75 research outputs found

    Emergency medical dispatch recognition, clinical intervention and outcome of patients in traumatic cardiac arrest from major trauma : an observational study

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    © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES: The aim of this study is to describe the demographics of reported traumatic cardiac arrest (TCA) victims, prehospital resuscitation and survival to hospital rate. SETTING: Helicopter Emergency Medical Service (HEMS) in south-east England, covering a resident population of 4.5 million and a transient population of up to 8 million people. PARTICIPANTS: Patients reported on the initial 999 call to be in suspected traumatic cardiac arrest between 1 July 2016 and 31 December 2016 within the trust's geographical region were identified. The inclusion criteria were all cases of reported TCA on receipt of the initial emergency call. Patients were subsequently excluded if a medical cause of cardiac arrest was suspected. OUTCOME MEASURES: Patient records were analysed for actual presence of cardiac arrest, prehospital resuscitation procedures undertaken and for survival to hospital rates. RESULTS: 112 patients were reported to be in TCA on receipt of the 999/112 call. 51 (46%) were found not to be in TCA on arrival of emergency medical services. Of the 'not in TCA cohort', 34 (67%) received at least one advanced prehospital medical intervention (defined as emergency anaesthesia, thoracostomy, blood product transfusion or resuscitative thoracotomy). Of the 61 patients in actual TCA, 10 (16%) achieved return-of-spontaneous circulation. In 45 (88%) patients, the HEMS team escorted the patient to hospital. CONCLUSION: A significant proportion of patients reported to be in TCA on receipt of the emergency call are not in actual cardiac arrest but are critically unwell requiring advanced prehospital medical intervention. Early activation of an enhanced care team to a reported TCA call allows appropriate advanced resuscitation. Further research is warranted to determine which interventions contribute to improved TCA survival.Peer reviewedFinal Published versio

    Chemokine gene expression in lung CD8 T cells correlates with protective immunity in mice immunized intra-nasally with Adenovirus-85A

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    <p>Abstract</p> <p>Background</p> <p>Immunization of BALB/c mice with a recombinant adenovirus expressing <it>Mycobacterium tuberculosis </it>(<it>M. tuberculosis</it>) antigen 85A (Ad85A) protects against aerosol challenge with <it>M. tuberculosis </it>only when it is administered intra-nasally (i.n.). Immunization with Ad85A induces a lung-resident population of activated CD8 T cells that is antigen dependent, highly activated and mediates protection by early inhibition of <it>M. tuberculosis </it>growth. In order to determine why the i.n. route is so effective compared to parenteral immunization, we used microarray analysis to compare gene expression profiles of pulmonary and splenic CD8 T cells after i.n. or intra-dermal (i.d.) immunization.</p> <p>Method</p> <p>Total RNA from CD8 T cells was isolated from lungs or spleens of mice immunized with Ad85A by the i.n. or i.d. route. The gene profiles generated from each condition were compared. Statistically significant (p ≤ 0.05) differentially expressed genes were analyzed to determine if they mapped to particular molecular functions, biological processes or pathways using Gene Ontology and Panther DB mapping tools.</p> <p>Results</p> <p>CD8 T cells from lungs of i.n. immunized mice expressed a large number of chemokines chemotactic for resting and activated T cells as well as activation and survival genes. Lung lymphocytes from i.n. immunized mice also express the chemokine receptor gene <it>Cxcr6</it>, which is thought to aid long-term retention of antigen-responding T cells in the lungs. Expression of CXCR6 on CD8 T cells was confirmed by flow cytometry.</p> <p>Conclusions</p> <p>Our microarray analysis represents the first <it>ex vivo </it>study comparing gene expression profiles of CD8 T cells isolated from distinct sites after immunization with an adenoviral vector by different routes. It confirms earlier phenotypic data indicating that lung i.n. cells are more activated than lung i.d. CD8 T cells. The sustained expression of chemokines and activation genes enables CD8 T cells to remain in the lungs for extended periods after i.n. immunization. This may account for the early inhibition of <it>M. tuberculosis </it>growth observed in Ad85A i.n. immunized mice and explain the effectiveness of i.n. compared to parenteral immunization with this viral vector.</p

    A Proposed Taxonomy of Anaerobic Fungi (Class Neocallimastigomycetes) Suitable for Large-Scale Sequence-Based Community Structure Analysis

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    Anaerobic fungi are key players in the breakdown of fibrous plant material in the rumen, but not much is known about the composition and stability of fungal communities in ruminants. We analyzed anaerobic fungi in 53 rumen samples from farmed sheep (4 different flocks), cattle, and deer feeding on a variety of diets. Denaturing gradient gel electrophoresis fingerprinting of the internal transcribed spacer 1 (ITS1) region of the rrn operon revealed a high diversity of anaerobic fungal phylotypes across all samples. Clone libraries of the ITS1 region were constructed from DNA from 11 rumen samples that had distinctly different fungal communities. A total of 417 new sequences were generated to expand the number and diversity of ITS1 sequences available. Major phylogenetic groups of anaerobic fungi in New Zealand ruminants belonged to the genera Piromyces, Neocallimastix, Caecomyces and Orpinomyces. In addition, sequences forming four novel clades were obtained, which may represent so far undetected genera or species of anaerobic fungi. We propose a revised phylogeny and pragmatic taxonomy for anaerobic fungi, which was tested and proved suitable for analysis of datasets stemming from high-throughput next-generation sequencing methods. Comparing our revised taxonomy to the taxonomic assignment of sequences deposited in the GenBank database, we believe that >29% of ITS1 sequences derived from anaerobic fungal isolates or clones are misnamed at the genus level

    Where Are All the Mycobacterium avium Subspecies paratuberculosis in Patients with Crohn's Disease?

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    Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic granulomatous inflammation of the intestines, Johne's disease, in dairy cows and every other species of mammal in which it has been identified. MAP has been identified in the mucosal layer and deeper bowel wall in patients with Crohn's disease by methods other than light microscopy, and by direct visualization in small numbers by light microscopy. MAP has not been accepted as the cause of Crohn's disease in part because it has not been seen under the microscope in large numbers in the intestines of patients with Crohn's disease. An analysis of the literature on the pathology of Crohn's disease and on possible MAP infection in Crohn's patients suggests that MAP might directly infect endothelial cells and adipocytes and cause them to proliferate, causing focal obstruction within already existing vessels (including granuloma formation), the development of new vessels (neoangiogenesis and lymphangiogenesis), and the “creeping fat” of the mesentery that is unique in human pathology to Crohn's disease but also occurs in bovine Johne's disease. Large numbers of MAP might therefore be found in the mesentery attached to segments of intestine affected by Crohn's disease rather than in the bowel wall, the blood and lymphatic vessels running through the mesentery, or the mesenteric fat itself. The walls of fistulas might result from the neoangiogenesis or lymphangiogenesis that occurs in the bowel wall in Crohn's disease and therefore are also possible sites of large numbers of MAP. The direct visualization of large numbers of MAP organisms in the tissues of patients with Crohn's disease will help establish that MAP causes Crohn's disease

    Cellular Immune Responses to Nine Mycobacterium tuberculosis Vaccine Candidates following Intranasal Vaccination

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    BACKGROUND: The identification of Mycobacterium tuberculosis vaccines that elicit a protective immune response in the lungs is important for the development of an effective vaccine against tuberculosis. METHODS AND PRINCIPAL FINDINGS: In this study, a comparison of intranasal (i.n.) and subcutaneous (s.c.) vaccination with the BCG vaccine demonstrated that a single moderate dose delivered intranasally induced a stronger and sustained M. tuberculosis-specific T-cell response in lung parenchyma and cervical lymph nodes of BALB/c mice than vaccine delivered subcutaneously. Both BCG and a multicomponent subunit vaccine composed of nine M. tuberculosis recombinant proteins induced strong antigen-specific T-cell responses in various local and peripheral immune compartments. Among the nine recombinant proteins evaluated, the alanine proline rich antigen (Apa, Rv1860) was highly antigenic following i.n. BCG and immunogenic after vaccination with a combination of the nine recombinant antigens. The Apa-induced responses included induction of both type 1 and type 2 cytokines in the lungs as evaluated by ELISPOT and a multiplexed microsphere-based cytokine immunoassay. Of importance, i.n. subunit vaccination with Apa imparted significant protection in the lungs and spleen of mice against M. tuberculosis challenge. Despite observed differences in the frequencies and location of specific cytokine secreting T cells both BCG vaccination routes afforded comparable levels of protection in our study. CONCLUSION AND SIGNIFICANCE: Overall, our findings support consideration and further evaluation of an intranasally targeted Apa-based vaccine to prevent tuberculosis

    Vaccines against Tuberculosis: Where Are We and Where Do We Need to Go?

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    In this review we discuss recent progress in the development, testing, and clinical evaluation of new vaccines against tuberculosis (TB). Over the last 20 years, tremendous progress has been made in TB vaccine research and development: from a pipeline virtually empty of new TB candidate vaccines in the early 1990s, to an era in which a dozen novel TB vaccine candidates have been and are being evaluated in human clinical trials. In addition, innovative approaches are being pursued to further improve existing vaccines, as well as discover new ones. Thus, there is good reason for optimism in the field of TB vaccines that it will be possible to develop better vaccines than BCG, which is still the only vaccine available against TB

    Out-of-hospital cardiac arrest following trauma: What does a helicopter emergency medical service offer?

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    Introduction Helicopter emergency medical services (HEMS) are often dispatched to patients in traumatic cardiac arrest (TCA) as they can provide treatments and advanced interventions in the pre-hospital environment that have the potential to contribute to an increased survival. This study, aimed to investigate the added value of HEMS in the treatment of TCA. Methods We performed a retrospective cohort study of all patients with a pre-hospital TCA who were attended by a non-urban HEMS (Kent, Surrey and Sussex Air Ambulance trust) between July 1st 2013 and May 1st 2018. We investigated how many patients got return of spontaneous circulation (ROSC) at scene, which HEMS specific advanced interventions were performed in these patients, and how these interventions were related to ROSC. Results During the study period 263 patients with a TCA were attended by HEMS with an average response time of 30 min [range 13–109]. 51 patients (20%) regained ROSC at scene (28 before- and 23 after arrival of HEMS). The HEMS specific interventions of blood product administration (OR 8.54 [2.84–25.72]), and RSI (2.95 [1.32–6.58]) were positively associated with ROSC. Most patients who had a ROSC had one or more HEMS specific interventions being performed – RSI (n = 19, 37%), blood product administration (n = 32, 62%), thoracostomies (n = 36, 71%) and thoracotomy (n = 1, 2%). HEMS also delivered other important interventions to these patients as IV/IO access (n = 20, 39.2%) and endotracheal intubation without drugs (n = 9, 17.6%). Conclusion HEMS teams should be involved in the treatment of patients with a TCA, even in non-urban areas with prolonged response times, as they provide knowledge and skills that contribute to regaining and maintaining a sustained ROSC in this critically ill and injured cohort of patients.</p
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