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  • 1995-1999
  • 1980-1984  (7,093)
  • 1970-1974  (5,583)
  • 1955-1959
  • 1982  (7,093)
  • 1972  (5,583)
  • Chemistry  (12,434)
  • Electron microscopy  (162)
  • Nuclear reactions
  • pharmacokinetics
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Years
  • 1995-1999
  • 1980-1984  (7,093)
  • 1970-1974  (5,583)
  • 1955-1959
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  • 1
    Electronic Resource
    Electronic Resource
    Heat of fusion and lamellar structure of polyethylene single crystal mats (1982)
    Springer
    Colloid & polymer science 260 (1982), S. 564-569 
    Details
    ISSN: 1435-1536
    Keywords: lin. Polyethylene ; Single crystals ; Heat of Fusion ; DSC ; Electron microscopy
    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 Recently published results for solution crystallized PE single crystals have shown, that the experimental heat of fusionΔH * is higher, if the solvent is exchanged to silicon oil (oil suspension samples) as compared with dried mats. This has been interpreted by the collapse of the original hollow pyramids during drying, inducing lateral defects within the lamellae. The present investigation does not confirm this unexpected result.ΔH * of dried mats (T c 66 to 91 °C) and of the corresponding oil suspension samples agree within the rather small limits of experimental error. The crystallinities as derived fromΔH *, density or WAXS are in excellent agreement. SEM micrographs of cold fractured dried mats show their spongy macromorphology, but TEM micrographs of stained ultra-thin sections reveal the lamellar morphology of the walls, consisting of curved lamellae and stacked hollow pyramides. If a dried mat is sintered at room temperature, a dense transparent film is obtained with a rather regular stacked morphology of large flat lamellae.ΔH * of these films agrees with that of the original mat.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01422587
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  • 2
    Electronic Resource
    Electronic Resource
    Macromolecular transport in the spiral prominence (1982)
    Springer
    European archives of oto-rhino-laryngology and head & neck 236 (1982), S. 41-51 
    Details
    ISSN: 1434-4726
    Keywords: Prominentia spiralis cochleae ; Meerrettichperoxidase ; Elektronenmikroskopie ; Inner ear spiral prominence ; Horseradish peroxidase ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Transport of macromolecules in the spiral prominence of the guinea pig was studied after perilymphatic and intravenous horseradish peroxidase (HRP) injection. HRP was taken up by the spiral prominence epithelium from the perilymphatic space and in a much higher degree from the endolymphatic space. A highly endocytic ativity was shown by the stroma cells surrounding the spiral prominence vessel. HRP particles were stored in the cytoplasm within vesicles and vacuoles of different sizes and different contrasts. The mode of tracer storage in the spiral prominence epithelium and in the stroma cells from the morphological point of view suggests lysosomal digestion. HRP was transported from the perilymphatic space into the spiral prominence vessel lumen by means of vesicular transport through the vessel wall, while transport of the tracer from the vessel lumen into the perilymphatic space after intravenous injection was not observed.
    Notes: Zusammenfassung Nach perilymphatischer und intravenöser Applikation von Meerrettichperoxidase wurde der Transport des Makromoleküls in der Prominentia spiralis des Meerschweinchens verfolgt. Die Tracer-Partikelchen wurden aus dem perilymphatischen Raum und vornehmlich jedoch aus dem Ductus cochlearis in das Oberflächenepithel der Prominentia spiralis aufgenommen. Die das Vas prominens umgebenden Stromazellen nahmen relativ viel Meerrettichperoxidase auf, die im Zytoplasma in unterschiedlich großen und unterschiedlich kontrastreichen Vesikeln und Vakuolen abgelagert wurde. Die Art der zytoplasmatischen Ablagerung des Tracers in den Epithelzellen und den Stromazellen spricht vom morphologischen Aspekt her für einen lysosomalen Abbau. Meerrettichperoxidase wurde von der Perilymphe in das Lumen des Vas prominens transportiert. Dieser Transport erfolgte vesikulär durch das Gefäßendothel. Ein Transport des Tracers in umgekehrter Richtung wurde nach intravenöser Applikation nicht beobachtet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00464056
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  • 3
    Electronic Resource
    Electronic Resource
    Elektronenmikroskopische Befunde am Bindegewebe von Nervus und Ganglion vestibuli bei Morbus Menière (1982)
    Springer
    European archives of oto-rhino-laryngology and head & neck 236 (1982), S. 67-79 
    Details
    ISSN: 1434-4726
    Keywords: Menière's disease ; Vestibular nerve ; Vestibular ganglion ; Pathologic alterations ; Electron microscopy ; Morbus Menière ; Nervus vestibularis ; Ganglion vestibuli ; Pathologische Veränderungen ; Elektronenmikroskopie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Vestibularisganglien von 17 Patienten mit einem Morbus Menière wurden nach transtemporaler oder translabyrinthärer Neurektomie elektronenmikroskopisch untersucht. Als Vergleichsmaterial dienten drei Ganglien, die bei anderer Indikation entnommen wurden und vier postmortale Entnahmen von Ohrgesunden. Bei allen Menière-Präparaten zeigten sich am Bindegewebe gleichartige pathologische Veränderungen von unterschiedlich starkem Ausmaß. Sie bestanden in einer Zunahme des Kollagens, wobei sowohl unterschiedliche Kaliber des Faserquerschnittes als auch Veränderungen der Periodizität der Querstreifung beobachtet wurden. Aktive Fibroblasten und reaktive Schwannsche Zellen, die isoliert lagen, keinem Axon zugeordnet waren und deren z. T. hirschgeweihförmig verzweigte, dünne Zellausläufer Kollagenbündel umhüllten, wurden als Zeichen einer noch ablaufenden Kollagenbildung gedeutet. Die Blutgefäße wiesen häufig eine Vervielfachung der Basalmembran auf, die von einem mehrfach breiteren Saum einer homogenen Matrix umgeben war. Die Perizyten waren oft entweder nekrotisch oder teilweise nicht mehr zu beobachten. Die Endothelzellen wiesen in der Regel kein aktives Zytoplasma auf. Sie erschienen teilweise autolytisch. Die pinozytotische Aktivität erwies sich als auffallend verringert. Diese qualitativen Veränderungen im interstitiellen Gewebe könnten auf ein primär lokales pathologisches Geschehen im Bereich des Nerven und des Ganglions hinweisen.
    Notes: Summary Vestibular ganglia of 17 patients with Menière's disease, obtained by transtemporal or translabyrinthine neurectomy, were studied by electron microscopy. Three ganglia removed because of other disease and four ganglia of normal ears taken post mortem served as controls. The neuronal fibrous tissue of Menière cases showed without exception pathologic changes of various extent. The amount of collagen was increased, whereby different fiber diameters were observed as well as changes in the periodicity of cross banding. Signs of continuing collagen formation were found: active fibroblasts and an increased number of isolated Schwann cells without axons, showing deerhorn-like ramifications which enveloped collagen bundles. The blood vessels were frequently surrounded by multiple basal membranes and broad bands of homogenous matrix. The pericytes were either necrotic or nonexistent. The endothelial cell cytoplasma was usually not in an active state. Sometimes it seemed to be autolytic. The pinocytotic activity was strikingly diminished. These qualitative changes of the interstitial tissue might point to a local pathologic event in the region of the vestibular nerve and ganglion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00464059
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  • 4
    Electronic Resource
    Electronic Resource
    Chordoid sarcoma (extraskeletal myxoid chondrosarcoma) (1982)
    Springer
    Virchows Archiv 399 (1982), S. 61-78 
    Details
    ISSN: 1432-2307
    Keywords: Chordoid sarcoma ; Chondrosarcoma ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Evaluation of a series of 12 chordoid sarcomas suggests that there is a wider range of histological features in this entity then previously appreciated. Six of the lesions had a typical tumor cell organization and a mixture of cellular and myxoid stromal components, while the remaining cases were atypical because of a more solid growth pattern. Four of the 12 cases, that included both typically myxoid and more cellular examples, had small foci with hyalinized stroma segragating individual or small groups of tumor cells with and without lacunar spaces. Two atypical cases revealed more extensive and obvious chondrocytic differentiation in recurrent or metastatic lesions and in one of these, the histological pattern was that of mesenchymal chondrosarcoma. Ultrastructural examination of three cases revealed fine structural features of both the tumor cell population and extracellular matrix compatible with chondrocytic differentiation. Results of light and electron microscopy of this series of chordoid sarcoma add further support for categorizing this tumor with other malignant chondrocytic neoplasms. It is probable that chordoid sarcoma and extraskeletal myxoid chondrosarcoma represent the same entity and that this lesion has a close histogenetic relationship to mesenchymal chondrosarcoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666219
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  • 5
    Electronic Resource
    Electronic Resource
    Adenoma of the human pituitary producing growth hormone and thyrotropin (1982)
    Springer
    Virchows Archiv 395 (1982), S. 59-68 
    Details
    ISSN: 1432-2307
    Keywords: Adenohypophysis ; Electron microscopy ; Growth hormone ; Immunocytology ; Pituitary adenoma ; Thyroid-stimulating hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A pituitary adenoma removed by surgery from a 22-year-old man was studied by histology, immunocytology, transmission electron microscopy and immunoelectron microscopy. Clinically, the patient had acromegaly and euthyroidism with elevated blood GH concentrations. Blood TSH and T4 levels were within the normal range. Histologically, the adenoma was chromophobic and exhibited no PAS, lead hematoxylin, aldehyde thionin or Grimelius silver positivity. By the immunoperoxidase technique GH, β-TSH and α-subunit but no PRL, ACTH, α-endorphin, β-FSH or β-LH were demonstrated in the adenoma cells. Electron microscopy revealed adenoma cells which were similar to TSH cells and showed no resemblance to GH cells of nontumorous pituitaries or GH-secreting tumors. Immunoelectron microscopy demonstrated GH and β-TSH in the secretory granules. It is concluded that pituitary adenomas composed of TSH-like cells may secrete GH, resulting in acromegaly. Production of GH by adenomatous TSH cells cannot be explained on the basis of the one cell- one hormone theory. The question is raised whether bihormonal or multihormonal clones, capable of synthesizing more than one hormone, exist in the human pituitary. These cells are apparently dormant under normal conditions, but in the course of neoplastic transformation may undergo functional dedifferentiation and acquire the ability to produce two or more different hormones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00443484
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  • 6
    Electronic Resource
    Electronic Resource
    Endothelium and “silver lines” (1982)
    Springer
    Virchows Archiv 395 (1982), S. 133-144 
    Details
    ISSN: 1432-2307
    Keywords: Endothelium ; Permeability ; Electron microscopy ; Electrolytes ; Silver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The significance of endothelial “silver lines” was studied by TEM in rat aortas after perfusion with glutaraldehyde followed by silver nitrate. Standard TEM technique proved unsatisfactory (coarse silver granules, imprecise localization, artefacts). Exposure of the silver-treated aortas to photographic fixer markedly improved the image of the deposits leaving fine, stable, uniform “residual granules” about 100 Å in diameter. Most of these granules were localized along the intercellular junctions; they also tended to pool in the basement membrane beneath each junction. This image suggests that the Ag+ ions pass through the junction, and react with its contents as well as with the basement membrane beyond it. A scheme is proposed to explain the reaction of Ag+ ions with anions and negatively charged radicals within the junction. It is concluded that the “silver lines” represent not only a histochemical effect, but also the visualization of a transendothelial electrolyte pathway.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00429607
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  • 7
    Electronic Resource
    Electronic Resource
    The ultrastructure of human fibrosing alveolitis (1982)
    Springer
    Virchows Archiv 395 (1982), S. 181-199 
    Details
    ISSN: 1432-2307
    Keywords: Lung disease ; Electron microscopy ; Interstitial pneumonia ; Fibrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This report describes the ultrastructural findings in 37 patients who underwent open lung biopsy which yielded diagnoses of fibrosing alveolitis. A spectrum of lesions are categorized for the capillary endothelium and its basement membrane, the interstitial space and its fibrocellular components, and the alveolar epithelium and its basement membrane. The findings typify the different pulmonary cellular reactions to injury. Evidence for cellular regeneration and death in both epithelial and endothelial cell populations include atypical epithelial cell proliferation, capillary basement membrane multilamination, decrease in capillary lumen size and prominent pericytic ensheathment of pulmonary capillaries. Within the interstitium of the lung, proliferation of collagen and elastic fibers are documented, but in addition, abundant myofibroblasts and smooth muscle cells are present. No ultrastructural evidence of immune complex deposition was found in this study. The morphologic findings of fibrosing alveolitis further support the widespread concept that the lung responds to various injuries in a similar manner and undergoes a common reparative response regardless of etiology.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00429611
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  • 8
    Electronic Resource
    Electronic Resource
    Primary sarcoma of the gallbladder (1982)
    Springer
    Virchows Archiv 396 (1982), S. 91-102 
    Details
    ISSN: 1432-2307
    Keywords: Primary gallblader sarcoma ; Electron microscopy ; Histopathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Six Swedish cases of primary sarcoma of the gallbladder from the period 1958–1973 and 1 case from 1975 were studied by light and electron microscopy. The literature was reviewed for the period after 1970. Ultrastructural features of sarcoma were investigated in order to exclude poorly differentiated carcinoma. One case was considered to be an embryonal rhabdomyosarcoma, three cases leiomyosarcoma and two were diagnosed as fibrosarcoma. One case, diagnosed as sarcoma of the gallbladder by light microscopy, was omitted because electron microscopical examination revealed a squamous cell carcinoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428502
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  • 9
    Electronic Resource
    Electronic Resource
    Arrest and extravasation of neoplastic cells (1982)
    Springer
    Virchows Archiv 396 (1982), S. 73-89 
    Details
    ISSN: 1432-2307
    Keywords: Human malignant cells ; K-562 cell line ; Vascular arrest ; Endothelial attrition ; Extravasation ; Nude and lasat mice ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The morphological aspects of the arrest and extravasation of malignant cells of human origin (K-562 cell line) in the lungs of athymic (nude) and asplenic-athymic (lasat) mice were studied by electron microscopy examination of serial sections. The specimens were obtained at sequential stages after the sc inoculation into newborn mice of 107 malignant cells. K-562 cells (105) were also injected iv into control groups of nude and lasat mice to assess the influence of the route of inoculation on the in vivo behavior of K-562 cells. Our results demonstrated that K-562 cells were arrested and proliferated within the pulmonary capillaries without the participation of platelets or fibrin. The neoplastic cells extravasated by attrition and penetration of the endothelium (rather than by diapedesis) and continued to proliferate in the interstitial tissue of the lung, developing into neoplastic nodules. Following iv injection, K-562 cells induced the formation of platelet-tumor cell aggregates within the pulmonary capillaries. However, under these conditions, the neoplastic cells did not adhere to the endothelium nor did they proliferate or extravasate. These aggregates were flushed out by the circulation, restoring the permeability of the capillaries.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428501
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  • 10
    Electronic Resource
    Electronic Resource
    An ultrastructural and morphometric study of bladder tumours (II) (1982)
    Springer
    Virchows Archiv 396 (1982), S. 291-301 
    Details
    ISSN: 1432-2307
    Keywords: Electron microscopy ; Bladder neoplasms ; Measurement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bladder tissues from 3 groups of patients were examined, using the light and electron microscopes (LM and TEM). One group of patients had a history of well-differentiated papillary transitional cell carcinomas and specimens were taken from cystoscopically normal areas. In a second group frank papillary carcinoma was biopsied. Finally, patients with no history of urothelial tumours and a normal cystoscopic appearance were biopsied during investigations for various benign conditions and these served as controls. In tissues from the first two groups certain differences were seen when these were compared to the controls and the frequency of these was significant. Light microscopic examination of 0.5 μ toluidine blue stained sections revealed an increased number of immature, small dark cells in the superficial layer of the epithelium (P〈0.001). Electron microscopic examination showed that in place of the characteristic asymmetric unit membrane of mature superficial cells, the surface was frequently covered with microvilli and the junctional complexes were often atypical. There was an increased number of abnormalities in the basal lamina (P〈0.001). These features were seen in the absence of cystoscopic and light microscopic changes in three out of eight patients with a history of tumours. It is, therefore, suggested that these are the earliest detectable morphological abnormalities in the pre-neoplastic urothelium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431388
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  • 11
    Electronic Resource
    Electronic Resource
    Ultrastructure of a virilizing ovarian Leydig-cell-tumor (1982)
    Springer
    Virchows Archiv 397 (1982), S. 17-27 
    Details
    ISSN: 1432-2307
    Keywords: Ovarian tumor ; Hilus cell tumor ; Leydig cell tumor ; Virilism ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of virilizing ovarian hilus cell tumor (Leydig-cell tumor) in a 37 year old female was studied by light and electron microscopy. The ultrastructural features of this rare and almost allways benign tumor are compared with those reported in the literature and with findings in normal and neoplastic interstitial cells of the testis. Tubulovesicular hyperplasia and formation of whorl structures of the endoplasmatic reticulum together with the presence of exocytosis vesicles on the cell surface may be the morphological manifestation of endocrine activity of the tumor. The identity of ultrastructural and optical diffraction characteristics of the crystal inclusions in both cells (hilar and testicular interstitial) favours the assumption of an homology of both cells and their neoplasms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00430890
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  • 12
    Electronic Resource
    Electronic Resource
    Synovial sarcoma arising in an anatomical bursa (1982)
    Springer
    Virchows Archiv 397 (1982), S. 93-101 
    Details
    ISSN: 1432-2307
    Keywords: Biphasic synovial sarcoma ; Semitendinosus bursa ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In previous studies, the origin of synovial sarcoma directly from synovium has not been satisfactorily established. This case report describes the light and electron microscopic features of a biphasic synovial sarcoma occurring within the popliteal fossa. At surgery, a cystic mass was identified in relationship to the semitendinosus tendon at the anatomical site of the semitendinosus bursa. The tumour originated from the inner surface of the bursa as multiple papillary projections with no evidence of extension beyond the capsule of the bursa. Portions of the synovial surface were hyperplastic but otherwise normal. The findings indicate that biphasic synovial sarcoma can arise directly from synovium and support the hypothesis of a mesenchymal histogenesis for this tumour.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00430896
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  • 13
    Electronic Resource
    Electronic Resource
    Tumor of mesonephric origin in a diverticulum of the urethra (1982)
    Springer
    Virchows Archiv 397 (1982), S. 335-345 
    Details
    ISSN: 1432-2307
    Keywords: Bladder neoplasm ; Mesonephric origin ; Urethral diverticulum ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of a rare tumor arising in a diverticulum of the urethra was studied. Light microscopy revealed the typical structures of mesonephric tumor with obvious infiltration of the muscularis. Electron microscopic appearance indicated that the tumor cells were immature and not totally characteristic of any tissue of origin. Apart from appearances suggesting rapid growth, cellular inclusions of various appearance were found.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00496574
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  • 14
    Electronic Resource
    Electronic Resource
    Observations on the ultrastructure of human urothelium: The response of normal bladder of elderly subjects to hyperthermia (1982)
    Springer
    Urological research 10 (1982), S. 227-237 
    Details
    ISSN: 1434-0879
    Keywords: Human ; Bladder urothelium ; Electron microscopy ; Hyperthermia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An electron microscopic study of normal bladder urothelium of elderly subjects treated by hyperthermic perfusions has shown that the tissue responds, sooner or later, in every instance by desquamation. There is no evidence of cell death prior to desquamation although various organelles undergo structural alterations. Mitochondria are especially prone to suffer varying degrees of damage. A short heat shock has revealed differences in the initial response of the thick and thin regions of bladder urothelium known to occur in elderly subjects. After a long, fractionated treatment, regeneration is evident within 3 daysof the end of treatment, and follow-up biopsies have revealed a hyperplastic urothelium within 10 to 12 weeks. The constituent cells show signs of cytodifferentiation at this time but it remains unknown when an ultrastructurally normal urothelium with characteristic cell layers will be restored. The various treatments in this study suggest that the stem cells in the epithelium are unaffected by the levels of hyperthermia employed and that their unimpaired proliferative capacity ensures regeneration of the urothelium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00255928
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  • 15
    Electronic Resource
    Electronic Resource
    The effect of tetraphenylporphinesulfonate (TPPS) on muscle end-plates in mice (1982)
    Springer
    Acta neuropathologica 56 (1982), S. 201-206 
    Details
    ISSN: 1432-0533
    Keywords: Muscle end-plates ; Porphyric neuropathy ; Electron microscopy ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Motor end-plates were studied in mice at various intervals after a single injection of a synthetic porphyrin, tetraphenylporphinesulfonate (TPPS). Ultrastructurally, excess accumulation of neurofilaments constituted the earliest abnormality. These were followed by atrophy of many nerve terminals and their separation from the postsynaptic area by interposed separation from the postsynaptic area by interposed Schwann cells. Five to 8 months after the injection some postsynaptic areas showed denervation and atrophy. These progressive changes in the nerve terminals were accompanied by secondary changes in the subneural apparatus. Morphometric analysis revealed marked atrophy of the end-plates and significant swelling of preterminal axons. The present findings are suggestive of partial denervation of muscle, occurring after the injection of a synthetic porphyrin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690636
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  • 16
    Electronic Resource
    Electronic Resource
    Intra-astrocytic glycogen granules and corpora amylacea stain positively for polyglucosans: A cytochemical contribution on the fine structural polymorphism of particulate polysaccharides (1982)
    Springer
    Acta neuropathologica 57 (1982), S. 99-102 
    Details
    ISSN: 1432-0533
    Keywords: Cytochemistry ; Electron microscopy ; Polyglucosan bodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A cytochemical procedure for polysaccharides was carried out on a brain biopsy specimen, the thin-section study of which had shown excess glucogen granules and the corpora amylacea variety of polyglucosan bodies. Both granules and amyloid bodies were stained positively in contrast to the remaining structures of the brain tissue which remained unstained. This demonstrates that β-granules as well as filamentous and amorphous components of amyloid bodies are just different aspects of the polysaccharide molecule. Up to now the same kind of cytochemical evidence has been supplied for Lafora bodies of human material and Lafora-like bodies of rat material. The present study on corpora amylacea of human material shows that amyloid. Lafora, and Lafora-like bodies all behave the same way when stained for polysaccharides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685376
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  • 17
    Electronic Resource
    Electronic Resource
    Spongiform-like changes in Alzheimer's disease (1982)
    Springer
    Acta neuropathologica 56 (1982), S. 146-150 
    Details
    ISSN: 1432-0533
    Keywords: Alzheimer's disease ; Creutzfeldt-Jakob disease ; Spongiform changes ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructural study of the cortex of four patients with sporadic or familial AD, of two agematched controls without dementia, and of one normal pressure hydrocephalus, revealed in all the cases in the neuropil only occasional vacuoles which had a morphology similar to those observed in CJD. The degree of spongiform-like changes was, however, far less prominent than in CJD and considered mild in all the cases examined. Moreover, curled fragments of membranes within the vacuoles were not observed. It is suggested that the mild vacuolization of the neuropil occasionally observed in cortical biopsies of AD is a non-specific finding and cannot be considered a neuropathologic link between AD and CJD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690586
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  • 18
    Electronic Resource
    Electronic Resource
    Central neurocytoma (1982)
    Springer
    Acta neuropathologica 56 (1982), S. 151-156 
    Details
    ISSN: 1432-0533
    Keywords: Central neuronal tumor ; Third ventricle tumor ; Synapses ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The authors report two cases of a rare tumor in adults which were inserted on the fornix and caused a frontal syndrome. By light microscopy, the tumors, highly calcified, were composed of small clear cells forming dense areas in a patchy fibrillary stroma. Electron microscopy revealed a striking neuronal differentiation with numerous synapses. These tumors, for which the term neurocytomas was proposed, were compared with the other CNS neuronal tumors described in the literature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690587
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  • 19
    Electronic Resource
    Electronic Resource
    Oculopharyngeal dystrophy: Ultrastructure of muscles distant from the primary myopathy (1982)
    Springer
    Acta neuropathologica 57 (1982), S. 7-12 
    Details
    ISSN: 1432-0533
    Keywords: Oculopharyngeal muscular dystrophy ; Electron microscopy ; Pectoral and psoas muscles ; Myofibrillar degeneration ; A band fragmentation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pectoral and psoas muscles from a 72-year-old man afflicted with oculopharyngeal muscular dystrophy were processed at autopsy for electron microscopy. The ultrastructural analyses of the pectoral muscle showed myofibrils which exhibited Z line streaming and a general breakdown in the organization of the sarcomere. In addition, some of the myofibrils displayed sites of degeneration at the center of the A band. The changes in the psoas muscles which are distant from the primary myopathic loci of oculopharyngeal muscular dystrophy were more extensive than that seen in the pectoral muscle. Control tissues showed intact myofibrils and little postmortem alteration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688872
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  • 20
    Electronic Resource
    Electronic Resource
    Zur Feinstruktur der Nervenendigungen in den Muskelspindeln des M. lumbricalis der Ratte nach Durchschneidung des Nerven (1982)
    Springer
    Acta neuropathologica 57 (1982), S. 23-36 
    Details
    ISSN: 1432-0533
    Keywords: Muscle spindle ; Electron microscopy ; Nerve endings ; Denervation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The nerve endings in muscle spindles from lumbricalis muscles of the hindpaw of the rat were studied by electron microscopy from 10 h to 7 days after section of the sciatic nerve. No sensory endings were found after 5 days and no motor endings after 3 days. Early changes in sensory endings included accumulation of lamellar bodies, mitochondrial swelling or shrinkage, an edematous appearance of the cytoplasm and disruption of membranes. The predominant way of removal was phagocytosis by activated mesenchymal cells; other endings were incorporated into the sarcoplasm as electrondense bodies. Early changes in motor endings included aggregation or swelling of synaptic vesicles, swelling or shrinkage of mitochondria, edematous change of the cytoplasm and disruption of membranes. The predominant way of removal was incorporation into the cytoplasm of adjacent Schwann cells and degradation to phagolysosomes. Sites of removed sensory endings could be identified by basement membrane reduplication, while the intact subsynaptic apparatus of removed motor endings was either loosely covered by Schwann cell processes, or by fibrillar material, or appeared empty. The differences in the removal of motor and sensory endings are explained by the differences in their anatomic structure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688874
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  • 21
    Electronic Resource
    Electronic Resource
    An electron-microscopic study of the brain of the fruit fly,Drosophila melanogaster, exposed to high-LET krypton (84Kr) particle radiation (1982)
    Springer
    Acta neuropathologica 57 (1982), S. 37-44 
    Details
    ISSN: 1432-0533
    Keywords: Radiation effects ; Nervous system ; Drosophila melanogaster ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fruit flies (Drosophila melanogaster) were exposed to high-LET krypton (84Kr) ions at low (4.2 rad) and high (1,584 rad) doses and killed to assess acute (36 h post-exposure) and late (35 days post-exposure) effects in the brain by means of electron microscopy. The main findings were: (a) glycogen granules appeared in the neuroglial compartment 36 h after exposure to either dose and were no longer present in flies killed 35 days later, (b) neuronal alterations (swelling and membrane disruption) were observed 35 days after exposure to both doses, (c) changes in the neuroglia (electron-dense masses of concentrically arranged membranous structures) were seen 35 days after exposure. The data are discussed in relation to previous research in the fruit fly using argon (40Ar) charged particles and to other radiation studies performed in the mammalian brain with the view of using the insect brain as a model for detailed study of radiation effects on neurons, neuroglia, and the neuron-neuroglia unit.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688875
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  • 22
    Electronic Resource
    Electronic Resource
    Hirano bodies in myelinated fibers of hepatic encephalopathy (1982)
    Springer
    Acta neuropathologica 58 (1982), S. 307-310 
    Details
    ISSN: 1432-0533
    Keywords: Hirano body ; Hepatic encephalopathy ; Oligodendroglia ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Inclusions, essentially identical to Hirano bodies, were observed in the substantia nigra, dentate nuclei, and frontal lobes in three autopsy cases of hepatic encephalopathy. Similar inclusions were not observed in these areas in nine controls. The inclusions were mainly seen in the inner loops of the myelinated fibers, between the myelin lamellae, and among degenerated myelin sheaths. The same inclusions were rarely observed in postsynaptic terminals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688615
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  • 23
    Electronic Resource
    Electronic Resource
    The permeability alteration of brain and spinal cord vasculature to horseradish peroxidase during experimental decompression sickness as compared to the alteration in permeability induced by hyperosmolar solution (1982)
    Springer
    Acta neuropathologica 57 (1982), S. 179-187 
    Details
    ISSN: 1432-0533
    Keywords: Decompression sickness ; Hypertonic solutions ; Blood-brain barrier ; Blood-spinal cord barrier ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The permeability of microvasculature in the cerebral cortex, neostriatum, and spinal cord to i. v. injected horseradish peroxidase (HRP) has been investigated in rats following experimental compression to 6.1 bars (abs.) air for 90 min, and subsequent decompression to the ambient pressure in 1 min. For comparison, 1 ml of 2.0 M urea was injected into the right common carotid artery of rats during 15 s. After exposure to compression-decompression, under the light microscope focal leaky areas were found in all the regions examined. The leakage was most prominent in the grey matter of the spinal cord, and the cerebral cortex. In decompressed rats, arterioles were most often the site of peroxidase extravasation, whereas extravasation of HRP was less frequently displayed by capillaries and venules. In urea-treated rats, capillaries and venules frequently displayed extravasation of HRP as well. Parenchymal cells accumulated the trace adjacent to the leaky areas. Under the electron microscope, the extravasation of HRP was associated with peroxidase-containing pleomorphic vesicular structures in the endothelium, both in decompressed and urea-injected rats. Moreover, in contrast to decompressed rats, the junctions between endothelial cells were penetrated by the trace in urea-treated rats. Accordingly, the results indicate that during decompression sickness the pathway for the extravasation of proteins is through vesicular transfer, whereas the injection of hyperosmolar urea induces extravasation, both through vesicular transfer and junctions between the endothelial cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685387
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  • 24
    Electronic Resource
    Electronic Resource
    Muscle fiber type morphology and distribution in paraplegic patients with traumatic cord lesion (1982)
    Springer
    Acta neuropathologica 57 (1982), S. 243-248 
    Details
    ISSN: 1432-0533
    Keywords: Skeletal muscle ; Paraplegia ; Complete spinal cord lesion ; Histopatology ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Biopsies of the rectus femoris muscle of 22 paraplegic patients with complete acute spinal cord transection due to trauma were taken for enzyme-histochemical and electron-microscopic studies in successive stages starting from the occurrence of the accident (1–17 months). Ingravescent muscular atrophy was demonstrated with a progressive decrease in the fiber diameter and changes in the fiber type distribution with predominant type II atrophy in the first stage and type I atrophy in the later stage of the cord transection. Muscular “neurogenic” changes, such as angular dark atrophic fibers, targetoid fibers, and type predominance are frequently observed. Myopathic alterations are observed in a low percentage in the later stages of the lesion. The ultrastructural findings are characterized by myofibrillar alterations and by dilatation and proliferative phenomena of the sarcoplasmic reticulum and T-system. There are ingravescent accumulation of lipid, interstitial fibrosis and microcirculatory alterations. The possible mechanism of “central” muscle atrophy is reviewed and discussed with reference to the morphological findings.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00692178
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  • 25
    Electronic Resource
    Electronic Resource
    The ultrastructural development of distal nephron segments in the human fetal kidney (1982)
    Springer
    Anatomy and embryology 164 (1982), S. 19-41 
    Details
    ISSN: 1432-0568
    Keywords: Human kidney ; Nephron development ; Distal segments ; Electron microscopy ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructural development of the human distal nephron was studied in fetuses 14–18 weeks of gestational age. The three-dimensional course of the nephrons was traced in serial semi-thin sections. Single semi-thin sections containing defined distal nephron segments were then reembedded, thin-sectioned and analyzed by electron microscopy. In stage I (renal vesicle) and stage II (S-shaped body) epithelial cells were essentially similar in ultrastructure. In stage III there were only minor variations in cell ultrastructure between distal nephron segments, but distinct differences were observed between proximal and distal tubule cells, the former being the most differentiated. The segments which are present in nephrons of adult kidneys could be identified in stage IV and some ultrastructural differences recognized between the cells. However, the amplification of the baso-lateral membrane, which is prominent in iontransporting mature distal segments, was almost absent and the baso-lateral membrane area per unit tubule length was similar in all distal segments. Intercalated cells were present towards the end of the distal convoluted and in the connecting tubule in stage IV but the ampulla of the collecting tubule was composed of cells with a uniform ultrastructure. Cell ultrastructure varied again to some extent in the collecting tubule. The present observations demonstrate that distal nephron segments in the human kidney are structurally undifferentiated in the early fetal development and suggest that they only to a limited extent are capable of modifying the composition of the tubular fluid.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00301876
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  • 26
    Electronic Resource
    Electronic Resource
    Immunoglobulin production and secretion in bence jones protein myeloma and “nonsecretory” myeloma (1982)
    Springer
    Annals of hematology 45 (1982), S. 121-129 
    Details
    ISSN: 1432-0584
    Keywords: Multiple myeloma ; Immunoglobulin ; Electron microscopy ; Fluorescent antibody technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using our electron microscopic method for polysome analysis and an immunofluorescent technique we studied Ig production and secretion by tumor cells in seven BJP myeloma patients and seven “nonsecretory” myeloma patients. In BJP myeloma Ig production and secretion is of three types: Type 1, only L-chains are synthesized and secreted; Type 2, the myeloma cells show fluorescence for H-chains, but upon polysome analysis there is no peak at polysomes corresponding to H-chain production; Type 3, the myeloma cells show fluorescence for H-chains, and polysome analysis shows two peaks corresponding to L- and H-chain production. Polysome analysis of “nonsecretory” myelomas show the presence of only very few membrane-bound polysomes and their distribution curves are entirely different from those of “ordinary” myeloma. Furthermore, the distribution patterns vary among seven cases. Results obtained by polysome analysis and immunofluorescent technique suggest that the “nonsecretory” myeloma could be divided into several subtypes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00319940
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  • 27
    Electronic Resource
    Electronic Resource
    Tubular aggregates in skeletal muscle of chronic alcoholic patients (1982)
    Springer
    Acta neuropathologica 56 (1982), S. 250-254 
    Details
    ISSN: 1432-0533
    Keywords: Skeletal muscle ; Chronic alcoholism ; Tubular aggregates ; Histochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The presence of tubular aggregates (TA) in type II muscle fibers in two of 20 alcoholic patients with chronic liver disease, and with no apparent neuromuscular disorder, is reported. The localization, histochemical reactions, and ultrastructural features of the TA are similar to those previously described in other conditions. In one of the two cases TA were demonstrated by E/M observations only and not by histochemistry. No correlations were found between the biochemical changes and the presence of tubular aggregates. We believe that TA are long-standing structures since the muscle biopsies were performed 12 and 13 days after the ingestion of alcohol had been discontinued. They may represent a non-specific response of the sarcoplasmic reticulum to compensate for the deficient calcium uptake reported in alcoholic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00691255
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  • 28
    Electronic Resource
    Electronic Resource
    Cerebrovascular pathogenesis in the telencephalon of the loop-tail mouse: A transmission electron-microscopic study (1982)
    Springer
    Acta neuropathologica 58 (1982), S. 177-182 
    Details
    ISSN: 1432-0533
    Keywords: Cerebral vessels ; Telencephalon ; Looptail mutant mouse ; Pathogenesis ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cerebral capillaries in the telencephalon of normal (+/+;Lp/+)_and abnormal (Lp/Lp) loop-tail mutant mice were studied chronologically by means of electron microscopy at stages ranging from 15 through 18 days of gestation. In the abnormal tissue, neural rosettes were common, and cellular material and red blood cells were often contained within the lumen of the rosettes. The endothelial cells of telencephalic blood vessels in the abnormal brains showed a persistence of cellular projections, subluminal vacuoles, and swollen mitochondria beyond the stage when these features ordinarily disappear in normal embryonic cerebral vessels. The endothelial cells in the abnormal brains also failed to become fully invested with pericytes, and red blood cells gradually infiltrated the neural tissue, particularly in subependymal regions, at 16–18 days of gestation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690798
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  • 29
    Electronic Resource
    Electronic Resource
    Fine structure of merkel cells after PUVA treatment (1982)
    Springer
    Archives of dermatological research 274 (1982), S. 373-375 
    Details
    ISSN: 1432-069X
    Keywords: Merkel cell ; PUVA ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403744
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  • 30
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of intravenous glibenclamide investigated by a high performance liquid Chromatographic assay (1982)
    Springer
    Diabetologia 23 (1982), S. 37-40 
    Details
    ISSN: 1432-0428
    Keywords: Glibenclamide ; pharmacokinetics ; high performance liquid chromatography ; plasma insulin ; blood glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A simple high performance liquid Chromatographic assay for the determination of plasma glibenclamide concentrations is described. This resolved glibenclamide from normal plasma constituents. The calibration curve of the assay was linear over the range 10–500 μg/1 and the minimum level of detection was 2 μg/1. Within-assay coefficients of variation were 11.6% (20 μg/1); 5.3% (50 μg/1); 6.8% (100 μg/1); between-assay coefficients of variation were 8.4% (20 μg/1); 4.7% (50 μg/1) and 7.4% (100 μg/1). The assay was used to study the pharmacokinetics of a 1 mg intravenous dose of glibenclamide in eight normal subjects. The mean half-life was found to be 1.47±0.42 h (SD) and no evidence for a non-linear β-phase or slowly equilibrating ‘deep’ compartment was found although this could not be rigorously excluded. The mean systemic drug clearance was 78±29 ml·h-1·kg-1 and the apparent volume of distribution in the β-phase was 155±44 ml/kg. The median time of maximum response of plasma immunoreactive insulin was 25 min and the median time of maximum blood glucose response was 53 min. No correlation could be found between the pharmacokinetics of glibenclamide and these responses in fasted normal individuals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00257728
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  • 31
    Electronic Resource
    Electronic Resource
    Ultrastructural evidence for inhibition of chitin synthesis by nikkomycin (1982)
    Springer
    Development genes and evolution 191 (1982), S. 205-207 
    Details
    ISSN: 1432-041X
    Keywords: Chitin inhibition ; Nikkomycin ; Cuticle ; Electron microscopy ; Epilachna varivestis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The nucleoside antibiotic nikkomycin has proved to be an effective inhibitor of chitin synthesis in the Mexican bean beetleEpilachna varivestis. Ultrastructural investigations show defects in the procuticular area after nikkomycin application which suggest the complete absence of chitin. A cuticle like this is inflexible and too brittle to satisfy its normal function as an exoskeleton. The individuals are not able to free themselves from the exuvia and finally die. Therefore nikkomycin seems to be a potential insecticide with high specifity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00848337
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  • 32
    Electronic Resource
    Electronic Resource
    Partial purification and characterization of the bone resorption factor fromActinomyces viscosus (1982)
    Springer
    Calcified tissue international 34 (1982), S. 49-53 
    Details
    ISSN: 1432-0827
    Keywords: Bacterial amphophile ; Purification ; Chemistry ; Resorption ; Ca influx ; Cyclic AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The bone resorptive factor and amphipathic antigen (AcA) previously identified by us in preparations fromActinomyces viscosus have been partially purified, characterized chemically, and compared. They elute at the same location on chromatography with Ac 22. The fatty acid composition of AcA and the bone resorptive factor is the same. Some differences in carbohydrate composition are observed. TheActinomyces factor does not affect calcium influx or cyclic AMP in isolated bone cells. Therefore it is concluded that AcA stimulates resorption either by gaining entrance into bone cells or by way of a yet undetermined second messenger.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02411208
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  • 33
    Electronic Resource
    Electronic Resource
    Long-term study of liver damage following subcutaneous injection of airborne particle extracts and polycyclic aromatic hydrocarbon fractions (1982)
    Springer
    International archives of occupational and environmental health 49 (1982), S. 305-314 
    Details
    ISSN: 1432-1246
    Keywords: Polycyclic aromatic hydrocarbon ; Liver ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Female NMRI mice aged 9–12 weeks were each given a single subcutaneous injection of 0.5 ml of a suspension containing either the total extracts or the polycyclic aromatic hydrocarbon (PAH) fraction of airborne particles. Both the total extracts and PAH fractions contain 3 Vg benzopyrene. After about 15 months the livers were removed from the animals, which had by that time developed tumors at the injection site, and were subjected to ectronmicroscopical study. The essential alterations were observed in the nucleoli and the cell nuclei, which had greatly proliferated and exhibited irregular nuclear membranes. Advanced fibrosis was observed in central liver specimens of all groups. Marked alterations were also observed in the mitochondria and the mitochondria) cristae as well as in the bile canaliculi. Intracytoplasmic glycogen usually occurred densely clustered along the periphery of the cell. It may be concluded from the observations that both the total extract of atmospheric suspended particulate matter and the PAH fraction cause hematogenic damage to the liver following subcutaneous injection, a finding which cannot be interpreted as metastatic carcinoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00377939
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  • 34
    Electronic Resource
    Electronic Resource
    Biologic characterization of human bone tumors I. Ewing's sarcoma (1982)
    Springer
    Journal of cancer research and clinical oncology 104 (1982), S. 171-180 
    Details
    ISSN: 1432-1335
    Keywords: Ewing's sarcoma ; Type IV collagen ; Factor-VIII-associated protein ; Endothelial differentiation ; Electron microscopy ; Immunofluorescence microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Six cases of Ewing's sarcoma were investigated by electron and immunofluorescence microscopy. A layer of basement membrane-like deposits was found between typical principal and secondary tumor cells. To clarify the nature of these ultrastructural deposits, antibodies against collagen type IV were applied to frozen sections of corresponding tumor tissue. This reaction revealed type IV collagen as a regular component of basement membranes in nonneoplastic tumor capillaries, but it was equally able to localize collagen type IV between single tumor cells in capillary-free areas. With the same method, factor-VIII-associated protein, predominantly found in endothelial cells, could be demonstrated in some tumor cells. These results demonstrate that, in addition to anaplastic cells, some tumor cells are found in Ewing's sarcoma that share certain differentiating features with the endothelial cell.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402065
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  • 35
    Electronic Resource
    Electronic Resource
    Ultrastructural pathology of human lymphocytes in lysosomal disorders: a contribution to their morphological diagnosis (1982)
    Springer
    European journal of pediatrics 138 (1982), S. 179-185 
    Details
    ISSN: 1432-1076
    Keywords: Lymphocytes ; Metabolic disorders ; Inclusions ; Lysosomes ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ultrastructural examination of peripheral lymphocytes was performed in 28 cases of various lysosomal diseases, including infantile, late infantile and juvenile neuronal ceroid-lipofuscinoses (NCL), mucopolysaccharidoses (MPS), juvenile and adult metachromatic leukodystrophies (MLD), GM1-gangliosidosis, one patient with presumed mucolipidosis type IV, mucolipidosis type III, and glycogenosis type II. Based on our own observations on the ultrastructure of lymphocytes in lysosomal disorders, our results may be divided into the following 3 groups: 1. pathological findings with specific inclusions: each type of NCL, presumed mucolipidosis type IV, glycogenosis type II; 2. pathological findings with vacuoles: types I-H, II, III-A and III-B, IV, VI-A and VI-B of MPS, GM1-gangliosidosis; 3. apparently no pathological findings: juvenile and adult MLD, mucolipidosis type III, GM2-gangliosidosis, Gaucher disease. These results led us to conclude that morphological investigations utilizing lymphocytes do not always offer sufficient diagnostic information although easy accessibility favors diagnostic ultrastructural studies of lymphocytes. Such morphological studies should be supplemented by diagnostic biochemical methods.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00441150
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  • 36
    Electronic Resource
    Electronic Resource
    The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide in essential hypertensives (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 287-291 
    Details
    ISSN: 1432-1041
    Keywords: tolmesoxide ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tolmesoxide is a new, direct-acting vasodilator drug for use in the management of both hypertension and cardiac failure. In 6 essential hypertensives inadequately controlled by combined β-blocker and diuretic therapy (average supine blood pressure 178/103 mm Hg) the addition of tolmesoxide (300–900 mg daily) was associated with a significant improvement in blood pressure control (average supine blood pressure 161/89 mmHg). The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide have also been studied because, particularly at higher doses, the drug has been associated with upper gastrointestinal upset and it has been empirically recommended that it be taken with food. The blood pressure and heart rate responses were not significantly different when tolmesoxide was taken fasting or with food. Food resulted in a significant reduction in the peak plasma tolmesoxide concentration (2.14 µg/ml compared to 2.97 µg/ml) and a significant increase in the time to reach peak plasma concentration (1.67 h compared to 0.63 h). Although there was no impairment of its hypotensive effect, food significantly altered the pharmacokinetics of tolmesoxide and may therefore be useful in reducing the gastrointestinal disturbance associated with its use. In the treatment of inadequately controlled hypertension, tolmesoxide has a limited role as an alternative vasodilator.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637615
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  • 37
    Electronic Resource
    Electronic Resource
    Kinetics of a high dose of piretanide in renal failure (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 307-310 
    Details
    ISSN: 1432-1041
    Keywords: piretanide ; renal failure ; high dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of piretanide was studied in patients with renal failure. After oral administration of a high dose of piretanide (96 mg), the pharmacokinetic parameters were: elimination rate constant 0.346±0.072 h−1, half life 2.00±0.35 h, and total plasma clearance 119.55±35.90 ml · min−1. Compared to the values obtained in adults with normal renal function, these results show a decrease in total plasma clearance, but conservation of the metabolic clearance which amounts to 45% of the total clearance in the healthy adult.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637618
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  • 38
    Electronic Resource
    Electronic Resource
    Correlation between pharmacokinetics and clinical effects of ergotamine in patients suffering from migraine (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 397-402 
    Details
    ISSN: 1432-1041
    Keywords: ergotamine ; migraine ; radioimmunoassay ; clinical effects ; adverse effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic availability of ergotamine after a single therapeutic oral or rectal dose was studied using a radioimmunoassay during the headachefree state in 24 patients suffering from migraine. Plasma concentrations of the drug were compared with anamnestic data about its clinical effects in the same patients. Among 12 patients with a good therapeutic response to medication, the mean plasma ergotamine levels stayed in the range 0.20 to 0.50 ng/ml for 6h. Their mean plasma levels at 30 min (0.33ng/ml) and 1h (0.40ng/ml) were significantly higher than those (0.06 and 0.08ng/ml, respectively) in 9 patients with only a moderate therapeutic response. In 9 patients with a moderate and 3 with a poor therapeutic response, the mean plasma level generally stayed below 0.10ng/ml. The mean peak concentrations in moderate (0.13 ng/ml) and poor (0.11ng/ml) responders appeared later (at 3h) than in good responders (at 1h). Side effects of the medication appeared to be associated with relatively low plasma levels of ergotamine and also with delayed maximum plasma concentrations of the drug. The present results suggest that the time of the maximum plasma drug level is an important determinant of the clinical effects of ergotamine, and that a good therapeutic response may be expected if a plasma ergotamine level of 0.20ng/ml or more is achieved within 1 hour after oral or rectal administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542326
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  • 39
    Electronic Resource
    Electronic Resource
    Difference between single and multiple dose pharmacokinetics of orphenadrine hydrochloride in man (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 343-350 
    Details
    ISSN: 1432-1041
    Keywords: orphenadrine ; single dose ; multiple doses ; bioavailability ; pharmacokinetics ; N-demethylorphenadrine ; metabolism ; dog ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of orphenadrine were measured by a specific gaschromatographic method in 5 healthy male volunteers after a single oral dose of orphenadrine hydrochloride 100mg. The single dose pharmacokinetic profile of orphenadrine was evaluated from these data. The elimination half-life ranged from 13.2–20.1 h after the commercial tablet formulation. Plasma concentrations, determined in volunteers and patients under different conditions of repeated oral administration of the same formulation of orphenadrine hydrochloride exceeded the theoretical values, predicted from the single dose pharmacokinetics, by a factor 2 to 3. The elimination half-lives after discontinuation of treatment showed a 2 to 3-fold increase over the single dose values. This demonstrates a clear discrepancy between the multiple and single dose pharmacokinetics of orphenadrine. Experiments in dogs suggested competition for biotransformation between orphenadrine and its metabolite N-demethylorphenadrine. Product inhibition of this type could explain the observed discrepancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637624
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  • 40
    Electronic Resource
    Electronic Resource
    Comparative pharmacokinetic analysis of amoxycillin using open two and three-compartment models (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 273-279 
    Details
    ISSN: 1432-1041
    Keywords: amoxycillin ; i.v. administration ; pharmacokinetics ; two- and three-compartment models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic characteristics of amoxycillin were studied in healthy volunteers after intravenous injection of 250 mg, 500 mg and 1,000 mg, and infusion of 2 g and 5 g. Serum concentrations were fitted using either bi- and tri- exponentional equations. Comparison of the regression curves obtained revealed that the three-compartment model gave a better fit to the serum concentration versus time curve. It was evident that there was a third, slow, dose dependent phase of disposition. This result has been confirmed by the fact that the terminal half life of amoxycillin on cessation of a continuous infusion is significantly greater than after acute administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545227
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  • 41
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and bioavailability of indapamide — A new antihypertensive drug (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 295-299 
    Details
    ISSN: 1432-1041
    Keywords: indapamide ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Two formulations of indapamide tablets (2.5 mg) were given as a 5.0 mg dose and the subsequent blood levels were compared to those obtained after administration of a 5.0 mg solution. The study was conducted as a randomized three-way crossover design using healthy male volunteers. The drug was well tolerated by all the subjects involved. The area under the blood concentration versus time curve, extrapolated to infinity was essentially the same for all three formulations (4.2, 4.7, and 4.4 µg-h/ml). Statistical comparison of the blood levels from the two tablets showed that one tablet had a significantly greater maximum blood concentration (263 vs 231 ng/ml) and a significantly shorter time of maximum blood concentration (2.3 vs 3.5 h). Cmax (333 ng/ml) and tmax (0.7 h) values for the solution were significantly higher than either tablet. The average half-life (β-phase) for all three formulations was 15 h, while the average systemic clearance was 20 ml/min. Indapamide has a low clearance rate and there was no evidence that the drug undergoes a first-pass effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548396
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  • 42
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of TRIS (hydroxymethyl-)aminomethane in healthy subjects and in patients with metabolic acidosis (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 257-264 
    Details
    ISSN: 1432-1041
    Keywords: TRIS buffer ; metabolic acidosis ; pharmacokinetics ; cellular uptake ; renal excretion ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To investigate the pharmacokinetics of TRIS, an infusion of the buffer was given to 6 healthy volunteers (121 mg/kg=1 mmol/kg; pH 7.4) and to 20 patients suffering from metabolic acidosis (109–376 mg/kg; pH 10.9). The drug exhibited two-compartment characteristics in volunteers (t0.5,β=5.6 h) and patients with intact renal function (t0.5,β=16.3–45.6 h). The final volume of distribution (Vβ) indicated uptake into tissues, but equilibration between body compartments was slow. Mainly unchanged TRIS was eliminated by the kidney; 82% of the administered dose was recovered from 24 h-urine of healthy subjects. In the patients a linear correlation between creatinine-clearance and TRIS-clearance was observed, the latter always being somewhat greater than the former. Only insignificant amounts of the drug were found in bile and gastric juice. In anuric patients the plasma concentration of TRIS declined monoexponentially, with a half-life between 10 and 58 h. Haemodialysis or haemofiltration did not influence this process. From the data it seems questionable whether cellular uptake of TRIS is an important factor in the therapy of intracellular acidosis, but the possibility of drug accumulation must be borne in mind if repeated doses are given to the same patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545225
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  • 43
    Electronic Resource
    Electronic Resource
    Influence of food on the kinetics of 8-methoxypsoralen in serum and suction blister fluid in psoriatic patients (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 75-80 
    Details
    ISSN: 1432-1041
    Keywords: psoriasis ; 8-methoxypsoralen ; food influence ; suction blister fluid ; serum ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food on the kinetics of 8-methoxypsoralen (8-MOP) in serum and suction blister fluid was evaluated in a cross-over study in 19 psoriatic patients under PUVA treatment. The peak serum concentration of 8-MOP was reached 1.5 h after ingestion on an empty stomach, and in suction blister fluid the maximum concentration was already present in the first sample taken after 2 h, the time when UVA radiation was given. The postprandial kinetics of 8-MOP in serum and suction blister fluid differed, the highest levels being reached, respectively, at 2.4 and 3 h after intake, i.e. in both body fluids after irradiation had started. The side effects of 8-MOP, such as nausea and dizziness, in the two groups were similar. The present results indicate that to optimize the therapeutic effect of PUVA in individual patients, 8-MOP should be given on an empty stomach.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061380
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  • 44
    Electronic Resource
    Electronic Resource
    Clinical pharmacology of a new β-adrenoceptor blocking drug, befunolol (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 189-195 
    Details
    ISSN: 1432-1041
    Keywords: befunolol ; propranolol ; pharmacokinetics ; pharmacodynamic effects ; beta-adrenoceptor blocking agent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Repeated doses of a new β-adrenoceptor blocking agent, befunolol, were administered orally to adult male volunteers for a cross-over comparison with propranolol. The β-adrenoceptor blocking activity of befunolol was greater than that of propranolol when assessed by the percentage reduction in exercise-induced tachycardia. The elimination half-life of drug was significantly prolonged on repeated administration of propranolol, but not of befunolol. The percentage reduction in exercise-induced tachycardia was highly correlated with the log plasma level of each drug. Both drugs produced a significant reduction in pre-exercise systolic and diastolic blood pressure, and significant attenuation of exercise-induced rise in systolic blood pressure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547552
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  • 45
    Electronic Resource
    Electronic Resource
    Kinetics of ergotamine after intravenous and intramuscular administration to migraine sufferers (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 235-240 
    Details
    ISSN: 1432-1041
    Keywords: ergotamine ; pharmacokinetics ; migraine ; plasma drug levels ; i.v. administration ; i.m. administration ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of ergotamine has been investigated in migrainous patients using a new, specific, sensitive HPLC assay (detection limit 100 pg/ml plasma). 10 patients were given ergotamine tartrate 0.5 mg i.v. and 5 of them received the same dose i.m. 2–3 weeks later. Blood samples were collected for up to 54 h following administration and the plasma concentration were analysed. After intravenous administration the plasma ergotamine declined rapidly, with an initial distribution half-life of 3 min followed by a mean terminal half-life of 1.86 h (range 90–155 min). The mean total plasma clearance was 11.0 ml kg−1 min−1, and the volume of distribution (Vdβ ) was 1847.6 ml kg−1. Individual t1/2β showed a positive linear correlation with the individual Vdβ . The intramuscular absorption of ergotamine was rapid and maximum plasma levels were usually obtained 10 min following administration. The biological availability was incomplete and variable at 46.6% (range 28.3–60.8%).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547560
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  • 46
    Electronic Resource
    Electronic Resource
    Does cantharides blister fluid provide access to the peripheral compartment? (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 327-330 
    Details
    ISSN: 1432-1041
    Keywords: bendroflumethiazide ; cantharides plasters ; blister fluid ; plasma levels ; pharmacokinetics ; compartmental analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of bendroflumethiazide (BFT) was investigated following the oral administration of 10 mg to 3 healthy volunteers. Each subject participated twice in the study. BFT was determined in plasma and cantharides blister fluid from 1/2 to 30 h post administration. Blister fluid was obtained from blisters 10–22 h old. Plasma levels were fitted to a tri-exponential equation and the concentration of the drug in the peripheral compartment was calculated from the microscopic rate constants. In 5 of 6 cases investigated, cantharides blister fluid levels paralleled the concentration of the drug in the peripheral compartment. The mean blister fluid levels exceeded the calculated concentration in Compartment 2 1.46 fold. In one case, the blister fluid level paralleled the plasma level. This subject clearly differed from the others as more than 10 h were required for blister formation in her. The results suggest that following the administration of BFT, cantharides blister fluid behaves as part of the peripheral compartment. The possible value of studying blister fluid levels in pharmacokinetic investigations is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613614
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  • 47
    Electronic Resource
    Electronic Resource
    The influence of free fatty acids on valproic acid plasma protein binding during fasting in normal humans (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 343-347 
    Details
    ISSN: 1432-1041
    Keywords: valproic acid ; fatty acids ; plasma protein binding ; pharmacokinetics ; drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of physiologic variations of free fatty acid levels on in vivo valproic acid plasma protein binding was studied in 6 healthy adult subjects. 14 blood samples were taken during a 12-h dosing interval at steady state while in a fed condition and also during a 27 h fast. Free fraction and total valproate concentration were determined by equilibrium dialysis and GLC, respectively. Free fatty acid levels were determined from both fresh samples and samples incubated at 37°C for 12 h, the latter in order to simulate equilibrium dialysis conditions. Fasting resulted in increased serum free fatty acid levels in all subjects, ranging from 34–182% (p〈0.01). Incubation also caused free fatty acid levels to rise, more so in fed samples (50–87%,p〈0.01) than in fasting samples (10–50%,p〈0.01). Fasting resulted in a 9% increase in the mean free fraction for all subjects combined (p〈0.01). Regression analysis of 180 sets of values for free fraction, total valproate concentration and free fatty acid level suggested that valproate concentration accounts for 17% and free fatty acid level for 37% of the variation in free fraction. Mean clearance was unchanged by fasting despite an increased free fraction suggesting decreased intrinsic clearance (i.e. decreased metabolism) of valproate under these conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613618
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  • 48
    Electronic Resource
    Electronic Resource
    Pharmacokinetic studies of oral L-threo-3,4-dihydroxyphenylserine in normal subjects and patients with familial amyloid polyneuropathy (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 463-468 
    Details
    ISSN: 1432-1041
    Keywords: L-threo-3,4-dihydroxyphenylserine ; familial amyloid polyneuropathy ; pharmacokinetics ; norepinephrine ; pressor response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of oralL-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was studied in 7 normal subjects and 7 patients with familial amyloid polyneuropathy. Each person swallowed a single 300 mg dose in the fasting state, andL-threo-DOPS in plasma and urine was determined by high performance liquid chromatography with an electrochemical detector after separation on a boric acid gel column.L-threo-DOPS was slowly absorbed by normal subjects; the maximum plasma concentration occurred 3 h after administration and 20% of the oral dose was recovered unchanged in the urine within 12 h. It induced a substantial elevation of plasma norepinephrine levels, the peak being attained at 5 h, but without any change in blood pressure. In the patients, the absorption and metabolism ofL-threo-DOPS were delayed, and a prolonged pressor response was observed, with a peak after 8 h. It was concluded that the effects on plasma norepinephrine and blood pressure of oralL-threo-DOPS were essentially equal to those of twice as large a dose ofDl-threo-DOPS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00605999
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  • 49
    Electronic Resource
    Electronic Resource
    Cimetidine dosage regimen for patients with renal failure and for geriatric patients (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 501-504 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; uraemia ; dosing regimen ; prediction ; computer program ; old age ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Using a recently developed computer program based on a correlation between methods to predict the elimination half-life and apparent volume of distribution of cimetidine and actual data from patients, ideal dosage regimens were generated for patients with renal impairment and for geriatric patients, together with the corresponding maximum and minimum steady state concentrations. Using the ideal dosage regimens, practical regimens with feasible dosing intervals of 6, 8 and 12 h were computed, which should result in therapeutic concentrations of 0.4 to 1.3 µg/ml. For uraemic patients and geriatric patients above the age of 75 years it would be desirable to have an additional oral 100 mg dosage form.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637496
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  • 50
    Electronic Resource
    Electronic Resource
    Overdosage of antidepressants: Clinical and pharmacokinetic aspects (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 513-521 
    Details
    ISSN: 1432-1041
    Keywords: amitriptyline ; imipramine ; clomipramine ; antidepressant overdose ; clinical effects ; pharmacokinetics ; cardiotoxicity ; maprotiline ; doxepine ; nortriptyline ; opipramol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24 h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 µg/l, with concentrations above 500 µg/l in 11 cases. The serum amitriptyline concentration remained high for 3–4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 µg/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidpressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60–500 µg/l) but not high (〉500 µg/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637499
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  • 51
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and pharmacodynamic studies of oral clonidine in normotensive subjects (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 1-5 
    Details
    ISSN: 1432-1041
    Keywords: clonidine ; noradrenaline ; pharmacokinetics ; arterial blood pressure ; plasma concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of clonidine and its relation to blood pressure response and side effects were studied after single oral doses of 75 µg, 150 µg and 250 µg in normotensive subjects. Following oral administration, the drug was absorbed rapidly after an initial lag time of 19–22 min and peak levels were reached between 2.4 and 2.9 h. Sampling over 48 h was necessary for accurate estimation of pharmacokinetic parameters. Post-peak plasma concentration declined in a monoexponential manner and the half-life of the elimination phase ranged from 9.0 to 15.1 h. Maximum plasma concentration (Cmax) and area under curve (AUC) increased proportionally with increasing doses. Clonidine produced significant reductions in the pulse rate and a dose dependent decrease in blood pressure. Clonidine (150 µg) also produced significant reductions in plasma catecholamine levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061368
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  • 52
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of intravenous timolol in patients with acute myocardial infarction and in healthy volunteers (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 43-47 
    Details
    ISSN: 1432-1041
    Keywords: timolol ; pharmacokinetics ; pharmacodynamics ; healthy subjects ; cardiac infarction patients ; i.v. therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Disappearance pharmacokinetics, pharmacodynamics and general tolerance of i.v. timolol were compared in 12 healthy volunteers and 10 patients with a definite or proven acute myocardial infarction. The drug was administered to the patients immediately on arrival at the hospital after a median delay time of 4 h. Tolerance to the injections was good in both volunteers and patients. The study revealed disappearance pharmacokinetics that were similar in volunteers and patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061376
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  • 53
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of metipranolol in normal man (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 293-301 
    Details
    ISSN: 1432-1041
    Keywords: metipranolol ; deacetyl metipranolol ; pharmacokinetics ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters of deacetyl metipranolol were determined after i.v. infusion of increasing doses (6–25 mg) in 17 normal volunteers. In a second cross-over trial, deacetyl metipranolol 10 and 20 mg were infused in a further 10 subjects, and in a third trial another 20 volunteers received metipranolol 40 mg orally. Metipranolol is very rapidly and completely deacetylated in man, so all pharmacokinetic data refer to deacetyl metipranolol, which was assayed by gas chromatography-mass spectrometry. The pharmacokinetic analysis was performed using a recently developed model, using a volume of distribution which is variable with time. The following data were obtained after oral administration: (mean values); lag-time 7.3 min; tmax 50 min, invasion half-life 6.3 min; elimination half-life 3 h; urinary excretion of unchanged drug approximately 4% of the dose. The experiments with infusion of increasing doses, as well as the cross-over study with 10 and 20 mg i.v., showed dose-linearity of the kinetics. The respective mean half-lives of elimination were 2.6, 2.9 and 2.8 h. The mean total, renal and extra-renal clearances amounted to 1237 ml/min, 149 ml/min and 1068 ml/min, respectively. The distribution coefficient was 3.5 l/kg, and protein binding amounted to 70% within the range of therapeutic concentrations. Absolute bioavailability was found to be approximately 50% by several different evaluation procedures. Thus, the pharmacokinetic profile of metipranolol shares features of both the lipophilic and the hydrophilic groups of β-blocking agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637616
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  • 54
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of bendroflumethiazide alone and in combination with propranolol and hydralazine (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 315-323 
    Details
    ISSN: 1432-1041
    Keywords: bendroflumethiazide ; propranolol ; hydralazine ; pharmacokinetics ; thin-layer chromatography ; fluorimetry ; fixed combination product
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bendroflumethiazide (Bft) was administered to 6 healthy subjects at 3 different dose levels (2.5, 5 and 10 mg) in a cross-over design, either as capsules (2.5 mg) or as tablets (5 mg). Its pharmacokinetics were evaluated then and following administration of a fixed combination of Bft with propranolol and hydralazine to a further 7 volunteers. Plasma and urinary concentrations of Bft were determined by a new fluorimetric — thin-layer chromotography procedure. Peak plasma levels occurred after 2–3 h and averaged 15, 27 and 45 µg/l in the three dose groups. Areas under the plasma concentration — time curves (AUC0→12), which were 75, 147 and 250 µg l−1 h respectively, and cumulative urinary recovery (20%) were independent of the dose administered and the type of formulation. Thus Bft kinetics proved to be linear within the dose range evaluated. The plasma clearance was calculated to be 505 ml/min, renal clearance 108 ml/min and nonrenal clearance 396 ml/min. Bioavailability of Bft was not altered following administration of the fixed combination. The amount of propranolol found in the circulation did not change, whereas that of hydralazine (determined as apparent hydralazine) increased by 59% when the fixed combination was administered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637620
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  • 55
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and biotransformation of the new benzodiazepine, lormetazepam, in man (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 421-425 
    Details
    ISSN: 1432-1041
    Keywords: benzodiazepine ; lormetazepam ; lormetazepam glucuronide ; transfer to milk ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentrations of lormetazepam and its glucuronide in plasma and milk were determined during administration of 10 daily doses of lormetazepam 2 mg (2 tablets of NOCTAMID® - 1) to five mothers delivered by Caesarian section. Their babies were breast-fed throughout the study, and the plasma levels of lormetazepam and its glucuronide were determined three times in the babies. At 12 and 24h after administration, the plasma level of lormetazepam was about 3.5 ng/ml and 1.8 ng/ml in mothers, and below 0.09 ng/ml in the children. In milk the lormetazepam concentration was below 0.2 ng/ml. The plasma level of glucuronide varied between 24 ng/ml at 12h and 11 ng/ml 24h after administration. Almost no accumulation of unchanged lormetazepam was observed (factor: 1.3). The ratio of the levels of lormetazepam in milk and plasma was estimated to be below 0.06, and for the glucuronide the ratio was 0.04. The quantity of free and conjugated active ingredient transferred to the children via breast milk was calculated to be at most 100 ng/kg, corresponding to 0.35% of the maternal dose, which is regarded as tolerable.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542330
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  • 56
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of gentamicin in malnourrished infants (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 499-504 
    Details
    ISSN: 1432-1041
    Keywords: gentamicin ; malnutrition ; pharmacokinetics ; infant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of gentamicin was investigated in normal and malnourished infants aged 4–10 months. Neither mean “elimination” nor “distribution half life” show any difference, but the volume of distribution was higher in malnourished babies, probably due to their larger total body water.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542045
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  • 57
    Electronic Resource
    Electronic Resource
    Metabolism of pindolol in patients with renal failure (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 423-428 
    Details
    ISSN: 1432-1041
    Keywords: pindolol ; renal failure ; metabolism ; pharmacokinetics ; 14C-pindolol ; blood metabolites ; urinary metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Increased metabolism of pindolol in renal impairment has previously been suggested by pharmacokinetic calculations. The present study was a pharmacokinetic and metabolic investigation in 7 patients with severe renal impairment (endogeneous creatinine clearance below 5 ml/min). All the patients received pindolol 5 mg t.d.s. 5 days. On the sixth day, after an overnight fast, 14C-pindolol 5 mg was given orally as a solution to drink. Blood samples were taken for up to 72 h and urine was collected at intervals up to 96 h for measurement of unchanged pindolol by a fluorimetric method and total radioactivity by liquid scintillation counting. Metabolites in blood and urine were analysed after separation by HPLC. It was found that the plasma levels following a single dose of 14C-pindolol were similar to those observed in healthy volunteers, but the elimination half-life was slightly increased up to 11.5 h. The observed steady state plasma concentrations of pindolol were twice as high but they are still in the therapeutic range of 10 to 100 ng/ml. Therefore, the dose of pindolol could have been reduced by a factor 2, but the reduction was not essential. No active metabolite of pindolol was found in plasma or urine, but elimination of the metabolites was decreased. The elimination half-life following multiple doses was prolonged compared to normal and it was quite comparable to that found for the pharmacodynamic half-life in renal patients. The discrepancy between the present findings and the previous results for metabolism and pharmacodynamic half-life was probably due to the sensitivity of the fluorimetric assay of pindolol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542547
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  • 58
    Electronic Resource
    Electronic Resource
    Modification in the pharmacokinetics of amikacin during development (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 155-160 
    Details
    ISSN: 1432-1041
    Keywords: amikacin ; pharmacokinetics ; development ; neonate ; infant ; child
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition kinetics of a single i.v. dose of amikacin was studied in 6 neonates (6–25 days old), 10 infants (4–18 months) and 8 young children (3–11 years). There was a progressive change in the distribution and elimination kinetics during development. The distribution coefficient of the antibiotic averaged of 0.429, 0.320 and 0.210 l/kg in the newborns, infants and young children, respectively and serum half-life (t1/2 β) in these three groups averaged 2.812, 1.803 and 1.196 h, respectively. Significant differences in certain pharmacokinetic parameters were found between the values in paediatric patients and in adults receiving the same dose. A linear relationship was established between the distribution volume of the antibiotic and the weight of the patients, as defined by the following equation: $${\text{Vd}}_{{\text{ss}}} \left( 1 \right) = 0.976 + 1.140 \cdot {\text{TBW}}\left( {{\text{kg}}} \right);r = 0.954$$ The results suggest that a regimen of very frequent administrations should be employed in infants and young children in order to maintain a therapeutic level throughout treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545971
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  • 59
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    Electronic Resource
    Clinical pharmacokinetics of high dose mebendazole in patients treated for cystic hydatid disease (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 161-169 
    Details
    ISSN: 1432-1041
    Keywords: mebendazole ; hydatid disease ; Echinococcus granulosus ; hepatic disease ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of mebendazole and its metabolites have been monitored in twelve patients after receiving a 10 mg/kg dose for cystic hydatid disease. The mebendazole plasma concentration-time profiles differed considerably between patients; elimination half-lives ranged from 2.8–9.0 h, time to peak plasma concentration after dosing ranged from 1.5–7.25 h and peak plasma concentrations ranged from 17.5 to 500 ng/ml. The mean peak plasma concentration of mebendazole after an initial dose (69.5 ng/ml) was lower than found in patients during chronic therapy (137.4 ng/ml). The plasma AUCTs for the major metabolites of mebendazole (methyl 5-(α-hydroxybenzyl)-2-benzimidazole carbamate and 2-amino-5 benzoylbenzimidazole) were about five times the plasma AUCT found for mebendazole in patients on chronic therapy. It is suggested that the slower clearance of these polar metabolites relative to mebendazole results from enterohepatic recycling. Since mebendazole is also highly plasma protein bound, caution should be observed in administering mebendazole to patients with liver disease. Concentrations of mebendazole found in the tissue and cyst material collected from two patients during surgery ranged from 59.5 to 206.6 ng/g wet weight.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542462
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  • 60
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    Electronic Resource
    Pharmacokinetics of parenteral and oral melperone in man (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 173-176 
    Details
    ISSN: 1432-1041
    Keywords: melperone ; neuroleptic drug ; dose dependent kinetics ; i.m. injection ; i.v. injection ; pharmacokinetics ; oral application
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of melperone (Buronil®, Ferrosan, Sweden) was studied after administration of various parenteral and oral doses to man. After parenteral administration, the data could be fitted to a two-compartment model, but after oral dosing the distribution phase could not be separated from the elimination phase, and so an one-compartment model gave the best fit. The half-lives were about 3–4 h, except after intramuscular injection, when the half-life was about 6 h. The bioavailability of oral doses was about 60% of the intravenous injection. After the highest oral dose of 100 mg, the pharmacokinetics, expressed as AUC or Cmax, showed non-linearity, possibly due to saturation of the hepatic elimination system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545974
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  • 61
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    Electronic Resource
    Distribution of oral ketoconazole to vaginal tissue (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 331-333 
    Details
    ISSN: 1432-1041
    Keywords: ketoconazole ; vaginal candidosis ; oral antimycotic ; distribution ; pharmacokinetics ; vaginal tissue concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma samples and biopsies of vaginal tissue were obtained from 23 healthy women undergoing operative sterilization, 1 to 6 h after a single oral dose of ketoconazole 200 mg. Drug concentrations in plasma and tissue, were measured by a specific gas chromatographic method. The vaginal tissue concentration averaged 2.4 times less than the corresponding plasma levels. Equilibrium between tissue, and plasma was established within 1 h after dosing, when vaginal tissue levels exceeded 1 µg/g. Ketoconazole concentrations decayed monoexponentially over the time interval studied (1–6 h), with the similar half-lives of 1.2 and 1.4 h in plasma and tissue, respectively. Following an oral 200 mg dose, a tissue concentration not less than 0.01 µg/ml was maintained over a 12 h period. This concentration has been shown to prevent outgrowth of the invasive (pseudo) mycelial form ofCandida albicans. Hence, a b.i.d. or t.i.d. dosage schedule of ketoconazole in vaginal candidosis would give continuously effective levels at the site of infection. Ketoconazole concentrations in vaginal fluid are thought to be much higher than in the tissue because of ion-trapping. The present data may explain the efficacy of oral ketoconazole in the treatment of vaginal candidosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613615
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  • 62
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    Electronic Resource
    Kinetics of furosemide in children with chronic renal failure undergoing regular haemodialysis (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 303-306 
    Details
    ISSN: 1432-1041
    Keywords: furosemide ; renal failure ; haemodialysis ; pharmacokinetics ; children ; dosage schedule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Furosemide was measured by gas-liquid chromatography in blood and dialysis fluid from 7 children with chronic renal failure, undergoing regular haemodialysis. It was administered chronically, in two or three daily doses (4.2–9.4 mg/kg). Two children received 1 mg/kg intravenously for determination of the pharmacokinetics. The half-life was longer than in adults and in anephric patients on haemodialysis. Systemic and renal clearance were also much lower. Plasma protein binding in 2 out of 6 cases was reduced as campared to normal adults. The data do not suggest any need to modify the present dosage schedule despite the 4–5 fold increase in the half-life of furosemide. The contribution of haemodialysis to drug clearance was minimal, and accounted for less than 10% of the total clearance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637617
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  • 63
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    Electronic Resource
    The pharmacokinetics of diclofenac sodium in patients with active rheumatoid disease (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 331-334 
    Details
    ISSN: 1432-1041
    Keywords: diclofenac sodium ; rheumatoid disease ; healthy subjects ; serum albumin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic data for diclofenac sodium has been well established in healthy volunteers, whereas in patients with rheumatoid arthritis very little information is available in the literature. A single oral dose of enteric-coated diclofenac sodium was given to 10 patients with active rheumatoid disease, adopting the same procedures used for a group of 10 healthy volunteers in whom pharmacokinetic data was already available. Plasma specimens were collected over a period of 8h following administration and concentrations of diclofenac determined by GLC. Resulting plasma concentration curves were similar to those obtained in the healthy subjects in that areas under curves and terminal half-lives were comparable. However, peak concentrations of diclofenac were significantly reduced in the rheumatoid patients. The lower peak concentrations were correlated with the lower serum albumin levels in the patients which are associated with active rheumatoid disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637622
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  • 64
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    Electronic Resource
    Pharmacokinetic aspects of caffeine in premature infants with apnoea (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 47-52 
    Details
    ISSN: 1432-1041
    Keywords: apnoea ; caffeine ; premature infants ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of caffeine was examined in 13 premature infants (gestational age 25–34 weeks, birth weight 920–2060 g, postnatal age 1–42 days) who received the drug for treatment of opnoea. Caffeine (1% aqueous solution) was given i.v. in single doses; guided by the clinical response infants received between one and seven (mean 2.6) doses of 15 mg/kg. Mean (± SE; range) Clb was extremely slow − 8.5 ml/kg/h (±0.4; 5.8–12.2), t1/2 was prolonged − 65.0 h (±3.7; 48.2–87.5 h) and Vd was 0.781/kg (±0.04; 0.47–1.01). No significant correlation was found between Clb, t1/2 and postnatal age in the whole group or in individual infants. Effective plasma concentrations varied over a wide range (12–36 µg/ml) and overlapped with subtherapeutic concentrations (⩽24 µg/ml). Single doses of 15 mg/kg i.v. or p.o. prevented apnoea in most cases, if necessary followed by additional doses. Monitoring the blood level of caffeine in infants receiving frequent repeated doses is necessary to prevent toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606424
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  • 65
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    Electronic Resource
    Pharmacokinetics of chlorpheniramine after intravenous and oral administration in normal adults (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 359-365 
    Details
    ISSN: 1432-1041
    Keywords: chlorpheniramine ; pharmacokinetics ; oral absorption ; half-life ; bioavailability ; volume of distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and urinary levels of chlorpheniramine (CPM) and its 2 demethylated metabolites were measured by HPLC after i.v. and oral dosing. In 5 mg (maleate) i.v. bolus studies in 2 subjects, plasma CPM levels were fitted to triexponential equations with terminal half-lives (t 1/2) of 23 and 22 h and area of 3.6 and 3.21/kg, respectively. Intravenous data predicted hepatic blood extraction ratios for the 2 subjects to be 0.06 and 0.07, respectively. Absolute bioavailability from oral solution (10 mg) was 59 and 34%, and from tablets (8 mg) 44 and 25%, respectively, indicating extensive gut first-pass metabolism. Mean t 1/2 from 7 oral fasting studies in 5 subjects was 28 h (19–43 h). Mean absorption lag time was 0.7 h (0.4–1.3 h), and mean peak time was 2.8 h (2–4 h). In 2 subjects, 6 mg solutions were given every 12 h for 9 doses; good correlation between single and multiple dose kinetics was found. Significant accumulation was demonstrated in simulation studies with frequent daily dosing. Estimated accumulation ratios vary from 4.1 to 9.4 (mean 6.5). The t 1/2 from urinary data (collected for 12 days) was consistent with plasma data. The above results suggest the need to reexamine the current practice of frequent daily dosing and the use of sustained or controlled release dosage forms of this drug. The possible cause of reduced plasma clearance of CPM in renal patients is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548406
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  • 66
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    Electronic Resource
    The clinical pharmacology of tolmesoxide (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 93-97 
    Details
    ISSN: 1432-1041
    Keywords: tolmesoxide ; vasodilator ; hypertension ; pharmacokinetics ; haemodynamics ; plasma renin activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic response and pharmacokinetics of single dose oral tolmesoxide were studied at various dose levels in 4 patients with severe hypertension. There was a reproducible fall in mean arterial pressure from baseline of 24.2% and a rise in heart rate of 37.6% following administration of tolmesoxide. The onset of antihypertensive action occurred within 1 h, with a peak effect at 3 h after dosing. The mean duration of action was up to 12.0 h. Tolmesoxide had a mean half-life of 3.0 h. It was rapidly absorbed with a mean peak plasma level occurring at 1.0 h. Plasma levels correlated well with the doses administered. Side-effects included mild nausea, facial flushing and postural symptoms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545961
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  • 67
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    Electronic Resource
    Variability of beta-blocker pharmacokinetics in young volunteers (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 37-42 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; propranolol ; oxprenolol ; pharmacokinetics ; acetubolol ; diacetolol ; oral contraceptive
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of metoprolol, propranolol oxprenolol, acebutolol and its metabolite diacetolol were measured after single oral doses in young healthy volunteers. In order to assess the inter-and intra-subject variability the following pharmacokinetic parameters were compared: AUC o 24 , Cmax, tmax and t1/2. The smallest variation in inter-subject variability was seen with oxprenolol and acebutolol: intrasubject variability was more uniform. Female volunteers taking an oral contraceptive generally had higher AUC o 24 and Cmax values than those not. This finding reached statistical significance only for metoprolol AUC o 24 .
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061375
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  • 68
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    Electronic Resource
    Clinical pharmacokinetics of verapamil in patients with atrial fibrillation (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 49-57 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; norverpamil ; pharmacokinetics ; atrial fibrillation ; oral administration ; i.v. administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters and oral bioavailability of the antiarrhythmic drug verapamil were determined in six patients with atrial fibrillation. Plasma samples were taken following i.v. injection of verapamil 10 mg (Isoptin® 2 ml), and oral verapamil 80 mg (Isoptin® 2 tablets of 40 mg). Verapamil and its N-demethylated metabolite, norverapamil, were analyzed to 1 ng/ml plasma by gas chromatography-mass spectrometry using deuterated standards. Following intravenous injection, the disposition of verapamil followed a biexponential pattern with a fast distribution phase and a slower elimination phase (t1/2β=5.79 h), corresponding to a plasma clearance of 0.26 1/kg/h. After oral administration, only an elimination phase was evident, with the same elimination rate (t1/2β=5.53 h). The oral bioavailability was 10.5%±7.5%. The norverapamil formed after i.v. and oral administration of verapamil had plasma half-lives of 5.86 h and 6.77 h, respectively. The elimination of verapamil in patients with atrial fibrillation was decreased compared to that in healthy young volunteers and the oral bioavailability was lower. Very good correlation between the percentage reduction in heart rate and the log plasma concentration of verapamil was found in every patient during the elimination phase, irrespective of the route of administration. There was also a high correlation when the plasma concentration — effect data from all the patients were pooled (r=0.59,n=71;p〈0.0005).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061377
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  • 69
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    Electronic Resource
    Pharmacokinetics of theophylline in infants with bronchiolitis (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 123-127 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; bronchiolitis ; infants ; pharmacokinetics ; single dose ; multiple doses ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Theophylline pharmacokinetics were studied in 12 infants (age 3 weeks–6.5 months) with bronchiolitis. 9 of the 12 patients received a single dose of aminophylline (5.0–8.5 mg/kg) whereas the remainder were at steady-state receiving multiple doses (2.5–5.0 mg/kg) of aminophylline. The dose was administered IV over 0.5–1.0 h. An HPLC method was used to measure theophylline concentrations in serum and urine. Peak serum concentrations of theophylline measured by HPLC ranged from 8.48–21.6 µg/ml. Total, renal and nonrenal clearance of theophylline ranged from 4.66 to 19.25, 1.07 to 5.76 and 3.59 to 16.83 ml/min/m2, respectively. Mean apparent volume of distribution and elimination half-life were 8.75 l/m2 and 11.38 h, respectively. Although no significant correlation was observed between age and theophylline kinetic parameters, clearance appeared to increase and half-life decrease with age. Our patients had a substantially lower clearance and longer half-life as compared to published data in children 〉1 year of age. A five-fold variation in theophylline clearance demonstrates the need for monitoring theophylline serum concentration to minimize the risk of potential toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545965
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  • 70
    Electronic Resource
    Electronic Resource
    Effect of chronic oral contraceptive steroids on theophylline disposition (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 129-134 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; ethinylestradiol ; oral contraceptives ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of chronic oral contraceptive (OC) usage on the disposition of theophylline was examined. Aminophylline solution (4 mg/kg) was given orally to 8 healthy female non-OC users and to 8 healthy women who were chronic (〉6 months) OC users. The OC user group had a significantly lower total plasma clearance of theophylline than women not using OC (35.1±5.6 vs. 53.1±14.5 ml/h/kg). The t1/2 was also significantly prolonged in the OC group (9.79±1.43 vs. 7.34±1.75 h) while the volume of distribution was similar between the 2 groups. The serum ethinylestradiol (EE) concentrations after oral OC administration were measured simultaneously. The apparent clearance of EE was about 30% lower in the OC users. A significant positive correlation was found between the apparent clearance of EE and the plasma clearance of theophylline. The effects of OC are predominantly due to chronic use with decreased elimination of both theophylline and EE.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545966
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  • 71
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    Electronic Resource
    Pharmacokinetics of ticarcillin in man (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 167-172 
    Details
    ISSN: 1432-1041
    Keywords: ticarcillin ; probenecid ; excretion ; pharmacokinetics ; automated chemical assay method
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The excretion of radioactivity has been investigated in 3 healthy volunteers following rapid intravenous administration of 5 g of [35S]-ticarcillin. The radioactive dose was rapidly and completely excreted, since within 4 days 98.5% was recovered, 95% in the urine and 3.5% in faeces. All the urine radioactivity was accounted for as ticarcillin and its penicilloic acid. Plasma and urine samples collected from the volunteers at frequent intervals during the first 6 h of the experiment were assayed for penicillin by an automated chemical method and also for radioactivity. The results obtained by the chemical autoanalyser method were in excellent agreement with the plasma levels of radioactivity. From the data it was possible to calculate the renal clearance of the penicillin, a mean value of 104 ml/min was observed in the 3 volunteers. A further three volunteers were dosed intravenously with a 5 g bolus of non-radiolabelled ticarcillin in a cross-over study with and without predosing with probenecid. Serum samples were analysed by the chemical method for penicillin and the data subjected to pharmacokinetic analysis using a two compartment open model. The results indicate a shift of the distribution equilibrium of ticarcillin from the serum into the peripheral compartment after predosing with probenecid. Furthermore, the mean half-life of ticarcillin in the serum of the three volunteers was significantly increased from 1.3 h to 2.1 h by predosing with probenecid.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545973
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  • 72
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    Electronic Resource
    Pharmacokinetics of oral dipyridamole (Persantine®) and its effect on platelet adenosine uptake in man (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 229-234 
    Details
    ISSN: 1432-1041
    Keywords: dipyridamole ; platelets ; plasma levels ; pharmacokinetics ; adenosine uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Two preparations of dipyridamole have been studied by oral administration to 11 normal volunteers. The plasma levels of dipyridamole and its glucuronide were determined simultaneously by high performance liquid chromatography. The instant form (I.F., 100 mg) was administered four times daily and the slow release preparation (SRP, 200 mg) twice daily, for 3 days. Multiple blood samples were collected on Days 1–4 to provide plasma for assay, and simulteneously, platelet rich plasma was prepared for ex vivo study of the effect of dipyridamole on platelet uptake of adenosine. The pharmacokinetics of absorption and distribution of dipyridamole were described using a two compartment model with lag time and prolonged absorption. Strong inhibition of the platelet adenosine uptake was observed at therapeutic plasma levels. The inhibition of platelet adenosine uptake may be related to some of the pharmacological properties of dipyridamole.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547559
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  • 73
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    Electronic Resource
    Pharmacokinetics and tolerance of slow-release indomethacin tablets in rheumatoid arthritis (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 349-351 
    Details
    ISSN: 1432-1041
    Keywords: indomethazine ; rheumatoid arthritis ; pharmacokinetics ; tolerance ; side effects ; slow-release tablets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics, efficacy and tolerance of a new formulation of slow-release indomethacin tablet were compared with those of a conventional indomethacin capsule in 30 patients with rheumatoid arthritis. The slow-release tablet was absorbed more slowly than the capsule (tmax 3.7 h and 〈 2 h, respectively) and produced more even serum drug levels in 10 subjects. Side-effects, especially dizziness and diarrhoea, were less frequent after the slow-release tablet than during the capsule period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613619
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  • 74
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    Electronic Resource
    Pharmacokinetics of3H-phenylephrine in man (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 335-341 
    Details
    ISSN: 1432-1041
    Keywords: phenylephrine ; pharmacokinetics ; bioavailability ; first-pass metabolism ; phenolic conjugates ; m-hydroxymandelic acid ; intravenous ; oral
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 7-3H-phenylephrine was given to 15 volunteers by a short-infusionn=4) or p.o. (10 volunteers, 1 patient with porto-caval anastomosis). Analysis of serum for free3H-phenylephrine and fractionation of urinary radioactivity was performed by ion-exchange and thin-layer chromatography. As almost the same3H-activity was excreted in urine after i.v. and p.o. administration, 86% and 80% of the dose respectively, complete enteral absorption can be assumed. A considerable difference was seen in the fraction of free phenylephrine, i.v. 16% of the dose versus p.o. 2.6%, which suggested reduced bioavailability. This was confirmed by comparison of the areas under the serum curve, which showed a bioavailability factor of 0.38. The result for the patient with porto-caval anastomosis was comparable to that in the normal volunteers. The biological half-life of 2 to 3h was comparable to that of structurally related amines, as were the total clearance of 2 1/h, and the volume of distribution of 340l. Metabolism to phenolic conjugates mainly after oral ingestion, and tom-hydroxymandelic acid after i.v. injection, again demonstrated thatm-hydroxylated amines are predominantly conjugated during the “first-pass” metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637623
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  • 75
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    Electronic Resource
    Pharmacokinetics of furosemide in patients with hepatic cirrhosis (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 315-320 
    Details
    ISSN: 1432-1041
    Keywords: furosemide ; cirrhotic patients ; ascitic fluid ; diuretic effect ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of furosemide was studied in 7 patients with diagnosed liver cirrhosis and in 7 healthy subjects. Furosemide in plasma and ascitic fluid was analyzed spectrofluorometrically. After a single intravenous dose, the cirrhotic patients showed lower initial plasma concentrations of furosemide because of the larger volume of distribution. The mean half-life in cirrhotic patients was significantly greater than in healthy volunteers. The longer half-life was associated with a reduction in the serum clearance of furosemide. Ascitic fluid volume in the patients ranged from 4.6 to 7.71. There was no significant amount of furosemide in the fluid. The diuretic interchange between this fluid and plasma was slow, as peak concentrations ranged from 0.3 to 0.5 µg/ml within 3 to 5 h after bolus administration of furosemide. Diuresis and urinary sodium excretion, 5 h after furosemide injection, were similar in both groups; larger potassium excretion was found in the cirrhotic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548399
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  • 76
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    Electronic Resource
    Pharmacokinetics of cimetidine and its sulphoxide metabolite during haemodialysis (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 325-330 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; renal failure ; cimetidine sulphoxide ; pharmacokinetics ; haemodialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single intravenous dose of cimetidine 200mg was administered to 6 patients with severe chronic renal failure one hour prior to haemodialysis. The plasma concentrations of cimetidine and its sulphoxide metabolite at the start of haemodialysis were 2.74±0.12 and 0.76±0.08 µg/ml, and after dialysis for 4h 1.08±0.10 and 0.51±0.08 µg/ml, respectively (mean ± SE). The average haemodialysis clearance (ClHDa) of cimetidine during dialysis was 46–92ml/min at a dialysate flow rate of 320ml/min and blood flow rates in the 6 patients between 160–240ml/min. The mean ClHDa of the sulphoxide metabolite was 44% higher than that of cimetidine, and ranged between 49–148ml/min. During haemodialysis the mean plasma elimination half-life (t1/2) of cimetidine was 3.24h (range 2.08–5.08) and of the sulphoxide metabolite 9.49h (range 4.70–14.39). There was a significant relationship between the elimination rate constant (β) and ClHDa of the sulphoxide metabolite (p〈0.01), but no such relationship was found between β and ClHDa of cimetidine. However, there was a tendency to a relationship between β of cimetidine and the capacity to metabolise the drug, expressed as the ratio between the plasma concentrations of the sulphoxide metabolite and cimetidine after dialysis for 4h. These ratios ranged between 0.23–0.76, and the lowest ratio was seen in the patient with the lowest β value of cimetidine. Thus, the large variations in the plained by differences in their capacity to metabolise the drug. The mean total amount of cimetidine eliminated during dialysis was 27.3mg (range 17.9–31.8), which was 9.0–15.9% of the given dose. Between 12.2–21.2mg (mean 15.3) of the sulphoxide metabolite was eliminated in the dialysate. Major adjustment of the dose of cimetidine on days of dialysis is not necessary.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637621
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  • 77
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    Electronic Resource
    Distribution of lithium elimination rates in a selected population of psychiatric patients (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 351-354 
    Details
    ISSN: 1432-1041
    Keywords: lithium ; plasma level decay curve ; elimination ; pharmacokinetics ; psychiatric patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Chronic treatment with conventional lithium carbonate was interrupted in a selected group of 40 psychiatric patients of mixed sex and race. All patients had normal renal function. Serum samples were taken 12, 24, 36 and 48 h after the last dose and lithium was assayed by atomic absorption spectrophotometry. Decay rates calculated for the 12–24 h and 36–48 h periods yielded different values. This was ascribed to the presence of an incomplete redistribution phase during the earlier period. The distribution of elimination rates determined during the later period gave a more symmetrical spread and approximated a normal distribution. The mode, median, mean and standard deviation of the lithium elimination half-lives were 12.5, 14, 18.2 and 7.3 h and 22.5, 24.5, 29.8 and 10.1 h for the two periods, respectively. The results contrast sharply with another report of the distribution spread of elimination half-lives in a much larger sample. The current values have implications for dosage prediction, serum level monitoring and dosage formulation, especially sustained-release preparations. The evidence was against the possibility that some individuals ‘retain’ lithium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637625
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  • 78
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    Electronic Resource
    Pharmacokinetics of propranolol and sotalol in hyperthyroidism (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 373-377 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; sotalol ; thyrotoxicosis ; bioavailability ; serum tri-iodothyronine ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The elimination and bioavailability of two beta-blocking agents, propranolol and sotalol, were studied in 10 thyrotoxic patients, both before and after treatment with iodine-131. Each subject received in random order propranolol 160 mg and sotalol 160mg as single oral doses both while hyperthyroid and after euthyroidism had been achieved. The pharmacokinetics of sotalol was not affected by hyperthyroidism, whereas serum propranolol concentrations were significantly lower during hyperthyroidism than in the euthyroid state. During hyperthyroidism, the bioavailability of propranolol was significantly reduced (p〈0.05) and its clearance was increased (p〈0.005), whereas there was no difference in its serum t1/2. This indicates that the bioavailability of propranolol in hyperthyroidism is reduced by a mechanism which may depend on increased first-pass metabolism in the liver, or on an increased distribution volume of the drug. Both propranolol and sotalol caused a slight decrease in serum tri-iodothyronine concentration. As the effects of beta-blocking agents on the symptoms of hyperthyroidism are correlated with the serum concentration of the drugs, sotalol, with its long half-life and unaltered elimination in hyperthyroidism, has certain advantages over propranolol in the treatment of thyrotoxicosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542321
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  • 79
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    Electronic Resource
    Studies of the different metabolic pathways of antipyrine in man (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 433-441 
    Details
    ISSN: 1432-1041
    Keywords: antipyrine ; antipyrine metabolites ; drug metabolism ; route of administration ; healthy volunteers ; urinary excretion ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of antipyrine in plasma and saliva, and urinary excretion of its major metabolites, were studied following i.v. and oral administration of antipyrine 500 mg to 6 healthy volunteers. Data from both plasma and saliva showed that the oral bioavailability of antipyrine given as an aqueous solution was complete. The saliva/plasma concentration ratio was constant with time from about 3 h onwards, with a mean value of 0.87 after oral and 0.91 after i.v. administration. It is concluded that the pharmacokinetic parameters of antipyrine can be satisfactorily established on the basis of salivary data, although the volume of distribution and clearance values are then slightly too high. After i.v. administration, 3.8±1.9% of the dose was excreted in urine as unchanged antipyrine in 48h, 24.9±6.3% as 4-hydroxyantipyrine, 16.5±3.2% as norantipyrine, 13.0±2.2% as 3-hydroxymethyl-antipyrine and 5.8±1.0% as 3-carboxy-antipyrine. No significant differences were observed following oral administration. The half-lives calculated from the linear part of the urinary excretion rate curves of the metabolites were about the same for oral and i.v. administration, and were of the same order of magnitude as the elimination half-life of parent drug in plasma and saliva. It is important for determination of the ultimate metabolite ratio that urine is collected for at least 36h, because there is a delay in the excretion of 3-hydroxymethyl-antipyrine in urine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542332
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  • 80
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    Electronic Resource
    Relationship between the plasma concentration of clomipramine and desmethylclomipramine in depressive patients and the clinical response (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 15-20 
    Details
    ISSN: 1432-1041
    Keywords: clomipramine ; desmethylclomipramine ; depressive syndrome ; plasma level ; pharmacokinetics ; clinical response ; benzodiazepines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty one in-patients suffering from depression were treated orally with clomipramine (Cl) at various dosage, for 28 days, after a “wash-out” period of three days. In 17 patients receiving 75 mg per day of Cl, steady state plasma levels of Cl were reached at Day 14, and steady state plasma levels of its active metabolite, desmethylclomipramine (DMCl), were reached at Day 21. In contrast, in 7 other patients receiving a dosage increasing to 150 mg per day at Day 7, mean plasma levels of Cl and DMCl continued to rise during the entire treatment period. At the steady state, a correlation was found between Cl dosage expressed as mg kg body weight and the plasma concentration of Cl and DMCl. Factors such as tobacco and alcohol consumption seem to modify the Cl/DMCl ratio. A comparison of clinical response with plasma levels of Cl, DMCl and Cl + DMCl showed a significant negative linear correlation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606419
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  • 81
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    Electronic Resource
    Kinetics of allopurinol after single intravenous and oral doses (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 77-84 
    Details
    ISSN: 1432-1041
    Keywords: allopurinol ; oxipurinol ; benzbromarone ; hydrochlorothiazide ; pharmacokinetics ; bioavailability ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An high-pressure liquid chromatographic method was used to measure allopurinol and oxipurinol in plasma and urine in 6 healthy volunteers after a single intravenous or oral dose of allopurinol. The influence of coadministrated benzbromarone and hydrochlorothiazide on the pharmacokinetics of allopurinol and oxipurinol was also investigated. After intravenous injection of allopurinol 300 mg the plasma disappearance was biexponential, with a mean distribution half-life of 2.32±1.08 min $$(\bar x \pm SD)$$ and an elimination half-life of 47.8±10.6 min. The total clearance of allopurinol was 11.37±2.70 ml/min/kg, whereas its renal clearance was only 1.73±0.79 ml/min/kg. Oxipurinol disappeared monoexponentially from plasma ith a mean half-life of 12.2±2.6 h. Its renal clearance was 0.42±0.091 ml/min/kg. After oral administration of allopurinol 300 mg the peak plasma concentration of 2.1±0.6 µg/ml (1.5×10−5 M) was reached within 30 to 120 min. The peak level of oxipurinol of 5.8±1.5 µg/ml (3.8×10−5 M) was found within 2 to 5 h after intravenous and oral allopurinol. The bioavailability of oral allopurinol computed from plasma data was 90.4±8.7%. The total recovery from urine was 77% (allopurinol 8%, oxipurinol 69%) after oral and 88% after i.v. administration. It was concluded that about 10% of the oral dose was not absorbed and that 12% was eliminated by an unknown mechanism, presumably as riboside. The pharmacokinetics of allopurinol and oxipurinol were not significantly influenced by coadministration of benzbromarone or hydrochlorothiazide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606429
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  • 82
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    Electronic Resource
    Pharmacokinetics of methadone during maintenance treatment: Adaptive changes during the induction phase (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 343-349 
    Details
    ISSN: 1432-1041
    Keywords: methadone ; opiate addicts ; pharmacokinetics ; single and multiple doses ; stable isotope technology ; methadone maintenance therapy ; deuterium technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Deuterated methadone (M-d30) and GC-MS were used to study the pharmacokinetics of methadone (M) during the induction stage of methadone maintenance treatment (MMT). A pulse dose of M-d3 was given on Days 1 and 25 of two dosage regimens, one with a continuous 30 mg dose (n=6), and the other with 30 mg for 10 days, followed by 60 mg as the maintenance dose (n=6). Plasma and urinary levels of M and M-d3 were measured throughout and plasma half-lives, oral bioavailabilities and volumes of distribution were calculated from the data of Days 1–2 and 24–26. The oral bioavailability of a methadone solution was found to be between 81 and 95%; elimination half-life in the β-phase varied between 19 and 58 h; the volume of distribution was 4.1±0.65 l/kg; and total body clearance of M was 54–195 ml/min and its renal clearance 3.4–34 ml/min. A consistent finding was a lower urinary pH and increased renal clearance during the first days of MMT as compared with after one month. In 4/12 of the patients dispositional tolerance was developed to methadone during the first month of treatment. The shorter elimination half-lives in those patients probably caused unacceptably high fluctuation in the body content of M during the 24 h dosage interval, and may have interfered therefore, with its therapeutic effectiveness
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548404
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  • 83
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    Pharmacokinetic and pharmacodynamic studies of tienilic acid in healthy volunteers (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 515-521 
    Details
    ISSN: 1432-1041
    Keywords: tienilic acid ; uricosuria ; pharmacokinetics ; pharmacodynamics ; uric acid ; diuretic ; plasma level assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A simple and reliable HPLC method for the determination of tienilic acid ((TA) Selacryn®, Selcryn®, Diflurex®, Ticrynafen®) and its alcoholic metabolite in plasma and urine has been developed. In 8 healthy adult volunteers the plasma and urinary levels of tienilic acid and its alcoholic metabolite, and plasma and urinary levels of sodium, creatinine and uric acid were measured after oral administration of tienilic acid 250 mg. The pharmacokinetic parameters found differed only slightly from those reported in the literature, as there was faster absorption and a shorter half-life. TA is probably excreted by a saturable renal tubular transport mechanism. The pharmacodynamic effects of tienilic acid developed quickly, the uricosuric effect being very impressive and the natriuretic effect moderate. These effects disappeared in about 8 h. An inverse relationship was found between the starting plasma uric acid level in an individual and the maximal uric acid clearance — the higher the plasma uric acid level, the lower was the maximum effect. Plasma tienilic acid level and natriuretic effect were correlative within individuals and intra-individually (p〈0.05). Urinary tienilic acid level and natriuretic effect were correlated, too (p〈0.05 top〈0.001), but only intraindividually. No correlation between drug level and uricosuric effect was found.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609624
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  • 84
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    Electronic Resource
    Pharmakokinetic properties of noscapine (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 535-539 
    Details
    ISSN: 1432-1041
    Keywords: noscapine ; pharmacokinetics ; absorption ; bioavailability ; intravenous application ; oral application ; ion exchange resin tablet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Noscapine was administred to five healthy volunteers in a randomized crossover design, as an intravenous infusion of 66 mg, and as an oral 150 mg dose of either rapidly dissolving tablets or a tablet containing ion exchange resin-bound noscapine. After i.v. administration, the disposition of noscapine was bi-exponential with an elimination half-life of 2.6 h; the total plasma clearance was 22 ml/min/kg and the volume of distribution (Vdarea) was 4.7 l/kg. The absolute oral bioavailability was 30%, with a 3.6-fold interindividual variation. There was no pharmacokinetic evidence to support a prolonged action of the ion exchange resin tablet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609627
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  • 85
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    Electronic Resource
    Pharmacokinetics of theophylline in patients following short-term intravenous infusion (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 417-422 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; obstructive airways disease ; short-term i.v. infusion ; log-normal distribution ; pharmacokinetics ; serum concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum theophylline concentrations after intravenous administration of a new short-term infusion (Euphyllin® Kurzzeitinfusion) were measured in 50 out-patients with chronic obstructive airways disease (COAD). An intravenous infusion of theophylline ethylenediamine 480 mg (corresponding to approximately 350 mg anhydrous theophylline) in 50 ml isotonic solution was given in 20 min. Blood samples were taken beforehand and 25 to 30 min and 1, 3 and 6 h after starting the infusion. 86% of the patients had a one-hour serum level in the therapeutic range of 8–20 mg/l, and 2 h later, this was true of 64% of the patients. The short-term infusion was well tolerated, even in cases with unknown high pre-infusion serum levels. Pertinent pharmacokinetic parameters were determined, such as total body clearance, apparent volume of distribution, and half-life of elimination. Geometric mean and 95%-confidence limits, derived from the log-normal distribution of these parameters, were: Cl=0.044 (0.018–0.109) l/h/kg ideal body weight, Vd=0.451 (0.258–0.789) l/kg ideal body weight, and t1/2(el)=7.1 (2.6–19.1) h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542546
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  • 86
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    Electronic Resource
    Pharmacokinetics of bacmecillinam and pivmecillinam in volunteers (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 249-252 
    Details
    ISSN: 1432-1041
    Keywords: mecillinam ; bacmecillinam ; pivmecillinam ; pharmacokinetics ; pro-drug ; healthy volunteers ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of bacmecillinam and pivmecillinam were studied in healthy fasting volunteers given tablets in a cross-over, randomized order. The mean (±SD) peak levels of plasma mecillinam were 1.43±0.34, 2.73±0.43, and 4.62±1.41 mg/l after bacmecillinam 100, 200, and 400 mg and 2.38±0.65 mg/l after pivmecillinam 400 mg. The corresponding areas under plasma Vs time curves (AUC) were 2.21±0.19, 3.99±0.63, and 7.74±1.38 mg·h·l−1 for bacmecillinam and 5.35±0.93 mg·h·l−1 for pivmecillinam. The elimination half-lives were 0.8–1.1h for bacmecillinam and 0.7h for pivmecillinam. The 12 h urinary recovery of unchanged mecillinam after the 400 mg doses was 41% for bacmecillinam and 30% for pivmecillinam. The 400 mg dose of bacmecillinam gave a significantly higher plasma peak (p〈0.001), AUC (p〈0.001) and urinary recovery (p〈0.001) than did pivmecillinam 400 mg. The plasma peaks appeared earlier and the rate of absorption was higher after bacmecillinam than after pivmecillinam (p〈0.05). In conclusion, bacmecillinam had a better bioavailability than pivmecillinam in the tablet formulations studied. The AUC increased linearly with increasing doses of bacmecillinam.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547563
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  • 87
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    Electronic Resource
    Pharmacokinetics of terodiline in human volunteers (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 267-270 
    Details
    ISSN: 1432-1041
    Keywords: terodiline ; human volunteers ; pharmacokinetics ; serum clearance ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of terodiline HCl was studied in nine healthy volunteers given 12.5 mg i.v. and p.o. or 20 mg i.v. and 25 mg p.o. on two different occasions. The serum concentrations were measured by gas chromatography — mass spectrometry, using deuterated terodiline HCl as the internal standard. After i.v. administration the kinetics could be described by a two-compartment model with a mean distribution half life of 0.3 h and a mean elimination half life of 63 h. The serum clearance and apparent volume of distribution varied about 4-fold with mean values of 4.8 l/h and 417 l, respectively. After oral administration, the mean half life of absorption was 0.7 h and that of elimination 65 h. The absolute bioavailability varied between 64% and 105% with a mean of 92%. The long serum half life of terodiline should permit its once daily administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547566
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  • 88
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    Electronic Resource
    Pharmacokinetics of pancuronium in man: A linear system (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 369-372 
    Details
    ISSN: 1432-1041
    Keywords: neuromuscular blockade ; pancuronium ; non-depolarizing neuromuscular blocking agent ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pancuronium in bolus doses of 40 to 350 µg/kg was administered to surgical patients in order to evaluate the linearity of its pharmacokinetics. The profile of the plasma decay curve and of its urinary elimination were compared with reference to the administered dose. It was possible to superimpose the dose-normalized plasma decay-curves. The parameters of the two compartment-open model used to describe the pharmacokinetics of pancuronium were not influenced by the dose. The elimination half-life was 89±20 min and the plasma clearance was 1.84±0.38 ml/min/kg. The profiles of cumulative urinary excretion were also dose-independent. After 6 and 24 h, 57% and 69% of the administered dose, respectively, had been excreted in the urine. The results indicate that the pharmacokinetics of pancuronium is linear.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613623
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  • 89
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    Electronic Resource
    Influence of acetylator phenotype on the pharmacokinetics of a new vasodilator antihypertensive, endralazine (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 523-527 
    Details
    ISSN: 1432-1041
    Keywords: endralazine ; acetylator phenotype ; hydralazine ; pharmacokinetics ; plasma concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five and 10 mg single oral doses of a new vasodilator antihypertensive, endralazine (E) were given on separate occasions to 17 normal male volunteers (8 slow, 7 heterozygous fast and 2 homozygous fast acetylators). The homozygous fast acetylators were excluded from statistical comparisons. Only small differences were observed in the pharmacokinetics of E between the phenotypes and there was no evidence of non-linearity at the 2 dose levels studied. Terminal half-lives ranged from 2.59 to 7.14 h with a mean of 4.30±1.08 h for the 5 mg dose and 4.25±1.09 h for the 10 mg dose. There was no significant difference in half-lives between slow and heterozygous fast acetylators. The mean area under the plasma level-time curve (AUC 0 ∞ ) was 18.2% lower (p〈0.05) in the heterozygous fast acetylators than in the slow acetylators following the 5 mg dose and 11.0% lower (p〉0.05) following the 10 mg dose. Extremely rapid absorption of the drug precluded accurate estimation of absorption rates. The AUC 0 ∞ of the acetylation metabolite (methyltriazoloendralazine) was small compared to that of E although higher in the heterozygous fast acetylators than in the slow acetylators (p〈0.01).
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    URL: http://dx.doi.org/10.1007/BF00637500
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  • 90
    Electronic Resource
    Electronic Resource
    Estimation of absorption ratios and their variation for orally administered drugs (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 265-272 
    Details
    ISSN: 1432-1041
    Keywords: pharmacokinetics ; variation of absorption ratios ; bioavailability ; dissection of variation due to absorption and intermediate processes ; oral drug application
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Differences in the plasma concentrations of drugs after oral administration are caused by two main factors: variation in absorption ratios and in the distribution processes in the body. A new method for the dissection of both types of factors is discussed. The method uses a reference regression of the AUC-values to the corresponding values after intravenous infusion of graded doses. The reference regression is estimated from an appropriate trial. Deviation of the determined AUC-values from the regression curve afford an estimate of the residual variance due to varying distribution volumes or similar random biological effects. For the estimation of absorption ratios after oral administration the drug is given orally to another sample of subjects and their AUC-values are calculated. The deviation of these AUC values due to the above mentioned random effects are simulated using the residual variance of the reference regression, and are subtracted from the observed AUC-values. Then, the differences in the corresponding absorbed doses are transformed by inverting the reference regression. From these doses the empirical distribution function and statistical parameters (e.g. quantiles) are determined. The method has the advantage that no restrictive assumptions are required, such as first order processes, dose linearity, homogeneity of variance or normal distribution of absorption ratios. Its applicability to substances with qualitative differences in their pharmacokinetics is demonstrated by appropriate examples.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545226
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  • 91
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    Electronic Resource
    Effect of urinary pH on the disposition of methadone in man (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 337-342 
    Details
    ISSN: 1432-1041
    Keywords: methadone ; pharmacokinetics ; urinary pH ; RBC level ; saliary level ; mass fragmentography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of urinary pH on the acute disposition of methadone in man was studied in five healthy volunteers. A cross-over experiment was performed in each subject. In the first experiment the subjects were treated with ammonium chloride (urinary pH ≈ 5.2) and in the other the urine was made alkaline (pH ≈ 7.8) by treatment with sodium hydrogen carbonate. d, 1-Methadone-HCl 10 mg (M) was administered intramuscularly on each occasion and blood, saliva and urine levels of M were determined by mass fragmentography. Plasma half-lives, volumes of distribution and body clearances of M were calculated in both experiments. The plasma half-lives in the β-phase were 19.5±3.6 h (acidic urine) and 42.1±8.8 h (alkaline urine), respectively (p〈0.001). The volumes of distribution were increased when the pretreatment was changed from ammonium chloride to sodium bicarbonate, namely from 3.51±0.41 l/kg to 5.24±0.83 l/kg (p〈0.01). The body clearance decreased from 134±21 ml/min (acidic) to 91.9±9.1 ml/min (alkaline urine) (p〈0.01). The ration Mplasma/MRBC was about 2.3 and the elimination of M from RBCs was in good agreement with the plasma kinetics of M under both experimental conditions. The salivary levels of M did not reflect the plasma kinetics and considerable variation was seen in the ratio Msaliva/Mplasma (0.26–2.98). Thus, the present experiments demonstrate that pretreatment either with ammonium chloride or bicarbonate had profound effects on both the distribution and elimination kinetics of methadone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548403
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  • 92
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    Electronic Resource
    Should erythromycin dose be altered in haemodialysis patients? (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 435-440 
    Details
    ISSN: 1432-1041
    Keywords: erythromycin ; haemodialysis ; dosage adjustment ; pharmacokinetics ; protein-binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Erythromycin kinetics were studied in 17 patients with end stage renal failure treated with maintenance haemodialysis and 9 normal volunteers to discover if dialysis patients needed a modified dose. The elimination half life in dialysis patients (on dialysis days) was similar to that reported in normal subjects. Only small amounts of drug appeared in the dialysate, no patient loosing more than 9 mg in one dialysis. Both patients and volunteers had similar plasma concentrations 8 h after the end of a 5-day course. Protein-binding did not change significantly during dialysis and was similar to that reported in normal subjects. We conclude that dialysis patients requiring 1.5 g of erythromycin stearate daily or less can be given normal doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00605994
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  • 93
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    Electronic Resource
    Comparative studies onChlorella cell walls: Induction of protoplast formation (1982)
    Springer
    Archives of microbiology 132 (1982), S. 10-13 
    Details
    ISSN: 1432-072X
    Keywords: Calcofluor White ; Cell wall structure ; Chlorella ; Electron microscopy ; Protoplast ; Ruthenium Red
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Among 12 strains ofChlorella ellipsoidea, C. vulgaris, andC. saccharophila tested, 4 strains (1,C. ellpsoidea; 2,C. vulgaris; 1,C. saccharophila) formed osmotically labile protoplasts after treatment with mixtures of polysaccharide degrading enzymes. The relationship between enzymatical digestibility and structure or composition ofChlorella cell walls were studied by electron microscopy and staining techniques with some specific dyes. The cell wall structures of the 12Chlorella strains were grouped into three types: (1) with a trilaminar outer layer, (2) with a thin outer monolayer, and (3) without an outer layer. Protoplasts were formed only from the strains with a cell wall of Type 2. In the strains with a cell wall of Type 1, the outer layer protected the inner major microfibrillar layer against enzymatic digestion. The cell wall of Type 3 was totally resistant to the enzymes; the chemical composition of the cell wall would be somewhat different from that of other types.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690809
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  • 94
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    Electronic Resource
    Thylakoid centers: Structures associated with the cyanobacterial photosynthetic membrane system (1982)
    Springer
    Archives of microbiology 133 (1982), S. 97-99 
    Details
    ISSN: 1432-072X
    Keywords: Cyanobacteria ; Thylakoid centers ; Photosynthetic membranes/thylakoids ; Membranes ; Membrane biogenesis ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract An ultrastructural study of four cyanobacteria (Anabaena cylindrica, Dermocarpa violaceae, Gleocapsa alpicola, Pleurocapsa minor) indicates the presence of previously undescribed thylakoid centers from which photosynthetic membranes (thylakoids) radiate. These peripherally located thylakoid centers are cylinders 30 nm wide by 320 nm long, consisting of globular subunits oriented in nonparallel stacked arrays. Thylakoids are attached to the outer surface of the cylinder along its longitudinal axis. Thylakoid centers appear to be functionally significant due to their structure, location and thylakoid association.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00413518
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  • 95
    Electronic Resource
    Electronic Resource
    Cell wall degradation ofStaphylococcus aureus by lysozyme (1982)
    Springer
    Archives of microbiology 131 (1982), S. 116-123 
    Details
    ISSN: 1432-072X
    Keywords: Cell wall ; Wall degradation ; Lysozyme ; Autolysines ; Electron microscopy ; Staphylococcus aureus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In contrast to former findings lysozyme was able to attack the cell walls ofStaphylococcus aureus under acid conditions. However, experiments with14C-labelled cell walls and ribonuclease indicated that, under these conditions, lysozyme acted less as an muralytic enzyme but more as an activator of pre-existing autolytic wall enzymes. Electron microscopic studies showed that under these acid conditions the cell walls were degraded by a new mechanism (i.e. “attack from the inside”). This attack on the cell wall started asymmetrically within the region of the cross wall and induced the formation of periodically arranged lytic sites between the cytoplasmic membrane and the cell wall proper. Subsequently, a gap between the cell wall and the cytoplasmic membrane resulted and large cell wall segments became detached and suspended in the medium. The sequence of lytic events corresponded to processes known to take place during wall regeneration and wall formation. In the final stage of lysozyme action at pH 5 no cell debris but “stabilized protoplasts” were to be seen without detectable alterations of the primary shape of the cells. At the same time long extended ribbon-like structures appeared outside the bacteria. The origin as well as the chemical nature of this material is discussed. Furthermore, immunological implications are considered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01053992
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  • 96
    Electronic Resource
    Electronic Resource
    Human osteogenic sarcoma (1982)
    Springer
    International orthopaedics 6 (1982), S. 171-179 
    Details
    ISSN: 1432-5195
    Keywords: Osteosarcoma ; Electron microscopy ; Acid phosphate ; Alkaline phosphate ; Bone tumour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La morphologie de 26 sarcomes ostéogéniques a été étudiée par microscopie électronique et la localisation des phosphatases acide et alcaline a pu être précisée au niveau ultrastructural. Quatre différents types de cellules ont été mis en évidence dans les tumeurs: cellules d'aspect ostéoblastique, fibroblastique et chondroblastique, ainsi que des cellules géantes multinuclées. Les cellules d'aspect ostéoblastique étaient présentes dans presque toutes les tumeurs étudiées. Une activité phosphatasique acide a été trouvée dans les lysosomes de toutes les cellules étudiées. Une activité phosphatasique alcaline a été observée dans — ou sur — la membrane plasmatique et dans les vésicules associées des cellules d'aspect ostéoblastique et fibroblastique ainsi que des cellules géantes. L'abondance des produits de réaction de la phosphatase alcaline contrastant avec une faible activité phosphatasique acide est en accord avec la nature de cette tumeur ostéogénique. Les résultats de l'étude histochimique ont aidé à comprendre la pathobiologie des différentes cellules qui constituent les sarcomes ostéogéniques.
    Notes: Summary The morphology of 26 cases of osteogenic sarcoma was studied using electron microscopic techniques, and the localization of acid and alkaline phosphatase activity at the ultrastructural level elucidated. Four different cells were present in the tumours: osteoblast-like, fibroblast-like, chondroblast-like, and multinucleated giant cells. The osteoblast-like cell was present in most of the tumours studied. Acid phosphatase activity was present in lysosome-like structures of almost all the cell-types studied. Alkaline phosphatase activity was noted in or on the plasma membranes and associated vesicles of osteoblast-like, fibroblast-like, and multinucleated giant cells. The abundant reaction product deposition of alkaline phosphatase as compared with the lower acid phosphatase activity is in agreement with the nature of this bone-forming tumour. The results of the histochemical studies have added to the understanding of the pathobiology of the different cells composing osteogenic sarcomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00267727
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  • 97
    Electronic Resource
    Electronic Resource
    Sensory organs inIps typographus (Insecta: Coleoptera) — Fine structure of antennal sensilla (1982)
    Springer
    Protoplasma 111 (1982), S. 206-214 
    Details
    ISSN: 1615-6102
    Keywords: Bark beetle ; Sensilla ; Chemoreceptors ; Mechanoreceptors ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The antennal sensilla inI. typographus are almost exclusively confined to the flattened terminal flagellar segment. The sensillar types have distinct distribution patterns in the three areas where they are found. Judging from the ultrastructural characteristics the following functions can be assigned to the sensillar types: chemoreception, single-walled and double-walled sensilla; chemoreception/mechanoreception, terminal-pore sensillum. Moreover there are two types of mechanoreceptors, one of which is connected to a bristle, whereas the other terminates within the cuticle of the flagellar segment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01281968
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  • 98
    Electronic Resource
    Electronic Resource
    Time course of blood ethanol in rats during alcohol dependence and withdrawal (1982)
    Springer
    Bulletin of experimental biology and medicine 94 (1982), S. 1069-1071 
    Details
    ISSN: 1573-8221
    Keywords: pharmacokinetics ; alcohol ; alcohol abstinence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00830715
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  • 99
    Electronic Resource
    Electronic Resource
    A model of the kinetics of blood levels of phenazepam and its metabolite 3-hydroxyphenazepam in cats (1982)
    Springer
    Bulletin of experimental biology and medicine 94 (1982), S. 1373-1375 
    Details
    ISSN: 1573-8221
    Keywords: pharmacokinetics ; phenazepam ; 3-hydroxyphenazepam ; cats ; blood ; metabolic model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00827203
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  • 100
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ethanol in narcotic doses and endogenous ethanol levels in female rats (1982)
    Springer
    Bulletin of experimental biology and medicine 94 (1982), S. 1689-1692 
    Details
    ISSN: 1573-8221
    Keywords: ethanol preference ; endogenous ethanol ; pharmacokinetics ; estrous cysle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00838911
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