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Introduction: Prehospital critical care teams comprising an appropriately trained physician and paramedic or nurse have been associated with improved outcomes in selected trauma patients. These teams are a scarce and expensive resource, especially when delivered by rotary air assets. The optimal tasking of prehospital critical care teams is therefore vital and remains a subject of debate. Emergency Medical Retrieval Service (EMRS) provides a prehospital critical care response team to incidents over a large area of Scotland either by air or by road., Methods: A convenience sample of consecutive EMRS missions covering a period of 18 months from May 2013 to January 2015 was taken. These missions were matched with the ambulance service information on geographical location of the incident. In order to assess the appropriateness of tasking, interventions undertaken on each mission were analysed and divided into two subcategories: 'critical care interventions' and 'advanced medical interventions'. A tasking was deemed appropriate if it included either category of intervention or if a patient was pronounced life extinct at the scene., Results: A total of 1279 primary missions were undertaken during the study period. Of these, 493 primary missions met the inclusion criteria and generated complete location data. The median distance to scene was calculated as 5.6 miles for land responses and 34.2 miles for air responses. Overall, critical care interventions were performed on 17% (84/493) of patients. A further 21% (102/493) of patients had an advanced medical intervention. Including those patients for whom life was pronounced extinct on scene by the EMRS team, a total of 42% (206/493) taskings were appropriate., Discussion: Overall, our data show a wide geographical spread of tasking for our service, which is in keeping with other suburban/rural models of prehospital care. Tasking accuracy is also comparable to the accuracy shown by other similar services.

This consensus statement provides profession-specific guidance in relation to tracheal intubation by paramedics - a procedure that the College of Paramedics supports. Tracheal intubation by paramedics has been the subject of professional and legal debate as well as crown investigation. It is therefore timely that the College of Paramedics, through this consensus group, reviews the available evidence and expert opinion in order to prevent patient harm and promote patient safety, clinical effectiveness and professional standards. It is not the purpose of this consensus statement to remove the skill of tracheal intubation from paramedics. Neither is it intended to debate the efficacy of intubation or the effect on mortality or morbidity, as other formal research studies will answer those questions. The consensus of this group is that paramedics can perform tracheal intubation safely and effectively. However, a safe, well-governed system of continual training, education and competency must be in place to serve both patients and the paramedics delivering their care., Competing Interests: None declared., (© 2018 The Author(s).)

Introduction: Trauma remains the fourth leading cause of death in western countries and is the leading cause of death in the first four decades of life. NICE guidance in 2016 advocated the attendance of pre-hospital critical care trauma team (PHCCT) in the pre-hospital stage of the care of patients with major trauma. Previous publications support dispatch by clinicians who are also actively involved in the delivery of the PHCCT service; however there is a lack of objective outcome measures across the current reviewed evidence base. In this study, we aimed to assess the accuracy of PHCCT clinician led dispatch, when measured by Injury Severity Score (ISS)., Methods: A retrospective cohort study over a 2 year period pre and post implementation of a PHCCT clinician led dispatch of PHCCT for potential major trauma patients, using national ambulance data combined with national trauma registry data., Results: A total of 99,702 trauma related calls were made to SAS including 495 major trauma patients with an ISS >15, and a total of 454 dispatches of a PHCCT. Following the introduction of a PHCCT clinician staffed trauma desk, the sensitivity for major trauma was increased from 11.3% to 25.9%. The difference in sensitivity between the pre and post trauma desk group was significant at 14.6% (95% CI 7.4%-21.4%, p < .001)., Discussion: The results from the study support the results from other studies recommending that a PHCCT clinician should be located in ambulance control to identify major trauma patients as early as possible and co-ordinate the response., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Ideal treatment in Parkinson's disease (PD) aims at relieving symptoms and slowing disease progression. Of all remedies, levodopa remains the most effective for symptomatic relief, but the medical need for neuroprotectant drugs is still unfulfilled. Safinamide, currently in phase III clinical trials for the treatment of PD, is a unique molecule with multiple mechanisms of action and a very high therapeutic index. It combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide has neuroprotective and neurorescuing effects in MPTP-treated mice, in the rat kainic acid, and in the gerbil ischemia model. Safinamide potentiates levodopa-mediated increase of DA levels in DA-depleted mice and reverses the waning motor response after prolonged levodopa treatment in 6-OHDA-lesioned rats. Safinamide has excellent bioavailability, linear kinetics, and is suitable for once-a-day administration. Therefore, safinamide may be used in PD to reduce l-dopa dosage and also represents a valuable therapeutic drug to test disease-modifying potential.

Insulin-like growth factor 1 (IGF-1) plays a critical role in CNS development. IGF-1 can block neuronal apoptosis in vitro and in vivo. IGF-1 is thought to be cleaved into des-N-(1-3)-IGF-1 and an amino terminal glycine-proline-glutamate (GPE tripeptide). Here we report a neuroprotective role for GPE tripeptide, with enhanced survival of the CA1-2 hippocampal neurons following an excitotoxic insult in vitro. Binding and displacement studies suggest uniquely distributed sites of action within the rat including the hippocampal CA1-2, pyriform cortex, amygdala, choroid plexus, blood vessels and to a lesser extent in the cortical regions. A similar pattern of binding was seen in the human. This finding could lead to new strategies to reduce neuronal death after injury and in disease.

Interleukin 2 (IL-2) is a cytokine produced by activated T cells that plays a crucial role in the immune response and exerts multiple functions in different tissues including the nervous system. The present study was carried out to investigate the effect of recombinant human IL-2 (rhIL-2) on the survival of differnet glial cells type and of cortical neurons in culture. The results demonstrate that rhIL-2 is selectively cytotoxic to oligodendrocytes only if preincubated in aqueous solution (1200 U/ml) for at least two days before being added to the culture. Other glial and neuronal cells were unaffected. The cytotoxic effect was temperature- and concentration-dependent occurring only when rhIL-2 was reincubated at 37 degrees C and was dose-dependently neutralized by antibodies raised against IL-2 indicating that an immunoreactive IL-2 like compound is the active principle. Polyacrilamide gel electrophoresis under native (PAGE) and denaturing (SDS-PAGE) conditions and gel filtration analysis of the rhIL-2 incubated solution suggest that rhIL-2 is cytotoxic to oligodendrocytes only after association into soluble high weight molecular aggregates., (Copyright 1997 Academic Press Limited.)

A combination of HPLC elution patterns and peptide sequencing has been used to characterize two distinct activities present in subcellular fractions of bovine aortic endothelial cells (BAECs) capable of converting human big endothelin-1 (big ET-1) to mature (ET-1). A pepstatin-inhibitable activity with an acidic pH optimum present in a lysosome-enriched fraction cleaved big ET-1 at positions 18 and 21 at similar rates. A neutral pH activity present in a postlysosomal organelles subfraction was also able to convert big ET-1, and was inhibited by EDTA, but not by 1-chloro-3-tosylamido-4-phenyl-2-butanone (TPCK), an inhibitor of chymotrypsin-like serine proteases.

Normal and established human epithelial cell lines obtained from the same organs were compared for their capacity to retract a fibrin clot. Fibrin clot retraction was maximal in normal epithelial cells, reduced in established nontumorigenic lines, and lost in tumorigenic cancer cell lines. Fibrin clot retraction efficiency seemed to be related to the degree of cellular spreading within the clot at the end of the test. Previous works and the present study suggest that fibrin clot retraction is correlated with some steps of cell transformation in vitro.

The procoagulant activity of cells from some experimental tumours isolated in culture or in single-cell suspensions from ascitic fluid was investigated. Cells from Lewis lung carcinoma (primary and metastasis), Ehrlich carcinoma ascites and JW sarcoma ascites were able to shorten markedly the recalcification time of normal, Factor VIII- and Factor VII-deficient but not of Factor X-deficient human plasma. The same cells generated thrombin when mixed with a source of prothrombin and Factor X, absorbed bovine serum (as a source of Factor V), phospholipid and calcium chloride. Thrombin formation was not influenced by the presence of Factor VII. Cells from Sarcoma 180 ascites were completely inactive in both test systems. It is concluded that cells from some experimental tumours have the capacity to activate Coagulation Factor X directly. These findings suggest the existence of an alternative "cellular" pathway in the initiation of blood clotting distinct from both the intrinsic and extrinsic mechanisms.

It is known that human and animal fibroblasts are able to induce the retraction of a fibrin clot. In the present study the correlation between (i) fibrin-fibroblasts during growth, (ii) the number of actin stress-lines in mouse fibroblasts during growth in culture, and (iii) the sensitivity of actin stress-lines to a powerful actin-depolymerizing factor (ADF), present in plasma and serum of humans and laboratory animals was investigated. Fibroblasts at early passages (2-4) were tested for these parameters at various intervals after seeding (24, 96, and 168 h). The number of actin stress-lines was progressively higher, while the sensitivity to ADF action was progressively lower in cells cultured from 24 to 168 h; the FCR capacity was significantly decreased at 168 h. These data suggest that cells containing weakly polymerized and/or stabilized actin are more active than those containing highly polymerized and/or stabilized actin in triggering fibroblast contraction.

This study aimed at evaluating by a quantitative assay the fibrin clot retractile activity (FCR) of C3H embryo fibroblasts during their growth and aging in culture. Cell from primary and subsequent subcultures were tested at defined times from seeding, in a specially devised micromethod. Results indicate that cell-induced FCR has a kinetic similar to platelet-induced FCR; it depends on the number of cells and time of incubation in the system. It is absent or low in cells harvested from primary culture, then increases and remains high in the following doublings decreasing sharply at the end of the replicative life span in culture.

The expression of transformation parameters (inhibition of cell division during cell crowding, anchorage dependence, loss of fibrin clot retractile activity and secretion of plasminogen activator) was studied in a heterospecific cellular hybrid, made between established L(TK-) cells and the normal human MRC-5 cells. The hybrid nature of the cross was confirmed by the ability to incorporate [3H]-thymidine, by growth in selective HAT medium, by the identification of human chromosomes and by the expression on the surface of 100% of hybrid cells of a human glycoprotein, which is recognized by the 4F2 monoclonal antibody. The hybrid cultures showed cell cycle inhibition which became less stringent with increasing population doublings and the loss of human chromosomes. Fibrin clot retraction and anchorage dependence were absent in spite of the presence of many human chromosomes. The two properties were present or lost simultaneously in the normal parent cells and in the transformed parent or hybrid cells respectively. The human type of plasminogen activator was secreted even with very little human genetic material left, and a complete dissociation between fibrin clot retraction and production of plasminogen activator was observed. The data strengthen the hypothesis that transformation is a multistep process that involves complex genetic control and where cells progressively express different phenotypes and escape growth control.

Fibroblast-like cells derived from C3H mice at the first passage in culture, and a line from the same origin, which had undergone spontaneous transformation at the eleventh passage, were seeded on fibrin plates and tested for their attachment and spreading. After 4-24 hours normal cells had a spider-like morphology, while transformed cells remained in round clusters, flattened on the substrate. This data represent the morphological counterpart of the abnormal fibroblast-fibrin interaction shown in a tridimensional model, where transformed cells were found unable to induce the retraction of a fibrin clot (FCR).

This study was originally designed to investigate whether there is any correlation between the type of procoagulant activity (PCA) and the tumorigenicity of transformed cells. The data obtained are relevant to this question and to defining the differences in the expression of cellular activities depending on the in vitro system used. PCA was measured and characterized in normal, immortalized, and tumorigenic mouse fibroblasts. In all the cell lines studied the activity was of tissue factor type, as established with functional, enzymatic, and immunochemical criteria. However, the PCA of cells freshly isolated from the tumors induced by tumorigenic cell lines was of cancer procoagulant type, i.e. a cysteine protease with direct factor X activator activity. The same cells, when cultured in vitro, expressed again PCA of tissue-factor type. These results suggest that either a tumor-host interaction is required for the expression of cancer procoagulant or the latter activity, produced by tumor cells under in vitro conditions, is destroyed or inactivated during the culture period. Our findings caution against defining the procoagulant activity of tumors based on experiments on cultured cells.

The development of transformed cell lines evolving from an embryo fibroblastic C3H primary culture was followed before and after the ageing crisis using different techniques. By flow cytometry, alteration of subpopulations having different DNA content and altered metabolic activity was observed after the crisis, with the trend to assume a near tetraploid DNA index at higher passages. The fibrin clot retractile activity was lost in all cases during the ageing crisis, but the outcome did not present uniform values of growth characteristics or chromosome number and tumorigenicity appeared to be a nonstable property of the transformed cell lines.

The presence of fibrin deposits in the microenvironment of tumor cells has been reported repeatedly and considered to play an important role in tumor biology. Among the mechanisms by which fibrin may be deposited in tumors, procoagulant activities (PCA) of different types have been described in cancer cells. The present study was aimed at establishing whether the nature of cellular PCA was a characteristic associated with malignant transformation. PCA of normal and transformed cells was investigated on pairs of murine and human origin. The transformed counterparts were obtained after treatment with low-dose radiation, chemical carcinogen, viral infection or after in vitro spontaneous immortalization. Both before and after any type of transformation cell PCA was of the tissue thromboplastin type, identified on the basis of biological criteria: requirement of factor VII for its expression and lack of inhibition by the serine protease inhibitor diisopropylfluorophosphate (DFP). Transformed cells of murine origin showed significantly lower activity than their normal counterparts, whereas all the transformed human cell lines expressed significantly higher activity than normal. An inverse correlation between the levels of PCA and the cell density in culture was observed in all but one of the lines tested. These findings suggest that the factor X activating property described in some tumors or in transformed cells cannot be considered as a general marker of transformation.

Mouse fibroblasts were cultured by three different procedures: (a) changing the 0.2 ml/cm2 of growth medium every 2nd d and seeding 1 X 10(5) cells/cm2 after confluency; (b) changing the 0.4 ml/cm2 of growth medium only at subculture performed at confluency by a 1:2 split and keeping the bottles incubated on a rocking platform; (c) the same as Method b but keeping the bottles stationary throughout culture. By Method a no lines were immortalized over 36 experiments whereas Method b gave 1/4 immortalized lines and Method c gave 10:12 immortalized lines. Cells always went into crisis at the 9th to 11th doubling. Immortalized lines had a tetraploid DNA content.