PubMed Health⌕ Search

Biomedical subjects

H R Büller

Publications and source records attributed to H R Büller.

At least 19 recordsLinked to original sources
PubMed1997

Diagnostic utility of ultrasonography of leg veins in patients suspected of having pulmonary embolism.

BACKGROUND: The standard diagnostic approach in patients suspected of having pulmonary embolism starts with perfusion-ventilation lung scanning. If the resulting scan is not diagnostic, pulmonary angiography should be done. The use of tests for deep venous thrombosis has been advocated as an adjunct to establishing the diagnosis of pulmonary embolism, but no prospective studies have provided adequate information about the value of these tests. OBJECTIVE: To determine the accuracy and potential clinical utility of compression ultrasonography in the diagnosis of pulmonary embolism. DESIGN: Prospective cohort study with blinded assessment of ultrasonographic results. SETTING: Teaching hospital. PATIENTS: 397 consecutive inpatients and outpatients in whom pulmonary embolism was clinically suspected. MEASUREMENTS: Sensitivity and specificity of compression ultrasonography. Perfusion-ventilation scanning and angiography were the conjoint gold standard for determining the presence or absence of pulmonary embolism. Also calculated were the number of angiograms and lung scans avoided and the number of patients unnecessarily treated when compression ultrasonography was included in the diagnostic strategy. RESULTS: The overall sensitivity of compression ultrasonography for deep venous thrombosis in patients with pulmonary embolism was 29% (95% CI 22% to 37%); the specificity was 97% (CI, 94% to 99%). Adding ultrasonography to the diagnostic approach before lung scanning would avoid approximately 14% of lung scans and 9% of angiograms but would lead to unnecessary treatment of 13% of patients who have an abnormal ultrasonographic result (2% to 4% of all those receiving anticoagulation). When compression ultrasonography is done only in patients with a nondiagnostic lung scan, 9% of angiographies are prevented at the cost of unnecessarily treating 26% of patients who have an abnormal ultrasonographic result (2% of all patients receiving anticoagulation). CONCLUSION: The diagnostic value of compression ultrasonography for the detection of deep venous thrombosis in patients suspected of having pulmonary embolism is limited; the gain in diagnostic efficiency obtained through the use of ultrasonography may be offset by a loss in diagnostic accuracy.

Adolescent↗
PubMed1997

Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis.

BACKGROUND: Post-thrombotic syndrome varies from mild oedema to incapacitating swelling with pain and ulceration. We investigated the rate of post-thrombotic syndrome after a first episode of deep-vein thrombosis and assessed the preventive effect of direct application of a sized-to-fit graded compression stocking. METHODS: Patients with a first episode of venogram-proven proximal deep-vein thrombosis were randomly assigned no stockings (the control group) or made-to-measure graded compression elastic stockings for at least 2 years. Post-thrombotic syndrome was assessed with a standard scoring system that combined clinical characteristics and objective leg measurements. Patients were assessed every 3 months during the first 2 years, and every 6 months thereafter for at least 5 years. The cumulative incidence of mild-to-moderate post-thrombotic syndrome was the primary outcome measure. FINDINGS: Of the 315 consecutive outpatients considered for inclusion, 44 were excluded and 77 did not consent to take part. 194 patients were randomly assigned compression stockings (n = 96) or no stockings (n = 98). The median follow-up was 76 months (range 60-96) in both groups. Mild-to-moderate post-thrombotic syndrome (score > or = 3 plus one clinical sign) occurred in 19 (20%) patients in the stocking group and in 46 (47%) control-group patients (p < 0.001). 11 (11%) patients in the stocking group developed severe post-thrombotic syndrome (score > or = 4), compared with 23 (23%) patients in the control group (p < 0.001). In both groups, most cases of post-thrombotic syndrome occurred within 24 months of the acute thrombotic event. INTERPRETATION: About 60% of patients with a first episode of proximal deep-vein thrombosis develop post-thrombotic syndrome within 2 years. A sized-to-fit compression stocking reduced this rate by about 50%.

Bandages↗
PubMed1996

Frequency of pregnancy-related venous thromboembolism in anticoagulant factor-deficient women: implications for prophylaxis.

BACKGROUND: It has been reported that women with an inherited deficiency of antithrombin, protein C, or protein S have an increased risk for developing venous thromboembolic disease during pregnancy and the postpartum period. However, because the available data on risk are flawed, it is difficult to define a rational, efficacious, and safe policy about prophylaxis for venous thromboembolism in these women. OBJECTIVE: To determine the frequency of venous thromboembolism during pregnancy and the postpartum period in women with heritable deficiencies of anticoagulant factors. DESIGN: Retrospective cohort study. SETTING: University outpatient clinics in the Netherlands and Italy. PARTICIPANTS: 129 otherwise asymptomatic female family members of patients with a history of venous thromboembolism and an established deficiency of antithrombin, protein C, or protein S. MEASUREMENTS: Medical history, with specific attention to episodes of venous thromboembolism and obstetric history, was taken. The anticoagulant factor status of the study participants was determined. If a patient had an episode of venous thromboembolism, subsequent pregnancies in that patient were not analyzed. RESULTS: Of the 129 women who participated in the study, 60 had anticoagulant factor deficiency and 69 did not. In the nondeficient group, 198 pregnancies occurred; 1 of these (0.5%) was complicated by an episode of venous thromboembolism during the postpartum period. In the deficient group, 169 pregnancies occurred; 7 of these (4.1%) were complicated by an episode of venous thromboembolism during the third trimester of pregnancy (2 pregnancies [1.2%]) and the postpartum period (5 pregnancies [3.0%]). The risk for venous thromboembolism was increased eightfold in deficient women compared with nondeficient women (hazard ratio, 8.0 [95% CI 1.2 to 184]). CONCLUSIONS: Anticoagulant factor-deficient women have an increased risk for venous thromboembolism during pregnancy and the postpartum period. Although data from an appropriate randomized clinical trial are lacking, the frequency of venous thromboembolism seen in deficient women might justify the use of anticoagulative prophylaxis during the third trimester of pregnancy and the postpartum period.

Adolescent↗
PubMed1996

[Costs of diagnosis and treatment for pulmonary embolism lower due to application of consensus strategy].

OBJECTIVE: To compare the costs of diagnosis and treatment of patients clinically suspected of pulmonary embolism, before and after the adoption of the Dutch consensus for the diagnosis of pulmonary embolism. DESIGN: Study of the records, followed by a prospective study with a follow-up lasting 6 months. SETTING: Academic Medical Centre and Slotervaart Hospital, Amsterdam, the Netherlands. METHOD: Data were collected on 120 patients from the preconsensus period and on 452 patients examined according to the consensus strategy. This established the average patterns of medical consumption of patients before and after adoption of consensus. The mean costs per patient were then estimated. RESULTS: Diagnosis and treatment of a patient according to the consensus strategy on the basis of our estimates were considerably less expensive than non-protocolled diagnosis and treatment (Dfl. 4,413 as against Dfl. 5,115 per patient). This difference mainly resulted from shorter hospital stays owing to more rapid completion of the diagnosis. Considering the large number of annual hospital admissions in the Netherlands in connection with this diagnosis, savings of up to Dfl. 26 million would appear possible if the consensus were followed nationwide. CONCLUSION: Considerable amounts are involved in the diagnosis and treatment of pulmonary embolism in the Netherlands. Accordingly, further research into possibilities to make these more efficient would appear advisable.

Clinical Protocols↗
PubMed1996

Comparison of sustained antithrombotic effects of inhibitors of thrombin and factor Xa in experimental thrombosis.

BACKGROUND: In the pathogenesis of (recurrent) thrombosis, clot-associated thrombin appears to play an important role. Antithrombin III-independent thrombin inhibitors have been shown to neutralize clot-bound thrombin effectively. We compared the sustained antithrombotic effects and the effects on endogenous fibrinolysis of several of these agents with recombinant tick anticoagulant peptide (rTAP), a selective factor Xa inhibitor, and low-molecular-weight heparin (LMWH) in an experimental venous thrombosis model. METHODS AND RESULTS: Rabbits received either recombinant hirudin (rHir), Hirulog-1, CVS#995 (a novel direct inhibitor of thrombin), rTAP, LMWH, or saline. The effect on thrombus growth was assessed by measuring the accretion of 125I-labeled fibrinogen onto preformed nonradioactive thrombi, and the effect on endogenous fibrinolysis was assessed by measuring the decline in radioactivity of preformed 125I-labeled thrombi in rabbit jugular veins. All direct thrombin inhibitors induced a sustained antithrombotic effect compared with either LMWH and rTAP. In addition, CVS#995 also further decreased thrombus size after stopping its infusion, which was due to a significant enhancement of endogenous fibrinolysis. CONCLUSIONS: Direct thrombin inhibition by rHir, Hirulog-1, or CVS #995 induces a sustained antithrombotic effect compared with rTAP and LMWH, which is most likely due to inhibition of clot-bound thrombin. CVS#995 was shown to also enhance the extent of endogenous fibrinolysis to a greater degree compared with rHir and might therefore be an interesting new antithrombotic agent for the treatment of venous and arterial thrombosis.

Animals↗
PubMed1996

Feasibility, safety and clinical utility of angiography in patients with suspected pulmonary embolism.

The purpose of our study was to assess feasibility, safety and clinical utility of selective pulmonary angiography in patients with suspected pulmonary embolism and a nondiagnostic lung scan. The design was a prospective, descriptive study. The subjects were consecutive patients with clinically suspected pulmonary embolism and a nondiagnostic lung scintigram in whom pulmonary angiography was considered. Angiography was withheld in cases of manifest heart failure, renal failure, mean pulmonary artery pressure above 40 mmHg, or if there were compelling clinical reasons. All patients were followed-up for 6 months. The outcome measures were successful angiography, morbidity, mortality and recurrent pulmonary embolism in patients with normal angiogram in whom anticoagulants were withheld during 6 months of follow-up. Of 487 patients, 196 (40%) had nondiagnostic lung scan findings. In 46 patients (23%) pulmonary angiography was withheld. Pulmonary embolism was excluded in 105 patients (70%), and proven in 40 (27%) patients. In 5 (3%) patients the angiogram was inadequate for interpretation. No fatal complications were encountered [95% confidence interval (CI) 0-2.4%]. Nonfatal complications occurred in 3 patients (2%; 95% CI 0.4-6.0%); all recovered spontaneously. None of 105 patients with a normal angiogram returned with thromboembolism during follow-up (0%; 95% CI 0-3.4%). Pulmonary angiography is safe, rules out pulmonary embolism in two thirds of patients with a nondiagnostic lung scan and can be performed in almost 80% of these patients. It is safe to withhold long-term anticoagulants if a normal angiogram is obtained in this subgroup of patients with clinically suspected pulmonary embolism.

Adolescent↗
PubMed1996

Absence of mutations at the activated protein C cleavage sites of factor VIII in 125 patients with venous thrombosis.

Resistance to activated protein C (APC), caused by a mutation at amino acid position Arg506 of the factor V gene, has recently been identified as the most prevalent genetic defect associated with venous thrombosis. Similarly to factor V, mutations at the cleavage sites of factor VIII for APC may occur in patients with venous thrombosis. Here we have analysed 125 consecutive patients with incidental or recurrent venous thromboembolism for the presence of mutations at the cleavage sites for APC at amino acid positions Arg336 and Arg562 of factor VIII. Our findings indicate that mutations at these amino acid positions of factor VIII do not occur in the patient group analysed.

Adult↗
PubMed1996

Short-term efficacy and safety of pravastatin in 72 children with familial hypercholesterolemia.

The safety, tolerability, and efficacy of a 12-wk treatment with pravastatin, 5, 10, and 20 mg/d, was evaluated in 72 children with heterozygous familial hypercholesterolemia (FH) in a double-blind, randomized and placebo-controlled study. The results show that pravastatin was well tolerated and that adverse events were mild and equally distributed among the three treatment groups. Plasma total and LDL cholesterol levels were significantly reduced in all pravastatin treatment groups, in comparison with the control group; -24.6% (-28.1 to 21.0) and -32.9% (-37.0 to -28.6), for mean change and 95% confidence interval, respectively. In four children plasma LDL cholesterol levels were reduced within normal limits for sex and age. HDL cholesterol increased in the pravastatin 20-mg group, +10.8% (+3.4 to +18.8), whereas plasma apo B100 and very LDL (VLDL) cholesterol levels were reduced within all pravastatin-treated groups -26.8% (-31.2 [corrected] to -21.7) and -24.5% (-35.0 to -12.3). These data show that short-term pravastatin treatment of children with FH is safe and effective, although long-term dose titration studies with 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors need to be performed, to reduce plasma LDL cholesterol levels below a predefined level. The results of these studies have to be awaited before new treatment strategies are to be considered in these children.

Adolescent↗
PubMed1996

Attenuation of the inflammatory response in an animal colitis model by neutrophil inhibitory factor, a novel beta 2-integrin antagonist.

BACKGROUND: Neutrophils are significant effector cells in acute inflammatory bowel disease. Recruitment of these cells is dependent on beta 2-integrin-mediated adhesion and transmigration. The efficacy of neutrophil inhibitory factor (NIF), an antagonist of the beta 2-integrin CD11b/CD18, in ameliorating inflammation was tested in an animal model of acute colitis. METHOD: Immune-complex colitis was induced in groups of rabbits by using various formalin concentrations (2%, 0.75%, and 0.5%). Animals were treated with rNIF, 10 mg/kg. After they had been killed the mucosal appearance was scored, and tissue saved for histology and quantitation of myeloperoxidase (MPO), leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and thromboxane B2 (TXB2). RESULTS: In the 2% formalin group therapy with rNIF resulted in lower LTB4 (p < 0.05) levels. For the 0.75% and 0.5% groups, MPO was lower with rNIF treatment (p < 0.03 and p < 0.05, respectively), as were LTB4 concentrations (both, p < 0.04). PGE2 and TXB2 levels remained unchanged. Histology showed polymorphonuclear cell infiltration to be reduced by rNIF in the 2% and 0.75% formalin-treatment groups (p < 0.05). CONCLUSION: These results suggest that blockade of CD11b/CD18-mediated mucosal neutrophil recruitment may form part of a strategy for targeted therapeutic intervention in inflammatory bowel disease.

Acute Disease↗
PubMed1996

Low molecular weight heparin and compression stockings in the prevention of venous thromboembolism in neurosurgery.

Perioperative anticoagulant prophylaxis for postoperative venous thromboembolism (VTE) in neurosurgical patients has not gained wide acceptance due to the fear of intracranial bleeding. Physical methods give a worthwhile reduction of postoperative VTE but there still remains a substantial residual incidence. In other clinical indications, low molecular weight heparins have proven to be effective for prophylaxis of VTE when administered postoperatively, with the advantage of no bleeding enhancement during surgery. Therefore, we performed a multicentre, randomized, double-blind trial in neurosurgical patients to investigate the efficacy and safety of adding a low molecular weight heparin (LMWH), nadroparin, initiated postoperatively, to graduated compression stockings in the prevention of VTE. Deep-vein thrombosis was detected by mandatory venography. Bleeding was determined according to pre-defined objective criteria for major and minor episodes. An adequate bilateral venogram was obtained in 166 of 241 LMWH patients (68.9%) and 179 of 244 control patients (73.4%). A total of 31 of 166 LMWH patients (18.7%) and 47 of 179 controls patients (26.3) had VTE up to Day 10 postoperatively (p = 0.047). The relative risk reduction (RRR) was 28.9%. The rates for proximal deep-vein thrombosis/pulmonary embolism were 6.9% and 11.5% for the two groups, respectively (RRR: 40.2%; p = 0.065). Secondary analyses involved all VTE up to day 56 post-surgery which was detected in 33 patients of 241 in the LMWH group (13.7%) and 51 of 244 control patients (20.9%; RRR 34.5%; p = 0.018). The corresponding percentages for proximal deep-vein thrombosis/pulmonary embolism were 5.8% and 10.2% for the two groups, respectively, giving a RRR of 43.3%; p = 0.36. Major bleeding complications, during the treatment period, occurred in six low molecular weight heparin treated patients (2.5%) and in two control patients (0.8%); p = 0.87. A higher mortality was observed in the low molecular weight heparin group over the 56-day follow-up period (22 versus 10; p = 0.026). However, none of these deaths was judged by a blinded adjudication committee to be related to the study drug. In conclusion, this study demonstrates that the low molecular weight heparin, nadroparin, added to graduated compression stockings results in a clinically significant decrease in VTE without inducing any significant increase of major bleeding.

Anticoagulants↗
PubMed1996

Reliable rapid blood test for the exclusion of venous thromboembolism in symptomatic outpatients.

UNLABELLED: In this study we assessed the reliability of a rapid bed-side whole blood D-dimer assay prospectively in patients with clinically suspected venous thromboembolism, referred to the Academic Medical Centre, Amsterdam. In consecutive outpatients with clinically suspected deep vein thrombosis or pulmonary embolism we measured the sensitivity, specificity and negative predictive value of the assay compared to the outcome of standard diagnostic tests and 3-month follow-up. A total of 234 patients were included; the prevalence of venous thromboembolism was 29%. A sensitivity, specificity and negative predictive value of 100% (95% CI: 95% - 100%), 58% (95% CI: 50%-65%) and 100% (95% CI:96% - 100%), respectively, were obtained. The exclusion rate was 41% of all referred patients. CONCLUSION: The SimpliRED whole blood D-dimer assay appears to be a simple and reliable method for the exclusion of venous thromboembolism in symptomatic outpatients.

Adolescent↗
PubMed1995

Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen.

Recent concern about the safety of combined oral contraceptives (OCs) with third-generation progestagens prompted an examination of data from a population-based case-control study (Leiden Thrombophilia Study). We compared the risk of deep-vein thrombosis (DVT) during use of the newest OCs, containing a third-generation progestagen, with the risk of "older" products. We also investigated the influence of family history of thrombosis, previous pregnancy, age, and the thrombogenic factor V Leiden mutation. We selected 126 women with DVT and 159 controls aged 15-49 (mean age 34.9) and premenopausal and found, as compared with non-users, the highest age-adjusted relative risks to be that for an OC containing desogestrel and 30 micrograms ethinyloestradiol (relative risk [RR] 8.7, 95% CI 3.9-19.3). We found lower relative risks for all other types of OC, ranging from 2.2 to 3.8. In a direct comparison, users of the desogestrel-containing oral contraceptive had a 2.5-fold higher risk (95% CI 1.2-5.2) than users of all other OC types combined. The relative risk for the desogestrel-containing OC was similar among women with and without a family history--ie, preferential prescription because of family history cannot explain our findings. Nor could the excess risk be explained by previous pregnancy, and it was highest in the youngest age categories, where we would expect most new users. The age-adjusted RR for the desogestrel-containing contraceptive was 9.2 (3.9-21.4) among non-carriers of the factor V Leiden mutation and 6.0 (1.9-19.0) among carriers of the mutation. This latter risk is superimposed on the 8-fold increased risk of venous thrombosis for carriers of the factor V Leiden mutation. The risk of carriers using the desogestrel-containing OC as compared with noncarrier non-users will therefore be increased almost 50-fold. Use of low-dose OCs with a third-generation progestagen carries a higher risk of DVT than the previous generation of OCs. The absolute risk of DVT associated with these OCs seems to be especially high among carriers of the factor V Leiden mutation and among women with a family history of thrombosis. However, the higher risk associated with OC with a third-generation progestagen compared with previous generations was also present in women without factor V Leiden and with no family history.

Adolescent↗
PubMed1995

Easier monitoring of aminoglycoside therapy with once-daily dosing schedules.

Little has been reported on serum levels attained using once-daily aminoglycoside regimens and their relation to dosage administered and renal function. Consecutive patients with serious infections were randomized to receive gentamicin 4 mg/kg q 24h i.v. (n = 69), gentamicin 1.33 mg/kg q 8h i.v. (n = 46) or netilmicin 5.5 mg/kg q 24h i.v. (n = 59) (with dose reduction in case of renal dysfunction). In the three groups, median first serum trough levels were 0.4, 1.0 and 0.4 mg/l, respectively, and median first serum peak levels were 9.5, 4.7 and 12.2 mg/l (p < 0.01 once-daily vs. thrice-daily regimens). Dose adjustment because of first trough concentrations of > 2 mg/l and/or peak concentrations of < 6 mg/l was required in 6%, 78% and 12% of patients, respectively. Second trough and peak concentrations were significantly higher in the thrice-daily gentamicin group; serum levels remained constant in the other two groups. The six patients in the once-daily groups who developed elevated trough levels later in therapy were characterized in most cases by a decline in renal function.

Adolescent↗
PubMed1995

Plasminogen activator and plasminogen activator inhibitor I release during experimental endotoxaemia in chimpanzees: effect of interventions in the cytokine and coagulation cascades.

1. Disseminated intravascular coagulation frequently accompanies Gram-negative sepsis and may contribute to widespread deposition of microthrombi. Besides the endotoxin-induced activation of coagulation, an important role for the fibrinolytic system has been postulated. The precise mechanisms underlying these fibrinolytic changes during endotoxaemia are not known but have been suggested to be mediated directly by cytokines or secondary to thrombin generation. 2. In the present study we have delineated in detail the fibrinolytic response to a bolus injection of endotoxin in non-human primates and analysed the contribution of cytokines and thrombin generation to the endotoxin-induced release of tissue-type plasminogen activator and plasminogen activator inhibitor 1. Chimpanzees received a bolus injection of endotoxin alone or in combination with blocking monoclonal antibodies directed against tumour necrosis factor or interleukin 6 or in combination with pentoxifylline. Furthermore, to assess the effect of coagulation activation on the activation of fibrinolysis, another group of chimpanzees received endotoxin in combination with either anti-tissue factor antibodies or recombinant hirudin. 3. Infusion of endotoxin induced a rapid increase in plasminogen activator activity and tissue-type plasminogen activator antigen levels and subsequent plasmin generation, reaching peak levels 2h after endotoxin administration. Plasminogen activator inhibitor 1 levels remained constant for the first 2 h, after which time a steep increase was observed. Plasminogen activator activity and plasmin generation decreased simultaneously with the rise in plasminogen activator inhibitor 1 levels. Fibrinolytic activity remained suppressed during the remainder of the study owing to sustained increased levels of plasminogen activator inhibitor 1. The administration of pentoxifylline strongly attenuated the release of tissue-type plasminogen activator and plasminogen activator inhibitor 1, whereas the antitumour necrosis factor antibodies blocked the fibrinolytic response entirely. In contrast, interleukin 6-neutralizing antibodies did not affect the fibrinolytic response. Although endotoxin-induced generation of thrombin was completely prevented by the administration of tissue factor-neutralizing antibodies or by hirudin, no effect on the fibrinolytic response was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Coagulation and platelet activation pathways. A review of the key components and the way in which these can be manipulated.

Acute coronary syndromes are caused by thrombotic obstruction of usually diseased arteries. The thrombotic plug consists of platelets and fibrin. Until recently only three antithrombotic drugs, aspirin, heparin and dicumarol were available for the prevention and treatment of acute coronary syndromes. A better understanding of the cellular and humoral mechanisms underlying these syndromes has broadened the arsenal of antithrombotic drugs dramatically. In this review the physiological activation process of platelets and the coagulation cascade are discussed. Furthermore, the ways in which these processes can be therapeutically manipulated are reviewed.

Anticoagulants↗