Phenazepam: More information coming in from the cold

Phenazepam is a 1-4 benzodiazepine that was developed in 1975 in the former USSR this article updates what is known about the pharmacokinetics of Phenazepam

The accuracy of interpretation of emergency abdominal CT in adult patients who present with non-traumatic abdominal pain: results of a UK national audit.

: To evaluate major/minor discrepancy rates for provisional (initial) and addendum (supplementary senior review) emergency computed tomography (CT) reports in patients presenting with non-traumatic abdominal pain. : Ethical approval for this type of study is not required in the UK. All radiology departments with an approved lead for audit registered with the Royal College of Radiologists were invited to participate in this retrospective audit. The first 50 consecutive patients (25 surgical, 25 non-surgical) who underwent emergency abdominal CT for non-traumatic abdominal pain in 2013 were included. Statistical analyses were performed to identify organisational and report/patient-related variables that might be associated with major discrepancy. : One hundred and nine (58%) of 188 departments supplied data to the study with a total of 4,931 patients (2,568 surgical, 2,363 non-surgical). The audit standard for provisional report major discrepancy was achieved for registrars (target &lt;10%, achieved 4.6%), for on-site consultants (target &lt;5%, achieved 3.1%) and consultant addendum (target &lt;5%, achieved 2.9%). Off-site reporters failed to meet the standard target (&lt;5%, achieved 8.7% overall and 12.7% in surgical patients). The standard for patients coming to harm was not met in the surgical group (target &lt;1%, achieved 1.5%) and was narrowly missed overall (target &lt;1%, achieved 1%). : This study should be used to provide impetus to improve aspects of out-of-hours CT reporting. Clear benefits of CT interpretation/review by on-site and more senior (consultant) radiologists have been demonstrated.<br/

What is the role of a specialist regional mesothelioma multidisciplinary team meeting?:A service evaluation of one tertiary referral centre in the UK

BACKGROUND: Multidisciplinary team meetings are standard care for cancer in the UK and Europe. Professional bodies recommend that mesothelioma cases should be discussed at specialist multidisciplinary team meetings. However, no evidence exists exploring the role of the specialist mesothelioma multidisciplinary team meeting. OBJECTIVES: To evaluate the clinical activity of 1 specialist mesothelioma multidisciplinary team meeting and to determine how often a definitive diagnosis was made, whether the core requirements of the meeting were met and whether there was any associated benefit or detriment. DESIGN AND SETTING: A service evaluation using routinely collected data from 1 specialist mesothelioma multidisciplinary team meeting in a tertiary referral hospital in the South-West of England. PARTICIPANTS: All cases discussed between 1/1/2014 and 31/12/2015. OUTCOME MEASURES: The primary outcome measure was whether a definitive diagnosis was made. Secondary outcomes included whether treatment advice was offered, information on clinical trials provided or further investigations suggested. Additional benefits of the multidisciplinary team meeting and time taken from referral to outcome were also collected. RESULTS: A definitive diagnosis was reached in 171 of 210 cases discussed (81%). Mesothelioma was diagnosed in 153/210 (73%). Treatment advice was provided for 127 of 171 diagnostic cases (74%) and further investigations suggested for all 35 non-diagnostic cases. 86/210 cases (41%) were invited to participate in a trial, of whom 43/86 (50%) subsequently enrolled. Additional benefits included the avoidance of postmortem examination if the coroner was satisfied with the multidisciplinary team decision. The overall process from referral to outcome dispatch was <2 weeks in 75% of cases. CONCLUSIONS: This specialist mesothelioma multidisciplinary team meeting was effective at making diagnoses and providing recommendations for further investigations or treatment. The core requirements of a specialist mesothelioma multidisciplinary team meeting were met. The process was timely, with most outcomes returned within 2 weeks of referral

Dose de-escalation of intrapleural tissue plasminogen activator therapy for pleural infection. The alteplase dose assessment for Pleural infection Therapy project

Rationale: Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for intrapleural tPA. The first of several planned studies is presented here. Objectives: To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. Methods: Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open-label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C-reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. Results: We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22–58] to 16% [8–31] of hemithorax; P &lt; 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247–2,984] over 72 h of therapy; P &lt;  0.05) and a reduction in blood C-reactive protein (P &lt; 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent surgery. Three patients (4.9%) received blood transfusions for gradual pleural blood loss; none were hemodynamically compromised. Pain requiring escalation of analgesia affected 36% of patients; none required cessation of therapy. Conclusions: These pilot data suggest that a starting dose of 5 mg of tPA administered intrapleurally twice daily in combination with 5 mg of DNase for the treatment of pl

Zoledronate upregulates MMP-9 and -13 in rat vascular smooth muscle cells by inducing oxidative stress

WOS: 000374502300001PubMed ID: 27143852Background: Bisphosphonates, including zoledronate, target osteoclasts and are widely used in the treatment of osteoporosis and other bone resorption diseases, despite side effects that include damaging the stomach epithelium. Beneficial and adverse effects on other organ systems, including the cardiovascular system, have also been described and could impact on the use of bisphosphonates as therapeutic agents. Vascular smooth muscle cells (VSMCs) are major constituents of the normal vascular wall and have a key role in intimal thickening and atherosclerosis, in part by secreting MMPs that remodel the extracellular matrix and cleave cell surface proteins or secreted mediators. In this study, we investigated the effects of zoledronate on MMP expression. Methods: Rat VSMCs were stimulated by PDGF (50 ng/mL) plus TNF-alpha (10 ng/mL) or left unstimulated for a further 24 hours in serum-free medium. In other series of experiments, cells were pre-treated either with SC-514 (50 mu M) or with apocynin (20 nM) for 2 hours, then zoledronate (100 mu M) was added into 2% fetal calf serum containing medium for 24 hours. Results and discussion: Using isolated rat VSMCs in culture, zoledronate (100 mu M) increased MMP-9 and -13 mRNA expressions but inhibited MMP-2 expression. MMP-9 and MMP-13 up-regulation was shown to depend on the NF-kappa B pathway; and this was activated by zoledronate. Furthermore, zoledronate elevated the levels of reactive oxygen species detected by either dichlorofluorescein in isolated VSMCs or lucigenin enhanced chemiluminescence in rat aortic rings in vitro. Apocynin, an inhibitor of NADPH oxidase, reversed NF-kappa B activation and MMP-9 and MMP-13 up-regulation by zoledronate. Conclusion: We conclude that zoledronate increases MMP-9 and MMP-13 expressions in rat VSMCs dependent upon stimulation of the NF-kappa B pathway by reactive oxygen species. Effects on MMP expression may contribute to the pharmacologic profile of bisphosphonates.British Heart FoundationBritish Heart Foundation [CH95/001]; British Heart FoundationBritish Heart Foundation [RG/09/006/27918]The authors would like to thank Dr Goksel Gokce, Ege University Faculty of Pharmacy and Dr Steve White, University of Bristol for valuable help and expertise on oxidative stress measurements. MZA would also like to thank Prof Levent Ustunes for kind help and encouragement. This study was supported by the British Heart Foundation grant CH95/001

Corrosion of metal samples rapidly measured

Corrosion of a large number of metal samples that have been exposed to controlled environment is accurately and rapidly measured. Wire samples of the metal are embedded in clear plastic and sectioned for microexamination. Unexposed wire can be included in the matrix as a reference

Cluster Performance reconsidered: Structure, Linkages and Paths in the German Biotechnology Industry, 1996-2003

This paper addresses the evolution of biotechnology clusters in Germany between 1996 and 2003, paying particular attention to their respective composition in terms of venture capital, basic science institutions and biotechnology firms. Drawing upon the significance of co-location of "money and ideas", the literature stressing the importance of a cluster's openness and external linkages, and the path dependency debate, the paper aims to analyse how certain cluster characteristics correspond with its overall performance. After identifying different cluster types, we investigate their internal and external interconnectivity in comparative manner and draw on changes in cluster composition. Our results indicate that the structure, i.e. to which group the cluster belongs, and the openness towards external knowledge flows deliver merely unsystematic indications with regard to a cluster's overall success. Its ability to change composition towards a more balanced ratio of science and capital over time, on the other hand, turns out as a key explanatory factor. Hence, the dynamic perspective proves effective illuminating cluster growth and performance, where our explorative findings provide a promising avenue for further evolutionary research

Oxygen-hydrogen torch is a small-scale steam generator

Standard oxygen-hydrogen torch generates steam for corrosion-rate analysis of various metals. The steam is generated through local combustion inside a test chamber under constant temperature and pressure control