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  • 1
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    Single Use of Rasburicase (rasb) Leads to Insufficient Tumor Lysis Syndrome (TLS) Control in Adults: Outcome and Resource Utilization in a One Year Real-Life Observational Study (2008)
    American Society of Hematology
    Details
    Publication Date: 2008-11-16
    Description: TLS due to the rapid lysis of tumor cells following initiation of chemotherapy can lead to the release of intracellular components into the extracellular space. Among these hyperuricemia might exceed the excretory capacity of the kidneys and lead to renal failure. Rasb is a recombinant urate oxidase given during the first 3–5 days of chemotherapy to effectively lower uric acid serum levels. Limited data suggest that a single prechemotherapy dose of rasb might be sufficiently efficacious and this single dose regimen is widely used to reduce treatment costs. We analyzed the clinical and economical data of all adults who received rasb for prophylaxis or treatment of TLS at a university hospital during a one year period. The goal was to describe treatment patterns and outcome outside of clinical trials and to verify whether patients with TLS can be treated cost-effectively. 38 patients (pts) received rasb, however 1/3 of the pts were treated off-label for other reasons then TLS. 24 pts (median age 66 yrs, 21 male) received rasb for malignancy-associated hyperuricemia and were eligible for further clinical and economical evaluation. 2/3 of these pts were treated for hematological malignancies (acute leukemia 6pts, lymphoma 8 pts) and 8 pts for solid tumors. Apart from hydration (mean volume 2 l per day; all pts), furosemide (mean dose 80 mg/day; all pts) and urinary alkalinization with sodium bicarbonate (pH 〉 7; 7 pts), 20 patients received a single 7,5 mg dose of rasb and 4 pts received multi dose. In 14 pts a tumor lysis was observed. 6 pts died, three fatalities were directly associated with TLS. Mortality was higher among pts with single dose rasb vs. multi dose rasb (30% vs. 0 %) and higher among patients with urinary alkalinization (71% vs. 5%). No anaphylaxis, hemolysis or methemoglobinemia was observed in this cohort. The mean duration of hospitalisation was 23 days, the mean treatment costs were 16.200 €. The costs exceeded the revenues based on diagnosis related groups for Germany (G-DRG) in 18 pts and resulted in a 7% funding gap. 107.000 € were spent for drugs for these patients, 10% of these for rasb. We conclude from this observational study that TLS is a menacing disease, resulted in a 12,5 % mortality and should therefore be cautiously monitored and treated, single dose rasb was associated with a higher mortality rate then multi dose, urinary alkalinization cannot be recommended when rasb is used, TLS leads to a 7 % underfunding in the respective G-DRGs, for TLS pts. the usage of rasb elevates the total drug expenses by 10%.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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    PAPER CURRENT
  • 2
    Electronic Resource
    Electronic Resource
    Der fremdgesteuerte Stromrichtersynchronmotor (1963)
    Springer
    Electrical engineering 48 (1963), S. 167-189 
    Details
    ISSN: 1432-0487
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Zusammenfassung Der fremdgesteuerte Stromrichtersynchronmotor ist eine Drehstrommaschine der Synchronbauart, die über einen Gleichrichter und einen Wechselrichter, also über einen Gleichstromzwischenkreis, aus dem Drehstromnetz gespeist wird. Ein von der Netzfrequenz unabhängiger Frequenzgenerator sehr kleiner Leistung steuert den Wechselrichter. Damit ist die Drehzahl des robusten, kollektorlosen Synchronmotors starr an die Frequenz dieses Generators gebunden. Durch Ändern der Steuerfrequenz des Wechselrichters wird die Drehzahl des Synchronmotors stetig verstellt. Bei konstanter Steuerfrequenz ist die Drehzahl unabhängig von der Belastung und nur von der Konstanz des Frequenzgenerators abhängig. Ohne Zusatzbeeinflussung läßt sich der fremdgesteuerte Stromrichtersynchronmotor nicht stoßartig belasten. Bei zusätzlicher Beeinflussung der Gleichspannung im Gelichstromzwischenkreis durch die zeitliche Änderung der Drehzahl kann man jedoch eine optimale Stabilitätsgüte erzielen. Die Maschine verhält sich jetzt besser als ein normaler Synchronmotor, der an einem starren Netz arbeitet. Die bei Belastung auftretende Winkelabweichung des Läufers kann sogar noch durch eine Phasenverschiebung der Steuerspannung ausgeglichen werden. Mit äußerst geringem Steueraufwand lassen sich also mit dem fremdgesteuerten Stromrichtersynchronmotor Ergebnisse erzielen, die beim drehzahlgeregelten Gleichstrommotor eine Überlagerung von analoger und digitaler Drehzahlregelung notwendig machen würden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01574823
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  • 3
    Electronic Resource
    Electronic Resource
    Contribution to the certification of B, Cd, Mg, Pb, Rb, Sr, and U in a natural water sample for the International Measurement Evaluation Programme Round 9 (IMEP-9) using ID-ICP-MS (2000)
    Springer
    Accreditation and quality assurance 5 (2000), S. 272-279 
    Details
    ISSN: 1432-0517
    Keywords: Key words IMEP-9 ; ID-ICP-MS ; IDMS ; Uncertainty budget ; Certification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract  The present paper describes the contribution of the Institute for Reference Materials and Measurements to the certification of B, Cd, Mg, Pb, Rb, Sr, and U amount contents in a natural water sample, in round 9 of the International Measurement Evaluation Programme (IMEP-9). The analytical procedure to establish the reference values for B, Cd, Mg, Pb, Rb, Sr, and U amount contents was based on isotope dilution inductively coupled plasma-mass spectrometry used as a primary method of measurement. Applying this procedure reference values, traceable to the SI, were obtained for the natural water sample of IMEP-9. For each of the certified amount contents presented here a total uncertainty budget was calculated using the method of propagation of uncertainties according to ISO and EURACHEM guidelines. The measurement procedures, as well as the uncertainty calculations are described for all seven elements mentioned above. In order to keep the whole certification process transparent and so traceable, the preparations of various reagents and materials as well as the sample treatment and blending, the measurements themselves, and finally the data treatment are described in detail. Explanations focus on Pb as a representative example. The total uncertainties (relative) obtained were less than 2% for all investigated elements at amount contents in the pmol/kg up to the high μmol/kg range, corresponding to low μg/kg and mg/kg levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007690000145
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  • 4
    Electronic Resource
    Electronic Resource
    Producing SI-traceable reference values for Cd, Cr and Pb amount contents in polyethylene samples from the Polymer Elemental Reference Material (PERM) project using isotope dilution mass spectrometry (2000)
    Springer
    Accreditation and quality assurance 5 (2000), S. 314-324 
    Details
    ISSN: 1432-0517
    Keywords: Key words PERM ; ICP-MS ; PTI-MS ; IDMS ; Uncertainty budget ; Certification ; Polyethylene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract  The present paper describes the certification of the amount content of Cd, Cr and Pb in two different polyethylene materials within the third phase of the Polyethylene Elemental Reference Material (PERM) project. The analytical procedure to establish the reference values for Cd, Cr and Pb amount contents in these materials is based on isotope dilution mass spectrometry used as a primary method of measurement. Cd and Pb were measured with inductively coupled plasma-mass spectrometry and Cr with positive thermal ionization-mass spectrometry. The decomposition of the polymer matrix was carried out using a high pressure asher. Reference values for amount content, traceable to the SI-system, have been obtained for these three elements in both of the polyethylene samples of PERM. For each of the certified amount content values an uncertainty budget was calculated using the method of propagation of uncertainties according to ISO and EURACHEM guidelines. The measurement procedures, as well as the uncertainty calculations, are described for all three elements. In order to keep the whole certification process as transparent as possible, the preparations of various reagents and materials as well as the sample treatment and blending are described in detail. The mass spectrometry measurements and the data treatment are also explained carefully. The various sources of uncertainty present in the procedure are displayed in the uncertainty budgets. The obtained combined uncertainties for the amount content values were less than 2% relative (k=1) for all investigated elements. The amount contents were in the μmol/kg range, corresponding to mg/kg levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007690000146
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  • 5
    Electronic Resource
    Electronic Resource
    Nuclear forward scattering of synchrotron radiation by deoxymyoglobin (2000)
    Springer
    European biophysics journal 29 (2000), S. 146-152 
    Details
    ISSN: 1432-1017
    Keywords: Key words Myoglobin ; Protein dynamics ; Nuclear forward scattering ; Mössbauer effect ; Synchrotron radiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract Nuclear forward scattering of synchrotron radiation is used to determine the quadrupole splitting and the mean square displacement of the iron atom in deoxymyoglobin in the temperature range between 50 K and 243 K. Above 200 K an abnormally fast decay of the forward scattered intensity at short times after the synchrotron flash is observed, which is caused by protein-specific motions. The results strongly support the picture that protein dynamics seen at the position of the iron can be understood by harmonic motions in the low temperature regime while in the physiological regime diffusive motions in limited space are present. The shape of the resonance broadening function is investigated. An inhomogeneous broadening with a Lorentzian distribution indicating dipole interactions results in a better agreement with the experimental data than the common Gaussian distribution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002490050260
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  • 6
    Electronic Resource
    Electronic Resource
    From metmyoglobin to deoxy myoglobin: relaxations of an intermediate state (1998)
    Springer
    European biophysics journal 27 (1998), S. 113-125 
    Details
    ISSN: 1432-1017
    Keywords: Key words Myoglobin ; Protein dynamics ; Ru(2 ; 2′ ; bipyridine) ; Intermediate states ; Photochemical reduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract Metmyoglobin has been reduced at low temperature (below 100 K) using x-rays or by excitation of tris(2,2′,bipyridine)ruthenium(II) chloride with visible light. Upon reduction, an intermediate state is formed where the structure of the protein is very similar to that of metmyoglobin with the water molecule still bound to the heme iron, but the iron is II low spin. The nature of the intermediate state has been investigated with optical spectroscopy. The Qo and Qv bands of the intermediate state are split, suggesting that the protoporphyrin is distorted. The intermediate state undergoes a relaxation observed by a shifting of the Soret band at temperatures above 80 K. Above 140 K, the protein begins to relax to the deoxy conformation. The relaxation kinetics of the protein have been monitored optically as a function of time and temperature from minutes to several hours and from 150 K to 190 K. By measuring the entire visible spectrum, we are able to distinguish between electron transfer processes and the protein relaxation from the intermediate state to deoxy myoglobin. The relaxation has been measured in both horse myoglobin and sperm whale myoglobin with the relaxation occurring on faster time scales in horse myoglobin. Both the reduction kinetics and the relaxation show non-exponential behavior. The reduction kinetics can be fit well to a stretched exponential. The structural relaxation from the intermediate state to the deoxy conformation shows a more complex, dynamical behavior and the reaction is most likely affected by the relaxation of the protein within the intermediate state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002490050117
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  • 7
    Electronic Resource
    Electronic Resource
    A reduction of protein specific motions in co-ligated myoglobin embedded in a trehalose glass (1998)
    Springer
    European biophysics journal 27 (1998), S. 173-176 
    Details
    ISSN: 1432-1017
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002490050123
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  • 8
    Electronic Resource
    Electronic Resource
    Determination of the phonon spectrum of iron in myoglobin using inelastic X-ray scattering of synchrotron radiation (1997)
    Springer
    European biophysics journal 25 (1997), S. 221-224 
    Details
    ISSN: 1432-1017
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002490050034
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  • 9
    Electronic Resource
    Electronic Resource
    Homologous recombination in the fission yeast Schizosaccharomyces pombe: different requirements for the rhp51+, rhp54+ and rad22+ genes (1997)
    Springer
    Current genetics 31 (1997), S. 248-254 
    Details
    ISSN: 1432-0983
    Keywords: Key wordsrhp51+ ; rhp54+ ; rad22+ ; Double-strand break repair ; Homologous recombination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The Schizosaccharomyces pombe rhp51 + , rad22 + and rhp54 + genes are homologous to RAD51, RAD52 and RAD54 respectively, which are indispensable in the recombinational repair of double-strand breaks (DSBs) in Saccharomyces cerevisiae. The rhp51Δ and rhp54Δ strains are extremely sensitive to ionizing radiation; the rad22Δ mutant turned out to be much less sensitive. Homologous recombination in these mutants was studied by targeted integration at the leu1-32 locus. These experiments revealed that rhp51Δ and rhp54Δ are equally impaired in the integration of plasmid molecules (15-fold reduction), while integration in the rad22Δ mutant is only reduced by a factor of two. Blot-analysis demonstrated that the majority of the leu+ transformants of the wild-type and rad22Δ strains have integrated one or more copies of the vector. Gene conversion events were observed in less than 10% of the transformants. Interestingly, the relative contribution of gene conversion events is much higher in a rhp51Δ and a rhp54Δ background. Meiotic recombination is hardly affected in the rad22Δ mutant. The rhp51Δ and rhp54Δ strains also show minor deficiencies in this type of recombination. The viability of spores is 46% in the rad22Δ strain and 27% in the rhp54Δ strain, as compared with wild-type cells. However, in the rhp51Δ mutant the spore viability is only 1.7%, suggesting an essential role for Rhp51 in meiosis. The function of Rhp51 and Rhp54 in damage repair and recombination resembles the role of Rad51 and Rad54 in S. cerevisiae. Compared with Rad52 from S. cerevisiae, Rad22 has a much less prominent role in the recombinational repair pathway in S. pombe.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002940050202
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  • 10
    Electronic Resource
    Electronic Resource
    Mitochondrial copper metabolism in yeast: mutational analysis of Sco1p involved in the biogenesis of cytochrome c oxidase (1999)
    Springer
    Current genetics 35 (1999), S. 103-108 
    Details
    ISSN: 1432-0983
    Keywords: Key words Yeast Sco1p ; Copper ; Cytochrome c oxidase ; Mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Saccharomyces cerevisiae Sco1p is believed to be involved in the transfer of copper from the carrier Cox17p to the mitochondrial cytochrome c oxidase subunits 1 and 2. We here report on the results of a mutational analysis of Sco1p. The two cysteine residues of a potential metal-binding motif (CxxxC) are essential for protein function as shown by their substitution by alanines. Chimeras consisting of Sco1p and its homolog S. cerevisiae Sco2p restrict the specificity of Sco1p function to the N-terminal half of the protein. A candidate region for conferring specificity on Sco1p is a stretch of hydrophobic amino acids, which act as a membrane anchor. In line with this suggestion is the result that alterations of individual amino acids within this region impair Sco1p function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002940050438
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