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Institution

St Bartholomew's Hospital

HealthcareLondon, United Kingdom
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.


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Journal ArticleDOI
TL;DR: There is a high relative risk of adhesion-related problems after open lower abdominal surgery and a correspondingly high workload associated with these readmissions, and the study provides sound justification for improved adhesion prevention strategies.
Abstract: PURPOSE: Postoperative adhesions are a significant problem after colorectal surgery. However, the basic epidemiology and clinical burden are unknown. The Surgical and Clinical Adhesions Research Study has investigated the scale of the problem in a population of 5 million. METHODS: Validated data from the Scottish National Health Service Medical Record Linkage Database were used to define a cohort of 12,584 patients undergoing open lower abdominal surgery in 1986. Readmissions for potential adhesion-related disease in the subsequent ten years were analyzed. The methodology was conservative in interpreting adhesion-related disease. RESULTS: In the study cohort 32.6 percent of patients were readmitted a mean of 2.2 times in the subsequent ten years for a potential adhesion-related problem. Although 25.4 percent of readmissions were in the first postoperative year, they continued steadily throughout the study period. After open lower abdominal surgery 7.3 percent (643) of readmissions (8,861) were directly related to adhesions. This varied according to operation site: colon (7.1 percent), rectum (8.8 percent), and small intestine (7.6 percent). The readmission rate was assessed to provide an indicator of relative risk of adhesion-related problems after initial surgery. The overall average rate of readmissions was 70.4 per 100 initial operations, with 5.1 directly related to adhesions. This rose to 116.4 and 116.5, respectively, after colonic or rectal surgery—with 8.2 and 10.3 directly related to adhesions. CONCLUSIONS: There is a high relative risk of adhesion-related problems after open lower abdominal surgery and a correspondingly high workload associated with these readmissions. This is influenced by the initial site of surgery, colon and rectum having both the greatest impact on workload and highest relative risk of directly adhesion-related problems. The study provides sound justification for improved adhesion prevention strategies.

343 citations

Journal ArticleDOI
TL;DR: The theory presented here suggests that chronic stress which activates the HPA will in certain susceptible people produce changes in central monoamines, and the high level of glucocorticoid receptors on such central neurons is postulated as mediating the alterations.
Abstract: Abnormalities in the hypothalamic-pituitary-adrenal axis (HPA) have been the most consistently demonstrated biological markers in depressive illness. Numerous other neuroendocrine disturbances have also been described, including blunted clonidine-induced growth hormone release and blunted fenfluramine-induced prolactin release. These disturbances are generally interpreted in terms of monoaminergic receptor dysfunction. The theory presented here suggests that chronic stress which activates the HPA will in certain susceptible people produce changes in central monoamines. The high level of glucocorticoid receptors on such central neurons is postulated as mediating the alterations. Thus monoamine abnormalities, rather than being a core aetiological feature of depression, are seen as secondary to HPA overdrive.

343 citations

Journal ArticleDOI
TL;DR: There is consensus that integrated treatment decisions should be made by a team including endocrinologists, surgeons, and radiation therapists in managing this complex metabolic disorder, reducing its comorbidities, and ultimately achieving favorable mortality outcomes.
Abstract: Treatment of acromegaly is determined by the availability of local neuroendocrine, imaging, and surgical expertise as well as patient access to costly evaluations and therapeutic choices, which may be unique for regions and countries. Nevertheless, controlled GH suppression should be optimized (37). In deciding on appropriate means to achieve biochemical control and relieve mass effects, the treating physician team should balance risk and benefits, and treatment contraindications and side-effects for each patient (2, 38). Factors to be considered include disease severity, tumor mass effect on central structures, tumor expression of somatostatin receptor subtypes, and potential for long-term pituitary damage, especially in younger reproductive-aged patients. In patients who have low GH levels and already have irreversible hypopituitarism, radiation therapy may be preferred because there is no further risk for this complication, although tumor resection often relieves compressive hypopituitarism. The depicted flowsheet recommends surgery as the first line therapy followed by medical therapy should surgery not be curative. In selected patients with unacceptable anesthetic risk, cardiovascular or pulmonary complications, and macroadenomas not impinging on the optic chiasm, primary SRL therapy may be offered (13, 39). If control is inadequately achieved with maximal doses of SRLs and added dopamine agonists, radiotherapy should be considered or no further action should be proposed, depending on clinical disease activity and degree of biochemical disease persistence. Reoperation or treatment with investigational GH receptor antagonists (25) should be considered for patients resistant to surgical, medical, and radiotherapeutic approaches (26). In conclusion, considering the potentially serious treatment adverse effects that limit their efficacy, there is consensus that integrated treatment decisions should be made by a team including endocrinologists, surgeons, and radiation therapists. The patient's choice of therapy should be based upon an informed understanding of the potential disadvantages of therapeutic approaches vs. their effectiveness in managing this complex metabolic disorder, reducing its comorbidities, and ultimately achieving favorable mortality outcomes.

342 citations

Journal ArticleDOI
TL;DR: The prospects for novel approaches in the prevention, diagnosis and treatment of malignant disease based on ASS1 pathophysiology and its rate‐limiting product, arginine are examined.
Abstract: Arginine, a semi-essential amino acid in humans, is critical for the growth of human cancers, particularly those marked by de novo chemoresistance and a poor clinical outcome. In addition to protein synthesis, arginine is involved in diverse aspects of tumour metabolism, including the synthesis of nitric oxide, polyamines, nucleotides, proline and glutamate. Tumoural downregulation of the enzyme argininosuccinate synthetase (ASS1), a recognised rate-limiting step in arginine synthesis, results in an intrinsic dependence on extracellular arginine due to an inability to synthesise arginine for growth. This dependence on extracellular arginine is known as arginine auxotrophy. Several tumours are arginine auxotrophic, due to variable loss of ASS1, including hepatocellular carcinoma, malignant melanoma, malignant pleural mesothelioma, prostate and renal cancer. Importantly, targeting extracellular arginine for degradation in the absence of ASS1 triggers apoptosis in arginine auxotrophs. Several phase I/II clinical trials of the arginine-lowering drug, pegylated arginine deiminase, have shown encouraging evidence of clinical benefit and low toxicity in patients with ASS1-negative tumours. In part, ASS1 loss is due to epigenetic silencing of the ASS1 promoter in various human cancer cell lines and tumours, and it is this silencing that confers arginine auxotrophy. In relapsed ovarian cancer, this is associated with platinum refractoriness. In contrast, several platinum sensitive tumours, including primary ovarian, stomach and colorectal cancer, are characterised by ASS1 overexpression, which is regulated by proinflammatory cytokines. This review examines the prospects for novel approaches in the prevention, diagnosis and treatment of malignant disease based on ASS1 pathophysiology and its rate-limiting product, arginine.

338 citations


Authors

Showing all 11065 results

NameH-indexPapersCitations
Philippe Froguel166820118816
Geoffrey Burnstock141148899525
Michael A. Kamm12463753606
David Scott124156182554
Csaba Szabó12395861791
Roger Williams122145572416
Derek M. Yellon12263854319
Walter F. Bodmer12157968679
John E. Deanfield12049761067
Paul Bebbington11958346341
William C. Sessa11738352208
Timothy G. Dinan11668960561
Bruce A.J. Ponder11640354796
Alexandra J. Lansky11463254445
Glyn Lewis11373449316
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20232
202216
2021390
2020354
2019307
2018257