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  • 1
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 210 (1966), S. 1364-1365 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] In this communication we describe the results of experiments to test the effect of quinidine and related compounds on the in vitro uptake of serotonin by human platelets as contained in platelet-rich plasma. Blood was taken from normal healthy donors, using 3-1 per cent sodium citrate as ...
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  • 2
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] IT has long been known that blood platelets are antigenic and that ant i-platelet antibodies produce shortening of the platelet life-span in vivo and agglutination and lysis of the platelets in vitro1-3. Further manifestations of platelet injury by antibody have more recently been shown by ...
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  • 3
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neurotoxicity in vincristine treatment has generally been considered a consequence of the cumulative dose of the drug, and liver dysfunction has been recognised as an indication to reduce the dosage. We demonstrate that neurotoxicity is also related to individual doses and that even when there is no other evidence of liver dysfunction, a raised level of serum alkaline phosphatase may predict severe neurotoxicity. Exposure to vincristine following IV injection of the drug was studied in 27 subjects by measuring the area under the vincristine plasma concentration time curve (AUC0–∞). A statistically significant relationship was found between the AUC0–∞ and the degree of neurotoxicity. The AUC0–∞ was related both to dose and to elevation of serum alkaline phosphatase, suggesting that elimination of the drug is impaired when serum alkaline phosphatase is raised. Among patients with elevated serum alkaline phosphatase, a small reduction in the dose of the drug resulted in lower vincristine plasma AUC0–∞ and less neurotoxicity.
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  • 5
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serum methotrexate (MTX) concentrations were measured by immunoassay in 28 children receiving maintenance therapy for acute lymphoblastic leukaemia. Patients were studied either after a single weekly dose or on the first day of a 5-day course of treatment. A standard dose (15 mg/m2) was given PO and/or IV. After PO dose the peak serum MTX concentration and its timing varied widely between cases and there was a significant positive correlation between the rate of serum concentration rise and the area under the concentration curve up to 4 h. The absorption rate constant showed a biphasic distribution and correlated less closely with early serum concentrations. After IV and PO administration drug disposition was triphasic with an initial rapid distribution phase, an intermediate phase, and a prolonged terminal elimination phase. The intermediate phase half-life was significantly longer after PO than after an IV dose. The MTX clearance rate was consistently lower than the glomerular filtration rate and there was no significant correlation between the two. The mean bioavailability (PO/IV) was 42%, but bioavail-ability was as low as 6% in some cases due to prolonged high serum concentrations after an IV dose, which was not seen with the equivalent PO dose.
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  • 6
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pharmacokinetic studies in ten patients with haematological disorders were undertaken on the first and second days of one course of chemotherapy. Patients received chlorambucil under fasting and non-fasting conditions. Plasma concentrations of chlorambucil were determined by a reversed-phase high-performance liquid chromatography assay. Statistical analysis by the Wilcoxon signed rank test for non-parametric data indicated that food caused a significant reduction in peak plasma levels (P〈0.01), elimination rate constants (P〈0.01) and area under the plasma chlorambucil/time curve (P=0.01). Food was also found to prolong the time taken to attain peak plasma levels (P〈0.01). Regression analysis of renal function with elimination rate constants showed that chlorambucil elimination was independent of renal function (n=8; r=-0.007; P=0.72). In view of these results we suggest that chlorambucil is given on an empty stomach.
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  • 7
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A radioimmunoassay has been used to investigate the pharmacokinetics of vincristine in 39 cancer patients who received between 0.4 and 1.54 mg vincristine/m2 as part of standard treatment protocols. There was wide interindividual variation in both the terminal elimination half-life of vincristine (t1/2β) and the associated volume of distribution (Vd), resulting in an 11-fold range of dose-corrected area under the plasma concentration versus time curve values (AUC0–∞). Elevated vincristine AUC0–∞ values were observed in those patients with raised serum alkaline phosphatase at the time of vincristine estimation. The t1/2β was significantly longer in these patients than in those with serum alkaline phosphatase within normal limits, suggesting that biochemical evidence of cholestasis is associated with reduced clearance of vincristine. Evidence is also presented to suggest that the clearance of vincristine is dose-dependent within the therapeutic dose range. We observed a disproportionate rise in vincristine plasma concentration at doses exceeding 1 mg/m2, due primarily to a lengthening of mean t1/2β compared with that observed for patients receiving 1 mg vincristine/m2 or less.
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  • 8
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pharmacokinetic studies in 11 patients with multiple myeloma were undertaken on the first and last days of one course of chemotherapy. The drug was administered PO in single doses of 6–14 mg daily. Melphalan concentrations were determined by high-performance liquid chromatography. The interpatient variability of pharmacokinetic parameters noted by other authors was observed. Regression analysis showed a significant positive correlation between the elimination rate constant for melphalan and renal function (P=0.003). The form of the line which describes the overall elimination rate constant for melphalan is given by the equation: Kel=5.67×10-3+[4.90×10-5xGFR]. There was also a significant negative correlation between renal function and the area under the plasma melphalan concentration/time curve (P=0.006). In vitro stability studies of melphalan in plasma at 37°C and pharmacokinetic data suggest that hydrolysis and renal clearance are the major mechanisms of melphalan elimination. This work shows quantitatively the relationship between renal function and drug elimination and how the data may be used in predicting melphalan half-life from creatinine clearance.
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  • 9
    ISSN: 1432-0428
    Keywords: Diabetes ; blood platelets ; adhesiveness ; fibrinogen ; factor VIII ; ischaemic heart disease ; blood glucose ; serum lipids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'adhésivité des plaquettes et les taux de deux facteurs de coagulation, le fibrinogène et le facteur VIII, ont été étudiés chez un groupe de diabétiques et chez des sujets témoins. Les trois mesures étaient significativement anormales chez les sujets diabétiques. L'augmentation de l'adhésivité des plaquettes permettait de distinguer les diabétiques sur une base de groupe, mains non d'après des résultats individuels. L'augmentation la plus grande de l'adhésivité des plaquettes a été démontrée chez les sujets atteints de maladie de coeur ischémique et de diabète. Une adhésivité accrue des plaquettes a été observée à la fois chez des individus du groupe diabétique et du groupe témoin, chez lesquels on n'a trouvé aucun signe clinique ou électrocardiographique de maladie de coeur ischémique. Ce résultat est discuté, ainsi que la relation entre les taux d'adhésivité des plaquettes et l'âge, le sexe, la durée de la maladie, la glycémie et les taux de lipides du sérum chez les sujets diabétiques.
    Abstract: Zusammenfassung Die Plättchen-Adhäsivität und die Spiegel zweier Coagulations-Faktoren, Fibrinogen und Faktor VIII wurden bei einer Serie von Diabetikern und nichtdiabetischen Vergleichspersonen untersucht. Die Zunahme der Thrombocyten-Adhäsivität ließ eine Abgrenzung der Diabetiker als Kollektiv, nicht aber für Einzelpersonen zu. Der stärkste Anstieg der PlättchenAdhäsivität fand sich bei Diabetikern mit coronarer Minderdurchblutung. Ein solcher Anstieg ließ sich aber auch bei Diabetikern und Vergleichspersonen nachweisen, bei denen keine klinischen oder elektrokardiographischen Zeichen einer ischämischen Herzerkrankung bestanden. Dieser Befund wird diskutiert ebenso wie die Beziehungen zwischen Thrombocyten-Adhäsivität und Alter, Geschlecht, Krankheitsdauer, sowie Blutzuckerund Blutfettspiegeln der Diabetiker.
    Notes: Summary Platelet adhesiveness and the levels of two coagulation factors, fibrinogen and factor VIII, were studied in a series of diabetic and nondiabetic control subjects. All three measurements were significantly abnormal in the diabetic patients. The increase in platelet adhesiveness was capable of distinguishing the diabetics on a group basis, but not on individual results. The greatest increase in platelet adhesiveness was demonstrated in patients with ischaemic heart disease and diabetes. Increased platelet adhesiveness was seen in individuals of both diabetic and control groups, in whom no clinical or electrocardiographic evidence of ischaemic heart disease was found. This finding is discussed, also the relationship between platelet adhesiveness levels and the age, sex, duration of disease, blood glucose and serum lipid levels of the diabetic patients.
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  • 10
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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