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H R Büller

Publications and source records attributed to H R Büller.

At least 19 recordsLinked to original sources
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

Ototoxicity and nephrotoxicity of gentamicin vs netilmicin in patients with serious infections. A randomized clinical trial.

In the treatment of serious infection by aminoglycoside antibiotics multiple daily treatment with netilmicin is considered to be the least toxic. Studies comparing netilmicin with gentamicin using the less toxic once-daily schedule are lacking. A randomized prospective study was designed to evaluate the efficacy and toxicity of once-daily netilmicin with gentamicin treatment in patients with serious infections. Consecutive patients with serious infections were randomized between gentamicin 4 mg/kg q24h iv or netilmicin 5.5 mg/kg q24h iv. Exclusion criteria were neutropenia or severe renal failure. A good clinical response was observed in 50 of the 54 evaluable patients (92.6%) treated with gentamicin and in 48/52 (92.3%) netilmicin treated patients. Nephrotoxicity developed in 5/72 (6.9%) gentamicin patients and in 10/69 (14.5%) treated with netilmicin. Audiometry was performed with high-frequency audiometry when possible; no significant differences were found between the two aminoglycosides. We conclude that with once-daily treatment no benefit of netilmicin over gentamicin regarding nephro- or ototoxicity could be demonstrated.

Adolescent↗
PubMed1995

A normal perfusion lung scan in patients with clinically suspected pulmonary embolism. Frequency and clinical validity.

STUDY OBJECTIVE: To assess the frequency of a normal perfusion lung scan in a consecutive series of patients with clinically suspected pulmonary embolism, to determine the complication risk of heparin therapy in those patients treated while awaiting lung scanning, and to evaluate the clinical validity of withholding anticoagulant therapy in patients with a normal lung scan result. DESIGN: Prospective cohort. SETTING: Two teaching hospitals in Amsterdam, the Netherlands. PATIENTS: Consecutive inpatients and outpatients referred for clinically suspected pulmonary embolism who underwent lung scintigraphy. INTERVENTIONS: Initiation of intravenous heparin therapy before lung scanning was left to the discretion of the attending physician. Anticoagulant therapy was withheld or withdrawn in patients with a normal lung scan. Patients were followed-up for 6 months. MEASUREMENTS AND RESULTS: A normal perfusion scan was obtained in 114 of 412 consecutive patients (28%; 95% confidence interval [CI] 23 to 32%). Major bleeding complications occurred in 2 of 30 patients (6.7%; 95% CI 0.8 to 22.1%) in whom heparin was administered while awaiting lung scintigraphy. One patient was lost to follow-up, and venous thromboembolism (0%; 95% CI 0 to 3.2%) did not develop in the remaining 113 patients. CONCLUSIONS: In a substantial proportion of patients with clinically suspected pulmonary embolism (28%) the diagnosis is excluded by lung scintigraphy. The test should be performed as soon as feasible to prevent unnecessary hospitalization and bleeding complications. Long-term anticoagulant therapy can be safely withheld in symptomatic patients with a normal perfusion lung scan.

Adolescent↗
PubMed1995

Complete inhibition of endotoxin-induced coagulation activation in chimpanzees with a monoclonal Fab fragment against factor VII/VIIa.

Gram-negative sepsis is oftentimes complicated by activation of coagulation with disseminated intravascular coagulation and microthrombosis. This may contribute to the associated morbidity, multiple organ failure and death. Recent studies have established that the tissue factor-dependent pathway of blood coagulation has a significant participatory role in the initial endotoxin-induced activation of coagulation. Tissue factor (TF), expressed on the surface of activated monocytes and endothelial cells forms cell surface complexes with free circulating factors VII and VIIa. The latter complex proteolytically activates factors X and IX. Recent in vivo experiments have shown that a rapidly neutralizing TF monoclonal antibody prevents and arrests the endotoxin-induced activation of coagulation and similar studies have shown to reduce mortality in baboons. In this study we describe the preparation of a factor VII/VIIa neutralizing monoclonal Fab fragment and characterize its effect on in vivo activation of coagulation during experimental endotoxemia in chimpanzees. Four chimpanzees received a bolus intravenous injection of 4 ng/kg endotoxin in combination with Fab fragments of a factor VII/VIIa neutralizing murine monoclonal antibody (12D10) at a dose of either 50 micrograms/kg (n = 2) or 100 micrograms/kg (n = 2). Four control animals received a bolus injection of endotoxin alone. Administration of the 12D10 Fab fragments, immediately preceding the endotoxin bolus injection, effectively blocked the endotoxin-induced activation of coagulation. Plasma levels of products of in vivo activation, namely F1 + 2, TAT complexes and FpA remained at baseline values. The administration of 12D10 resulted in a rapid decline in factor VII/VIIa antigen levels which remained below 5 ng/ml for 180-240 min, followed by a rapid return to baseline levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Antithrombin III concentrate in the treatment of DIC: a retrospective follow-up study.

OBJECTIVE: To assess the clinical utility of antithrombin III (AT-III) substitution in adults with septicaemia in an intensive care unit. METHODS: A retrospective follow-up study was performed in the adult intensive care unit of a large teaching hospital. Adults with septicaemia and AT-III levels less than 0.45 IU/ml were identified. AT-III administration, consisting of an intravenous bolus injection of 20 IU/kg, followed by continuous infusion of 20 IU/kg per 24 h, was given to 21 patients, while this was withheld in 21 age- and sex-matched controls. The severity of diffuse intravascular coagulation (DIC), APACHE II score, and type of septicaemia were analysed. The odds ratio was calculated for survival. RESULTS: The base-line characteristics with regards to severity of DIC, APACHE scores and types of sepsis were comparable for the patients who received AT-III concentrates and those who did not. Mortality in the treated and non-treated groups was 76% (95% CI: 53-92%) and 57% (95% CI: 34-78%), respectively (p = 0.24). The odds ratio for survival was 2.4 if no AT-III concentrate was administered (95% CI: 0.537-11.5; p = 0.24). CONCLUSIONS: The use of AT-III concentrates in the doses applied in adult intensive care patients with septicaemia does not appear to improve outcome in terms of mortality.

Adult↗
PubMed1993

Interleukin-6 mediates host defense responses induced by abdominal surgery.

BACKGROUND: Cytokines have been implicated as pivotal mediators of the host defense reaction. In patients undergoing surgery we investigated the relationship between such mediators and postoperative host defense responses. METHODS: Tumor necrosis factor (TNF) was determined with an immunoradiometric assay, interleukin (IL)-6 by a B9-cell bioassay, and endotoxin by a chromogenic limulus lysate assay. C-reactive protein, alpha 1-antitrypsin, and alpha 2-macroglobulin were quantified by nephelometric assay. RESULTS: In 19 consecutive patients undergoing pancreaticoduodenectomy, a large increase in portal, and a significantly lower increase in peripheral, IL-6 levels was observed. No significant increase in TNF levels was noted. Fever developed in 16 patients within 24 hours (84%). The highest peripheral IL-6 levels correlated logarithmically (R = 0.59; p = 0.0039) with the peak body temperatures. C-reactive protein levels correlated with IL-6 levels (R = 0.49; p = 0.020). Increased IL-6 levels were observed in all nine patients undergoing either hemihepatectomy, breast reduction, or extensive breast reconstruction; however, only patients undergoing hemihepatectomy had endotoxemia. CONCLUSIONS: We conclude that abdominal surgery causes acute release of IL-6, but not TNF, in the portal circulation. IL-6 seems to be a major endogenous mediator of fever and the acute-phase response. The presence of endotoxin might be synergistic but is not obligatory for the host defense response after surgical trauma.

Acute-Phase Proteins↗
PubMed1992

Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal-vein thrombosis.

BACKGROUND: In most countries, heparin is used in the initial treatment of patients with deep-vein thrombosis. Well-designed studies establishing the efficacy of heparin therapy are lacking, however. Treatment with acenocoumarol alone, according to the hypothesis that high dosages of oral anticoagulants obviate the need for heparin, is considered an effective alternative in some countries. METHODS: In a randomized, double-blind study we compared the efficacy and safety of continuous intravenous heparin plus acenocoumarol with the efficacy and safety of acenocoumarol alone in the initial treatment of outpatients with proximal-vein thrombosis. The principal study end point was a confirmed symptomatic extension or recurrence of venous thromboembolism during six months of follow-up. In addition, we assessed asymptomatic extension or pulmonary embolism by repeating venography and lung scanning after the first week of treatment. The incidence of major bleeding was determined during three months of follow-up. RESULTS: The study was terminated early by the Data Safety and Monitoring Committee because of an excess of symptomatic events in the group that received acenocoumarol alone (in 12 of 60 patients [20 percent], as compared with 4 of 60 patients [6.7 percent] in the combined-therapy group by intention-to-treat analysis; P = 0.058). Asymptomatic extension of venous thrombosis was observed in 39.6 percent of the patients in the acenocoumarol group and in 8.2 percent of patients treated with heparin plus acenocoumarol (P < 0.001). Major bleeding complications were infrequent and comparable in the two groups. CONCLUSIONS: Patients with proximal-vein thrombosis require initial treatment with full-dose heparin, which can safely be combined with acenocoumarol therapy.

Acenocoumarol↗
PubMed1992

Deep-vein thrombosis and the incidence of subsequent symptomatic cancer.

BACKGROUND: In contrast to the established relation between overt cancer and subsequent venous thromboembolism, it is unclear whether symptomatic deep-vein thrombosis is associated with a risk of subsequent overt malignant disease. METHODS: Two hundred sixty consecutive patients with symptomatic, venographically proved deep-vein thrombosis were enrolled in a study, of whom 250 were followed during a two-year period. Among those assessed during follow-up, the incidence of subsequently detected cancer in the 105 patients with secondary venous thrombosis (i.e., thrombosis associated with a well-recognized risk factor other than cancer) was compared with the incidence of cancer in the 145 patients with idiopathic venous thrombosis. RESULTS: Routine examination at the time of diagnosis of the venous thrombosis revealed cancer in 5 of the 153 enrolled patients with idiopathic venous thrombosis (3.3 percent) and in none of the 107 enrolled patients with secondary venous thrombosis. During follow-up, overt cancer developed in 2 of the 105 patients with secondary venous thrombosis (1.9 percent) and in 11 of the 145 patients with idiopathic venous thrombosis (7.6 percent; odds ratio, 2.3; 95 percent confidence interval, 1.0 to 5.2; P = 0.043). Of the 145 patients with idiopathic venous thrombosis, 35 had confirmed recurrent thromboembolism. Overt cancer subsequently developed in 6 of the 35 (17.1 percent). The incidence of cancer in the patients with recurrent idiopathic venous thrombosis was higher than that in the patients with secondary venous thrombosis (P = 0.008; odds ratio, 9.8; 95 percent confidence interval, 1.8 to 52.2) or in the patients with idiopathic venous thrombosis that did not recur (P = 0.024; odds ratio, 4.3; 95 percent confidence interval, 1.2 to 15.3). CONCLUSIONS: There is a statistically significant and clinically important association between idiopathic venous thrombosis and the subsequent development of clinically overt cancer, especially among patients in whom venous thromboembolism recurs during follow-up.

Aged↗
PubMed1992

Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis.

Low-molecular-weight heparins (LMWHs) have theoretical advantages over standard heparin as postoperative thromboprophylactic agents. We conducted a meta-analysis of studies reported between 1984 and April, 1991, in which LMWHs were compared with standard heparin for postoperative prophylaxis. We included only randomised studies (reported in English, French, or German) in which investigators compared currently recommended doses of the agents and used adequate screening techniques for deep vein thrombosis. For all surgical studies the relative risk (LMWH versus standard heparin) for deep vein thrombosis was 0.74 (95% Cl 0.65-0.86), for pulmonary embolism 0.43 (95% Cl 0.26-0.72), and for major bleeding 0.98 (95% Cl 0.69-1.40). Comparable relative risks were observed for the general and orthopaedic surgery studies separately. When the analysis for the general surgery studies was limited to those of strong methodology, assessed by eight criteria defined in advance, the benefit/risk ratio was less favourable--relative risk for deep vein thrombosis 0.91 (95% Cl 0.68-1.23), for major bleeding 1.32 (95% Cl 0.69-2.56). There is at present no convincing evidence that in general surgery patients LMWHs, compared with standard heparin, generate a clinically important improvement in the benefit to risk ratio. However, LMWHs may be preferable for orthopaedic surgery patients, in view of the larger absolute risk reduction for venous thrombosis.

Clinical Trials as Topic↗
PubMed1992

Tumor necrosis factor induces von Willebrand factor release in healthy humans.

Tumor necrosis factor (TNF) is an important mediator of the host responses to systemic infection. To investigate the effect of TNF on the release of von Willebrand factor (vWF) into the circulation, we performed a controlled study in six healthy men, sequentially measuring the plasma concentrations of vWF antigen after a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). TNF induced a marked increase in vWF antigen plasma levels, becoming significant after 45 min and peaking after 4 h (percentage increase from base line: 351 +/- 46; p less than 0.0001, TNF versus saline). The multimeric organization of circulating vWF was not affected by TNF. We conclude that TNF may be an early mediator of increased vWF secretion in systemic infection.

Adult↗
PubMed1992

The use of the D-dimer test in combination with non-invasive testing versus serial non-invasive testing alone for the diagnosis of deep-vein thrombosis.

We studied the usefulness of the determination of plasma D-dimer levels (using an ELISA) in combination with non-invasive testing with impedance plethysmography (IPG) or real-time ultrasonography (US) for the diagnosis of deep-vein thrombosis (DVT), in outpatients with clinically suspected DVT. This combined approach was compared to serial non-invasive testing alone in these patients. The sensitivity of a positive D-dimer test (greater than 300 micrograms/l) for the presence of DVT was 100% (70/70 patients; 95% C.I.: 95-100%), whereas the specificity was 29% (69/239 patients; 95% C.I.: 23-34%). The proportion of patients in which a definitive decision about the presence or absence of DVT could be made on the day of referral, was calculated for both approaches. When applying the combined approach, in 42% of all referred patients the diagnosis of DVT could either be established or refuted on entry, as opposed to only 19% of patients using serial non-invasive testing alone. Also, the costs per DVT diagnosed were calculated for the two diagnostic approaches. For the diagnosis of DVT the costs using serial IPG were comparable to the costs using the combination of IPG and the D-dimer test. The same conclusion holds for the comparison of serial US with the combination of US and D-dimer testing. We conclude that for the diagnosis of DVT in symptomatic outpatients the combination of non-invasive testing with the D-dimer test might be preferred over serial non-invasive testing alone, although the safety of such an approach remains to be established in future management studies.

Cost-Benefit Analysis↗
PubMed1992

Venous thrombosis during pregnancy: leg and trimester of presentation.

In order to determine the relative frequencies of left and right leg venous thrombosis during pregnancy and the frequencies of venous thrombosis during the three trimesters, a cohort study of 60 consecutive patients with a first episode of venous thrombosis during pregnancy was performed. Fifty-eight women had isolated left leg thrombosis, two patients had bilateral venous thrombosis and no patient had isolated right leg venous thrombosis. Thirteen patients had venous thrombosis during the first trimester (21.7%), 28 during the second trimester (46.7%) and 19 during the third trimester (31.7%). These findings indicate that patients with symptoms in the right leg rarely have venous thrombosis. Because leg pain and swelling occur most frequently during the third trimester but venous thrombosis is relatively equally distributed during all three trimesters, patients presenting earlier during pregnancy are more likely to have venous thrombosis than patients presenting later during pregnancy.

Female↗
PubMed1992

Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis.

In view of the potential of low-molecular-weight heparins (LMWH) to simplify initial therapy and allow outpatient treatment of proximal deep-vein thrombosis, we undertook a randomised comparison of fixed-dose subcutaneous LMWH with adjusted-dose intravenous standard heparin in the initial treatment of this disorder. Our main objectives were to compare the efficacy of these regimens for 6 months of follow-up and to assess the risk of clinically important bleeding. Of 170 consecutive symptomatic patients with venographically proven proximal deep-venous thrombosis, 85 received standard heparin (to achieve an activated partial thromboplastin time of 1.5 to 2.0 times the pretreatment value) and 85 LMWH (adjusted only for body weight) for 10 days. Oral coumarin was started on day 7 and continued for at least 3 months. The frequency of recurrent venous thromboembolism diagnosed objectively did not differ significantly between the standard-heparin and LMWH groups (12 [14%] vs 6 [7%]; difference 7% [95% confidence interval -3% to 15%]; p = 0.13). Clinically important bleeding was infrequent in both groups (3.5% for standard heparin vs 1.1% for LMWH; p greater than 0.2). We conclude that fixed-dose subcutaneous LMWH is at least as effective and safe as intravenous adjusted-dose heparin in the initial treatment of symptomatic proximal-vein thrombosis. Since there is no need for laboratory monitoring with the LMWH regimen, patients with venous thrombosis can be treated at home.

Aged↗
PubMed1992

Subcutaneous heparin compared with continuous intravenous heparin administration in the initial treatment of deep vein thrombosis. A meta-analysis.

OBJECTIVE: To quantitatively assess the efficacy and safety of published randomized trials comparing subcutaneous heparin with continuous intravenous heparin for the initial treatment of deep vein thrombosis. DATA IDENTIFICATION: Studies published between January 1986 and April 1991 were identified through computer searches of the MEDLINE database and through reviews of the Science Citation Index, Current Contents, proceedings and abstract books, and references cited in the identified articles. Complete manuscripts were obtained from the authors if only abstracts were available. STUDY SELECTION: Eight clinical trials were identified that compared subcutaneous with intravenous heparin administration in patients with venographically confirmed deep vein thrombosis. DATA EXTRACTION: Each study was independently analyzed for the percentage distribution of thrombosis, the method of outcome measurement, and the heparin dose. The methodologic strength of each study was assessed using predefined standards for the proper evaluation of a therapeutic intervention with particular emphasis on the type of patient allocation and objective measurements. RESULTS OF DATA ANALYSIS: The overall relative risk for efficacy (defined as prevention of extension and recurrence of venous thromboembolism) of subcutaneous compared with intravenous heparin treatment was 0.62 (95% CI, 0.39 to 0.98), whereas for safety (defined as major hemorrhage) it was 0.79 (CI, 0.42 to 1.48). CONCLUSIONS: The results of our meta-analysis indicated that heparin administered subcutaneously twice daily in the initial treatment of deep vein thrombosis is more effective and at least as safe as continuous intravenous heparin administration. Administration of heparin subcutaneously may simplify patient treatment and could facilitate home treatment.

Hemorrhage↗