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Institution

Guy's and St Thomas' NHS Foundation Trust

HealthcareLondon, United Kingdom
About: Guy's and St Thomas' NHS Foundation Trust is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 7686 authors who have published 9631 publications receiving 399353 citations. The organization is also known as: Guy's and St Thomas' National Health Service Foundation Trust & Guy's and St Thomas' National Health Service Trust.


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Journal ArticleDOI
TL;DR: This study has identified critical amino acids needed for the normal subcellular localization and function of Nav1.7 sodium channel, a protein highly expressed in pain‐sensing neurons, and describes the identification and functional characterization of two novel non‐truncating mutations in families with CIP.
Abstract: SCN9A encodes the voltage-gated sodium channel Nav1.7, a protein highly expressed in pain-sensing neurons. Mutations in SCN9A cause three human pain disorders: bi-allelic loss of function mutations result in Channelopathy-associated Insensitivity to Pain (CIP), whereas activating mutations cause severe episodic pain in Paroxysmal Extreme Pain Disorder (PEPD) and Primary Erythermalgia (PE). To date, all mutations in SCN9A that cause a complete inability to experience pain are protein truncating and presumably lead to no protein being produced. Here, we describe the identification and functional characterization of two novel non-truncating mutations in families with CIP: a homozygously-inherited missense mutation found in a consanguineous Israeli Bedouin family (Nav1.7-R896Q) and a five amino acid in-frame deletion found in a sporadic compound heterozygote (Nav1.7-ΔR1370-L1374). Both of these mutations map to the pore region of the Nav1.7 sodium channel. Using transient transfection of PC12 cells we found a significant reduction in membrane localization of the mutant protein compared to the wild type. Furthermore, voltage clamp experiments of mutant-transfected HEK293 cells show a complete loss of function of the sodium channel, consistent with the absence of pain phenotype. In summary, this study has identified critical amino acids needed for the normal subcellular localization and function of Nav1.7. © 2010 Wiley-Liss, Inc.

116 citations

Journal ArticleDOI
TL;DR: A Type 1 Diabetes Combination Therapy Assessment Group was convened and the recommendations, the recommendations of which are discussed in this Perspective paper, are discussed.
Abstract: Like many other complex human disorders of unknown aetiology, autoimmune-mediated type 1 diabetes may ultimately be controlled via a therapeutic approach that combines multiple agents, each with differing modes of action. The numerous advantages of such a strategy include the ability to minimize toxicities and realize synergies to enhance and prolong efficacy. The recognition that combinations might offer far-reaching benefits, at a time when few single agents have yet proved themselves in well-powered trials, represents a significant challenge to our ability to conceive and implement rational treatment designs. As a first step in this process, the Immune Tolerance Network, in collaboration with the Juvenile Diabetes Research Foundation, convened a Type 1 Diabetes Combination Therapy Assessment Group, the recommendations of which are discussed in this Perspective paper.

116 citations

Journal ArticleDOI
TL;DR: Clinical management of major haemorrhage in trauma patients has changed radically, and the previous approach of maintaining an adequate circulating volume and oxygen carrying capacity before, as a secondary event, dealing with coagulopathy, has changed to haemostatic resuscitation.
Abstract: : Over the last 10 years, the management of major haemorrhage in trauma patients has changed radically. This is mainly due to the recognition that many patients who are bleeding when they come in to the emergency department have an established coagulopathy before the haemodilution effects of fluid resuscitation. This has led to the use of new terminology: acute traumatic coagulopathy, acute coagulopathy of trauma shock or trauma-induced coagulopathy. The recognition of acute traumatic coagulopathy is important, because we now understand that its presence is a prognostic indicator, as it is associated with poor clinical outcome. This has driven a change in clinical management, so that the previous approach of maintaining an adequate circulating volume and oxygen carrying capacity before, as a secondary event, dealing with coagulopathy, has changed to haemostatic resuscitation as early as possible. While there is as yet no universally accepted assay or definition, many experts use prolongation of the prothrombin time to indicate that there is, indeed, a coagulopathy. Hypoxia, acidosis and hypothermia and hormonal, immunological and cytokine production, alongside consumption and blood loss, and the dilutional effects of resuscitation may occur to varying extents depending on the type of tissue damaged, the type and extent of injury, predisposing to, or amplifying, activation of coagulation, platelets, fibrinolysis. These are discussed in detail within the article.

116 citations

Journal ArticleDOI
01 Apr 2009-Thorax
TL;DR: Dietary counselling and food fortification resulted in weight gain and improvements in outcome in nutritionally at-risk outpatients with COPD, both during and beyond the intervention period.
Abstract: Background: Malnutrition in chronic obstructive pulmonary disease (COPD) is associated with a poor prognosis, yet evidence to support the role of dietary counselling and food fortification is lacking. A study was undertaken to assess the impact of dietary counselling and food fortification on outcome in outpatients with COPD who are at risk of malnutrition. Methods: A randomised controlled unblinded trial was performed in 59 outpatients with COPD (6 months intervention and 6 months follow-up). The intervention group received dietary counselling and advice on food fortification and the controls received a dietary advice leaflet. Outcome measures were nutritional status, respiratory and skeletal muscle strength, respiratory function, perceived dyspnoea, activities of daily living (ADL) and quality of life. Results: The intervention group consumed more energy (difference 194 kcal/day; p = 0.02) and protein (difference 11.8 g/day; p Conclusion: Dietary counselling and food fortification resulted in weight gain and improvements in outcome in nutritionally at-risk outpatients with COPD, both during and beyond the intervention period.

116 citations


Authors

Showing all 7765 results

NameH-indexPapersCitations
Christopher J L Murray209754310329
Bruce M. Psaty1811205138244
Giuseppe Remuzzi1721226160440
Mika Kivimäki1661515141468
Simon I. Hay165557153307
Theo Vos156502186409
Ali H. Mokdad156634160599
Steven Williams144137586712
Igor Rudan142658103659
Mohsen Naghavi139381169048
Christopher D.M. Fletcher13867482484
Martin McKee1381732125972
David A. Jackson136109568352
Graham G. Giles136124980038
Yang Liu1292506122380
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202316
202298
20211,488
20201,123
2019829
2018767