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  • 1985-1989  (595)
  • 1975-1979
  • 1935-1939
  • 1830-1839
  • 1985  (595)
  • Engineering  (422)
  • pharmacokinetics  (95)
  • Electron microscopy
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  • 1985-1989  (595)
  • 1975-1979
  • 1935-1939
  • 1830-1839
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  • 1
    Electronic Resource
    Electronic Resource
    Das Rückstandsverhalten von Chloramphenicol nach intramuskulärer Applikation beim Schwein (1985)
    Springer
    European journal of nutrition 24 (1985), S. 113-119 
    Details
    ISSN: 1436-6215
    Keywords: Chloramphenicol ; pharmacokinetics ; residue ; pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary Residues of Chloramphenicol (CAP) were examined in 24 pigs after intramuscular injection of 30 mg CAP/kg body weight. Two pigs were slaughtered after 3, 6, 12,18, 24, 36 hours, 2, 3, 6, 10, 21 and 30 days, respectively. CAP-concentrations were determined in muscle, blood, urine, liver, kidney, bile, and fat. Methods used were gas-liquid chromatography and radioimmunoassay. Detection limits reached were 1−5 ppb. The concentration-time curves obtained reflected a long elimination phase and allowed only calculation of this half-life. Elimination half-life was estimated to be for muscle, blood and urine 160–170 hours, for kidney 310 and for bile 250 hours. Significant correlations were found to exist between CAP-concentrations in plasma and muscle. It appears that blood would be a good body fluid for monitoring CAP-residues in tissue.
    Notes: Zusammenfassung Zur Untersuchung des Rückstandsverhaltens von Chloramphenicol (CAP) wurden 24 Mastschweine, 24–28 Wochen alt, intramuskulär mit 30 mg CAP/kg Körpergewicht behandelt und je 2 Tiere nach 3, 6, 12, 18, 24, 36 Stunden, 2, 3, 6, 10, 21 und 30 Tagen geschlachtet. Die CAP-Gehalte in Muskulatur, Blut, Urin, Leber, Niere, Galle und Fett wurden gaschromatographisch und radioimmunologisch bestimmt. Die Nachweisgrenze beider Methoden liegt in Abhängigkeit von der Matrix zwischen 1 und 5 ppb. Die erhaltenen Kinetiken weisen eine terminale Elimination auf, deren Halbwertszeiten für Muskulatur, Blut und Urin ca. 160–170 Stunden, für Niere 310 Stunden und für Galle 250 Stunden betragen. Die CAP-Konzentration in Muskulatur und Blut weisen eine signifikante, lineare Korrelation auf. Blutuntersuchungen könnten deshalb als Screening-Methode bei umfangreichen Rückstandskontrollen eingesetzt werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02020458
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  • 2
    Electronic Resource
    Electronic Resource
    On the morphology of oriented nylon-12 (1985)
    Springer
    Colloid & polymer science 263 (1985), S. 116-119 
    Details
    ISSN: 1435-1536
    Keywords: Electron microscopy ; staining ; morphology ; nylon-12 ; orientation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The morphology of drawn and annealed sheets of nylon-12 was investigated by transmission electron microscopy of stained sections, and the results compared with equivalent small-angle X-ray scattering (SAXS) patterns. A three-component structure was observed, consisting of crystalline (C) and amorphous (A) regions in the microfibrils and an interfibrillar component whose density was deduced to be intermediate between that of the C and A regions. The crystallite width was given satisfactorily by a Guinier analysis of the SAXS profile.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01412785
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  • 3
    Electronic Resource
    Electronic Resource
    The formation of ultrastructural epithelial and subepithelial connective tissue changes in experimentally induced cholesteatomas in guinea pigs (1985)
    Springer
    European archives of oto-rhino-laryngology and head & neck 241 (1985), S. 267-270 
    Details
    ISSN: 1434-4726
    Keywords: Cholesteatoma ; Histoacryl ; Early stages ; Light microscopy ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Histoacryl-induced cholesteatomas were produced in guinea pigs at the posterosuperior part of the external ear canal adjacent to the tympanic membrane. Semithin and ultrathin tissue sections were used to study primary formation of the cholesteatoma as well as the influence of the altered epithelium upon the bordering zone of connective tissue. Quantitative and qualitative tissue changes were analyzed by electron microscopy and showed degradation and new formation of collagen and activation of fibroblasts. Our findings are similar to those previously reported on human cholesteatomas and indicate that the bordering subepithelial tissue seems to be influenced through the basilar membrane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00453699
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  • 4
    Electronic Resource
    Electronic Resource
    Megakaryoblastic micromegakaryocytic crisis in chronic myeloid leukemia (1985)
    Springer
    Annals of hematology 51 (1985), S. 275-285 
    Details
    ISSN: 1432-0584
    Keywords: Chronic myeloid leukemia ; Megakaryoblastic crisis ; Cytomechistry. Cytogenetics ; Cytophotometry ; Electron microscopy ; In vitro culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Atypical megakaryoblasts (MKB) or megakaryocytes (MK) are occasionally present in the peripheral blood during the terminal development of chronic myeloid leukemia (CML). We report on a 49-year-old female suffering from Ph1 chromosome-positive CML with typical megakaryoblastic transformation in the peripheral blood and in the bone marrow. The small “blasts” were at the most only slightly larger and were occasionally even smaller than lymphocytes but showed megakaryoblastic or atypical megakaryocytic differentiation. The cytoplasmic cytochemical pattern of the atypical megakaryocytic cells was identical to that of large atypical thrombocytes. Platelet peroxidase was detected upon electron-microscopic (EM) examination. Immunologic characterization disclosed the presence of MK-specific antigens. When cultured in vitro on agar, the blasts transformed spontaneously into large mature MK, exhibiting characteristic cytochemical and immunological patterns. Cytogenetic examination of peripheral blood showed severe abnormalities. The patient did not respond to therapy and died 3 months after manifestation of the blast crisis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00320522
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  • 5
    Electronic Resource
    Electronic Resource
    Ultrastructural development of the dorsal lateral geniculate nucleus of genetically microphthalmic mice (1985)
    Springer
    Experimental brain research 60 (1985), S. 527-534 
    Details
    ISSN: 1432-1106
    Keywords: Electron microscopy ; Lateral geniculate nucleus ; Mouse ; Mutant ; Microphthalmia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructure of the dorsal lateral geniculate nucleus (dLGN) of microphthalmic mice is described in affected white homozygotes (mi/mi) and their apparently normal grey littermates. In the dLGN of mi/mi animals populations of apparently normal axon terminals were observed, including some with flattened synaptic vesicles and other small terminals with round vesicles and dark mitochondria (RSD), possibly of cortico-thalamic origin, just as in normal mice. However, no typical large retinal endings with round vesicles and pale mitochondria (RLP) are visible. Instead they appear to be replaced by other large boutons with round vesicles and dark mitochondria (RLD). Eye enucleation does not cause degeneration of these RLD terminals. In apparently normal grey littermates RLP terminals are present and they degenerate when an eye is enucleated. But RLD endings are also found in these animals, and never degenerate after enucleation. The origin of the RLD terminals is unclear but seems not to be cortical. These findings are compared with those of Cullen and Kaiserman-Abramof (1976) in a different strain (ZRDCT-An) of anophthalmic mouse in which they found large replacement terminals similar to our RLD boutons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00236938
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  • 6
    Electronic Resource
    Electronic Resource
    Biophysikochemische Strukturen des glomerulären Filters (1985)
    Springer
    Journal of molecular medicine 63 (1985), S. 835-849 
    Details
    ISSN: 1432-1440
    Keywords: Renal glomerulus ; Filtration apparatus ; Polyanion ; Tracer studies ; Electron microscopy ; Nierenglomerulus ; Filterapparat ; Polyanion ; Traceruntersuchungen ; Elektronenmikroskopie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Feinstrukturen sowie die biophysikalischen und biochemischen Eigenschaften des glomerulären Filters für die Permeation von Makromolekülen werden dargestellt. Unter Berücksichtigung der unterschiedlich lokalisierten Immunkomplexablagerungen bei den verschiedenen Formen der Glomerulonephritis des Menschen orientieren sich Beschreibung und Diskussion an bestimmte Schichten des Filters: 1. endothelial — subendothelial (=porenhaltiges Endothel und lamina rara interna der Basalmembran), 2. membranös (=Lamina densa der Basalmembran) und 3. subepithelial — epithelial (=Lamina rara externa der Basalmembran und Podozyten mit Fußfortsätzen und Schlitzmembranen). Dabei wird hervorgehoben, daß die genannten Schichten Eigenschaften aufweisen, die eine zunehmend feinere Siebung von Makromolekülen aus dem Blut gewährleisten. Auf bekannte feinstrukturelle Besonderheiten des glomerulären Filters aufbauend, haben die experimentellen Untersuchungen der letzten 10 Jahre offenbart, daß ein Netzwerk von insbesondere Typ IV Collagen und die Existenz negativ geladener Heparansulfat-Proteoglykane („glomeruläres Polyanion“) wichtig für eine solche Siebung sind. Die Tatsache, daß die genannten Komponenten innerhalb der einzelnen Schichten in bestimmter Folge zellulär und extrazellulär lokalisiert sind, führt zu einem differenziert siebenden Filterapparat, der die Molekülgröße, die Konfiguration sowie die Ladung der Makromoleküle berücksichtigt. Dadurch wird der Durchtritt der zumeist negativ geladenen Blutproteine, insbesondere der von Albuminen, normalerweise verhindert.
    Notes: Summary The ultrastructural and the biophysical and biochemical qualities of glomerular permeability to protein molecules are reviewed. With regard to differently located immune deposition in human glomerulonephritis, description and discussion are addressed in a fixed order of layers: 1. endothelial-subendothelial, i.e. the endothelial cells with fenestrae and the lamina rara interna of the basement membrane (bm), 2. membranous, i.e. the lamina densa of the bm, 3. subepithelial-epithelial, i.e. the lamina rara externa of the bm and the podocytes with food processes and slit diaphragms. It is emphasized that the 3 layers act as gradually (coarse to fine) filter barriers. On the basis of well known structural peculiarities, in the last 10 years experimental studies revealed that the meshwork of type IV collagen and the negatively charged heparan sulfate-proteoglycans — “the glomerular polyanion” — are integrated in sieving of protein molecules. These components are differently located in the stratified cellular and extracellular layers of the glomerular filter and their combined action is the basis of a size, charge and configuration dependend filtration of macromolecules. In this way the passage of the mostly negative charge blood proteins, expecially albumin, is prevented under normal conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01738136
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  • 7
    Electronic Resource
    Electronic Resource
    Immunologische und elektronenmikroskopische Befunde eines ungewöhnlichen Falles von M. Whipple (1985)
    Springer
    Journal of molecular medicine 63 (1985), S. 176-183 
    Details
    ISSN: 1432-1440
    Keywords: Whipple's disease ; Electron microscopy ; Disturbed cellular immunology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Whipple's disease is a curious disorder with the involvement of many organ systems, primarily gut, synovium and the central nervous system, characterized by the presence of numerous proliferating bacteria in tissue macrophages and other cell types. While clinically this disease entity has previously been defined by the classical triad of diarrhoea, malabsorption and weight loss, some patients do not show these features. In this report, a clinically unusual case of Whipple's disease is described presenting with high persistent fever, severe arthralgias and headaches, but without malabsorption, diarrhoea or weight loss. Nevertheless, the histological and electron microscopical pictures demonstrated the typical findings of intracellular micro-organisms along with the presence of bacteria in Schwann nerve cells, which has only once been described previously. Immunological findings before treatment demonstrated a decrease of T cells with the helper/inducer phenotype, and a concomitant rise in cells with the suppressor/cytotoxic phenotype, an elevation of “activated” Ia positive T cells and a significant reduction of T cell mitogenic responsiveness. Of special interest, after a successful treatment these immunological abnormalities shifted to normal with the exception of a still elevated number of Ia+ T cells. The discussion of this unusual case of Whipple's disease includes — besides possible cellular immunological abnormalities — genetic factors, especially since this patient was HLA-B-27-positive as was his son who is suffering from ankylosing spondylitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01732172
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  • 8
    Electronic Resource
    Electronic Resource
    Hepatitis non-A, non-B (HNANB): Epidemiologische, klinische, serologische und morphologische Aspekte (1985)
    Springer
    Journal of molecular medicine 63 (1985), S. 389-404 
    Details
    ISSN: 1432-1440
    Keywords: Hepatitis non-A, non-B ; Epidemiology ; Serology ; Light microscopy ; Electron microscopy ; Virus particles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hepatitis non-A, non-B (HNANB) is due to one or more transmissible agents, probably viruses. Epidemiologically, HNANB is transmitted predominantly by transfusion of blood or plasma derivatives, and percutaneous inoculation, but a non-percutaneous transmission by the fecal-oral route is also established. However, despite 10 years of intense world-wide research, the transmissible agent, or agents, have not been identified and there are no serological assays for either an antigen or an antibody that can be used to detect this infection. The clinical diagnosis of HNANB remains, therefore, a diagnosis of exclusion mainly of hepatitis A and B, Epstein-Barr virus, cytomegalovirus and drug-induced liver disease. In contrast to hepatitis A and B, the clinical and biochemical course of HNANB tends to be less severe and the proportion of asymptomatic and anicteric cases is higher, but fulminant hepatitis and fatalities also occur. Typically, there is a fluctuating waxing and waning pattern of the serum aminotransferase activities in HNANB. HNANB has a relative high tendency to progress to a chronic stage. The exact frequency of HNANB-induced liver cirrhosis and convincing evidence for an association with hepatocellular carcinoma cannot be assessed, although the persistence of the infectious agent in chronic HNANB and the existence of a chronic asymptomatic carrier state have been proved. By light microscopy there is a broad morphologic spectrum of acute and chronic viral hepatitis, but no single pathognomonic lesion exists that allows a reliable distinction to be made of HNANB from hepatitis A and B. Electron microscopy of liver biopsy specimens of chimpanzees, experimentally infected with HNANB agents, permits the visualisation of cytoplasmic changes, which appear to be specific for infection with HNANB viruses. In human liver biopsy specimens from patients with HNANB, identical ultrastructural cytoplasmic changes could not consistently be demonstrated. In contrast, intranuclear aggregates of spherical and tubular particles measuring 20–29 nm, first described in experimental HNANB in chimpanzees, have been repeatedly demonstrated in acute and chronic HNANB in man. These nuclear particles have been considered as compelling evidence of human HNANB infection. The specificity has been challenged, however, by the demonstration of identical particles in other viral and non-viral hepatopathies and in liver biopsies of healthy volunteers. By immune electron microscopy, a multiplicity of virus-like particles are described in association with HNANB. The particles have been identified in sera of patients with HNANB, in sera of experimentally infected chimpanzees, and in infectious factor VIII and fibrinogen preparations. The great variability in morphology and size of the observed particles suggests the possibility that most of these particles are not specific for HNANB.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01733664
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  • 9
    Electronic Resource
    Electronic Resource
    Angiomatoid malignant fibrous histiocytoma (1985)
    Springer
    Virchows Archiv 406 (1985), S. 59-66 
    Details
    ISSN: 1432-2307
    Keywords: Angiomatoid malignant fibrous histiocytoma ; Histiocytic origin ; Immunocytochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The results of an histological, immunocytochemical and electron microscopic study of an angiomatoid malignant fibrous histiocytoma are reported. Our results support an histiocytic, rather than an endothelial origin for the tumor cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00710557
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  • 10
    Electronic Resource
    Electronic Resource
    Membranocystic lesions of the lung in Nasu-Hakola disease (1985)
    Springer
    Virchows Archiv 408 (1985), S. 211-217 
    Details
    ISSN: 1432-2307
    Keywords: Nasu-Hakola disease ; Membranocystic lesion ; Pulmonary involvement ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Massive membranocystic lesions of the lung were found in an autopsy case of Nasu-Hakola disease. The membranocystic structures are virtually identical to those found in adipose tissue, including bone marrow. Capillary endothelia and alveolar epithelial lining cells do not participate in membranous structure formation, these structures being found in the alveolar septa and not apparently of an embolic nature. They may be related to alveolar septal cells in a broad sense. The pathogenesis of this disease is discussed in relation to the lesions of the lung.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00707983
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  • 11
    Electronic Resource
    Electronic Resource
    Development and regression of pulmonary arterial lesions after experimental air embolism (1985)
    Springer
    Virchows Archiv 406 (1985), S. 203-212 
    Details
    ISSN: 1432-2307
    Keywords: Pulmonary artery ; Air embolism ; Intima ; Oedema ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Repeated systemic venous air embolism produces pulmonary vascular lesions, the nature of which is still a subject of controversy. We investigated the pulmonary arterial lesions produced by repeated air embolism in rabbits, both at light and electron microscopic level. We found that they form a remarkable histopathological entity, consisting of initial pronounced vasoconstriction, combined with severe intimal inflammatory changes. Within 4 days after the last injection of air, peculiar sheet-like structures consisting of oedematous tissue and lined by endothelium, projected into the lumen. These structures probably resulted from the shearing stress of the blood, streaming over the severely oedematous intima. They subsequently became thinner and disappeared after two weeks. Various types of blood-borne and mesenchymal cells were present in the thickened intima and within the sheets. The origin of the latter cells remained undecided. They may originate from medial smooth muscle cells penetrating the internal elastic lamina as well as by transition from blood-borne cells into mesenchymal cells, or both.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00737086
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  • 12
    Electronic Resource
    Electronic Resource
    Tubular ultrastructure in acute renal failure in man: Epithelial necrosis and regeneration (1985)
    Springer
    Virchows Archiv 406 (1985), S. 75-89 
    Details
    ISSN: 1432-2307
    Keywords: Acute renal failure ; Renal tubules ; Necrosis ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is not clear whether tubular cell necrosis is present or not in acute renal failure (ARF) of ischaemic type (“acute tubular necrosis”). In order to get quantitative data, using precisely defined criteria for tubular cell necrosis, 25 renal biopsies from 24 patients with ARF (11 obtained in the active phase, 14 in the early recovery period) were compared with 12 control biopsies. In all 1959 proximal cells and 1603 distal cells were analysed by electron microscopy. Cellular disintegration was very rare in all groups. Shrinkage necrosis (apoptosis) was not present in the proximal tubules of the controls and was rare in ARF (1.6–2.1%). In the distal tubules of controls 2.7% of all cells showed shrinkage necrosis. The incidence in ARF was not significantly increased. “Non-replacement sites” in distal tubules (probablyloci where cells have recently been desquamated) were significantly increased in number (5.2%) in the active phase in ARF compared to controls and recovery. The relative number of regenerating cells was not increased. These data show that there is no widespread necrosis of tubular cells in ARF. The increased incidence in distal tubules of focal, denuded areas of the basement membrane in the active phase of ARF indicates a slightly increased desquamation of cells and/or a failure to cover such sites by adjacent cells. This process is not restricted to the brief induction phase of ARF but continues during the whole active phase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00710559
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  • 13
    Electronic Resource
    Electronic Resource
    Light and electron microscopic localization of the N-terminal fragment of human pro-opiomelanocortin in the human pituitary gland and in neoplasms (1985)
    Springer
    Virchows Archiv 408 (1985), S. 281-287 
    Details
    ISSN: 1432-2307
    Keywords: Immunohistochemistry ; Electron microscopy ; ACTH ; Pituitary gland ; Neoplasm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunohistochemical localization of theN-terminal fragment (1–76) (NTF) of human pro-opiomelanocortin (POMC) was studied in human adult and fetal pituitary glands, as well as in pituitary adenomas associated with Cushing's syndrome and in ectopic ACTH-producing tumors. Comparison of localization between NTF and ACTH was performed using mirror sections. Our results indicated concomitant localization of NTF and ACTH in the same cells, not only in normal adult and fetal pituitaries but also in pituitary adenomas and ectopic ACTH producing tumours. Specificity of the NTF staining was confirmed by immunoabsorption. Negative staining of the bovine pituitary gland indicated the immunohistochemical localization ofN-terminal (1–45) of human POMC as there is a known species difference in the sequence 1–45 between human and the bovineN-terminal fragment. Presence of NTF in cisterna of rough endoplasmic reticulum indicates its production by small cell carcinoma. These findings, together with the previous studies, suggest that the complete form of POMC is produced in the tumours as well as in normal pituitaries.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00707990
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  • 14
    Electronic Resource
    Electronic Resource
    Glomerular monocyte infiltration in human nephropathies: Prevalence and correlation with clinical and morphological variables (1985)
    Springer
    Virchows Archiv 405 (1985), S. 483-496 
    Details
    ISSN: 1432-2307
    Keywords: Glomerulonephritis ; Monocytes ; Electron microscopy ; Proteinuria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glomerular monocyte infiltration was evaluated by histochemical means (nonspecific esterase) and/or electron microscopy in 305 renal biopsies belonging to a wide variety of human renal diseases. Significant monocyte infiltration was never observed in a first group of nepropathies (minimal change disease, nephrotic syndrome with IgM deposits, focal segmental glomerulosclerosis, membranous GN, Berger's GN, healed GN, dense deposit disease, chronic non specific GN, benign familial haematuria, Alport's disease, renal amyloidosis, arteriosclerotic kidney, light chain GN). Conversely, it was present at varying frequency in a second group of nephropathies including: acute GN (58.3%), persistent GN (10%), membranoproliferative GN (25.2%), eryoglobulinaemic GN (82.6%), lupus GN (36%), extracapillary proliferative GN (50%) and Schoenlein-Henoch GN (40%). The results indicate: 1) there is an evident association between monocyte infiltration and the subendothelial site of deposits; 2) the presence of monocytes is not affected by the size and extension of subendothelial deposits; 3) monocytes were more frequently observed when IgG, IgM and fibrinogen were present in the subendothelial deposits, Conversely, complement fractions do not seem to affect monocytic activity; 4) polymorphonuclear leukocyte exudation is less frequently found and mostly associated with monocyte infiltration; 5) in some GNs (persistent GN, cryoglobulinaemic GN and membranoproliferative GN), proteinuria was significantly higher in patients with than in those without monocyte infiltration, giving support to the hypothesis that in human beings as in experimental animals monocytes play a role in the pathogenesis of proteinuria.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00737174
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  • 15
    Electronic Resource
    Electronic Resource
    An ultrastructural and morphometric study of bladder tumours (III) (1985)
    Springer
    Virchows Archiv 406 (1985), S. 7-16 
    Details
    ISSN: 1432-2307
    Keywords: Electron microscopy ; Bladder neoplasms ; Measurement ; CIS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Quadrant biopsies were taken at cystoscopy from 12 male patients previously diagnosed on light microscopy as having flat carcinoma in situ (CIS) of the urinary bladder. There was also material available from 3 cystectomy specimens with widespread CIS associated with papillary or solid urothelial tumours. Sections of normal ureter from kidney transplant donors and biopsies from two patients investigated for non-malignant bladder conditions servered as controls. The biopsies from 4 patients were classified as mild dysplasia of the urothelium, while those from 11 patients were categorised as CIS. Biopsies categorised as mild dysplasia on light microscopy showed an increase in the number of cells with large nuclei and nucleoli when compared to controls. The number of desmosomes was significantly reduced compared to controls, while the frequency of abnormalities of the basal lamina was increased. These features were more pronounced in the CIS group. Biopsies from the CIS group could be divided into “classical” and “large cell” CIS, the latter showing a higher frequency of ultrastructural abnormalities than the “classical” type. The patients diagnosed as having CIS fell into two clinical categories, the “early onset” and the “late onset” group. The five patients in the former had been diagnosed as having CIS with or without urothelial tumours elsewhere within 3 months of presentation. In the remaining four patients CIS was observed after recurring episodes of papillary or solid tumours during the previous 9 months to 20 years. The biopsies of 3 out of 5 patients with early onset CIS had been classified “large cell” CIS, wheras only one patient out of 4 in the late onset group came into this category. An early appearance of CIS is thought to have a worse prognosis, and it is therefore suggested that “large cell” CIS is a more severe form of the disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00710552
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  • 16
    Electronic Resource
    Electronic Resource
    Tubular ultrastructure in acute renal failure: Alterations of cellular surfaces (Brush-border and basolateral infoldings) (1985)
    Springer
    Virchows Archiv 406 (1985), S. 91-104 
    Details
    ISSN: 1432-2307
    Keywords: Acute renal failure ; Renal tubule ; Electron microscopy ; Brush border ; Basolateral infoldings
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using a blind, semiquantitative technique, the degree of reduction of proximal tubular brush border (BB) and proximal and distal basolateral infoldings (BI) were measured in 25 renal biopsies from patients with acute renal failure (ARF) of ischaemic type. For comparison 12 biopsies from patients without ARF were studied, 6 were normal controls, six were from patients with minor change disease and slight glomerulonephritis. The mean scores for reduction of BB as well as proximal and distal BI were strongly increased in ARF compared to controls and the differences were highly significant. Some of the biopsies were taken during recovery and there was a significant negative correlation between the individual scores for reduction of BB and BI and simultaneous renal function. The disappearance of BB microvilli was correlated to tubular dilatation, but it could not be explained exclusively by “stretching” of the luminal surface due to dilatation. There was no correlation between reduction of BI and tubular dilatation. The data indicate a disturbance of cell membrane turnover in the active phase of ARF, possibly due to decreased synthesis, and they are consistent with a pathogenetic hypothesis implicating a decreased proximal Na+ resorption and consequently a pre-glomerular vasoconstriction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00710560
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  • 17
    Electronic Resource
    Electronic Resource
    Quantitative ultrastructure of human proximal tubules and cortical interstitium in chronic renal disease (hydronephrosis) (1985)
    Springer
    Virchows Archiv 406 (1985), S. 389-406 
    Details
    ISSN: 1432-2307
    Keywords: Atrophy ; Proximal tubule ; Human nephropathy ; Electron microscopy ; Quantitative changes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Surgically removed perfusion-fixed human kidneys with chronic renal disease (hydronephrosis) were studied by electron microscopy in order to determine whether there is a quantitative relationship between ultrastructural changes in proximal tubules in atrophy and changes in the surrounding cortical interstitium. Morphometric techniques were applied to montages of electron micrographs each covering several tubular profiles in the cortical labyrinth and to montages representing cross-sections of individual proximal convoluted tubules at a higher magnification. In order to enable a quantification of the spatial relations between individual tubular cross-sections and adjacent peritubular capillaries a tubulo-capillary index (TCI) was defined. This index was based on the mean distances between individual tubular cross-sections and adjacent peritubular capillaries and on the fraction of tubular circumference facing capillaries. Normal tissue from similarly fixed human nephrectomy specimens, which had been removed mainly because of neoplastic disorders, served as control material. In the hydronephrotic kidneys the relative volume of cortical interstitium (excluding capillaries) covered a range from 19.2–70.3%. Inverse correlations were demonstrated between the relative volume of cortical interstitium and various structural variables of proximal convoluted tubules, including tubular wall volume, the volume of mitochondria and the surface area of basolateral membranes. The TCI showed positive correlations with these tubular variables. No significant correlation was found between the volume fractions of cortical interstitium and capillaries. Finally, it was found that an increase in the volume fraction of the cortical interstitium from 16.2% in controls to 24.7% in cortical areas of hydronephrotic kidneys was associated with a 40–50% reduction in the volume of mitochondria and in the surface area of basolateral membranes in proximal tubules. The results are consistent with a pathogenic interrelationship between tubular and interstitial changes. An important factor in this relationship might be disturbed topographic associations between tubules and blood capillaries caused by the increase in cortical interstitium. The results further show that even slight increases in the cortical interstitial volume are associated with significant quantitative changes in tubular fine structure suggesting impaired tubular functions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00710231
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  • 18
    Electronic Resource
    Electronic Resource
    Ultrastructural evaluation of murine bladder epithelium exposed to verapamil (1985)
    Springer
    Urological research 13 (1985), S. 233-235 
    Details
    ISSN: 1434-0879
    Keywords: Urothelium ; Electron microscopy ; Verapamil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of single or multiple instillations of high verapamil concentrations on the cytoarchitecture of the bladder epithelium was assessed by electron microscopy. Ruthenium red was used to evaluate the surface mucopolysaccharide coats and the integrity of junctional complexes between luminal or nonluminal cells was found in any experimental animals, nor was there a breakdown of the junctional complexes between luminal cells. These data suggest that verapamil may be safely used intravesically as adjunct to standard chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00261582
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  • 19
    Electronic Resource
    Electronic Resource
    Sodium orthophosphate hydrate (NA3PO4·12H2O): A new type of human urinary stone (1985)
    Springer
    Urological research 13 (1985), S. 301-304 
    Details
    ISSN: 1434-0879
    Keywords: Electron microscopy ; Urolith ; Sodium phosphate ; New stone component
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a series of electron microscopic studies of human urinary stones, a stone composed of sodium orthophosphate hydrate was identified. The stone was recovered from a patient who succumbed to advanced renal failure. A massive failure of the sodium pump, which cotransports phosphate across the brush border membrane of the proximal tubules is thought to be responsible for such an exceptional stone. This appears to be the first description of sodium phosphate crystal in a human urinary stone. Electron microscopy is a useful tool for stone analysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00262661
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  • 20
    Electronic Resource
    Electronic Resource
    The ultrastructure of early cephalic neural crest cell migration in the mouse (1985)
    Springer
    Anatomy and embryology 172 (1985), S. 33-38 
    Details
    ISSN: 1432-0568
    Keywords: Neural crest ; Embryology ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A study of the ultrastructural changes associated with the detachment of the presumptive neural crest cells from the neuroepithelium in the midbrain region in mouse embryos at 9 and 91/2 days of gestation was carried out. The first sign of neural crest cell formation occurred in this region before fusion of the neuroepithelium had occurred. Neural crest cells arose from both the neural plate and the adjoining surface ectoderm. Initially, the cells of the neural plate and the surface ectoderm were attached to each other by zonula occludens and zonula adherans at their apical surfaces however, these junctions disappeared just prior to the beginning of the migration of the crest cells. The first sign of migration of the crest cells was the disappearance of the basal lamina in the region of the presumptive crest cells. Once the basal lamina was lost, cell junctions were formed between the epithelial cells and the underlying mesenchymal cells. Once the crest cells had migrated into the underlying mesenchyme, they tended to form clumps of closely related, irregularly shaped cells. Phagosomes and accumulations of glycogen particles were found within some crest cells when they were still within 50 to 100 microns of the epithelium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318941
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  • 21
    Electronic Resource
    Electronic Resource
    Differences in synaptic size in the superficial and deep layers of the molecular layer of the cerebellar cortex of the cat (1985)
    Springer
    Anatomy and embryology 172 (1985), S. 303-309 
    Details
    ISSN: 1432-0568
    Keywords: Synaptology ; Cerebellum ; Quantitative analysis ; Autoradiography ; Electron microscopy ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a previous study observations in semithin sections of E-PTA-stained cerebellar cortex of the cat revealed differences in size of synaptic grids between the molecular and granular layer (Van der Want et al. 1984). In addition, synaptic size differences were observed between superficial and deep levels in the molecular layer. The present study was an attempt to analyze synapses in ultrathin sections of the cerebellar cortex with special emphasis on size differences of distinct types of synapses at different levels in the molecular layer. Climbing fibers were identified by means of anterograde transport of 3H-leucine injected in the inferior olive and parallel fibers were identified on account of fine structural criteria. Synaptic profiles were measured semi-automatically in the neuropil of the cerebellar cortex at the supra-Purkinje level and the subpial level. Measurements of the trace- and chordlength were obtained from random sections. The frequency distribution of the true diameters of the synapses was reconstructed with a discrete “unfolding”-procedure. The overall diameter at the superficial level was 390.2±1.5 nm, at the deep level 406.6±1.5 nin. Climbing fibers exhibited mean values of 431.9±4.7 and 461.3±4.1 nm at these levels and parallel fiber terminals mean values of 370.7±2.9 and 395.8±3.0 nm. The frequency distributions showed remarkable and statistically significant differences compared with the overall distributions observed at the superficial and the deep levels respectively. The frequency distributions of synaptic diameters at the superficial and deep levels also differ significantly. The results suggest that synapses are characterized by a specific size which might be related to the region of termination or might be determined by the afferent neuron. This is in agreement with earlier observations in E-PTA treated material.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318978
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  • 22
    Electronic Resource
    Electronic Resource
    Immunocytochemical localization of uteroglobin in the rabbit endometrium (1985)
    Springer
    Anatomy and embryology 172 (1985), S. 295-301 
    Details
    ISSN: 1432-0568
    Keywords: Uteroglobin ; Rabbit ; Endometrium ; Immunoperoxidase ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Uteroglobin, the progesterone dependent pregnancy-characteristic endometrial protein in the rabbit, is found within the endometrial epithelium on the fourth and sixth day of pregnancy at the electron-microscopic level by use of the immunoperoxidase technique and a specific anti-uteroglobin serum from the sheep. As known from earlier studies, uteroglobin is the predominant protein synthesized of the endometrial secretion. In the present study, it is localized exclusively in the non-ciliated epithelial cells. A common route of secretory proteins within these cells is observed by uteroglobin labelling: rough endoplasmatic reticulum → Golgi complex → condensing vesicles → secretory products. Uteroglobin occurs in small vesicles on the trans-face of the Golgi complex, and in addition beneath the apical plasma membrane where it appears in membranebound vesicles, which apparently are extruded into the unterine lumen. Most of the uteroglobin is located in the luminal secretion. The distribution of intracellular uteroglobin is found only in cells of the basal endometrial gland, adjacent to the myometrium. The cytoplasm of uterine epithelial cells facing the cavum does not show uteroglobin reaction products.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318977
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  • 23
    Electronic Resource
    Electronic Resource
    The origin of inner membranes in chronic subdural hematomas (1985)
    Springer
    Acta neuropathologica 67 (1985), S. 219-225 
    Details
    ISSN: 1432-0533
    Keywords: Inner membrane ; Chronic subdural hematoma ; Dural border cell ; Arachnoid cell ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Electron-microscopic findings of inner membranes of chronic subdural hematomas showed multilayered tiers of flattened cells. The basis characteristics of these cells were similar to dural border cells in the human dura-arachnoid interface layer. The cells covering the hematoma surface had indented nuclei with a prominent nucleolus and were abundant in enlarged rough ER, glycogen granules, lipid droplets, and caveolae. The cells in the intermediate layer had thin cytoplasmic extensions containing tonofilaments, which were oriented almost parallel to the long axis of inner membranes. The cells facing the arachnoid surface sometimes showed disintegration of cellular organelles and dissolution of nuclear chromatin. Between these cells and the tiers was an increased amount of extracellular substance, such as collagen fibrils, clastins, and finely granular material, which were often intermingled with blood pigments or fibrins, especially toward the arachnoid surface. In two of the ten cases studied, there was a syncytial mass of arachnoid cells which reinforced the arachnoid surface of inner membranes. Conceivably, a primary extravasation of blood within the dura-arachnoid interface layer may cleave a few tiers of dural border cells, which envelope the inner surface of the hematoma, proliferate, and later on form inner membranes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00687804
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  • 24
    Electronic Resource
    Electronic Resource
    Electron-microscopic observation of the nucleus basilis of Meynert in human autopsy cases (1985)
    Springer
    Acta neuropathologica 68 (1985), S. 130-137 
    Details
    ISSN: 1432-0533
    Keywords: Nucleus basalis of Meynert ; Electron microscopy ; Human autopsy cases ; Dementia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The large neurons of the nucleus basalis of Meynert (nbM) were examined with the electron microscope in 13 autopsied human adults. The neurons were characterized by a prominent Nissl substance and accumulation of lipofuscin granules. Lamellar bodies were often observed among the Nissl substance. Many of the lipofuscin granules were large and had a characteristic pronounced mosaic pattern of pale areas within gray zones. Menbranous structures within the nucleus and periodic transverse processes in the cristae of the mitochondria were regarded as postmortem alterations. Alzheimer's neurofibrillary tangles (NFT) were observed in two cases. Intranuclear fibrillary bundles were identified in four cases. Crystalloid formation in rough endoplasmic reticulum was identified in two cases. Hirano body was observed in a case of parkinsonism with dementia. Axonal swelling was seen in three cases and interpreted as axonal dystrophy, an age-related phenomenon. A basal body, which is unusual in neurons of the central nervous system (CNS), was observed in one case. Lewy bodies were observed in a case of parkinsonism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688634
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  • 25
    Electronic Resource
    Electronic Resource
    A quantitative and ultrastructural study of substantia nigra and nucleus centralis superior in Alzheimer's disease (1985)
    Springer
    Acta neuropathologica 68 (1985), S. 218-223 
    Details
    ISSN: 1432-0533
    Keywords: Alzheimer's disease ; Electron microscopy ; Substantia nigra ; Nucleus centralis superior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In four patients with presenile Alzheimer's disease (AD) and three age-matched controls a quantitative study of neurons and neurofibrillary tangles (NFT) in the substantia nigra (SN) and nucleus centralis superior (NCS) was performed. A significant neuronal loss, similar in both nuclei, was found in AD cases, while the incidence of NFT was remarkably higher in NCS. Moreover, no significant correlation between neuronal loss and number of NFT was detected. An electron-microscopic study revealed that the subcortical NFT in NCS are made up of paired helical filaments in spite of their globose round shape.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690198
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  • 26
    Electronic Resource
    Electronic Resource
    Serial section analysis of mouse hepatic peroxisomes (1985)
    Springer
    Anatomy and embryology 172 (1985), S. 21-32 
    Details
    ISSN: 1432-0568
    Keywords: Peroxisomes ; DAB-cytochemistry ; Electron microscopy ; Serial sectioning ; Liver ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructure and organization of mouse hepatic peroxisomes were investigated using serial thin sections and the alkaline diaminobenzidine technique for visualization of the peroxidatic activity of catalase. Mouse periportal hepatocytes exhibit three classes of peroxisomes which display morphological and cytochemical heterogeneity: 1) large, circular to ovoid organelles containing a crystalline nucleoid, 2) small, circular to elongate, anucleoid particles, and 3) tail-like extensions which are devoid of both catalase activity (only traces of reaction deposits) and a crystaline core. Serial section analysis reveals that these profiles correspond to three diverse interconnecting peroxisomal segments which constitute a highly complex organelle. In particular, the large nucleoid-containing peroxisomal segment exhibits an intimate relationship to the endoplasmic reticulum. However, direct membrane continuities between the two compartments are never observed. With respect to the complex structure of the organelle the following conclusions can be drawn concerning biochemical studies on liver peroxisomes: 1) During homogenization and subcellular fractionation procedures, fragmentation of peroxisomes into particles of different size classes should be expected. 2) These peroxisomal fragments are inhomogeneous with respect to their matrix contents and possess at least one rupture site on their membrane surface. 3) Soluble matrix and, to a lesser degree, membrane components of peroxisomes contribute to the soluble fraction. 4) Crude microsomal fractions are regularly contaminated by peroxisomal membrane fragments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318940
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  • 27
    Electronic Resource
    Electronic Resource
    An ultrastructural study of meconium corpuscles in human foetal colon (1985)
    Springer
    Anatomy and embryology 171 (1985), S. 373-376 
    Details
    ISSN: 1432-0568
    Keywords: Meconium corpuscles ; Apoptosis ; Foetal intestine ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In human foetal colon meconium corpuscles were observed in the colonic epithelium during the stage of secondary lumina development and enlargement. Transmission electron microscopy of these specimens revealed inclusion bodies in the superficial and deeper layers of the epithelium. Many of the membrane-bounded inclusion bodies contained well-preserved organelles and some inclusions contained nuclear fragments. There was evidence of nuclear fragmentation with condensed chromatin arranged in crescentic caps. The ultrastructural observations are typical of apoptosis, a mode of cell death first described in 1972 by Kerr and colleagues. Thus, meconium corpuscles are apoptotic bodies found as a result of the deletion of healthy normal cells during the reshaping and development of organs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00347026
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  • 28
    Electronic Resource
    Electronic Resource
    On the development of the pyramidal tract in the rat (1985)
    Springer
    Anatomy and embryology 172 (1985), S. 195-204 
    Details
    ISSN: 1432-0568
    Keywords: Pyramidal tract ; Growth cones ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An electron microscopic study has been made of the tip of the growing pyramidal tract in the rat. This part of the developing bundle, designated as the growthzone, has been examined at the levels of the medulla oblongata and the third spinal segment at embryonic day 20 and on the day of birth, respectively. The tip of the pyramidal tract contains, apart from axons, numerous larger profiles. An analysis of serial sections revealed that these represent either growth cones or preterminal periodic varicosities. In the growth cones of the corticospinal axons three zones can be distinguished: a proximal “tubular”, an intermediate ”vesicular-reticular” and a distal “fine-granular” zone. As distinct from the classical descriptions the corticospinal growth cones end in a single or, less frequently, in two more or less parallel filopodia. None of the growth cones analyzed in this study showed multiple filopodia radiating from the terminal expansion as observed at the end of growing axons in tissue cultures and in developing spinal fibre tracts of nonmammalian vertebrates. As regards the varicosities, most of these structures are characterized by a light cytoplasmic density. Others, however, contain a denser cytoplasm, closely resembling that of the vesiculo-reticular part of growth cones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00319602
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  • 29
    Electronic Resource
    Electronic Resource
    Glial proliferation in the irradiated rat spinal cord (1985)
    Springer
    Acta neuropathologica 68 (1985), S. 169-172 
    Details
    ISSN: 1432-0533
    Keywords: Astroglia ; Oligodendroglia ; Gliogenesis ; Developing spinal cord ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The identity of mitotic cells in the ventral half of the irradiated spinal cord in 13-day-old rats was studied by light and electron microscopy. At this post-irradiation interval, astrocytes as well as oligodendrocytes are markedly reduced in both gray and white matter, and few myelin sheaths are present. Earlier studies showed incorporation of3H-thymidine into cells identified light-microscopically as neuroglia. In the present study, a number of mitotic cells were identified in thick plastic sections. When adjacent thin sections were examined by electron microscopy, these mitotic cells were identified ultrastructurally as astroglia on the basis of the bundles of filaments in their cytoplasm and the irregular outline of the cell body and its processes. It is apparent from this study that astroglia proliferate prior to the delayed myelination that occurs later in the glial cell deprived ventral irradiated cord.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688641
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  • 30
    Electronic Resource
    Electronic Resource
    Accumulation of amyloid in pituitary adenomas (1985)
    Springer
    Acta neuropathologica 68 (1985), S. 87-92 
    Details
    ISSN: 1432-0533
    Keywords: Pituitary neoplasm ; Anterior pituitary hormone ; Amyloid ; Electron microscopy ; Bromocriptine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The accumulation of amyloid in pituitary adenomas was examined in relation to the types of adenoma and the effect of bromocriptine treatment. Amyloid had accumulated in 34 of 48 adenomas (71%). The occurrence in prolactin-secreting adenomas and growth hormone-secreting adenomas was 79%, respectively, while that in non-functioning adenomas was 50%. Treatment with bromocriptine enhanced the occurrence and extent of the amyloid accumulation in prolactin- or growth hormone-secreting adenomas. Electron microscopy revealed the initial appearance of the amyloid fibrils in the smooth endoplasmic reticulum and a possible sequential process of their release from the cells. The presence of secretory granules in vesicles containing amyloid fibrils and their simultaneous release with amyloid fibrils suggested that degradation of secretory granules was involved in the formation of amyloid.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688628
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  • 31
    Electronic Resource
    Electronic Resource
    Blood-nerve barrier studies in experimental allergic neuritis (1985)
    Springer
    Acta neuropathologica 68 (1985), S. 101-109 
    Details
    ISSN: 1432-0533
    Keywords: Experimental allergic neuritis ; Blood-nerve barrier ; Evans blue-albumin ; Horseradish peroxidase ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The integrity of the blood-nerve barrier (BNB) was studied during the development of experimental allergic neuritis (EAN). Lewis rats immunized with bovine nerve or myelin plus complete Freund's adjuvant developed histological lesions of EAN in nerve roots by 10–12 days and in sciatic nerves by 12–14 days. Evans blue-albumin (EBA) and horseradish peroxidase (HRP) were injected i.v. 1 h prior to killing on days 6–18. Perivascular and diffuse endoneurial leakage of the tracers was seen in nerve roots by 10–12 days post immunization (p.i.) and in sciatic nerves by 12–14 days. This coincided with the appearance of endoneurial infiltration with inflammatory cells and endoneurial proteinaceous edema at a time when Schwann cell and myelin changes were still minimal. Therefore, an alteration in BNB permeability occurs early in EAN, coincident with inflammatory cell infiltration. This could be an expression of delayed hypersensitivity, yet it would also facilitate the entry of anti-myelin antibodies into the endoneurium where they could initiate demyelination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688630
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  • 32
    Electronic Resource
    Electronic Resource
    Early changes in experimental denervated rat gastrocnemius muscle (1985)
    Springer
    Acta neuropathologica 67 (1985), S. 114-120 
    Details
    ISSN: 1432-0533
    Keywords: Image analysis ; Morphometry ; Rat muscle ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Computer-aided image analysis of EM images reveals important morphometric alterations after only 10 days of rat gastrocnemius denervation. The increasing importance of early quantitative changes in human diagnostics is stressed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688131
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  • 33
    Electronic Resource
    Electronic Resource
    Myxoid meningioma: Histochemistry and electron microscopy (1985)
    Springer
    Acta neuropathologica 68 (1985), S. 80-82 
    Details
    ISSN: 1432-0533
    Keywords: Meningioma ; Histochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two meningiomas were investigated that consisted largely of myxoid tissue. Staining with Alcian blue and incubation with staphylococcal, Streptomyces or testicular hyaluronidase revealed that the matrix of the myxoid tissue contained hyaluronic acid and chondroitin sulphate. Special fixation was used for ultrastructural preservation of the myxoid matrix, and its ultrastructural appearance was that of thse glycosaminoglycans. The previous appellations of microcystic or vacuolated meningioma applied to this type of meningioma relate apparently to poor preservation of myxoid tissue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688961
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  • 34
    Electronic Resource
    Electronic Resource
    Transplantation of fetal lateral geniculate nucleus to the occipital cortex: connectivity with host's area 17 (1985)
    Springer
    Experimental brain research 58 (1985), S. 473-489 
    Details
    ISSN: 1432-1106
    Keywords: Transplantation ; Visual cortex ; Lateral geniculate nucleus ; Electron microscopy ; Connectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The developing lateral geniculate complex was excised from fetal albino rats at 18 days of gestation and implanted into the occipital cortex of host animals at 5 days of postnatal age. Groups of host animals were sacrificed at 10, 20 and 30 days following this procedure. The transplant tissue of selected animals was stereotaxically lesioned 2 days prior to scheduled sacrifice and their brains subjected to either Fink-Heimer or electron microscopic analysis of the distribution and density of degenerating efferents from the transplant. The remaining animals were analysed by means of Bodian, Golgi-Cox or electron microscopic techniques. Transplanted neurons displayed typical dendritic branching patterns of geniculate relay neurons by 20 days following implantation. Intrinsic neurons, characterized by a small ovoid soma and two main stem dendrites, only became evident in transplant tissue by 30 days and were much reduced in number. Synapses developed by 10 days and rapidly increased in number by 20 and 30 days. Most complexes were simple axo-dendritic, asymmetric junctions. Multiple serial and reciprocal complexes, as well as the characteristic glomerular complex, failed to appear. Analysis of Bodian stained material revealed a dense network of fibers coursing about the transplant. Distinct bundles of these fibers were observed extending from the medial edge of the transplant into area 17 by 20 days following implantation. A Fink-Heimer analysis of animals whose transplants were stereotaxically lesioned revealed degeneration in Layers II–VI of the primary visual cortex but the majority of these fibers terminated within the lateral two-thirds of Layer IV. Few degenerated fibers could be found in the underlying white matter indicating that efferents from the transplant found their way to their “correct” target zone by growing through a complex neuropil which provided minimal physical substrates to guide such growth. Most of the contacts formed by these fibers were simple junctions along the shafts of dendrites with a wide range in diameter. It is concluded that the nearby host visual neurons, which are the correct target cells for the afferents arising in the transplant, induced a directed growth of these fibers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00235864
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  • 35
    Electronic Resource
    Electronic Resource
    Establishment of synaptic connections between explants of embryonic neural tissue in culture: experimental ultrastructural studies (1985)
    Springer
    Experimental brain research 57 (1985), S. 337-347 
    Details
    ISSN: 1432-1106
    Keywords: Co-cultured explants ; Transection of fibre bundles ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of synaptic interconnections between co-cultured explants of central and peripheral nervous tissue from chick embryos has been investigated by light and electron microscopy. Two sets of co-cultured explants were used: (a) dorsal root ganglion (DRG) and spinal cord and (b) retina and tectum. Both sets of co-cultured explants became linked by bundles of fibres but the most consistent results were obtained with the DRG-spinal cord explants. Thus axons from the DRG extended large distances across the culture substrate to reach and enter mainly the dorsal horn region of the spinal cord explants. In contrast retina-tectum links were less frequently established and were less extensive, possibly because there are fewer cells in retinal explants capable of establishing contacts in tectal explants than there are cells in DRG explants capable of establishing contacts in the spinal cord. In order to distinguish between synapses involving only neuronal elements within an expiant and those involving ingrowing fibres, fibre bundles linking adjacent explants were transected and the preparations fixed two to six hours later. Electron microscope study of such cultures revealed degenerating neurites and terminals in the spinal cord explants receiving DRG fibres but none in the corresponding DRG explants. Retinal explants contain numerous synapses of many types but degenerating terminals could not be found within the retinal explants after nerve fibre transections. Degenerating neurites and terminals were found within tectal explants but they were fewer and more difficult to locate than those found within spinal cord explants. The reasons for such differences are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00236539
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  • 36
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    Electronic Resource
    Absorption of iohexol from cerebrospinal fluid to blood: pharmacokinetics in humans (1985)
    Springer
    Neuroradiology 27 (1985), S. 172-175 
    Details
    ISSN: 1432-1920
    Keywords: Iohexol ; contrast media ; CSF ; pharmacokinetics ; myelography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The absorption of iohexol from the subarachnoid space was studied in 9 patients. Serum concentrations of iohexol were measured for a minimum of 24 hours after injection. Peak serum concentrations were observed after 2.2 (1.7–2.7) hours. The half-life of the subsequent decrease in serum concentrations was 3.4 (2.2–7.9) hours. Concentrations of iohexol in cerebrospinal fluid were 0.29–4.3 mg I/ml 24 hours after injection (7 patients). Serum and cerebrospinal fluid concentrations of iohexol are comparable to those found after intrathecal injection of metrizamide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00343791
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  • 37
    Electronic Resource
    Electronic Resource
    Influences of endurance training on the ultrastructural composition of the different muscle fiber types in humans (1985)
    Springer
    Pflügers Archiv 403 (1985), S. 369-376 
    Details
    ISSN: 1432-2013
    Keywords: Mitochondria ; Intracellular lipid ; Electron microscopy ; Morphometry ; Histochemistry ; Muscle biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate changes in the ultrastructure of the different muscle fiber types induced by endurance training ten sedentary subjects (five women and five men) were exercised on bicycle ergometers 5 times a week for 30 min. After 6 weeks of training there were significant changes in $$\dot V_{{\text{O}}_{{\text{2max}}} } $$ (+14%), in the percentage of type I (+12%) and type IIB fibers (−24%) as well as in the volume densities of mitochondria. The latter increased 35% in type I, 55% in type IIA and 35% in type IIB fibers. The relative increase in subsarcolemmal mitochondria was larger than in interfibrillar mitochondria in all fiber types. There was also a significant increase in the volume density of intracellular lipid in type II fibres. It is concluded that high intensity endurance training leads to an enhancement of the oxidative capacity in all muscle fiber types.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00589248
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  • 38
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of penbutolol and its metabolites in renal insufficiency (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 215-219 
    Details
    ISSN: 1432-1041
    Keywords: penbutolol ; renal impairment ; beta-adrenoceptor blocking agents ; metabolism ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of penbutolol, its 4-hydroxylated metabolite and of their conjugates was studied in hypertensive patients with various degrees of renal impairment. A single oral dose of penbutolol 40 mg, was rapidly absorbed after a lag-time of 0.34 h. Its plasma concentration reached a maximum after 0.84 h and then declined bi-exponentially, with an apparent elimination half-life of 21.8 h. The hydroxylation of penbutolol was negligible and conjugation was of major importance for its elimination. Consequently, the kinetics of unchanged penbutolol were not altered by renal impairment. The 48 h-urinary excretion of penbutolol and its metabolites reached 13–14% of the administered dose, which is consistent with extensive metabolism of the drug. After treatment for 30 days with penbutolol 40 mg/d there was no accumulation of the parent drug but the concentration of its conjugates was increased. It is concluded that the dose of penbutolol need not be changed in patients with mild renal insufficiency, 4-hydroxypenbutolol is unlikely to participate in the anti-hypertensive effect of the drug, due to its low concentrations, and biotransformation of penbutolol may be enhanced during chronic treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547425
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  • 39
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of fenfluramine and norfenfluramine in volunteers given d- and dl-fenfluramine for 15 days (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 221-224 
    Details
    ISSN: 1432-1041
    Keywords: fenfluramine ; norfenfluramine ; isomers ; pharmacokinetics ; healthy volunteers ; chronic treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of accumulation and elimination of d- and l-fenfluramine (F) and norfenfluramine (NF) have been studied in 8 young healthy volunteers given daily doses of 60 mg of sugar-coated tablets of 20 mg dl-F hydrochloride (dl-F) t.i.d. and capsules of 15 mg d-F hydrochloride (d-F) b.i.d. for 15 days. Repeated doses of d-F plus l-F gave the same values for the parameters measured as did d-F administered alone. Steady-state concentrations of all compounds were achieved within 4–8 days. The predicted mean steady-state concentrations of d-F and elimination half-lives calculated from the results of a previous single dose study were similar to those measured at steady state in this study, confirming the lack of effect of the drug on hepatic microsomal enzymes and on kinetics after repeated dosing. d-NF concentrations were approximately half those of the parent drug and the half-life was almost twice as long. Steady state concentrations both of L-f and l-NF were consistently about 40–50% higher than of the d-isomers and there was a comparable in the half-life.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547426
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  • 40
    Electronic Resource
    Electronic Resource
    Comparison of the pharmacokinetic profile of metaclazepam in old and young volunteers (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 247-249 
    Details
    ISSN: 1432-1041
    Keywords: metaclazepam ; benzodiazepines ; (KC-2547) ; N-desmethyl-methaclazepam KC-3755) ; pharmacokinetics ; old and young volunteers ; side-effects ; age effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single-centre, open, Phase I-study comparison of the pharmacokinetics of a single dose of metaclazepam 10 mg, a new 1,4-benzodiazepine has been done in 10 older and 20 younger volunteers. No important age-related effect was found on the kinetics of metaclazepam or its N-desmethyl derivative, the principal metabolite in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547431
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  • 41
    Electronic Resource
    Electronic Resource
    Pharmacokinetic study of a paediatric formulation of amoxycillin and clavulanic acid in children (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 235-239 
    Details
    ISSN: 1432-1041
    Keywords: amoxycillin ; clavulanic acid ; pharmacokinetics ; side-effects ; paediatric formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A combination of amoxycillin and clavulanic acid 4:1 was administered to 35 children (aged 2 to 10 years) with infections. The combination was administered orally as a suspension, every 8 h for 5 to 7 days. Sixteen children (aged 2 to 5 years), received 125 mg amoxycillin and 31.25 mg clavulanic acid, and 19 (6 to 10 years) received 250 mg amoxycillin and 62.5 mg clavulanic acid per dose. Following the first dose serum concentrations of amoxycillin and clavulanic acid were determined by microbiological assay. In the younger group receiving the lower dosage (mean: amoxycillin 9.11 mg/kg and clavulanic acid 2.34 mg/kg), the mean peak concentration of amoxycillin was 3.5 mg/l and of clavulanic acid 1.2 mg/l, occurring 1.32 h and 1.39 h, respectively, after administration. In the older group receiving the higher dosage (mean: amoxycillin 12.35 mg/kg and clavulanic acid 3.14 mg/kg) the mean peak serum level of amoxycillin was 4.0 mg/l and of clavulanic acid 1.3 mg/l, occurring 1.43 h and 1.23 h, respectively, after administration. The higher dose per kilogram body weight resulted in a higher peak serum concentration both of amoxycillin and clavulanic acid. The formulation was well tolerated by all the children and no serious side-effects were recorded. Treatment was considered clinically effective in all cases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547429
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  • 42
    Electronic Resource
    Electronic Resource
    Protein binding and disposition of lignocaine in the elderly (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 323-329 
    Details
    ISSN: 1432-1041
    Keywords: lignocaine ; pharmacokinetics ; proteinbinding ; indocyanine green ; ageing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single dose studies were performed in six young and six elderly nonsmokers using lignocaine as a model drug with high intrinsic clearance. Subjects received lignocaine 250 mg orally and 50 mg intravenously in random order and drug concentrations in blood and plasma were measured for up to 8 h after dose. Protein binding was estimated at 37 °C by equilibrium dialysis. Indocyanine green kinetics were also calculated in each individual following 0.15 mg/kg intravenously. Bioavailability of lignocaine was greater in the elderly but there was no apparent difference in the rate of absorption. Intrinsic clearance of lignocaine was lower in the aged. Elimination half-life was longer in the elderly but there was no significant difference in apparent volume of distribution or systemic clearance of lignocaine. Plasma clearance of indocyanine green showed no correlation with systemic lignocaine clearance and was lower in the aged subjects. Blood/plasma lignocaine ratio was less than unity in both groups. Binding of lignocaine to plasma proteins showed concentration-dependence and was higher in the geriatric group. Maximum binding capacity of lignocaine was greater in the elderly but the binding affinity did not significantly change with age. Greater oral bioavailability of drugs like lignocaine may produce higher plasma concentrations in the elderly. Unlike indocyanine green, the systemic clearance of lignocaine was unaltered by age in this group of non-smokers. The protein-binding of lignocaine, like many other basic drugs, is increased in elderly subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544089
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  • 43
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of pefloxacin in renal insufficiency (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 345-349 
    Details
    ISSN: 1432-1041
    Keywords: pefloxacin ; renal insufficiency ; pharmacokinetics ; haemodialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of pefloxacin has been studied after a single intravenous infusion of 8 mg·kg−1 in 15 male patients with various degrees of renal failure. No difference in distribution or elimination of the drug was observed between patients with mild or severe renal impairment. The mean volume of distribution (Vd area) and the mean plasma clearance were 2.03l·kg−1 and 121.3 ml·min−1, respectively. The mean apparent elimination half-life was 13.5 h. These values are close to those observed in healthy subjects. No accumulation of the active N-desmethylmetabolite was observed in cases of severe failure as compared to mild impairment; its apparent elimination half-life was about twice that of the parent drug. The efficacy of a 4 h haemodialysis in 6 additional anuric subjects done to remove pefloxacin from the body was poor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544092
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  • 44
    Electronic Resource
    Electronic Resource
    Ro 31-1118, a new cardioselective β-adrenoceptor antagonist (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 395-399 
    Details
    ISSN: 1432-1041
    Keywords: Ro 31-1118 ; cardioselectivity ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five patients with mild hypertension were given single oral doses of Ro 31-1118 (10, 20, 40, and 80 mg) and placebo in a randomized, double-blind, within-patient study. Plasma concentrations of Ro 31-1118 and supine, standing, exercise, and post-exercise heart rates and blood pressures were measured before and at regular intervals after drug administration. The pharmacokinetic data were consistent with a one-compartment model with first-order absorption and a variable time lag. Peak plasma concentrations and area under curve were linearly related to dose, whereas time to peak concentration, half-time, clearance and apparent volume of distribution were dose-independent. There was a reduction in exercise and post-exercise heart rate of approximately 10% after 10 mg and 20 mg Ro 31-1118, and of approximately 15% after 40 mg and 80 mg. At all doses standing systolic blood pressure was reduced by approximately 5%. A similar fall was seen in exercise and post-exercise systolic blood pressures. There was no substantial effect of Ro 31-1118 on supine or standing heart rates nor on diastolic blood pressure. No adverse effects were reported. It is concluded that Ro 31-1118 has linear pharmacokinetics over the dose range 10–80 mg, and has a weak antihypertensive effect when administered in single doses to patients with mild hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613451
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  • 45
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of amiodarone, desethylamiodarone and other iodine-containing amiodarone metabolites (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 417-423 
    Details
    ISSN: 1432-1041
    Keywords: amiodarone ; desethylamiodarone ; iodine ; pharmacokinetics ; thyroid function ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 23 patients treated with the iodine-containing antiarrhythmic drug amiodarone, the plasma concentrations of amiodarone, desethylamiodarone and iodine have been studied. Besides amiodarone and desethylamiodarone, a pool of iodine-containing substances, NANDAI (non-amiodarone-, non-desethylamiodarone-iodine), was present. At steady state the iodine content of NANDAI amounted to 64% and the iodine content of amiodarone plus desethylamiodarone to 36% of total serum iodine. At steady state 26% of the NANDAI fraction was made up of inorganic iodide, the average plasma concentration of which was at least 40 times above the upper limit of the normal range. The serum elimination half-life of NANDAI of 57–160 days exceeded that of amiodarone (35–68 days) and of desethylamiodarone (31–110 days). At steady state the serum concentration of desethylamiodarone appears to be related to the concentration of amiodarone by a Michaelis-Menten type function, yielding a Km of amiodarone of 2.45 µmol/l and a maximal desethylamiodarone concentration of 3.61 µmol/l.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613455
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  • 46
    Electronic Resource
    Electronic Resource
    Baclofen in the elderly stroke patient its side-effects and pharmacokinetics (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 467-469 
    Details
    ISSN: 1432-1041
    Keywords: baclofen ; stroke ; elderly patients ; pharmacokinetics ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A double blind crossover trial of baclofen against placebo in elderly stroke patients was discontinued because the drug produced an unacceptably high level of drowsiness. In a subsequent study baclofen 10 mg was given orally to 12 elderly stroke patients, and drug concentrations measured from a series of plasma samples. A group of healthy subjects given the same dose in a previous study were used as controls. Elderly patients took longer to achieve peak plasma baclofen concentrations, but healthy controls had higher peak values and eliminated the drug more rapidly; areas under the curve were similar in the two groups. Simulations based on mean data suggest that increased drowsiness in the elderly was probably not due to changes in the drug's pharmacokinetic behaviour.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613463
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  • 47
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of carteolol in relation to renal function (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 461-465 
    Details
    ISSN: 1432-1041
    Keywords: carteolol ; chronic renal failure ; pharmacokinetics ; dosage adjustment ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma levels and urinary excretion of carteolol and its main metabolites 8-hydroxycarteolol and carteolol glucuronide were investigated in 6 healthy subjects and 9 patients with varying degrees of renal impairment following a single oral dose of 30 mg carteolol hydrochloride. In healthy subjects the half-life of carteolol was 7.1 h. 63% of the administered dose was recovered unchanged in urine, and in all 84% was excreted by the kidneys. The renal clearance of carteolol was 255 ml/min. In chronic renal failure (CRF) the terminal half-life was increased to a maximum of 41 h. Both the elimination rate constant and renal clearance were closely related to the creatinine clearance. In CRF the recovery of carteolol and its metabolites from urine was considerably reduced, suggesting that another pathway of drug elimination becomes relevant in renal disease. To avoid an increase in side-effects due to drug accumulation, the dosage of carteolol should be adjusted in relation to the reduction in creatinine clearance. The maintenance dose should be reduced to a half in patients with a creatinine clearance below 40 ml/min and above 10 ml/min. In those with a creatinine clearance of 10 ml/min or less, the dose should be reduced to 1/4.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613462
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  • 48
    Electronic Resource
    Electronic Resource
    Separate and combined effects of nadolol and nifedipine on the cardiac response to exercise (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 113-117 
    Details
    ISSN: 1432-1041
    Keywords: nadolol ; nifedipine ; tachycardia ; cardiovascular response ; healthy volunteers ; pharmacokinetics ; exercise heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a placebo controlled exercise protocol using healthy volunteers the effects of nadolol 80 mg and 160 mg orally and of nadolol 80 mg during treatment with nifedipine 20 mg 8 hourly were compared. Resting systolic and diastolic blood pressures were reduced by both nifedipine (p〈0.05) and nadolol (p〈0.01) acting alone. An unexpected finding was that nifedipine alone significantly inhibited exercise tachycardia (p〈0.01) (8 to 12 h post dose). Predictably both doses of nadolol produced significant reduction in exercise tachycardia which was still apparent at 24 h. There was a linear relationship between log10 plasma nadolol concentration and reduction in exercise heart rate. The combined inhibitory effects of nifedipine and nadolol 80 mg on exercise heart rate showed partial additivity but did not summate. There was no pharmacokinetic interaction between the 2 drugs. The inhibition of exercise tachycardia by nifedipine, not previously documented, is consistent with an effect of the drug on the sinus node, as has been reported in in-vitro studies, and may contribute to the drugs efficacy in angina.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609676
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  • 49
    Electronic Resource
    Electronic Resource
    Pharmacokinetic study of IV infusions of adriamycin (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 205-212 
    Details
    ISSN: 1432-1041
    Keywords: adriamycin ; cancer patients ; infusion ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma pharmacokinetics of adriamycin has been studied in 21 cancer patients (31–85 years old) without liver tumours after short (3.00 min) and prolonged (45 min-16h) i.v. infusions. The area under the plasma concentration-time curve and the maximum plasma concentration compensated for dose variation showed a more than 3-fold individual variation. The pharmacokinetics of adriamycin was linear. There was no pharmacokinetic rational for variation of the dose with the age of the patients. There was good agreement between the measured plasma concentration-time curves for prolonged infusions and curves predicted from pharmacokinetic data from short term infusions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609693
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  • 50
    Electronic Resource
    Electronic Resource
    Effect of concomitant food intake on absorption kinetics of erythromycin in healthy volunteers (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 231-233 
    Details
    ISSN: 1432-1041
    Keywords: erythromycin ; pharmacokinetics ; steady-state ; food effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady state absorption of erythromycin from enteric-coated pellets of erythromycin base was compared with that from enteric-coated tablets in a randomized, two-way cross-over study in 24 healthy adult volunteers. A higher mean individual peak concentration (p〈0.01), and a greater mean area under the serum concentration-time (0–8 h) curve (AUC,p〈0.01) was produced by the enteric-coated pellets, when the preparations were administered 1 hour before breakfast. No significant differences in the kinetic parameters between the two preparations were observed when they were taken during a non-standardized breakfast, as concomitant food intake was found to reduce both the peak levels and the AUC-values (p〈0.01) produced by the pelleted preparation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609699
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  • 51
    Electronic Resource
    Electronic Resource
    Single-dose and steady-state pharmacokinetics of piroxicam in elderly vs young adults (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 305-309 
    Details
    ISSN: 1432-1041
    Keywords: piroxicam ; pharmacokinetics ; geriatrics ; renal insufficiency ; drug safety ; non-steroidal anti-inflammatory drugs ; osteoarthritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Age-dependent changes in pharmacokinetics are considered a possible factor contributing to a higher risk of side-effects from drug treatment in the elderly. However, very little is known about the kinetics and metabolism of most NSAI agents in geriatric subjects. In a prospective age-comparison study, the single dose and steady-state pharmacokinetics of piroxicam 20 mg once daily were determined in 44 subjects ranging in age from 30 to 80 years. Plasma concentrations, elimination half-life, AUC, and volume of distribution were not influenced by age or sex and were in agreement with previously reported results in young adults. Pharmacokinetic parameters in 18 patients with evidence of mild or moderate renal impairment at study entry were not different from those in patients without impairment. Based on this and other studies, elderly patients receiving the recommended dose of piroxicam are not exposed to undue risk related to pharmacokinetic considerations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543328
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  • 52
    Electronic Resource
    Electronic Resource
    Effect of probenecid on isofezolac kinetics (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 433-437 
    Details
    ISSN: 1432-1041
    Keywords: isofezolac ; probenecid ; pharmacokinetics ; anti-inflammatory drug ; drug interaction ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The interaction between isofezolac and probenecid has been studied with the aid of a specific HPLC assay for isofezolac in plasma and urine. 8 healthy adult volunteers received a single 40 mg oral dose of isofezolac before and after 3 days of loading with 0.5 g probenecid t.i.d. There was an increase in the maximum plasma isofezolac concentration from 2.44 to 3.38 µg · ml−1 when probenecid was given. The AUC of isofezolac in plasma increased from 6.73 to 11.28 µg · h · ml−1. After the last dose in a 7 day treatment with 40 mg isofezolac t.i.d., there was an increase in the maximum plasma isofezolac level from 2.84 to 4.96 µg · ml−1 when probenecid was given. The rate of absorption of isofezolac was not affected. An increase in the AUC of isofezolac in plasma was observed from 11.74 to 26.34 µg · h · ml−1. The major effect of probenecid on isofezolac metabolism was a 50% reduction in total isofezolac (free+conjugates) excreted inurine. Because of this interaction, patients given isofezolac combined with probenecid will have a higher steady-state plasma level of isofezolac than when probenecid is not administered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544363
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  • 53
    Electronic Resource
    Electronic Resource
    Influence of renal failure on the kinetics of zimeldine and norzimelidine (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 453-456 
    Details
    ISSN: 1432-1041
    Keywords: zimeldine ; norzimelidine ; pharmacokinetics ; renal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of zimeldine (Z) and its demethylated metabolite, norzimelidine (NZ), were determined after administration of a single 200 mg oral dose of Z to 6 healthy volunteers (Group I), and to patients with mild (Group II) and severe renal failure (Group III). Z and NZ concentrations were assayed by HPLC in serial plasma and urine samples over 6 days following the dose. In Group I Z was rapidly absorbed and metabolized into NZ, and then the plasma concentrations declined with apparent elimination half-lives of 8.4 h and 24.9 h for Z and NZ respectively, whilst the renal clearance of both compounds was low, Z 15.7 ml/min and NZ 33.0 ml/min. The plasma level of Z differed little between Groups I and III, but the area under the curve was significantly higher in Group III than in Group I subjects (AUC0–144=17.3 and 6.8 µmol·l−1·h, respectively). Severe renal failure did not affect the peak plasma concentration of NZ but it did significantly increase peak time, apparent elimination half-life, and the area under the plasma concentration curve. A significant inverse relationship was found between renal clearance of NZ and plasma creatinine. Since NZ is as pharmacologically potent as Z, the results suggest that the dose of Z should be reduced in patients with severe renal insufficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544366
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  • 54
    Electronic Resource
    Electronic Resource
    Evaluation of infusion regimens for thiopentone as a primary anaesthetic agent (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 543-552 
    Details
    ISSN: 1432-1041
    Keywords: thiopentone ; anaesthesia ; intravenous anaesthesia ; multi-stage infusion ; exponential infusions ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Several multi-stage infusion regimens and a computer controlled exponentially decreasing infusion regimen were evaluated in twelve patients undergoing head and neck surgery or neurosurgery. Thiopentone dosage was based on the mean of pharmacokinetic parameter values from the literature and adjusted for each patient's lean body mass in order to rapidly achieve a predetermined plasma thiopentone concentration of 15 or 20 µg/ml in the period following the initial bolus dose to induce anaesthesia. Anaesthesia was satisfactory in all cases. Plasma thiopentone concentrations were maintained between 10–20 µg/ml during infusion in the five patients who received either a four or five stage infusion and in the six patients who received the exponential infusion, but not in the single patient who received a two-stage infusion. The mean recovery time was 111 min. The plasma concentrations of total and unbound thiopentone at awakening showed little intersubject variability, despite considerable differences in total dose and duration of infusion, suggesting the absence of acute tolerance to the drug. Plasma clearance of total thiopentone correlated strongly with calculated lean body mass and to a lesser extent with total body weight suggesting that lean body mass, in particular, should be an accurate predictor of thiopentone maintenance dose requirements. This study shows that it is feasible to use thiopentone as a primary anaesthetic agent during surgery by administering the drug either as an exponentially decreasing infusion or as an infusion comprising 4 or 5 stepwise decreasing rates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544065
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  • 55
    Electronic Resource
    Electronic Resource
    The pharmacokinetics and haemodynamics of BTS 49465 and its major metabolite in healthy volunteers (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 659-664 
    Details
    ISSN: 1432-1041
    Keywords: BTS 49465 ; hypertension ; pharmacokinetics ; blood pressure effect ; heart rate effect ; side-effects ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic and haemodynamic effects of a 200 mg oral dose of BTS 49465 (7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) were investigated in a double-blind placebo controlled study. BTS 49465 was rapidly absorbed and cleared from the systemic circulation with a half-life of 1.6 h by oxidation to the sulphone metabolite. The metabolite was cleared with a half-life of 37.6 h. Saliva concentrations of both BTS 49465 and its metabolite correlated well with the plasma concentrations. Compared to placebo, BTS 49465 produced statistically significant reductions in blood pressure and increases in heart rate both supine and after a 60° head up tilt. The time course of the haemodynamic changes suggested that the sulphone metabolite contributed to the overall hypotensive response. Plasma Renin Activity was only marginally elevated and there was no evidence of acute fluid retention. BTS 49465 was well tolerated in terms of haematological and biochemical parameters and subjective side-effects.
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    URL: http://dx.doi.org/10.1007/BF00607911
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  • 56
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    Electronic Resource
    Antipyrine metabolite formation and excretion in patients with chronic renal failure (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 589-595 
    Details
    ISSN: 1432-1041
    Keywords: antipyrine ; chronic renal failure ; drug metabolism ; metabolism ; cumulation ; renal excretion ; pharmacokinetics ; clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In the present study the influence of chronic renal insufficiency on antipyrine clearance, metabolite formation and excretion was investigated in 8 patients. After oral administration of antipyrine, the parent compound, its metabolites and their conjugates were assayed in plasma and urine. Besides the parent drug, 3-hydroxymethylantipyrine (HMA) was present in plasma in the free and conjugated forms, whereas 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) were found only in the conjugated form. The same was true for urine. The plasma concentrations of these metabolites are too low to be measured in subjects with normal renal function. Plasma antipyrine clearance in the patients was in the same range as in healthy subjects. Investigation of metabolite kinetics, however, revealed that the rate of formation of NORA was preferentially decreased, whereas that of OHA and HMA were unaltered. Renal clearance of the metabolites of antipyrine was severely impaired in patients with renal insufficiency, and the resulting accumulation made it possible for the first-time to measure the antipyrine metabolites in plasma. Mean residence times of metabolites were longer than that of the parent compound. Renal clearances of the conjugates were correlated with the creatinine clearance, but were somewhat higher. Renal clearance of free HMA was lower and was also correlated with creatinine clearance. The mean clearance for glucuronidation of HMA was 93.1 ml/min. The results suggest that in healthy subjects Phase I metabolism is the rate-limiting step in the elimination of antipyrine, which is essential for its application as a model drug in metabolism studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544072
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  • 57
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    Electronic Resource
    Acute and subacute effects on psychomotor performance of femoxetine alone and with alcohol (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 641-647 
    Details
    ISSN: 1432-1041
    Keywords: Femoxetine ; alcohol interaction ; psychomotor performance ; pharmacokinetics ; amitriptyline ; plasma 5HT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects on human psychomotor performance of femoxetine (FEMO), a 5-hydroxytryptamine-selective antidepressant, alone and in combination with alcohol (EtOH) were compared with those of amitriptyline (AMI) and placebo in a controlled double-blind crossover trial in 11 student volunteers. Objective measurements (body sway, choice reaction, flicker fusion, tracking, nystagmus, digit symbol substitution, backwards recall) and subjective self-assessment (visual analogue scales, reporting of side-effects) were done after single doses of FEMO, AMI and placebo, and subacute administration of FEMO and placebo. Single doses of 200 mg FEMO did not impair psychomotor performance, but 50 mg AMI did so in several respects. AMI but not FEMO increased the objective and subjective effects of EtOH. After FEMO 600 mg/d for 10 days almost no objective difference from placebo was noted, although mild sedation at home was reported as a side-effect. FEMO either did not increase or slightly decreased the effect of EtOH on reactive and co-ordination skills. The plasma concentrations of FEMO varied widely from 0 to 156 ng/ml, as in previous clinical trials but reduced a blood 5-hydroxytryptamine concentration in each subject indicating an effect of FEMO on serotoninergic mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607908
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  • 58
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and metabolic effects of glibenclamide and glipizide in type 2 diabetics (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 697-704 
    Details
    ISSN: 1432-1041
    Keywords: glibenclamide ; glipizide ; pharmacokinetics ; metabolic effects ; Type 2 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifteen Type 2 diabetics were treated for 4-week periods with once daily (10 mg) glibenclamide, glipizide and placebo according to a double-blind cross-over protocol. Post-dose glipizide concentrations were three times higher than those of glibenclamide, due to the incomplete bioavailability of the latter. On the other hand, pre-dose drug levels were similar, as an expression of the slower absorption and/or elimination of glibenclamide. Both active treatments reduced postprandial blood glucose concentrations and 24-hour urinary glucose excretion to a similar degree, but fasting blood glucose concentrations were slightly lower during glibenclamide treatment. Both active treatments enhanced fasting and postprandial insulin and C-peptide concentrations, the C-peptide response being greater after glipizide than after glibenclamide. Plasma glucagon and GIP concentrations were not significantly affected. Insulin sensitivity was increased by glibenclamide but not by glipizide. Neither therapy affected insulin binding to erythrocytes. It appears that both glibenclamide and glipizide improved glucose metabolism by sustained stimulation of insulin secretion, which was most pronounced with glipizide. Only glibenclamide improved insulin sensitivity and was slightly more active than glipizide on fasting blood glucose levels. The differences may be consequences of the pharmacokinetics, but differences in pharmacodynamics cannot be excluded.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607919
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  • 59
    Electronic Resource
    Electronic Resource
    Pharmacodynamic and pharmacokinetics of BW 825C: A new antihistamine (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 197-204 
    Details
    ISSN: 1432-1041
    Keywords: triprolidine ; BW 825C ; pharmacokinetics ; pharmacodynamics ; sedation ; intradermal histamine ; human performance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The new H1-receptor antagonist BW 825C and triprolidine (2.5 and 5 mg) were administered to 12 healthy male volunteers in a double blind placebo controlled, balanced, crossover design. Histamine antagonism was measured by assessment of flare and weal areas after intradermal injection of histamine. The 2 compounds were approximately equipotent in blocking the flare and weal response to intradermal histamine and had a similar duration of action. Triprolidine impaired performance of vigilance and reaction time (p〈0.05) compared with placebo while BW 825C did not. Drowsiness measured using visual analogue scales followed both triprolidine treatments, but not BW 825C. BW825C had a plasma half-life (t1/2) of 1.7±0.2 h and triprolidine of 4.6±4.3 h. The peak plasma level of BW 825C was approximately 6 times that of triprolidine. It was concluded that BW 825C might be a clinically active H1-antagonist with reduced sedative side-effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609692
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  • 60
    Electronic Resource
    Electronic Resource
    Food reduces the rate but not the extent of the absorption of theophylline from an aqueous solution (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 225-227 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; absorption ; food intake ; aqueous solution ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of food on the rate and extent of absorption of theophylline was studied in healthy adults given a single dose of theophylline (aqueous solution of choline theophyllinate containing 270 mg of theophylline) in the evening either on an empty stomach or together with supper. Food appeared to decrease the absorption rate of theophylline significantly, tmax being prolonged from 1.34 h (mean) to 4.40 h and cmax decreased from 7.82 mg·l−1 to 5.47 mg·l−1. The area under the plasma concentration-time curve (AUC) after drug intake with supper was slightly but not significantly smaller, indicating that theophylline (as a solution of choline theophyllinate) can be taken together with food without substantial loss of the quantity of drug absorbed. The elimination rate was not influenced by concomitant intake of supper.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609697
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  • 61
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and plasma-concentration-effect relationships of prenalterol in cardiac failure (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 397-403 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; cardiac failure ; pharmacokinetics ; concentration-effect relationships
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prenalterol was administered as an intravenous infusion at three incremental rates (60, 120 and 240 nmol/min) to five patients with severe cardiac failure. Haemodynamic, hormonal and metabolic variables were measured at the same time as plasma prenalterol concentrations, and the pharmacokinetics of the drug were studied by following plasma concentrations and urinary excretion during and after the infusion. Concentration-dependent increases in cardiac index, stroke index and stroke work index were observed without increases in arterial pressure, heart rate or myocardial oxygen demand. The reninangiotensin-aldosterone system was stimulated, although the extent of stimulation varied among patients. No strong correlations were found between the logarithm of the plasma prenalterol concentration and effect. Plasma clearance of the drug was lower in cardiac patients than in normal volunteers, but a large decrease in renal clearance was partially balanced by an increase in nonrenal clearance. Over the observed range of concentrations, no deviation from linearity was evident, and plasma concentrations of about 150 nmol/l were effective in improving cardiac function without significant side-effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544357
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  • 62
    Electronic Resource
    Electronic Resource
    Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 425-428 
    Details
    ISSN: 1432-1041
    Keywords: caffeine ; oral contraceptives ; pharmacokinetics ; elimination half-life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of chronic (〉3 months) administration of low-dose oestrogen-containing (〈50 µg oestrogen) oral contraceptives (OCS) on the pharmacokinetics of caffeine has been examined in a treated females matched with 9 non-smoking, drug-free, healthy control females of similar age, weight and ethnic origin. Each subject received 162 mg caffeine base orally after an overnight fast. OCS subjects had a prolonged elimination half-life of caffeine, (mean 7.88 h vs 5.37 h in the controls). This was the result of marked impairment of the plasma clearance of caffeine (1.05 vs 1.75 ml/min/kg, respectively) with no change in apparent volume of distribution (0.685 in OCS vs 0.750 l/kg in the control group). The absorption parameters determined were peak plasma caffeine concentration (3.99 vs 4.09 µg/ml) and time to peak concentration after drug administration (1.52 vs 0.79), which was moderately prolonged in OCS users. Thus, caffeine clearance, previously reported to be a specific marker of cytochrome P-448 activity in man, is decreased by chronic OCS use. This suggests that OCS may cause significant impairment of this enzyme activity as assessed in vivo. With chronic caffeine consumption, OCS users are predicted to have an increased steady-state plasma caffeine concentration as compared to non-OCS users.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544361
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  • 63
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    Electronic Resource
    Personality and theophylline pharmacokinetics (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 429-431 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; personality measures ; pharmacokinetics ; volunteers ; patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirteen volunteers received an iv dose of theophylline followed by blood sampling for 8 h to calculate pharmacokinetic parameters. Ten patients with asthma undergoing chronic dosing with slow release aminophylline underwent 12 h of blood sampling to calculate theophylline clearance. Both groups completed an Eysenck Personality Inventory (EPI) from which was derived scores for neuroticism (N) and extroversion (E). Using multiple regression analysis no independent effect of either N or E score on theophylline clearance or half-life could be demonstrated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544362
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  • 64
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of acetohydroxamic acid in patients with staghorn renal calculi (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 439-445 
    Details
    ISSN: 1432-1041
    Keywords: acetohydroxamic acid ; staghorn renal calculi ; pharmacokinetics ; 14C-labeled drug ; acetamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetohydroxamic acid (AHA), a bacterial urease inhibitor, has been recently approved by the United States Food and Drug Administration as a potential drug for the successful treatment of patients with infection induced staghorn renal calculi. The present study was designed to evaluate the disposition of 14C-AHA following oral administration to patients. The results of the study, while in a limited number of patients, indicate that upon oral administration, AHA is very rapidly absorbed from the gastrointestinal tract. Evaluation of urinary excretion data suggests that patients with compromised renal function have low recoveries of AHA in the urine. These data are supported by a strong linear correlation between creatinine clearance and AHA elimination. Acetamide and CO2 are identified as the two major metabolites of AHA in man. CO2 is eliminated in the breath and accounts for 20–45% of the administered dose, while acetamide is eliminated in the urine and accounts for only 9–14% of the administered dose. The remaining dose is eliminated as intact AHA in the urine (19–48%). Saliva concentrations of total radioactivity depict a strong positive correlation with their respective plasma concentrations. Parameter estimates from 14CO2 concentrations in breath as a function of time data closely correspond to the pharmacokinetic parameters of AHA in patients indicating that CO2 may be a primary metabolite derived directly from AHA rather than a secondary metabolite formed by the metabolism of an intermediate product. Upon multiple dose administration of AHA, there is the potential for significant accumulation of acetamide due to its relatively long half-life.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544364
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  • 65
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    Electronic Resource
    Clinical pharmacokinetics of 6-hour infusion of high-dose methotrexate. Preliminary trial of monitoring high infusion doses (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 457-462 
    Details
    ISSN: 1432-1041
    Keywords: methotrexate ; osteosarcoma ; high parenteral dose ; pharmacokinetics ; drug monitoring ; computer prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Methotrexate (MTX) in serum was measured by RIA in 12 cancer patients receiving high doses of MTX (2 to 8 g/m2) in 6 hour infusions 69 treatments were studied. The peak serum level was proportional to the dose administered and was always greater than 10−4 M. 2 elimination phases were seen: the first had a mean half-life of 2.36 h and the second a mean half-life of 16.14 h. 24 hours after beginning the infusions there were very large variations in individual serum concentrations of MTX, from 2.4 10−6 M to 1.9 10−5 M by 24 h after 8 g/m2. To control these variations, a mathematical model for prediction of the individual pharmacokinetic pattern of a 6 hour-infusion of high-dose MTX by kinetic analysis of a low-test dose is proposed. A program was created for an Apple III computer using toxic and therapeutic serum levels of MTX selected by the clinician. The computer program is adaptable to any infused substance for variable infusion times, thus introducing new advances over existing methods.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544367
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  • 66
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of tocainide in patients with severe renal failure (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 665-670 
    Details
    ISSN: 1432-1041
    Keywords: tocainide ; renal failure ; pharmacokinetics ; oral dosing ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma levels of tocainide have been followed after oral administration of 600 mg p.o. to 20 patients with renal failure due to various causes, and to 8 healthy controls. The peak plasma concentrations in the patients with pyelonephritis (3.80 µg/ml) and interstitial nephritis (3.74 µg/ml) but not in those with glomerulonephritis (3.17 µg/ml) differed from that in healthy volunteers (3.24 µg/ml). The renal clearance of tocainide was well correlated with the endogenous creatinine clearance and was dependent on urine pH. No difference in renal clearance was observed between the patients groups. It is suggested that the changes in plasma levels are a consequence of decreased renal clearance. Creatinine clearance was shown to be a poor estimator of tocainide clearance, which suggests that extrarenal clearance plays an important role in the handling of the drug in the body. The findings are used to suggest a safe dosage regimen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607912
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  • 67
    Electronic Resource
    Electronic Resource
    Further support for changes in chloroquine disposition and metabolism between a low and a high dose (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 721-722 
    Details
    ISSN: 1432-1041
    Keywords: chloroquine ; rheumatoid disease ; desethylchloroquine ; capacity limitation ; pharmacokinetics ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of chloroquine and its major metabolite desethylchloroquine were studied in patients with rheumatoid disease after single oral doses of chloroquine phosphate corresponding to 150 and 300 mg chloroquine base. The findings strengthen the previous finding that the disposition of chloroquine involves rate limiting steps.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607924
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  • 68
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of oral moclobemide in healthy human subjects and effects on MAO-activity in platelets and excretion of urine monoamine metabolites (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 89-95 
    Details
    ISSN: 1432-1041
    Keywords: moclobemide ; Ro 11-1163 ; pharmacokinetics ; bioavailability ; MAO activity in platelets ; monoamine metabolites in urine ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of the MAO-inhibitor moclobemide (Ro 11-1163) were determined in six healthy male subjects after oral (tablets) administration. Effects on MAO activity in platelets and excretion of monoamine metabolites in urine were investigated. The design of the study was a double-blind cross-over study with single oral doses of placebo, 50, 100 and 200 mg of moclobemide. The elimination profile of the drug showed that the half life of the unchanged drug ranged between 1 and 2 h except in one subject with a half-life of about 4 h. The mean bioavailability calculated using flow model concepts was F=0.43 after 50 mg, F=0.47 after 100 mg and F=0.59 after 200 mg. The outlier with a t1/2 of 4 h was found to have a bioavailability of more than 0.80 after all 3 doses. The slightly increasing bioavailability with higher doses was interpreted as evidence of saturable hepatic first-pass elimination of the drug. MAO activity in platelets was measured before and 2, 6 and 24 h after drug administration. No inhibition of platelet MAO was obtained at any point in time or dose level, as to be expected since moclobemide preferentially inhibits MAO A. Urine excretion of the monoamine metabolites homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxy-phenylglycol (MOPEG) and 5-hydroxyindoleacetic acid (5-HIAA) was followed during 48 h after placebo, 50 and 200 mg of moclobemide. Time but not dose contributed significantly to the variability in excretion of the monoamine metabolites. An apparent reduction of HVA and DOPAC levels was obtained in the early phase after the administration of 200 mg of moclobemide. In 1 subject with a mild drug reaction a pronounced decrease in the levels of all the metabolites was obtained. In the other 5 subjects, the compound was very well tolerated with a few reported side-effects like increased activity, somnolence or sweatings. There was a slight but significant increase in blood pressure following 50 and 100 mg but not 200 mg of moclobemide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00635714
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  • 69
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of sulphinpyrazone and its major metabolites after a single dose and during chronic treatment (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 97-103 
    Details
    ISSN: 1432-1041
    Keywords: sulphinpyrazone ; metabolism ; single dose ; chronic treatment ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulphinpyrazone and its major metabolites (sulfide, sulfone, p-hydroxysulfone and p-hydroxy-sulphinpyrazone) were investigated in 9 volunteers after a single oral dose as well as after chronic treatment for 23 days. Chronic administration of sulphinpyrazone, in comparison with a single oral dose, led to significant changes in plasma AUC (115.86 to 42.90 mg/l·h), in renal clearance (1.06 to 1.80l/h), in hepatic intrinsic clearance (319.0 to 598.0l/h), and in the unbound fraction in plasma 1.15 to 1.69%) and in tissue (2.73 to 1.31%). The volume of distribution changed from 20.24 to 52.041. The steady state concentrations predicted from the single dose were significantly higher than the values found after chronic treatment. The results suggest that sulphinpyrazone induces its own metabolism. The metabolism of the sulfone, p-hydroxysulfone and the p-hydroxy-sulphinpyrazone to further degradation products was also induced. Chronic treatment with sulphinpyrazone reduced the plasma AUC of the sulfide and caused a decrease in its elimination half-life (20.9 to 14.3 h). Since considerable amounts of the sulfide are formed in the G.I. tract, it is suggested that besides the induction of metabolism, bacteria which reduce sulphinpyrazone to the sulfide may also be responsible for the observed pharmacokinetic changes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00635715
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  • 70
    Electronic Resource
    Electronic Resource
    Limitation on the use of amiloride in early renal failure (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 61-66 
    Details
    ISSN: 1432-1041
    Keywords: amiloride ; kidney function ; Na+ ; K+ ; Ca++ ; Mg++ excretion ; renal amiloride clearance ; chronic renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a single oral dose of 10 mg amiloride was studied on urinary excretion of Na+, K+, Ca++ and Mg++ in healthy subjects and in patients with varying degrees of renal impairment. Amiloride produced a moderate diuresis and sodium excretion, and a slight calciuresis. Urinary excretion of potassium was significantly reduced as compared to the controls. Despite its diuretic and natriuretic effects, amiloride did not change the excretion of Mg++ as compared to the pretreatment period. When the creatinine clearance was below 50 ml/min, the net excretion of Na+ and Ca++ was drastically reduced. However, K+ retention and neutrality of Mg++ excretion were maintained down to end-stage renal disease. In the healthy volunteers the mean elimination half-life of amiloride was 20 h, and it rose to about 100 h in end-stage renal disease. This was because about 3/4 of native amiloride was eliminated through the kidney. Nonrenal elimination of amiloride was calculated to amount to only 1/4 of the total elimination. Therefore, the antikaliuretic amiloride is a valuable comedication in subjects with normal kidney function to prevent K+ and Mg++ loss. However, its use is hazardous if plasma creatinine is raised.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00635709
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  • 71
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    Electronic Resource
    Pharmacokinetics and metabolism of isosorbide-dinitrate after intravenous and oral administration (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 637-644 
    Details
    ISSN: 1432-1041
    Keywords: isosorbide-dinitrate ; pharmacokinetics ; analytical method ; bioavailability ; drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailabilities of a conventional and two slow release 20 mg isosorbide dinitrate (ISDN) formulations were compared after oral administration in a three way cross-over study in 8 male volunteers. In a further group of 6 male volunteers the pharmacokinetics and metabolism of ISDN were investigated after intravenous infusion of a median dose of 14.1 mg for 2.5 h. A new analytical procedure was developed for the determination of isosorbide-5-mononitrate-2-glucuronide (IS-5-MN-2-Glu) and of isosorbide (IS). Kinetic data analysis on a molar basis was performed by the program package KINPAK providing model independent parameters. The median elimination half-lives of ISDN, IS-5-MN, IS-2-MN and IS-5-MN-2-Glu were 0.7, 5.1, 3.2 and 2.5 h, respectively. The systemic clearance of ISDN was 3.7 l/min and the distribution volume 2521 (3.1 l/kg). Apart from IS-5-MN-2-Glu, with a renal clearance of 5.9 l/min which suggested substantial glucuronidation in the kidney, the renal clearances of ISDN, IS-5-MN, IS-2-MN and the corresponding amounts excreted were negligible. 27.8% of the administered ISDN was excreted as IS-5-MN-2-Glu (8.7%) and IS (19.1%). Calculations based on the two mononitrate metabolites formed from ISDN showed an incomplete recovery of 84.1%, leading to the assumption that a simultaneous denitration to IS must have occurred. The rate of denitration at each nitro group in ISDN was almost twice as high as for the same position in the corresponding mononitrate. The bioavailability of the conventional ISDN formulation was 19%, although complete absorption was indicated by comparison of the percentages of mononitrate metabolites formed after the different routes of administration. On the same basis the absorption of the two sustained release formulations was found to be poor.
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    URL: http://dx.doi.org/10.1007/BF00547041
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  • 72
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    Electronic Resource
    Comparative β-adrenoceptor blocking effect and pharmacokinetics of bucindolol and propranolol in man (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 649-656 
    Details
    ISSN: 1432-1041
    Keywords: bucindolol ; propranolol ; beta-adrenoceptor blockade ; intrinsic sympathomimetic activity ; vasodilator ; pharmacokinetics ; blood pressure ; plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The β-adrenoceptor blocking properties and pharmacokinetics of bucindolol 150 mg were compared to those of propranolol 80 mg and a placebo in a double-blind trial in 6 healthy volunteers. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures and peak expiratory flow rate (PEFR) at rest and during vigorous exercise, and plasma renin activity (PRA) at rest, were measured before and at intervals up to 24 h after oral administration of the drugs. Bucindolol reduced exercise tachycardia and decreased exercise PEFR, thus behaving as a non-selective β-adrenoceptor blocking drug. In contrast to propranolol, bucindolol did not reduce resting HR and PRA, probably because of its intrinsic sympathomimetic activity. It decreased resting DBP in relation to its peripheral vasodilator properties. The effects of bucindolol developed as early as 30 min after administration and lasted up to 24 h, whereas its Tmax and T1/2 were 1.6 and 3.6 h respectively. Comparison of the time courses of plasma bucindolol and the cardiac β-adrenoceptor blockade strongly suggests that in man bucindolol undergoes an extensive first-pass effect, leading to the formation of one or more active metabolites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547043
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  • 73
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    Electronic Resource
    CSF and plasma pharmacokinetics of intramuscular morphine (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 677-681 
    Details
    ISSN: 1432-1041
    Keywords: morphine ; analgesic ; pharmacokinetics ; intramuscular administration ; CSF/plasma-morphine levels ; CSF kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Morphine concentrations in plasma and cerebrospinal fluid (CSF) were measured in 58 elderly patients after intramuscular administration of 10 mg morphine. The assay employed gas chromatography with electron capture detection. From 49 of the patients undergoing urological procedures plasma and lumbar CSF samples were obtained simultaneously as spinal analgesia was given, and in addition, repeated venous samples were obtained over 4 hours from 35 of the patients. A plasma-morphine concentration vs time plot was drawn from the mean values and a CSF-morphine vs time plot was calculated by pooling individual CSF concentrations and using the sliding mean technique. The individual CSF/plasma-morphine concentration ratio vs time was also plotted. In addition, 2 or 3 CSF and plasma samples were collected simultaneously from 3 patients undergoing thoracotomy. Large interindividual variation in the CSF concentration was found. The peak CSF level was reached after 3 h and, following pseudoequilibrium, CSF-morphine levels appeared only slightly lower than those found in plasma. The availability to spinal CSF amounted to no more than 0.005% of the administered dose. CSF-morphine concentrations were not related to plasma protein or albumin concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547048
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  • 74
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and distribution of flucloxacillin in pacemaker patients (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 713-719 
    Details
    ISSN: 1432-1041
    Keywords: flucloxacillin ; cardiac pacemaker ; pharmacokinetics ; protein binding ; tissue fluid ; elderly patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of flucloxacillin in plasma and tissue fluid after i.v. infusion of 1 g was analyzed according to an open two-compartment model in 19 patients with bradyarrhythmias (mean age 70.8 years) admitted for implantation or replacement of a permanent pacemaker system. After the first infusion of flucloxacillin (5 min), the distribution phase was rapid (t1/2α=0.13 h). The plasma half-life of elimination (t1/2β) was 1.51 h, which is almost twice as long as reported in healthy volunteers. Total plasma clearance (93.1 ml/min) was also lower than is usually found in healthy individuals, due to low renal clearance of flucloxacillin (60.2 ml/min). The total apparent volume of distribution during the β-phase (Vdarea) was 0.172 l/kg and distribution in the central compartment (Vc) 0.064 l/kg. In each patient plasma protein binding and drug distribution to plasma water, proteins and blood cells in whole blood were determined. Binding in plasma to proteins was 91.0% and distribution to blood cells in whole blood 13.8%. The mean distribution volume of free flucloxacillin during the β-phase (Vdβ free) was 2.18 l/kg, which exceeds total body water, suggesting possible intracellular distribution and substantial tissue binding. Plasma concentrations of flucloxacillin after the fourth dose (1 g t.i.d.) were very similar to those obtained after the first infusion and those predicted from the single dose kinetics. The concentration of flucloxacillin in fluid from the pacemaker pockets in 5 patients averaged 12.1 µg/ml and 9.5 µg/ml at 1 and 5 h, respectively, which was more than ten times the MIC-values for Staphylococcus aureus and S. epidermidis. The average concentration ratio (tissue fluid/plasma) was 0.57. Thus the pharmacokinetics of flucloxacillin in these elderly patients exhibited marked differences from what has been found in healthy volunteers. Despite the high degree of plasma protein binding, flucloxacillin appears to distribute rapidly and efficiently to extravascular compartments, such as a pacemaker pocket.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547055
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  • 75
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    Electronic Resource
    The pharmacodynamics and pharmacokinetics of a new calcium antagonist nisoldipine in normotensive and hypertensive subjects (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 21-24 
    Details
    ISSN: 1432-1041
    Keywords: nisoldipine ; nifedipine ; pharmacokinetics ; pharmacodynamics ; calcium channel blocking drugs ; hypertension ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacodynamic and pharmacokinetic profiles of nifedipine and nisoldipine were compared in a double blind, placebo-controlled study. Nisoldipine, 10 mg significantly reduced systolic blood pressure but nifedipine 20 mg retard did not, although both drugs had significant pharmacodynamic effects as evidenced by increased heart rates. The terminal elimination half-life in plasma was similar for both drugs with a mean of 2 h. The pharmacodynamics of nisoldipine were studied in 8 hypertensives following both acute and chronic administration. Antihypertensive efficacy was demonstrated after acute dosing and was maintained over 4 weeks of twice daily treatment as monotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547363
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  • 76
    Electronic Resource
    Electronic Resource
    On the interaction between phenytoin and digoxin (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 49-53 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; digoxin serum concentration ; drug interaction ; digoxin clearance ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An open, randomized, single-blind cross over trial to investigate phenytoin-digoxin interactions at steady state was performed in 6 healthy male volunteers. Coadministration of phenytoin caused a significant reduction in the elimination half-life of digoxin from 33.9 to 23.7 h and a diminution in AUC0–48 from 31.6 to 24.4 ng · ml−1 · h. Renal digoxin clearance was not significantly altered from 135.7 to 120.3 ml · min−1. Assuming no change in β-acetyldigoxin absorption, the in decrease time-course the serum digoxin concentration was due to a significantly increased total digoxin clearance from 258.6 to 328.3 ml · min−1. An insignificant reduction in the digoxin distribution volume from 749.4 to 668.0 l was also observed. No relevant change in the pharmacokinetic parameters (elimination half-life, area under the serum concentration time-curve, protein binding) of phenytoin was observed when phenytoin and digoxin were co-administered. The data suggest that with this drug combination the serum digoxin concentration should be carefully monitored and, if necessary, the daily digoxin dose should be increased.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547368
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  • 77
    Electronic Resource
    Electronic Resource
    Linear pharmacokinetics of intravenous ergotamine tartrate (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 61-66 
    Details
    ISSN: 1432-1041
    Keywords: ergotamine ; pharmacokinetics ; blood/plasma concentration ratio ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ergotamine tartrate 0.5, 0.25 and 0.125 mg was administered i.v. to 6 volunteers in a cross-over study. Its pharmacokinetic characteristics were evaluated from plasma concentration-time data determined by HPLC. The clearance and volume of distribution were independent of the dose. The ratio between blood and plasma ergotamine concentrations in 4 subjects ranged from 0.41–0.67, indicating the lack of binding to blood cells. Ergotamine was found to be a high clearance drug, average 2.21/min/70kg body wt. suggesting extrahepatic clearance. A possible transient decrease in liver blood flow caused by ergotamine did not seem to affect the linearity of its kinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547370
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  • 78
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    Electronic Resource
    Pharmacokinetics of pirprofen in young volunteers and elderly patients (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 73-77 
    Details
    ISSN: 1432-1041
    Keywords: pirprofen ; arthritic disease ; pharmacokinetics ; elderly patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of pirprofen were measured in 11 elderly arthritic patients and 6 healthy young volunteers at the beginning and end of 8 days treatment with 400 mg doses twice daily. The mean ages of the two groups were 74.5 and 21.8 years, respectively. There were no statistically significant differences in peak concentrations, times to peak, areas under the curve or terminal elimination half-lives between the groups after single dosing. Repeated dosing increased plasma drug concentrations in both groups but the extent was as predicted from the single dose data. Again there were no statistically significant differences between the groups, although pre-dosing plasma concentrations were higher in the elderly compared with the young individuals. The results of this relatively small study suggest that advancing age and arthritic disease appear to have little influence on the pharmacokinetics of pirprofen and no modification in the dosage recommendation in elderly patients without overt renal or hepatic impairment is indicated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547372
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  • 79
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of triamcinolone acetonide and its phosphate ester (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 85-89 
    Details
    ISSN: 1432-1041
    Keywords: triamcinolone acetonide ; triamcinolone acetonide phosphate ; pharmacokinetics ; high dose ; glucocorticoids ; renal excretion ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Triamcinolone acetonide in the form of its phosphate ester was given intravenously in two different doses (10 mg/kg and 80 mg). Plasma levels of the ester and triamcinolone acetonide were measured and pharmacokinetic parameters were calculated. The pharmacokinetics both of the phosphate and the free alcohol were dose-dependent. No unchanged ester was found in the urine, indicating complete conversion of the pro-drug. Triamcinolone was not a major metabolite of triamcinolone acetonide in humans. Renal clearance was low and independent of the dose. Only about 1% of the dose was found in the urine as triamcinolone acetonide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547374
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  • 80
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    Electronic Resource
    Dextropropoxyphene kinetics after single and repeated oral doses in man (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 79-84 
    Details
    ISSN: 1432-1041
    Keywords: dextropropoxyphene ; norpropoxyphene ; pharmacokinetics ; single dose ; multiple dose ; prediction ; saturation ; auto-induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of dextropropoxyphene (DP) and its main metabolite norpropoxyphene (NP) were studied in 6 healthy male subjects after a single oral dose of 195 mg DP HCl, and during and after 12 daily single oral doses of 195 mg DP HCl. The kinetics varied up to five-fold between individuals after the single dose, the apparent mean elimination half-life (t1/2) was 16 h for DP and 29 h for NP. The mean apparent overall plasma clearance (CL) for DP was 2.61/min. There was no systematic difference in DP clearance between the single and multiple doses, but the accuracy of individual predictions from single to multiple doses was poor, probably because of imprecise determinations of the AUC and t1/2 in the single dose experiments. The individual correlation between single and multiple dose kinetics was good for NP, although the predicted plasma levels during steady state were significantly higher than the observed levels (mean AUCss/AUCsd: 0.81). There was no sign of saturation kinetics on repeated administration. In fact, autoinduction, resulting in significantly lower plasma concentrations after treatment for 1 week was found for NP and was indicated for DP. On discontinuing DP after 12 days of treatment, the apparent mean t1/2 of DP was 23 h and of NP 25 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547373
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  • 81
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    Electronic Resource
    Dose dependent pharmacokinetics of midazolam (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 91-95 
    Details
    ISSN: 1432-1041
    Keywords: midazolam ; 1-hydroxymethylmidazolam ; pharmacokinetics ; dose proportionality ; benzodiazepine ; healthy volunteers ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were investigated following oral administration of 7.5, 15 and 30 mg doses of midazolam in solution to 12 healthy subjects. Compared to the 7.5 mg dose, the Cmax and AUC parameters of both midazolam and 1-hydroxymethylmidazolam increased proportionally after the 15 mg dose and more than proportionally after the 30 mg dose. The t1/2 for midazolam remained relatively constant between the 7.5 and 15 mg doses whereas it increased slightly but significantly after the 30 mg dose. These data indicated that the pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were linear between the 7.5 and 15 mg oral dose range. However, after the 30 mg dose, the systemic availability of midazolam and the AUC for 1-hydroxymethylmidazolam appeared to be greater than that anticipated from the lower doses, possibly due to saturation of midazolam first-pass metabolism. This ist not expected to have any clinical significance under the conditions of therapeutic use.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547375
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  • 82
    Electronic Resource
    Electronic Resource
    The disposition of bupropion and its metabolites in healthy male volunteers after single and multiple doses (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 97-103 
    Details
    ISSN: 1432-1041
    Keywords: bupropion ; metabolites ; pharmacokinetics ; single and multiple dose ; side-effects ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of bupropion and 3 of its basic metabolites were determined in 8 young, healthy, male volunteers after single and multiple oral doses of bupropion. Plasma profiles were obtained: 1) after a single 100 mg oral dose of bupropion hydrochloride, 2) following administration of 100 mg 8-hourly for 14 days and 3) again after a single 100 mg dose 14 days later. Plasma concentrations of the parent drug and metabolites were determined by high-performance liquid chromatography. Saliva secretion and pupil diameters were measured, subjective assessments of sleep made using visual analogue scales and side effects, blood counts and biochemistry were monitored. After the first dose mean elimination half lives (t1/2) of bupropion, and metabolites I and II were 8, 19 and 19 h respectively. On repeated administration there was little accumulation of the parent drug and no evidence for induction of its own metabolism. Accumulation of I was consistent with its rate of elimination after single doses while that of II was greater than predicted with prolongation of t1/2 to 35 h. Metabolite III was barely detectable after single doses but its accumulation on multiple dosing was consistent with its long half life (35 h) determined on occasion 2. Saliva secretion was significantly reduced during the multiple dosing period but there were no complaints of dry mouth. Subjective assessments of sleep were not significantly altered though one subject reported vivid dreams. There were no other adverse reactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547376
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  • 83
    Electronic Resource
    Electronic Resource
    Human plasma and skin blister fluid levels of griseofulvin following a single oral dose (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 109-113 
    Details
    ISSN: 1432-1041
    Keywords: griseofulvin ; skin blister fluid levels ; pharmacokinetics ; healthy subjects ; bioavailability ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Griseofulvin and 6-demethylgriseofulvin (6-DMG) in plasma, suction blister fluid (SBF) and cantharides blister fluid (CBF) and urinary excretion of 6-DMG, were evaluated following administration of single oral doses of an ultramicrosize and a microsize formulation of griseofulvin to 6 healthy volunteers. The bioavailability of griseofulvin was higher following the ultramicrosize formulation when 64% of the dose was recovered (via metabolites) versus 52% after the microsize preparation. Penetration into skin blister fluid was delayed as compared to plasma levels; the peak concentration in plasma was observed at 3–4 h, whereas griseofulvin in CBF increased up to 6 h. The terminal half-live was calculated from plasma levels to 9.3 h. The half-lives calculated from SBF and CBF concentrations were 9.2 and 9.8 h, respectively, (n=5). In plasma 84% of griseofulvin was bound to proteins, predominantly to albumin; binding in SBF and CBF was 72 and 82%, respectively. 3 h after drug administration the free concentration in plasma significantly exceeded the free concentrations in SBF and CBF. Distribution equilibrium between plasma and skin blister fluid was observed after 27 h. Thus, during chronic administration, the plasma griseofulvin level should reflect its concentration in the target organ.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547378
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  • 84
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of theophylline and enprofylline in patients requiring a high or low dose of theophylline (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 115-117 
    Details
    ISSN: 1432-1041
    Keywords: enprofylline ; theophylline ; pharmacokinetics ; patients ; theophylline requirement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In patients requiring a high or low dose of theophylline the pharmacokinetics of theophylline and enprofylline were studied. The low-dose group took an average daily dose of 8.91 mg/kg body wt. and the high-dose group 24.75 mg/kg body wt. The average half-life of theophylline in the former was 7.11 h and in the latter 4.72 h. The average clearances (CL) of theophylline were 2.83 and 4.58 l/h, respectively. The daily oral intake of theophylline was negatively correlated with the theophylline t1/2 (r=−0.63). While the t1/2 of enprofylline was similar in the two groups, CL and volume of distribution (Vc) were slightly (about 30%) but significantly higher in patients requiring a high dose of theophylline. CL of enprofylline did not correlate with CL of theophylline, nor was the Vc of the two drugs correlated. Interindividual variability in t1/2 and CL was considerably lower for enprofylline than for theophylline.
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    URL: http://dx.doi.org/10.1007/BF00547379
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  • 85
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    Electronic Resource
    Pharmacokinetics of gentamicin in protein-energy malnutrition (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 255-256 
    Details
    ISSN: 1432-1041
    Keywords: gentamicin ; malnutrition ; protein-energy deficiency ; malnourished children ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of i.m. gentamicin was the same in malnourished (n=6) and normal (n=4) children.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547433
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  • 86
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    Electronic Resource
    The effect of cimetidine on the pharmacokinetics, pharmacodynamics and alpha1-adrenoceptor responsiveness of trimazosin in man (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 301-306 
    Details
    ISSN: 1432-1041
    Keywords: trimazosin ; cimetidine ; pharmacokinetics ; alpha-adrenoceptor antagonism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of cimetidine treatment on the pharmacokinetics and pharmacodynamics of single doses of trimazosin was studied in 6 normotensive volunteers. Co-administration of cimetidine did not significantly affect the overall magnitude of the hypotensive effect of trimazosin. However, the time profile of the blood pressure response was significantly modified particularly with attenuation of the delayed component. Co-administration of cimetidine did not alter alpha1-adrenoceptor antagonism by trimazosin. There was no significant change in the clearnace and volume of distribution of trimazosin but there was a significant reduction in the area under the concentration-time curve for the metabolite, 1-hydroxytrimazosin. The reduction in the AUC of 1-hydroxy-trimazosin corresponds in time with the attenuation of the delayed hypotensive response. This is consistent with the suggestion that the delayed hypotensive response is related to an active metabolite, probably 1-hydroxytrimazosin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544084
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  • 87
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    Electronic Resource
    Pharmacokinetics of the loop diuretic piretanide in renal failure (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 337-343 
    Details
    ISSN: 1432-1041
    Keywords: piretanide ; renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Piretanide 60 mg was administered intravenously over 30 min to 15 men with different degrees of renal failure. The mean piretanide serum concentration at the end of the infusion period was 5.72±1.51 µg/ml. Serum piretanide concentration-time curves declined biexponentially and 24 hours after medication the serum level had fallen to less than twice the detection limit. The terminal half-life ranged from 1.63 to 3.44 h. A relationship to creatinine clearance was not demonstrable. The mean metabolic clearance of piretanide was 107.7±47.6 ml/min/1.73 m2 body surface area and was the same as that reported for healthy subjects. The renal clearance of piretanide ranged from 3.33 to 43.9 ml/min/1.73 m2 body surface area and very closely correlated with the creatinine clearance (p〈0.01). Its renal clearance dependend principally on active secretion of the drug into the tubule, and glomerular filtration appeared unimportant. There was a close relationship between the amount of piretanide excreted in the urine and the creatinine clearance. Because the diuretic effect of piretanide depends on the concentration of the drug in the tubule, the observed correlation might be of use in evaluating the appropriate dosage of piretanide in patients with renal failure. The present data suggest that single daily doses of piretanide will not result in accumulation, even when high doses are administered to patients with advanced renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544091
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  • 88
    Electronic Resource
    Electronic Resource
    Human plasma and skin blister fluid levels of griseofulvin after its repeated administration (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 351-354 
    Details
    ISSN: 1432-1041
    Keywords: griseofulvin ; skin blister fluid ; plasma concentration ; blister fluid concentration ; pharmacokinetics ; microsize formulation ; urinary excretion ; bioavailability ; different formulations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Griseofulvin was administered orally to 6 healthy volunteers for 6 days. The subjects received 500 mg of a microsize formulation and 330 mg of an ultramicrosize formulation, according to a cross-over design. The drug was determined in plasma, suction blister fluid (SBF) and cantharides blister fluid (CBF) following the last dose. Urinary excretion of the main metabolites 6-demethylgriseofulvin (6-DMG) and its glucuronic acid conjugate was also measured. The pharmacokinetic parameters were compared with those obtained from a recent single dose experiment. On repeated administration, the bioavailability of griseofulvin was significantly lower from the microsize formulation; the urinary recovery of total 6-DMG was 33.8% versus 53.6% on administration of the ultramicrosize material. Bioavailability was reduced as compared to ingestion of a single dose. The reduction was more prominent following the microsize (36%) than the ultramicrosize (17%) formulation. Penetration into skin blister fluid was not altered as compared to the single dose experiment. Relative areas under the blister fluid-time curves amounted to 51% (SBF) and 80% (CBF) of the area under the plasma level-time curve. The concentration of unbound griseofulvin in these body fluids was identical throughout the entire dosage interval. Unbound griseofulvin levels were low in comparison with the minimum inhibitory concentrations for strains of trichophyton and microsporum.
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    URL: http://dx.doi.org/10.1007/BF00544093
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  • 89
    Electronic Resource
    Electronic Resource
    β-Adrenoceptor blocking effects and plasma levels of bornaprolol and propranolol in man (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 405-411 
    Details
    ISSN: 1432-1041
    Keywords: bornaprolol ; propranolol ; beta-adrenoceptor blockade ; duration of action ; pharmacokinetics ; plasma renin activity ; bronchoconstriction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The β-adrenoceptor blocking effects and pharmacokinetics of bornaprolol (FM 24), a new β-adrenoceptor blocking agent, have been compared with those of propranolol and a placebo in a double-blind trial in 6 healthy volunteers. Heart rate, systolic and diastolic blood pressures and peak expiratory flow rate were measured at rest and at the end of 3 min vigorous exercise on a bicycle ergometer, before and 2, 24 and 48 h after single oral doses of bornaprolol (120, 240 and 480 mg) and propranolol (40, 80 and 160 mg). Plasma renin activity at rest and the plasma concentrations of the two drugs were determined. Bornaprolol significantly reduced resting heart rate, dose-dependently lowered exercise-induced tachycardia and decreased peak expiratory flow rate and plasma renin activity. In addition, exercise-induced tachycardia was significantly reduced by bornaprolol up to 48 hours after drug intake (pharmacodynamic half-life approximately 63–86 h) and there was a correlation between this reduction and the log plasma bornaprolol concentration over the 48-h period. Thus, bornaprolol behaved in man as a non-cardioselective and long-lasting β-adrenoceptor blocking drug, probably devoid of intrinsic sympathomimetic activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613453
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  • 90
    Electronic Resource
    Electronic Resource
    Intra-uterine pressure and serum ibuprofen: Observations after oral administration of 400 mg ibuprofen to a patient with primary dysmenorrhoea (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 443-446 
    Details
    ISSN: 1432-1041
    Keywords: dysmenorrhoea ; ibuprofen ; intra-uterine pressure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Intra-uterine pressure was recorded in a dysmenorrhoeic patient for 10 h before and after administration of a single dose of ibuprofen 400 mg. Bloodsamples were obtained at regular intervals during the recording for determination of the serum concentration of ibuprofen by reverse HPLC. The maximum serum concentration (37.4 µg Ml−1) was achieved after 1 h and the terminal half-life of ibuprofen was approximately 2 h. A marked reduction in intra-uterine pressure and the severity of pain was recorded 1.5 h following the administration of ibuprofen. Despite low or non-detectable serum concentrations of ibuprofen after 4 h, intra-uterine pressure never regained the level recorded before treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613459
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  • 91
    Electronic Resource
    Electronic Resource
    Nasal bioavailability and systemic effects of the glucocorticoid budesonide in man (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 477-481 
    Details
    ISSN: 1432-1041
    Keywords: budesonide ; glucocorticoid ; nasal administration ; pharmacokinetics ; bioavailability ; systemic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Budesonide, a topically potent glucocorticoid, was administered to 4 healthy volunteers by i.v. infusion and by nasal instillation of 100 µg tritium-labelled drug. Plasma was analyzed by liquid chromatography plus scintillation counting of collected fractions. After i.v. administration the plasma clearance was 0.92 l/min and the apparent volume of distribution was 2.8 l/kg. After nasal administration, the time to reach the peak plasma level was approximately 30 min, and the systemic availability was 102%. Budesonide had marginal effects on plasma cortisol and white blood cell counts either after i.v. or nasal administration. Thus, nasally instilled budesonide in solution is rapidly and completely absorbed from the nasal mucosa. The systemic effects after this clinically recommended nasal dose were negligible.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613465
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  • 92
    Electronic Resource
    Electronic Resource
    Comparison of renal excretion of pethidine (meperidine) and its metabolites in old and young patients (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 171-175 
    Details
    ISSN: 1432-1041
    Keywords: pethidine ; drug metabolism ; pethidine metabolites ; renal excretion ; pharmacokinetics ; geriatrics ; old age ; meperidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a previous study old subjects were found to eliminate pethidine and its active metabolite norpethidine more slowly than young people. To investigate whether this was due to the decline in renal function with age, the urinary output of pethidine and its metabolites pethidinic acid, norpethidine and norpethidinic acid was compared in old and young patients. The cumulative urinary excretion of pethidine and pethidinic acid over 24 h was similar in old and young patients. The slower elimination rate of pethidine from plasma might therefore be due to slower biotransformation of pethidine to norpethidine and norpethidinic acid. The cumulative urinary excretion of norpethidine and norpethidinic acid during 24 h was significantly lower in old patients than in young: 2.7% versus 7.1% (p〈0.001), and 5.5% versus 10.5% (p〈0.001). The renal clearance of norpethidine was inversely correlated with age. Thus, the slower disappearance of norpethidine from plasma in old patients is due to slower renal excretion of this metabolite. The renal clearance of pethidine showed pH-dependence and was usually smaller than the creatinine clearance. In contrast, renal clearance of norpethidine was correlated with creatinine clearance and was of the same magnitude. The difference in renal handling may be explained by the more polar character of norpethidine compared to its parent compound. The present study shows that not only the excretion of unchanged drugs may decline with increasing age but also that of drug metabolites, which may therefore reach higher plasma levels in old patients. If they are pharmacologically active they will increase and prolong the response to medication and possibly increase the risk of side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609687
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  • 93
    Electronic Resource
    Electronic Resource
    Determination of thiamine in human plasma and its pharmacokinetics (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 213-219 
    Details
    ISSN: 1432-1041
    Keywords: thiamine ; plasma level ; pharmacokinetics ; nonlinear renal elimination ; assay for clinical use
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A sensitive assay for thiamine suitable for clinical use has been developed. It is based on precolumn oxidation of thiamine to thiochrome followed by HPLC-separation and fluorescence detection. The assay is applicable to various biological materials, including human plasma. The minimum amount detectable was 5 fmol, minimum plasma concentration 0.5 nmol/l and minimum sample volume 0.3 ml plasma. Each chromatographic run took 3 min. Inter- and intra-assay relative standard deviations (RSD) were 8.3% and 6.3%, respectively, at a stock plasma concentration of 10.8 nmol/l. At 38.8 nmol/l, interassay RSD was reduced to 3.4%. The recovery of 5 nmol/l added thiamine was 102 (SD±17)%, that of 30 nmol/l was 94±5%. Plasma levels in 91 volunteers ranged from 6.6 to 43 nmol/l, showing a log normal distribution with a median of 11.6 nmol/l. Thiamine kinetics were studied in plasma and urine from 8 men after intravenous and oral doses of 50, 100 and 200 mg thiamine hydrochloride. In all individuals, nonlinear renal elimination kinetics were demonstrated by plotting the fractional amount of thiamine excreted unchanged in urine against the corresponding area under the plasma concentration — time curve.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609694
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  • 94
    Electronic Resource
    Electronic Resource
    Pharmacokinetic studies of cefoxitin in continuous ambulatory peritoneal dialysis (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 333-337 
    Details
    ISSN: 1432-1041
    Keywords: cefotoxin ; renal failure ; peritoneal dialysis ; pharmacokinetics ; CAPD (continuous ambulatory dialysis) ; dialysate concentration ; intra peritoneal administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefoxitin was examined in 9 patients undergoing peritoneal dialysis for chronic renal failure. Cefoxitin was administered intraperitoneally in the dialysate fluid every 6 h for 24 h, in two different concentrations, 50 µg/ml and 100 µg/ml. The plasma half-life of cefoxitin was 20.2 h. The major route of elimination was non-renal, with a clearance of 8.0 ml/min. Peritoneal clearance was 4.1 ml/min. As expected, renal clearance was negligible. The peak plasma concentrations of cefoxitin at the two dose levels used were 7 µg/ml and 15 µg/ml, respectively, when assayed by HPLC, and 12 µg/ml and 24 µg/ml when determined by a microbiological assay. The cefoxitin concentration in the dialysate decreased from 50 µg/ml to 14 µg/ml and from 100µg/ml to 37 µg/ml during the 6 h of its retention in the peritoneal cavity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543333
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  • 95
    Electronic Resource
    Electronic Resource
    Mechanism of warfarin potentiation by amiodarone: Dose — and concentration — Dependent inhibition of warfarin elimination (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 257-261 
    Details
    ISSN: 1432-1041
    Keywords: amiodarone ; warfarin ; drug interaction ; metabolism ; inhibition ; plasma concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Potentiation of the anticoagulant-effect of warfarin by amiodarone was studied in 30 patients. Thirteen received both drugs concurrently, and 17 received warfarin alone and the combination sequentially. Warfarin doses were adjusted to maintain the prothrombin time between 25–30% of control and its kinetics were compared to those in 20 control patients who received warfarin alone. Potentiation occurred in 28/30 patients, presenting as a 35%–65% reduction in the required dose of warfarin, and was correlated with the dose of amiodarone (r=0.77, p〈0.01). The free warfarin fraction was not affected by amiodarone (1.8% vs 1.6% in the controls). Warfarin clearance was lower in amiodarone-treated patients than in the controls (1.4 vs 3.1 ml/min, p〈0.01) with similar plasma concentrations (1.5 vs 1.2 µg/ml) despite administration of lower doses (23.3 vs 39 mg/week respectively). The amiodarone concentration was significantly correlated with the warfarin concentrations independent of the effect of amiodarone on the dose of warfarin. Amiodarone hat no effect on prothrombin other than through its actions on the dose and plasma concentration of warfarin. The mechanism of the amiodarone-warfarin interaction is pharmacokinetic through dose — and concentration — dependent inhibition of warfarin elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543320
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  • 96
    Electronic Resource
    Electronic Resource
    Effect of oxidative polymorphism (debrisoquine/sparteine type) on hepatic first-pass metabolism of bufuralol (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 317-320 
    Details
    ISSN: 1432-1041
    Keywords: bufuralol ; debrisoquine ; sparteine ; genetic/oxidative polymorphism ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bufuralol is a beta-adrenoceptor blocking drug whose oxidative metabolism is under the same genetic control as debrisoquine and sparteine. The pharmacokinetics of bufuralol were studied in 10 healthy subjects (7 extensive and 3 poor metabolizers of debrisoquine) after oral and intravenous administration. In extensive metabolizers the systemic availability of bufuralol was 43%. Poor metabolizers were characterized by a considerable increase in systemic availability due to a corresponding decrease in hepatic first-pass metabolism. After oral administration of bufuralol non-linear kinetics may occur.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543330
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  • 97
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of famotidine, a new H2-receptor antagonist, in relation to renal function (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 327-331 
    Details
    ISSN: 1432-1041
    Keywords: famotidine ; renal failure ; H2-receptor antagonist ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a new, potent H2-receptor antagonist, famotidine, 20 mg i.v. was studied in 7 subjects with normal renal function and in 24 patients with varying degrees of renal impairment. The volume of distribution at steady state was 1.14 l/kg in normal subjects and was not altered in renal failure. The half-life of elimination was 2.59 h in normal subjects and was unchanged in mild renal failure (creatinine clearance, CLCR 90–60 ml/min/1.48 m2) but was increased to 4.72 h in moderate renal failure (CLCR 60–30 ml/min/1.48 m2), and to 12.07 h in severe renal failure (CLCR below 30 ml/min/1.48 m2). The cumulative urinary excretion and renal clearance of famotidine were correspondingly reduced in patients with impaired kidney function. In normal subjects and in patients with mild to moderate renal failure, about 70% of famotidine was excreted through the kidney, mainly by tubular secretion. In patients with a CLCR above 60 ml/min/1.48 m2 the normal daily dose of famotidine can be employed, but in those with a CLCR between 60 and 30 ml/min/1.48 m2 the dose should be reduced by half, and in patients with a CLCR below 30 ml/min/1.48 m2 a reduction by three quarters of the normal dose is recommended.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543332
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  • 98
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of verapamil in patients with renal failure (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 405-410 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; renal failure ; norverapamil ; pharmacokinetics ; haemodialysis ; ECG ; blood pressure ; heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of verapamil was studied in patients with end-stage chronic renal failure and in normal subjects after i.v. injection of 3 mg and a single oral dose of 80 mg. Plasma levels of verapamil and its active metabolite norverapamil were measured by HPLC. After i.v. injection, the terminal phase half-life and total plasma clearance of verapamil in both groups were similar. Haemodialysis did not change the time course of plasma verapamil levels after i.v. administration. After a single oral dose, the plasma levels of verapamil and norverapamil in both groups of subjects were similar. Subsequently, normal volunteers and patients with renal failure were treated for 5 days with oral verapamil 80 mg t.d.s. There was no difference between the 2 groups of subjects in the trough and peak levels of verapamil or of norverapamil. Intravenous and oral administration of the calcium channel blocking agent had similar effects on blood pressure, heart rate and the PR-interval in the electrocardiogram in both groups. The study demonstrated that the disposition of verapamil was similar in normal subjects and in patients with renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544358
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  • 99
    Electronic Resource
    Electronic Resource
    Bioavailability and pharmacokinetics of ketanserin in elderly subjects (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 411-417 
    Details
    ISSN: 1432-1041
    Keywords: ketanserin ; ketanserinol ; pharmacokinetics ; age ; healthy volunteers ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of ketanserin has been examined in a cross-over experiment in 21 elderly subjects (aged 59–72 years) by administration of tablets (40 mg), solution (40 mg) and injectable solution (10 mg). After two weeks of treatment with 40 mg ketanserin tablets further 18 blood samples for analysis were collected under steady-state conditions. Plasma levels were measured by HPLC. The absolute bioavailability of ketanserin tablets was 52.7%; their relative bioavailability compared to a solution containing an equal quantity of active compound was 85.5%. Therefore, the low absolute bioavailability of ketanserin cannot be attributed to the formulation. The active compound was rapidly liberated from the tablet, reaching a peak of 103.8 ng/ml after 0.97 h. Individual plasma level-time curves were fitted to an open three compartment model and a half-life of 17.7±7.26 h was calculated for the terminal elimination phase. An average terminal elimination half-life of 15.4±4.2 ng/ml was found after administration of the ketanserin solution. Multiple dosing with 40 mg tablets b.d.s. resulted in an AUC over one dosing interval at steady-state of 666±201 ng × h/ml. The AUC extrapolated to infinity was 1200±405 ng × h/ml for the last tablet. This is 1.8-times the AUC in one dosing interval, and 2.3-times the AUC of a single dose. Under steady-state conditions, the mean peak plasma level was 155.1 ng/ml (1.08 h after dosing) and the terminal half-life was 19.1±5.1 h. For the metabolite ketanserinol terminal half-lives of 21.4 h after a single tablet and 31.0 h after discontinuation of multiple dosing were calculated. Compared to the parent compound there was much more marked accumulation of ketanserinol. Despite moderate accumulation and prolongation of the terminal half-life of ketanserin under steady-state conditions, dosage adjustment is not required in elderly people. First-pass metabolism and bioavailability remained in the range found in previous studies of ketanserin in young subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544359
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  • 100
    Electronic Resource
    Electronic Resource
    Intravenous and intramuscular pharmacokinetics of recombinant leukocyte a interferon (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 469-471 
    Details
    ISSN: 1432-1041
    Keywords: interferon ; cancer patients ; recombinant leukocyte A interferon ; rIFN-αA ; i.v.-/i.m. administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Interferon is currently being evaluated for the treatment of disseminated cancer and viral diseases. Alpha interferons have shown to be effective in the treatment of a number of malignancies. Recombinant leukocyte A interferon (rIFN-αA) is an alpha interferon produced by recombinant DNA techniques. A kinetic evaluation of rIFN-αA following intravenous and intramuscular administration has not been adequately defined. The present study was designed to evaluate the kinetics of rIFN-αA following intravenous and intramuscular administration of 3, 9 or 18×106 units to patients with disseminated cancer. A preliminary report of this study was presented at the meeting of the American Society for Clinical Pharmacology and Therapeutics in San Diego, March 1983 (1).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544369
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