tbuckley/cabot-search huggingface dataset:
Alitretinoin abrogates innate inflammation in palmoplantar pustular psoriasis
Authors: N. Irla, A.A. Navarini, N. Yawalkar
Journal: British Journal of Dermatology (2012)

Background Palmoplantar pustular psoriasis is often recalcitrant to therapy. Here we evaluated the therapeutic effect of alitretinoin in patients with recalcitrant palmoplantar pustular psoriasis and investigated subsequent immunopathological alterations. Methods Seven patients with palmoplantar pustular psoriasis were treated with oral alitretinoin 30 mg once daily for 12 weeks. Efficacy was assessed by palmoplantar pustular psoriasis area and severity index (PPPASI), visual analogue scales (VAS) on intensity of pain and pruritus and an overall patient assessment. Immunohistochemical staining for neutrophil elastase, CD3, CD4, CD8, CD1a CD11c, CD303,CD68, CD69, CD208 and HLA‐DR was on lesional skin biopsies obtained before and after 12 weeks of treatment. Results PPPASI and VAS for pruritus and pain decreased significantly after 12 weeks of treatment with alitretinoin. The overall patient assessment ranged from 60% to 90% clinical improvement. In correlation with clinical improvement a significant reduction, particularly of neutrophils, macrophages and dendritic cells, was also observed in the skin sections. Alitretinoin was well tolerated except for headache during the first month of treatment in two patients. Limitations of the study are a missing control group and the concomitant usage of topical therapy. Discussion Our findings suggest that alitretinoin may represent a new and promising therapy for recalcitrant palmo‐plantar psoriasis and warrants further controlled studies to confirm efficacy and safety of alitretinoin in this disease.
Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study
Authors: Dirk Vlasselaers, Ilse Milants, Lars Desmet, Pieter J Wouters, Ilse Vanhorebeek, Ingeborg van den Heuvel, Dieter Mesotten, Michael P Casaer, Geert Meyfroidt, Catherine Ingels, Jan Muller, Sophie Van Cromphaut, Miet Schetz, Greet Van den Berghe
Journal: The Lancet (2009)
A reliable and safe gastrotomy closure technique assessed in a porcine survival model pilot study: success of the Queen’s closure
Authors: L. Hookey, B. Bielawska, A. Samis, D. Jalink, R. Ellis, V. Khokhotva, D. Hurlbut, D. Mercer
Journal: Endoscopy (2009)

Background and study aims: The evolution of NOTES to clinical implementation has been hampered by lack of a reliable, safe, and easy-to-implement technique for closure of the opening created in accessing the peritoneum. The Queen's closure uses a combination of endoscopic clips and loop devices to seal such defects in the stomach wall. This study aimed to assess the Queen's closure in a porcine survival model.
Quantification of Effects of Global Ischemia on Dynamics of Ventricular Fibrillation in Isolated Rabbit Heart
Authors: Ravi Mandapati, Yukio Asano, William T. Baxter, Richard Gray, Jorge Davidenko, José Jalife
Journal: Circulation (1998)

Ventricular fibrillation (VF) leads to global ischemia of the heart. After 1 to 2 minutes of onset, the VF rate decreases and appears more organized. The objectives of this study were to determine the effects of no-flow global ischemia on nonlinear wave dynamics and establish the mechanism of ischemia-induced slowing of the VF rate.Activation patterns of VF in the Langendorff-perfused rabbit heart were studied with the use of 2 protocols: (1) 15 minutes of no-flow global ischemia followed by reperfusion (n=7) and (2) decreased excitability induced by perfusion with 5 micromol/L of tetrodotoxin (TTX) followed by washout (n=3). Video imaging ( approximately 7500 pixels per frame; 240 frames per second) with a voltage-sensitive dye, ECG, and signal processing (fast Fourier transform) were used for analysis. The dominant frequency of VF decreased from 13.5+/-1.3 during control to 9.3+/-1.4 Hz at 5 minutes of global ischemia (P<0.02). The dominant frequency decreased from 13.9+/-1.1 during control to 7.0+/-0.3 Hz at 2 minutes of TTX infusion (P<0.001). The rotation period of rotors on the epicardial surface (n=27) strongly correlated with the inverse dominant frequency of the corresponding episode of VF (R2=0. 93). The core area, measured for 27 transiently appearing rotors, was 5.3+/-0.7 mm2 during control. A remarkable increase in core area was observed both during global ischemia (13.6+/-1.7 mm2; P<0.001) and TTX perfusion (16.8+/-3.6 mm2; P<0.001). Density of wave fronts decreased during both global ischemia (P<0.002) and TTX perfusion (P<0.002) compared with control.This study suggests that rotating spiral waves are most likely the underlying mechanism of VF and contribute to its frequency content. Ischemia-induced decrease in the VF rate results from an increase in the rotation period of spiral waves that occurs secondary to an increase in their core area. Remarkably, similar findings in the TTX protocol suggest that reduced excitability during ischemia is an important underlying mechanism for the changes seen.
Angiotensin II–Mediated Oxidative DNA Damage Accelerates Cellular Senescence in Cultured Human Vascular Smooth Muscle Cells via Telomere-Dependent and Independent Pathways
Authors: Karl E. Herbert, Yogita Mistry, Richard Hastings, Toryn Poolman, Laura Niklason, Bryan Williams
Journal: Circulation Research (2007)

Angiotensin II (Ang II) induces reactive oxygen species (ROS) production by human vascular smooth muscle cells (hVSMCs). ROS have been implicated in the development of both acute stress-induced premature senescence (SIPS) and chronic replicative senescence. Global oxidative DNA damage triggers SIPS and telomere DNA damage accelerates replicative senescence, both mediated via p53. This study tests the hypothesis that DNA is an important target for Ang II–induced ROS leading to senescence via telomere-dependent and independent pathways. DNA damage was quantified using the Comet assay, telomere DNA length by Southern blotting and hVSMC senescence by senescence-associated β-galactosidase staining. Exposure to Ang II increased DNA damage in hVSMCs within 4 hours. Inhibition by an AT 1 receptor antagonist (losartan metabolite: E3174) or catalase, confirmed that Ang II–induced DNA damage was AT 1 receptor-mediated, via the induction of ROS. Acute exposure to Ang II resulted in SIPS within 24 hours that was prevented by coincubation with E3174 or catalase. SIPS was associated with increased p53 expression but was not dependent on telomere attrition because overexpression of human telomerase did not prevent Ang II–induced SIPS. Exposure to Ang II over several population doublings accelerated the rate of telomere attrition (by &gt;2-fold) and induced premature replicative senescence of hVSMCs—an effect that was also attenuated by E3174 or catalase. These data demonstrate that Ang II–induced ROS-mediated DNA damage results in accelerated biological aging of hVSMCs via 2 mechanisms: (1) Acute SIPS, which is telomere independent, and (2) accelerated replicative senescence which is associated with accelerated telomere attrition.
Unrelated donor bone marrow transplantation for thalassemia: the effect of extended haplotypes
Authors: Giorgio La Nasa, Claudio Giardini, Francesca Argiolu, Franco Locatelli, Marcella Arras, Piero De Stefano, Antonio Ledda, Antonella Pizzati, Maria A. Sanna, Adriana Vacca, Guido Lucarelli, Licinio Contu
Journal: Blood (2002)
Decoy Receptor 2 (<i>DcR2</i>) Is a p53 Target Gene and Regulates Chemosensitivity
Authors: Xiangguo Liu, Ping Yue, Fadlo R. Khuri, Shi-Yong Sun
Journal: Cancer Research (2005)

Abstract Decoy receptor 2 (DcR2) is one of the tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptors and suppresses TRAIL-induced apoptosis. Its expression, like the other three TRAIL receptors (i.e., DR4, DR5, and DcR1), is regulated by p53. Here, we report that DcR2 is a p53 target gene and regulates chemosensitivity. In this study, we identified a p53-binding site (p53BS) in the first intron of the DcR2 gene. This p53BS is almost identical to the ones found in the first introns of other three TRAIL receptor genes. By a chromatin immunoprecipitation assay, we detected that the p53 protein bound to the DcR2 p53BS in intact cells. Subcloning of the DcR2 p53BS into a luciferase reporter vector driven by a SV40 promoter exhibited enhanced luciferase activity when transiently cotransfected with a wild-type (wt) p53 expression vector in p53-null cell lines or stimulated with DNA-damaging agents in cell lines having wt p53. Moreover, when the DcR2 p53BS, together with its own corresponding promoter regions, was subcloned into a basic luciferase vector without a promoter element, its transcriptional activities were strikingly increased by cotransfection of the wt p53 gene. However, when this p53BS was deleted from the construct, wt p53 failed to transactivate this reporter construct. Collectively, we conclude that p53 directly regulates the DcR2 gene expression via an intronic p53BS. In addition, overexpression of DcR2 conferred resistance to TRAIL-mediated apoptosis and attenuated cell response to DNA-damaging agents, whereas silencing of DcR2 expression enhanced chemotherapeutic agent–induced apoptosis. These results suggest that DcR2 regulates chemosensitivity.
Steroids and oral disease
Authors: THOMAS LEHNER
Journal: British Journal of Dermatology (1976)

Journal Article Steroids and oral disease Get access THOMAS LEHNER THOMAS LEHNER Department of Oral Immunology and Microbiology, Guy's Hospital, London, SE1 9RT Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 94, Issue s12, 1 March 1976, Pages 59–60, https://doi.org/10.1111/j.1365-2133.1976.tb02270.x Published: 01 March 1976
GPs and hospitals do not communicate adequately about patients' medicines
Authors: A. O'Dowd
Journal: BMJ (2009)

A failure by GPs and hospital doctors to share information about patients’ medicines could be harming patients, a report from the Care Quality Commission, the independent regulator of the English NHS, says.

The report, published on October 27 , says that the NHS must do more to prevent patients coming to harm from the medicines they take after discharge from hospital. 

Sharing of vital information when people move between services has to improve, says the report, for which the commission visited 12 primary care trusts (PCTs) and surveyed 280 of their general practices.

Incidents involving drugs, such as …
Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and mice
Authors: R.S. Surwit, M.N. Feinglos, J. Rodin, A. Sutherland, A.E. Petro, E.C. Opara, C.M. Kuhn, M. Rebuffe-Scrive
Journal: Metabolism (1995)

We have previously demonstrated that the C57BL/6J (B/6J) mouse will develop severe obesity, hyperglycemia, and hyperinsulinemia if weaned onto a high.fat,high-sucrose (HH) diet.In the present study, we compared the effects of fat and sucrose separately and in combination on diabetes-and obesity-prone B/6J and diabetes-and obesity-resistant A/J mice.After 4 months, the feed efficiency ([FE] weight gained divided by calories consumed) did not differ across diets in A/J mice, but B/6J mice showed a significantly increased FE for fat.That is, B/6J mice gained more weight on high-fat diets without consuming more calories than A/J mice.The increase in FE was related to adipocyte hyperplasia in B/6J mice on high-fat diets.Fat-induced obesity in B/6J mice was unrelated to adrenal cortical activity.In the absence of fat, sucrose produced a decreased in FE in both strains.Animals fed a low-fat, high-sucrose (LH) diet were actually leaner than animals fed a high-complexcarbohydrate diet.Fat was also found to be the critical stimulus for hyperglycemia and hyperinsulinemia in B/6J mice.In the absence of fat, sucrose had no effect on plasma glucose or insulin.These data clearly show that across these two strains of mice, genetic differences in the metabolic response to fat are more important in the development of obesity and diabetes than the increased caloric content of a high-fat diet.
6-minute walk distance as a predictor of outcome in idiopathic pulmonary fibrosis
Authors: Roland M. du Bois
Journal: European Respiratory Journal (2014)

From the authors: 

We thank M. Mura for reminding us of the study published in the European Respiratory Journal ( ERJ ) in 2012 that confirmed the increasing importance of the 6-min walk test (6MWT) in the evaluation and prediction of outcome in patients suffering from idiopathic pulmonary fibrosis (IPF) [1]. In this prospective study by Mura et al. [1], of factors that predicted survival in 70 patients with newly diagnosed IPF, the major 6MWT findings were that the 6-min walk distance (6MWD) % predicted, but not 6MWD defined as metres walked, was independently associated with 3-year survival, and …
CD40 engagement enhances eosinophil survival through induction of cellular inhibitor of apoptosis protein 2 expression: Possible involvement in allergic inflammation
Authors: Fabrice Bureau, Grégory Seumois, Fabrice Jaspar, Alain Vanderplasschen, Bruno Detry, Paul-Pierre Pastoret, Renaud Louis, Pierre Lekeux
Journal: Journal of Allergy and Clinical Immunology (2002)
Metastatic Renal Cell Carcinoma Treated with Sunitinib: Early Evaluation of Treatment Response Using Dynamic Contrast-Enhanced Ultrasonography
Authors: Nathalie Lassau, Serge Koscielny, Laurence Albiges, Linda Chami, Baya Benatsou, Mohamed Chebil, Alain Roche, Bernard J. Escudier
Journal: Clinical Cancer Research (2010)

To determine the utility of dynamic contrast-enhanced ultrasonography (DCE-US) as a prognostic tool for metastatic renal cell carcinoma patients receiving sunitinib and to identify DCE-US parameters that correlate with early treatment response.Thirty-eight patients received 50 mg/d sunitinib on schedule 4/2 (4 weeks on followed by 2 weeks off treatment). After two cycles, response evaluation criteria in solid tumors were used to classify patients as responders or nonresponders. DCE-US evaluations were done before treatment and at day 15; variations between days 0 and 15 were calculated for seven DCE-US functional parameters and were compared for responders and nonresponders. The correlation between DCE-US parameters and disease-free survival (DFS) and overall survival (OS) was assessed.The ratio between DCE-US examinations at baseline and day 15 significantly correlated with response in five of the seven DCE-US parameters. Two DCE-US parameters (time to peak intensity and slope of the wash-in) were significantly associated with DFS; time to peak intensity was also significantly associated with OS.DCE-US is a useful tool for predicting the early efficacy of sunitinib in metastatic renal cell carcinoma patients. Robust correlations were observed between functional parameters and classic assessments, including DFS and OS.
Chronic Kidney Disease, Cardiovascular Risk, and Response to Angiotensin-Converting Enzyme Inhibition After Myocardial Infarction
Authors: Mariya P. Tokmakova, Hicham Skali, Satish Kenchaiah, Eugene Braunwald, Jean L. Rouleau, Milton Packer, Glenn M. Chertow, Lemuel A. Moyé, Marc A. Pfeffer, Scott D. Solomon
Journal: Circulation (2004)

Persons with end-stage renal disease and those with lesser degrees of chronic kidney disease (CKD) have an increased risk of death after myocardial infarction (MI) that is not fully explained by associated comorbidities. Future cardiovascular event rates and the relative response to therapy in persons with mild to moderate CKD are not well characterized.We calculated the estimated glomerular filtration rate (eGFR) using the 4-variable Modification of Diet in Renal Disease method in 2183 Survival And Ventricular Enlargement (SAVE) trial subjects. SAVE randomized post-MI subjects (3 to 16 days after MI) with left ventricular ejection fraction < or =40% and serum creatinine <2.5 mg/dL to captopril or placebo. Cox proportional hazards models were used to evaluate the relative hazard rates for death and cardiovascular events associated with reduced eGFR. Subjects with reduced eGFR were older and had more extensive comorbidities. The multivariable adjusted risk ratio for total mortality associated with reduced eGFR from 60 to 74, 45 to 59, and <45 mL x min(-1) x 1.73 m(-2) (compared with eGFR > or =75 mL x min(-1) x 1.73 m(-2)) was 1.11 (0.86 to 1.42), 1.24 (0.96 to 1.60) and 1.81 (1.32 to 2.48), respectively (P for trend =0.001). Similar adjusted trends were present for CV mortality (P=0.001), recurrent MI (P=0.017), and the combined CV mortality and morbidity outcome (P=0.002). The absolute benefit of captopril tended to be greater in subjects with CKD: 12.4 versus 5.5 CV events prevented per 100 subjects with (n=719) and without (n=1464) CKD, respectively.CKD was associated with a heightened risk for all major CV events after MI, particularly among subjects with an estimated glomerular filtration rate <45 mL x min(-1) x 1.73 m(-2). Randomization to captopril resulted in a reduction of CV events irrespective of baseline kidney function.
Anaemia and survival in COPD patients with acute hypercapnic respiratory failure
Authors: Gemma Probert, Helmy Haja Mydin, Stephen Murphy
Journal: European Respiratory Journal (2012)

Background 

Previous studies have shown a relationship between anaemia and survival in COPD but the aetiology and natural history remains unclear.

Aim 

To determine the temporal relationship between anaemia, nutritional status, co-morbidity and survival in severe COPD.

Methods 

Patients with COPD and acute hypercapnic respiratory failure treated with non-invasive ventilation were included in the study. Data collected: Charlson co-morbidity index (CCI), GOLD stage, BMI, albumin, haemoglobin (Hb) at intervals up to 2 years prior to and after index admission, haematinics, and CRP. The temporal change in prevalence of anaemia and relationship with other factors was determined. Impact on survival was assessed by Cox's regression analysis.

Results 

65 patients mean (SD) age 71 (10.5) years, GOLD stage: IV 63%, III 21%, II 19%. During interval of 6-24 months prior to admission mean (SD) Hb fell from 13.3 (1.7) g/dl to 12.6 (2.0) g/dl; p=0.03. The fall in Hb was greatest in those who died: 0.88 (1.19) v 0.18 (0.88) g/dl p=0.013. Anaemia prevalence increased from 20% to 43% OR 3.0 (95% CI 1.29-7.14), and was greatest in GOLD stage IV disease: 59% v 17.4% OR 6.8 (1.72-29.4) and if age-adjusted CCI ≥4: 53.8% v 27% OR 3.1 (1.08-9.2). There was no association between anaemia and BMI, albumin or CRP. In-patient death was associated with a lower Hb (11.5 (1.73) v 13.30 (1.97) p<0.001) and haematocrit (37.1(5.0) v 41.6 (6.0) p<0.005). Survival was worse if anaemic: median (IQ range) 12 (1-674) v 475 (63-720) days, HR 3.15 (1.65-6.0) p=0.0002.

Conclusion 

Anaemia is common in severe COPD, often unrecognised and rarely investigated. Anaemia increases with disease progression and is associated with shortened life expectancy.
Quantifying the functional rehabilitation of injured football players
Authors: C W Fuller, J Walker
Journal: British Journal of Sports Medicine (2006)

Objective: To determine whether quantified, auditable records of functional rehabilitation can be generated using subjective assessments of players’ performance in fitness tests routinely used in professional football. Method: Ten sequential test elements grouped into three phases (fitness, ball and match skills, match pace football) were used to monitor players’ functional recovery from injury. Physiotherapists subjectively assessed players’ performance in each test element using a six point subjective rating scale. Satisfactory performance in each element of the assessment programme added 10% to the injured player’s recovery score. Daily recovery scores for injured players were recorded against the time spent in functional rehabilitation. Results: Rehabilitation data for 118 injuries sustained by 55 players over two seasons were recorded. The average time in functional rehabilitation depended on the time spent in pre-functional rehabilitation and the nature and location of injury. Benchmark functional rehabilitation curves (y = mln(x) + c) were developed for thigh (n = 15) and lower leg (n = 8) muscle strains and knee (n = 7) and ankle (n = 9) ligament sprains ( R 2 = 0.95–0.98). Conclusions: A structured, quantified rehabilitation programme based on routine fitness and skills exercises and a graded subjective assessment of performance provides an auditable record of a player’s functional recovery from a range of lower limb injuries and a transparent exit point from rehabilitation. The proposed method provides a permanent record of the functional rehabilitation of players’ injuries and evidence based data to support management’s return to play decisions.
A prospective randomized trial comparing stenting with off-pump coronary surgery for high-grade stenosis in the proximal left anterior descending coronary artery
Authors: Derk J Drenth, Nic J.G.M Veeger, Jobst B Winter, Jan G Grandjean, Massimo A Mariani, A.d J Boven van, Piet W Boonstra
Journal: Journal of the American College of Cardiology (2002)
Lung function in sarcoidosis: An investigation of the disease as seen at a clinic in England and a comparison of the value of various lung function tests
Authors: R. Marshall, A. J. Karlish
Journal: Thorax (1971)

<h3>Abstract</h3> <h3>Objective</h3> The risk of developing type 2 diabetes associated with poor sleep quality is comparable to that of traditional risk factors (e.g. overweight, physical inactivity). In the United Kingdom, these traditional risk factors could not explain the two to three-fold excess risks in South Asian and African Caribbean men compared to Europeans. This study investigates the (i)the association between mid-life sleep quality and later-life type 2 diabetes risk and (ii)a potential modifying effect of ethnicity. <h3>Research Design and Methods</h3> The Southall and Brent REvisited (SABRE) cohort comprised Europeans, South Asians, and African Caribbeans (median follow-up = 19 years). Complete case analysis was performed on 2190 participants without diabetes at baseline (age= 51.7± 7SD). Competing risks regressions were used to estimate the hazard ratios (HRs) of developing type 2 diabetes associated with four self-reported baseline sleep exposures (difficulty falling asleep, early morning waking, waking up tired and snoring) while adjusting for confounders. Modifying effects of ethnicity were analysed by (i) testing for interactions and (ii) performing ethnicity-stratified analysis. <h3>Results</h3> Snoring was strongly associated with increased type 2 diabetes risk but only among South Asians in a fully-adjusted model (HR 1.42, 95%CI=1.08-1.85, P=0.011). Our results revealed no elevated risk for any of the sleep exposures across all three ethnic groups. <h3>Conclusions</h3> The association between snoring and type 2 diabetes appeared to be modified by ethnicity, with South Asians at greatest risk.