St Bartholomew's Hospital

About: St Bartholomew's Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Cancer. The organization has 11054 authors who have published 13229 publications receiving 501102 citations. The organization is also known as: St. Bartholomew's Hospital & The Royal Hospital of St Bartholomew.

ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma

Abstract: The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pre-therapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.

The role of cAMP regulation in controlling inflammation

Abstract: In 1958, Sutherland and Rail identified adenosine 3', 5'-monophosphate (cAMP) as an intracellular second messenger of hepatic glycogenolysis [1]. Subsequently, cAMP was shown to act as second messenger for a variety of hormones, inflammatory mediators and cytokines, and has been shown to modulate models of immune and non-immune inflammation in vivo and a variety of cellular processes in vitro. Indeed, the current paper by Ottonello et al. is typical of research in this area. The authors show that in a population of adherent neutrophils, the oxidative burst induced by exposure to granulocyte-monocyte colony-stimulating factor is reduced by agents that elevate cAMP [2]. They speculate that therapeutic elevation of cAMP will result in reduced oxidative damage to tissues in neutrophildominated inflammatory reactions. Production of cAMP in leucocytes is stimulated by /3adrenergic catecholamines, histamine and the E series prostaglandins by a receptor-coupled activation of adenylate cyclase, an enzyme which catalyses the conversion of adenosine triphosphate to cAMP [3]. Rises in intracellular cAMP are usually transient, cAMP being rapidly broken down by phosphodiesterases (PDEs) to 5'AMP. A role for cAMP in a particular cell function can be inferred from the use of agents that activate adenylate cyclase (receptor-coupled activation or direct activation with agents such as cholera toxin [4] or forskolin [5]), duplication of the cell response with a\" hydrophobic (i.e. membrane-permeable) analogue of cAMP (e.g. dibutyryl cAMP), inhibition of PDEs with methylxanthines (e.g. theophylline [6]) or isoenzyme-specific agents (see below) and by assessing the effects of these various treatments on intracellular cAMP levels. At an infiammatory site, mast cells are stimulated to degranulate, causing release of vasoactive and other infiammatory mediators. Circulating leucocytes adhere to vascular endothelium and accumulate at the infiamed site under the direction of chemotactic factors. Phagocytic stimuli cause release of lysosomal enzymes and reactive oxygen species (ROS) from neutrophils, eosinophils and macrophages. Antigen recognition causes proliferation and differentiation of lymphocyte subsets. In vitro work has suggested that following cell stimulation, agents that elevate cAMP reduce: immunological release of histamine and leukotrienes from mast cells [7], monocyte [8] and neutrophil [9,10] locomotion, release of

GH feedback occurs through modulation of hypothalamic somatostatin under cholinergic control: studies with pyridostigmine and GHRH.

Abstract: We have studied the effect of increased cholinergic tone on the GH response to growth hormone-releasing hormone (GHRH) and on GH feedback, using pyridostigmine, an acetylcholinesterase inhibitor. In six healthy male adult volunteers 120 mg oral pyridostigmine increased basal GH secretion compared to placebo and augmented the GH response to 100 micrograms i.v. GHRH (1-29) NH2; the effect was more than the additive effect of pyridostigmine and GHRH when each was given alone. Pretreatment with 2 IU methionyl-hGH given i.v. abolished the serum GH response to GHRH given 3 h later, demonstrating a negative feedback loop of GH on the response to GHRH; this inhibited response to GHRH was restored in subjects given pyridostigmine as well as methionyl-hGH. The data demonstrate that enhanced cholinergic tone releases GH, augments the serum GH response to GHRH and unblocks the negative feedback effect of methionyl-hGH pretreatment on the GH response to GHRH. These results suggest that GH negative feedback effects on its own secretion occur predominantly through increased hypothalamic somatostatin secretion; this somatostatin secretion is under inhibitory cholinergic control.

Sudden Cardiac Death and Arrhythmias.

Abstract: Sudden cardiac death (SCD) and arrhythmia represent a major worldwide public health problem, accounting for 15-20 % of all deaths. Early resuscitation and defibrillation remains the key to survival, yet its implementation and the access to public defibrillators remains poor, resulting in overall poor survival to patients discharged from hospital. Novel approaches employing smart technology may provide the solution to this dilemma. Though the majority of cases are attributable to coronary artery disease, a thorough search for an underlying cause in cases where the diagnosis is unclear is necessary. This enables better management of arrhythmia recurrence and screening of family members. The majority of cases of SCD occur in patients who do not have traditional risk factors for arrhythmia. New and improved large scale screening tools are required to better predict risk in the wider population who represent the majority of cases of SCD.