ABSTRACT
OBJECTIVES AND BACKGROUND: For the first time in the Emergency Department (ED), to assess the use of rotational thromboelastometry (ROTEM) in patients presenting with all-cause haemodynamic shock, specifically (a) to establish whether a 5- min (A5) or a 10-min result (A10) is accurate compared with a final maximum clot firmness (MCF) result; (b) to compare time to A10 and formal laboratory coagulation result; (c) to assess whether bleeding ED trauma, gastrointestinal and aortic aneurysm patients are coagulopathic according to ROTEM; and (d) to compare ROTEM results with formal laboratory coagulation parameters. METHODS: Patients presenting to the ED in haemodynamic shock were recruited. A citrated coagulation sample was taken and once a ROTEM researcher arrived in the ED, was subjected to ROTEM analysis. RESULTS: Between 28 September 2010 and 31 August 2011, 40 patients were recruited (15 gastrointestinal bleeds, 20 major trauma cases and five ruptured abdominal aortic aneurysms). A10 and MCF correlated well (κ=0.98); A5 and MCF correlated less well (κ=0.91). The mean time to result (SD) was 57 (28) min for the formal laboratory coagulation result and 50 (45) min for the ROTEM A10 result (including delay to start of analysis). Seven patients were coagulopathic on ROTEM. CONCLUSION: Eighteen percent of bleeding ED patients are coagulopathic using ROTEM including 25% of trauma patients. A 10-min ROTEM clot firmness (A10) is an excellent surrogate for MCF and allows a result to be obtained earlier than formal laboratory results and potentially within 10 min of the patient arriving in the ED.
Subject(s)
Shock/therapy , Thrombelastography/methods , Adolescent , Adult , Aged , Aged, 80 and over , Emergency Service, Hospital , Female , Humans , Male , Middle Aged , Point-of-Care Systems , Prospective Studies , Reproducibility of Results , Shock/physiopathology , Treatment Outcome , Young AdultABSTRACT
The use of Intraoperative Cell Salvage (ICS) is an important facet in establishing the recommendations of Better Blood Transfusion (DH 2007). Training in ICS often varies and has been identified as a challenge in the establishment of the routine use of ICS (UKCSAG 2007a). To help address this, the UK Cell Salvage Action Group, has developed a number of tools to assist in the delivery of both theory and practical elements of ICS training. The aim of this work is to provide standardised educational materials to support ICS training in hospitals throughout the UK.
Subject(s)
Blood Transfusion, Autologous , Clinical Competence , Educational Measurement/methods , Erythrocyte Transfusion , Inservice Training/methods , Blood Loss, Surgical , Curriculum , Humans , Intraoperative Care , Teaching Materials , United KingdomABSTRACT
Anaplastic lymphoma kinase (ALK) is a promising new target for therapy of certain cancers such as anaplastic large-cell lymphoma (ALCL) and inflammatory myofibroblastic tumor (IMT). We have identified a series of novel pyridones as kinase inhibitors of ALK by application of a stepwise process involving in vitro screening of a novel targeted library followed by iterative template modification based on medicinal chemistry insights and computational ranking of virtual libraries. Using this process, we discovered ALK-selective inhibitors with improved potency and selectivity. Herein the details of the design process and synthesis of these novel pyridones, along with their enzymatic and cell-based activity, are discussed.
Subject(s)
Amides/chemical synthesis , Antineoplastic Agents/chemical synthesis , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyridones/chemical synthesis , Amides/chemistry , Amides/pharmacology , Anaplastic Lymphoma Kinase , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Combinatorial Chemistry Techniques , Databases, Factual , Drug Design , Humans , Mice , Models, Molecular , Pyridones/chemistry , Pyridones/pharmacology , Receptor Protein-Tyrosine Kinases , Structure-Activity RelationshipABSTRACT
The development of potent and selective urokinase-type plasminogen activator (uPA) inhibitors based on the lead molecule 2-(2-hydroxy-3-ethoxyphenyl)-1H-benzimidazole-5-carboxamidine (3a) is described.
Subject(s)
Amidines/pharmacology , Benzimidazoles/pharmacology , Serine Proteinase Inhibitors/pharmacology , Urokinase-Type Plasminogen Activator/antagonists & inhibitors , Amidines/chemistry , Benzimidazoles/chemistry , Binding Sites , Crystallography, X-Ray , Drug Design , Models, Molecular , Protein Binding , Receptors, Cell Surface/chemistry , Receptors, Cell Surface/metabolism , Serine Proteinase Inhibitors/chemistry , Stereoisomerism , Structure-Activity RelationshipABSTRACT
The structure-based design of potent and selective urokinase-type plasminogen activator (uPA) inhibitors with 4-aminoarylamidine or 4-aminoarylguanidine S1 binding groups, is described.
