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  • 1
    ISSN: 1432-1041
    Keywords: Oxcarbazepine ; 10,11-dihydro-10-hydroxy-carbamazepine ; renal impairment ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We have studied the effect of renal impairment on the pharmacokinetics of oxcarbazepine, its active monohydroxy-metabolite (which predominates in plasma), their glucuronides, and the inactive dihydroxy-metabolite after a single oral dose of oxcarbazepine (300 mg). Six subjects with normal renal function and 20 patients with various degrees of renal impairment participated. The mean areas under the plasma concentration-time curves of oxcarbazepine and its monohydroxy-metabolite were 2–2.5-times higher in patients with severe renal impairment (CLCR〈10 ml·min−1) than in healthy subjects. The apparent elimination half-life of the monohydroxy-metabolite [19 (SD 3) h] in these patients was about twice that in healthy subjects. The effect of renal impairment on the plasma concentrations of glucuronides was more marked. The renal clearances of the unconjugated monohydroxy-metabolite and its glucuronides (the main compounds recovered in urine) correlated well with creatinine clearance. The maximum target dose in patients with slight renal impairment (CLCR〉30 ml·min−1) should not be changed. In patients with moderate renal impairment (CLCR10–30 ml·min−1) it should be reduced by 50%. In patients with severe renal impairment (CLCR〈10 ml·min−1), the glucuronides of oxcarbazepine and its monohydroxy-metabolite are likely to accumulate during repeated administration, and dosage adjustment of oxcarbazepine in these patients could not be proposed from this single administration study.
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  • 2
    ISSN: 1432-0584
    Keywords: Fever ; Neutropenia ; Infection Pneumonia ; Antimicrobial therapy ; Antifungals Risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this prospective multicenter trial, treatment strategies for 1573 patients with neutropenia 〈1000/μl and fever ≥38.5° C after cytotoxic chemotherapy were compared. Patients with unexplained fever were randomized to a three-phase sequential study for different established drug regimens. If an infection could be defined microbiologically or clinically, treatment modifications were determined. In phase I, treatment for all patients consisted of acylaminopenicillin (PEN) plus aminoglycoside (AMG); or third-generation cephalosporin (CEPH) plus AMG; or PEN plus CEPH. In 800 patients with unexplained fever the response rates were: PEN/AMG (n=258): 74.4%, CEPH/AMG (n=252): 73.4%; PEN/CEPH (n=290): 70.0%. Total response rate was 72.5%. In phase II, patients not responding after 3 days received PEN/CEPH/vancomycin (n=70) or PEN/CEPH/AMG (n=74). The respective response rates were 52.9% and 55.4%, total 54.2%. If fever did not resolve, the patients received either PEN/CEPH (n=40) or imipenem/cilastatin (n=59) both in combination with amphotericin-B/5-flucytosin/ rifampin. The response rates were 62.5% and 79.7%, respectively (p=0.07), total 72.7%. No significant differences between the treatment modalities compared were found. Analyzing all three phases together, 91.3% of patients with unexplained fever were cured. The response rate was also analyzed according to patients with gram-positive bacteremia (n=183), response rate =82.5%; gram-negative organisms (n=145) 78.6%; fungemia (n=51) 43.1% (p〈0.001); lung infiltrates (n=269) 61.3% (p〈 0.001); clinically documented infections (n=198) 84.4%; and clinically and microbiologically documented infections (n=84) 82.1%. If infections were diagnosed after at least 5 febrile days, more lung infiltrates and fungal infections occurredp〈0.001). Leukocytes rising above 500/μ during the infection predicted better response rates (p〈0.001): in unexplained fever 97.8% vs 86.5% and lower death rates 1.5% vs 8.5%. In documented infections the response rates were then 89.9% vs 62.3% and the death rates 7.0% vs 20.5%. Therapy of neutropenic fever and infections must be adapted according to risk factors and should include early empiric antifungal therapy. The therapeutic and prophylactic use of hematopoietic growth factors to overcome neutropenia should be evaluated.
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  • 3
    ISSN: 1432-0584
    Keywords: Interferon-γ ; Hematopoiesis ; γ/δ ; γ/δ T cells ; Cutaneous T-cell lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recently we described a cutaneous T-cell lymphoma expressing the γ/δ T-cell receptor [5]. The patient suffering from this lymphoma showed low numbers of myeloid and T cells in peripheral blood, while B and NK cells were relatively increased. In vitro culture of the patient's bone marrow (BM) cells revealed a significant suppression of myeloid/monocyte colony formation (GM-CFU) compared with normal controls. This was not due to infiltration of the BM with lymphoma cells. We speculated that a soluble factor either secreted or induced by the lymphoma cells might be responsible for the marked suppression of hematopoiesis in this patient. From a skin biopsy with infiltrating γ/δ T-lymphoma cells we established T-cell clones bearing the γ/δ T-cell receptor and resembling the phenotype of the lymphoma cells. The supernatant (SN) of these γ/δ T-cell clones reduced the number of colonies in a CFU-GM assay (using normal control BM) in comparison to SN of α/β T-cell clones established from the same biopsy. This suppression was seen mainly on day 7 of culture and was not neutralized by the addition of placenta-CM. The main mediator of this suppression seems to be IFN-γ,since it was detectable in high amounts in the SN of these γ/δ T-cell tumor clones as well as in the serum of the patient. In addition, anti-IFN-γ antibodies can reverse the T-cell SN-mediated suppression of CFU-GM. We conclude that high serum levels of interferon-γ, which is secreted in high amounts from γ/δ T-cells grown from a biopsy of a cutaneous lymphoma, can suppress hematopoiesis.
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  • 4
    ISSN: 1617-4623
    Keywords: Transgenic plants ; Gene expression ; Copy number ; Promoter methylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary ThePetunia hybrida mutant RL01 is white flowering due to a genetic block in the anthocyanin pathway. The introduction of the maize Al cDNA under the control of the CaMV 35S RNA promoter leads to the production of pelargonidin derivatives, resulting in a brick red flower phenotype. Among the transgenic petunia plants the pigmentation of the petals exhibited different expression patterns which could be categorized into the ‘red’, the ‘variegated’, and the ‘white’ phenotype. This system proved to be especially suitable for the investigation of gene expression by simply looking at the pigmentation pattern of the petals. The uniformity of floral pelargonidin pigmentation is inversely correlated with the number of integrated Al copies. Furthermore, a correlation was found between the methylation status of the 35S RNA promoter and the instability of the floral pelargonidin coloration. The status of promoter methylation controlling the expression of the Al gene seems to be influenced by the copy number and the chromosomal position of the transferred gene.
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  • 5
    ISSN: 1617-4623
    Keywords: DNA methylation ; Transgenic plants ; Isochore organisation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We analysed de novo DNA methylation occurring in plants obtained from the transgenic petunia line R101-17. This line contains one copy of the maize A1 gene that leads to the production of brick-red pelargonidin pigment in the flowers. Due to its integration into an unmethylated genomic region the A1 transgene is hypomethylated and transcriptionally active. Several epigenetic variants of line 17 were selected that exhibit characteristic and somatically stable pigmentation patterns, displaying fully coloured, marbled or colourless flowers. Analysis of the DNA methylation patterns revealed that the decrease in pigmentation among the epigenetic variants was correlated with an increase in methylation, specifically of the transgene DNA. No change in methylation of the hypomethylated integration region could be detected. A similar increase in methylation, specifically in the transgene region, was also observed among progeny of R101-17del, a deletion derivative of R101-17 that no longer produces pelargonidin pigments due to a deletion in the A1 coding region. Again de novo methylation is specifically directed to the transgene, while the hypomethylated character of neighbouring regions is not affected. Possible mechanisms for transgene-specific methylation and its consequences for long-term use of transgenic material are discussed.
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  • 6
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Review of Scientific Instruments 61 (1990), S. 1779-1807 
    ISSN: 1089-7623
    Source: AIP Digital Archive
    Topics: Physics , Electrical Engineering, Measurement and Control Technology
    Notes: The subject of air pollution monitoring is reviewed. First, we discuss the main conventional techniques currently applied to the detection of gaseous air pollutants, as well as the state of the art of novel detection schemes. We distinguish between nonspectroscopic and spectroscopic methods. Spectroscopic techniques are of primary interest since they offer several advantages, e.g., the simultaneous monitoring of numerous substances. Photoacoustic (PA) spectroscopy represents a promising spectroscopic technique due to its intrinsically high sensitivity, the large dynamic range, and the comparatively simple experimental arrangement. Emphasis is put on detection selectivity which often may restrict the range of applications of the technique for pollution monitoring due to the lack of powerful, continuously tunable IR laser sources. The theoretical aspects of PA spectroscopy with respect to trace gas detection and multicomponent analysis are thus discussed in detail. Some characteristics of a portable PA system built by us are outlined in order to illustrate the usefulness of such systems.
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  • 7
    ISSN: 1573-0972
    Keywords: Acetic acid ; l-aribinose ; Candida blankii ; chemostat ; hemicellulose hydrolysate ; d-xylose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The growth characteristics ofCandida blankii as a function of temperature and pH in a simulated bagasse hemicellulose hydrolysate were determined in chemostat culture. The highest maximum specific growth rate of 0.44h−1 was reached at 38°C and at pH 5.5, with a sharp decrease in growth rate on either side of this temperature. Growth occurred at 46°C but not at 48°C. The protein and cell yields varied little below 40°C and the respective values were 0.22 and 0.5 g/g at 38°C. At the lower pH values, a severe linear decrease in cell and protein yields occurred, whereas a small increase in these yields at decreasing pH values was found when acetic acid was omitted from the medium. In the presence of acetic acid, a very sharp decrease in the growth rate at pH values below pH 4.5 was noted, despite the very low residual acetic acid concentrations, of less than 50 mg/l, in the culture.
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  • 8
    ISSN: 1573-0972
    Keywords: Ammonia ; astaxanthin ; carotenoids ; fructose ; glucose ; grape juice ; Phaffia rhodozyma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract During fermenter cultivation of Phaffia rhodozyma on a grape juice medium, the presence of glucose initially delayed fructose utilization, although fructose was consumed before glucose depletion. Total pigment and astaxanthin production were growth associated and reached maximum values of 15.9 μg/ml and 9.8 μg/ml, respectively, after depletion of the carbon source. The total cellular pigment and astaxanthin content increased during the stationary growth phase due to a decrease in biomass, reaching final values of 2120 μg/g and 1350 μg/g, respectively, without the volumetric concentration in the culture changing. The final cell yield was 0.33 g/g sugar utilized. High sugar concentrations in shake-flasks as well as O2 limitation decreased the astaxanthin content of the cells. Addition of yeast extract to a grape juice minimal medium markedly increased the maximum specific growth rate, total pigment and astaxanthin content of the cells. An excess of ammonia decreased the intracellular astaxanthin content, which reached a maximal value in cultures with no residual glucose or ammonia.
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  • 9
    ISSN: 1573-0972
    Keywords: Astaxanthin ; mannitol ; mutants ; NTG ; Phaffia rhodozyma ; succinate ; valine ; yeast
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Mutagenesis of Phaffia rhodozyma with NTG yielded a mutant with an astaxanthin content of 1688 μg (g dry biomass)-1, a cell yield coefficient of 0.47 on glucose and a maximum specific growth rate of 0.12 h-1. Re-mutation of the mutant decreased the cell yield and maximum specific growth rate but increased the astaxanthin content. The use of mannitol or succinate as carbon sources enhanced pigmentation, yielding astaxanthin contents of 1973 μg g-1 and 1926 μg g-1, respectively. The use of valine as sole nitrogen source also increased astaxanthin production, but severely decreased the maximum specific growth rate and cell yield coefficient. The optimum pH for growth of P. rhodozyma was between pH 4.5 and 5.5, whereas the astaxanthin content remained constant above pH 3.
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  • 10
    ISSN: 1435-926X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
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