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  • 1
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 20 (2004), S. 0 
    ISSN: 1365-2036
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Aim : To assess the pharmacokinetics of alosetron, its effect on in vivo enzyme activities, and influence of demographic factors during repeated dosing.Methods : Thirty healthy men and women received 1 mg oral alosetron twice-daily for 29.5 days and a single oral dose of a metabolic probe cocktail before and on the last day of alosetron dosing. Serum alosetron concentrations were measured on days 1, 8, 15, 22 and 29. Probe-substrate and metabolite concentrations were measured after each cocktail dose.Results : Alosetron accumulation in serum was negligible. Exposure to alosetron did not alter probe-metabolite/substrate ratios associated with CYP2C19, 2E1, 2C9, or 3A4 activity, but modestly decreased those associated with CYP1A2 and N-acetyltransferase activity. Systemic exposure to alosetron was higher in women, positively correlated with age and body mass index, and negatively correlated with CYP1A2 activity. Incidence of constipation was higher in women, but not associated with alosetron concentration.Conclusions : Single dose data can reliably predict the pharmacokinetics of alosetron after repeated doses. Alosetron exhibits limited potential for inhibition of cytochrome P450-mediated metabolism. Interindividual differences in alosetron pharmacokinetics associated with demographic factors may be related to strong dependence on metabolism by CYP1A2.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Oxford BSL : Blackwell Science
    Alimentary pharmacology & therapeutics 11 (1997), S. 0 
    ISSN: 1365-2036
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Background: Ranitidine hydrochloride (Zantac) is one of the most extensively studied and widely used drugs of all time. This has provided an excellent opportunity to define its safety profile. Methods: Data from 189 controlled clinical trials in which more than 26000 patients received daily doses of ranitidine for 4 weeks or more were reviewed. More than 80% of patients were treated with up to 300 mg ranitidine daily; the remaining patients received doses of up to 1200 mg daily. Eighty-seven trials were placebo controlled. Analyses of post-marketing surveillance and a database of all spontaneously reported adverse events were also evaluated. Results: Overall in the clinical trial programme adverse events were reported by 20% of those receiving ranitidine compared with 27% of those receiving placebo. The pattern of events was similar in all treatment groups with no evidence of dose-related toxicity in regimens encompassing an eightfold range of therapeutic doses. Similarly in a programme of studies designed to evaluate a dose of ranitidine of 75  mg for non-prescription (over-the-counter) use in the treatment of heartburn, ranitidine was not associated with an adverse event profile distinct from that of placebo. Analysis of spontaneously reported adverse event data allowed identification of rare idiosyncratic events. Conclusions: Review of data from a large population of controlled clinical trials with analyses of postmarketing surveillance studies and spontaneously reported adverse events confirmed the excellent safety profile of ranitidine.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 47 (1996), S. 509-540 
    ISSN: 1040-2519
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie
    Notizen: Abstract Plant gene responses to changing carbohydrate status can vary markedly. Some genes are induced, some are repressed, and others are minimally affected. As in microorganisms, sugar-sensitive plant genes are part of an ancient system of cellular adjustment to critical nutrient availability. However, in multicellular plants, sugar-regulated expression also provides a mechanism for control of resource distribution among tissues and organs. Carbohydrate depletion upregulates genes for photosynthesis, remobilization, and export, while decreasing mRNAs for storage and utilization. Abundant sugar levels exert opposite effects through a combination of gene repression and induction. Long-term changes in metabolic activity, resource partitioning, and plant form result. Sensitivity of carbohydrate-responsive gene expression to environmental and developmental signals further enhances its potential to aid acclimation. The review addresses the above from molecular to whole-plant levels and considers emerging models for sensing and transducing carbohydrate signals to responsive genes.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Journal of geodesy 72 (1998), S. 436-441 
    ISSN: 1432-1394
    Schlagwort(e): Key words. Kalman filter ; Robust estimation ; Rank deficiency
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Architektur, Bauingenieurwesen, Vermessung
    Notizen: Abstract. A robust Kalman filter is derived for rank deficient observation models. The datum for the Kalman filter is introduced at the zero epoch by the choice of a generalized inverse. The robust filter is obtained by Bayesian statistics and by applying a robust M-estimate. Outliers are not only looked for in the observations but also in the updated parameters. The ability of the robust Kalman filter to detect outliers is demonstrated by an example.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1420-908X
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Inflammation research 45 (1996), S. 435-437 
    ISSN: 1420-908X
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 52 (1997), S. 229-234 
    ISSN: 1432-1041
    Schlagwort(e): Key words Ranitidine ; Renal impairment; dose adjustment ; pharmacodynamics ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Objective: The pharmacodynamics and pharmacokinetics of ranitidine were examined in subjects with varying degrees of renal function to determine the effect of this condition on acid-antisecretory activity. Methods: Subjects with creatinine clearances (CCr) ranging from 0 to 213 ml · min−1 received single 50-mg and 25-mg i.v. doses of ranitidine. This was followed by determination of serum and urine ranitidine concentrations, and continuous gastric pH monitoring for 24 h. Results: Serum ranitidine concentrations were described by a two-compartment model linked to a sigmoidal Emax model describing gastric pH. Ranitidine renal clearance, ranging from 0 to 1003 ml · min−1, correlated with CPAH (r 2 = 0.707), while non-renal clearance was unaltered. Steady-state volume of distribution decreased by half in severe renal impairment. No changes in the effective concentration at half-maximal response (EC50), maximal response (Emax), or basal response (E0) were observed. Thus, renal elimination of ranitidine declined in parallel with renal function, while sensitivity to the pharmacologic effect (gastric pH elevation) was unaltered. Ranitidine was well tolerated in these renally impaired subjects. Conclusion: These data indicate that the current recommendation for renal impairment dose reduction (by two-thirds when CCr〈50 ml · min−1) might result in under-treating moderately impaired patients, and suggests a less conservative dose reduction (by half when CCr〈10 ml · min−1) to avoid therapeutic failure while remaining within the wide margin of safety for this drug.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1432-1238
    Schlagwort(e): Key words Severity of illness index ; Multiple organ failure ; Critically ill ; Morbidity ; Organ failure ; Outcome
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Objective: To evaluate the use of the Sequential Organ Failure Assessment (SOFA) score, the total maximum SOFA (TMS) score, and a derived variable, the ΔSOFA (TMS score minus total SOFA score on day 1) in medical, cardiovascular patients as a means for describing the incidence and severity of organ dysfunction and the prognostic value regarding outcome. Design: Prospective, clinical study. Setting: Medical intensive care unit in a university hospital. Patients: A total of 303 consecutive patients were included (216 men, 87 women; mean age 62 ± 12.6 years; SAPS II 26.2 ± 12.7). They were evaluated 24 h after admission and thereafter every 24 h until ICU discharge or death between November 1997 and March 1998. Readmissions and patients with an ICU stay shorter than 12 h were excluded. Main outcome measure: Survival status at hospital discharge, incidence of organ dysfunction/failure. Interventions: Collection of clinical and demographic data and raw data for the computation of the SOFA score every 24 h until ICU discharge. Measurements and main results: Length of ICU stay was 3.7 ± 4.7 days. ICU mortality was 8.3 % and hospital mortality 14.5 %. Nonsurvivors had a higher total SOFA score on day 1 (5.9 ± 3.7 vs. 1.9 ± 2.3, p 〈 0.001) and thereafter until day 8. High SOFA scores for any organ system and increasing number of organ failures (SOFA score ≥ 3) were associated with increased mortality. Cardiovascular and neurological systems (day 1) were related to outcome and cardiovascular and respiratory systems, and admission from another ICU to length of ICU stay. TMS score was higher in nonsurvivors (1.76 ± 2.55 vs. 0.58 ± 1.39, p 〈 0.01), and ΔSOFA/total SOFA on day 1 was independently related to outcome. The area under the receiver-operating characteristic curve was 0.86 for TMS, 0.82 for SOFA on day 1, and 0.77 for SAPS II. Conclusions: The SOFA, TMS, and ΔSOFA scores provide the clinician with important information on degree and progression of organ dysfunction in medical, cardiovascular patients. On day 1 both SOFA score and TMS score had a better prognostic value than SAPS II score. The model is closely related to outcome and identifies patients who are at increased risk for prolonged ICU stay.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1434-601X
    Schlagwort(e): PACS. 25.80.Ls Pion inclusive scettering and absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Physik
    Notizen: Abstract: The absorption of π+ on Ar was studied at pion energies of 70, 118, 162, 239 and 330MeV, and on N and Xe at 239MeV. Twenty-six absorption reaction channels with at least two energetic charged particles in the final state have been evaluated. Partial cross-sections have been determined according to the number of protons, neutrons and deuterons in the final state.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    Der Internist 39 (1998), S. 684-696 
    ISSN: 1432-1289
    Schlagwort(e): Schlüsselwörter Koronare Herzkrankheit ; Diagnostik ; Koronare Herzkrankheit ; Prognose ; Perfusionsszintigraphie ; Stress-Echokardiographie ; Belastungs-EKG
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Zum Thema In letzter Zeit spielen nichtinvasive Untersuchungen in der Diagnostik der koronaren Herzkrankheit wieder eine größere Rolle. Dies dürfte sicher nicht nur eine Folge weltweiter ökonomischer Zwänge im Gesundheitswesen sein sondern auch einem präzisierten medizinischen Denken entsprechen, das sich mehr um eine rationelle Stufendiagnostik bemüht. Allerdings ermöglichen auch verbesserte Methoden, besonders durch Perfusionsszinitigraphie und Stress-Echokardiographie, zunehmend höhere Sensivitäten und Spezifitäten nichtinvasiver Verfahren. Aus neuerer Zeit liegen auch zahlreiche Untersuchungen nicht nur zur diagnostischen sondern auch zur prognostischen Wertigkeit nichtinvasiver Methoden und somit zur Abschätzung koronarbedingter Risiken vor. Es ist geradezu ein generelles Anliegen der Zeitschrift DER INTERNIST, die gezielte Stufendiagnostik zu fördern; viele Hefte der letzten Jahre zeugen dafür. In dieses Konzept fügt sich auch die vorliegende Arbeit über nichtinvasive Methoden der Koronardiagnostik, die sich vorwiegend auf das Belastungs-EKG, die Perfusionsszintigraphie und die Stress-Echokardiographie fokussiert.
    Materialart: Digitale Medien
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