Cyclooxygenase-2 inhibition decreases primary and metastatic tumor burden in a murine model of orthotopic lung adenocarcinoma

AbstractObjectiveTo assess cyclooxygenase-2 inhibition on primary tumor and mediastinal metastases in a murine model of orthotopic lung adenocarcinoma.MethodsHuman lung adenocarcinoma cells (CRL5908, female nonsmoker with cyclooxygenase-2 expression by Western blot) were implanted under direct visualization through the parietal pleura in the upper lobe of the left lung (2 × 106 cells/animal) of SCID mice. Mice were randomly assigned to 2 groups, either untreated (n = 62) or celecoxib-treated (n = 60). Celecoxib, a selective cyclooxygenase-2 antagonist, was solubilized in the animals' drink (25 mg/kg per day). Mice were arbitrarily killed at 1, 2, 3, and 4 weeks. A blinded observer assessed primary tumor volume and metastatic disease grossly and histologically.ResultsGross metastatic lymph nodes were present at 3 weeks in none of 15 (0%) treated and 12 of 15 (80.0%) untreated animals (P < .0001). Mean primary tumor volumes at 3 weeks for treated mice were 7.9 ± 10.0 mm3 and for untreated mice were 533.1 ± 453.6 mm3 (mean ± SD, P < .0001). Gross metastatic lymph nodes were present at 4 weeks in 3 of 15 (20%) treated and 17 of 17 (100%) untreated animals (P < .0001). Mean primary tumor volumes at 4 weeks for treated mice were 37.1 ± 46.2 mm3 and for untreated mice were 809.6 ± 1226.4 mm3 (mean ± SD, P < .0001). Mean blood levels of celecoxib in treated mice were 236.8 ± 34.2 ng/mL (mean ± SD).ConclusionsCyclooxygenase-2 inhibition results in decreased primary and metastatic tumor burden in a murine model using human lung adenocarcinoma. Cyclooxygenase-2 inhibition has the potential to decrease tumor progression and metastases in patients with lung adenocarcinoma

A Rare Case of Bilateral Optic Neuritis and Guillain-Barré Syndrome Post Mycoplasma pneumoniae Infection

Neurological complications are the most commonly encountered extra-pulmonary manifestation of infection with Mycoplasma pneumoniae (M. pneumoniae). Here the authors report the case of a 39-year-old woman who was admitted with acute-onset bilateral visual loss coinciding with ascending numbness. Clinical examination, neurological imaging, and nerve conduction studies revealed a syndrome of bilateral optic neuritis and Guillain-Barré syndrome (GBS). Serological testing confirmed recent exposure to M. pneumoniae. The patient did not experience any clinical benefit with pulsed intravenous methylprednisolone but demonstrated marked clinical and radiological improvement following 5 days of plasma exchange. This report will explore the diagnostic and therapeutic approach to patients with neuro-ophthalmological and neurological complications of M. pneumoniae infection in addition to discussing previously encountered cases

Effect of increasing fruit and vegetable intake by dietary intervention on nutritional biomarkers and attitudes to dietary change : a randomised trial

This work was funded by The Scottish Government Rural and Environmental Science and Analytical Sciences Division (RESAS) and supported by the Rank Prize Funds.Peer reviewedPublisher PD

Perceptual grouping ability in Williams syndrome: Evidence for deviant patterns of performance

Williams syndrome (WS) is a rare genetic disorder. At a cognitive level, this population display poor visuo-spatial cognition when compared to verbal ability. Within the visuo-spatial domain, it is now accepted that individuals with WS are able to perceive both local and global aspects of an image, albeit at a low level. The present study examines the manner in which local elements are grouped into a global whole in WS. Fifteen individuals with WS and 15 typically developing controls, matched for non-verbal ability, were presented with a matrix of local elements and asked whether these elements were perceptually grouped horizontally or vertically. The WS group were at the same level as the control group when grouping by luminance, closure, and alignment. However, their ability to group by shape, orientation and proximity was significantly poorer than controls. This unusual profile of grouping abilities in WS suggests that these individuals do not form a global percept in a typical manner

Reciprocity as a foundation of financial economics

This paper argues that the subsistence of the fundamental theorem of contemporary financial mathematics is the ethical concept ‘reciprocity’. The argument is based on identifying an equivalence between the contemporary, and ostensibly ‘value neutral’, Fundamental Theory of Asset Pricing with theories of mathematical probability that emerged in the seventeenth century in the context of the ethical assessment of commercial contracts in a framework of Aristotelian ethics. This observation, the main claim of the paper, is justified on the basis of results from the Ultimatum Game and is analysed within a framework of Pragmatic philosophy. The analysis leads to the explanatory hypothesis that markets are centres of communicative action with reciprocity as a rule of discourse. The purpose of the paper is to reorientate financial economics to emphasise the objectives of cooperation and social cohesion and to this end, we offer specific policy advice

The Glasgow Coma Scale and Evidence-Informed Practice: a critical review of where we are and where we need to be

Aims and Objectives This critical review considers the evidence since the Glasgow Coma Scale (GCS) was first launched, reflecting on how that evidence has shaped practice. It illustrates the lack of clarity and consensus about the use of the tool in practice and draws upon existing evidence in order to determine the route to clarity for an evidence-informed approach to practice. Background The GCS has permeated and influenced practice for over 40 years, being well-established worldwide as the key tool for assessing level of consciousness. During this time, the tool has been scrutinised, evaluated, challenged and relaunched in a plethora of publications. This has led to an insight into the challenges, and to some extent the opportunities, in using the GCS in practice but has also resulted in a lack of clarity. Design This is a discursive paper that invites readers to explore and arrive at a more comprehensive understanding of the GCS in practice and is based on searches of Scopus, Web of Knowledge, PubMed, Science Direct and CINAHL databases. Results While the GCS has been rivalled by other tools in an attempt to improve upon it, a shift in practice to those tools has not occurred. The tool has withstood the test of time in this respect, indicating the need for further research into its use and a clear education strategy to standardise implementation in practice. Conclusion Further exploration is needed into the application of painful stimuli in using the GCS to assess level of consciousness. Additionally, a robust educational strategy is necessary to maximise consistency in its use in practice

Late Pleistocene sediments, landforms and events in Scotland: a review of the terrestrial stratigraphic record

Lithostratigraphical studies coupled with the development of new dating methods has led to significant progress in understanding the Late Pleistocene terrestrial record in Scotland. Systematic analysis and re-evaluation of key localities have provided new insights into the complexity of the event stratigraphy in some regions and the timing of Late Pleistocene environmental changes, but few additional critical sites have been described in the past 25 years. The terrestrial stratigraphic record remains important for understanding the timing, sequence and patterns of glaciation and deglaciation during the last glacial/interglacial cycle. Former interpretations of ice-free areas in peripheral areas during the Last Glacial Maximum (LGM) are inconsistent with current stratigraphic and dating evidence. Significant challenges remain to determine events and patterns of glaciation during the Early and Middle Devensian, particularly in the context of offshore evidence and ice sheet modelling that indicate significant build-up of ice throughout much of the period. The terrestrial evidence broadly supports recent reconstructions of a highly dynamic and climate-sensitive British–Irish Ice Sheet (BIIS), which apparently reached its greatest thickness in Scotland between 30 and 27ka, before the global LGM. A thick (relative to topography) integrated ice sheet reaching the shelf edge with a simple ice-divide structure was replaced after the LGM by a much thinner one comprising multiple dispersion centres and a more complex flow structure

A decade of living lobar lung transplantation: recipient outcomes

AbstractObjectiveLiving lobar lung transplantation was developed as a procedure for patients considered too ill to await cadaveric transplantation.MethodsOne hundred twenty-eight living lobar lung transplantations were performed in 123 patients between 1993 and 2003. Eighty-four patients were adults (age, 27 ± 7.7 years), and 39 were pediatric patients (age, 13.9 ± 2.9 years).ResultsThe primary indication for transplantation was cystic fibrosis (84%). At the time of transplantation, 67.5% of patients were hospitalized, and 17.9% were intubated. One-, 3-, and 5-year actuarial survival among living lobar recipients was 70%, 54%, and 45%, respectively. There was no difference in actuarial survival between adult and pediatric living lobar recipients (P = .65). There were 63 deaths among living lobar recipients, with infection being the predominant cause (53.4%), followed by obliterative bronchiolitis (12.7%) and primary graft dysfunction (7.9%). The overall incidence of acute rejection was 0.8 episodes per patient. Seventy-eight percent of rejection episodes were unilateral. Age, sex, indication, donor relationship, preoperative hospitalization status, use of preoperative steroids, and HLA-A, HLA-B, and HLA-DR typing did not influence survival. However, patients on ventilators preoperatively had significantly worse outcomes (odds ratio, 3.06, P = .03; Kaplan-Meier P = .002), and those undergoing retransplantation had an increased risk of death (odds ratio, 2.50).ConclusionThese results support the continued use of living lobar lung transplantation in patients deemed unable to await a cadaveric transplantation. We consider patients undergoing retransplantations and intubated patients to be at significantly high risk because of the poor outcomes in these populations