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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 309 (1984), S. 107-114 
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 528 (1990), S. 163-171 
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Psychiatry Research 6 (1982), S. 223-234 
    ISSN: 0165-1781
    Keywords: Depression ; amitriptyline ; habituation ; nortriptyline ; plasma levels ; pulse rate ; skin resistance
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Amitriptyline ; Nortriptyline ; 10-Hydroxy-nortriptyline ; Plasma drug levels ; Plasma protein binding ; Drug response ; 3-Methoxy-4-hydroxyphenylglycol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 27 inpatients with primary affective disorder the urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured prior to a 4-week treatment with 150 mg amitriptyline (AT)/day. Ratings according to the Hamilton depression scale were performed before therapy and repeated after 2 and 4 weeks. Plasma levels of AT, nortriptyline (NT), and E-10-hydroxynortriptyline (OHNT) were assayed weekly, and binding of AT to plasma proteins was determined in one sample. Better therapeutic results were obtained at intermediate, as compared to low and high concentrations of AT or AT plus NT. Independent evaluation of AT and metabolite levels revealed that patients with AT of 50–125 mg/ml responded particularly well when NT did not exceed 95 ng/ml or when NT plus OHNT was below 150 ng/ml. Outside this ‘therapeutic window’ the outcome was markedly poorer. Interindividual variation of AT binding was much smaller than variation of total concentrations. Evaluation of free, instead of total levels did not help to clarify the relationship between clinical and pharmacokinetic variables. Plasma levels within the optimal ranges were found in more patients with high than with low MHPG excretion. The frec fraction of OHNT in plasma of healthy subjects was about 35%.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0533
    Keywords: Zidovudine ; Myopathy ; Nucleus ; Mitochondria ; AIDS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Zidovudine (formerly azidothymidine) is a potent inhibitor of the human immunodeficiency virus (HIV) reverse transcriptase and represents the first approved drug showing clinical efficacy in HIV-associated diseases. However, considerable toxicity causing macrocytic anemia, neutropenia, and myopathy has been reported, with severe mitochondrial alterations as a special feature of this myopathy. The mitochondrial changes are consistent with the fact that zidovudine acts as an inhibitor of the mitochondrial gamma-polymerase. Electron microscopically, we could confirm the presence of severely altered mitochondria in a 32-year-old male, who developed a necrotizing myopathy after daily administration of 1,000 mg zidovudine over a period of 15 months. In addition, there were even more severe nuclear changes that, for the most part, have not been documented electron microscopically in HIV-related myopathy either with or without zidovudine treatment, especially in non-necrotic and non-regenerating fibers. Since various in vitro studies have shown interference of zidovudine with nuclear DNA metabolism even in human cell lines, we assume that the nuclear changes that we observed are at least in part related to zidovudine treatment.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    International archives of occupational and environmental health 52 (1983), S. 329-339 
    ISSN: 1432-1246
    Keywords: Vigilance ; EEG ; Secondary motor task ; Occupational monotony ; Central nervous arousal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The SIFA is a paced secondary motor task, which is expected to monitor the train driver's ‘fitness for service’ on engines of the German Federal Railway. Disregard of the device leads to an emergency braking. As, in contrast to a true vigilance test, the SIFA cycles are characterized by paced and clearly supraliminal signals; we presumed that adequate operation of the device does not necessarily correspond to sustained attention of the driver. This study shows how the SIFA can be effectively tested under laboratory conditions. Our design allows the reduction of vigilance as evident from the EEG, and a controlled investigation of the possible connection between different modes of SIFA operation, physical load, and different levels of vigilance. Finally, some sample registrations show that phases of low vigilance do occur and do not prevent adequate operation of the device. It is suggested that SIFA-trained persons can operate the SIFA in phases of low vigilance because a specific central nervous arousal reaction enables them to raise their level of vigilance in synchronisation with the SIFA cycles to a degree that makes the successful performance of this task possible. A future report will provide a quantified analysis of the correlation between vigilance reduction and SIFA operation.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    International archives of occupational and environmental health 52 (1983), S. 341-352 
    ISSN: 1432-1246
    Keywords: EEG ; Job monitoring ; Occupational monotony ; Secondary task ; Vigilance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The SIFA is a paced secondary motor task used on modern rail engines. Adequate performance of this task is regarded as a guarantee for the train-driver's long-term attention. Observation as well as several preliminary studies made us doubt this claim. Our considerations, which led to the development of an experiment that allows SIFA-simulation and vigilance reduction under laboratory conditions, have been reported in an earlier part of this study. Our present investigation of the SIFA device under laboratory conditions of sensory deprivation, using a test-group of 12 experienced train drivers of the German Railway, proves that a paced secondary motor task like the SIFA can be operated in stages of reduced vigilance down to light sleep. Under conditions of impaired vigilance, the SIFA is correctly operated either in response to a warning signal or spontaneously within a physiological arousal reaction, which raises the driver's vigilance sufficiently to allow a goal-directed motor activity. Attendance of the SIFA interrupts, but does not prevent, phases of low vigilance. The inefficiency of the SIFA as a vigilance monitor was proved by means of EEG recordings which allowed us to establish a relationship between different stages of vigilance and the modes of SIFA-operation. Finally, it became evident that the number of warnings, respectively spontaneous operations of the device, does not correspond to the drivers' average stage of vigilance.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1041
    Keywords: cyclobarbital ; aminopyrine ; liver disease ; 14CO2 breath test ; barbiturate ; pharmacokinetics ; hepatic drug metabolism ; cirrhosis ; alcoholic liver disease ; viral hepatitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The exhalation of 14CO2 derived from an i.v. tracer dose of [dimethylamine-14C]aminopyrine has been investigated in normal controls and patients. They subsequently ingested 200 mg cyclobarbital calcium in the evening and the decline in the plasma drug level over the following 2 days was measured by thin-layer chromatography. The peak specific activity of exhaled 14CO2 occurred 0.5–2 h after 14C-aminopyrine injection in the absence of liver disease and in non-cirrhotic liver disorders. It was delayed in certain patients with cirrhosis. Compared to 8 medically healthy subjects, 10 patients with acute viral hepatitis, 8 with cirrhosis and 10 with fatty liver exhibited a significantly increased half-life of 14CO2 exhalation. Normal mean values were found in 12 patients with non-cirrhotic alcoholic liver disease and in 14 patients with non-hepatic diseases. The cyclobarbital (CB) half-life was prolonged and the clearance reduced in patients with viral hepatitis, cirrhosis, or alcoholic liver damage as compared to data from 17 control subjects. Due to a larger apparent volume of distribution, patients with fatty liver disease had an increased CB half-life, although its clearance was normal. A close negative correlation was detected between the clearance and the logarithm of the CB level measured 36 h after drug ingestion. The oral CB test evaluated from a single blood sample taken about 36 h after drug administration appears to be a useful indicator of human drug metabolising capacity. Discrimination between patients with and without disordered liver function was similar in the two drug elimination tests.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    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.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 21 (1982), S. 521-528 
    ISSN: 1432-1041
    Keywords: aminopyrine ; breath test ; metabolites ; plasma levels ; drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary [Dimethylamine-14C]-aminopyrine was given i.v. to 5 healthy volunteers and 5 medical patients in a dose of 1.67 mg/kg, containing 0.02 µCi/kg 14C. In 4 volunteers the experiment was repeated using oral administration of aminopyrine. Exhalation of 14CO2 was followed for 6–10 h and plasma levels of the drug and of its metabolites 4-methylamino-antipyrine, 4-amino-antipyrine, 4-acetylamino-antipyrine and 4-formylamino-antipyrine, were measured by thin-layer chromatography. The concentration-time profiles of the metabolites mostly failed to conform to a Bateman function. Areas under the curves from 1 to 6 h after dosing indicated distinct interindividual differences in metabolite patterns even in the absence of disturbed liver function, whereas the intraindividual data were closely reproducible. In most subjects, the area of 4-formylamino-antipyrine exceeded that of the acetyl analogue. The metabolite patterns did not exhibit a consistent relationship to the ratios between 14CO2 half-life in breath and aminopyrine half-life in plasma, which varied from 1.4 to 3.2.
    Type of Medium: Electronic Resource
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