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.

Arrhythmogenic right ventricular cardiomyopathy: Evaluation of the current diagnostic criteria and differential diagnosis

Abstract: Domenico Corrado *, Peter J. van Tintelen, William J. McKenna, Richard N.W. Hauer, Aris Anastastakis, Angeliki Asimaki, Cristina Basso, Barbara Bauce, Corinna Brunckhorst, Chiara Bucciarelli-Ducci, Firat Duru, Perry Elliott, Robert M. Hamilton, Kristina H. Haugaa, Cynthia A. James, Daniel Judge, Mark S. Link, Francis E. Marchlinski, Andrea Mazzanti, Luisa Mestroni, Antonis Pantazis, Antonio Pelliccia, Martina Perazzolo Marra, Kalliopi Pilichou, Pyotr G.A. Platonov, Alexandros Protonotarios,

Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy.

Abstract: Bortezomib is a highly selective, reversible inhibitor of the 26S proteasome that is indicated for single-agent use in the treatment of patients with multiple myeloma who have received at least 2 prior therapies and are progressing on their most recent therapy. Clinical investigations have been completed or are under way to evaluate the safety and efficacy of bortezomib alone or in combination with chemotherapy in multiple myeloma, both at relapse and presentation, as well as in other cancer types. The antiproliferative, proapoptotic, antiangiogenic, and antitumor activities of bortezomib result from proteasome inhibition and depend on the altered degradation of a host of regulatory proteins. Exposure to bortezomib has been shown to stabilize p21, p27, and p53, as well as the proapoptotic Bid and Bax proteins, caveolin-1, and inhibitor κB-α, which prevents activation of nuclear factor κB-induced cell survival pathways. Bortezomib also promoted the activation of the proapoptotic c-Jun-NH2 terminal kinase, as well as the endoplasmic reticulum stress response. The anticancer effects of bortezomib as a single agent have been demonstrated in xenograft models of multiple myeloma, adult T-cell leukemia, lung, breast, prostate, pancreatic, head and neck, and colon cancer, and in melanoma. In these preclinical in vivo studies, bortezomib treatment resulted in decreased tumor growth, angiogenesis, and metastasis, as well as increased survival and tumor apoptosis. In several in vitro and/or in vivo cancer models, bortezomib has also been shown to enhance the antitumor properties of several antineoplastic treatments. Importantly, bortezomib was generally well tolerated and did not appear to produce additive toxicities when combined with other therapies in the dosing regimens used in these preclinical in vivo investigations. These findings provide a rationale for further clinical trials using bortezomib alone or in combination regimens with chemotherapy, radiation therapy, immunotherapy, or novel agents in patients with hematologic malignancies or solid tumors.

Langerhans cell histiocytosis in adults

Abstract: Langerhans cell histiocytosis in the adult is rare, but it is important to recognize its occurrence, as it must be differentiated from lymphoma, myeloma, and a variety of skin conditions and endocrinopathies. It has been reported in patients up to the ninth decade of life, and occurs equally in men and women. Local disease has a good prognosis, but associated diseases--particularly malignancy--may be the cause of death in some adults. The optimal treatment is not known. Coordinated investigation of the epidemiology and therapy of this disease is needed.

A single sleeping midnight cortisol has 100% sensitivity for the diagnosis of Cushing's syndrome

Abstract: OBJECTIVE The diagnosis of Cushing's syndrome remains a major challenge in clinical endocrinology. Various screening tests are commonly used to support a biochemical diagnosis in the context of clinical suspicion. The aim of this study was to compare the sensitivity in the diagnosis of Cushing's syndrome of a single in-patient sleeping midnight cortisol to a standard 48-hour in-patient low-dose dexamethasone suppression test (LDDST) during the same admission. DESIGN A retrospective analysis was performed on 150 patients investigated in our department between the years 1970 and 1994 with a confirmed diagnosis of Cushing's syndrome. PATIENTS One hundred and fifty patients with a diagnosis of Cushing's syndrome were analysed : 110 with Cushing's disease ; 12 with tumours with ectopic ACTH secretion ; 8 with ACTH dependent Cushing's syndrome of so far undetermined origin ; 17 with cortisol secreting adrenal tumours ; 3 with adrenocortical nodular hyperplasia. Twenty normal volunteers and nine patients with non-endocrine conditions were also investigated as controls. MEASUREMENTS Plasma cortisol was measured by radioimmunoassay (RIA) in the 122 patients presenting after 1980, and by fluorimetry prior to this date. RESULTS In all the control subjects the sleeping midnight cortisol was < 50 nmol/l, below the lowest standard of the routine in-house RIA. In every patient with Cushing's syndrome the sleeping midnight cortisol was detectable with a value greater than 50 nmol/l, with a range of 70-2000 nmol/l. In contrast, in three cases, all of whom had proven Cushing's disease on histology, there was uncharacteristic complete suppression of plasma cortisol to < 50 nmol/l following the LDDST. CONCLUSION In this series of 150 cases, a single in-patient sleeping midnight cortisol above 50 nmol/l had a 100% sensitivity for the diagnosis of Cushing's syndrome, clearly different from normal subjects. In contrast, the low-dose dexamethasone suppression test had a sensitivity of 98% even when the drug was administered as an in-patient. We recommend that a low-dose dexamethasone suppression test should not be used alone for confirmation of Cushing's syndrome since it may miss 2% of cases.