Evaluation of oxidative stress and efficacy of antioxidant therapy in dogs with haemorrhagic gastroenteritis

The present study was conducted to evaluate the alterations in oxidative stress parameters in dogs suffering from haemorrhagic gastroenteritis (HGE). Dogs presented with vomiting and diarrhoea were screened and fifteen animals with signs suggestive of HGE were included in the study. The oxidative stress parameters, serummalondialdehyde (MDA) level, total antioxidant status (TAS) and plasma glutathione peroxidase (GSH-Px) activity were studied. The values were compared with the values from six apparently healthy dogs. A significant increase was noticed in the mean values of serum MDA and TAS of diseased animals at the time of presentation when compared to healthy animals whereas the activity of plasma GSH-Px was found to be lower than in healthy dogs. Supplementation with N-acetyl cysteine @ 70 mg/kg or five days was found effective in managing the oxidative injury in the affected animals

Applicability of RNA standards for evaluating RT-qPCR assays and platforms

The availability of diverse RT-qPCR assay formats and technologies hinder comparability of data between platforms. Reference standards to facilitate platform evaluation and comparability are needed. We have explored using universal RNA standards for comparing the performance of a novel qPCR platform (Fluidigm® BioMark™) against the widely used ABI 7900HT system. Our results show that such standards may form part of a toolkit to evaluate the key performance characteristics of platforms

Using equity premium survey data to estimate future wealth

We present the first systematic methods for combining different experts' responses to equity premium surveys. These techniques are based on the observation that the survey data are approximately gamma distributed. This distribution has convenient analytical properties that enable us to address three important problems that investment managers must face. First, we construct probability density functions for the future values of equity index tracker funds. Second, we calculate unbiased and minimum least square error estimators of the future value of these funds. Third, we derive optimal asset allocation weights between equities and the risk-free asset for risk-averse investors. Our analysis allows for both herding and biasedness in expert responses. We show that, unless investors are highly uncertain about expert biases or forecasts are very highly correlated, many investment decisions can be based solely on the mean of the survey data minus any expected bias. We also make recommendations for the design of future equity premium surveys

Clinical risk stratification of paediatric renal transplant recipients using C1q and C3d fixing of de novo donor-specific antibodies

Introduction: We have previously shown that children who developed de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) had greater decline in allograft function. We hypothesised that patients with complement-activating DSA would have poorer renal allograft outcomes. Methods: A total of 75 children developed DSA in the original study. The first positive DSA sample was subsequently tested for C1q and C3d fixing. The primary event was defined as 50% reduction from baseline estimated glomerular filtration rate and was analysed using the Kaplan–Meier estimator. Results: Of 65 patients tested, 32 (49%) and 23 (35%) tested positive for C1q and C3d fixing, respectively. Of the 32 C1q-positive (c1q+) patients, 13 (41%) did not show concomitant C3d fixing. The mean fluorescence intensity values of the original immunoglobulin G DSA correlated poorly with complement-fixing positivity (C1q: adjusted R2 0.072; C3d: adjusted R2 0.11; p < 0.05). C1q+ antibodies were associated with acute tubulitis [0.75 ± 0.18 (C1q+) vs. 0.25 ± 0.08 (C1q−) episodes per patient (mean ± standard error of the mean; p < 0.05] but not with worse long-term renal allograft dysfunction (median time to primary event 5.9 (C1q+) vs. 6.4 (C1q−) years; hazard ratio (HR) 0.74; 95% confidence ratio (CI) 0.30–1.81; p = 0.58]. C3d-positive (C3d+) antibodies were associated with positive C4d histological staining [47% (C3d+) vs. 20% (C3d−); p = 0.04] and with significantly worse long-term allograft dysfunction [median time to primary event: 5.6 (C3d+) vs. 6.5 (C3d−) years; HR 0.38; 95% CI 0.15–0.97; p = 0.04]. Conclusion: Assessment of C3d fixing as part of prospective HLA monitoring can potentially aid stratification of patients at the highest risk of long-term renal allograft dysfunction

UK pneumonectomy outcome study (UKPOS): a prospective observational study of pneumonectomy outcome

<p>Abstract</p> <p>Background</p> <p>In order to assess the short term risks of pneumonectomy for lung cancer in contemporary practice a one year prospective observational study of pneumonectomy outcome was made. Current UK practice for pneumonectomy was observed to note patient and treatment factors associated with major complications.</p> <p>Methods</p> <p>A multicentre, prospective, observational cohort study was performed. All 35 UK thoracic surgical centres were invited to submit data to the study. All adult patients undergoing pneumonectomy for lung cancer between 1 January and 31 December 2005 were included. Patients undergoing pleuropneumonectomy, extended pneumonectomy, completion pneumonectomy following previous lobectomy and pneumonectomy for benign disease, were excluded from the study.</p> <p>The main outcome measure was suffering a major complication. Major complications were defined as: death within 30 days of surgery; treated cardiac arrhythmia or hypotension; unplanned intensive care admission; further surgery or inotrope usage.</p> <p>Results</p> <p>312 pneumonectomies from 28 participating centres were entered. The major complication incidence was: 30-day mortality 5.4%; treated cardiac arrhythmia 19.9%; unplanned intensive care unit admission 9.3%; further surgery 4.8%; inotrope usage 3.5%. Age, American Society of Anesthesiologists physical status ≥ P3, pre-operative diffusing capacity for carbon monoxide (DLCO) and epidural analgesia were collectively the strongest risk factors for major complications. Major complications prolonged median hospital stay by 2 days.</p> <p>Conclusion</p> <p>The 30 day mortality rate was less than 8%, in agreement with the British Thoracic Society guidelines. Pneumonectomy was associated with a high rate of major complications. Age, ASA physical status, DLCO and epidural analgesia appeared collectively most associated with major complications.</p

Extracellular matrix defects in aneurysmal Fibulin-4 mice predispose to lung emphysema

Background: In this study we set out to investigate the clinically observed relationship between chronic obstructive pulmonary disease (COPD) and aortic aneurysms. We tested the hypothesis that an

A phase I, open-label, randomized crossover study to assess the effect of dosing of the MEK 1/2 inhibitor Selumetinib (AZD6244; ARRY-142866) in the presence and absence of food in patients with advanced solid tumors

&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; This Phase I study assessed whether food influences the rate and extent of selumetinib absorption in patients with advanced solid malignancies and determined the safety, tolerability, and pharmacokinetic (PK) profile of selumetinib and its active metabolite N-desmethyl-selumetinib in fed and fasted states.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; A single dose of 75 mg selumetinib was to be taken with food on Day 1 followed by a single dose of 75 mg after fasting for at least 10 h on Day 8, or vice versa, followed by twice daily dosing of 75 mg selumetinib from Day 10. Plasma concentrations and PK parameters were determined on Days 1 and 8. Patients could continue to receive selumetinib for as long as they benefitted from treatment.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; In total, 31 patients were randomized to receive selumetinib; 15 to fed/fasted sequence and 16 to fasted/fed sequence. Comprehensive PK sampling was performed on 11 and 10 patients, respectively. The geometric least-squares means of C&lt;sub&gt;max&lt;/sub&gt; and AUC for selumetinib were reduced by 62% (ratio 0.38 90% CI 0.29, 0.50) and 19% (ratio 0.81 90% CI 0.74, 0.88), respectively, under fed compared with fasting conditions. The rate of absorption (t&lt;sub&gt;max&lt;/sub&gt;) of selumetinib (fed) was delayed by approximately 2.5 h (median). The food effect was also observed for the active metabolite N-desmethyl-selumetinib. Selumetinib was well tolerated.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The presence of food decreased the extent of absorption of selumetinib. It is recommended that for further clinical studies, selumetinib be taken on an empty stomach. Selumetinib demonstrated an acceptable safety profile in the advanced cancer population.&lt;/p&gt