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Biomedical subjects

P Roebruck

Publications and source records attributed to P Roebruck.

At least 19 recordsLinked to original sources
PubMed1997

Treatment of deep vein thrombosis with low-molecular-weight heparins: a consensus statement of the Gesellschaft für Thrombose-und Hämostaseforschung (GTH).

Recent studies have led to a new concept for the management of deep vein thrombosis. The German Society on Thrombosis and Haemostasis decided to work up the clinical studies in this field published until June 1996 for a consensus statement. The consensus group concluded that (1) high-dose, APTT-controlled subcutaneous administration of unfractionated heparin is as effective as high-dose, APTT-controlled continuous intravenous infusion of unfractionated heparin (grade B recommendation); (2) the anticoagulation with heparin may start at day 1 or 2, overlapping with oral anticoagulants for 7 to 10 days (grade C recommendation); (3) high-dose subcutaneous low-molecular-weight heparins are almost as effective and safe as continuous intravenous infusion of unfractionated heparins (grade B recommendation); (4) no agreement was obtained for the other concomitant treatments of DVT, such as duration of bed rest, use of antiphlogistic drugs, whether LMW heparins are comparable, and whether outpatient treatment can be recommended using LMW heparins.

Anticoagulants↗
PubMed1995

Comparison of tests and sample size formulae for proving therapeutic equivalence based on the difference of binomial probabilities.

To prove the hypothesis that a new treatment is as effective as a standard one, a possibility is to test the one-sided null hypothesis of a clear inferiority of the new treatment against the alternative hypothesis that, if at all, it is only negligibly inferior. Such a problem is of clinical relevance if, for instance, a new treatment with an effectiveness which is comparable to that of the standard one would be preferred if it is less toxic. If the difference between the two treatments is measured by the difference of failure rates, approximate statistical tests and sample size formulae have to be used. This paper reports the results of an extensive empirical investigation comparing the well known calculations proposed by Blackwelder, Rodary, ComNougue and Tournade, which propose a sample size formula for the test of Dunnett and Gent, and Farrington and Manning. The investigation was conducted in order to allow more comprehensive conclusions than those which may be drawn from the limited examples given by the last authors. For the usual settings in clinical trials, the formulae of Farrington and Manning are recommended. However, there are combinations of statistical parameters for which they are not preferred.

Binomial Distribution↗
PubMed1992

Heparin Study in Internal Medicine (HESIM): design and preliminary results.

The Heparin Study in Internal Medicine (HESIM) compares the efficacy and safety of an unfractionated (UF) heparin with a low molecular weight (LMW) heparin (CY 216 D) for prevention of proximal deep vein thrombosis (DVT) and pulmonary embolism (PE) in medical inpatients with a high risk for development of thromboembolism. Patients are randomized and receive three times daily 5000 IU UF heparin or once daily 3100 IU LMW heparin and two placebo injections subcutaneously for 10 days. All patients are screened for the presence of proximal DVT at day 1 and 10 by real-time B-mode compression sonography and for PE by repeated clinical examinations. Perfusion scintigraphy is used for confirmation of the clinical diagnosis of PE. The study protocol includes a stratified randomization of patients on admission to the hospital according to one of the following main diagnoses: malignant disease, cardiovascular disease, bronchopulmonary disease, neurologic disease, and other diseases. The present study may serve as a model for further clinical trials in medical inpatients using the biometric approach of statistical analysis for proving equivalence of drug efficacy, and to adopt less sensitive but noninvasive methods for the detection of primary endpoints.

Aged↗
PubMed1991

Increased plasma viscosity and erythrocyte aggregation: indicators of an unfavourable clinical outcome in patients with unstable angina pectoris.

OBJECTIVE: To determine the prognostic significance of altered plasma viscosity and erythrocyte aggregation in unstable angina. DESIGN: A prospective study of 96 consecutive patients with unstable angina allocated to one of two groups according to predefined threshold values for plasma viscosity and erythrocyte aggregation at study entry. The patients received a standardised treatment and were followed up for six months or until angioplasty or bypass surgery. MAIN OUTCOME MEASURE: Frequency of myocardial infarction. RESULTS: Myocardial infarctions occurred in 7/26 patients with a plasma viscosity greater than or equal to 1.38 mPa s and in 8/35 with a rate constant of erythrocyte aggregate formation greater than or equal to 0.5 mPa (corrected for plasma viscosity) but in only 4/70 with a plasma viscosity less than 1.38 mPa s and in 3/61 with an erythrocyte aggregation less than 0.5 mPa (odds ratios: 6.1 (95% confidence interval 1.3 to 31), p = 0.008, and 5.7 (95% CI 1.2 to 35), p = 0.016). Plasma viscosity and erythrocyte aggregation were more predictive of myocardial infarction than age, male gender, fibrinogen concentration, ST segment abnormalities, or coronary score. Furthermore, Holter monitoring with ST segment analysis showed that ischaemic episodes were more common in patients in whom the rate constant of erythrocyte aggregate formation was greater than 0.5 mPa (15/27 v 17/50, p = 0.029). Cardiac troponin T release was increased in patients with a plasma viscosity of greater than 1.38 mPa s (10/26 v 9/70, p = 0.010). CONCLUSIONS: In patients with unstable angina a considerable increase in plasma viscosity and erythrocyte aggregation identified a subgroup of patients at a high risk of acute myocardial infarction in whom medical treatment was likely to be unsuccessful.

Aged↗
PubMed1991

[Modification of coronary arteriosclerosis in man by calcium antagonists?].

Calcium channel blockers may retard development and progression of coronary arteriosclerosis in man because of protective effects on membranes, (especially the endothelium), relaxation of vessel walls, inhibition of various platelet functions, impairment of proliferation and migration of smooth muscle cells in the vessel wall, and an improvement of vascular cholesterol metabolism. In animal trials development of atheromas in large arteries induced by cholesterol-rich food and other stimuli of atherogenesis could be successfully retarded by a broad variety of calcium channel blockers. Some clinical observations in patients with coronary artery disease pointed at positive effects of calcium antagonists in coronary arteriosclerosis. To date, the results of three prospective placebo-controlled trials with calcium antagonists in coronary arteriosclerosis are available. In all trials progression of atherosclerosis was assessed by serial angiograms: 1) INTACT (nifedipine: 20 mg four times daily; observation period: 3 years, two coronary angiograms); 2) Study of the Montreal Heart Institute (nicardipine: 30 mg three times daily; observation period: 2 years, two coronary angiograms); 3) FIPS (Frankfurt Isoptin Progression Study) (verapamil: 120 mg three times daily; observation period: 3 years, three coronary angiograms). Target variables in these studies were progression or regression of preexisting lesions, development of new lesions and the incidence of vessel occlusions. The INTACT and the Nicardipine studies preferably included patients in early stages of coronary artery disease. The patients of FIPS who were entered into the study immediately after coronary bypass surgery suffered from severe, advanced coronary artery disease. In the latter study progression of coronary artery disease was assessed separately in different vascular regions (bypassed and non-bypassed segments) and in the bypass grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Channel Blockers↗
PubMed1990

[Biochemical aspects of the evaluation of fixed drug combinations].

Various disciplines have to contribute to the general problem of the evaluation of fixed dose combination drugs, as for instance (clinical) pharmacology, biometry, scientific drug regulations and public health officials. The EC guideline 75/318/EWG and its eludications as well as the German "Arzneimittelprüfrichtlinien" of Dec. 14, 1989 (as referred to in the "Arzneimittelgesetz" of 1986) required that such issues concerning fixed dosage combination drugs must be considered and taken into account. In this framework it is the responsibility of biometry to both to guarantee the use of a valid study design to assure interpretation of the results and to quantify the reliability of pharmacological and clinical considerations. The following paper is concerned with biometrical aspects of the combination drug problem. Basic considerations from a clinical or a pharmacological point of view with respect to the question of whether fixed combination drugs are reasonable or not are not discussed. To support the use of combinations of drugs, a central argument is the improvement of the benefit risk relation compared with that of an adequate monotherapy. Beyond this the fixed combination drugs require additional arguments regarding the enhencement of the safety or the simplicity of the therapy fixing the ratio. It follows that fixed combination drugs have to be supported twice, first with respect to the combination itself, and second with respect to the fixed mixing ratio of its components. The biometrical aspects of the assessment of the gains from (fixed) drug combinations are related to the kind of benefit/risk improvement that is expected. In the first section we discuss some possible types of benefit and risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Retardation of development and progression of coronary atherosclerosis: a new indication for calcium antagonists?

Development of atherosclerotic lesions in animals, preferrably induced by a high-cholesterol diet, can be successfully suppressed by calcium channel blockers such as verapamil, nifedipine, nicardipine and diltiazem. The issue of a beneficial effect of calcium channel blockers on human coronary atherosclerosis is however not yet settled. At present, three prospective randomized clinical trials with calcium channel blockers (Nifedipine, Verapamil, Nicardipine) are being conducted (INTACT, FIPS, Study of the Montreal Heart Institute). Target variable for assessment of progression in these studies is the severity of coronary atherosclerosis evaluated by angiography both at entry into the study and after 2-3 years of treatment. A total of 445 patients after coronary bypass surgery (CABG) were entered in FIPS (Frankfurt Isoptin Progression Study) and randomly allocated to either verapamil 120 mg t.i.d. or placebo. The extent of coronary atherosclerosis is assessed by repeat angiography both 1 year and 3 years after randomization. Three vessel regions are evaluated separately. 1. Native vessels without bypass grafts and segments distal to the peripheral graft anastomosis ("core region") 2. Segments bridged by bypass grafts and 3. Bypass grafts. The 1-year follow-up was completed by 162 patients (Group A = 80 patients; Group B = 82 patients). There was a homogeneous distribution in the two groups for all clinical variables, graft patency rates, and the incidence of clinical events (myocardial infarction, need for cardiac surgery or PTCA, cardiac death). The overall progression rate of atherosclerosis in the first year was expectedly low.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Haemorrheological abnormalities in unstable angina pectoris: a relation independent of risk factor profile and angiographic severity.

Plasma viscosity, photometric erythrocyte aggregation index, and erythrocyte filterability were measured in 194 patients with coronary artery disease. Patients with unstable angina (n = 64) had a higher plasma viscosity and photometric erythrocyte aggregation index than patients with stable angina (95% confidence intervals for the mean difference: 0.052-0.100 mPa.s for plasma viscosity, and 43%-72% for the photometric erythrocyte aggregation index). Multiple regression with fibrinogen, cholesterol, high density lipoprotein cholesterol, triglycerides, blood pressure, smoking habits, coronary artery score, and left ventricular ejection fraction as independent variables showed a significant partial correlation between fibrinogen and the photometric erythrocyte aggregation index (r2 = 0.20) and plasma viscosity (r2 = 0.09), between triglycerides and plasma viscosity (r2 = 0.05), and between aortic pressure and erythrocyte filterability (r2 = 0.03). Logistic regression for unstable/stable angina with the haemorrheological variables as independent variables correctly identified 72% of the patients with stable angina and 78% of those with unstable angina. Inclusion of all the variables investigated did not substantially improve the discriminative potential of the logistic regression model. Unstable angina is associated with an impairment of blood fluidity that is essentially independent of risk factor profile and angiographic data.

Angina Pectoris↗
PubMed1989

[Can the progression of coronary heart disease be modified by calcium antagonists?].

Experimental atherosclerosis in animals preferentially induced by cholesterol-rich food can be successfully suppressed by calcium channel blocking agents such as verapamil, nifedipin, nicardipin, and diltiazem. The question whether calcium channel blockers can favorably influence atherosclerosis in humans remains a matter of debate. A few observational investigations in the past showed positive results of calcium channel blocker therapy in patients with angiographically proven coronary artery disease (CAD). At present three prospective randomized clinical trials are under way (INTACT-study, FIPS-study, study from the Montreal Heart Institute). Target variable is the severity of coronary atherosclerosis assessed by angiography both at entry into the study and after 2-3 years of treatment. 445 patients after coronary bypass surgery were included in the FIPS study (Frankfurt Isoptin Progression Study) and were randomly allocated to either verapamil 120 mg t.i.d. or placebo treatment. Extent of coronary atherosclerosis, assessed by repeat angiography 1 and 3 years after randomization, is expressed by scores with separate evaluation of non-bypassed vessels, segments distal to the peripheral bypass insertion, bypassed segments and grafts. The 1-year follow-up was completed for 162 patients (Group A = 80 patients; group B = 82 patients). There was a homogeneous distribution in both groups for all clinical variables, graft patency rates (76%/75%), and the incidence of clinical events (myocardial infarct, need for cardiac surgery or PTCA, cardiac death: 5%). The overall progression of atherosclerosis in the first year after bypass surgery was small. Thus, the question of whether calcium channel blockers can retard progression of coronary atherosclerosis cannot be answered before completion of the aforementioned trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Prevalence, risk factors and rheological profile of arterial vascular disease; first results of the Aachen study.

During a prospective cohort-study of several year's duration the results of a survey regarding prevalence of arterial occlusive disease, as well as classical risk factors and rheological profile of patients suffering from vascular disease were examined. 364 patients out of a total of 2,498 individuals suffered from vascular disease. 168 (6.7%) had cardiovascular, 151 (6.0%) cerebrovascular and 109 (4.4%) peripheral vascular disease. Compared to to healthy individuals, the patients showed a significant accumulation of classical risk factors (elevated cholesterol and triglyceride values, decreased HDL-cholesterol concentration, obesity, smoking, high blood pressure, gout or diabetes mellitus). Only 30.2% of the healthy controls presented two or more risk factors, whereas the angiological patients showed two or more risk factors in 71.9%. Rheological parameters measured in the survey were: Plasma viscosity, erythrocyte and platelet aggregation, erythrocyte rigidity and hematocrit. Only 14.2% of the healthy individuals had two or more rheological parameters exceeding the 1-s range, whereas 56.6% of the patients showed two or more elevated rheological parameters.

Aged↗
PubMed1986

[Predictor function of hemorheologic parameters with reference to the incidence of manifest circulatory disorders: Concept of the Aachen study].

The prevention of cardiovascular disease has up till now generally been limited to control of the classical risk factors. The primary problem of the risk factor model is, that although a statistically verified relationship exists between risk factors and vascular disease, an individual prognosis is presently impossible. Surveys that show a relation between risk factors and impaired blood fluidity support the conception that a change in blood fluidity could be considered an early detection screening of vascular diseases. Prospective studies have shown that the hematocrit is related to circulatory disturbances. The main aim of the present study was to determine the clinical relevance of rheological parameters (hematocrit, plasma viscosity, erythrocyte rigidity, thrombocyte aggregation, erythrocyte aggregation), and the importance of altered blood fluidity as a predictor of manifest cerebral, cardiac or peripheral vascular disturbance.

Blood Viscosity↗
PubMed1986

Tolerance to monovalent dextran of human mast cells.

In the present study it was investigated if monovalent dextran (Dx 1, HR 573, Promit) possibly involving activated complement is capable of inducing mediator (histamine) release from isolated human mast cells. Dx 1 in the absence or in the presence of 20% fresh human serum did not induce a histamine release from human mast cells. The "non-release" could be established statistically using a new sequential test which provides a substantial reduction of the average sample size required to reach a prescribed test power. In contrast, concanavalin A (Con A) or ionophore A 23187 caused a marked histamine release in the absence of human serum. In the presence of human serum the spontaneous histamine release was increased but the Con A- or ionophore-induced release was inhibited.

Dextrans↗
PubMed1984

Explorative statistical analysis and the valuation of hypotheses.

Clinical research has to include data from various sources. In many cases, the structure of the data allows explorative analysis only. This paper is concerned with situations in which no special hypotheses from a large set of possible ones have been predetermined for statistical testing or wherein tests are planned for hypotheses on only very few variables out of a high dimensional response as in controlled clinical trials. Explorative analysis of those experiments frequently uses p-values for the valuation of the hypotheses not designated for testing. It is shown by means of an example to what extent conclusions may be wrong if they result from ignoring (or misunderstanding) the explorative character of such p-values. Posterior probabilities with respect to suitable priors are proposed as an alternative explorative method for the valuation of hypotheses. The advantages of this procedure are discussed.

Research↗
PubMed1983

The diagnostic potential of the combined determination of serum monoamine oxidase and N-acetyl-beta-D-glucosaminidase for fibroproliferative liver diseases.

The simultaneous determination of the catalytic activities in serum of monoamine oxidase (EC 1.4.3.4) and N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30) was performed in patients with various non-liver diseases, acute hepatitis and fibroproliferative liver disorders (cirrhosis and fibrosis) and the predictive values of the positive (both activities are pathologically elevated) and negative test results (normal activity of monoamine oxidase and/or N-acetyl-beta-D-glucosaminidase) were estimated. It was found that the incidence of the positive result is extremely low (0.024, 5/207) in patients suffering from a great variety of non-liver and liver diseases (except cirrhosis) but rather great in liver cirrhotic subjects (0.44, 18/41). A fraction of only 0.07 of liver fibrotic patients had a positive test result. Based on these data the estimated predictive value of the positive result for liver cirrhosis at a prevalence of 0.03 is 0.47. This value increases strongly with higher prevalence of cirrhosis (population preselected for chronic liver diseases). The negative predictive value for cirrhosis and the positive value for fibrosis are low. Thus, the probability of the presence of cirrhosis in patients with suspected chronic liver diseases is great in cases of abnormally high activities of both monoamine oxidase and N-acetyl-beta-D-glucosaminidase. Negative test results (normal catalytic activities of one or both enzymes), however, do not prove the absence of liver cirrhosis and/or liver fibrosis.

Acetylglucosaminidase↗
PubMed1983

Microprocessor-based long term cardiorespirography. I. Heart rate changes and apneic attacks.

Cardiorespirography is a well-known method of continuous monitoring in neonatal intensive care. Apneic attacks, bradycardia and tachycardia are registered. In our experience we connected a cardiorespirography recorder to a microprocessor system. The processor consisted of a hardware part including a program (software) and a printer which provided printouts of alarm events. As alarm situations, which cause an alarm printout, we defined: 1. apneic episodes (duration 10, 20 or 30 seconds) 2. tachycardiac (beat-to-beat rate greater than 180/minute) 3. V-shaped and U-shaped bradycardia (beat-to-beat heart rate less than 80/min) and combinations. The reliability of the system of recognizing and classifying alarm situations was tested by comparing the alarm printouts with the simultaneously recorded cardiorespirograms. Fifty eight 12 hour records of 41 patients were evaluated. Six hundred alarm situations were counted. The alarm printouts were found in concordance with the cardiograms in all tachycardia alarms. Nearly all bradycardia (V-shaped, U-shaped bradycardia, combination of bradycardia and apnea) were correctly classified. A preset apnea duration of 10 seconds resulted in many false positive alarm printouts. With 20 second apnea time only few false positive alarms were seen, but nine apneic attacks were not recognized. Altogether 81.5% of alarm printouts were correct, 16.8% were false alarms, or V-shaped bradycardia were really U-bradycardia. Only 2% of all alarms were not recognized by the microprocessor system. We suggest to combine the microprocessor with a special alarm recorder, which is able to store beat-to-beat heart rate and respiration wave before alarm situations.

Apnea↗
PubMed1983

Microprocessor-based long term cardiorespirography. II. Status evaluation in term and premature newborns.

In 1965 URBACH et al. and RUDOLPH et al. [35, 39] described a loss of heart rate variability in severely ill neonates. In this study we investigated the correlation between instantaneous heart rate patterns and status diagnosis. We used a microprocessor-based cardiorespirography system. Seventy five newborn infants (51 prematures and 24 term neonates) were studied for about 12 hours each. Twenty nine patients had a second record after the first investigation. Parameters were: Type of frequency and oscillation, long time variability (LTV), short time variability (STV) and the newly introduced P-value (maximal difference between two successive R-peaks in five minutes). We found clear differences between the study groups. With increasing severity of illness mean values ("group mean values") of long time variability, short time variability and P-value decreased. Fixed heart rate became predominant. The most pronounced loss of heart rate variability was seen in infants with severe intracranial bleeding, thus offering a tentative diagnosis. For statistical analysis long time variability and the silent oscillation type have been proved as best parameters for this diagnosis. Severely decreased heart rate variations also have been seen in infants with acute renal failure--possibly because of brain edema--, after application of muscle relaxants, repeated doses of sedatives, and after prolonged anesthesia. Otherwise, the heart rate variability was probably dependent on age and gestational age in prematures and newborn infants without intracranial bleeding. It is possible to use microprocessor-based long time cardiorespirography as a simple screening method for the diagnosis of neonatal intracerebral bleeding. In future experiences transcutaneous measurements of oxygen tension should be included.

Cerebral Hemorrhage↗