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Biomedical subjects

H R Büller

Publications and source records attributed to H R Büller.

At least 109 records · Page 6Linked to original sources
PubMed2000

Abrupt versus gradual withdrawal of vitamin K antagonist treatment in patients with venous thromboembolic disease: assessment of hypercoagulability and clinical outcome.

BACKGROUND: It is yet unclear whether vitamin K antagonist treatment should be stopped abruptly or gradually after an episode of venous thromboembolism. The mode of withdrawal might influence a potential development of a hypercoagulable state, which could influence the risk for recurrent disease. METHODS: We prospectively studied 37 consecutive patients in whom acenocoumarol was discontinued either abrupt (18) or gradually (19) (2/3 and 1/3 of the initial dose for one week). Blood sampling was performed at various time points up to 18 days after complete withdrawal and was analysed for INR, prothrombin fragment F1 + 2 and D-dimer. All patients were clinically followed-up for the assessment of the association between hypercoagulability and occurrence of disease such as recurrent venous thromboembolism or malignancy. RESULTS: An approximately fourfold increase was observed (median increase from 0.3 to 1.3 nmol/l) in the F1 + 2 levels after both abrupt and gradual withdrawal and in the D-dimer concentrations in the abrupt withdrawal group (0.10 to 0.44 mg/l), while those in whom acenocoumarol was discontinued gradually showed a less pronounced increase of the D-dimer levels (0.11 to 0.29 mg/L) (not significant). During follow-up one recurrent venous thromboembolic event occurred in each group, and a diagnosis of cancer was made four times. All these patients had the highest D-dimer concentrations measured in the entire study group. CONCLUSIONS: This study indicates the potential for a hypercoagulable state after acenocoumarol discontinuation, which was not prevented by tapering the acenocoumarol dose. D-dimer, measured 2 to 3 weeks after acenocoumarol withdrawal, might be an important tool to identify patients at risk for recurrent venous thromboembolism and/or for the presence of an underlying malignancy.

Acenocoumarol↗
PubMed2000

Successful attenuation of venous thrombus growth in rabbits after the administration of a novel oral thrombin inhibitor.

Current antithrombotic compounds have several limitations in clinical practice. The present study was designed to investigate a novel orally available direct thrombin inhibitor, BSF 208791. Intravenous administration of BSF 208791 showed superior antithrombotic properties as compared with Polyethylenglycol-Hirudin (PEG-Hirudin) and low molecular weight heparin (LMWH) in a model of venous thrombosis in rabbits. The thrombus growth was 22%, 30%, 37% and 50% after BSF 208791, PEG-Hirudin. LMWH, and saline administration, respectively. Moreover, bleeding time was less affected after administration of BSF 208791 as compared with PEG-Hirudin. The oral administration of BSF 208791 resulted in adequate bioavailability and significantly reduced venous thrombus growth to 36% as compared with 60% in the saline treated rabbits. The antithrombotic effect of BSF 208791 appears to be superior to PEG-Hiridin and LMWH without affecting the bleeding time. BSF 208791 is an orally available agent that might be a promising candidate for future antithrombotic therapy.

Administration, Oral↗
PubMed2000

Compression ultrasonography of the leg veins in patients with clinically suspected pulmonary embolism: is a more extensive assessment of compressibility useful?

We performed a multi-center study in consecutive patients with suspected pulmonary embolism to compare the diagnostic accuracy of a two-point compression ultrasonography (only the common femoral vein and popliteal vein) with an extensive examination of compressibility (from the common femoral vein until the trifurcation of calf veins). A total of 479 patients underwent the two-point compression ultrasonography. The prevalence of pulmonary embolism was 32%. The sensitivity and specificity of this procedure were 23% (95% CI 19-26) and 98% (95% CI 96-99), respectively. Extensive compression ultrasonography was performed in 461 (96%) of these 479 patients and showed comparable accuracy indices (sensitivity 25%, 95% Cl 20-28 and specificity 97%, 95% CI 95-99). We conclude that compression ultrasonography has a limited sensitivity for the detection of thrombosis in patients with acute pulmonary embolism within 24 h of presentation. A more extensive assessment of compressibility of the leg veins in these patients has no additional value as compared to the two-point assessment.

Adult↗
PubMed1999

Low-dose oral contraceptives and acquired resistance to activated protein C: a randomised cross-over study.

BACKGROUND: We have reported previously that, compared with use of second-generation oral contraceptives, the use of third-generation oral contraceptives is associated with increased resistance to the anticoagulant action of activated protein C (APC). Owing to the cross-sectional design of that study, these observations may have been subject to unknown bias or uncontrolled effects of the menstrual cycle. We aimed to overcome these sources of bias by doing a cycle-controlled randomised cross-over trial. METHODS: The response to APC in plasma was assessed in 33 women who received two consecutive cycles of a second-generation oral contraceptive (150 microg levonorgestrel and 30 microg ethinyloestradiol) or a third-generation oral contraceptive (150 microg desogestrel and 30 microg ethinyloestradiol), and who switched preparations after two pill-free cycles. Normalised APC sensitivity ratios were calculated by measurement of the effect of APC on thrombin generation in the plasma of these women and in pooled plasma from 90 controls. FINDINGS: Of the 33 women, five were excluded because not all required plasma samples were available. In the remaining 28 women, the normalised APC sensitivity ratio increased during treatment with both preparations. Compared with levonorgestrel, desogestrel-containing oral-contraceptive treatment caused a highly significant (p<0.0001) additional increase in normalised APC sensitivity ratio (0.51 [95% CI 0.37-0.66]). Normalised APC sensitivity ratios during oral-contraceptive treatment correlated with the values before oral-contraceptive use. INTERPRETATION: Oral-contraceptive treatment diminishes the efficacy with which APC down-regulates in-vitro thrombin formation. This phenomenon, designated as acquired APC resistance, is more pronounced in women using desogestrel-containing oral contraceptives than in women using levonorgestrel-containing preparations. Whether acquired APC resistance induced by oral contraceptives explains the increased risk of venous thromboembolism in oral-contraceptive users remains to be established.

Activated Protein C Resistance↗
PubMed1999

Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints.

BACKGROUND: Excessive bleeding may complicate cardiac surgery, and is associated with increased morbidity and mortality. Pharmacological strategies to decrease perioperative bleeding have been investigated in a large number of controlled trials, most of which have shown a decrease in blood loss. However, most studies lacked sufficient power to detect a beneficial effect on clinically more relevant outcomes. We did a meta-analysis of all randomised, controlled trials of the three most frequently used pharmacological strategies to decrease perioperative blood loss (aprotinin, lysine analogues [aminocaproic acid and tranexamic acid], and desmopressin). METHODS: Studies were included if they reported at least one clinically relevant outcome (mortality, rethoracotomy, proportion of patients receiving a transfusion, or perioperative myocardial infarction) in addition to perioperative blood loss. In addition, a separate meta-analysis was done for studies concerning complicated cardiac surgery. FINDINGS: We identified 72 trials (8409 patients) that met the inclusion criteria. Treatment with aprotinin decreased mortality almost two-fold (odds ratio 0.55 [95% CI 0.34-0.90]) compared with placebo. Treatment with aprotinin and with lysine analogues decreased the frequency of surgical re-exploration (0.37 [0.25-0.55], and 0.44 [0.22-0.90], respectively). These two treatments also significantly decreased the proportion of patients receiving any allogeneic blood transfusion. By contrast, the use of desmopressin resulted in a small decrease in perioperative blood loss, but was not associated with a beneficial effect on other clinical outcomes. Aprotinin and lysine analogues did not increase the risk of perioperative myocardial infarction; however, desmopressin was associated with a 2.4-fold increase in the risk of this complication. Studies in patients undergoing complicated cardiac surgery showed similar results. INTERPRETATION: Pharmacological strategies that decrease perioperative blood loss in cardiac surgery, in particular aprotinin and lysine analogues, also decrease mortality, the need for rethoracotomy, and the proportion of patients receiving a blood transfusion.

Aminocaproates↗
PubMed1999

The incidence of venous thromboembolism in asymptomatic carriers of a deficiency of antithrombin, protein C, or protein S: a prospective cohort study.

Deficiencies of antithrombin, protein C, and protein S are associated with an increased risk of venous thromboembolism. The objective of this study was to prospectively assess the incidence of venous thromboembolism in nontreated asymptomatic subjects with such a deficiency. We conducted a prospective cohort study in asymptomatic family members of unselected patients who presented with a venous thromboembolic event and who were found to have a deficiency of antithrombin, protein C, or protein S. No anticoagulant prophylaxis was given to the study participants, except during risk periods for venous thromboembolism. All venous thromboembolic events were diagnosed by objective diagnostic tests. A total of 208 individuals with a mean age of 37 years (range, 15 to 79) were included in the study. A total of 611 patient observation years was obtained. Nine venous thromboembolic events occurred, resulting in an annual incidence of 1.5% (95% confidence interval [CI], 0.7 to 2.8) for the 3 deficiencies combined. Five of these events occurred spontaneously, resulting in an annual incidence of spontaneous venous thromboembolism of 0.8% (95% CI, 0.3 to 1.9). For antithrombin, protein C, and protein S deficiencies separately, this figure was 1.6%, 1.0%, and 0.4%, respectively. Thirty-four subjects experienced a total of 40 risk periods during which 4 venous thromboembolic events occurred (10% per risk period). We conclude that the use of continuous anticoagulant prophylaxis seems not warranted in asymptomatic individuals with a deficiency of antithrombin, protein C, or protein S. During risk periods for venous thromboembolism, adequate anticoagulant prophylaxis is necessary.

Adult↗
PubMed1999

[Thrombocyte receptors: current views and therapeutic options].

In the action of thrombocytes during stemming of a bleeding after damage to a blood vessel, receptors on the thrombocyte membrane play an important part. Adhesion of platelets takes place via specific binding of receptors; the main binding is that of glycoprotein (Gp) Ib to Von Willebrand factor which is synthetized by endothelial cells. Activation of thrombocytes is stimulated by adhesion and by agonists. Weak agonists, through production of thromboxane A2 and release of agonists from granules cause a self-fortifying process of thrombocyte stimulation; strong agonists (like thrombin) lead also to activation of Gp IIb/IIIa receptors. Aggregation of thrombocytes occurs after activation of Gp IIb/IIIa receptors. During stimulation, a change of shape occurs which enables binding to suitable plasma proteins of which the main one is fibrinogen. Knowledge of thrombocyte receptors enhances the insight into the prognosis and efficacy of certain treatments in diseases in which platelet aggregation is pivotal. Of the six categories of antiplatelet drugs, antagonists of Gp IIb/IIIa receptors are the most potent. In clinical trials good results have been obtained in patients with coronary disease of the intravenously administered form added to acetylsalicylic acid.

Blood Platelets↗
PubMed1999

[Physical examination--the significance of Homan's sign].

Homans's sign is often used in the diagnosis of deep venous thrombosis of the leg. A positive Homans's sign (calf pain at dorsiflexion of the foot) is thought to be associated with the presence of thrombosis. However, Homans's sign has a very poor predictive value for the presence or absence of deep vein thrombosis, like any other symptom or clinical sign of this disease.

Humans↗
PubMed1999

[Clinical research and pharmaceutical industry. A relationship with advantages and disadvantages].

Medical specialists and biomedical scientists are increasingly participating in research into the efficacy and safety of new drugs developed by the pharmaceutical industry. Participation may mean a position as an independent member of committees that monitor safety and effectiveness of the research for the patient, or are responsible for publication after termination of the research. This co-operation with the pharmaceutical industry has substantial advantages, such as the occupation of a prominent scientific position in developing and protocolling trials, promotion of employment and doctoral research, and of the quality of the research, particularly if it is followed by inspection by drugs registration colleges. However, the co-operation has adverse effects as well, especially if personal financial interests of the research workers become the main motivation. This applies also to an excessively dominant position of industry-sponsored research, diminishing the chances of medical scientific research which, although necessary, is difficult or almost impossible to finance.

Clinical Trials as Topic↗
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↗
PubMed1999

Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism.

OBJECTIVES: To construct and validate the bleeding risk prediction score, which is based on variables identified in the literature that can be easily obtained before the institution of anticoagulant therapy, in a large independent cohort of patients who were treated with anticoagulant therapy for established venous thromboembolism to allow for quantitative assessment of the risks and benefits of the therapy and to adapt the patient's management accordingly. METHODS: We constructed a bleeding risk prediction score, based on variables and their odds ratios identified in the literature, which can be easily obtained before the institution of anticoagulant therapy (score = [ 1.6 X age] + [1.3 x sex] + [2.2 X malignancy]). Subsequently, we evaluated the score in a test group of 241 patients treated with anticoagulant therapy for venous thromboembolism to determine the optimal cutoff points for the prediction of hemorrhagic complications, using receiver operating characteristic curve analysis. We then validated this score in an independent cohort of 780 patients. A score of 3 or more points, 1 to 3 points, or 0 points represented a high, intermediate, or low bleeding risk, respectively. RESULTS: The score in about one fifth of the patients in the test group was classified as predicting high risk for bleeding complications. The risk of all bleeding complications was 26% in this group and the risk of major bleeding complications was 14%. The area under the curve was 0.75 (95% confidence interval, 0.64-0.84) and 0.82 (95% confidence interval, 0.66-0.98) for all bleeding complications and major bleeding complications, respectively. When validated, there was a moderate loss of predictive power of the score, but the categorization of the patients by the score remained clinically useful; 20% of the patients were classified as high risk, and the bleeding rate was 17% for all bleeding complications and 7% for major bleeding complications compared with 4% and 1%, respectively, in those categorized as low risk. CONCLUSIONS: With the use of 3 easily obtainable, clinical variables in a prediction model, it is possible to identify a subgroup of patients at the start of anticoagulant therapy who have a high risk of developing hemorrhagic complications. Further studies should address whether additional measures to prevent bleeding decrease the bleeding incidence without compromising efficacy.

Anticoagulants↗
PubMed1999

Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis.

BACKGROUND: There is no consensus on the efficacy of physical training, smoking cessation, and pharmacological therapy (pentoxifylline or nafronyl oxalate) in the treatment of patients with intermittent claudication at Fontaine stage II of disease. METHODS: A MEDLINE and manual search was used to identify relevant publications. Uncontrolled or retrospective studies, double reports, and trials without clinically meaningful outcomes were excluded. Included studies were graded level 1 (randomized and double- or assessor-blind), level 2 (open randomized), or level 3 (nonrandomized). Pain-free and total walking distance were the main outcomes considered; when feasible, end-of-treatment results were combined with appropriate meta-analytical procedures. RESULTS: In 5 level 2 studies, physical training increased pain-free and total walking distance significantly (139.0 m [95% confidence interval {CI}, 31.0 to 246.9 m] and 179.1 m [95% CI, 60.2 to 298.1 m], respectively). In a level 3 study, smoking cessation resulted in a nonsignificant increase in total walking distance of 46.7 m (95% CI, -19.3 to 112.7 m). In 6 level 1 studies, pentoxifylline increased both pain-free and total walking distance by 21.0 m (95% CI, 0.7 to 41.3 m) and 43.8 m (95% CI, 14.1 to 73.6 m), respectively. In 4 level 1 trials, nafronyl significantly increased pain-free walking distance (58.6 m [95% CI, 30.4 to 86.8 m]) and total walking distance (71.2 m [95% CI, 13.3 to 129.0 m]). CONCLUSIONS: Physical training increased pain-free and total walking distance in level 2 studies. Only level 3 studies support the usefulness of smoking cessation. In level 1 studies, pentoxifylline and nafronyl increased pain-free and total walking distance, but the average effects were relatively small.

Clinical Trials as Topic↗
PubMed1999

Deep-vein thrombosis.

Deep-vein thrombosis is an important complication of several inherited and acquired disorders, but may also occur spontaneously. Prevention of recurrent venous thrombosis and pulmonary embolism is the main reason for accurate diagnosis and adequate treatment. This seminar discusses only symptomatic deep-vein thrombosis. The diagnosis can be confirmed by objective tests in only about 30% of patients with symptoms. Venous thromboembolic complications happen in less than 1% of untreated patients in whom the presence of venous thrombosis is rejected on the basis of serial ultrasonography or ultrasonography plus either D-dimer or clinical score. Initial anticoagulant treatment (intravenous or subcutaneous heparin) should continue until oral anticoagulant treatment, started concurrently, increases the international normalised ratio above 2.0 for more than 24 h. The optimum duration of oral anticoagulant treatment is unresolved, but may be guided by the presence of temporary or persistent risk factors or presentation with recurrent venous thromboembolism.

Humans↗
PubMed1999

Risk of venous thrombosis with use of current low-dose oral contraceptives is not explained by diagnostic suspicion and referral bias.

BACKGROUND: The magnitude of the relative risk of venous thrombosis caused by low-dose oral contraceptive use is still debated because previous studies might have been affected by diagnostic suspicion and referral bias. METHODS: We conducted a case-control study in which the effect of diagnostic suspicion and referral bias was excluded. The study was performed in 2 diagnostic centers to which patients with clinically suspected deep vein thrombosis of the leg were referred. History of oral contraceptive use was obtained before objective testing for thrombosis. Young females with an objective diagnosis of deep vein thrombosis were considered case patients, and those who were referred with the same clinical suspicion but who had no thrombosis served as control subjects. Participants were seen between September 1, 1982, and October 18, 1995: 185 consecutive patients and 591 controls aged 15 to 49 years with a first episode of venous thrombosis and without malignant neoplasms, pregnancy, or known inherited clotting defects. RESULTS: The overall odds ratio for oral contraceptive use was 3.2 (95% confidence interval [CI], 2.3-4.5); after adjustment for age, family history of venous thrombosis, calendar time, and center, the odds ratio was 3.9 (95% CI, 2.6-5.7). In the idiopathic group (120 patients and 413 controls, excluding recent surgery, trauma, or immobilization), the odds ratio for oral contraceptive use was 3.8 (95% CI, 2.5-5.9); after adjustment, the odds ratio was 5.0 (95% CI, 3.1-8.2). CONCLUSIONS: In this study, in which patients and controls were subj ect to the same referral and diagnostic procedures, we found similar relative risk estimates for oral contraceptive use as in previous studies. We conclude that diagnostic suspicion and referral bias did not play an important role in previous studies and that the risk of venous thrombosis with use of current brands of oral contraceptives still exists.

Adolescent↗
PubMed1999

High prevalence of hemostatic abnormalities in women with a history of severe preeclampsia.

OBJECTIVE: In patients with a history of severe preeclampsia, an increased frequency of hemostatic abnormalities has recently been suggested in small studies without control groups. Our purpose was to investigate the prevalence of such abnormalities in a large patient group with a history of severe hypertensive disorder in pregnancy, in comparison with an appropriate control group. STUDY DESIGN: A total of 345 patients with a history of severe preeclampsia were investigated at a minimum of 10 weeks post partum for the presence of activated protein C resistance, the associated factor V mutation, hyperhomocysteinemia and anticardiolipin antibodies. The control group consisted of 67 healthy women with a history of uncomplicated pregnancies only. Blood was obtained during the second half of a normal menstrual cycle, and none of the patients or control subjects used oral contraceptives. RESULTS: Of all patients, 11.3% had activated protein C resistance (control subjects 1.5%, P =.025). Only half of these patients had the factor V mutation. Hyperhomocysteinemia was present in 12.1% of all patients, in comparison with 4.5% in the control group (P =.115). Anticardiolipin antibodies were observed in 20.9% of the patients, whereas these antibodies were found in 7.5% of the control subjects (P =.016). In general, the prevalence of these abnormalities was 1.5 to 2 times higher in patients who were delivered before 28 weeks, in comparison with patients who were delivered after 28 weeks. CONCLUSIONS: Hemostatic abnormalities, associated with an increased risk of thrombosis, are present in approximately 40% of patients with a history of severe preeclampsia, which is almost 4 times higher than in control subjects. These findings might suggest a cause of preeclampsia and could have implications in subsequent pregnancies and general health.

Antibodies, Anticardiolipin↗