Hayes J.,St Jamess Hospital |
Peruzzi P.P.,Ohio State University |
Lawler S.,Harvard University
Trends in Molecular Medicine | Year: 2014
The emergence of microRNAs has been one of the defining developments in cancer biology over the past decade, and the explosion of knowledge in this area has brought forward new diagnostic and therapeutic opportunities. The importance of microRNAs in cancer has been underlined by the identification of alterations in microRNA target binding sites and the microRNA processing machinery in tumor cells. Clinical trials utilizing microRNA profiling for patient prognosis and clinical response are now underway, and the first microRNA mimic entered the clinic for cancer therapy in 2013. In this article we review the potential applications of microRNAs for the clinical assessment of patient outcome in cancer, as well as in cancer monitoring and therapy. © 2014 Elsevier Ltd.
Gray S.G.,St Jamess Hospital
Arthritis Research and Therapy | Year: 2013
Rheumatic disease can loosely be described as any painful condition affecting the loco-motor system, including joints, muscles, connective tissues, and soft tissues around the joints and bones. There is a wide spectrum of rheumatic diseases, many of which involve autoimmunity, including systemic lupus erythematosus and rheumatoid arthritis. A significant body of evidence now links aberrant epigenetic regulation of gene expression with rheumatic disease and points toward the use of epigenetic targeting agents as potential new treatment options, particularly for those conditions associated with an autoimmune element. In this perspective, I will briefly cover the current knowledge surrounding this area in the field of rheumatology. © 2013 BioMed Central Ltd.
Hill A.,St Jamess Hospital
Blood | Year: 2013
The most frequent and feared complication of paroxysmal nocturnal hemoglobinuria (PNH) is thrombosis. Recent research has demonstrated that the complement and coagulation systems are closely integrated with each influencing the activity of the other to the extent that thrombin itself has recently been shown to activate the alternative pathway of complement. This may explain some of the complexity of the thrombosis in PNH. In this review, the recent changes in our understanding of the pathophysiology of thrombosis in PNH, as well as the treatment of thrombosis, will be discussed. Mechanisms explored include platelet activation, toxicity of free hemoglobin, nitric oxide depletion, absence of other glycosylphosphatidylinositol-linked proteins such as urokinase-type plasminogen activator receptor and endothelial dysfunction. Complement inhibition with eculizumab has a dramatic effect in PNH and has a major impact in the prevention of thrombosis as well as its management in this disease.
Elliott M.W.,St Jamess Hospital
Thorax | Year: 2011
Non-invasive ventilation (NIV) has been remarkably effective in the management of chronic respiratory failure, despite initially rudimentary equipment and limited understanding of what was actually happening, minute by minute when ventilation was applied. Modern ventilators, controlled by complex algorithms, and with integrated monitoring allow for sophisticated customisation of ventilatory support to an individual. However, if problems with ventilation are not recognised, and their significance understood, they cannot be fixed. Experience of monitoring during sleep from patients predominantly with sleep apnoea can be transferred and extended to patients receiving NIV. This article, the first in a series, explores the rationale for NIV and how its application to an individual patient can be monitored using simple tools and, when problems are identified, the causes can be identified using sophisticated interpretation of more detailed monitoring. This requires a detailed understanding of how different modes of ventilation work and some knowledge of the algorithms that control each machine. These themes are explored in this article and developed in subsequent articles in the series.
Harji D.P.,St Jamess Hospital
The British journal of surgery | Year: 2013
Locoregional recurrence of colonic cancer includes anastomotic recurrence, associated nodal masses, masses that involve the abdominal wall and pelvic masses. The aim of this study was to report the outcome of resection of such recurrences and to provide guidance on the management of this disease. Patients were identified from a prospectively maintained database. Data were obtained on demographics, surgical procedure, morbidity, histopathology and outcome. Univariable and multivariable analyses of factors influencing survival were performed using stepwise Cox logistic regression. Forty-two patients (21 men; median age 61 (range 41-82) years) underwent resection of recurrent colonic cancer between 2003 and 2011. The median interval between resection of the primary and recurrent colonic tumour was 37·5 (interquartile range 7-91) months. The recurrences developed at the previous anastomosis (9 patients), elsewhere within the abdominal cavity or wall (8) and as discrete masses within the pelvic cavity (25). Eighteen of 42 patients underwent resection of hepatic or pulmonary metastases at some stage after resection of the primary tumour. Median survival was 29 months after R0 resection and 26 months after R1 resection of the recurrent tumour (P = 0·226). The survival benefit depended on the location of the recurrence (median survival after resection of recurrent disease: anastomotic 33 months, pelvic 26 months, abdominal 19 months; P = 0·010). This study described a classification system, management algorithm and prognostic factors for recurrent colonic cancer. The distribution of disease influenced survival. Long-term survival was achieved, including a subset of patients with drop metastases and/or previous metastasectomy. © 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.