Zur Darstellung der 4-(Pyrrolidyl-2)-buttersaure, der 5-(Pyrrolidyl-2)-valeriansaure und des 1-Aza-bicyclo-[0,3,5]decans

Ausgehend von 4-(Tetrahydro-2-furyl)-buttersaureathylester (I) und 5-(Tetrahydro-2-furyl)-valeriansaureathylester (II) werden durch Aufsprengung des Tetrahydrofuranrings mit Bromwasserstoff die entsprechenden Dibromester (II, V) erhalten. Durch nachfolgendes Erhitzen mit methylalkoholischem Ammoniak werden 4-(Pyrrolidyl-2)-buttersaure und 5-(Pyrrolidyl-2)-valeriansaure als Ester (III, VI) dargestellt. Ferner wird eine neue Synthese des 1-Aza-bicyclo-[O, 3, 5]-decans (VIII) beschrieben

Synthesen in der Pyrrolizidin- und Indolizidin-Reihe

Ausgehend von 4-(Tetrahydro-2-furyl)-buttersaure (I) und 5-(Tetrahydro-2-furyl)-va~eriansaure (V) werden durch Bromierung mit Brom und rotem Phosphor und ausschlissender Behandlung mit Methanol 2-Brom-(tetrahydro-2-furyl)-saureester als ein Gemisch von bromhaltigen Stoffen erhalten. Die so gewonnenen Bromsaure ester werden mittels Bromwasserstoff in die entsprechenden Tribromester II und VI ilberfilhrt welche dann durch Erhitzen mit methylalkoholischem Ammoniak Pyrrolizidin-3-carborisauremethylester (III) und Indolizidin-5-carbonsauremethylester (VII) lieferten. Durch Reduktion des Esters III und VII mit Lithiumaluminiumhydrid wurden aus III 3-0xymethylpyrrolizidin und aus VII 5-0xymethyl-indolizidin erhalten

Vascular endothelial growth factor in children with neuroblastoma: a retrospective analysis

BACKGROUND: Despite aggressive therapy, advanced stage neuroblastoma patients have poor survival rates. Although angiogenesis correlates with advanced tumour stage and plays an important role in determining the tumour response to treatment in general, clinical data are still insufficient, and more clinical evaluations are needed to draw conclusions. The aim of this study was to evaluate vascular endothelial growth factor (VEGF) expression in patients with neuroblastoma, determine whether it correlates with other prognostic factors and/or therapeutic response, and to assess should VEGF be considered in a routine diagnostic workup. ----- MATERIALS AND METHODS: VEGF expression was determined by immunohistochemistry using anti-VEGF antibody in paraffin embedded primary tumour tissue from 56 neuroblastoma patients. Semiquantitative expression of VEGF was estimated and compared with gender, age, histology, disease stage, therapy, and survival. Statistical analyses, including multivariate analysis, were performed. ----- RESULTS: VEGF expression correlated with disease stage and survival in neuroblastoma patients. Combination of VEGF expression and disease stage as a single prognostic value for survival (P-value = 0.0034; odds ratio (OR) (95%CI) = 26.17 (2.97-230.27) exhibited greater correlation with survival than individually. Hematopoietic stem cell transplantation significantly improved survival of the advanced stage patients with high VEGF expression. ----- CONCLUSION: VEGF expression should be considered in a routine diagnostic workup of children with neuroblastoma, especially in those more than 18 months old and with advanced disease stage. High VEGF expression at the time of disease diagnosis is a bad risk prognostic factor, and can be used to characterize subsets of patients with an unfavourable outcome

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries