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  • 1
    Language: German
    In: Facility Management : Messe und Kongress, Düsseldorf, 20. - 22. Mai 2003 ; [Tagungsband, Proceedings], pp. 217-226
    ISBN: 3-8007-2759-5
    Source: Deutsche Zentralbibliothek für Wirtschaftswissenschaften
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  • 2
    In: Anesthesia & Analgesia, 1998, Vol.86(1), pp.184-190
    Description: The context-sensitive half-time, the time required for a 50% decrease in drug concentration, has been proposed to predict the speed of recovery after infusions of IV anesthetics. We studied 40 patients to compare the clinical recovery characteristics of alfentanil and sufentanil. Patients were randomly allocated to receive either sufentanil/propofol (Group 1) or alfentanil/propofol (Group 2) total IV anesthesia by target-controlled infusions (TCI), assuming an equipotency ratio of 500:1. After discontinuation, times to tracheal extubation and to discharge from the postanesthesia care unit were measured, as were drug concentrations up to 24 h. The TCI bias was -17.1% for sufentanil and -16.9% for alfentanil. We found no difference in mean extubation times between the groups (48.7 min in Group 1 versus 46.4 min in Group 2), whereas discharge criteria were fulfilled significantly (P = 0.039) earlier after alfentanil (99.5 min) compared with sufentanil (131.3 min). The relative decrement values to tracheal extubation were 62.1% for sufentanil and 48.0% for alfentanil, compared with 75.7% and 65.0% for discharge, respectively. Based on a difference in propofol requirements, we suggest an actual sufentanil to alfentanil equipotency ratio of 1:300. We conclude that the decay in pharmacodynamic effect is not only the result of pharmacokinetics. Implications: Computer simulations may help to anticipate the clinical behavior of anesthetic drugs. In a clinical setting, we tested whether the recovery characteristics after IV anesthesia could be explained by a pharmacokinetic value, which describes the decline of drug concentrations in the body. This was not fully achieved.
    Keywords: Alfentanil -- Pharmacokinetics ; Anesthetics, Intravenous -- Pharmacokinetics ; Sufentanil -- Pharmacokinetics;
    ISSN: 0003-2999
    E-ISSN: 15267598
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  • 3
    In: Anesthesiology, 2001, Vol.94(1), pp.38-46
    Description: BACKGROUND: The value of exercise electrocardiography in the prediction of perioperative cardiac risk has yet to be defined. This study was performed to determine the predictive value of exercise electrocardiography as compared with clinical parameters and resting electrocardiography. METHODS: A total of 204 patients at intermediate risk for cardiac complications prospectively underwent exercise electrocardiography before noncardiac surgery. Of these, 185 were included in the final evaluation. All patients underwent follow-up evaluation postoperatively by Holter monitoring for 2 days, daily 12-lead electrocardiogram, and creatine kinase, creatine kinase MB, and troponin-T measurements for 5 days. Cardiac events were defined as cardiac death, myocardial infarction, minor myocardial cell injury, unstable angina pectoris, congestive heart failure, and ventricular tachyarrhythmia. Potential risk factors for an adverse event were identified by univariate and multivariate logistic regression analysis. RESULTS: Perioperative cardiac events were observed in 16 patients. There were 6 cases of myocardial infarction and 10 cases of myocardial cell injury. The multivariate correlates of adverse cardiac events were definite coronary artery disease (odds ratio, 8.8; 95% confidence interval [CI], 1.1–73.1;P = 0.04), major surgery (odds ratio, 4.7; 95% CI, 1.3–16.3;P = 0.02), reduced left ventricular performance (odds ratio, 2.0; 95% CI, 1.1–3.8;P = 0.03), and ST-segment depression of 0.1 mV or more in the exercise electrocardiogram (odds ratio, 5.2; 95% CI, 1.5–18.5;P = 0.01). A combination of clinical variables and exercise electrocardiography improved preoperative risk stratification. CONCLUSIONS: This prospective study shows that a ST-segment depression of 0.1 mV or more in the exercise electrocardio-gram is an independent predictor of perioperative cardiac complications.
    Keywords: Electrocardiography ; Exercise Test ; Preoperative Care ; Risk Assessment;
    ISSN: 0003-3022
    E-ISSN: 15281175
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  • 4
    In: Synlett, 2009, Issue 7, pp.1059-1062
    Description: Substituted enamides were prepared by a three-component reaction of lithiated alkoxyallenes, nitriles, and carboxylic ­acids. Their subsequent condensation with ammonium salts provided alkoxy-substituted pyrimidine derivatives. This two-step method is highly flexible with respect to the substitution pattern at C-2 and C-6. The C-4 and C-5 positions can smoothly be functionalized employing either Pd-catalyzed couplings or oxidation methods.
    Keywords: Allenes ; Enamides ; Pyrimidines ; Ammonium Salts ; ­nonaflates ; Pd Catalysis
    ISSN: 0936-5214
    E-ISSN: 1437-2096
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  • 5
    Language: English
    In: Journal of Clinical Anesthesia, 1999, Vol.11(5), pp.391-396
    Description: Study Objectives: To examine the possible pharmacodynamic interaction of propofol and sufentanil with respect to the induction of loss of consciousness. Design: Prospective, randomized, double-blinded study. Setting: University hospital. Patients: 30 female, ASA physical status I and II patients undergoing elective gynecologic surgery. Interventions: Patients were allocated randomly to receive an individual combination of propofol (1, 2, 3, 4, 5, or 6 μg/ml) and sufentanil (0.1, 0.2, 0.3, 0.5, or 1.0 ng/ml) target blood concentrations using target-controlled infusions. Measurements and Main Results: Study endpoint was loss of consciousness, which was tested by response to verbal commands and classified as responder or nonresponder, as assessed by the anesthetist, who was blinded to the drugs’ target blood concentrations. Nonlinear association (interaction) of both drugs was accomplished with logistic regression analysis using the maximum likelihood method, based principally on the hypothesis of interaction: ln [p/(1 − p)] = β 0 + β 1 · C prop + β 2 · C suf + β 3 · C prop · C suf with a p -value 〈0.05 for coefficient estimates considered significant. In the logistic regression model, sufentanil and propofol showed no supra-additive interaction regarding loss of consciousness ( p = 0.5916). Conclusions: Our results give no evidence of additional hypnotic properties of sufentanil compared to the other fentanyl congeners, although logistic regression may be of limited value in modeling interaction of hypnotic-analgesic combinations.
    Keywords: Analgesics ; Opioid ; Sufentanil ; Anesthetics ; Intravenous ; Propofol ; Drug Interaction ; Target-Controlled Infusion
    ISSN: 0952-8180
    E-ISSN: 1873-4529
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  • 6
    In: Survey of Anesthesiology, 1999, Vol.43(1), pp.12-13
    ISSN: 0039-6206
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  • 7
    Language: English
    In: Cardiology, December 2001, Vol.96(2), pp.100-105
    Description: Noninvasive cardiokymography has been further developed to be able to record wall motion abnormalities during exercise. The study was designed to evaluate the diagnostic accuracy of stress cardiokymography and electrocardiography in the diagnosis of coronary artery disease. 223 patients were included in a prospective investigation using a newly developed computerized cardiokymography device. Sensitivity, specificity, and positive predictive value were 61, 69 and 90% for exercise cardiokymography, and 57, 74 and 91% for exercise electrocardiography, respectively. There was no statistically significant difference between cardiokymography and electrocardiography. The combination of electrocardiography and cardiokymography did not produce a significant improvement in diagnostic accuracy in comparison to exercise electrocardiography alone.
    Keywords: Noninvasive and Diagnostic Cardiology ; Cardiokymography ; Exercise Electrocardiography ; Exercise Stress Testing ; Coronary Artery Disease ; Medicine
    ISSN: 0008-6312
    E-ISSN: 1421-9751
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  • 8
    Language: English
    In: Regulatory Toxicology and Pharmacology, April 2018, Vol.94, pp.91-100
    Description: Biological drugs comprise a wide field of different modalities with respect to structure, pharmacokinetics and pharmacological function. Considerable non-clinical experience in the development of proteins (e.g. insulin) and antibodies has been accumulated over the past thirty years. In order to improve the efficacy and the safety of these biotherapeutics, Fc modifications (e.g. Fc silent antibody versions), combinations (antibody-drug conjugates, protein-nanoparticle combinations), and new constructs (darpins, fynomers) have been introduced. In the last decade, advanced therapy medicinal products (ATMPs) in research and development have become a considerable and strongly growing part of the biotherapeutic portfolio. ATMPs consisting of gene and cell therapy modalities or even combinations of them, further expand the level of complexity, which already exists in non-clinical development strategies for biological drugs and has thereby led to a further diversification of expertise in safety and PKPD assessment of biological drugs. It is the fundamental rationale of the BioSafe meetings, held yearly in the EU and in the US, to convene experts on a regular basis and foster knowledge exchange and mutual understanding in this fast growing area. In order to reflect at least partially the variety of the biotherapeutics field, the 2016 EU BioSafe meeting addressed the following topics in six sessions: (i) In vitro Meets to Leverage Biologics Development (ii) New developments and regulatory considerations in the cell and gene therapy field (iii) CMC Challenges with Biologics development (iv) Minipigs in non-clinical safety assessment (v) Opportunities of PKPD Assessment in Less Common Administration Routes In the breakout sessions the following questions were discussed: (i) Cynomolgus monkey as a reprotoxicology Species: Impact of Immunomodulators on Early Pregnancy Maintenance (ii) Safety Risk of Inflammation and Autoimmunity Induced by Immunomodulators (iii) Experience with non-GMP Material in Pivotal Non-clinical Safety Studies to Support First in Man (FiM) Trials (iv) Safety Assessment of Combination Products for Non-oncology
    Keywords: Biotherapeutics ; Gene and Cell Therapy ; Pharmacokinetics ; Non-Clinical Safety ; Immunogenicity ; Cross-Reactive Species ; Pharmacy, Therapeutics, & Pharmacology ; Public Health
    ISSN: 0273-2300
    E-ISSN: 1096-0295
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  • 9
    Language: English
    In: Chemical Engineering Science, April 1999, Vol.54(8), pp.1029-1043
    Description: In this contribution, the nonlinear dynamic behaviour of reactive distillation columns for the production of MTBE and TAME is studied. The focus is on steady-state multiplicity and a rigorous bifurcation analysis of pilot plant reactive distillation columns for both processes is presented. The different sources and physical causes for the existence of multiple steady-states in MTBE and TAME synthesis are discussed. Further, a rigorous experimental verification of steady-state multiplicity in a pilot plant reactive distillation column for the production of TAME is presented. Finally, some remarks on the implications of multiple steady-states on column operation are made.
    Keywords: Reactive Distillation ; Fuel Ethers (Mtbe and Tame) ; Nonlinear Dynamics ; Numerical Analysis ; Multiple Steady-States ; Experimental Verification ; Engineering
    ISSN: 0009-2509
    E-ISSN: 1873-4405
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  • 10
    Language: English
    In: Malaria Journal, 01 May 2004, Vol.3(1), p.11
    Description: Abstract Background The erythrocyte binding antigen-175 (EBA-175) on Plasmodium falciparum merozoites mediates sialic acid dependent binding to glycophorin A on host erythrocytes and, therefore, plays a crucial role in cell invasion. Dimorphic allele segments have been found in its encoding gene with a 342 bp segment present in FCR-3 strains (F-segment) and a 423 bp segment in CAMP strains (C-segment). Possible associations of the dimorphism with severe malaria have been analysed in a case-control study in northern Ghana. Methods Blood samples of 289 children with severe malaria and 289 matched parasitaemic but asymptomatic controls were screened for eba-175 F- and C-segments by nested polymerase chain reaction. Results In children with severe malaria, prevalences of F-, C- and mixed F-/C-segments were 70%, 19%, and 11%, respectively. The C-segment was found more frequently in severe malaria cases whereas mixed infections were more common in controls. Infection with strains harbouring the C-segment significantly increased the risk of fatal outcome. Conclusion The results show that the C-segment is associated with fatal outcome in children with severe malaria in northern Ghana, suggesting that it may contribute to the virulence of the parasite.
    Keywords: Public Health
    ISSN: 1475-2875
    E-ISSN: 1475-2875
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