Der Lehrer als Kulturträger und Kulturvermittler: Eduard Spranger

Eduard Spranger ist am 17.9.1963 gestorben. 1982 wäre er 100 Jahre alt geworden. Im Rahmen einer Vortragsreihe, welche die Paulus-Akademie in Zürich und die Höhere Pädagogische Lehranstalt des Kantons Aargau aus Anlass dieser Gedenktage durchführten, sprach Dr. Urs P. LATTMANN zum Thema „Lehrerbild und Lehrerbildung im Wandel - Eduard Sprangers Beitrag". Wie Urs P. LATTMANN u. a. ausführte, entwickelte Spranger in seiner Schrift "Gedanken über die Lehrerbildung" aus dem Jahr 1920 ein Konzept für die Volksschul-Lehrerbildung, das auch heute noch als wegweisend bezeichnet werden kann. Nach diesem Konzept sollten die künftigen Volksschullehrer im Anschluss an das Abitur während drei Jahren an einer eigenständigen Institution ausgebildet werden

International Protection of Human Rights

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Kombinierte dorsale und palmare Plattenosteosynthese bei distalen intraartikulären Radiusfrakturen

Zusammenfassung: Hintergrund: Behandlungsziel bei komplexen distalen intraartikulären Radiusfrakturen ist die anatomische Gelenkrekonstruktion. In seltenen Fällen kann dies nur mit einer kombinierten, dorsalen und palmaren Abstützung erreicht werden, trotz der zunehmenden Erfahrung mit winkelstabilen palmaren Implantaten. Diese retrospektive Qualitätskontrollstudie untersucht das funktionelle, radiologische und subjektive Outcome der mit dieser Technik operierten Patienten. Patienten und Methoden : An der Klinik für Unfallchirurgie des Universitätsspital Zürich wurden zwischen März 1999 und Januar 2003 von 360 Patienten mit instabiler distaler Radiusfraktur 30 Patienten mit komplexer C2-/C3-Fraktur über einen kombinierten dorsopalmaren Zugang mit einer 3,5-mm-T-Platte und dorsal mit zwei 1/4-Rohr-Platten behandelt und in die Studie eingeschlossen (9 Frauen, 21Männer, Mittelwert des Alters 52). Nachkontrolliert werden konnten 25 der 30 Patienten im Mittel 29 Monate nach Unfall. Ergebnisse: Die angestrebte anatomische Rekonstruktion gelang nicht bei allen Patienten: 56% zeigten leichte, 28% schwere Zeichen der Arthrose. Die Flexion erreichte 66%, die Extension 75% der gesunden Seite, Pronation und Supination sogar 98 bzw. 91%. Die Kraft beim Faustschluss betrug 75% der kontralateralen Seite. Zehn Patienten (40%) entwickelten im Verlauf ein komplexes regionales Schmerzsyndrom (CRPS). Die Rückkehr zur Arbeit war nach 120 Tagen möglich. Schlussfolgerung: Die dorsopalmare Plattenosteosynthese komplexer, distaler intraartikulärer Radiusfrakturen erlaubt eine Gelenkrekonstruktion mit gutem subjektivem, funktionellem und radiologischem Resultat, dies trotz des durch den beidseitigen Zugang verursachten zusätzlichen Weichteilschaden. Das hohe CRPS-Risiko, aber auch der lange Arbeitsausfall müssen bei der Patientenaufklärung berücksichtigt werde

Role of the amino terminal RHAU-specific motif in the recognition and resolution of guanine quadruplex-RNA by the DEAH-box RNA helicase RHAU

Under physiological conditions, guanine-rich sequences of DNA and RNA can adopt stable and atypical four-stranded helical structures called G-quadruplexes (G4). Such G4 structures have been shown to occur in vivo and to play a role in various processes such as transcription, translation and telomere maintenance. Owing to their high-thermodynamic stability, resolution of G4 structures in vivo requires specialized enzymes. RHAU is a human RNA helicase of the DEAH-box family that exhibits a unique ATP-dependent G4-resolvase activity with a high affinity and specificity for its substrate in vitro. How RHAU recognizes G4-RNAs has not yet been established. Here, we show that the amino-terminal region of RHAU is essential for RHAU to bind G4 structures and further identify within this region the evolutionary conserved RSM (RHAU-specific motif) domain as a major affinity and specificity determinant. G4-resolvase activity and strict RSM dependency are also observed with CG9323, the Drosophila orthologue of RHAU, in the amino terminal region of which the RSM is the only conserved motif. Thus, these results reveal a novel motif in RHAU protein that plays an important role in recognizing and resolving G4-RNA structures, properties unique to RHAU among many known RNA helicase

Analgesic effects of 5-alkyloxy-4-amino-2(5H)-furanones as cholecystokinin-2 antagonists

4-Amino-2(5H)-furanones were synthesized in high yields over two synthetic steps from readily available mucochloric acid. These 5-alkyloxy-4-amino-2(5H)-furanones were screened in a ([125]) I-CCK-8 radioligand receptor binding assay for CCK2 affinity and novel active ligands in the nanomolar range were identified. SAR was optimized leading to the cyclohexyl derivative 25 with an IC50 of 27 nM. Furanone 18 was obtained as a stable crystalline material with an IC50 of 85 nM, but had a higher CCK2 selectivity. It was subsequently tested in the isolated guinea pig ileum assay with sulfated CCK8 , and the CCK antagonizing properties of the ligand were confirmed. The CCK2 selective antagonist 18 was found to potentiate analgesia in the tail flick assay in mice, for the strong opiate morphine, the partial opiate agonist tramadol and the tricyclic antidepressant desimipramine

N‒substituted 5‒hydroxy‒pyrrol‒2‒ones based cholecystokinin‒2 antagonists as experimental anticancer agents for the treatment of lung cancer

Background: Cholecystokinin and gastrin are endocrine growths factors for certain tumours and CCK1 R and CCK2R receptors are ideal molecular targets for novel smart chemo‒ therapeutics with a beneficial overall profile due to their anxiolytic and antidepressant properties. Lung cancers are fuelled by gastrin and therefore, selective gastrin (CCK2 R) antagonists are ideal experimental drug candidates. Objective: Synthesis and evaluation of novel CCK antagonists, most preferred CCK2 / gastrin selective for the treatment of lung cancers. Methods: A fast and efficient synthesis of hydroxy‒pyrrolones in 2 steps from renewable biomass was performed. After initial radiolabelled receptor binding studies with hot CCK8, subsequent in vitro evaluation with isolated duodenum preparations confirmed CCK antagonism. Cell based studies using the MTT assay provided a candidate for in vivo xenograft models with nude mice. Rational drug design was supported by molecular modelling experiments. Results: Potent and selective CCK antagonists were prepared as stable crystalline materials in high yields. Gastrin antagonists were in vitro active on isolated tissue preparations and inhibited breast, colon and lung cancer cell lines in vitro with IC50 to 45nM for the privileged hydroxyl‒pyrrolone lead structure in the MTT assay for human cancer cell lines. PNB‒101, a fluorinated 5‒hydroxy‒5‒aryl‒pyrrol‒2‒one, gave up to 80% inhibition of tumour growths by oral administration in athymic mice transplanted with the human lung cancer cell line H727. Conclusion: PNB‒101 is a potential chemotherapeutic agent for CCK‒gastrin related cancers and entered preclinical development

Surgical Treatment of Neer Group VI Proximal Humeral Fractures: Retrospective Comparison of PHILOS® and Hemiarthroplasty

Background: Neer Group VI proximal humeral fractures often are related to persistent disability despite surgical treatment. We retrospectively compared the outcome after open reduction and internal fixation with the PHILOS® plate or primary hemiarthroplasty in patients with Neer Group VI fractures focusing on complications, shoulder function, health-related quality of life (SF-36), and potential risk factors for complications. Questions/purposes: The aim of this study was to compare the PHILOS® plate with primary hemiarthroplasty for treatment of specific Neer Group VI fractures. We asked whether (1) both procedures have comparable clinical and radiologic complication rates; (2) one procedure is superior in terms of revision rate; (3) objective and subjective shoulder function (Constant-Murley score) and health-related quality of life (SF-36) were comparable in both groups at final followup; and (4) there are clinical or radiologic predictors for complications in any group? Methods: Between 2002 and 2007, 44 consecutive patients (mean, 75.2years) with a Neer Group VI proximal humeral fracture were included. Twenty-two patients treated with a PHILOS® plate were compared with 22 patients treated by primary hemiarthroplasty. Both groups were similar in all criteria. At minimum followup of 12months (mean, 30months; range, 12-83months), radiographic control, Constant-Murley score, and SF-36 were performed. Results : Fourteen patients with complications (63.6%) were counted in the PHILOS® plate group, of which 10 (45.4%) needed revision surgery, mostly as a result of avascular necrosis and screw cut-outs. In the primary hemiarthroplasty group, only one patient needed revision surgery (4.5%). Smoking and steroid therapy were substantially associated with complications in the PHILOS® plate group. There were no differences between the two groups regarding Constant-Murley or SF-36 scores. Conclusions : Angular stable open reduction and internal fixation was associated with high complication and revision rates, especially in patients who smoked and those receiving steroid therapy. Primary hemiarthroplasty provides limited function, which had little influence on the quality of life in this elderly collective. There are predictive factors for complications after the treatment of Neer Group VI proximal humeral fractures with the PHILOS® plate. Primary hemiarthroplasty remains a good option, especially when treating elderly patients. Level of Evidence: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidenc

Cholecystokinin-1 receptor antagonists:5-hydroxy-5-aryl-pyrrol-2-ones as anticancer agents

A new class of 5-arylated 5-hydroxypyrrolones was derived from mucochloric acid in 2 synthetic steps and the chemical structure was confirmed additionally by X-ray analysis. Using a radiolabelled binding assay, potent CCK1 selective ligands were identified (CCK1: 12 nM) and the antagonism was confirmed by using isolated tissue preparations. A series of isobutyl derivatives displayed unsurmountable CCK antagonistic properties and in vitro excellent inhibition of proliferation was obtained in cholecystokinin related cancer cell lines in the nanomolar range. Finally, using xenograft studies in nude mice, two selected pyrrolone derivatives, X = H and X = F a fluorinated analogue (PNB-028), showed a strong inhibition of tumour growth in a chemo-resistant colon cancer-(MAC 16) and a human pancreatic cell line (MIAPACA) at 50 mg kg-1 by oral administration

Cholecystokinin-2/gastrin antagonists:5-hydroxy-5-aryl-pyrrol-2-ones as anti-inflammatory analgesics for the treatment of inflammatory bowel disease

Arylated 5-hydroxy-pyrrol-2-ones were prepared in 2 synthetic steps from mucochloric acid and optimised as CCK2-selective ligands using radiolabelled binding assays. CCK antagonism was confirmed for the ligands in isolated tissue preparations. DSS (dextran sulfate sodium)-induced inflammation was analysed for derivative 7 and PNB-001 with L-365,260 as a standard. The IC50 of PNB-001 was determined to be 10 nM. Subsequent in vivo evaluation confirmed anti-inflammatory activity with respect to IBD assays. The best molecule, PNB-001, showed analgesic activity in the formalin test and in the hotplate assay, in which the analgesic effect of 1.5 mg kg−1 PNB-001 was equivalent to 40 mg kg−1 tramadol. The CCK2-selective antagonist PNB-001 protected rats against indomethacin-induced ulceration at similar doses. The GI protection activity was found to be more potent than that of the 10 mg kg−1 dose of prednisolone, which served as a standard

Komplexe proximale Humerusfraktur beim alten Menschen: Winkelstabile Plattenosteosynthese vs. Hemiarthroplastik

Zusammenfassung: Hintergrund: Ziel der vorliegenden Untersuchung ist ein direkter Vergleich der Schulterhemiarthroplastik (SHA) mit der winkelstabilen Plattenosteosynthese (WSPOS) beim alten Patienten mit komplexer proximaler Humerusfraktur. Patienten und Methoden: Zwischen 2003 und 2005 wurden alle Patienten (n=52, Alter ≥70Jahre) mit 3- und 4-Segment-Frakturen des proximalen Humerus, welche mit einer WSPOS (PHILOS®) versorgt wurden, prospektiv erfasst und nach einem Jahr mittels Constant-Score (CS), Oxford Shoulder Score (OSS) und radiologisch nachkontrolliert. Verglichen wurde die WSPOS mit einem historischen Kollektiv mit identischen Einschlusskriterien, welches zwischen 1995 und 1997 an der gleichen Institution mittels SHA versorgt wurde (n=59). Ergebnisse: Beide Patientenkollektive zeigten keine Unterschiede bezüglich Alter, Geschlechterverteilung und Frakturtypen. Der CS war signifikant besser für die WSPOS (median 71 vs. 41). Bezüglich Schmerzen zeigte sich im OSS kein Unterschied zwischen den Gruppen. In der WSPOS-Gruppe mussten signifikant mehr Revisionseingriffe durchgeführt werden (25% vs. 2%). Schlussfolgerung: Die WSPOS liefert beim alten Patienten, bei komplexen proximalen Humerusfrakturen deutlich bessere funktionelle Resultate, ist jedoch mit mehr Rezidiveingriffen behaftet. Die Selbständigkeit der Patienten kann bei beiden Operationsmethoden bei guter Schmerzfreiheit meist erhalten werde