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  • 1
    Keywords: CHAIN ; POLYMERASE ; BIOLOGY ; POLYMERASE-CHAIN-REACTION ; PCR
    Type of Publication: Book chapter
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2017); 20171024-20171027; Berlin; DOCWI11-20 /20171023/
    Publication Date: 2017-10-23
    Keywords: Planung ; Endoprothetik ; Hüfte ; Anatomie ; Kalibration ; ddc: 610
    Language: German
    Type: conferenceObject
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2017); 20171024-20171027; Berlin; DOCWI11-21 /20171023/
    Publication Date: 2017-10-23
    Keywords: Planung ; Endoprothetik ; Hüfte ; Anatomie ; Kalibration ; ddc: 610
    Language: German
    Type: conferenceObject
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  • 4
    Keywords: CANCER ; SURVIVAL ; TOXICITY ; DEATH ; RISK ; COMPLEX ; MUTATIONS ; ABNORMALITIES ; ACUTE PROMYELOCYTIC LEUKEMIA ; TOPOISOMERASE-II ; RECOMMENDATIONS ; CELL TRANSPLANTATION ; MYELODYSPLASTIC SYNDROMES ; MITOXANTRONE ; SECONDARY LEUKEMIAS
    Abstract: To study the characteristics and clinical impact of therapy-related acute myeloid leukemia (t-AML). 200 patients (7.0%) had t-AML and 2653 de novo AML (93%). Patients with t-AML were older (P 〈 .0001) and they had lower white blood counts (P = .003) compared with de novo AML patients; t-AML patients had abnormal cytogenetics more frequently, with over-representation of 11q23 translocations as well as adverse cytogenetics, including complex and monosomal karyotypes, and with underrepresentation of intermediate-risk karyotypes (P 〈 .0001); t-AML patients had NPM1 mutations (P 〈 .0001) and FLT3 internal tandem duplications (P = .0005) less frequently. Younger age at diagnosis of primary malignancy and treatment with intercalating agents as well as topoisomerase II inhibitors were associated with shorter latency periods to the occurrence of t-AML. In multivariable analyses, t-AML was an adverse prognostic factor for death in complete remission but not relapse in younger intensively treated patients (P 〈 .0001 and P = .39, respectively), relapse but not death in complete remission in older, less intensively treated patients (P = .02 and P = .22, respectively) and overall survival in younger intensively treated patients (P = .01). In more intensively treated younger adults, treatment-related toxicity had a major negative impact on outcome, possibly reflecting cumulative toxicity of cancer treatment.
    Type of Publication: Journal article published
    PubMed ID: 21127174
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  • 5
    Abstract: A promising approach to the treatment of multiple myeloma (MM) involves agents that target not only the myeloma cells directly, but also the tumor microenvironment which promotes tumor cell growth, angiogenesis, and MM bone disease. Here we investigate the orally available multikinase inhibitor, regorafenib (BAY 73-4506), for its therapeutic efficacy in MM. Regorafenib is a potent inhibitor of angiogenic (VEGFR 1-3, PDGFR-b) as well as oncogenic (c-KIT, RET, FGFR, Raf) kinases. We show that regorafenib induces apoptosis in all MM cell lines at below clinically achievable concentrations. Regorafenib overcomes the growth advantage conferred by a stroma cell MM and an endothelial cell MM, co-culture systems, and abrogates growth factor-stimulated MEK, ERK, and AKT phosphorylation at nanomolar to micromolar concentrations. Moreover, it inhibits endothelial cell growth and tubule formation, abrogates both VEGF secretion and VEGF-induced MM cell migration, inhibits osteoclastogenesis, and shows synergistic cytotoxicity with dexamethasone, the immunomodulatory drug pomalidomide, and the p110delta inhibitor idelalisib. Most importantly, regorafenib significantly delays tumor growth in a xenograft mouse model of human MM. These results provide the rationale for further clinical evaluation of regorafenib, alone and in combination, in the treatment of MM.
    Type of Publication: Journal article published
    PubMed ID: 29359239
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  • 6
    Keywords: THERAPY ; DIAGNOSIS ; TRIAL ; STEM-CELL TRANSPLANTATION ; CRITERIA ; RECOMMENDATIONS
    Abstract: To determine the prognostic impact of monosomal karyotype (MK) in acute myeloid leukemia (AML) in the context of the current World Health Organization (WHO) classification and to evaluate the outcome of MK+ patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of 1058 patients with abnormal cytogenetics, 319 (30%) were MK positive (MK+). MK+ patients were significantly older (p=0.0001), had lower white blood counts (p=0.0006) and lower percentages of bone marrow blasts (p=0.0004); MK was associated with the presence of -5/5q-, -7, 7q-, abnl(12p), abnl(17p), -18/18q-, -20/20q-, inv(3)/t(3;3), complex karyotype (CK), and myelodysplasia (MDS)-related cytogenetic abnormalities (p〈0.0001, each); NPM1 mutations (p〈0.0001), FLT3 internal tandem duplications (p〈0.0001) and tyrosine kinase domain mutations (p=0.02) were less frequent in MK+. Response to induction therapy and overall survival in MK+ patients were dismal with a complete remission rate of 32.5% and a 4-year survival of 9%. MK retained its prognostic impact in AML with CK, AML with MDS-related cytogenetic abnormalities, and in a revised definition (MK-R) excluding cases with recurrent genetic abnormalities according to WHO classification and those with derivative chromosomes not leading to true monosomies. In younger patients allogeneic HSCT from matched related and unrelated donors resulted in a limited improvement of overall survival. These trials are registered at www.clinicaltrials.gov as NCT00151255 and NCT00151242.
    Type of Publication: Journal article published
    PubMed ID: 22096250
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  • 7
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  3. Wissenschaftlicher Kongress der Deutschen Gesellschaft für Essstörungen; 20120223-20120225; Hannover; DOC12dgess018 /20120208/
    Publication Date: 2012-02-08
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 8
    ISSN: 1433-0563
    Keywords: Key words Renal transplantation • Living organ donation • Enlightenment of donor and recipient ; Schlüsselwörter Nierentransplantation • Lebendspende • Aufklärung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Auf Grund der weiter zunehmenden Diskrepanz zwischen der Anzahl der zur Transplantation zur Verfügung stehenden Organe und der Anzahl der Patienten auf der Warteliste wird die Lebendspende zukünftig einen festen Platz im Rahmen der Nierentransplantation auch in Deutschland einnehmen. Das nun vorliegende Transplantationsgesetz gibt hierzu Rechtssicherheit und verbietet zusätzlich alle Formen des Organhandels. Neben der Feststellung der medizinischen Eignung des potentiellen Lebendspenders und der psychologischen Eignung des Paares obliegt dem Transplantationsteam auch die Pflicht zur ausführlichen Aufklärung des Spenders und des Empfängers hinsichtlich der Risiken, Komplikationen und Langzeitfolgen des Eingriffes. Gerade hierbei kommt es oft zu Unsicherheiten bezüglich eventueller Haftungs- und Schadensersatzansprüche. In dieser Arbeit werden die Aufklärungsstrategie des Transplantationszentrums Jena und die gemeinsame Erklärung von Spender und Empfänger in Vorbereitung einer Lebendspende vorgestellt. Zusammenfassend wird eingeschätzt, daß eine Nierenlebendspende nach umfassender medizinischer und psychologischer Vorbereitung sowie nach ausführlicher Aufklärung des Spenders und des Empfängers vor dem rechtlichen Hintergrund des Deutschen Transplantationsgesetzes unproblematisch durchführbar ist.
    Notes: Summary It has been observed an increasing discrepancy between the supply and demand of cadaveric organs for transplantation for a few years, particularly in renal transplantation. For this living organ donation will occupy an lasting place also in Germany. The new regulation organ donatio and transplantation in Germany provides a legal protection and prohibits all forms of organ trading. First of all the transplant team have to take into consideration medical and psychological aspects of donor and recipient but a detailed enlightenment of the pair concerning risks, complications and long term outcome is important as well. In this paper is introduced the enlightenment procedure and the common declaration of donor and recipient of the transplant center Jena. The authors conclude, that living organ donation is not a problem after intensive preparation and enlightenment of donor and recipient with the new Transplant Law in the background.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Blutersatz: Hämoglobin ; bovin ; Chirurgie: Leberresektion ; Hämodilution: Hydroxyäthylstärke ; Hämodynamik: pulmonal ; systemisch ; Sauerstofftransport ; Key words Blood substitute: haemoglobin ; bovine ; Haemodilution: hydroxyethyl starch ; Haemodynamics: pulmonary ; systemic ; oxygen transport ; Surgery: liver resection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Haemoglobin solutions can be an alternative to allogeneic red-cell transfusions because they combine colloid osmotic with oxygen transport properties. Since severe toxic side effects have been overcome by ultrapurification, clinical interest has been focused on haemodynamics changes during application of haemoglobin preparations. The present clinical study examines changes of haemodynamic and oxygen transport parameters during and after haemodilution with ultrapurified polymerized bovine haemoglobin (HBOC-201) in comparison to hydroxyethyl starch (HES). Methods: After approval of the Ethics Committee, 12 patients (6 males and 6 females, mean age 59±10 years, ASA 1-2) undergoing elective liver resection were randomly allocated to receive either 3 ml·kg−1 6% HES 70000/0.5 (group 1) or 0.4 g· kg−1 HBOC-201 (group 2) within 30 min following autologous blood donation of 1 l and substitution with 2 l Ringer’s lactate. Measurements of blood gases, haemodynamics, and oxygen transport parameters were performed after induction of general anaesthesia, prior to and after blood donation, during and after infusion, at the beginning of surgery, and in the intensive care unit. Results: Demographic characteristics did not differ between groups. In contrast to the HES group, mean arterial pressure increased by 18% over baseline measurements in group 2. While pulmonary vascular resistance showed a trend to higher values in group 2, systemic vascular resistance increased to a maximum of 42% over baseline in group 2 and was twice as high as in the HES group. The cardiac index was lower in the HBOC-201 group than in the HES group. During and after HBOC-201 infusion, mixed-venous oxygen saturation and content and calculated oxygen delivery were lower in group 2 in comparison to group 1, while the oxygen extraction ratio was higher in group 2. Free haemoglobin reached a maximal concentration of 1.0±0.2 g·dl−1 30 min after the HBOC-201 infusion was started, but was not detectable in urine over time. The mean intravascular half-life of HBOC-201 was 8.5 h. Conclusions: Patients did not show any severe complications during and after infusion of HBOC-201. However, vasoconstrictive side effects resulted in increased systemic but not pulmonary resistance. Ongoing studies with higher doses of HBOC-201 applied in a larger number of patients will probably reveal potential clinical consequences of the demonstrated haemodynamic changes.
    Notes: Zusammenfassung Hämoglobinlösungen sind kolloidale Volumenersatzpräparate, die Sauerstoff transportieren und damit eine Alternative zur homologen Transfusion von Erythrozyten darstellen können. Ziel der vorliegenden klinischen Studie war es, ein polymerisiertes ultragereinigtes Rinderhämoglobin (HBOC-201) im Vergleich zu Hydroxyäthylstärke (HES) auf Veränderungen der Hämodynamik und der O2-Transportparameter während und nach Hämodilution zu untersuchen. Material und Methoden: Nach Zustimmung durch die Ethikkommission wurden 12 Patienten (6 m. u. 6 w., Alter 59±10 J., ASA I–II, die sich einer Leberteilresektion unterziehen mußten, randomisiert auf 2 Gruppen verteilt. In Gruppe 1 erhielten die Patienten im Anschluß an eine präoperative Eigenblutspende von 1 l eine Infusion von 3 ml·kg−1 6% HES 70000/0,5 über 30 min sowie 2 l Ringerlaktat. Patienten der Gruppe 2 erhielten 2 l Ringerlaktat und über 30 min 0,4 g·kg−1 HBOC-201. Blutgasanalysen, Hämodynamik und Parameter des O2-Transports wurden vor und nach Eigenblutspende, während und nach Infusion, bei Operationsbeginn und auf der Intensivstation gemessen. Ergebnisse: Der arterielle Mitteldruck stieg unter Infusion von HBOC-201 im Gegensatz zu HES um maximal 18% gegenüber der Ausgangsmessung an. Während der pulmonale Gefäßwiderstand in der HBOC-201-Gruppe einen Trend zu höheren Werten als in der HES-Gruppe zeigte, stieg der systemische Gefäßwiderstand unter Infusion von HBOC-201 im Vergleich zum Ausgangswert um maximal 42% und war doppelt so hoch wie in der HES-Gruppe. Der Cardiac-Index lag in der HBOC-201-Gruppe unter den Werten der HES-Gruppe. Gemischt-venöse O2-Konzentrationen und -Sättigung sowie das errechnete O2-Angebot waren während und nach HBOC-201 Applikation niedriger als in der HES-Gruppe, während die O2-Extraktion nach Infusion von HBOC-201 höher war als nach HES. Die maximale Plasmakonzentration von HBOC-201 betrug 1,0±0,2 g·dl−1, die intravasale Halbwertszeit im Mittel 8,5 h. Im Urin war kein freies Hämoglobin nachweisbar. Schlußfolgerung. Die Ergebnisse zeigen bei guter Verträglichkeit der HBOC-201-Lösung einen vasokonstriktorischen Nebeneffekt, der zu einer Steigerung insbesondere des systemischen Gefäßwiderstands führt.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Technik ; kontinuierliche Spinalanästhesie ; Mikrokatheter ; kombinierte Spinal- Epiduralanästhesie ; Effektivität ; Key words Technique ; Continuous spinal anaesthesia ; Microcatheter ; Combined spinal-epidural anaesthesia ; Efficacy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract In this prospective study we investigated the efficacy of microcatheter spinal anaesthesia in comparison with a combined spinal-epidural technique in trauma patients. Methods: After institutional approval 60 patients undergoing urgent lower-limb surgery randomly received either CSA (22 G Sprotte needle, 28 G nylon catheter) in group 1 or CSE (18 G Tuohy needle, 22 G epidural catheter and 25 G pencil-point needle) in group 2. An initial subarachnoid bolus of 2 ml of plain bupivacaine 0.5% was injected in both groups. Difficulties with the lumbar puncture or catheter insertion, the time required for performance of either technique and the onset of analgesia at T12 were documented. If analgesia did not reach T12 within 20 min, supplemental bupivacaine was injected either intrathecally or epidurally up to a maximum of 5 ml in the CSA group or 16 ml in the CSE group. Results: The number of lumbar punctures (CSA: n=1.8±1.5; CSE: n=2.6±1.8; P=0.05) and the incidence of technical problems (CSA: 13%, CSE: 47%; P=0.012) was higher in the CSE group. In contrast to CSA, performance of CSE was more time consuming (CSA: 8±3 min, CSE: 15±8 min; P=0.0003), and the total dose of local anaesthetics was higher in the CSE group (CSA: 3.2±1 ml, CSE: 9.7±5 ml; P〈0.0001). Conclusions: Because of the higher incidence of technical problems, more time was required for the performance of CSE. As a consequence, microcatheter CSA might be preferred over CSE in trauma patients.
    Notes: Zusammenfassung Ziel der prospektiv randomisierten Studie war der Vergleich von kontinuierlicher Spinalanästhesie mit Mikrokatheter (CSA) und kombinierter Spinal-Epiduralanästhesie im Hinblick auf die Effektivität der Methoden und die Inzidenz technischer Probleme bei Patienten in der Unfallchirurgie. Methodik: Sechzig traumatologische Patienten, die sich dringlichen Eingriffen an der unteren Extremität unterziehen mußten, erhielten entweder eine CSA (22 G Sprotte Nadel und 28 G Nylonkatheter) in Gruppe 1 oder eine CSE (18 G Tuohy-Nadel, 22 G Epiduralkatheter und 25 G Pencil-Point-Nadel) in Gruppe 2. In beiden Gruppen folgte eine initiale Bolusinjektion von 2 ml Bupivacain 0,5% isobar in den Subarachnoidalraum. Schwierigkeiten bei Punktion oder Katheterinsertion, die Zeit für die Durchführung des Anästhesieverfahrens und die Anschlagzeit der Analgesie bei Th 12 wurden dokumentiert. Bei unzureichender Analgesie (〈Th 12) wurde 20 min nach Bolusgabe zusätzlich Lokalanästhetikum entweder subarachnoidal (CSA: maximal 5 ml) oder epidural (CSE: maximal 16 ml) injiziert. Im Vergleich zur CSA waren bei der CSE die Punktionshäufigkeit (CSA: n=1,8±1,5; CSE: n=2,6±1,8; p=0,05) und die Inzidenz technischer Probleme (CSA: 13%, CSE: 47% p=0,012) höher, die für die Durchführung der Technik benötigte Zeit länger (CSA: 8±3 min, CSE: 15±8 min; p=0,0003) sowie der Gesamtbedarf an Lokalanästhetikum höher (CSA: 3,2±1 ml, CSE: 9,7±5 ml; p〈0,0001). Fazit: Aufgrund der schwierigeren Handhabung und des damit verbundenen höheren Zeitaufwands bei der Durchführung bietet die CSE zumindest bei unfallchirurgischen Patienten keine Vorteile gegenüber der CSA mit Mikrokatheter.
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