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  • 1
    Electronic Resource
    Electronic Resource
    Human Interindividual Variability in Parameters Related to Health Risks (1999)
    Springer
    Risk analysis 19 (1999), S. 711-726 
    Details
    ISSN: 1539-6924
    Keywords: variability ; exposure ; susceptibility ; risk assessment ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure-related parameters and parameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non-cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: •Contact Rate (Breathing rates per body weight; fish consumption per body weight) •Uptake or Absorption as a Fraction of Intake or Contact Rate •General Systemic Availability Net of First Pass Elimination and Dilution via Distribution Volume (e.g., initial blood concentration per mg/kg of uptake) •Systemic Elimination (half life or clearance) •Active Site Concentration per Systemic Blood or Plasma Concentration •Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) •Functional Reserve Capacity–Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process–differences among people in “functional reserve capacity.” This has the implication that relevant information for estimating effective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants that are thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007045922532
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  • 2
    Electronic Resource
    Electronic Resource
    Reizkorrelierte Gleichspannungsänderungen der primären Hörrinde an der wachen Katze (1969)
    Springer
    Pflügers Archiv 306 (1969), S. 281-289 
    Details
    ISSN: 1432-2013
    Keywords: Hearing ; Auditory Cortex ; Evoked d-c Potentials ; Intensity Function ; Gehör ; Hörrinde ; evozierte Gleichspannungspotentiale ; Intensitätsfunktion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Schallreizkorrelierte Gleichspannungsänderungen der primären Hörrinde (CGA=corticale Gleichspannungsantwort) wurden über subdurale implantierte Ag−AgCl Elektroden von der Katze abgeleitet und mit einem LINC-8-Rechner ausgewertet. Die CGA sind während der ganzen Reizdauer vorhanden, sie sind abhängig von der Reizqualität (z. B. Tonfrequenz), der Narkosetiefe und der Reizintensität. Die Intensitätsfunktion (Zusammenhang zwischen CGA-Amplitude und Reizintensität) wurde genauer untersucht und durch die Steigungskoeffizienten der Ausgleichsgeraden in Abhängigkeit von der Analysezeit (Zeitdifferenz zwischen Reizbeginn und Analysezeitpunkt) unter Berücksichtigung der Korrelation charakterisiert. Der Steigungskoeffizienn variiert mit der Analysezeit. Während er sich in der ersten Sekunde zwischen den Werten 0,7 und 0,4 bewegt, tendiert er mit wachsender Analysezeit gegen 0,3.
    Notes: Summary Sound evoked d-c changes in the primary auditory cortex (CGA= corticale Gleichspannungsantwort) of the cat were recorded with subdural implanted Ag-AgCl electrodes and analysed with a LINC-8-Computer. The CGA were maintained for the whole duration of stimulus, they depend on the stimulus quality (e.g. tone frequency), on the level of anesthesia and on the stimulus intensity. The intensity function (relation between CGA amplitude and stimulus intensity) has been investigated. It is characterised by the rising coefficient of the approximating line in dependence of the time of analysis (time of analysis starts with the stimulus beginning) with respect to correlation. The rising coefficientn varies with the time of analysis. Whereas in the first second it varies between the values 0.7 and 0.4 it tends with increasing time of analysis to 0.3.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00589154
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  • 3
    Electronic Resource
    Electronic Resource
    Akustischen Reizen zugeordnete Gleichspannungsänderungen am intakten Schädel des Menschen (1969)
    Springer
    Pflügers Archiv 309 (1969), S. 362-367 
    Details
    ISSN: 1432-2013
    Keywords: Hearing ; Evoked d-c Potentials ; Intensity Function ; Schlüsselwörter ; Gehör ; evozierte Gleichspannungspotentiale ; Intensitäts-funktion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Schallreizkorrelierte Gleichspannungsänderungen wurden mit AgCl-Elektroden vom intakten Schädel erwachsener Menschen (RGA = reizkorrelierte Gleichspannungsantwort) abgeleitet und mit einem LINC-8-Rechner ausgewertet. Die RGA sind während der ganzen Reizdauer vorhanden. Sie sind am Vertex am größten und sind von der Reizintensität abhängig. Die Intensitätsfunktion (Zusammenhang zwischen RGA-Amplitude und Reizintensität) wurde genauer untersucht und durch die Steigungskoeffizienten der Ausgleichsgeraden in Abhängigkeit von der Analysezeit (Zeitdifferenz zwischen Reizbeginn und Analysezeitpunkt) unter Berücksichtigung der Korrelation zwischen Ausgleichsgeraden und Meßwerten charakterisiert.
    Notes: Summary Sound evoked d-c changes (RGA = Reizkorrelierte Gleichspannungs-Antwort) were recorded with AgCl-electrodes from the intact heads of grown up human subjects and analysed with a LINC-8 Computer. The RGA were maintained during the whole duration of stimulus. They are largest at the Vertex and depend on stimulus intensity. The intensity function (relation between RGA amplitude and stimulus intensity) has been investigated and is characterised by the rising coefficient of the approximation line in dependence of the time of analysis (time of analysis starts with the beginning of the stimulus) with respect to the correlation between the approximating line and the measured data.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00587759
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  • 4
    Electronic Resource
    Electronic Resource
    Die mit Mikroelektroden ableitbare Reaktion einzelner Elemente des colliculus inferior und des corpus geniculatum mediale auf akustische Reize verschiedener Form und verschiedener Intensität (1968)
    Springer
    Pflügers Archiv 299 (1968), S. 83-93 
    Details
    ISSN: 1432-2013
    Keywords: Hearing ; Inferior colliculus ; Stimulus Dependent ; Activity ; Intensity Function of Single Acoustic Neurons ; PST-Histogramm ; Gehör ; colliculus inf., reizabhängige Aktivität ; Intensitätsfunktion einzelner Neurone ; PST-Histogramm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Zur Ermittlung der reizintensitätsabhängigen Aktivitätsänderung einzelner Neurone wurden die durch Reizung mit Tonbursts, Rauschbursts und Clicks ausgelösten Entladungen einzelner Elemente im colliculus inferior und im corpus geniculatum mediale mit Mikroelektroden extracellulär abgeleitet. Dabei wurde festgestellt, daß die Menge der sich im PST-Histogramm präsentierenden Entladungsmuster in wenige Klassen unterteilt werden kann, die jeweils durch einen Grundtyp charakterisiert sind. Es wurden: 1. Diese Klassen beschrieben und die Häufigkeitsverteilung von an 9 Katzen untersuchten 129 Einzelelementen hinsichtlich der Klassenzugehörigkeit angegeben. 2. Die Intensitätsfunktion der Einzelelemente untersucht und auf der Grundlage einer von Ranke (1952) aufgestellten Überlegung deren Verlauf diskutiert. 3. Ein einfaches Schema dargestellt, das den Zusammenhang zwischen den Intensitätsfunktionen der Einzelelemente und den von Elementkomplexen beschreiben soll.
    Notes: Summary To evaluate the activity variations of single neurons as a function of stimulus intensity the discharges of single elements were recorded extracellularly with microelectrodes from colliculus inferior and geniculate mediale. As stimuli served noise bursts, tone bursts and clicks. It is found that the number of response patterns in the PST-histogramm can be classified into a few groups everyone characterized by a groundtype. 1. These groups are described and the frequency distribution of 129 single elements of 9 cats is studied with regard to the classification. 2. The intensity function of single elements is studied on the basis of Ranke's adaptation theory and the curve is discussed. 3. A simple scheme is shown to describe the relation between the intensity functions of single elements and that of element complexes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00362543
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  • 5
    Electronic Resource
    Electronic Resource
    Reizfrequenzkorrelierte “untersetzte” neuronale Entladungsperiodizität im Colliculus inferior und im corpus geniculatum mediale (1969)
    Springer
    Pflügers Archiv 309 (1969), S. 11-20 
    Details
    ISSN: 1432-2013
    Keywords: Hearing ; Inferior Colliculus ; Geniculatum Mediale ; Frequency Discrimination ; Gehör ; Colliculus inferior ; Geniculatum mediale ; Frequenzdiskrimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die in der Literatur für alle Teile der Hörbahn unterhalb des Geniculatum mediale beschriebenen reizkorrelierten Entladungsperiodizitäten einzelner Neurone wurden für den Colliculus inferior bestätigt. Darüber hinaus wird über eine ganz andersartige Entladungsperiodizität im Geniculatum mediale berichtet. Davon ausgehend werden Strukturmodelle für die neuronale zeitliche Koinzidenzmessung angegeben. Schließlich wird auf eine Unterscheidungsmöglichkeit von intramodalitätsspezifischen und intramodalitätsunspezifischen neuronalen Verarbeitungsmechanismen hingewiesen.
    Notes: Summary The stimulus correlated discharge periodicities of single neurons described in the literature for all parts of the acoustic channel below the geniculatum mediale were confirmed for the colliculus inferior. Furthermore a quite different kind of discharge periodicity in the geniculatum mediale is reported. With these results structure models are given for the neuronal temporal measurement of coincidence. Finally a possibility of discrimination between intra-modality-specific and intra-modality-nonspecific processing mechanism is shown.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00592278
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  • 6
    Electronic Resource
    Electronic Resource
    Phenobarbital Disposition in Adult and Neonatal Rabbits (1994)
    Springer
    Pharmaceutical research 11 (1994), S. 1204-1206 
    Details
    ISSN: 1573-904X
    Keywords: phenobarbital ; pharmacokinetics ; milk ; rabbit ; neonate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018957420197
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  • 7
    Electronic Resource
    Electronic Resource
    Attenuation of furosemide's diuretic effect by indomethacin: Pharmacokinetic evaluation (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 265-274 
    Details
    ISSN: 1573-8744
    Keywords: furosemide ; indomethacin ; prostaglandin ; pharmacokinetics ; pharma-codynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and pharmacodynamics of intravenous furosemide, 40 mg, were studied in four normal males in a crossover fashion with and without indomethacin pretreatment. In each study 16 plasma and 10 urine samples were collected over 24 hr. Fluid and electrolyte urinary losses were replaced orally throughout the study. Unchanged furosemide and indomethacin were measured using HPLC; urinary sodium was measured by flame photometry. Pretreatment with indomethacin resulted in increased and prolonged furosemide plasma levels, increased area under the curve, decreased plasma clearance, decreased renal clearance, increased half-life, no change in volume of distribution, and decreased sodium excretion and urine volume. Analysis of sodium excretion rate with time shows that the inhibiting effect of indomethacin was greater during the first 2 hr than at later times.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01060017
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  • 8
    Electronic Resource
    Electronic Resource
    Determinants of bumetanide response in the dog: Effect of probenecid (1983)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 31-46 
    Details
    ISSN: 1573-8744
    Keywords: bumetanide ; probenedd ; pharmacokinetics ; pharmacodynamics ; doseresponse relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and pharmacodynamics of intravenous bumetanide (0.250 mg/kg), alone (treatment I) and after probenecid pretreatment (treatment II), were studied in four mongrel dogs. Lactated Ringer's solution was administered by vein throughout both treatments at a flow rate of 2 ml/min to avoid fluid and electrolyte depletion. Bumetanide and probenecid concentrations were analyzed by HPLC, sodium by flame photometry, and creatinine by colorimetry. Although the probenecid markedly reduced the plasma and renal clearances of bumetanide, as well as the fraction excreted unchanged in the urine, there was no significant difference between treatments I and II in the 4-hr natriuretic and diuretic responses. However, analysis of the dose-response curves between treatments I and II showed that sodium, excretion was better correlated with bumetanide urinary excretion rate than with plasma concentration. The reasons for a poor correlation between treatments during the early time periods are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061766
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  • 9
    Electronic Resource
    Electronic Resource
    Interspecies Pharmacokinetics of a Novel Hematoregulatory Peptide (SK&F 107647) in Rats, Dogs, and Oncologic Patients (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 794-797 
    Details
    ISSN: 1573-904X
    Keywords: allometric scaling ; peptide ; pharmacokinetics ; hematology ; infection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To study the pharmacokinetics of SK&F 107647, a novel hematoregulatory agent, in rats, dogs, and patients with non-lymphoid solid tumor malignancy. Methods. Sprague Dawley rats and beagle dogs (n = 6 each; 3 M, 3 F) were given 25 mg/kg of SK&F 107467 as an iv bolus injection, and patients (n = 6; 4 M, 2 F) received 100 ng/kg as a 2 hour iv infusion. Plasma samples were assayed for drug using either HPLC (rat and dog) or RIA (human). Results. In each species the plasma clearance (CL) of SK&F 107647 was low in relation to hepatic blood flow, and the volume of distribution (Vdss) was reflective of distribution to extracellular body water. The plasma CL in humans was near that of average glomerular filtration rate. Using allometric equations for interspecies scaling (Y = a·Wb), body-weight normalized human pharmacokinetic data were reasonably predicted using either the body weight normalized rat or the dog data. The allometric exponents (b) for CL, Vdss, and T1/2 of SK&F 107647 were 0.63, 0.94, and 0.29, respectively. Conclusions. Use of a limited pool of available animal data allowed for reasonable predictions of human pharmacokinetics of SK&F 107647.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016020221300
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