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• 1995-1999  (34)
• 1
Electronic Resource
Springer
ISSN: 1432-1041
Keywords: Atrial natriuretic peptide ; Hypertension ; SCH 42354 ; blood pressure ; neutral metalloendopeptidase ; pharmacodynamics ; pharmacokinetics
Source: Springer Online Journal Archives 1860-2000
Topics: Chemistry and Pharmacology , Medicine
Notes: Abstract SCH 42354, a neutral metalloendopeptidase (NEP) inhibitor, is the pharmacologically active form of the prodrug SCH 42495. It exerts antihypertensive effects by potentiating atrial natriuretic peptide (ANP) activity through inhibition of its hydrolysis by NEP. The objective of this study was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of SCH 42354 in hypertensive males. SCH 42495 12.5 to 400 mg was administered orally to hypertensive men twice daily in a double-blind, placebo controlled multiple-dose parallel group design. Plasma SCH 42354 concentration and diastolic blood pressure (DBP) data were used to develop a PK-PD model using two approaches. In the first (non-integrated) approach, the “link” model was used to predict effect-site concentrations, and was applied to data obtained at the 300 and 400 mg BID doses only; data at the other (lower) doses were not amenable to modeling because of high variability. Effect-site concentration and DBP data were then fit to a sigmoid Emax PD model. For the 300 mg BID dose, PD parameters were: maximum effect (Emax), 8.1mmHg; no-drug effect (Eo), 3.6 mmHg; concentration corresponding to 50% of maximum response (EC50), 0.87 μg·ml−1; and gamma, 3.9. In the second (time-integrated) approach, plasma SCH 42354 concentration and effect data obtained over the entire dose range were integrated with respect to time. Average plasma concentration and DBP data were then fit to a simple Emax PD model. PD parameters obtained over the dose range were: Emax, 10.3 mmHg; Eo, 2.0 mmHg; and EC50, 0.7 μg·ml−1. These were similar to the estimates obtained from the first approach, demonstrating that the integrated (average) data allow PK-PD modeling over the (entire) dose range. The analysis showed that, at steady-state, a 400 mg BID dose of SCH 42495 produced an approximate 10 mmHg decrease in DBP in hypertensive males; the average plasma SCH 42354 concentration attained at this dose was approximately 1.8 μg·ml−1.
Type of Medium: Electronic Resource
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• 2
Electronic Resource
Springer
Der Nervenarzt 70 (1999), S. 657-661
ISSN: 1433-0407
Keywords: Schlüsselwörter EKT ; Elektrokrampftherapie ; Betreuungsgesetz ; Key words ECT ; Electroconvulsive therapy ; § 1904 German Civil Code
Source: Springer Online Journal Archives 1860-2000
Topics: Medicine
Description / Table of Contents: Summary If patients who need electroconvulsive therapy are unable to consent, it is necessary to gain the guardian’s permission to carry out the treatment. It remains unclear if, due to possible side effects, it is necessary to gain an additional approval from the Guardianship Court according to § 1904 of German Civil Code (BGB). The high court of Hamburg (Landgericht Hamburg) decided that legal permission is necessary as a result of the risk of persisting retrograde amnesia and the ensuing danger of permanent damage to the patient’s health. This paper points out however, that electroconvulsive therapy, even considering the contraindications, is a safe and effective treatment for depression and schizophrenic psychoses. Application of unilateral short-pulse stimulation reduces the frequency and intensity of cognitive side effects. In particular, retrograde amnesia is very rare with regard to frequency and intensity and is negligible when compared with the dangers of the illness itself. There- fore, it is not necessary to apply for approval from the Guardianship Court.
Notes: Zusammenfassung Besteht bei einwilligungsunfähigen Patienten die Indikation zur Durchführung einer Elektrokrampftherapie (EKT), ist die Genehmigung des Betreuers zur Durchführung der Heilbehandlung erforderlich. Unklar ist, ob aufgrund von eventuellen Nebenwirkungen zusätzlich eine vormundschaftsgerichtliche Genehmigungspflicht im Sinne des § 1904 BGB anzunehmen ist. Das Landgericht Hamburg war unter Verweis auf das Risiko persistierender retrograder Amnesien von der begründeten Gefahr eines länger dauernden gesundheitlichen Schadens ausgegangen und hatte die Genehmigungspflicht bejaht. Die Elektrokrampftherapie ist jedoch unter Beachtung der Kontraindikationen eine sichere und effektive Therapiemaßnahme zur Behandlung von Depressionen und schizophrenen Psychosen. Die Anwendung der unilateralen Kurzpulsstimulation reduziert die Häufigkeit und Ausprägung der kognitiven Nebenwirkungen. Insbesondere retrograde Amnesien treten nur sehr selten und in einer Ausprägung auf, die angesichts der Gefährdungen durch die Grunderkrankung zu vernachlässigen ist. Eine vormundschaftsgerichtliche Genehmigungspflicht im Rahmen des Betreuungsgesetzes ist nach Meinung der Autoren zu verneinen.
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• 3
Electronic Resource
Springer
ISSN: 1432-0959
Source: Springer Online Journal Archives 1860-2000
Topics: Physics
Notes: Abstract We study a class of problems involving the motion of a linear elastic body in frictional contact with a linear elastic half space. The dynamic effects considered are the inertial properties of the body regarded as rigid. We study only those regimes of contact interaction for which the slip velocity with the body taken as absolutely rigid and the time rate of change of the elastic displacements of points of the body and the half space that are on the contact surface are of the same order of magnitude. This work generalizes previous work on similar problems in that we simultaneously consider inertia forces of the body and the convective term in the slip-velocity due to the rigid-body velocity of the slider/indentor. Thus regimes of contact interaction investigated include rolling/sliding and shift-torsion type. We propose a variational formulation of the following two problems: (a) finite contact area and shift-torsion type of contact kinematics, (b) local contact area and general kinematics at the contact surface. Results for an elastic cylinder contacting an elastic half-plane are also given.
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• 4
Electronic Resource
Springer
ISSN: 1432-0959
Source: Springer Online Journal Archives 1860-2000
Topics: Physics
Notes: Abstract. We study a class of problems involving the motion of a linear elastic body in frictional contact with a linear elastic half space. The dynamic effects considered are the inertial properties of the body regarded as rigid. We study only those regimes of contact interaction for which the slip velocity with the body taken as absolutely rigid and the time rate of change of the elastic displacements of points of the body and the half space that are on the contact surface are of the same order of magnitude. This work generalizes previous work on similar problems in that we simultaneously consider inertia forces of the body and the convective term in the slip-velocity due to the rigid-body velocity of the slider/indentor. Thus regimes of contact interaction investigated include rolling/sliding and shift-torsion type. We propose a variational formulation of the following two problems: (a) finite contact area and shift-torsion type of contact kinematics, (b) local contact area and general kinematics at the contact surface. Results for an elastic cylinder contacting an elastic half-plane are also given.
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• 5
Electronic Resource
Springer
International urogynecology journal 7 (1996), S. 267-269
ISSN: 1433-3023
Source: Springer Online Journal Archives 1860-2000
Topics: Medicine
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• 6
Electronic Resource
Springer
Pharmaceutical research 13 (1996), S. 1283-1290
ISSN: 1573-904X
Keywords: toxicokinetics ; sparse sampling ; pharmacokinetics ; toxicology
Source: Springer Online Journal Archives 1860-2000
Topics: Chemistry and Pharmacology
Notes: Abstract Purpose. The objective of this work was to develop and validate blood sampling schemes for accurate AUC determination from a few samples (sparse sampling). This will enable AUC determination directly in toxicology studies, without the need to utilize a large number of animals. Methods. Sparse sampling schemes were developed using plasma concentration-time (Cp-t) data in rats from toxicokinetic (TK) studies with the antiepileptic felbamate (F) and the antihistamine loratadine (L); Cp-t data at 13–16 time-points (N = 4 or 5 rats/time-point) were available for F, L and its active circulating metabolite descarboethoxyloratadine (DCL). AUCs were determined using the full profile and from 5 investigator designated time-points termed “critical” time-points. Using the bootstrap (re-sampling) technique, 1000 AUCs were computed by sampling (N = 2 rats/point, with replacement) from the 4 or 5 rats at each “critical” point. The data were subsequently modeled using PCNONLIN, and the parameters (ka, ke, and Vd) were perturbed by different degrees to simulate pharmacokinetic (PK) changes that may occur during a toxicology study due to enzyme induction/inhibition, etc. Finally, Monte Carlo simulations were performed with random noise (10 to 40%) applied to Cp-t and/or PK parameters to examine its impact on AUCs from sparse sampling. Results. The 5 time-points with 2 rats/point accurately and precisely estimated the AUC for F, L and DCL; the deviation from the full profile was ~10%, with a precision (%CV) of ~15%. Further, altered kinetics and random noise had minimal impact on AUCs from sparse sampling. Conclusions. Sparse sampling can accurately estimate AUCs and can be implemented in rodent toxicology studies to significantly reduce the number of animals for TK evaluations. The same principle is applicable to sparse sampling designs in other species used in safety assessments.
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• 7
Electronic Resource
Springer
Pharmaceutical research 13 (1996), S. 1280-1282
ISSN: 1573-904X
Source: Springer Online Journal Archives 1860-2000
Topics: Chemistry and Pharmacology
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• 8
Electronic Resource
Springer
Acta mechanica 113 (1995), S. 185-203
ISSN: 1619-6937
Source: Springer Online Journal Archives 1860-2000
Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
Notes: Summary We study plane strain dynamic thermomechanical deformations of a FCC single crystal deformed at an average strain-rate of 1 000 s−1 along the crystallographic direction [380] with the plane of deformation parallel to the plane (001) of the single crystal. Four different situations are studied; in the first two there is no initial imperfection assumed in the crystal and it is either compressed or pulled, and in the other two the crystal is compressed but either the initial temperature is nonuniform or a small region around the centroid of the cross-section is misoriented relative to the rest of the cross-section. In each case, all twelve slip systems are assumed to be potentially active, and the crystal material is presumed to exhibit strain hardening, strain-rate hardening, and thermal softening. These effects are modelled by using a simple combined isotropic-kinematic hardening expression for the critical resolved shear stress, proposed by Weng, and modified to incorporate the effect of thermal softening of the material. It is found that each one of the slip systems $$(111) [\bar 110], (11\bar 1) [\bar 110], (\bar 111) [110]$$ , and $$(\bar 11\bar 1) [110]$$ contributes essentially equally to the plastic deformations of the crystal and these slip systems become active soon after the load is applied. The same holds for the slip systems $$(111) [01\bar 1], (11\bar 1) [011], (\bar 111) [101]$$ , and $$(1\bar 11) [\bar 101]$$ except that they are active in a region different from that of the previous one. The remaining four slip systems either stay inactive throughout the deformation process, or become active at late stages of the deformation.
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• 9
Electronic Resource
Springer
Acta mechanica 116 (1996), S. 239-243
ISSN: 1619-6937
Source: Springer Online Journal Archives 1860-2000
Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
Notes: Summary Backman and Finnegan [1] have pointed out that shear bands initiate from a defect such as a second phase particle, microcrack, or a void. The defect has been modeled as a sinusoidal variation in the thickness of the tubular specimens tested in torsion by Chi [2] and Murphy [3]. Here we simulate their torsional tests numerically and consider different shapes and sizes of defects.
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• 10
Electronic Resource
Springer
Acta mechanica 110 (1995), S. 139-150
ISSN: 1619-6937
Source: Springer Online Journal Archives 1860-2000
Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
Notes: Summary We study the title nonlinear problem for a rubberlike material by using the domain perturbation method. The perturbation is deviation from unity of the ratio of the minor to the major axes of the ellipse. For the body containing an ellipsoidal void, two different loadings are considered; one in which the void surface is taken to be traction free and a uniform compressive load is applied at infinity, and the other in which a uniform pressure is applied to the void surface and null tractions at infinity. For the case of a rigid inclusion, uniform normal tensile tractions are applied at infinity. It is shown that a slight deviation from the circular shape of the cavity or the inclusion has a noticeable effect on the maximum stresses induced in the nonlinear elastic body.
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