No abstract

This report should be referenced as follows:Thompson SG, Brown LC, Sweeting MJ, Bown MJ, Kim LG, Glover MJ, et al. Systematic review and meta-analysis of the growth and rupture rates of small abdominal aortic aneurysms: implications for surveillance intervals and their cost-effectiveness. Health Technol Assess 2013;17(41). Health Technology Assessment is indexed in MEDLINE, CINAHL, EMBASE, The Cochrane Library and the ISI Science Citation Index and is assessed for inclusion in the Database of Abstracts of Reviews of Effects. Health Technology Assessment is indexed and abstracted inThis journal is a member of and subscribes to the principles of the Committee on Publication Ethics (COPE) (www.publicationethics.org/).Editorial contact: nihredit@southampton.ac.ukThe full HTA archive is freely available to view online at www.journalslibrary.nihr.ac.uk/hta. Print-on-demand copies can be purchased from the report pages of the NIHR Journals Library website: www.journalslibrary.nihr.ac.uk Criteria for inclusion in the Health Technology Assessment journalReports are published in Health Technology Assessment (HTA) if (1) they have resulted from work for the HTA programme, and (2) they are of a sufficiently high scientific quality as assessed by the reviewers and editors.Reviews in Health Technology Assessment are termed 'systematic' when the account of the search appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others. HTA programmeThe HTA programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care.The journal is indexed in NHS Evidence via its abstracts included in MEDLINE and its Technology Assessment Reports inform National Institute for Health and Care Excellence (NICE) guidance. HTA research is also an important source of evidence for National Screening Committee (NSC) policy decisions.For more information about the HTA programme please visit the website: www.hta.ac.uk/ This reportThe research reported in this issue of the journal was funded by the HTA programme as project number 08/30/02. The contractual start date was in November 2009. The draft report began editorial review in July 2012 and was accepted for publication in November 2012. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors' report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.This report presents independent research...

Purified endothelial cells isolated from guinea pig hearts by enzymatic perfusion were grown in monolayer culture and used to test the ability of a variety of vasoactive agents to stimulate ATP release from these cells. Stimulation of endothelial cells with the peptide agonist bradykinin (1 nmol/L), acetylcholine (1 mumol/L), serotonin (1 mumol/L), or adenosine 5'-diphosphate (10 mumol/L) resulted in the rapid appearance of ATP in the incubation medium determined with the firefly luciferase assay for ATP. Addition of antagonists for muscarinic (atropine, 0.1 mumol/L) and purinergic (suramin, 100 mumol/L; reactive blue-2, 100 mumol/L) receptors suggested that ATP release from these cells was receptor-mediated. Bradykinin-induced release of ATP was rapid (peak < 30 seconds at 3 nmol/L bradykinin), dose-dependent (EC50, 0.18 nmol/L), and diminished with repeated administration of agonist. Desensitization to bradykinin also affected the ability of acetylcholine to induce release and was reversible when cells were returned to growth conditions for short periods. Measurement of released adenyl purines as their fluorescent N6-ethenopurine derivatives by high-performance liquid chromatography revealed the origin of the purine released to be ATP and confirmed its rapid dephosphorylation. Addition of the purine nucleotide analogues 2-methylthio-ATP (2-methyl-S-ATP), ADP, and beta gamma-methylene ATP to endothelial cell cultures resulted in a dose-dependent increase in the appearance of ATP measured in the medium bathing the cells at 30 seconds, suggesting the presence of ATP-induced ATP release.(ABSTRACT TRUNCATED AT 250 WORDS)

How to obtain copies of this and other HTA programme reports An electronic version of this title, in Adobe Acrobat format, is available for downloading free of charge for personal use from the HTA website (www.hta.ac.uk). A fully searchable DVD is also available (see below).Printed copies of HTA journal series issues cost £20 each (post and packing free in the UK) to both public and private sector purchasers from our despatch agents.Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is £2 per issue and for the rest of the world £3 per issue. How to order:-fax (with credit card details) -post (with credit card details or cheque) -phone during office hours (credit card only).Additionally the HTA website allows you to either print out your order or download a blank order form. Contact details are as follows:Synergie UK (HTA Department) Digital House, The Loddon Centre Wade Road Basingstoke Hants RG24 8QW Email: orders@hta.ac.uk Tel: 0845 812 4000 -ask for 'HTA Payment Services' (out-of-hours answer-phone service) Fax: 0845 812 4001 -put 'HTA Order' on the fax header Payment methods Paying by chequeIf you pay by cheque, the cheque must be in pounds sterling, made payable to University of Southampton and drawn on a bank with a UK address.Paying by credit card You can order using your credit card by phone, fax or post. SubscriptionsNHS libraries can subscribe free of charge. Public libraries can subscribe at a reduced cost of £100 for each volume (normally comprising 40-50 titles). The commercial subscription rate is £400 per volume (addresses within the UK) and £600 per volume (addresses outside the UK). Please see our website for details. Subscriptions can be purchased only for the current or forthcoming volume.How do I get a copy of HTA on DVD?Please use the form on the HTA website (www.hta.ac.uk/htacd/index.shtml). HTA on DVD is currently free of charge worldwide.The website also provides information about the HTA programme and lists the membership of the various committees. HTA NIHR Health Technology Assessment programmeThe Health Technology Assessment (HTA) programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care. The research findings from the HTA programme directly influence decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that they form a key component of the 'National Knowledge Service' . The HTA programme is needs led in that it fills gaps in the evidence needed by the NHS. There are three routes to the start of project...

Cardiac alpha-adrenergic receptors mediate cellular responses to norepinephrine through an undefined series of molecular events. We examined the possibility that phosphoinositide hydrolysis was stimulated through alpha-adrenergic receptors in cardiomyocytes purified from adult rat ventricle. Phosphoinositide stores were labeled with [3H]inositol, and [3H]inositol phosphate formation was assessed after the addition of lithium chloride and norepinephrine. Norepinephrine increased the accumulation of [3H]inositol phosphate by approximately 5-fold, giving a maximal response at approximately 30 microM and a half-maximal response at approximately 1 microM. There was a significant increase in [3H]inositol phosphate formation in response to norepinephrine at 5 minutes, and the response was linear over 40 minutes. Norepinephrine-stimulated [3H]inositol phosphate formation was not blocked by propranolol (1 microM) or yohimbine (0.1 microM) but was completely antagonized by the alpha 1-selective antagonist prazosin (0.1 microM). Muscarinic cholinergic receptor activation by carbachol also stimulated [3H]inositol phosphate formation in rat ventricular myocytes. The maximal effect of carbachol (approximately 2-fold) was always less than that of norepinephrine. The combined effects of norepinephrine and carbachol were additive, suggesting that the two hormones do not share a common rate-limiting step. Removal of extracellular calcium and addition of ethylene glycol bis(beta-amino ether)-N,N'-tetraacetic acid, attenuated, but did not abolish, norepinephrine- or carbachol-stimulated [3H]inositol phosphate formation. Neither the calcium ionophore A23187 nor the calcium channel blockers verapamil and nifedipine had any effect on basal or hormone-stimulated [3H]inositol phosphate formation. We suggest that some of the physiological and metabolic effects of adrenergic and cholinergic stimulation on the rat myocardium are secondary to receptor-mediated hydrolysis of phosphoinositides.

The Nucleotide Axis Hypothesis, defined and supported herein, proposes that ATP stimulates the release of vasoactive mediators from endothelium, including ATP itself. Here, we show rapid endothelium-dependent, agonist-stimulated ATP elaboration in coronary vessels of guinea pigs. Measurement of extracellular ADP metabolism in intact vessels results in the time- and substrate-dependent formation of ATP in the coronary perfusate in amounts greater than can be accounted for by release from endothelium alone. ATP formation by endothelial cells is saturable (K(M) = 38.5 micromol/l, where K(M) is substrate concentration at which rate is half-maximal.) and trypsin-sensitive, membranes from [gamma-(32)P]ATP-labeled cells support ADP-dependent transphosphorylation by a 20-kDa protein, Western blots reveal the presence of a nucleoside diphosphate kinase (NDPK) of approximately 20 kDa in endothelial membranes, and analysis of NDPK antibody binding by flow cytometry is consistent with the presence of an ecto-NDPK on cardiac endothelial cells. Sequencing of the endothelial cell ecto-NDPK reveals a predicted amino acid sequence with 85% identity to human Nm23-H1 and consistent with a protein whose properties may confer membrane association as well as sites of regulation of activity. Our data underscore the potential importance of a nucleotide axis in cardiac blood vessels.

EVAR is unlikely to be cost-effective on the basis of existing devices, costs and evidence, but there remains considerable uncertainty.

MDA-MB-435S human breast cancer cells (435S) secrete nucleoside diphosphate kinase (NDPK) that supports metastases and is inhibited by epigallocatechin gallate (EGCG) and ellagic acid (EA). We hypothesise that 435S cell-secreted NDPK-B supports tumour formation by modulating ATP levels locally to activate endothelial cell (EC) P2Y receptor-mediated angiogenesis. Epigallocatechin gallate (IC 50 ¼ 8-10 mM) and EA (IC 50 ¼ 2-3 mM) suppressed 435S cell growth, but had less effect on human CD31 þ EC growth. Epigallocatechin gallate (IC 50 ¼ 11 mM) and EA (IC 50 ¼ 1 mM) also prevented CD31 þ EC tubulogenesis on Matrigelt. 435S cellconditioned media induced tubulogenesis in a cell number, time, and nucleotide-dependent manner. Ellagic acid (1 mM), but not equimolar EGCG, reduced cell number-dependent angiogenesis. P2Y 1 receptor activation by NDPK-generated nucleotide (100 mM ATP) or by 10 mM 2-methyl-thio-ATP (2MS-ATP) promoted tubulogenesis on collagen and was blocked by the P2Y 1 antagonist MRS2179 (10 mM). Physiological amounts of purified as well as 435S cell-secreted NDPK also promoted angiogenesis that was attenuated by NDPK depletion or 10 mM MRS2179, indicating a P2Y 1 receptor-mediated pathway. These results support the notion that secreted NDPK mediates angiogenesis via P2Y receptor signalling and suggests that novel inhibitors of NDPK may be useful as therapeutics.