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  • 1985-1989  (3)
  • 1
    ISSN: 1432-1041
    Keywords: ceftizoxime ; cephalosporins ; renal excretion ; tubular reabsorption ; tubular secretion ; healthy volunteers ; biliary excretion ; clearance studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of ceftizoxime, a newly developed cephalosporin, were evaluated in 6 healthy subjects, with respect to its excretory pathways especially by the biliary route. Total, renal and biliary clearance were determined at two different steady states. Steady state was achieved by constant intravenous infusion (604.1 mg/h) over 6 h after an initial loading dose (750 mg); 1.5 h after discontinuation of that infusion, a further infusion was commenced at a lower rate (284 mg/h) over 3 h, the second steady state being reached 0.5 to 1.0 h later. The drug was mainly excreted by the kidneys (56.7 to 92.9% of the dose). Biliary excretion, measured by the duodenal perfusion and marker dilution technique, was low (0.2 to 7.8% of the dose). Urinary and biliary excretion as well as total clearance were not dose-dependent. However, there was pronounced interindividual variation in total (35.2 to 236 ml/min) and renal clearance (10.6 to 208 ml/min), which could both be explained by varying interindividual urinary flow rates (mean flow rate: 0.99 ml/min to 3.14 ml/min). Intraindividual variation in renal clearance was less pronounced, but in the same subject changes in renal clearance were correlated with changes in urinary flow rate. From the varying renal clearance, which exceeded the glomerular filtration rate at high urinary flow rates and was below it at low urinary flow rates, it can be concluded that, in addition to glomerular filtration, tubular secretion and tubular reabsorption are involved in the renal excretion of ceftizoxime. The half-life calculated from two point estimates after discontinuation of the infusion at the higher rate tended to be longer in subjects with high total clearance (e. g. 1.4 h, clearance 223 ml/min) and shorter in subjects with low total clearance (e.g. 0.85 h, clearance 35.2 ml/min). From this it is concluded that the true half-life was not observed after discontinuation of the infusion.
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  • 2
    ISSN: 1432-1351
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary 1. The neural audiogram of the common long-eared bat,Plecotus auritus was recorded from the inferior colliculus (IC). The most sensitive best frequency (BF) thresholds for single neurones are below 0 dB SPL between 7–20 kHz, reaching a best value of -20 dB SPL between 12–20 kHz. The lower and upper limits of hearing occur at 3 kHz and 63 kHz, respectively, based on BF thresholds at 80 dB SPL. BF threshold sensitivities are about 10 dB SPL between 25–50 kHz, corresponding to the energy band of the sonar pulse (26–78 kHz). The tonotopic organization of the central nucleus of the IC (ICC) reveals that neurones with BFs below 20 kHz are disproportionately represented, occupying about 30% of ICC volume, occurring in the more rostral and lateral regions of the nucleus. 2. The acoustical gain of the external ear reaches a peak of about 20 dB between 8–20 kHz. The gain of the pinna increases rapidly above 4 kHz, to a peak of about 15 dB at 7–12 kHz. The pinna gain curve is similar to that of a simple, finite length acoustic horn; expected horn gain is calculated from the average dimensions of the pinna. 3. The directional properties of the external ear are based on sound diffraction by the pinna mouth, which, to a first approximation, is equivalent to an elliptical opening due to the elongated shape of the pinna. The spatial receptive field properties for IC neurones are related to the directional properties of the pinna. The position of the acoustic axis of the pinna and the best position (BP) of spatial receptive fields are both about 25° from the midline between 8–30 kHz but approach the midline to 8° at 45 kHz. In elevation, the acoustic axis and the BP of receptive fields move upwards by 20° between 9–25 kHz, remaining stationary for frequencies up to 60 kHz. 4. The extremely high auditory sensitivity shown by the audiogram and the directionality of hearing are discussed in terms of the adaptation of the auditory system to low frequencies and the role of a large pinna inP. auritus. The functional significance of low frequency hearing inP. auritus is discussed in relation to hunting for prey by listening and is compared to other gleaning species.
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  • 3
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 16 Patienten wurden im Rahmen von operativen Eingriffen an der Bauchspeicheldrüse die Konzentrationen von Mezlocillin und Metronidazol im humanen Pankreasgewebe, Pankreassaft und Zystenflüssigkeit bestimmt. Die beiden Substanzen wurden analysiert, da sie das Spektrum an Bakterien abdecken, welche im Rahmen von Infektionen an der Bauchspeicheldrüse relevant sind. Zusätzlich wurde bei einem Patienten mit einer superinfizierten pankreatikokutanen Fistel das Fistelsekret bezüglich der Konzentrationen von Mezlocillin, Metronidazol und Netilmicin untersucht. Die Antibiotika-Konzentrationen in den verschiedenen Bauchspeicheldrüsenkompartimenten wurden mittels HPLC bestimmt nach intravenöser Injektion von 4g Mezlocillin, 500 mg Metronidazol bzw. 150 mg Netilmicin. Der mediane Bestimmungszeitpunkt lag bei 74 min. (16–210 min.) nach intravenöser Gabe des jeweiligen Antibiotikums. Die mediane Konzentration für Mezlocillin entsprach 23,2 mg/kg (3,1–37,4) in humanem Pankreasgewebe, 15,9 mg/l (4,2–55,0) im Pankreassaft und 9,9 mg/l (5,2–14,8) in der Zystenflüssigkeit. Die entsprechenden medianen Konzentrationen für Metronidazol waren 5,05 mg/kg (1,8–13,0) im Pankreasgewebe, 8,5 mg/l (3,6–16,2) im Pankreassaft und 1,15 mg/l (0,9–1,4) im Pankreaspseudozysteninhalt. Bei dem Fistelpatienten wurden sieben verschiedene Keime (fünf aerobe und zwei anaerobe) in Konzentrationen zwischen 105–107 KBE/ml isoliert. Die Keime, welchein vitro für Mezlocillin und Metronidazol empfindlich waren, verschwanden aus dem Fistelsekret innerhalb von vier Tagen nach intravenöser Therapie. Demgegenüber zeigten diein vitro für Netilmicin empfindlichen Keime ein verstärktes Wachstum im Fistelsekret. Die Spitzen-Konzentrationen für Mezlocillin, Metronidazol und Netilmicin in der Fistelflüssigkeit wurden mit 6,8 mg/ml, 5,6 mg/l und 〉0,1 mg/l ermittelt.
    Notes: Summary In order to analyse the penetration of two antibiotics (mezlocillin and metronidazole) which cover the spectrum of microorganisms involved in pancreatic infection, we determined their concentration in pancreatic tissue, juice and cyst fluid in 16 patients undergoing pancreatic surgery. In addition, the external pancreatic fistula fluid of one patient was analysed for antibiotic concentration and bacterial counts during a seven-day treatment with mezlocillin, metronidazole and netilmicin (i.v.). Antibiotic concentrations were determined by HPLC between 16 and 210 (median 74) min after i.v. administration of 4 g mezlocillin and 500 mg metronidazole, respectively. The median concentration of mezlocillin was 23.2 (range: 3.1–37.4) mg/kg, 15.9 (range: 4.2–55.0) mg/l and 9.9 (range: 5.2–14.8) mg/l in pancreatic tissue, juice and cyst fluid, respectively. The median concentration of metronidazole was 5.1 (range: 1.8–13.0) mg/kg, 8.5 (range: 3.6–16.2) mg/l and 1.2 (0.9–1.4) mg/l in pancreatic tissue, juice and cyst fluid, respectively. From the fistula patient, seven different bacteria were cultured (five aerobic and two anaerobic isolates); their concentration in fistula fluid ranged from 105 to 107 CFU/ml. The bacteria sensitive for mezlocillin and metronidazole disappeared after four days of i.v. treatment, whereas the two isolates sensitive for netilmicin showed continuous growth seven days after i.v. treatment. The peak concentrations for mezlocillin, metronidazole and netilmicin in the fistula fluid were 6.8 mg/l, 5.6 mg/l and 〈0.1 mg/l, respectively.
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