 1.39 to 3.04, p = 0.0004). Myocardial infarction (15% vs. 7.6%, OR 2.15, 95% CI 1.24 to 3.75, p = 0.013) and recurrent angina (26.7% vs. 15.4%, OR 2.00, 95% CI 1.28 to 3.11, p = 0.004) occurred most frequently. Multivariate regression analysis did not identify gender as an independent risk factor for graft occlusion or the clinical end points. Graft occlusion was an independent predictor of the composite primary clinical end point (OR 2.75, 95% CI 1.59 to 4.75, p = 0.0003) and each of the secondary clinical end points. The observed differences were due to an imbalance of risk factors at baseline and to surgical and graft characteristics. CONCLUSIONS: One-year occlusion rates of vein and IMA grafts were comparable in women and men. Clinical outcome was related to graft patency and was less favorable in women owing to their uneven distribution of risk factors among both groups.

Aged↗

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↗

Natural history of hepatitis C in HIV-negative patients with congenital coagulation disorders.

BACKGROUND/AIMS: Knowledge of the natural history of hepatitis C is useful for counselling patients and planning treatment. More data are needed from unselected patient groups without concomitant disease. The aim of this study was to describe the natural history of hepatitis C, two decades after infection, in a homogeneous and well-defined group of HIV-negative patients with congenital coagulation defects who had not received specific therapy for chronic hepatitis C. METHODS: Medical history, physical examination, laboratory tests and abdominal ultrasonography were performed in 45 HCV-RNA positive, HIV-negative patients, mainly haemophiliacs, from a single centre. Patients were classified according to results of ultrasonography. RESULTS: Two patients had experienced an episode of variceal bleeding; all others were asymptomatic. None had ascites. HCV-RNA titres were >500000 copies/ml in 23 patients, genotype was 1 in 31 patients. Forty (89%) had elevated transaminases, liver synthesis function was diminished in 7 (16%), and platelet count in 8 (18%). Ultrasonography was normal in 26 (58%) patients, 12 (27%) had isolated splenomegaly, and 7 (16%) had liver nodularity compatible with cirrhosis. Univariate analysis disclosed higher transaminases and gammaGT, higher age at acquisition of infection and higher present age as risk factors for more advanced disease. Of these, only higher present age was an independent predictor in multivariate analysis. CONCLUSIONS: Median 19 years after infection, 58% of patients had no other signs of liver disease than raised transaminases, 16% had cirrhosis on ultrasonography. Only 2/45 patients had symptomatic disease. Higher present age is the main risk factor for advanced disease in this group.

Adolescent↗

Transfection of small numbers of human endothelial cells by electroporation and synthetic amphiphiles.

OBJECTIVES: This study compared the efficiency of electroporation and synthetic amphiphiles. (SAINT-2pp/DOPE) in transfecting small numbers of human endothelial cells. METHODS AND RESULTS: Optimal transfection conditions were tested and appeared to be 400 V and 960 microF for electroporation and a 10:1 ratio for concentrations of SAINT-2pp/DOPE: plasmid. Using these conditions, cell concentrations were lowered step-wise and we were able to transfect as few as one thousand cells with both methods. For detection of transfection of a small number of cells a sensitive assay was needed (Luciferase). A plasmid containing the neomycin resistance gene was used to determine the transfection rate expressed in colony forming units by counting colonies after selection. At low plasmid concentrations this transfection rate was within the same range for both electroporation and SAINT-2pp/DOPE transfection. Fluorescent in situ hybridisation of metaphase chromosomes of transfected endothelial cells using the plasmid as a probe showed that stable integration was possible with both methods. CONCLUSIONS: Electroporation and a synthetic amphiphile, SAINT-2pp, provide the possibility of transfecting small numbers of cells resulting in stable integration of low plasmid concentrations. The availability of this technology is important in order to obtain functional endothelial cell lines from various human blood vessels for research purposes.

Cell Line, Transformed↗

Recurrent spontaneous intracerebral hemorrhage in a congenitally afibrinogenemic patient: diagnostic pitfalls and therapeutic options.

BACKGROUND: Coagulation disorders can cause intracerebral bleeding that may be difficult to detect since subsequent aberrant clot formation may mask early detection. This is an important pitfall because, when diagnosed early, bleeding in these patients is treatable. CASE DESCRIPTION: A patient with congenital afibrinogenemia presented with recurrent hemiparesis. Spontaneous intracerebral hemorrhage was diagnosed, despite an initial negative CT scan. Diagnosis, therapy, and complications of therapy are discussed. CONCLUSIONS: Intracerebral hemorrhage must be strongly suspected in any patient with a coagulation disorder presenting with matching clinical symptoms. Therapy must be installed immediately, before additional investigations, and should be continued even when initial neuroimaging is negative.

Afibrinogenemia↗

Acquired APC resistance in neurosurgical patients may not be a risk factor for postoperative deep vein thrombosis.

Acquired resistance to activated protein C has been reported during oral contraception and pregnancy. Its thrombogenic potential was studied in 41 neurosurgical patients who were enrolled in the placebo group of a thromboprophylaxis trial. Normalized activated protein C sensitivity ratio (nAPC-SR), clotting activity of factors V and VIII, and levels of protein C antigen were measured prior to and at days 3 and 7 after surgery. Bilateral venography was done in all patients at days 8-10 to demonstrate deep vein thrombosis. A lowered nAPC-SR was found in 76% (baseline), 80% (day 3), and 88% (day 7) of patients. It was inversely related to factor VIII clotting activity (p = .0003) and protein C antigen, (p = .02). Deep vein thrombosis was demonstrated in 30% of patients with a normal nAPC-SR and in 23% of patients with a lowered nAPC-SR. Pulmonary embolism was not observed. Multivariate analysis did not identify a lowered nAPC-SR as a thrombotic risk factor, in contrast with gender (women, p = .02) and Quetelet index (> or = 25 kg/m2, p = .006). Our data provide no evidence that acquired activated protein C resistance, frequently found in neurosurgical patients, contributes to their high risk of postoperative deep vein thrombosis.

Activated Protein C Resistance↗

['Public health status and perspectives' 1997. VI. Effects of health care].

The aim of this study was to investigate whether more health improvement might be attained with existing medical interventions. The interventions for ten diseases were studied to assess their efficacy (effect in ideal, experimental situation), their effectiveness (effect in daily practice) and the discrepancy between the efficacy and effectiveness. In addition, the causes of unexpectedly low effectiveness were studied. Interventions with proven efficacy were identified for all ten diseases. The effectiveness was less often studied. Existing health care registrations could provide information on the effectiveness for only three diseases (tuberculosis, colorectal tumours, and acute myocardial infarction). Causes of unexpectedly low effectiveness were observed in several of the five phases of the process of care: contacting the health care system, diagnosing the disease, prescribing the appropriate intervention, executing the intervention and patient compliance.

Colorectal Neoplasms↗

[Notes on the visitation of medical schools in 1997].

The members of the Visitation Committee who audited the medical education process in the Netherlands carefully formed their opinions based on a vast amount of information. Their judgement can be considered fair and well-balanced. Several critical remarks were made, especially on the coaching of students during their internships. The scientific education was also found wanting. Some faculties were given bad marks, and scores of recommendations were made. Surprisingly, however, the committee was of the opinion that students graduating from all faculties were equally and sufficiently competent to enter the medical workforce. It is recommended that next time this audit process be carried out on a much smaller scale.

Curriculum↗

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↗

Excision of a haemophilic pseudotumour of the ilium, complicated by fistulation.

We report the case of a patient with a haemophilic pseudotumour of the ilium who developed chronic fistulation, 6 months after en-bloc resection. During the initial resection, the large defect in the iliac wing was filled with bone cement, which may have contributed to fistula formation. A second surgical procedure consisted of excision of the fistula and bone cement and the dead space was obliterated by bringing the gluteus medius muscle into the defect. The fistula recurred, however. Reexcision of the fistula and obliteration of the dead space by a pedicled rectus abdominis muscle flap resulted in eradication of the fistula. We emphasize the importance of obliteration of dead space, resulting from large pseudotumour resection. The use of bone cement is not advocated. If a fistula does occur, a pedicled rectus abdominis muscle flap may be considered.

Adult↗

Factor V:Q506 mutation-resistance to activated protein C (APC): clinical implications with respect to family screening.

Resistance to activated protein C (APC), which is almost exclusively caused by a point mutation in the factor V gene (FV:Q506 mutation or FV Leiden) is a recently discovered, prevalent risk factor for the occurrence of venous thromboembolism. It is unknown whether relatives of known patients with this mutation should be screened for the presence of the mutation and what the consequences for asymptomatic carriers would be. This paper addresses the possible benefits and disadvantages of family screening of patients with venous thromboembolism who carry the mutation. Possible prophylactic strategies are discussed and weighed on the basis of estimated incidence rates of venous thromboembolism that are deduced from known relative risks and available population studies.

Activated Protein C Resistance↗

Hyperfibrinogenolysis in disseminated adenocarcinoma.

We present the case of a 42-year-old woman with a recently acquired bleeding tendency. Coagulation studies and response to antifibrinolytic therapy suggested primary hyperfibrinogenolysis: markedly low levels of fibrinogen and alpha2-antiplasmin, normal levels of antithrombin III, protein C and protein S combined with an only borderline low number of platelets without evidence of microangiopathic haemolytic anaemia. A suspected causative adenocarcinoma of the lung was demonstrated. She was treated successfully with tranexamic acid and cryoprecipitate, until the tumor progressed and hyperfibrinogenolysis progressed to diffuse intravascular coagulation. Differential diagnosis of these coagulation disorders, with similar etiology, clinical and laboratory findings is reviewed. Therapeutic implications are discussed.

Adenocarcinoma↗

Differences in immune response between HCV positive, HIV negative haemophilia A and B patients.

We measured numbers of lymphocytes and subsets in seven HIV negative, HCV positive severe haemophilia B patients, before and after substitution was changed from prothrombin complex concentrate to monoclonally purified concentrate. Data were compared with controls and our previous findings in haemophilia A. At baseline, haemophilia B patients did not differ from controls. After two years, T helper cells showed an increase (p = 0.028), while a rise in B cells approached statistical significance (p = 0.063). Haemophilia A patients showed increased numbers of activated non-B lymphocytes (p = 0.003) and lowered numbers of B cells (p = 0.001) at baseline. After two years activated non-B lymphocytes decreased (p = 0.004), as did the CD4/CD8 ratio (p = 0.002), due to increasing numbers of CD8 positive cells (p = 0.087). Our data suggest minor inhibition of the immune system in haemophilia B patients, which recovers after changing therapy to a monoclonally purified product. These findings contrast with the excessive immune stimulation in haemophilia A. The observed differences might be due to the administered concentrates.

Adolescent↗