tbuckley/cabot-search huggingface dataset:
Association of DLG5 variants with gluten-sensitive enteropathy
Authors: E A Festen, A Zhernakova, C Wijmenga, R K Weersma
Journal: Gut (2008)

Both gluten-sensitive enteropathy (GSE) and inflammatory bowel diseases (IBDs) are characterised by inflammation of the intestinal mucosa and enhanced intestinal epithelial permeability. Previous studies have identified shared susceptibility genes for IBD and GSE. Myosin IXB , first identified as associated with GSE, was also proven to be associated with ulcerative colitis (UC).1 We would like to respond to the recent study performed by Wapenaar et al that identified two tight-junction genes, PARD3 and MAGI2 , to be associated with both GSE and UC ( Gut 2008; 57 :438). We have also found IBD-associated genetic variants in DLG5 to be associated with GSE.2 DLG5 is, like Myosin IXB , PARD3 and MAGI2 , involved in maintaining the epithelial integrity, which makes it a suitable candidate gene for …
Involvement of Reactive Oxygen Species in Thrombin-induced Pulmonary Vasoconstriction
Authors: Jun Maki, Mayumi Hirano, Sumio Hoka, Hideo Kanaide, Katsuya Hirano
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Pulmonary vascular thrombosis and thrombotic arteriopathy are common pathological findings in pulmonary arterial hypertension. Thrombin may thus play an important role in the pathogenesis and pathophysiology of pulmonary arterial hypertension.The present study aimed to elucidate the contractile effect of thrombin in the pulmonary artery and clarify its underlying mechanisms.The changes in cytosolic Ca²(+) concentrations ([Ca²(+)](i)), 20-kD myosin light chain (MLC20) phosphorylation, and contraction were monitored in the isolated porcine pulmonary artery. The production of reactive oxygen species (ROS) was evaluated by fluorescence imaging.In the presence of extracellular Ca²(+), thrombin induced a sustained contraction accompanied by an increase in [Ca²(+)](i) and the phosphorylation of MLC20. In the absence of extracellular Ca²(+), thrombin induced a contraction without either [Ca²(+)](i) elevation or MLC20 phosphorylation. This Ca²(+)- and MLC20 phosphorylation-independent contraction was mimicked by hydrogen peroxide and inhibited by N-acetyl cysteine. Fluorescence imaging revealed thrombin to induce the production of ROS. A Rho-kinase inhibitor, Y27632, inhibited not only the thrombin-induced Ca²(+)- and MLC20 phosphorylation-dependent contraction, but also the Ca²(+)- and MLC20 phosphorylation-independent contraction and the ROS production. These effects of thrombin were mimicked by a proteinase-activated receptor 1 (PAR₁)-activating peptide.This study elucidated the Ca²(+)- and MLC20 phosphorylation-independent ROS-mediated noncanonical mechanism as well as Ca²(+)- and MLC20 phosphorylation-dependent canonical mechanism that are involved in the thrombin-induced PAR₁-mediated pulmonary vasoconstriction. Rho-kinase was suggested to play multiple roles in the development of thrombin-induced pulmonary vasoconstriction.
Occupational asthma due to latex in health care workers.
Authors: A. Ho, H. Chan, K. S. Tse, M. Chan-Yeung
Journal: Thorax (1996)

Immediate hypersensitivity reactions ranging from mild urticaria to life threatening anaphylaxis after exposure to natural rubber latex have been reported frequently in health care workers while occupational asthma due to latex exposure is less well studied. The results of specific challenge tests and immunological tests in four health care workers with work related respiratory and skin disorders induced by the use of latex gloves are described. Occupational asthma was confirmed in three subjects by specific challenge tests. All had a positive skin test reaction to the latex extract; specific IgE antibodies were detected in only one subject. The fourth subject had a negative specific inhalation and skin test reaction to the latex extract. Peak expiratory flow monitoring at work and away from work showed a pattern consistent with work related asthma. These findings confirm that latex is a cause of occupational asthma in health care workers.
Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model
Authors: Johannes Riegler, Malte Tiburcy, Antje Ebert, Evangeline Tzatzalos, Uwe Raaz, Oscar J. Abilez, Qi Shen, Nigel G. Kooreman, Evgenios Neofytou, Vincent C. Chen, Mouer Wang, Tim Meyer, Philip S. Tsao, Andrew J. Connolly, Larry A. Couture, Joseph D. Gold, Wolfram H. Zimmermann, Joseph C. Wu
Journal: Circulation Research (2015)

Rationale: Tissue engineering approaches may improve survival and functional benefits from human embryonic stem cell–derived cardiomyocyte transplantation, thereby potentially preventing dilative remodeling and progression to heart failure. Objective: Assessment of transport stability, long-term survival, structural organization, functional benefits, and teratoma risk of engineered heart muscle (EHM) in a chronic myocardial infarction model. Methods and Results: We constructed EHMs from human embryonic stem cell–derived cardiomyocytes and released them for transatlantic shipping following predefined quality control criteria. Two days of shipment did not lead to adverse effects on cell viability or contractile performance of EHMs (n=3, P =0.83, P =0.87). One month after ischemia/reperfusion injury, EHMs were implanted onto immunocompromised rat hearts to simulate chronic ischemia. Bioluminescence imaging showed stable engraftment with no significant cell loss between week 2 and 12 (n=6, P =0.67), preserving ≤25% of the transplanted cells. Despite high engraftment rates and attenuated disease progression (change in ejection fraction for EHMs, −6.7±1.4% versus control, −10.9±1.5%; n&gt;12; P =0.05), we observed no difference between EHMs containing viable and nonviable human cardiomyocytes in this chronic xenotransplantation model (n&gt;12; P =0.41). Grafted cardiomyocytes showed enhanced sarcomere alignment and increased connexin 43 expression at 220 days after transplantation. No teratomas or tumors were found in any of the animals (n=14) used for long-term monitoring. Conclusions: EHM transplantation led to high engraftment rates, long-term survival, and progressive maturation of human cardiomyocytes. However, cell engraftment was not correlated with functional improvements in this chronic myocardial infarction model. Most importantly, the safety of this approach was demonstrated by the lack of tumor or teratoma formation.
Increased mortality after coronary artery bypass graft surgery is associated with increased levels of postoperative creatine kinase-myocardial band isoenzyme release
Authors: Karen Klatte, Bernard R. Chaitman, Pierre Theroux, Jeffrey A. Gavard, Karen Stocke, Steven Boyce, Claus Bartels, Birgit Keller, Andreas Jessel
Journal: Journal of the American College of Cardiology (2001)
Biomechanical variables associated with Achilles tendinopathy in runners
Authors: L B Azevedo, M I Lambert, C L Vaughan, C M O’Connor, M P Schwellnus
Journal: British Journal of Sports Medicine (2008)

Objective: The aim of this study was to investigate the kinetics, kinematics and muscle activity in runners with Achilles tendinopathy. Design: Case–control study. Setting: Biomechanics laboratory. Participants: 21 runners free from injury and 21 runners with Achilles tendinopathy performed 10 running trials with standardised running shoes. Injured runners were diagnosed clinically according to established diagnostic criteria. Uninjured runners had been injury-free for at least 2 years. Main outcome measurements: During each trial, kinetic and lower limb kinematic data were measured using a strain gauge force plate and six infrared cameras respectively. Electromyographic (EMG) data from six muscles (tibialis anterior (TA), peroneus longus (PE), lateral gastrocnemius (LG), rectus femoris (RF), biceps femoris (BF) and gluteus medius (GM)) were measured with a telemetric EMG system. Results: Knee range of motion (heel strike to midstance) was significantly lower in injured runners than in uninjured runners. Similarly, preactivation (integrated EMG (IEMG) in 100 ms before heel strike) of TA was lower for injured runners than uninjured runners. RF and GM IEMG activity 100 ms after heel strike was also lower in the injured group. However, impact forces were not different between the two groups. Conclusion: Altered knee kinematics and reduced muscle activity are associated with Achilles tendinopathy in runners. Rehabilitation exercises or other mechanisms (e.g. footwear) that affect kinematics and muscle activity may therefore be beneficial in the treatment of runners with Achilles tendinopathy.
P08 Spontaneous bacterial peritonitis prophylaxis: reducing the incidence of c difficile infection
Authors: H. Jafferbhoy, M. H. Miller, C. Shekar, M. Lockhart, J. F. Dillon
Journal: Gut (2011)

<h3>Introduction</h3> Spontaneous bacterial peritonitis is a serious and life-threatening complication of cirrhosis, especially common in hospitalised patients. Antibiotic prophylaxis is effective but can lead to an increased incidence of hospital-acquired infections such as <i>Clostridium difficle</i>. <h3>Aim</h3> We evaluated whether two alternative prophylaxis agents were equally efficacious in preventing SBP, and the impact on risk of <i>C difficile</i> infection. <h3>Method</h3> A consecutive, cohort study of hospitalised patients with cirrhosis and ascites, over a 3-year period in a tertiary hospital. In the first cohort (2007–2009), ascitic patients requiring prophylaxis received Norfloxacin 400 mg/d during their hospital admission. In the second cohort (2009–2010) patients received prophylactic Co-trimoxazole 960 mg/d during their hospital admission. Data were extracted by case note review and the two cohorts compared. <h3>Results</h3> 174 patients admitted during 2007–2010 accounted for 231 hospital episodes with ascites. The Norfloxacin group had 154 episodes and the Co-trimoxazole group had 77. The mean age of the cohort was 57.4 years (SD 12.4) and 62% were male. Alcoholic cirrhosis was the major aetiology accounting for 79% of cases. The mean Child-Pugh and UKELD scores were 10.7 and 54 respectively. The overall incidence of SBP in our cohort was 19%. Abstract P08 table 1 demonstrates that the incidence of hospital acquired SBP, prophylaxis failure and mortality was not statistically different between the two therapies. However, selective bowel sterilisation with Co-trimoxazole did not lead to an increase <i>C difficle</i> infection rate. <h3>Conclusion</h3> Survival of cirrhotic patients with ascites is inversely related to severity of Liver disease, worsened with development of infections such as spontaneous bacterial peritonitis and <i>C difficle</i>. This study shows that Co-trimoxazole inpatient prophylaxis against SBP is as effective as quinolone based regimes, but has the advantage of a dramatic reduction in <i>C difficle</i> infection. At the same time the importance of measures like hand hygiene compliance, environmental cleanliness and strict policy of in hospital antibiotic prescribing cannot be underestimated.
Emergency Management of Unexpected Defects of Hemostatic Function in Surgical Patients
Authors: W. B. Wilson
Journal: JAMA (1967)

From time to time the surgeon is faced with the problem of an apparent defect of hemostatic function in a patient during surgery or postoperatively. This usually requires prompt and rational management, if undesirable complications are to be avoided. <h3>Preoperative Screening.—</h3> Although this paper deals primarily with operative and postoperative management of unexpected defective hemostasis, it is appropriate to mention first the preoperative screening of patients for bleeding tendency, since this is by far the most important approach to the problem. It should go without saying that surgery should never be undertaken lightly in patients with a known or suspected true defect of coagulation, no matter how mild the defect is supposed to be. Elective operation on the so-called mild hemophiliac, without proper preparation, can especially give cause for regret, since the postoperative management of these patients is always complicated and costly. A brief but appropriate history is the easiest
A randomised, placebo controlled, comparative trial of the gastrointestinal safety and efficacy of AZD3582 versus naproxen in osteoarthritis
Authors: L S Lohmander
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To evaluate the gastrointestinal safety and efficacy of the COX inhibiting nitric oxide donator AZD3582 in patients with hip or knee osteoarthritis. <b>Methods:</b> 970 patients were randomised (7:7:2) to AZD3582 750 mg twice daily, naproxen 500 mg twice daily, or placebo twice daily in a double blind study. The primary end point was the six week incidence of endoscopic gastroduodenal ulcers (diameter ⩾3 mm). Overall damage measured on the Lanza scale was a secondary end point. Safety and tolerability assessments included endoscopic upper gastrointestinal erosions and the gastrointestinal symptom rating scale (GSRS). Efficacy was primarily assessed by WOMAC. <b>Results:</b> The incidence of ulcers with AZD3582 was 9.7% and with naproxen 13.7% (p = 0.07, NS), <i>v</i> 0% on placebo. The incidence of Lanza scores &gt;2 was higher with naproxen (43.7%) than with AZD3582 (32.2%) (p&lt;0.001). Compared with baseline, significantly fewer ulcers and erosions developed in stomach and stomach/duodenum combined, and fewer erosions developed in stomach, duodenum, and both combined on AZD3582 than on naproxen. GSRS reflux and abdominal pain subscale scores were lower for AZD3582 than for naproxen but there was no difference for indigestion, constipation, and diarrhoea. AZD3582 was as effective as naproxen at improving WOMAC scores. Both agents were well tolerated, with no significant effects on blood pressure. <b>Conclusions:</b> At doses with similar efficacy in relieving osteoarthritis symptoms, the primary end point of six week endoscopic gastroduodenal ulcer incidence was not significantly different between AZD3582 and naproxen. Most secondary endoscopic gastrointestinal end points favoured AZD3582.
A forensic perspective of the AFL investigation into peptides: an antidoping investigation case study
Authors: Peter Rex Harcourt, Francois Marclay, Brett Clothier
Journal: British Journal of Sports Medicine (2014)

The World Anti-Doping Agency (WADA) is introducing enhancements to doping investigations in its 2015 Code, which include improved sharing of information between antidoping organisations (including sporting bodies) and enhanced accountability of athlete support staff. These additions will improve the control of links between sports doping and organised crime. In February 2013 the Australian Crime Commission released a report that linked several professional sporting codes, professional athletes with links to organised crime, performance enhancing drugs and illicit substances. Following this report the Australian Football League (AFL) partnered the Australian national antidoping organisation to investigate peptide use in Australian football.This review compared the model proposed by Marclay, a hypothetical model for anti-doping investigations that proposed a forensic intelligence and analysis approach, to use the forensic capabilities of the AFL investigation to test the model's relevance to an actual case.The investigation uncovered the use of peptides used to enhance athlete performance. The AFL investigation found a high risk of doping where athlete support staff existed in teams with weak corporate governance controls. A further finding included the need for the investigation to provide a timely response in professional team sports that were sensitive to the competition timing. In the case of the AFL the team was sanctioned prior to the finals as an interim outcome for allowing the risk of use of performance-enhancing substances. Doping violation charges are still being considered.Antidoping strategies should include the investigation of corporate officers in team doping circumstances, the mandatory recording of all athlete substance use during competition and training phases, the wider sharing of forensic intelligence with non-sporting bodies particularly law enforcement and collaboration between antidoping and sporting organisations in doping investigations.The AFL investigation illustrated the importance of the 2015 WADA Code changes and highlighted the need for a systematic use of broad forensic intelligence activities in the investigation of doping violations.
Teaching of cultural diversity in medical schools in the United Kingdom and Republic of Ireland: cross sectional questionnaire survey
Authors: Nisha Dogra, Sue Conning, Paramjit Gill, John Spencer, Margot Turner
Journal: BMJ (2005)

focus on their own perceived areas of difficulty and makes the course work pertinent to their needs. 7 We have used these types of "trigger" tapes successfully in our previous research with nurses and doctors working in oncology. 6 7The intervention reported here was valued highly by all participants.The positive findings from the course included an increase in participants' reported self confidence about recruiting patients into trials, and objective analyses revealed behavioural changes in the style and content of the participants' discussions.There is strong evidence that if both competence and self confidence are improved then behavioural changes often do transfer successfully into the clinical setting and endure, even without support or consolidation courses. 7 8 Our training course is now being rolled out by the national cancer research networks in England and Wales, and research to see if real patient outcomes are affected is planned.
A salutary lesson: Patients sometimes behave like our Snoopy
Authors: T. Fox
Journal: BMJ (1999)

Hummingbirds need a lot of food in the evening. Then they roost and drop their body temperature. This bedtime calorie load and reduced metabolic rate enables them to survive the night.

We had just moved a few blocks across a suburb in the north of San Diego. Some young relatives of my German wife visited us almost immediately in a new house that was in chaos. An afternoon project was to obtain and install a new hummingbird feeder (I could not bear to harm …
In vitro analysis of allogeneic lymphocyte interaction. I. Characterization and cellular origin of an Ia-positive helper factor- allogeneic effect factor
Authors: TL Delovitch, HO McDevitt
Journal: The Journal of Experimental Medicine (1977)

A soluble allogeneic effect factor (AEF) was produced by using H-2 congenic mouse strains and a serum.free cell culture medium. An AEF derived from untreated activated responder cells and irradiated stimulator cells provided helper cell function in a primary and secondary antibody response for both T-cell-depleted responder B cells and stimulator B cells. This interaction may be determined by genes situated in the I-A and I-B regions: additional K-region control was not excluded. Ia antigens, but neither H-2 nor Ig determinants are molecular constituents of AEF. The active components of this AEF consist, in part, of Ia antigens derived from both the activated responder cell population and irradiated stimulator cell population. An AEF derived from Ia negative responder cells and irradiated T-cell- depleted stimulator cells helps a secondary antibody response of T-cell- depleted stimulator B cells but not responder B cells. This genetically restricted AEF contains Ia antigens determined by the stimulator haplotype but not the responder haplotype. The priming antigen, DNP- keyhole limpet hemocyanin, is not a component of restricted AEF. The data suggest that restricted AEF may be a product of a stimulator B cell and/or macrophage. They support the hypothesis that the recognition by allogeneic T cells of Ia antigens on B cells activates the B cell to IgG antibody production.
Evidence-based recommendations on the investigation of acute pulmonary embolism
Authors: S Cowman
Journal: Thorax (2007)

▴ Stein PD, Woodard PK, Weg JG, et al . Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators. Am J Med2006;119:1048–55.

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



This paper from the PIOPED (Prospective Investigation Of Pulmonary Embolism Diagnosis) II investigators presents updated guidelines on diagnostic algorithms for pulmonary embolism (PE).

In all cases, an objective clinical assessment of the probability of PE is initially recommended. In patients at low or moderate risk of PE this should be followed by a rapid ELISA-based …

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Apoptosis and Cell Proliferation After Porcine Coronary Angioplasty
Authors: Nadim Malik, Sheila E. Francis, Cathy M. Holt, Julian Gunn, Graham L. Thomas, Lynda Shepherd, Janet Chamberlain, Christopher M. H. Newman, David C. Cumberland, David C. Crossman
Journal: Circulation (1998)

Background —Angioplasty initiates a number of responses in the vessel wall including cellular migration, proliferation, and matrix accumulation, all of which contribute to neointima formation and restenosis. Cellular homeostasis within a tissue depends on the balance between cell proliferation and apoptosis. Methods and Results —Profiles of apoptosis and proliferation were therefore examined in a porcine PTCA injury model over a 28-day period. Forty-two arteries from 21 pigs, harvested at the site of maximal injury at 1, 6, and 18 hours, and 3, 7, 14, and 28 days after PTCA, were examined (n=3 animals per time point). Uninjured arteries were used as controls. Apoptosis was demonstrated by the terminal uridine nick-end labeling (TUNEL) method, transmission electron microscopy (TEM), and DNA fragmentation. Cells traversing the cell cycle were identified by immunostaining for proliferating cell nuclear antigen (PCNA). Apoptosis was not detected in control vessels at all time points nor at 28 days after PTCA. Apoptotic cells were identified at all early time points with a peak at 6 hours (5.1±0.26%; compared to uninjured artery, P &lt;0.001) and confirmed by characteristic DNA ladders and TEM findings. Regional analysis showed apoptosis within the media, adventitia, and neointima peaked at 18 hours, 6 hours, and 7 days after PTCA, respectively. In comparison, PCNA staining peaked at 3 days after PTCA (7.16±0.29%; compared to 1.78±0.08% PCNA-positive cells in the uninjured artery, P &lt;0.001). Profiles of apoptosis and cell proliferation after PTCA were discordant in all layers of the artery except the neointima. These profiles also differed between traumatized and nontraumatized regions of the arterial wall. Immunostaining with cell-type specific markers and TEM analysis revealed that apoptotic cells included vascular smooth muscle cells (VSMCs), inflammatory cells, and adventitial fibroblasts. Conclusions —These results suggest that the profile of apoptosis and proliferation after PTCA is regional and cell specific, and attempts to modulate either of these events for therapeutic benefit requires recognition of these differences.