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Llanelli, United Kingdom

Kaczynski J.,University of Swansea | Wilczynska M.,Prince Phillip Hospital | Fligelstone L.,University of Swansea | Hilton J.,University of Swansea
European Journal of Trauma and Emergency Surgery | Year: 2015

Background: The acute coagulopathy of trauma and shock is associated with significant mortality and, currently, there are no validated laboratory tests which allow for a rapid recognition and treatment of this condition. Therefore, early detection of any clot abnormality in trauma could improve the diagnosis of trauma-associated coagulopathy and subsequent interventions. Methods: Review of the literature. Results: The standard laboratory tests, including prothrombin time and activated partial thromboplastin time, are unreliable and describe only an isolated fragment of the complex coagulation pathways. Additionally, thromboelastography and thromboelastometry operate in a non-linear regime which implies that clot formation is the product of both the clotting process and the effect of the measurement. The assessment of the clot microstructure using a scanning electron microscope has resulted in a subjective analysis of a clot structure, showing also poor correlation between the coagulation pathways and clot development. The fractal dimension provides information on the structure and quality of the initial clot, which subsequently acts as a template for how the mature clot will behave. However, these data require further verification in an in vivo setting. At present, the treatment of the coagulopathy is delivered by empirically administered massive transfusion protocols, which lack a specific target for replacement therapy. Conclusions: There is enough evidence to demonstrate that we urgently need a robust test, which would determine and quantify both the rate and the extent of coagulation abnormalities. This could help to tailor the treatment of coagulopathy according to the patient’s needs. © 2013, Springer-Verlag Berlin Heidelberg.

Cameron S.J.S.,Institute of Biological | Lewis K.E.,Prince Phillip Hospital | Lewis K.E.,University of Swansea | Beckmann M.,Institute of Biological | And 4 more authors.
Lung Cancer | Year: 2016

Objectives: Developing screening and diagnosis methodologies based on novel biomarkers should allow for the detection of the lung cancer (LC) and possibly at an earlier stage and thereby increase the effectiveness of clinical interventions. Here, our primary objective was to evaluate the potential of spontaneous sputum as a source of non-invasive metabolomic biomarkers for LC status. Materials and methods: Spontaneous sputum was collected and processed from 34 patients with suspected LC, alongside 33 healthy controls. Of the 34 patients, 23 were subsequently diagnosed with LC (LC+, 16 NSCLC, six SCLC, and one radiological diagnosis), at various stages of disease progression. The 67 samples were analysed using flow infusion electrospray ion mass spectrometry (FIE-MS) and gas-chromatography mass spectrometry (GC-MS). Results: Principal component analysis identified negative mode FIE-MS as having the main separating power between samples from healthy and LC. Discriminatory metabolites were identified using ANOVA and Random Forest. Indications of potential diagnostic accuracy involved the use of receiver operating characteristic/area under the curve (ROC/AUC) analyses. This approach identified metabolites changes that were only observed with LC. Metabolites with AUC values of greater than 0.8 which distinguished between LC+/LC- binary classifications where identified and included Ganglioside GM1 which has previously been linked to LC. Conclusion: This study indicates that metabolomics based on sputum can yield metabolites that can be used as a diagnostic and/or discriminator tool. These could aid clinical intervention and targeted diagnosis of LC within an 'at risk' LC- population group. The use of sputum as a non-invasive source of metabolite biomarkers may aid in the development of an at-risk population screening programme for lung cancer or enhanced clinical diagnostic pathways. © 2016 Elsevier Ireland Ltd.

Lewis M.J.,University of Swansea | Balaji G.,Prince Phillip Hospital | Dixon H.,Prince Phillip Hospital | Syed Y.,Prince Phillip Hospital | And 2 more authors.
Clinical Physiology and Functional Imaging | Year: 2010

Many smokers attempt to quit without using nicotine replacement therapy (NRT) or pharmacotherapy, i.e. 'cold-turkey'. The cardiac implications of this are important but are incompletely understood. Previous studies have associated smoking cessation with improvements in heart rate (HR) and its variability, but its influence on QT time-series is unclear. Furthermore, the relative influence on these parameters of acute nicotine withdrawal and of NRT has not been adequately compared. Additional insight might come from analysing the dynamic (e.g. fractal) properties of electrocardiographic data during different levels of nicotine exposure. We examined the influence of smoking cessation, during cold-turkey and subsequent NRT, on HR and QT time-series during 30 days of smoking abstinence. Seven smokers and sixteen healthy non-smokers received ECG monitoring at baseline (Day 0). Smokers subsequently refrained from smoking without using NRT for 24 h, and then received NRT for 29 days. ECG monitoring was repeated at Days 1, 7, 30. Following smoking cessation we observed that: HR and rate-corrected QT were both reduced, heart rate variability (HRV) increased (improved), and QT variability index (QTVI) showed signs of improvement (trend only). Improvements in HR and QT were maintained throughout NRT use, whilst improvements in HRV and QTVI were sustained for at least the early stages of NRT. The dynamic (multifractal) properties of HR and QT were similar for smokers and non-smokers, and were unchanged by smoking abstinence or NRT. Our results provide tentative evidence that electrocardiographic improvements during a cold-turkey smoking quit attempt (acute nicotine withdrawal) are maintained during NRT pharmacotherapy. © 2009 The Authors. Journal compilation © 2009 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Lewis P.D.,University of Swansea | Lewis K.E.,University of Swansea | Ghosal R.,Prince Phillip Hospital | Bayliss S.,University of Swansea | And 5 more authors.
BMC Cancer | Year: 2010

Background: Survival time for lung cancer is poor with over 90% of patients dying within five years of diagnosis primarily due to detection at late stage. The main objective of this study was to evaluate Fourier transform infrared spectroscopy (FTIR) as a high throughput and cost effective method for identifying biochemical changes in sputum as biomarkers for detection of lung cancer.Methods: Sputum was collected from 25 lung cancer patients in the Medlung observational study and 25 healthy controls. FTIR spectra were generated from sputum cell pellets using infrared wavenumbers within the 1800 to 950 cm-1"fingerprint" region.Results: A panel of 92 infrared wavenumbers had absorbances significantly different between cancer and normal sputum spectra and were associated with putative changes in protein, nucleic acid and glycogen levels in tumours. Five prominent significant wavenumbers at 964 cm-1, 1024 cm-1, 1411 cm-1, 1577 cm-1and 1656 cm-1separated cancer spectra from normal spectra into two distinct groups using multivariate analysis (group 1: 100% cancer cases; group 2: 92% normal cases). Principal components analysis revealed that these wavenumbers were also able to distinguish lung cancer patients who had previously been diagnosed with breast cancer. No patterns of spectra groupings were associated with inflammation or other diseases of the airways.Conclusions: Our results suggest that FTIR applied to sputum might have high sensitivity and specificity in diagnosing lung cancer with potential as a non-invasive, cost-effective and high-throughput method for screening. © 2010 Lewis et al; licensee BioMed Central Ltd.

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