102 research outputs found
sj-jpg-1-crd-10.1177_14799731211070844 – Supplemental Material for Comparison of forehead and finger oximetry sensors during the six minute walk test
No full textSupplemental Material, sj-jpg-1-crd-10.1177_14799731211070844 for Comparison of forehead and finger oximetry sensors during the six minute walk test by Lucy Robertson, Rachel Lowry, Karl Sylvester, Helen Parfrey, Beverley Moseley, Karen Sheares and Katrina Oates in Chronic Respiratory Disease</p
sj-jpg-2-crd-10.1177_14799731211070844 – Supplemental Material for Comparison of forehead and finger oximetry sensors during the six minute walk test
No full textSupplemental Material, sj-jpg-2-crd-10.1177_14799731211070844 for Comparison of forehead and finger oximetry sensors during the six minute walk test by Lucy Robertson, Rachel Lowry, Karl Sylvester, Helen Parfrey, Beverley Moseley, Karen Sheares and Katrina Oates in Chronic Respiratory Disease</p
sj-jpg-3-crd-10.1177_14799731211070844 – Supplemental Material for Comparison of forehead and finger oximetry sensors during the six minute walk test
No full textSupplemental Material, sj-jpg-3-crd-10.1177_14799731211070844 for Comparison of forehead and finger oximetry sensors during the six minute walk test by Lucy Robertson, Rachel Lowry, Karl Sylvester, Helen Parfrey, Beverley Moseley, Karen Sheares and Katrina Oates in Chronic Respiratory Disease</p
sj-jpg-4-crd-10.1177_14799731211070844 – Supplemental Material for Comparison of forehead and finger oximetry sensors during the six minute walk test
No full textSupplemental Material, sj-jpg-4-crd-10.1177_14799731211070844 for Comparison of forehead and finger oximetry sensors during the six minute walk test by Lucy Robertson, Rachel Lowry, Karl Sylvester, Helen Parfrey, Beverley Moseley, Karen Sheares and Katrina Oates in Chronic Respiratory Disease</p
sj-pdf-5-crd-10.1177_14799731211070844 – Supplemental Material for Comparison of forehead and finger oximetry sensors during the six minute walk test
No full textSupplemental Material, sj-pdf-5-crd-10.1177_14799731211070844 for Comparison of forehead and finger oximetry sensors during the six minute walk test by Lucy Robertson, Rachel Lowry, Karl Sylvester, Helen Parfrey, Beverley Moseley, Karen Sheares and Katrina Oates in Chronic Respiratory Disease</p
Targeting a surface cavity of 1-antitrypsin to prevent conformational disease
No full textConformational diseases are caused by a structural rearrangement within a protein that results in aberrant intermolecular linkage and tissue deposition. This is typified by the polymers that form with the Z deficiency variant of alpha(1)-antitrypsin (Glu-342-->Lys). These polymers are retained within hepatocytes to form inclusions that are associated with hepatitis, cirrhosis, and hepatocellular carcinoma. We have assessed a surface hydrophobic cavity in alpha(1)-antitrypsin as a potential target for rational drug design in order to prevent polymer formation and the associated liver disease. The introduction of either Thr-114-->Phe or Gly-117-->Phe on strand 2 of beta-sheet A within this cavity significantly raised the melting temperature and retarded polymer formation. Conversely, Leu-100-->Phe on helix D accelerated polymer formation, but this effect was abrogated by the addition of Thr-114-->Phe. None of these mutations affected the inhibitory activity of alpha(1)-antitrypsin. The importance of these observations was underscored by the finding that the Thr-114-->Phe mutation reduced polymer formation and increased the secretion of Z alpha(1)-antitrypsin from a Xenopus oocyte expression system. Moreover cysteine mutants within the hydrophobic pocket were able to bind a range of fluorophores illustrating the accessibility of the cavity to external agents. These results demonstrate the importance of this cavity as a site for drug design to ameliorate polymerization and prevent the associated conformational disease
P9 nintedanib for the treatment of idiopathic pulmonary fibrosis – initial clinical experience in a UK cohort
No full textIntroduction and objectives: nintedanib (OFEV®) is the second drug licensed for the treatment of Idiopathic Pulmonary Fibrosis (IPF). Evidence from the INPULSIS study demonstrated that it reduced annual FVC decline by approximately 50%. Nintedanib has been available in the UK from October 2014 through the Individual Patient Supply Programme (IPSP); initially for those with FVC >50% predicted, latterly available for all with a diagnosis of IPF regardless of FVC. We present preliminary findings of clinical experience with nintedanib in routine UK clinical practice.Methods: a multi-centre, cohort review was undertaken across 6 NHS Trusts. Data were collected from clinical records of individuals receiving nintedanib for the treatment of IPF from October 2014 to July 2015.Results: 210 patients (161 male) had consented to nintedanib IPSP by July 2015. Mean age (±S. D.) at diagnosis was 70.0 ± 7.7 years. Reasons for starting nintedanib included ineligibility for pirfenidone (FVC >80% predicted: 67 (31.9%) and FVC Mean duration of treatment was 2.4 months (range 0 – 8 months) and 78 patients had completed 3-month follow up. Of these 14/78 patients (17.9%) had discontinued nintedanib due to diarrhoea (5 patients), other GI side effects (3), death/lung transplant (2/1), miscellaneous reasons (3). The commonest potential adverse drug reaction (ADR) was diarrhoea occurring in 21/78 (26.9%), which required a dose reduction in 11 patients. Other common ADRs included nausea 11/78 (14.1%), abdominal pain 11/78 (14.1%), decreased appetite 7/78 (9.0%), and weight loss 5/78 (6.4%).Conclusions: these data demonstrate that at 3 months follow up, Nintedanib is generally well tolerated when used in routine UK practice in patients with IPF across a wide range of FVC’s. The incidence of diarrhoea at 3 months is much lower than the 12 month reported rate in the INPULSIS study. Ongoing longitudinal follow up of this cohort will further inform our understanding of the use of nintedanib for the treatment of IPF
Safety and tolerability of nintedanib for the treatment of idiopathic pulmonary fibrosis in routine UK clinical practice
No full textIn IPF, commencement of antifibrotic therapy in patients with preserved lung volume may increase the duration of therapy http://ow.ly/4HeM30lFS67
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