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  • 1975-1979  (14,077)
  • Polymer and Materials Science  (13,298)
  • Electron microscopy  (597)
  • pharmacokinetics
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  • 1
    ISSN: 1432-2307
    Keywords: Glomerulonephritis ; Cryoglobulinemia ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Renal tissue from five patients with cryoglobulinemia was studied by light and electron microscopy and immunofluorescence. None of the histologic features observed at the light microscopic level seems to be specific for cryoglobulinemia. Electron microscopic investigations have shown very large electron dense deposits in almost every examined lobule in all cases. The deposits displayed two main patterns; a homogeneous texture in two cases and tubular or annular structures in three cases. The patients with typically structured deposits had IgG-IgM cryoglobulinemia (2 cases) or monoclonal IgM cryoglobulinemia (1 case). The presence of IgM in cryoglobulinemia may be the cause of the peculiar structure of the deposits.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European archives of oto-rhino-laryngology and head & neck 224 (1979), S. 17-23 
    ISSN: 1434-4726
    Keywords: Eighth nerve ; Inner ear ; Human ; Fluorescence microscopy ; Electron microscopy ; Menière ; Neurilemoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fluorescence microscopy was used to examine the adrenergic, bloodvessel-independent innervation of the 8th nerve and inner ear specimens in patients with otoneurological diseases. Specifically fluorescent adrenergic axons were scantily seen among the myelinated nerve fibers in the 8th nerve and in the subepithelial regions of the end organs but not in the endolymphatic sac.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 227 (1979), S. 103-117 
    ISSN: 1432-0711
    Keywords: Decidua ; Interzelluläre Verbindungen ; Gefrierätzen ; Elektronenmikroskopie ; Fibrinoid ; Decidua ; Intercellular junctions ; Freeze-fracturing ; Electron microscopy ; Fibrinoid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Cell contacts between developing decidual cells were examined in thin sections and in replicas of freeze-cleaved tissue of rat uterus. At the time of implantation only puncta adhaerentia were found between stromal cells. Gap junctions appeared 24 h after decidualization and thereafter increased in number and extent. Thus, there is little morphological evidence for a propagation of the initial stimulus for decidualization via gap junctions. An increase in amorphous, extracellular material is noted after decidualization with a concomitant decrease of collagen fibers. This amorphous material probably represents fibrinoid.
    Notes: Zusammenfassung Die Zellkontakte zwischen sich entwickelnden Deciduazellen wurden sowohl mit der Dünnschnittechnik als auch mit der Gefrierätzmethode im Rattenuterus untersucht. Zum Zeitpunkt der Implantation wurden nur Puncta adhaerentia zwischen Stromazellen gefunden. Nexus (gap junctions) erschienen 24 h nach Beginn der Decidualisierung und nahmen danach an Zahl und Größe zu. Diese morphologischen Befunde widersprechen der Ansicht, daß sich der initiale Reiz für die Decidualisierung der Stromazellen über Nexus ausbreitet. Nach der Decidualisierung wurde eine Zunahme von amorpher, extrazellulärer Substanz gleichzeitig mit einer Abnahme von Kollagenfasern gesehen. Diese amorphe Substanz stellt wahrscheinlich Fibrinoid dar.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0827
    Keywords: Parathyroid hormone ; Osteoclasts ; Electron microscopy ; Morphometry ; Metaphysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The effects of parathyroid hormone (PTH) on the size of the osteoclasts, nuclei, ruffled borders, and clear zones in long bones of thyroparathyroidectomized (TPTX) rats were quantitated as a function of time. These data were compared with the number of osteoclasts in the bone and with plasma calcium levels. A significant increase in the average size of the ruffled borders was demonstrated 30 min after injection of 50 U of purified bovine PTH, and of the clear zones 30–90 min after PTH. This was followed at 90 min by an increase in the average size of the cells. The sizes of ruffled borders and clear zones dropped sharply to control levels after 6 h, whereas the size of the cells remained elevated up to 12 h and returned to control values at 24 h. Plasma calcium levels were increased, but not significantly, between 30 min and 6 h. An increase in the number of osteoclasts was significant after 12 h. Removal of the parathyroid glands did not diminish the normal activity of osteoclasts. In animals with intact glands injection of 50 U of PTH did not cause a significant change in cell size or resorbing apparatus. It is concluded that PTH acts to rapidly stimulate the bone resorptive activity of osteoclasts and to cause a delayed increase in their number.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 34 (1979), S. 201-215 
    ISSN: 1432-1106
    Keywords: Intrahypothalamic connections ; Deafferentation ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Terminal degeneration within the hypothalamus was studied by electron microscopy 1 or 2 days (1) after carefully placed microlesions in the arcuate, anterior periventricular, ventromedial, premammillary and posterior hypothalamic nuclei and (2) after microlesions placed in the hypothalamus deafferented 3 weeks earlier. In the median eminence terminal degeneration was found after each of these lesions. Projections from the ventromedial nucleus reach the arcuate, suprachiasmatic, and anterior periventricular nuclei. Projections from the arcuate nucleus terminate in the medial preoptic, anterior periventricular, and ventromedial nuclei. After lesioning the premammillary nuclei degeneration was found in the supraoptic, arcuate, anterior hypothalamic and ventromedial nuclei.
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  • 6
    ISSN: 1432-1106
    Keywords: Hypothalamic paraventricular nucleus ; Spinal projection neuron ; Hypophyseal projection neuron ; Horseradish peroxidase ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of labeled neurons in the paraventricular nucleus of the hypothalamus (PVN) was studied following injections of horseradish peroxidase (HRP) into the spinal cord (C8 to T1) or the hypophysis in the rat. Injections were also made in the spinal cord in another group of animals, which were subjected to water deprivation for a period of 3 days, and the PVN of these animals was examined with the electron microscope. Spinal projection neurons (paraventriculospinal tract, PVST, neurons) formed two groups; the dorsal and the ventral groups. They were located within the parvocellular part of the PVN and fused into one at the caudal level. The neurons of the dorsal group were well assembled whereas those of the ventral group were intermingled with paraventriculohypophyseal tract (PVHT) neurons, which were concentrated in the magnocellular part. Electron microscopic observations revealed that HRP-labeled neurons after spinal injections did not contain neurosecretory granules and that they were not affected by water deprivation. On the other hand, neurons containing a number of neurosecretory granules displayed a significant degree of dilatation of the endoplasmic reticulum as the result of water deprivation. These neurons contained no HRP granules. The present findings suggest that the PVST neurons are distinct from the PVHT neurons and that the neuronal groups of both systems form different cell columns within the nucleus.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2307
    Keywords: Cerebro-hepato-renal syndrome ; Zellweger's syndrome ; Peroxisome deficiency ; Liver cirrhosis ; Liver biopsy ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary For histologic differential diagnosis of fibrotic and cirrhotic liver changes in early infancy Zellweger's cerebro-hepato-renal syndrome has to be considered. A case is reported where a female newborn failed to thrive and developed severe muscular hypotonia, defective intelligence, and seizures. At an age of 12 months an open biopsy was taken from the enlarged liver. Biochemical tests for disorders of carbohydrate metabolism were negative. The light microscopic examination showed severe fibrosis, lobular disarray, and single cell necroses. Neither siderin nor bile pigment could be detected. There were no changes of the small bile ducts and no signs of inflammation — the child died at 18 months. A postmortem needle biopsy of the liver showed the advanced stage of micronodular cirrhosis. The electron microscopic examination of the first biopsy revealed hypertrophy of smooth endoplasmic reticulum, probably induced by anticonvulsive drugs. The mitochondria showed an increase in the density of their matrix and in the number of sometimes tubular cristae. In accordance with reports in literature, no regular peroxisomes (microbodies) could be found in the hepatocytes. Only a very few profiles with an average diameter of 0.16 μm looked like rather small peroxisomes. The cytoplasmic volume fraction of those organelles, however, amounted to 3×10−5 which is only 1/500 of the normal value in human hepatocytes. Although the significance of the absence of peroxisomes is not yet definitively proved, the term ‘Peroxisome Deficiency’ is proposed as a name which probably is more closely related to the pathogenetic mechanism than the hitherto usual designation cerebro-hepato-renal syndrome.
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  • 8
    ISSN: 1432-2307
    Keywords: Emiocytosis ; Endocrine cells ; Human embryo, child and adult ; Large intestine ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In endocrine cells of the colon of adults, children and fetuses, exocytotic granule release without any specific stimulation is reported. Omega-invaginations are observed on both the lateral and basal surfaces of all types of colonic endocrine cells. Several explanations for the phenomenon are suggested: 1) emiocytosis is probably more frequent in the colon than in the proximal gut, this allows its observation without requiring an exogenous stimulus, 2) since most of the exocytotic figures are from anaesthetized subjects it is also assumed that contraction of the muscular layer induced by anaesthetics and the resulting increase in intraluminal pressure were the possible causes of granule release, 3) in non-anaesthetized subjects release may have taken place in response to a normal endogenous physiological stimulus, or to the dilation of colon during colonoscopy. Less likely is an effect associated with the preparation for colonoscopy. Certain figures on lateral surfaces between endocrine and adjacent cells i.e., bulges of parallel plasma membranes surrounding a secretory granule, were observed. Their significance is unknown.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 383 (1979), S. 167-179 
    ISSN: 1432-2307
    Keywords: Amyloidosis ; cyclic hematopoiesis ; Animal model ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Electron microscopy studies were made on tissues of cyclic hematopoietic (CH) dogs of various ages presenting a high incidence of spontaneous amyloidosis. The distribution and morphologic characteristics of amyloidosis in this animal model closely correspond to the secondary and familial forms of the disease in humans. Plasma cells and, particularly, macrophages presented marked changes during the evolution of amyloid deposition. Residual bodies in the macrophages contained abundant cell debris, a result of both endocytic and autophagocytic activities. Intracellular amyloid fibrils were not observed by conventional electron microscopy. A few reticular cells contained intracytoplasmic fibrils which were morphologically different from amyloid. There was no correlation between the amount of intracellular fibrils and the size of the extracellular amyloid deposits. On the contrary, a temporal association between the magnitude of the amyloid deposits and cytoplasmic changes in the macrophages at sequential stages of the evolution of the disease was evident. It is suggested that the hematopoietic defect in the CH dog could play an important role in the production of amyloidosis, making this animal an excellent experimental model for studies of that disease.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 385 (1979), S. 117-124 
    ISSN: 1432-2307
    Keywords: Liposarcoma ; Breast ; Histopathology ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of primary liposarcoma of the breast in a 65-years-old woman is described by light- and electron microscopy. The patient had previously had a cystosarcoma phyllodes removed from the same area. A review of the literature showed 34 previously published cases of liposarcoma of the breast, which regarding age distribution, histological type and pattern of metastasis corresponded to liposarcomas of the lower limbs.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 155 (1979), S. 209-219 
    ISSN: 1432-0568
    Keywords: Electron microscopy ; Metrial gland (rat) ; Pregnant uterus ; Degeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructural changes occurring in the metrial gland in the latter half of pregnancy in the rat have been studied. Typical palely stained granulated cells are present in the metrial gland up to day 20 but many granulated cells show variations in appearance which may be associated with degeneration. In some the cytoplasm is more darkly stained and such cells often have apparently empty areas of cytoplasm adjacent to the granules. From day 14 onwards many areas of the gland show cellular debris, apparently resulting from lysis of the granulated cells. However, occasionally normal granulated cells are present in blood vessels and have been observed apparently penetrating the vascular endothelium. A variety of changes was also noted in the stromal cell population. Inclusions became apparent in many of these cells; some of these consisted of lipid while others resembled granules from the typical granulated cells. Other cells with numerous inclusions appeared to be macrophages. Lysis of granulated cells in situ is compatible with suggestions that the metrial gland produces a holocrine secretion, though some normal granulated cells enter blood vessels. The stromal cells may have a phagocytic role in late pregnancy but evidence for this was inconclusive.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 157 (1979), S. 121-132 
    ISSN: 1432-0568
    Keywords: Limb bud ; Periderm ; Apical ectodermal ridge ; Electron microscopy ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Development of periderm cells covering fore-and hindlimb buds of mouse em`ryos was observed by scanning and transmission electron microscopy at half day intervals from day 9.5 to 12.5 of gestation (vaginal plug=day 0). At day 9.5, the epidermis is single layered. Occasional periderm cells are present at day 10.5. By day 11.5 a complete layer of periderm cells has covered the entire limb bud. By scanning electron microscopic observation, periderm cells covering the apical ectodermal ridge (AER) are characterized by a small surface size and an elongated polygonal shape with the long axis parallel to the antero-posterior contour of the apical rim. Periderm cells covering the dorsal and ventral surfaces of the limb bud are relatively large and have a polygonal surface shape. The periderm covering the apical tip reflects well the developmental state of the AER. Hence, it is possible to estimate the development of the AER by observing the surface features of the apical periderm by scanning electron microscopy.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 158 (1979), S. 41-50 
    ISSN: 1432-0568
    Keywords: Placenta (human) ; Syncytiotrophoblast ; Intercellular junctions ; Electron microscopy ; Freeze-fracturing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Inter-and intrasyncytiotrophoblastic junctions within the human full term placenta were electronmicroscopically investigated using thin sections and freeze-fracturing. Narrow clefts were occasionally situated between surface areas where adjacent chorionic villi exhibited close contact. Whithin these clefts, extensive zonulae and maculae occludentes and numerous maculae adherentes were found. The zonulae occludentes showed a continuous and irregular course on the membrane surface, and the maculae occludentes were irregularly distributed over extended membrane areas. Besides these areas, maculae occludentes and maculae adherentes were observed on infoldings and invaginations of the syncytiotrophoblastic surface membrane. Investigations of the inner surface of the syncytiotrophoblastic layer, that is, the layer facing the villous stroma, also revealed invaginations joined by maculae adherentes. The functional significance of the inter-and intrasyncytiotrophoblastic junctions is discussed with respect to the differentiation of the trophoblast.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 158 (1979), S. 51-62 
    ISSN: 1432-0568
    Keywords: Cerebellar cortex ; Pre-and postterminal blood vessels ; Rhesus monkey, cat, rat ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the rhesus monkey, cat and rat, pial arteries give off branches which run vertically through all three layers of the cerebellar cortex. The large cortical arteries are surrounded by a perivascular space in the molecular layer. Their wall consists of several layers of smooth-muscle cells and the luminal endothelium. As the arteries reach the deeper layers of the cerebellar cortex, the number of smooth-muscle cells is reduced. In the rat, sometimes no smooth-muscle cells are detectable in the preterminal arterial vessels. If these deep arteries branch off by dichotomy of terminal vessels there occurs a gradual or complete loss of myocytes in all three species. In the cat, where cortical arteries give off branches at rightangles, there is a sphincter-like accumulation of smooth-muscle cells at the opening to the smaller branch. The postterminal vessels and veins in all species exhibit the smae mural structure found in capillaries. The wall consists only of an endothelium and occasional pericytes embedded in the basal lamina. Even the large veins which run to the pial veins show this simple mural structure.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 45 (1979), S. 53-59 
    ISSN: 1432-0533
    Keywords: Tangier disease ; Peripheral nerve ; Electron microscopy ; Cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A sural nerve biopsy was performed in a 55-year-old male patient with Tangier disease (familiallipoprotein deficiency). Light-microscopy showed an increase in the endoneural connective tissue and a loss of nerve fibers indicating a chronic peripheral neuropathy. Electron-microscopy revealed an accumulation of lipid droplets within Schwann cells of myelinated and unmyelinated nerve fibers. When compared with age-matched controls the myelinated fiber density was reduced with a relative preponderance of small myelinated fibers. In addition, distributional cytometric studies of nerve vibers in relation to the perineurium and endoneurial capillaries showed: Contrary to 4.6–7.5 μm thick nerve fibers, which accumulated in the center of the nerve fascicle, small (0.5–4.5 μm) and large (7.6–10.0 μm) fibers lay nearby the perineurium. The measured increase in small myelinated nerve fibers around endoneurial capillaries may be explained as a sign of regeneration.
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 45 (1979), S. 133-140 
    ISSN: 1432-0533
    Keywords: Alexander's disease ; Rosenthal's fibers ; Peripheral Nerve ; Electron microscopy ; Neurochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The authors report the results of a cerebral and of a neuromuscular biopsies and of the autopsy findings in another infantile case of Alexander's disease in a girl. They review the 17 previously reported cases of this disease and the various etiopathogenic hypotheses mentioned. The presence of numerous, sometimes abnormal enlarged mitochondria and of abundant membranous cytoplasmic bodies in the astrocytic cytoplasm seems to be unreported elsewhere. Peripheral nerve changes are mentioned for the first time.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 46 (1979), S. 1-10 
    ISSN: 1432-0533
    Keywords: Dog ; Canine distemper virus ; Cell fusion ; Demyelination ; Encephalomyelitis ; Immunofluorescence ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The early neuropathological development of demyelinating Canine Distemper Encephalomyelitis (CDE) was studied in SPF dogs. Neural tissues were examined up to 30 days post infection (PI). Three phases of activity were observed. The primary event (first observed 8 days PI) was a nonsuppurative encephalomyelitis associated with the initiation of central nervous system (CNS) infection by virus-laden lymphocytes. At 24 days PI noninflammatory demyelination occurred in well defined, subependymal foci. Cell fusion and syncytia formation accompanied this early demyelination. The third phase, found at day 30 PI in one dog showing signs of recovery, was a second wave of nonsuppurative inflammation. The initial encephalomyelitis was widely disseminated throughout the CNS but subsequent demyelination appeared to be initiated from within the ventricular system. Myelin was phagocytosed by endogeneous CNS macrophages often infected with Canine Distemper Virus (CDV). The possible importance of viral induced cell fusion as well as immune factors in the mechanism of demyelination are discussed.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 46 (1979), S. 25-32 
    ISSN: 1432-0533
    Keywords: Cerebral blood vessels ; “Overgrowth” ; Embryonic development ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cerebral capillaries in “overgrown” neural tissue of chick embryo brains ranging in age from 5–18 days of incubation were studied by means of electron microscopy. The vessels in the abnormal tissue showed more extensive and prolonged interdigitations and overlapping of adjacent endothelial cells than did those in normal control brains. In the abnormal neural tissue the appearance and distribution of endothelial cell organelles was similar to that in normal tissue; however, the Golgi complex was less highly developed, and there was an increased amount of coated vesicles in the capillaries of the abnormal brains.
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  • 19
    ISSN: 1432-0533
    Keywords: Paramyxovirus infection ; Ependyma ; Choroid plexus ; Electron microscopy ; Immunofluorescence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of intracerebral inoculation of Sendai virus into young adult mice were investigated by immunofluorescence, light, and electron microscopy. Immunofluorescence of virus-specific antigens was maximal on the third day after inoculation, revealing infection of leptomeninges, ependyma, and choroid plexus. Histologically, meningitis, ependymitis, and choroiditis occurred between the second and third days. The choroiditis was associated with formation of vacuoles within the cytoplasm of epithelial cells. The vacuoles reached diameters up to 50 μm. The ubiquitous vacuolization of plexus epithelia resulted in a honeycomb-like pattern. Opaque viral inclusions were visible within the cytoplasm of choroidal and ependymal epithelium as well as in mononuclear inflammatory cells. On electron microscopy, they were composed of intracytoplasmic nucleocapsid accumulations. Viria lay free between microvilli of plexus epithelial cells, and budding virus structures were observed at cellular surfaces. Occasionally, complete viria occurred in the cytoplasm of plexus epithelial cells and were surrounded by a unit membrane from which they appeared to arise by budding. The formation of this small cavity can be interpreted as the first stage of vacuole formation.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 46 (1979), S. 169-172 
    ISSN: 1432-0533
    Keywords: Giant axonal neuropathy ; CNS ; Dog ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pathology of the central nervous system (CNS) in a dog with giant axonal neuropathy (GAN) is presented. Swollen axons containing excessive and disorganised neurofilaments were present in the spinal cord, mainly at the distal portions of long tracts. The fasciculus gracilis and dorsal spinocerebellar tracts were affected only in the rostral cervical cord while the lateral cortico spinal tract was principally involved in the lower thoracic and lumbar cord. Occasional swellings were also found in the central dorsal columns of the rostral lumbar segments and in the dorsal and intermediate grey matter. The nuclei gracilis and cuneatus, restiform body and ventral spinocerebellar tracts were all involved in the brain stem. Spheroids were seen in the white matter of the rostral cerebellar vermis and in the granule cell layer. The brachium of the superior colliculus contained swollen axons and the cortex was diffusely involved with spheroids. The distribution was of a distal axonopathy and the cortical changes provided an explanation for the abnormal EEG and mental retardation found in some human patients.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 47 (1979), S. 1-11 
    ISSN: 1432-0533
    Keywords: Experimental Concussion ; Peroxidase, neuronal uptake ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neuronal inundation with i.v. infused horseradish peroxidase was studied following concussive brain injury by means of both light and electron microscopy. In animals sustaining mechanical brain injury of insufficient intensity as to elicit either microscopic intraparenchymal hemorrhage or other neuropathological change, yet of sufficient intensity as to provoke a physiological concussive response, vascular peroxidase exudation concomitant with neuronal peroxidase inundation occurred throughout the raphe and reticular core. Initially such inundated neurons were totally flooded with the tracer and as such appeared reminiscent of cells visualized in Golgi preparations. However, over the course of a 24-h period these peroxidase flooded neurons apparently organized the peroxidase into vesicles and vacuoles which assumed a perinuclear position from where the peroxidase ultimately reached both the nucleus und nucleolus. It was remarkable that these events occurred without any evidence of subcellular alteration. We interpret such initial inundation with this protein tracer, its ultimate reorganization, and its nuclear and nucleolar uptake as being consistent with some form of subtle and transient neuronal perturbation. We speculate that as such this neuronal perturbation may constitute a morphological correlate of the concussive episode.
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  • 22
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 47 (1979), S. 237-240 
    ISSN: 1432-0533
    Keywords: Herpes simplex type 2 ; Herpes simplex encephalitis ; Cerebral metastasis ; Metastases and viral encephalitis ; Immunofluorescence ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 62-year-old woman developed neurologic deficits 7 months after pulmonary lobectomy for alveolar cell carcinoma of the lung. CT scan of the head demonstrated two metastases with marked peritumoral edema. Administration of Decadron, chemotherapy and 3,000 rad cranial radiation resulted in dramatic inprovement of dysphasia and right hand paresis. Almost 2 months later, rhythmic, involuntary movements of the left hand developed. There was progression to multifocal seizures, grand mal seizures, postictal depression, status epilepticus, and coma, with death 9 days after onset of the movement disorder. Bronchoalveolar carcinoma was widely disseminated in lungs and bones, and as three metastases in brain. Bland “ischemic” necrosis in a pseudolaminar pattern was present in the neocortex. Innumerable Cowdry type A intranuclear inclusion bodies were seen in neurons, astrocytes, and oligodendroglia. Immunofluorescence demonstrated Herpes simplex virus type 2 antigen and electron microscopy revealed virions with the morphology of the Herpes group. The case is significant for (1) the concurrence of intracranial metastases and Herpes simplex encephalitis, and (2) the causal agent, Herpes simplex virus type 2. The implication for the clinical neurocientist is the potential in a patient with systemic cancer, for the causation of neurologic complications by more than one factor or mechanism.
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  • 23
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 48 (1979), S. 113-125 
    ISSN: 1432-0533
    Keywords: Complete cerebral ischemia ; Postischemic recirculation ; Electron microscopy ; Nuclear perturbations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neuronal, astrocytic, and oligodendrocytic elements in several brain loci of the cat were examined at the light and electron microscopic level immediately after periods of complete cerebral ischemia (CCI) uncomplicated by post-ischemic recirculation. Such CCI episodes ranged from 1.5–25 min duration and were methodically produced in a cat model employing rigorous physiological controls. Subsequent to these CCI insults, morphological alterations occurred in a homogeneous manner within each cell type of all loci examined; however, variation in the temporal onset and magnitude of alterations among the various cell types was observed. With brief ischemic insults all cell nuclei demonstrated pronounced nuclear alterations, while their cytoplasmic organelles displayed minimal change. Chromatin clumping and nucleolar condensation were observed in both neurons and glia subsequent to 1.5–5 min of CCI, respectively. With increasing durations of CCI such changes were more dramatic and conspicuous alterations of the cytoplasmic organelles were observed. On the basis of extensive morphological analyses the present study illustrates that nuclear alterations are the first to occur subsequent to CCI. The homogeneity of neuronal involvement seen subsequent to CCI uncomplicated by post-ischemic recirculation is inconsistent with the “selective vulnerability” purported to occur by others. The significance of this inconsistency remains to be assessed; yet, the suggestion is advanced that post-ischemic recirculation may be a factor in the genesis of such vulnerability.
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  • 24
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 155 (1979), S. 23-36 
    ISSN: 1432-0568
    Keywords: Parotid gland ; Miniature pig ; Electron microscopy ; Innervation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This communication reports on the morphology of the parotid gland of miniature pigs (Göttingen strain). 1. The glandular system consists in its terminal portions of acinar secretory parts. Between the basal lamina and the secretory epithelial cells myoepithelial cells are located. 2. The cytoplasmic organization of the acinar cells represents the features of mucous secretory cells. By electron microscopic means, light secretory granules have been demonstrated which frequently are coalescent. Between the bulk of secretory material only small remnants of cytoplasm are visible. The electron dense nuclei are located in basal parts of the cells. Intercellular canaliculi have not been observed. 3. The intercalary ducts, located between the acinar portions and the striated ducts of the gland, are long and narrow tubules, frequently branched. Their epithelium is simple cuboidal, and there is no indication of any secretory activity. 4. The epithelium of the striated ducts is simple columnar. The orientation of mitochondria parallel to the cell axis, and also the invaginations of the basal cell membrane give the basal cytoplasm a vertically striated appearance. 5. The paravascular nerves of the gland's connective tissue consist of bundles of unmyelinated axons. These branch into smaller bundles, and finally into single unmyelinated axons which reach the acinar portions. These axons appear to be only partly surrounded by Schwann cells. Very thin axons alone penetrate the basal lamina and reach the secretory cells of the acini; moreover, these axons may occasionally reach the intercellular spaces between the secretory cells. Within these terminal parts of the axons groups of synaptic vesicles appear.
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  • 25
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    Archives of dermatological research 266 (1979), S. 253-267 
    ISSN: 1432-069X
    Keywords: Kaposi's sarcoma ; Histochemistry ; Electron microscopy ; Venous capillary endothelium ; Angioblast ; Kaposi-Sarkom ; Histochemie ; Elektronenmikroskopie ; venöse Kapillarendothelien ; Angioblast
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Histochemische und ultrastrukturelle Untersuchungen bei zwei Patienten mit Kaposi-Sarkom ergaben, daß die Spindelzellen die Merkmale von venösen Capillarendothelien aufweisen.
    Notes: Summary Histochemical and ultrastructural studies in two patients with Kaposi's sarcoma revealed that spindle cells have the pattern of venous capillary endothelium.
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  • 26
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    Archives of dermatological research 266 (1979), S. 295-310 
    ISSN: 1432-069X
    Keywords: Fibronectin ; Skin ; Basement membranes ; Immunohistochemistry ; Electron microscopy ; Fibronectin ; Haut ; Basalmembran ; Immunohistochemie ; Elektronenmikroskopie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Verteilung des extracellulären Glykoproteins Fibronectin im Haut- und Zungengewebe der Ratte wurde unter Verwendung von spezifischem Antiserum licht- und elektronenmikroskopisch mit Hilfe der Immunofluorescenz- und Immunoperoxidasemethoden untersucht. Aus den Ergebnissen schließen wir, daß Fibronectin weder in stabilen, differenzierten Gewebeteilen wie Talgdrüsen, Matrix, Mark, Rinde oder Cuticula des Haares oder der inneren und äußeren Haarwurzelscheide, noch in Geweben, in denen die Zellen zum Teil beweglich sind (z. B. Epidermis), vorkommt. Es ist aber charakteristisch für Zonen, wo Zellteilung in Berührung mit einem extracellulären Gerüst vor sich geht, wie z. B. an einer Basalmembran oder in lockerem Bindegewebe. Auffallende Beispiele waren die mit Follikelepithelien verbundene Hyalinmembran und Bindegewebsscheide, die unter Gefäßendothelzellen liegende Basalmembran, die Bindegewebe, welche die Nerven- und Muskelfaserbündel umgeben und durchsetzen und das Bindegewebe der Dermis. Im letzteren Falle war das Fibronectin oft mit Kollagenfasern eng verbunden. In der Basalmembran an der Grenze zwischen Dermis und Epidermis war Fibronectin an der Plasmamembran der basalen Zellen und im Gebiet der Lamina lucida zu finden. Es bestand kein Zusammenhang mit spezifischen Stellen der Zellen-Substrat-Adhäsion wie den Hemidesmosomen. Das endoplasmatische Reticulum der Fibroblaste ließ sich stark färben — ein Hinweis, daß diese Zellen einen wichtigen Ort der Synthese darstellen.
    Notes: Summary Specific antiserum was used to investigate the distribution of the extracellular glycoprotein, fibronectin, in rat skin and tongue tissue by light and electron microscopy with immunofluorescence and immunoperoxidase techniques. We conclude that fibronectin is absent from stable, differentiated parts of tissues, such as the sebaceous glands or the matrix, medulla, cortex, and cuticles of the hair and the inner and outer root sheaths, or even in tissues in which there is some cell movement, such as the epidermis. It is, however, characteristic of sites at which cell division is occurring in contact with an extracellular scaffolding, such as basement membrane or loose connective tissue. Conspicuous examples were in the glassy membrane and connective tissue sheath associated with the follicular epithelium, the basement membrane underlying vascular endothelial cells, the connective tissues surrounding and investing nerve and muscle fibre bundles, and the dermal connective tissue where fibronectin was often associated closely with collagen fibres. At the basement membrane of the dermal/epidermal junction, fibronectin occurred at the plasma membrane of the basal cells and in the lamina lucida area. There was no correlation with specific areas of cell-substrate adhesion, such as the hemidesmosomes. The endoplasmic reticulum of fibroblasts stained strongly suggesting that these cells represent a major site of synthesis.
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  • 27
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    Acta neuropathologica 48 (1979), S. 95-103 
    ISSN: 1432-0533
    Keywords: Schmidt-Lanterman incisures ; Electron microscopy ; Nerve crush ; Wallerian degeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The electron microscopy of changes at Schmidt-Lanterman incisures in Wallerian degeneration has been described only briefly previously. We have demonstrated that the changes up to 36 h after nerve crush are chiefly peri-incisural. At 12h and 24h ‘incisural dilatation’ consisted of an intraperiod line separation of peri-incisural myelin lamellae, which began among inner (adaxonal) lamellae extending later to outer (abaxonal) lamellae. The incisure itself showed little or no change. At 36 h, ovoid formation was apparent in most fibres. The sites of fibre cleavage to form ovoids occurred adjacent to incisures at the focal regions of myelin lamellae separation. Even within ovoids the incisures themselves remained intact at 36 h. The fine structural changes at incisures following nerve crush provide an understanding of the increased perceptibility of incisures by light microscopy during early Wallerian degeneration.
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  • 28
    ISSN: 1432-0533
    Keywords: Mucopolysaccharidosis II ; Prenatal diagnosis ; Electron microscopy ; Lysosomal storage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Light and electron microscopic findings in the nervous system of a 23-week-old fetus are reported, in which MPS II was diagnosed prenatally. The degrees of myelination and neuronal differentiation were similar as in a normal fetus of the same age. A storage of mucopolysaccharides in typical vacuolar inclusion bodies was present throughout the peripheral and central nervous system, mainly in cells of mesenchymal origin. “Zebra” bodies and granulo-membranous bodies, which are thought to represent secondary ganglioside accumulation were only found in the well developed neurons of the spinal cord and spinal ganglia, but not in the poorly developed neurons of the cerebellar and cerebral cortex. Mucopolysaccharide storage in endothelial cells of cerebral blood vessels precedes the appearance of lipid storage in cerebral neurons.
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  • 29
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    Acta neuropathologica 48 (1979), S. 219-221 
    ISSN: 1432-0533
    Keywords: Herpes simplex virus ; Organotypic nerve cell cultures ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In HSV-2 infected cultures, intranuclear tubule-like structures were found more commonly in fibroblasts and central nervous system (CNS) neurons than in oligodendrocytes, astrocytes, satellite and Schwann cells, but were found least often in peripheral neurons.
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  • 30
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    Archives of dermatological research 265 (1979), S. 195-206 
    ISSN: 1432-069X
    Keywords: Hyalinosis ; Electron microscopy ; Glycosaminoglycan ; Glycoprotein ; Cross-banded structure ; Schlüsselwörter ; Hyalinose ; Elektronenmikroskopie ; Glykosaminoglykan ; Glykoprotein ; Struktur mit Querstreifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Systematisierte Hyalinose (Juvenile Hyaline Fibromatose) ist durch die hyalinisierten Hautefflorescenzen gekennzeichnet. Die elektronenmikroskopische Untersuchung eines hyalinisierten Hauttumors von einem 19jährigen Mann mit diesem Syndrom ergab, daß die Hyalinsubstanz sich aus den Rutheniumrot-positiven Ultrastrukturen des Glykosaminoglykans oder des Glykoproteins (d. h. Körnchen, Fäden und einer Struktur mit Querstreifen) und einigen dünnen Kollagenfibrillen zusammensetzte. Mit unserer neuen Rutheniumrotfärbung in der Kombination mit der Enzymverdauungsmethode wurde demonstriert, daß die Struktur mit Querstreifen und die Körnchen aus Chondroitinsulfat-Proteoglykan und/oder Glykoprotein besteht, und daß es sich bei der Struktur mit Querstreifen höchstwahrscheinlich um ein nichtkollagenes Aggregationsprodukt der Körnchen handelt, die eng an die parallel angeordneten, Hyaluronsäure-ähnlichen Fäden angelegt sind.
    Notes: Summary Systematic hyalinosis (juvenile hyaline fibromatosis) is characterized by hyalinized skin lesions. Electron microscopic examination of a hyalinized skin tumor from a 19-year-old man with this syndrome revealed that the hyaline was composed of ruthenium red-positive ultrastructures (granules, filaments, and a kind of cross-banded structure), indicating the presence of glycosaminoglycan or glycoprotein, and a small number of thin collagen fibrits. Using a new ruthenium red staining method combined with an enzymatic digestion procedure, it was demonstrated that the cross-banded structure and granules consisted of chondroitin sulfate-proteoglycan and/or glycoprotein, and that the cross-banded structure is probably a noncollageneous aggregate of the granules attached to the parallel-arranged filaments of hyaluronic acid-like nature.
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  • 31
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    Archives of dermatological research 265 (1979), S. 91-99 
    ISSN: 1432-069X
    Keywords: Electron microscopy ; Civatte body ; Atrophy ; Light sensitivity ; Heredity ; Elektronenmikroskopie ; Civatte-Körperchen ; Atrophie ; Lichtempfindlichkeit ; Vererbung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Zwei Patienten (insgesamt 4), zwei Brüder, mit »The diffuse and macular atrophic dermatosis» wurden beobachtet. Das familiäre Vorkommen, die «peau citréine»-Plaquen an der dorsalen Seite des Rumpfes, sowie eine kongenitale Phimose mit einer oberflächlichen Atrophie des Glans Penis, sind die neuen Befunde. Licht- und elektronenmikroskopische Befunde einer «peau citréine»-Plaque und einer erythematösen, skleroatrophischen Plaque werden geschildert. Es wurde auch gezeigt, daß die elastischen, färbungspositiven kugelähnlichen Strukturen, die in ungewöhnlich großer Zahl in der oberen Dermis gefunden wurden, fortgeschrittenere transformierte Civatte-Körperchen darstellen, die epidermale Zellen enthalten.
    Notes: Summary Two brothers with the “diffuse and macular atrophic dermatosis” making a total of 4 patients are reported. The familial occurrence, numerous large “peau citréine” plaques situated on the dorsum of the upper trunk and congenital phimosis with superficial atrophy of glans penis, represent the additional features reported. The light and electron microscopic findings of the least affected site on the arm, of a “peau citréine” and of an erythemoscleroatrophic plaque, none previously studied, have been reported. Among other items, it was also found that the elastic stain-positive globe-like structures found in an unusually large number throughout the edematous upper dermis represent more advancely transformed “Civatte bodies” containing epidermal filamentous cell material.
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  • 32
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    Annals of hematology 39 (1979), S. 177-190 
    ISSN: 1432-0584
    Keywords: Chronische myelo-monozytäre Leukämie ; Seeblaue Histiozyten ; Knochenmarksbiopsie ; Elektronenmikroskopie ; Chronic myelomonocytic leukemia ; Sea-blue histiocytes ; Bone marrow biopsy ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Clinical data and light and electron microscopic findings are presented in a patient with chronic myelomonocytic leukemia of about 5 years' duration and no need for specific therapy. Cytogenetic studies failed to demonstrate a Philadelphia-chromosome. The leading clinical symptoms were anemia, moderate hepatomegaly, and leukocytosis with monocytes in the peripheral blood count. Light microscopy of bone marrow cores showed hypercellularity of neutrophil granulocytic and monocytic cell lines including some precursor forms. Electron microscopy confirmed the existence of a biphasic myelomonocytic cell proliferation with predominance of mature forms in both lineages; there were no gross cellular abnormalities and no “hiatus leukaemicus”. Conspicuous were cells of an undeterminated origin apparently neither belonging to the neutrophil granulocytic nor monocytic series and large histiocytic cells, possibly corresponding to the so-called sea-blue histiocytes of light microscopy. The high degree of maturation of both cell lines in the bone marrow is in accordance with the relatively benign and prolongated course of this rare type of leukemia.
    Notes: Zusammenfassung Von einem Patienten mit einer chronischen myelo-monozytären Leukämie von etwa 5 Jahren Dauer und ohne spezifische Therapie werden klinische sowie licht- und elektronenmikroskopische Befunde vorgestellt. Zytogenetische Untersuchungen ließen ein Philadelphia-Chromosom nicht erkennen. Die führenden Symptome waren eine geringe Anämie, eine mäßige Lebervergrößerung und Leukozytose mit Monozyten im peripheren Blutausstrich. Lichtmikroskopische Untersuchungen des Knochenmarkes zeigten eine Zellvermehrung der neutrophilen granulozytären und der monozytären Zellreihen einschließlich einiger Frühformen. Die Elektronenmikroskopie bestätigte das Vorhandensein einer biphasischen myelo-monozytären Zellproliferation mit Vorwiegen der reifen Formen in beiden Zellinien. Es bestanden keine bemerkenswerten zellulären Anomalien und kein „hiatus leucaemicus“. Auffallend waren Zellen unbestimmbarer Herkunft, die weder der neutrophilgranulozytären oder monozytären Reihe sicher zuzuordnen waren, und große histiozytäre Zellen, die wahrscheinlich den sogenannten „seeblauen Histiozyten“ der Lichtmikroskopie entsprechen. Der hohe Grad der Ausreifung in beiden Zellinien im Knochenmark steht in Übereinstimmung mit dem relativ gutartigen und langen Verlauf dieses seltenen Types einer Leukämie.
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  • 33
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    Acta neuropathologica 45 (1979), S. 187-194 
    ISSN: 1432-0533
    Keywords: Human adenovirus 12 ; Hamsters ; Subcutaneous neuroblastomatous tumor ; T-antigens ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Single subcutaneous inoculation of human adenovirus type 12 (Ad. 12), 0.05–0.1 ml of 108.0 TCID50 HEK cells/0.1 ml, was made on the back of 0-day-old hamsters. In 21 of 25 hamsters (84.0%), multiple solid tumors developed close to the inoculation site within 3 months. No control hamsters developed tumors. Tumor histopathology revealed the characteristic Homer Wright rosettes of neuroblastoma. Ad. 12-specific tumor antigens were demonstable in both the primary and the cultured tumor cells by the hnmunofluorescein technique. Histochemical demonstration of cholinesterase and NADH oxidoreductase gave rise to a predominantly positive intracytoplasmic granule within the tumor cells. Electron microscopy showed remarkably iniform cell morphology: small, undifferentiated neuroblastic cells with poorly developed intracytoplasmic organelles; many possessed characteristic solitary cilia in a 9+0 tubules pattern. Intercellular junctions were poorly developed. Search for an incipient tumor cell aggregate by means of immunofluorescein T-antigen detection was carried out through a 240-h period following Ad. 12 inoculation. A sequential study in parallel with electron microscopic examination of the normal subcutaneous tissue proved that neuroblastic cells closely associated with the muscle spindle anlage could preferentially become the most sensitive target for Ad. 12 tumorigenesis.
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  • 34
    ISSN: 1432-0533
    Keywords: Sensory neuropathy ; Nerve biopsy ; Electron microscopy ; Quantitative study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An electron microscope study and quantitation of myelinated and unmyelinated fibers of seven nerve biopsies performed in sporadic cases of idiopathic sensory neuropathy is reported. The number of myelinated fibers is markedly decreased or absent in every case. On the contrary, the unmyelinated fiber numbers are normal or increased. In most cases, the small diameter myelinated and unmyelinated fibers proportions are higher than those of control biopsies. The electron microscope study discloses evidence of degeneration of Wallerian type and regeneration is also indicated by quantitative studies. Regenerative phenomena seem more obvious in sporadic cases than in previously reported studies of familial cases.
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  • 35
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    Acta neuropathologica 47 (1979), S. 205-211 
    ISSN: 1432-0533
    Keywords: Brain tumor cells ; Chemical carcinogen ; Benzo(a)pyrene ; Oncogenesis ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An ultrastructural study was performed on normal and Benzo(a)-pyrene (B(a)P)-transformed fetal mouse brain cells. Early subcultures of a strain initiated from whole brain presented three cell types in vitro: astroglial, poorly differentiated glial, and spongioblastic types. After B(a)P-treatment, there was an exclusive transformation and the growth of neuroglia sometimes without gliofibrillary maturation, but with the presence of glial fibrillary acidic protein (GFAP) in the cytoplasm. Early subcultures of another strain initiated from cortex only presented poorly differentiated neuroglial cells. After transformation, cell maturation as evidenced by gliofibrillogenesis and GFAP production by these cells was observed. In both cases, the potentiality of glial differentiation after in vitro malignant transformation by a chemical carcinogen seemed preserved.
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  • 36
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    Acta neuropathologica 46 (1979), S. 239-241 
    ISSN: 1432-0533
    Keywords: Acromegaly ; Electron microscopy ; Growth hormone ; Pituitary adenoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Unusually large, oval and pleomorphic secretory granules were noted by electron microscopy in an acidophilic adenoma of the pituitary. The tumor, which was removed by surgery from a 42-year-old woman with elevated blood growth hormone levels and the clinical features of acromegaly, was found to contain growth hormone by the immunoperoxidase technique. This ultrastructural abnormality of secretory granules was not reported so far and was not seen among the 58 cases of growth hormone-producing adenomas investigated in our laboratory. The present case clearly shows that the cytogenesis and cellular composition of pituitary adenomas cannot be determined by solely examining the size and shape of secretory granules.
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  • 37
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    Acta neuropathologica 47 (1979), S. 189-196 
    ISSN: 1432-0533
    Keywords: Childhood dermatomyositis ; Muscle biopsy ; Electron microscopy ; Tubular arrays
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Muscle biopsies from 12 patients with a typical clinical picture of dermatomyositis have been examined by electron microscopy. Endothelial cells of intramuscular blood vessels, their basal lamina, pericytes, muscle fibers, and satellite cells show degenerative or regenerative alterations. In nine patients, tubular arrays were noted in the cisterns of endoplasmic reticulum of endothelial cells, pericytes, lymphocytes, macrophages and satellite cells. Other types of inclusions were also observed. The pathogenesis of the disease is discussed.
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  • 38
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    Acta neuropathologica 47 (1979), S. 61-66 
    ISSN: 1432-0533
    Keywords: Experimental tumors ; Tissue culture ; Scanning ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serially transplanted neurogenic tumors of experimental origin were explanted in vitro and analyzed by scanning electron microscopy. In explants of intracerebrally transplanted gliomas, small stellate cells with branching processes were observed; in transplanted tumors of the peripheral nervous system, slender bipolar cells as well as fibroblasts emerged. The stereoscopic features were compared with the picture of conventional light microscopy. The findings are consistent with the assumption of the glial derivation of CNS-tumors induced with neurotropic alkylating carcinogens. The peripheral tumors are composed of Schwann-cell like elements and fibroblasts. The significance of the results for the cytogenetic derivation of brain tumors are discussed.
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  • 39
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    Acta neuropathologica 46 (1979), S. 139-144 
    ISSN: 1432-0533
    Keywords: Perineurium ; Peripheral ganglion ; Diffusion barrier ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The perineurial diffusion barrier to horseradish peroxidase (HRP) and ferritin was investigated in superior cervical ganglia of rats and mice. The ganglion was surrounded by a delicate epineurium and 2–5 perineurial lamellae joined by zonulae occludentes and desmosomes. Following local application of tracers the animals were killed after 5, 30, and 60 min and the distribution of HRP and ferritin was studied by light and electron microscopy. The inner layers of the ganglionic perineurium prevented diffusion of both HRP and ferritin into the endoneurium. Owing to the fewness of the perineurial lamellae investing the ganglion. HRP had often extended to the innermost lamella 60 min after application. HRP and ferritin were present in vesicles of ganglionic perineurial cells. There was no passage of tracers via intercellular junctions.
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  • 40
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    Acta neuropathologica 46 (1979), S. 163-166 
    ISSN: 1432-0533
    Keywords: Electron microscopy ; Pituitary adenoma ; Annulate lamellae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Electron microscopy revealed the presence of annulate lamellae in the cytoplasm of a heavily granulated prolactin cell adenoma that had been removed from a 34-year-old male patient presenting impotence. To our knowledge this is the third case of pituitary adenomas where annulate lamellae are reported.
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  • 41
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    Acta neuropathologica 47 (1979), S. 55-59 
    ISSN: 1432-0533
    Keywords: Virus-like particle ; Nucleic acid ; Muscle ; Cytochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Picornavirus-like crystalline arrays were found in the skeletal muscle of a victim of a traffic accident. Individual particles measured approximately 22 nm in diameter and were arrayed in a hexagonal or triangular pattern. Cis-platinum (II) staining of these virus-like particles showed that these particles were not glycogen but contained nucleic acids, and the staining according to Bernhard also showed these particles contained RNA. Through the combination of the methods of Heinen (1977) and Bernahrd (1969), we can confirm that virus-like crystalline structures found electron microscopically contain nucleic acids and possibly represent virions.
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  • 42
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    Acta neuropathologica 48 (1979), S. 63-66 
    ISSN: 1432-0533
    Keywords: Acute multiple sclerosis ; Virus-like particles ; Demyetination ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Novel, superficially ‘virus-like’ hollow-cored particles 50–60 nm in diameter were found in the perivascular extracellular space of the brain from a patient who died with acute multiple sclerosis (MS). It is concluded that they are not virions but are derived from myelin undergoing vesicular demyelination. This case demonstrates the need for caution in the interpretation of unusual electron microscopic appearances.
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  • 43
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    Acta neuropathologica 45 (1979), S. 241-245 
    ISSN: 1432-0533
    Keywords: Myelin formation ; Ganglioglioma ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Formation of myelin sheaths by neoplastic cells was found in a spinal ganglioneuroma. All phases of initial myelination were observed including the formation of a mesaxonal spiral and the fusion of its famellae into a major dense line. A unique aspect of neoplastic myelin formation was the formation of sheaths around bundles of extracellular fibrils rather than axons or cell processes. Formation of myelin sheaths around extracellular material has never been observed before. The findings have implications on the mechanisms controlling initial myelination.
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  • 44
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    Acta neuropathologica 45 (1979), S. 147-152 
    ISSN: 1432-0533
    Keywords: Progressive supranuclear palsy ; Neurofibrillary tangles ; Electron microscopy ; Straight filaments ; Twisted tubules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The fine structure of subcortical neurofibrillary tangles was investigated in pallidum, substantia nigra, periaqueductal gray, pontine reticular gray, and dentate nucleus of 5 autopsy cases of Progressive Supranuclear Palsy. Only tangles due to straight 150 Å wide filaments have been detected. These findings, obtained from a large series of cases and areas examined, confirm previous observations on the fine structure of neurofibrillary tangles in Progressive Supranuclear Palsy and suggest that the association between tangles due to straight filaments and tangles due to twisted tubules, so far described in one case, is probably exceptional.
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  • 45
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    Acta neuropathologica 46 (1979), S. 235-237 
    ISSN: 1432-0533
    Keywords: Paraganglioma ; Cauda equina region ; Neurosecretory granules ; Nerve fibers ; Endothelial cells ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Some new ultrastructural observations are documented in a paraganglioma in the cauda equina region. These include the presence of nerve fibers in the tumor capsule, clear vesicles and tubulo-vesicular structures in some cytoplasmic processes in the tumor, fenestrated endothelial cells, and numerous tubular bodies in some endothelial cells.
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  • 46
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    Acta neuropathologica 47 (1979), S. 163-165 
    ISSN: 1432-0533
    Keywords: Dysplastic gangliocytoma ; Cerebellum ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The fine structure of a dysplastic gangliocytoma of the cerebellum is studied by means of the Golgi method and electron microscopic examination. Thick proximally unbranched dendrites with terminal arborizations and varicose influorescences in the form of a basket are stained with the Golgi method. Axons are always descendant to the inner myelinated layer of the redistributed cerebellar cortex, while ascendant collaterals are observed at the level of the outer myelinated layer. Clear and dense-core vesicles and synapses are common in the cellular profiles under electron microscopic examination. From these data and because of the lack of putative connections through the white matter, an organized, self-regulated, catecholamine-mediated complex may be postulated.
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  • 47
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    Calcified tissue international 29 (1979), S. 101-105 
    ISSN: 1432-0827
    Keywords: Osteon ; X-ray diffraction ; Pole figures ; Electron microscopy ; Calcification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The X-ray diffraction method based on pole figures has been applied to single osteon samples in order to obtain information about the texture of the inorganic bone fraction and the way it changes during calcification. The osteon samples were cylindrically shaped, with axes corresponding to those of the haversian canals. Selection was carried out according to the degree of calcification and the orientation of collagen bundles and inorganic particles. Osteons at both the initial and final stages of calcification were chosen. Arrangements of fiber bundles and inorganic particles in successive lamellae characteristic of three types of osteons were selected: longitudinal, alternate, and transversal. The results indicate that in all three types of osteons, the long axis of the sample is apparently the only direction of orientation because the transversally oriented crystallites give an isotropic diffuse scattering as would be expected if all the inorganic particles were irregularly oriented around the osteon axis. The number of longitudinally oriented crystallites increases progressively from transversally oriented osteons to alternately and longitudinally oriented ones. The crystallite orientation in an axial direction increases in fully calcified osteons. This last result is in agreement with the electron microscopic finding that the long needle-shaped crystallites covering much more than a major collagen period and measuring 40–45 Å in width increase in number as calcification proceeds.
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  • 48
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    International archives of occupational and environmental health 44 (1979), S. 25-43 
    ISSN: 1432-1246
    Keywords: Electron microscopy ; Morphometry ; Freeze etching ; Liver ; Aging ; Polychlorinated biphenyls ; Elektronenmikroskopie ; Morphometrie ; Gefrierätzung ; Leber ; Altern ; polychlorierte Biphenyle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In der vorliegenden Untersuchung wurden jungen und alten männlichen Wistarratten polychlorierte Biphenyle (PCB) i.p. appliziert. Die altersbedingten und die hepatotoxischen Veränderungen in der Leber wurden licht- und elektronenmikroskopisch erfaßt. Des weiteren wurden Membranveränderungen mit der Gefrierätzung nachgewiesen. Neben den altersbedingten Veränderungen im Vergleich der beiden Kontrollkollektive fällt vor allem die exzessive Proliferation des glatten endoplasmatischen Retikulums auf, welche nach PCB-Applikation in den Hepatocyten nachzuweisen ist. Bei den jungen Ratten betrug die Vermehrung der Oberflächen-dichte dieser Membranen im Vergleich zu den Kontrolltieren 803% (P〈0,001) und bei den alten Ratten 282% (P〈0,001). Bei alten anderen untersuchten Parametern wurden sowohl bei den jungen als auch bei den alten Ratten statistisch signifikante Verringerungen nach PCB-Gabe festgestellt.
    Notes: Summary Thin-section and freeze-fracture techniques have been employed to investigate the ultrastructure of PCB-intoxicated rat liver of different ages. Besides alterations in the supramolecular structure of the plasma membranes, excessive proliferation of smooth endoplasmic reticulum (SER) in the hepatocytes was observed. In young rats, the surface density increased by up to 803% (P〈0.001) and in old rats up to 282% (P〈0.001) compared with the control rats. All other investigated parameters decreased significantly after the application of PCB.
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  • 49
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    Pflügers Archiv 381 (1979), S. 127-135 
    ISSN: 1432-2013
    Keywords: Na+−K+-ATPase ; Rat kidney ; Electron microscopy ; Substructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purified membrane-bound Na+−K+-ATPase from rat kidney outer medulla was studied by freeze-fracturing, by freeze-etching and by negative staining. Freeze-fracturing of purified Na+−K+-ATPase membranes shows intramembraneous particles with a diameter of about 100 Å. The frequency of these intramembraneous particles — as estimated from the particle densities on the two fracture faces — lies between 4700 and 5600 particles per μm2. Applying rotary shadowing a four partite substructure could be detected in these intramembraneous particles observed on the fracture planes. The same four partite substructure was detected in particles observed on freeze-fractured and rotary shadowed intact baso-lateral plasma membranes of the thick ascending limb of Henle's loop. Particles could be also detected on both membrane surfaces of the purified Na+−K+-ATPase. These surface particles have about the same diameter and are present at about the same frequency as those observed within the freeze-fractured membranes. Negative staining of isolated Na+−K+-ATPase membranes showed particles on both membrane surfaces with a diameter between 30 and 50 Å, at a frequency of about 19,000 per μm2. On aspects of membrane edges we observed structures which suggest a transmembraneous connection of the negatively stained particles on both membrane surfaces. Our results suggest that the Na+−K+-ATPase protein is composed of four units and that each unit spans the cell membrane. The native enzyme structure of the Na+−K+-ATPase protein seems to be preserved during freeze-fracturing and freeze-etching. It is proposed that the four enzyme units of the Na+−K+-ATPase complex are dissociated during the negative staining procedure.
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  • 50
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    European journal of clinical pharmacology 16 (1979), S. 203-209 
    ISSN: 1432-1041
    Keywords: dantrolene sodium ; spasticity ; twitch tension ; dose response ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dantrolen sodium is a muscle relaxant, which is used in the treatment of spasticity. Although it is given chronically, little is known about its pharmacokinetic behaviour. The relationship between the effect of a single oral dose of dantrolene sodium and its plasma concentration in healthy volunteers was studied by measuring the effect on the twitch tension, and in spastic patients on the decrease in muscle hypertonia. On the twitch tension dantrolene gave a depression of 49.1±9.4% (±SD) within 1.15 and 3.45 h after ingestion of 100 mg. The mean maximal plasma concentration was 1.24±0.32 µg/ml (±SD). The effect and the plasma concentration were correlated. No relationship between the plasma concentration of dantrolene sodium and its effect could be established in patients, although definite activity in 6 out of 7 patients was observed after a single oral dose of 100 mg, and plasma concentration of dantrolene sodium greater than 0.3 µg/ml were consistently associated with better results than placebo treatment in 6 out of 7 patients.
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  • 51
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    European journal of clinical pharmacology 16 (1979), S. 287-293 
    ISSN: 1432-1041
    Keywords: linear system theory ; perfusion model ; cardiac output ; pulmonary extraction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Assessment of pharmacokinetics in terms of circulatory drug transport is proposed using the methods of linear system theory. In this model-independent approach drug distribution and disposition are characterized by the total extraction ratio, the mean residence time in the body and the volume of distribution at steady state. In analyzing concentration(c)-time(t) data, the procedure requires calculation only of the areas under the c(t)-and c(t)×t-curves to estimate kinetic parameters, and for prediction of the steady state concentration following continuous infusion or multiple doses. Pulmonary clearance of drugs is included in the theory.
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  • 52
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    European journal of clinical pharmacology 15 (1979), S. 275-280 
    ISSN: 1432-1041
    Keywords: Parkinson's disease ; bromocriptine ; pharmacokinetics ; plasma concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma kinetics of bromocriptine (BCT), a long-acting dopamine agonist, was studied in twelve patients with Parkinson's disease, using a newly developed gas chromatographic method of analysis. Each patient received BCT for at least three weeks in a constant but different dose regimen. Concomitant treatment with 1-DOPA was not allowed. During a 6-day hospitalization period, a blood sample was taken immediately before the afternoon dose at 14.00 h (Cmin) to determine the steady-state level. On the 6th day blood samples were collected every hour during two 8 h dose intervals. The results showed a significant correlation between the mean values of the AUC and the Cmin. First order elimination kinetics appeared to be followed by BCT, at least for the plasma concentrations commonly found. Considerable inter-individual variation was demonstrated both for the dose/plasma concentration ratio and for calculated plasma clearances. No serious side-effects were observed during the investigation.
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  • 53
    ISSN: 1432-1041
    Keywords: indobufen ; platelet aggregation ; food effect on bioavailability ; repeated administration ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of food on bioavailability of indobufen tablets was investigated in 6 healthy volunteers. Subsequently, the same subjects took 100 mg b.i.d. for 7 days. Plasma levels and urinary excretion of indobufen were determined by GLC. Platelet aggregation induced by several concentrations of adrenaline was determined turbidimetrically at various times after the first and last doses. The absorption of indobufen tablets was not substantially impaired by the presence of food in the GI tract, although peak plasma levels and AUCs were slightly reduced after food. Pharmacokinetic analysis of plasma and urinary levels of indobufen did not indicate any change in drug disposition after repeated dosing. Adrenaline-induced platelet aggregation was markedly inhibited for up to 12 h after the first dose and the intensity and duration of this effect did not change after repeated administration. A twice-daily dosing appears suitable for clinical trials.
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  • 54
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    European journal of clinical pharmacology 15 (1979), S. 341-347 
    ISSN: 1432-1041
    Keywords: clofibrate ; chlorophenoxyisobutyric acid ; disposition ; hepatitis ; cirrhosis ; renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of clofibrate over 96 hours was observed following single oral dose in six patients with acute viral hepatitis, six patients with liver cirrhosis, seven patients with renal insufficiency, and six control subjects. No parameter of the disposition of CPIB (active form of clofibrate) was significantly altered in acute hepatitis. In liver cirrhosis, the mean plasma half-life was unchanged compared to controls (20.9 vs. 17.5 h), but plasma clearance of the non-protein bound drug was reduced (115 vs. 243 ml×min−1), plasma protein binding was reduced (92.8 vs. 97.2 percent), and the apparent volume of distribution was increased (0.20 vs. 0.141×kg−1). In renal insufficiency plasma half-life was prolonged 2 to 6-fold, depending on the degree of renal impairment. Total plasma clearance (3.4 vs. 7.1 ml×min−1) and plasma clearance of the unbound drug (81 vs. 243 ml×min−1 were reduced in patients with renal failure, the clearance of the unbound drug being inversely correlated with the serum creatinine concentration. Renal failure was also associated with decreased protein binding and an increased volume of distribution of CPIB, and with reduced urinary excretion of CPIB and its glucuronide metabolite. The dose of clofibrate should be halved in patients with cirrhosis. In renal insufficiency, the dose should be adjusted according to the individual serum creatinine level: only 10 to 15% of the usual weekly dose should be given in complete renal failure.
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  • 55
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    European journal of clinical pharmacology 15 (1979), S. 363-366 
    ISSN: 1432-1041
    Keywords: methotrexate ; protein binding ; ultrafiltration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The protein binding of methotrexate by serum from eight normal volunteers was assessed by continuous ultrafiltration at pH 7.4 and 37°C. Methotrexate concentrations were measured by radioimmunoassay and the data analysed by the method of Scatchard. The major binding protein was albumin which bound 87.3% of the drug in serum. Analysis of the Scatchard plots indicated two distinct groups of binding sites. Class I was found to have 0.16±0.05 (S D) binding sites with an intrinsic association constant of 71.15±35.98 (S D)×104 M−1: Class II had 2.01±0.93 (S D) binding sites and an affinity of 0.18±0.15×104 M−1. No great change in the percentage of methotrexate bound occurred until the total concentration of the drug exceeded 50 µMol 1−1.
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  • 56
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    European journal of clinical pharmacology 16 (1979), S. 243-249 
    ISSN: 1432-1041
    Keywords: timolol ; beta blockade ; pharmacokinetics ; pharmcodynamics ; acute administration ; chronic administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and effects of various oral doses of timolol administered either acutely or after chronic medication for 7 days were studied in healthy volunteers. After acute administration of timolol maximum plasma concentrations were attained within 1–2 h and thereafter declined exponentially with time. The mean apparent half-life of elimination from plasma was 2.5 h and was independent of dose. Area under the plasma concentration-time curve (AUC) was proportional to the orally administered dose. Plasma concentrations, apparent elimination half-life and AUC were not altered after one week of chronic administration. The effect of timolol on heart rate and blood pressure response to three sequentially increasing ‘steady state’ work loads were studied. After acute administration of timolol maximum reduction of systolic blood pressure, resting heart rate, and the different parameters of the work-heart rate (or blood pressure) relationships were produced by 5 mg timolol. Increasing the dose prolonged the duration over which these variables were reduced. The relationship between timolol plasma concentration and inhibition of different parameters of the exercise response was hyperbolic with half maximum inhibition at concentrations of about 3–4 ng/ml of timolol and maximum inhibition above 30 ng/ml. Maximum drug effects and duration of action of timolol on the different variables were similar after acute and chronic administration.
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  • 57
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    European journal of clinical pharmacology 16 (1979), S. 263-270 
    ISSN: 1432-1041
    Keywords: diazepam ; alcoholic beverages ; plasma level ; pharmacokinetics ; co-ordination skills ; red wine ; white wine ; whisky
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty paid healthy students ingested diazepam 10 mg 30 min after the administration of ethanol 0.8 g/kg. The alcoholic beverage used was varied in randomized double-blind experiments, which were repeated at one-month intervals. Psychomotor performance, plasma diazepam, and alcohol concentration in breath were measured 30, 60, 90 min and 2, 3, 4, 6 and 24 h after the ingestion of diazepam. Beer and white wine elevated the plasma level of diazepam and the effect lasted for up to 2 h. Whisky elevated the diazepam level for 90 min. Red wine did not affect it significantly. The alcohol-diazepam combination impaired tracking skills and oculomotor co-ordination and enhanced nystagmus, more than diazepam alone. Red wine produced a breath alcohol concentration higher than after white wine. More nystagmus was recorded after red wine and diazepam, although white wine led to a higher plasma diazepam concentration. It appears that simultaneous ingestion of alcohol and diazepam accelerates the absorption of diazepam. This pharmacokinetic alteration may not contribute much to the combined psychomotor effects of diazepam and alcohol, which were mainly due to pharmacodynamic interaction at receptor level.
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  • 58
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    European journal of clinical pharmacology 16 (1979), S. 271-277 
    ISSN: 1432-1041
    Keywords: lithium ; litarex ; single dose ; multiple dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An analysis of the single and multiple dose pharmacokinetics of lithium in 7 healthy volunteers is presented. A solution of lithium chloride was administered in single dose experiments and the same solution and a sustained release preparation were employed in multiple dose experiments, which were carried out at steady state. A fixed dose of 24 mmol was used in the single dose experiments and in the subsequent multiple dose experiments in the same subjects the same dose was administered once daily for a week. Distinct two-compartment characteristics were found, with a mean disposition rate constant (β) of 0.035 h−1±0.010 SD, corresponding to a mean biological half-life of about 19.8 h. The mean half-time of the distributory α-phase was about 1.15 h. The absorption of lithium from an orally administered solution took place with a half-time of about 0.15 h in the single dose experiments. The apparent volume of distribution of the central compartment (Vc) was 0.307 1 kg−1±0.046 SD, less than half that of Vde at equilibrium. Vdβ (Vdarea) was 0.8291 kg−1±0.184 SD and mean total body clearance was 27.6 ml kg−1 h−1±4.7 SD.
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  • 59
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    European journal of clinical pharmacology 16 (1979), S. 255-262 
    ISSN: 1432-1041
    Keywords: spironolactone ; canrenone ; fluorimetry ; high performance liquid chromatography ; linear kinetics ; saturation kinetics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In Study I 20 normal volunteers received a single oral dose of spironolactone 100 mg. In Study II a further 20 normal volunteers were given first spironolactone 100 mg b.i.d. and subsequently spironolactone 100 mg once a day for a further 4 days. In Study III 5 normal subjects were given a single dose of spironolactone 500 mg. The concentration of canrenone in serum was determined both by fluorimetry and HPLC for 0–48 h in Study I, 120–168 h in Study II and 0–36 h in Study III. The total AUCs after the single 100 mg dose did not differ from the AUCs within the dosing interval during steady state. The half-lives of the terminal log-linear phases were almost identical (14.99±0.80 h and 15.69±0,80 h) when determined by fluorimetry, and were sligthly, but significantly (p〈0.01), longer when determined by HPLC — 20.14±1.62 and 18.71±1.04. The mean ratio of the specific AUC determined by HPLC and the fluorimetrically determined AUC was 0.3 after the single 100 mg dose. It did not differ from the corresponding value during steady state (0.34). In contrast, the ratio after the single 500 mg dose was approximately 50% higher. Fluorimetrically determined AUCs after 100 and 500 mg doses did not show dose-proportionality in contrast to the HPLC-determined AUCs. It was concluded that Canrenone contributes much less to the conventional fluorimetric determination than was previously assumed. It may not provide more than 1/10 and 1/4 of the antimineralocorticoid activity of spironolactone after single dose and multiple doses, respectively. Whereas linear kinetics apply after single and multiple 100 mg doses of spironolactone, after 500 mg saturation kinetics must be assumed with respect to metabolism. Thus, in bioavailability studies high doses of spironolactone should be avoided. For such studies the fluorimetric assay seems to be the appropriate bioanalytical method in spite of its lower specificity.
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  • 60
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    European journal of clinical pharmacology 15 (1979), S. 187-192 
    ISSN: 1432-1041
    Keywords: quinidine ; plasma protein binding ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition and plasma protein binding of quinidine after intravenous administration were studied in 13 healthy subjects. Plasma protein binding, expressed as the fraction of quinidine unbound ranged from 0.134–0.303 (mean 0.221). Elimination rate constant (β) varied from 0.071 to 0.146 h−1 (mean 0.113), and apparent volume of distribution (Vβ) varied from 1.39–3.20 l · kg−1β (mean 2.27). Total body clearance was 2.32–6.49 ml min−1 · kg−1. There was a positive linear correlation between the plasma fraction of unbound quinidine and both Vβ (r=0.885, p〈0.01) and total body clearance (r=0.668, p〈0.05). No significant correlation existed between the fraction of unbound quinidine in plasma and the elimination rate constant. The results show that both the apparent volume of distribution and total body clearance of quinidine are proportional to the unbound fraction in plasma. This implies that the total plasma concentration of quinidine at steady state will change with alterations in plasma binding, whilst the concentration of unbound compund and its elimination rate will remain unaffected.
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  • 61
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    European journal of clinical pharmacology 15 (1979), S. 153-157 
    ISSN: 1432-1041
    Keywords: cimetidine ; renal failure ; elimination half life ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration curve after a single oral dose of cimetidine 200 mg was followed in 27 patients with varying degrees of chronic renal failure (creatinine clearance 1–52 ml/min) and in 46 patients with normal serum creatinine. Compared to the latter patients, the plasma concentration was higher and the elimination rate was slower in all uraemic subjects, including a group with moderate renal impairment. The preliminary recommendations of dosage for patients with a creatinine clearance below 5 ml/min, and for patients on regular haemodialysis, is cimetidine 200 mg every 12 h, 5–15 ml/min 200 mg every 12 to 8 h, 15–30 ml/min 200 mg every 8 h and 30–52 ml/min 200 mg every 6 h.
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  • 62
    ISSN: 1432-1041
    Keywords: nitrazepam ; epilepsy ; age ; disease ; plasma concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of nitrazepam were measured by gas-liquid chromatography in: young healthy volunteers, in geriatric and psychiatric patients and in epileptic children. The disposition of nitrazepam was described in terms of a two-compartment open model. After a single oral dose of nitrazepam 5 mg the most prominent differences between the experimental groups were in the β-phase half-life-mean 29 h in the young volunteers and 40 h in geriatric patients, and in the apparent volume of distribution during the β-phase of 2.4 vs 4.8 l/kg. Total plasma clearance and the average steady state concentration in both groups were equal. The plasma level rose at a rate proportional to the β-phase half-life, and so, they were achieved more rapidly in the young than in the old subjects (3.5 vs 7.5 d). No change in steady-state level or in the half-life of nitrazepam were found during long term treatment, which indicates lack of enzyme induction or inhibition. In 95% of the epileptic children with a good to fair clinical response, the plasma concentration of nitrazepam was 40–180 ng/ml (mean 114 ng/ml). As all of the patients were on combined antiepileptic therapy, no attempt was made to correlate plasma level with therapeutic response.
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  • 63
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    European journal of clinical pharmacology 15 (1979), S. 175-180 
    ISSN: 1432-1041
    Keywords: clorazepate ; nordiazepam ; pregnancy ; pharmacokinetics ; intramuscular injection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single dose of clorazepate 20 mg was injected i.m. in 7 pregnant and 7 non-pregnant women. Blood samples were collected for one week, and urine was collected for 24 h after the dose. The concentrations of clorazepate and its metabolite nordiazepam were determined by electron capture gas liquid chromatography. There was no difference between the two groups on physical examinations. Clorazepate was rapidly absorbed and the peak concentration was reached within 2h. Mean pharmacokinetic parameters for clorazepate were absorption half life 0.77h in pregnant women and 0.56h in non-pregnant women; elimination half life 1.3h in pregnant women and 2.0h in non-pregnant women; volume of distribution: 0.43 l · kg−1 in the pregnant women and 0.33 l · kg−1 in non-pregnant women. Nordiazepam reached its peak concentration within 12h after dosing; its mean half life of elimination was 180h in pregnant women and 60h in non-pregnant women. Within 24h, 1.3% of the clorazepate was recovered in urine from pregnant women and 7% in urine from the non-pregnant women.
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  • 64
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    European journal of clinical pharmacology 15 (1979), S. 257-261 
    ISSN: 1432-1041
    Keywords: cimetidine ; H2-receptor antagonist ; aging ; single dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The blood level versus time curve for unchanged cimetidine after a 200 mg oral dose has been determined in 20 apparently healthy subjects, ranging from 22 to 84 years of age. A significant relationship between the area under the curve (AUC) and age was found (r=0.81; P〈0.001). The peak concentrations of cimetidine were significantly inversely related to body weight (r=−0.71; P〈0.001). The age-related increase in bioavailability of oral cimetidine, as measured by AUC, was probably due to decreased total clearance of the drug, which resulted from the opposed changes (by themselves not significant) of distribution volume towards a decrease and of half-life towards an increase with age. Reduction in the standard oral dose of cimetidine by one third to one half should be feasible in the elderly without loss of efficacy, and it may be advisable in order to obviate extreme individual responses that may occur in this population.
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  • 65
    ISSN: 1432-1041
    Keywords: chlorthalidone ; pharmacokinetics ; oral and i.v. doses ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven normal human volunteers each received a constant-rate infusion of chlorthalidone for 2 h, and the same (commonly 50 mg) single oral dose on separate occasions. The concentration of unchanged chlorthalidone was analyzed over a 100 to 220 h period in plasma, red blood cells, urine and faeces after both dosage forms. A three compartment model was required to describe the intravenous plasma concentrations in five of the subjects. A two compartment model sufficed to account for the decay of the oral plasma concentrations in all seven subjects. The mean plasma t1/2 after i.v. dosing was 36.5 h (±10.5 SD), and the mean plasma t1/2 after oral doses was 44.1 h (±9.6 SD). The mean red blood cell concentration t1/2 after i.v. doses was 46.4 h (±9.9 SD), and the mean red blood cell t1/2 after the oral doses was 52.7 h (±9.0 SD). The shorter i.v. half-live was not equally manifest in all subjects, being mainly apparent in three of them. In all cases the urinary excretion rate plots were parallel to the plasma concentration curves. As the faster decay after i.v. administration was not accompanied by increased renal clearance, the difference must have been due to non-renal mechanism. The mean total of 65.4 (±8.6 SD) % of the intravenous dose was excreted in urine over infinite time, whereas the mean total excretion after the oral dose was 43.8 (±8.5 SD) %. Faecal excretion ranged from 1.3–8.5% of dose in the i.v. study to 17.5–31.2% of dose in the oral study. The sum of the amounts present in urine plus faeces pointed strongly to an important metabolic route of elimination of chlorthalidone. Bioavailability estimates (F) from three sets of data were — a mean F of 0.61 from plasma concentrations, 0.67 from urinary excretion measurements and 0.72 from the erythrocyte concentrations. Simulations with a non-linear model indicated lesser validity of the estimate from erythrocyte concentrations. It was concluded that the average of plasma and urine data, F=0.64, yielded the best estimate of the oral availability of chlorthalidone 50 mg in man.
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  • 66
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    European journal of clinical pharmacology 15 (1979), S. 121-125 
    ISSN: 1432-1041
    Keywords: guanethidine ; chronic therapy ; urinary excretion ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma level and urinary excretion rate of guanethidine have been measured in 30 patients during oral maintenance therapy, and in 5 patients following discontinuation of therapy. A significant correlation was found between the daily average urinary excretion and the maintenance dose, although wide interindividual variation was noted among patients maintained on the same dose. A statistically significant correlation was also observed between the area under the plasma level curve during the dose interval and the oral maintenance dose. After discontinuation of chronic therapy, the half-life of 1.5 days of the initial phase of elimination was essentially in agreement with the half-life of almost 2 days determined in acute studies. In addition, a second phase of elimination with a half-life of 4 to 8 days was observed.
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  • 67
    ISSN: 1432-1041
    Keywords: clorazepate ; nordiazepam ; pregnancy ; placental transfer ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clorazepate 20mg was given i. m. to 49 mothers during the first stage of labour. The elimination of the drug was studied in 27 newborns produced by these mothers. The same dose was given to 13 women who underwent amniocentesis and to 7 women who were breast-feeding. “Total nordiazepam”, i.e. the sum of clorazepate and its metabolite nordiazepam, was determined by gas-liquid chromatography in maternal blood, umbilical cord blood (both arterial and venous), amniotic fluid and in milk. Clorazepate was found to cross the placental barrier slowly, but nordiazepam was transferred more rapidly. Nordiazepam was found in the milk and in the blood of neonates after breast-feeding had started.
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  • 68
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    European journal of clinical pharmacology 16 (1979), S. 31-38 
    ISSN: 1432-1041
    Keywords: bezafibrate ; hyperlipoproteinemia ; bioavailability ; pharmacokinetics ; GC-MS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition kinetics of bezafibrate, a newly developed drug of great lipid-lowering potency, were investigated in normal male subjects. Five male volunteers received14C-labelled bezafibrate orally in solution, and a further 10 were given the same dose (300 mg) of un-labelled drug as tablets. The concentration of bezafibrate in serum and urine from the latter was determined by GC, and in the former total radioactivity in serum, urine and feces was followed for 48 h, and urinary excretion products were analysed by TLC and GC-MS. Rapid absorption from the gastrointestinal tract led to peak serum levels 30 min and 2 h after administration of solution and tablets, respectively. Since approximately 95% of the administered14C-bezafibrate was excreted in urine within 48 h, and almost all the remainder was detected in feces, absorption can be regarded as complete after administration in solution. The relative optimal bioavailability from the tablets was also complete, since in both cases approximately 50% of the administered dose was detected as unchanged bezafibrate in urine within 24 h by GC in the tablet study, and by TLC in the solution study. Of the decomposition products, more than 20% of the dose was present as glucuronides and the remainder consisted of several more polar compounds, one of which was identified as a hydroxyderivative of bezafibrate. Since the apparent halflife of bezafibrate in serum was 2.1 h, this new drug possesses favourable pharmacokinetic features: rapid and complete absorption, even from tablets, combined with a conveniently short half-life, and clearance which is half renal (56 ml/min) and half metabolic (43 ml/min), giving a total clearance of 99 ml/min.
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  • 69
    ISSN: 1432-1041
    Keywords: indobufen ; platelet aggregation ; single dose ; bioavailability ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six healthy volunteers received single iv and oral doses of 2-[p-(1-oxo-2-isoindolinyl)phenyl] butyric acid 100 mg (indobufen; K 3920), an inhibitor of platelet aggregation. Plasma levels and urinary excretion of the drug were determined by GLC. Collagen-induced platelet aggregation was assessed turbidimetrically at various intervals after administration. The plasma half-life of the drug was 7–8 h and more than 70% of the administered dose was recovered within 48 h in urine, as unchanged drug and as the glucuronide of indobufen. After oral administration of tablets of two different formulations, the drug was completely absorbed, but one formulation showed faster absorption. The maximal inhibitory effect on platelet aggregation was observed 1 to 4 h after iv administration, and it had decreased by 8 h. After tablets, peak effect and the time of the peak were similar, but activity was significantly prolonged, in accordance with the higher plasma levels found at 8 h. The data suggest that the effect of indobufen on platelets is reversible, and that for this drug platelets behave as a compartment that slowly equilibrates with plasma.
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  • 70
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    European journal of clinical pharmacology 15 (1979), S. 433-441 
    ISSN: 1432-1041
    Keywords: cyclobarbital ; barbiturates ; pharmacokinetics ; drug interaction ; volunteers ; patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disappearance of cyclobarbital from plasma has been followed in healthy volunteers and in neurological and psychiatric patients after oral administration of one tablet of Phanodorm®, containing cyclobarbital calcium 200 mg. Plasma levels were measured by a thin-layer chromatographic method with in situ densitometry. The average t1/2 in healthy female and male volunteers was 13.3 h, and with the assumption of complete availability a mean distribution coefficient of 0.69 l/kg−1 and a clearance of 40.4 ml/min−1 were calculated. Repeated experiments in seven volunteers revealed good reproducibility of all values. When the healthy volunteers were combined with a group of untreated epileptics, a dependence of t1/2 and of the apparent volume of distribution on age was found, while clearance did not change with increasing age (range 17–54 years). Long half-lives caused by low clearance values were observed in several individuals with moderate obesity. No consistent change in cyclobarbital kinetics followed acute exposure of volunteers to alcohol or on treatment of neurological patients with carbamazepine. Patients under treatment with perazine exhibited more or less normal kinetic values. In terms of drug interaction, cyclobarbital differs from phenazone in several respects, and so it may prove a useful additional substance for measurement of the rate of drug oxidation in humans.
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  • 71
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    European journal of clinical pharmacology 16 (1979), S. 1-6 
    ISSN: 1432-1041
    Keywords: lorcainide ; ventricular premature beats ; plasma levels ; pharmacokinetics ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma level and antiarrhythmic effect of lorcainide (R 15889) have been investigated in 15 patients with ventricular premature beats (VPB). Therapy was initiated with an intravenous dose of 1.9 mg/kg given over 10 min, followed by a constant infusion of 0.18 mg/kg/h for 24 h. In 8 patients the corresponding doses were increased to 2 mg/kg and 0.27 mg/kg/h. After the intravenous doses patients were treated orally with 100 mg tid for 6–7 days. The two dosage regimens were selected so as to achieve theoretical steady-state plasma levels (css) of 200 and 300 ng/ml, respectively. The combined intravenous treatment approached (181 ± 6.8 ng/ml and 273±28.5 ng/ml, respectively) the desired css within 2 to 4 h. During the oral administration, the minimal plasma concentrations following the lower intravenous dose (184±18 ng/ml) were significantly (p=0.0001) lower than after the higher intravenous dose (264±20.5 ng/ml). The dealkylated metabolite of lorcainide was not detectable after the intravenous doses, but it accumulated during oral treatment, when its concentration exceeded that of the parent compound. In 5 of the 7 patients receiving the lower dose VPB were effectively reduced. However, in only 4 of the 8 patients on the higher dosage schedule could a significant antiarrhythmic effect be demonstrated. In addition, side effects were observed in 6 of the subjects.
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  • 72
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    European journal of clinical pharmacology 16 (1979), S. 23-29 
    ISSN: 1432-1041
    Keywords: valproate ; epilepsy ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In four refractory epileptic patients, peak plasma levels of sodium valproate occurred within 1.5 to 3 h after a single oral dose of valproate and the decline in plasma levels followed a monoexponential course with a t1/2 of 11.4 ± 0.1 h. The mean value for apparent volume of distribution was 0.176 ± 0.013 l/kg and for total plasma clearance 0.0106 ± 0.0009 l/h/kg. Steady state plasma levels were predicted using the method of superposition utilizing pharmacokinetic parameters determined following a single dose of valproate and were 78–123% of the predicted values for two patients receiving valproate alone, and 37–64% of the predicted values for the two patients receiving carbamazepine in addition to valproate. In a further group of 20 patients the mean daily doses of valproate for 8 patients receiving valproate alone (25.4 ± 4.9 mg/kg) was significantly less than those for the 12 patients receiving concomitant anticonvulsant therapy (41.6 ± 12.3 mg/kg) (p〈0.005). In addition, the steady state predose plasma levels of valproate were significantly higher in the valproate alone patients (90.3 ± 8.7 µg/ml) compared to the patients receiving additional anticonvulsants (75.3 ± 13.8 µg/ml) (p〈0.01). The higher dose requirements of valproate and lower predose and steady state plasma levels for those patients on multiple anticonvulsants indicate an interaction between valproate and other anticonvulsants.
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  • 73
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    European journal of clinical pharmacology 16 (1979), S. 45-48 
    ISSN: 1432-1041
    Keywords: quinidine ; slow release formulation ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of quinidine in two sustained release preparations A and B has been compared in three females and three males with i.v. administration of quinidine. The initial rate of oral absorption did not differ between the two drug preparations; the peak concentration was observed after 4 h both for A and B, but was significantly higher after B. A slower decrease in plasma concentration was observed after preparation A than B. Absolute bioavailability did not differ significantly between A (median value 78.4%) and B (median 87.1%). Drug absorption in vivo was in good agreement with the results of in vitro dissolution tests on both preparations. The slower decrease in plasma concentration found for the new sustained release form of quinidine should be of clinical advantage.
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  • 74
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    European journal of clinical pharmacology 16 (1979), S. 49-52 
    ISSN: 1432-1041
    Keywords: cephacetrile ; haemodialysis ; pharmacokinetics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cephacetrile were studied after its administration as a single i.v. bolus injection of 15 mg/kg body weight to 11 patients with terminal renal inpairment undergoing haemodialysis for 6 h. A two-compartment kinetic model was used to describe the biphasic decrease in plasma concentration. The quantities of antibiotic in the central and peripheral compartments, and the amounts eliminated, were calculated for different times. During haemodialysis sessions, the average pharmacokinetic parameters of cephacetrile determined at the dialyser input were: α=5.03 h−1,β=0.458 h−1, K12=2.337 h−1, K21=1.996 h−1 K13=1.154 h−1, Vc=5.508 l, Vp=6.448 l, Vdss=11.956 l. As a function of the pharmacokinetic parameters of cephacetrile, a regimen of multiple doses was established for patients with terminal renal impairment, which will guarantee safe and effective concentrations of the antibiotic.
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  • 75
    ISSN: 1432-1041
    Keywords: methadone ; mass fragmentography ; pulse labeling ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A technique is presented for study of steady state kinetics of methadone using pulse labeling with deuterated methadone (d3) and mass fragmentography to measure both unlabeled and labeled methadone in blood. Seven subjects maintained on methadone for at least 10 months were admitted to a closed metabolic ward. The daily dose of unlabeled methadone (d0) was substituted by one dose of methadone-d3 and plasma levels of methadone-d0 and methadone-d3 were followed for 48 h using a precise (SD±5%) and sensitive (30 pmol/ml) mass fragmentographic technique. Plasma half-lives (t1/2) for both methadone-d0 and metadone-d3 were calculated from samples obtained 8–24 h following the dose of methadone-d3. The t1/2 of oral methadone-d3 was shorter (22±2 h) than that of methadone-d0 (52±20 h). The same pattern was observed after intravenous administration. The results indicate multiple pools of methadone in the body.
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  • 76
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    European journal of clinical pharmacology 16 (1979), S. 177-181 
    ISSN: 1432-1041
    Keywords: prazosin ; alpha receptor blockade ; blood pressure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and effects of prazosin have been studied after intravenous and oral dosing (1 mg) to 6 normal male volunteers. The mean terminal (β) half-life was 2.9 h after intravenous and oral routes. Oral bioavailability was 56.9%. The effects of prazosin on blood pressure were more pronounced after intravenous than oral administration, and the hypotensive effect greater on erect blood pressure. There was a significant correlation (P〈0.02) between the fall in blood pressure and the plasma drug concentration after intravenous prazosin.
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  • 77
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    European journal of clinical pharmacology 16 (1979), S. 189-194 
    ISSN: 1432-1041
    Keywords: sparteine ; pharmacogenetic defect ; defective metabolism ; pharmacokinetics ; renal excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sparteine is metabolized by N1-oxidation, which in some subjects is defective. The defect has a pronounced effect on the kinetics of the drug. In non-metabolisers elimination of sparteine proceeds entirely via renal excretion by a capacity-limited process, 99,9% of the dose being excreted as unchanged drug. In metabolisers the drug is mainly eliminated by metabolic degradation. Pronounced differences in β-phase half-life and total plasma clearance were observed between metabolisers (156 min; 535 ml · min−1) and nonmetabolisers (409 min; 180 ml · min−1).
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  • 78
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    European journal of clinical pharmacology 16 (1979), S. 195-202 
    ISSN: 1432-1041
    Keywords: metformin ; biguanides ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of14C-metformin have been studied in five healthy subjects after oral and intravenous administration. The intravenous dose was distributed to a small central compartment of 9.9±1.61 ( $$\bar X$$ ±SE), from which its elimination could be described using three-compartment open model. The elimination half-life from plasma was 1.7±0.1 h. Urinary excretion data revealed a quantitatively minor terminal elimination phase with a half-life of 8.9±0.7 h. After the intravenous dose, metformin was completely excreted unchanged in urine with a renal clearance of 454±47 ml/min. Metformin was not bound to plasma proteins. The concentration of metformin in saliva was considerably lower than in plasma and declined more slowly. The bioavailability of metformin tablets averaged 50–60%. The rate of absorption was slower than that of elimination, which resulted in a plasma concentration profile of “flip-flop” type for oral metformin.
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  • 79
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    European journal of clinical pharmacology 16 (1979), S. 327-330 
    ISSN: 1432-1041
    Keywords: atenolol ; food intake ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the bioavailability of the beta-adrenoceptor blocker atenolol was assessed by measurement of its single-dose kinetics in ten healthy volunteers, who took 100 mg both in the fasting state and together with a standardized breakfast. Food intake significantly shortened the time to reach peak concentration (2.7 h vs 1.5 h), but caused a significant reduction in AUC values, the mean decrease being 20%. The elimination half-life was unaffected. Atenolol, which is relatively hydrophilic, is incompletely absorbed in the fasting state, and escapes first-pass metabolism. The present findings indicate that food intake causes further impairment of its absorption, even though the absorption rate may initially be enhanced. This contrasts with previous observations on the more lipophilic beta-adrenoceptor blockers propranolol and metoprolol.
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  • 80
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    European journal of clinical pharmacology 16 (1979), S. 331-334 
    ISSN: 1432-1041
    Keywords: netilmicin ; radioenzymatic assay ; drug accumulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a single dose of netilmicin (NM) was studied in 6 healthy volunteers. Elimination of the drug was followed in serum and urine for 24 h and 72 h, respectively. NM concentrations were measured with a modified radioenzymatic assay. A three compartment open model was employed to calculate the pharmacokinetic parameters. Following the rapid initial distribution, biphasic elimination with half lives of 1.99 h (t1/2β) and 36.89 h (t1/2γ) was demonstrated. Measurable amounts of NM were excreted in the urine for up to 72 h. The volume of distribution at steady-state (Vdss) of 0.68 l/kg was 3 to 4 times larger than previously reported for this antibiotic. NM plasma clearance was 91 ml/min and the renal clearance was 67 ml/min. The data indicate that on repetitive dosing the amount of drug in the body would be considerably underestimated if the prolonged terminal elimination phase were not taken into account. During prolonged treatment, accumulation of NM in renal and other tissues is likely to occur, as has been described for other aminoglycosides. The possible consequences of this pharmacokinetic behaviour are discussed.
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  • 81
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    European journal of clinical pharmacology 16 (1979), S. 335-340 
    ISSN: 1432-1041
    Keywords: cimetidine ; enterohepatic circulation ; irregular absorption ; bioavailability ; pharmacokinetics ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability and pharmacokinetics of cimetidine have been studied in healthy volunteers after administration of single intravenous (100 mg) and oral doses (100, 400 and 800 mg). After i.v. administration, the kinetics of cimetidine could be described by a linear, two compartment open model. Substantial variation in half-life was observed between subjects, with a mean value of 2.1 h (range 0.9–4.7). Cimetidine had a low hepatic extraction ratio and a high total plasma clearance, due to extensive urinary excretion of unchanged drug. After oral administration, the plasma concentration vs time curves in most subjects exhibited two marked peaks, an observation that seemed to be constant within individuals and was independent of dose. Bioavailability, estimated as the area under the plasma concentration vs time curves (AUC), after oral doses as compared to the intravenous dose, in most cases exceeded 100%. There was no correlation between bioavailability estimated as AUC and as urinary excretion of unchanged drug. These observations may indicate an enterohepatic circulatory mechanism, predominantly after oral administration. Both unchanged drug and its sulphoxide metabolite appear to be excreted in bile. The latter was shown in vitro to be reduced to cimetidine by fecal bacteria.
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  • 82
    ISSN: 1432-1041
    Keywords: prenalterol ; metoprolol ; haemodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of the selectiveβ 1-adrenoceptor agonist prenalterol were studied in healthy subjects before and after therapeutic doses of the selectiveβ 1-adrenoceptor blocker metoprolol. Plasma levels of the drugs were also determined in order to calculate certain pharmacokinetic variables. Intravenous infusion of prenalterol 0.13, 0.25 and 0.50 mg induced a dose-dependent decrease in total electromechanical systole (QA2) and pre-ejection period (PEP). The effect on left ventricular ejection time (LVET) was not significant. Increases in systolic blood pressure and heart rate were dose-dependent. Diastolic blood pressure did not change significantly. When metoprolol had been administered in a cumulative dose of 150 mg (mean maximal plasma level, 284 nmol/1) prenalterol had to be administered in doses that were twelve times higher than before theβ-blocker in order to induce the same haemodynamic effects. Prenalterol was rapidly distributed with an average half life of 8 min. This indicates that distribution equilibrium will be achieved within 30 min after intravenous administration. The overall elimination rate in the post-distributive phase corresponded to an average half life of 2.0 h.
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  • 83
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    European journal of clinical pharmacology 15 (1979), S. 269-274 
    ISSN: 1432-1041
    Keywords: phenytoin ; food-intake ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the absorption of phenytoin was examined in eight healthy volunteers, by study of single-dose kinetics following ingestion of phenytoin 300 mg either with a standardized breakfast or on an empty stomach. Blood samples were collected at regular intervals from 0 to 48 h, and serum concentrations of unmetabolized phenytoin were determined by gas chromatography. Serum concentrations of the major metabolite of phenytoin, 4-hydroxyphenytoin, were measured by mass fragmentography. Concurrent intake of food and phenytoin appeared to accelerate absorption of the drug from the formulation used, and the peak concentrations were significantly higher (mean increase 40%) in the postprandial than in the preprandial state. As reflected by the AUC (area under the curve), the amount of drug absorbed was increased during postprandial conditions, although the difference only reached borderline significance. It is suggested that phenytoin should always be taken in a defined relation to meals.
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  • 84
    ISSN: 1432-1041
    Keywords: myasthenia gravis ; neostigmine ; gas chromatography-mass spectrometry ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To permit rational evaluation of the empirical pharmacotherapy of myasthenia with cholinesterase inhibitors, a sensitive and selective method for the determination of neostigmine has been developed. Analysis is based on ion-pair extraction of neostigmine into methylene chloride and determination by gas chromatography-mass spectrometry (chemical ionization). As neostigmine was found to be metabolized in plasma in vitro, deuterated (d6) neostigmine was immediately added to the plasma sample as the internal standard. The limit of quantitation of the method was about 1 ng/ml (∼ 3nmol/l). The kinetics following i. v. administration were studied in four patients, who received neostigmine 2.5–3.0 mg iv to antagonize pancurone administered during anaesthesia. Elimination was rapid with a half-life t1/2 (β-slope) of 0.89±0.05 h (mean ± SE). The volume of distribution was 1.08±0.11 l/kg and plasma clearance was 0.84±0.04 l/kg/h. In three fasting myasthenic patients plasma concentrations of neostigmine were followed for 5 h after a single oral dose of 30 mg. Considerable interindividual differences in absorption were expressed in the peak concentrations, which occurred 1–2 h following drug ingestion. The bioavailability of neostigmine was estimated to be 1–2% of the ingested dose. Neostigmine concentration in plasma was found to differ considerably (up to forty-fold) between myasthenic patients on their ordinary dose-schedules of cholinesterase inhibitors.
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  • 85
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    European journal of clinical pharmacology 16 (1979), S. 101-105 
    ISSN: 1432-1041
    Keywords: dihydroquinidine ; congestive heart failure ; intravenous administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of dihydroquinidine were studied in 8 patients with congestive heart failure following a 22 min intravenous infusion of a quinidine preparation that contained 5.9% dihydroquinidine as an impurity. Using a thin layer chromatography-fluorometric assay procedure for dihydroquinidine, the post-infusion plasma dihydroquinidine concentrations declined biexponentially. The half-life of the fast and slow dispositional processes was 4.42±1.81 min and 6.52±2.40 h, respectively. The central compartment volume for dihydroquinidine in these patients was 0.44±0.11 l/kg with an overall apparent volume of distribution of 1.14±0.38 l/kg. The computed values of total body plasma clearance of dihydroquinidine ranged from 1.29 to 2.69 ml/min/kg with a mean value of 1.94±0.60 ml/min/kg. In these patients, approximately 16% of the administered dihydroquinidine dose was excreted intact into the urine in 48 h. The estimated value of renal clearance was 0.314±0.129 ml/min/kg. When compared to control cardiac patients, the data showed that the apparent volume of distribution for dihydroquinidine is smaller in patients with congestive heart failure and as a result of this diminished volume, the clearance rate of dihydroquinidine was slower. The net effect of these differences was the production of higher plasma concentrations of dihydroquinidine in the heart failure group.
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  • 86
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    European journal of clinical pharmacology 16 (1979), S. 119-124 
    ISSN: 1432-1041
    Keywords: cefoxitin ; renal impairment ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefoxitin have been determined after a single i.v. injection of 15 mg/kg body weight in 10 patients with normal renal function and 20 patients with varying degrees of renal impairment. The kinetics of the antibiotic followed an open two-compartment model. In patients with normal renal function the following pharmacokinetic parameters were found: $$\begin{gathered} \begin{array}{*{20}c} {\alpha = 8.66 h^{ - 1} } & {\beta = 1.21 h^{ - 1} } & {K_{12} = 3.47 h^{ - 1} } \\ \end{array} \hfill \\ \begin{array}{*{20}c} {K_{21} = 3.17 h^{ - 1} } & {K_{13} = 3.15 h^{ - 1} } & {V_c = 4.24 l.} \\ \end{array} \hfill \\ \begin{array}{*{20}c} {V_p = 4.87 l.} & { Vd_{ss} = 9.11 l.} \\ \end{array} \hfill \\ \end{gathered}$$ In the patients with renal impairment there was a significant decrease in $$\mathop \alpha \limits_, \mathop \beta \limits_, $$ K12, K21 and K13, and an increase in the apparent volume of distribution. The degree of plasma protein binding in patients with normal renal function was 73.6% and this was diminished in patients with renal impairment. A linear relationship between K13 of cefoxitin and creatinine clearance was demonstrated. The dosage regimen for patients with renal impairment should be adjusted by modifying the dosage interval whilst maintaining the amount administered.
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  • 87
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    European journal of clinical pharmacology 16 (1979), S. 133-139 
    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; pharmacokinetics ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six children, aged 2 months – 4 years, received theophylline 5–6 mg/kg intravenously. Its disposition could be described by a two-compartment open model, the mean serum half life (t1/2 β) was 3.75 h, i. e., shorter than in adults, but there was a considerable interindividual variation (1.8–7.0 h, in one patient 13.3 h). Thirteen children (2 months – 4 years) received theophylline suppositories in a dose of 3.8–5.0 mg/kg, and ten (6 months – 4 years) in a dose of 8.4–14.5 mg/kg. Absorption was slow (mean half-time 43 min), incomplete and variable (biological availability 8–100%, mean 80%). Only four of the patients given the higher dose and none given the lower dose reached a therapeutic serum concentration (10–20 µg/ml). Nine children (6 months – 4 years) received rectal enemas of theophylline 4.1–9.2 mg/kg. Absorbtion was rapid (mean half-time 5.5 min) and biological availability averaged 100%. Six patients reached a serum concentration within the therapeutic range. Using the mean values of the calculated pharmacokinetic parameters, rectal enemas providing a dose of theophylline of 6–8 mg/kg t. i. d. were computed to give serum concentrations between 8–20 µg/ml, without producing too high a level during the absorption phase.
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  • 88
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    European journal of clinical pharmacology 16 (1979), S. 279-285 
    ISSN: 1432-1041
    Keywords: salicylate ; synovitis ; osteoarthritis ; arthritis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Samples of blood and joint fluid from 30 patients who had taken buffered acetylsalicylic acid were examined for concentrations of total salicylates (TSA), acetylsalicylate (ASA) and salicylate (SA). The data were arranged in groups according to diagnosis of the joint disease. Analysis of the data did not show significant difference in the kinetics of TSA into blood. In groups the time to first appearance of 0.3 mg/l averaged 6.3 min for TSA; these values averaged 7.7 min for ASA and 10.9 min for SA. Close to maximum concentrations in blood averaged 18.9 mg/l for TSA, 3.3 mg/l for ASA, and 23.3 mg/l for SA. The time for first appearance of 0.3 mg/l of total salicylates in joint fluid ranged from 10 to 34 min with an average of 18.1 min; the values of ASA averaged 19.4 min and those of SA 21.9 min. The maximum concentration in joint fluid averaged 15.7 mg/l for TSA, 2.5 mg/l for ASA, and 14.5 mg/l for SA. Transport of salicylates from blood to joint fluid showed a pattern consistent with the type of joint disease. Support was found for the hypothesis that diffusion was the major factor in the movement of salicylates from blood to joint fluid.
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  • 89
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    European journal of clinical pharmacology 16 (1979), S. 411-416 
    ISSN: 1432-1041
    Keywords: doxapram ; intravenous infusion regimen ; pharmacokinetics ; data-point weighting ; healthy subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of intravenous doxapram in healthy individuals is consistent with a three-compartment open model. Doxapram was administered by bolus injection (1.5 mg · kg−1) and by intravenous infusion (6.5 mg · kg−1 for 2 h) to 5 subjects on separate occasions. There was no significant difference in mean terminal plasma half-lives (355 and 448 min) or in mean total body clearances (5.9 and 5.6 ml · min−1 · kg−1) following i. v. bolus injection or infusion respectively. In 3 subjects plasma doxapram concentrations during and after i. v. infusion agreed with those predicted from pharmacokinetic values obtained from the bolus injection study. Since mean steady-state concentrations (9.9 µg · ml−1) would be reached only after an extended interval (mean 15.2 h), a variable-rate infusion regimen was calculated to produce and maintain a concentration of 2 µg · ml−1 from 15–25 min onwards. A regimen in which the infusion rate is reduced step-wise is recommended to achieve early near-constant plasma doxapram concentrations.
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  • 90
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    European journal of clinical pharmacology 15 (1979), S. 105-108 
    ISSN: 1432-1041
    Keywords: muzolimine ; cardiac failure ; pharmacokinetics ; high ceiling diuretics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a new “high ceiling” diuretic, muzolimine (Bay g 2821), were investigated after a single oral dose of 40 mg in 7 patients with cardiac failure (Stages I–IV, New York Heart Association classification), and in 2 healthy subjects. Plasma concentrations peaked 1–3 h after administration and declined according to a two-compartment model. The α-phase (distribution phase) lasted until 12–16 h after administration and the mean t1/2α was 3.6 h (range 2.3–4.7) in patients, and 2.6 h (range 2.3–2.9) in healthy subjects. The mean t1/2β was 13.5 h (range 7.4–22.4) in the patients and 14.0 h (range 12.4–14.6) in healthy subjects. T1/2β was not correlated with the degree of heart failure or with the area beneath the plasma concentration curve, which varied three-fold. The renal clearance of muzolimine was in the range 2.7–15.3 ml · min−1 in 5 subjects in whom it was investigated. The pharmacokinetics of muzolimine appear not to be significantly altered by cardiac failure. The prolonged half-lives of the drug are probably responsible for the longer duration of diuretic action reported for muzolimine than for furosemide and bumetamide.
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  • 91
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    European journal of clinical pharmacology 15 (1979), S. 115-120 
    ISSN: 1432-1041
    Keywords: digoxin ; right heart failure ; absorption ; absolute bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of digoxin has been investigated in 8 patients before and after successful treatment of severe right heart failure.3H-digoxin 0.1 mg as a solution, and un-labelled digoxin 0.25 mg as a tablet, were given to fasted patients. Blood samples were taken at various time intervals up to 120 hours and urine was collected over the same period. The concentrations of labelled digoxin in plasma and urine were measured in a liquid scintillation counter, unlabelled digoxin was estimated by radioimmunoassay, and various pharmacokinetic parameters were calculated. There was no significant difference in the plasma concentration curves in severe right heart failure and after its successful treatment, nor did any of the calculated pharmacokinetic parameters change significantly. Therefore, inhibition of the absorption of digoxin appears unlikely. In an additional study to estimate absolute bioavailability two different groups of patients in severe right heart failure were given3H-digoxin 0.1 mg or unlabelled digoxin 0.25 mg i. v. and the pharmacokinetic parameters were compared with those from the previous study. The bioavailability of the3H-digoxin solution and of the digoxin tablet were in the same range as values previously published for healthy volunteers, and patients both with and without cardiac failure.
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  • 92
    ISSN: 1432-1041
    Keywords: metoprolol ; tachycardia ; healthy subjects ; conventional tablets ; slow release tablets ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels and associated reduction in exercise-induced tachycardia have been examined following the administration of single doses of metoprolol in conventional and slow-release tablets at different times to six healthy male subjects. The study was carried out in two parts. Initially, the tablets were given at 9 a. m. and the subjects were studied up to 14 h and then at 24 h. Subsequently, the same doses were given at 9 p. m. and the subjects were studied 12–24 h after drug administration (i. e. 9 a. m.–9 p. m. the next day). After giving the slow-release tablets the peak plasma levels were significantly lower but the drug persisted in the plasma at higher levels than after the conventional tablet. However, the beta-blocking effect was comparable from the two dosages. The results obtained for the period 12–24 h after the evening dose differed from the corresponding values after morning administration in that the plasma levels were higher and the betablocking effects more marked. Furthermore, the half-life values calculated from these data were significantly longer.
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  • 93
    ISSN: 1432-1041
    Keywords: triamterene ; pharmacokinetics ; diuretic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma and urinary levels of triamterene and two metabolites were measured using a specific method of analysis. Urinary excretion was completed after 48 h, which permitted a rough estimate of its half-life as longer than two hours. The areas under the curve were 672.5±160.3 and 1.311.3±399.1 µg/ml × h after the triameterene 150 mg and 300 mg p.o., respectively and correspondingly 4.2±1.4% and 3.7±0.6% of the dose were excreted as unchanged drug. The principal metabolite of triamterene found was the sulfate conjugate. The area under the curve of this metabolite amounted to 6.672±2.120 and 11.941±5.005 µg/ml × h after the of 150 mg and 300 mg triamterene doses, respectively. The urinary excretion of the metabolite varied between 25.0±4.0% and 17.5±3.5% of the dose after either dose. In healthy subjects an effect on sodium excretion was observed after a dose of 150 mg, whereas the potassium-retaining effect was observed only after the dose of 300 mg.
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  • 94
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    Journal of molecular medicine 57 (1979), S. 451-456 
    ISSN: 1432-1440
    Keywords: Menschliches Plasma ; DNS ; Elektronenmikroskopie ; Konzentration ; Human plasma ; DNA ; Electron microscopy ; Concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The DNA content in plasma of five healthy human individuals has been estimated. Structures ascertained by electron microscopy have been identified as double-stranded DNA. Depending on the isolation procedure applied the DNA molecules found may originate from free and/or complexed forms of DNA. The lengths range from less than 0.2 µm up to about 13 µm. DNA concentration is in the range of 3 to 11 ng/ml.
    Notes: Zusammenfassung Es wurde der DNS-Gehalt im Plasma fünf gesunder Testpersonen ermittelt. Elektronenmikroskopisch darstellbare Strukturen konnten als doppelsträngige DNS charakterisiert werden. Bedingt durch die Isolierungsmethode resultiert die gefundene DNS sowohl von freier und/oder DNS, die in komplexierter Form im Plasma vorliegt. Die Moleküllängen variieren von weniger als 0,2 µm bis zu ca. 13 µm. Die Konzentration liegt im Bereich von 3–11 ng DNS/ml.
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  • 95
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    Journal of cancer research and clinical oncology 95 (1979), S. 197-207 
    ISSN: 1432-1335
    Keywords: Telangiectatic osteosarcoma ; Histogenesis ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent investigations have shown that telangiectatic osteosarcoma has a poorer prognosis than other osteosarcomas. To elucidate the histogenesis of TOS two cases were investigated on the electron microscopic level. The results show that besides anaplastic, osteoblast-like, and fibroblast-like tumor cells angiosarcomatous components can be observed in this malignant bone tumor, which are characterized by endothelial cells with pinocytotic vesicles, tight intercellular junctions, fine fibrils, and so-called Weibel-Palade bodies in their cytoplasm. From these results, it is concluded that telangiectatic osteosarcoma is derived from multipotent mesenchymal cells with potential differentiation into various directions, such as osteoblast-like cells, endothelial cells, and fibroblast-like cells.
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  • 96
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    Journal of molecular medicine 57 (1979), S. 641-646 
    ISSN: 1432-1440
    Keywords: Mitochondria ; Membranes ; Cytochrome oxidase ; Fluorescence methods ; Electron microscopy ; Mitochondrien ; Membranen ; Cytochromoxidase ; Fluoreszenzmethoden ; Elektronenmikroskopie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Biologische Membranen sind im wesentlichen asymmetrische zwei-dimensionale Lösungen von Proteinen in einer bimolekularen Lipidschicht. Das allgemeine Aufbauprinzip und viele physikalische Eigenschaften biologischer Membranen lassen sich dadurch erklären, daß sowohl die Membranproteine als auch die Membranlipide hydrophile und hydrophobe Stellen besitzen. Die meisten biologischen Eigenschaften einer Membran werden durch die Membranproteine bestimmt, die richtungsgebundene Prozesse katalysieren können. Anhand des Membranproteins Cytochromoxidase wird gezeigt, wie die räumliche Anordnung von Membranproteinen durch chemische, fluorometrische und elektronenoptische Methoden studiert werden kann. In den meisten Fällen ist es allerdings heute noch nicht möglich, die Funktionen einer Membran aufgrund ihres molekularen Bauprinzips zu erklären.
    Notes: Summary Biological membranes are essentially asymmetric two-dimensional solutions of proteins in a bimolecular lipid layer. The overall structure and many physical properties of biological membranes can be explained by the fact that membrane proteins and membrane lipids contain hydrophilic as well as hydrophobic domains. Most biological properties of the membrane are determined by the membrane proteins which can catalyze directional processes. With the membrane protein cytochrome oxidase it will be demonstrated how the three-dimensional arrangement of membrane proteins can be studied by chemical, fluorometric, and electron optical methods. However, it is in most cases still impossible to explain the function of a membrane on the basis of its molecular architecture.
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  • 97
    ISSN: 1432-072X
    Keywords: Acetobacter suboxydans ; Bacteriophage A-1 ; Restriction ; Modification ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A bacteriophage ofAcetobacter suboxydans was isolated and found to correspond to type A phage according to Bradley's classification. The phage contains double stranded DNA. The length of the latency period and burst size could not be precisely determined because of apparent non-synchronous release of phage from single infective cycles. The host range was determined using 24 strains ofAcetobacter andGluconobacter species. Evidence for a probable occurence of host determined restriction and modification was obtained withAcetobacter suboxydans strain ATCC 621. The phage is designated A-1 and it is the first one to be reported forAcetobacter.
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  • 98
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    Archives of microbiology 123 (1979), S. 101-103 
    ISSN: 1432-072X
    Keywords: Bdellovibrio ; Cyanobacteria ; Marine sponges ; Symbiosis ; Infection ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A bdellovibrio-like bacterium was observed infecting unicellular symbiotic cyanobacteria in two coral reef sponges, Neofibularia irata and Jaspis stellifera. The infecting bacterium, which was located between the cell wall and the cytoplasmic membrane of the cyanobacteria, was similar in size and appearance to previously described bdellovibrios. This observation is believed to extend the host range of the bdellovibrios.
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  • 99
    ISSN: 1432-072X
    Keywords: Alcohol dehydrogenase ; Acetaldehyde dehydrogenase ; Clostridium kluyveri ; Electron microscopy ; Polygonal bodies ; Enzyme complex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The alcohol-acetaldehyde dehydrogenase complex of Clostridium kluyveri has been separated from contaminating β-hydroxybutyryl-CoA dehydrogenase by repeated precipitation with manganese and ammonium sulfate. Mn++ was required for maximum alcohol dehydrogenase activity. The molecular weight of the enzyme complex was 194,000 as determined by sucrose density gradient centrifugation. The enzyme complex has been shown to contain two types of subunits with molecular weights of 55,000±2,600 and 42,000±1,200, respectively which are arranged in “H”-shaped particles. In solutions with an ionic strength above 25 mM the enzyme complex precipitated in the form of lumps as has been shown with specific ferritin-conjugated antibodies. These lumps are assumed to be aggregated polygonal bodies present in C. kluyveri.
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  • 100
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    Archives of microbiology 121 (1979), S. 9-15 
    ISSN: 1432-072X
    Keywords: R-Bodies ; Kappa particles ; Free-living hydrogen bacteria ; Induction ; Electron microscopy ; Chemical composition ; Defective prophages ; Plasmids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract R-Bodies have been found in a recently isolated pseudomonas-like free-living hydrogen oxidizing bacterium. Their isolation, fine structure and chemical composition are described and compared with the R-bodies from the kappa particles (Caedobacter), obligate endosymbionts of Paramecium aurelia. The 2K 1 R-bodies exhibited essential characteristics of the kappa R-bodies; however, their size and some other structural aspects proved that they represent a new type of R-bodies. The presence of phage tail-like particles in cells induced with Mitomycin C is in favour of the hypothesis that the R-bodies might be coded by defective prophages, or by extrachromosomal elements.
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