tbuckley/cabot-search huggingface dataset:
PTU-039 Should Mr Enterography Be The Preferred Surveillance Modality Compared To Small Bowel Capsule Endoscopy In Peutz-jegher’s Syndrome?
Authors: R Rameshshanker, A Gupta, A O’Rourke, S Clark, R Phillips, C Fraser
Journal: Gut (2014)

<h3>Introduction</h3> Peutz-Jeghers syndrome (PJS) causes multiple hamartomatous polyp formation throughout the gastrointestinal tract. Large polyps within the small bowel (SB) may cause complications and morbidity including obstruction, bleeding, an increased risk of cancer and post surgical adhesional disease. Regular surveillance and removal of large polyps are important to prevent complications from occurring. <h3>Methods</h3> The aim of our study was to assess the utility of SB capsule endoscopy (SBCE) compared with MR enterography (MRE) for the detection of small bowel PJS polyps. We performed a retrospective review of all adult PJS patients under the care of the St Mark’s Polyposis Registry between 2006–2012. Participants’ MRE and SBCE findings, enteroscopy reports and case notes were reviewed. Polyps &gt;10 mm were regarded as clinically relevant. Large polyps (&gt;15mm) resected at push enteroscopy (PE), double balloon enteroscopy (DBE) or intraoperative enteroscopy (IOE) were correlated in terms of size, location, number and need for resection with both MRE and SBCE findings. <h3>Results</h3> 95 patient episodes involving 83 patients (median age 38yrs, 60% female) were included. SBCE was performed in 78 patient episodes, either alone (n = 29) or prior to MRE (n = 49). Reasons for MRE post SBCE were: previous study involvement (n = 19), post-polypectomy reassessment (n = 10), persistent symptoms (n = 9) and confirmation of significant polyp findings (n = 11). There was no significant difference between patients in whom &gt;10 mm polyps were detected (77 vs. 106 for SBCE and MRE, respectively; p = 0.124). In 6 patients, large polyps (&gt;15 mm) not detected at SBCE, were identified at MRE. Endoscopic removal of large polyps was performed during 63 patient episodes. 22 patients episodes did not require polypectomy. DBE’s were incomplete due to failure of deep intubation in 7 patients (19%) but 4 of these patients subsequently underwent laparoscopic assisted DBE and successful polypectomy. Concordance with DBE findings for polyp size for SBCE vs. MRE was 61% and 79%, respectively (p = 0.18). Concordance with DBE findings for polyp location for SBCE vs. MRE was 79% and 92%, respectively (p = 0.76). <h3>Conclusion</h3> MRE appears at least as effective as the current iteration of SBCE for small-bowel polyp surveillance in adults with PJS. MRE may be less prone to missing large polyps and more accurate in polyp size assessment and localisation and in post-polypectomy reassessment of the SB. <h3>Disclosure of Interest</h3> None Declared.
N-propionylated group B meningococcal polysaccharide mimics a unique epitope on group B Neisseria meningitidis.
Authors: H J Jennings, A Gamian, F E Ashton
Journal: The Journal of Experimental Medicine (1987)

Antibodies induced in mice by the N-propionyl (N-Pr)-group B meningococcal polysaccharide (GBMP)-tetanus toxoid (TT) conjugate were bactericidal for GBM organisms independent of protein serotype. The antisera contained two populations of N-Pr-GBMP-specific antibodies, only one of which crossreacted with the GBMP. Particularly significant was the fact that the bactericidal activity was mainly associated with the population of antibodies that did not crossreact with the GBMP. Therefore it can be inferred from the above evidence that the N-Pr-GBMP mimics a unique epitope on the surface of GBM organisms that is not present on the exogenous GBMP.
Botulinum toxin potentiates cancer radiotherapy and chemotherapy.
Authors: R√©ginald Ansiaux, Christine Baudelet, Greg O Cron, J√©r√¥me Segers, Chantal Dessy, Philippe Martinive, Julie De Wever, Julien Verrax, Val√©rie Wauthier, Nelson Beghein, Vincent Gr√©goire, Pedro Buc Calderon, Olivier Feron, Bernard Gallez
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: Structural and functional abnormalities in the tumor vascular network are considered factors of resistance of solid tumors to cytotoxic treatments. To increase the efficacy of anticancer treatments, efforts must be made to find new strategies for transiently opening the tumor vascular bed to alleviate tumor hypoxia (source of resistance to radiotherapy) and improve the delivery of chemotherapeutic agents. We hypothesized that Botulinum neurotoxin type A (BoNT-A) could interfere with neurotransmitter release at the perivascular sympathetic varicosities, leading to inhibition of the neurogenic contractions of tumor vessels and therefore improving tumor perfusion and oxygenation. EXPERIMENTAL DESIGN: To test this hypothesis, BoNT-A was injected locally into mouse tumors (fibrosarcoma FSaII, hepatocarcinoma transplantable liver tumor), and electron paramagnetic resonance oximetry was used to monitor pO(2) in vivo repeatedly for 4 days. Additionally, contrast-enhanced magnetic resonance imaging was used to measure tumor perfusion in vivo. Finally, isolated arteries were mounted in wire myograph to monitor specifically the neurogenic tone developed by arterioles that were co-opted by the surrounding growing tumor cells. RESULTS: Using these tumor models, we showed that local administration of BoNT-A (two sites; dose, 29 units/kg) substantially increases tumor oxygenation and perfusion, leading to a substantial improvement in the tumor response to radiotherapy (20 Gy of 250-kV radiation) and chemotherapy (cyclophosphamide, 50 mg/kg). This observed therapeutic gain results from an opening of the tumor vascular bed by BoNT-A because we showed that BoNT-A could inhibit neurogenic tone in the tumor vasculature. CONCLUSIONS: The opening of the vascular bed induced by BoNT-A offers a way to significantly increase the response of tumors to radiotherapy and chemotherapy.
Kruppel-Like Factor 2 (KLF2) Regulates Endothelial Thrombotic Function
Authors: Zhiyong Lin, Ajay Kumar, Sucharita SenBanerjee, Kristine Staniszewski, Kush Parmar, Douglas E. Vaughan, Michael A. Gimbrone, Viji Balasubramanian, Guillermo García-Cardeña, Mukesh K. Jain
Journal: Circulation Research (2005)

The vascular endothelium maintains blood fluidity by inhibiting blood coagulation, inhibiting platelet aggregation, and promoting fibrinolysis. Endothelial cells lose these nonthrombogenic properties on exposure to proinflammatory stimuli. We recently identified the Kruppel-like factor KLF2 as a novel regulator of endothelial proinflammatory activation. Here it is found that KLF2 differentially regulates key factors involved in maintaining an antithrombotic endothelial surface. Overexpression of KLF2 strongly induced thrombomodulin (TM) and endothelial nitric oxide synthase (eNOS) expression and reduced plasminogen activator inhibitor-1 (PAI-1) expression. Furthermore, overexpression of KLF2 inhibited the cytokine-mediated induction of tissue factor (TF). In contrast, siRNA mediated knockdown of KLF2 reduced antithrombotic gene expression while inducing the expression of pro-coagulant factors. The functional importance of KLF2 was verified by in vitro clotting assays. By comparison to control infected cells, KLF2 overexpression increased blood clotting time as well as flow rates under basal and inflammatory conditions. In contrast, siRNA-mediated knockdown of KLF2 reduced blood clotting time and flow rates. These observations identify KLF2 as a novel transcriptional regulator of endothelial thrombotic function. The full text of this article is available online at http://circres.ahajournals.org.
Aggressive form of pleural epithelioid haemangioendothelioma: complete response after chemotherapy
Authors: C. Pinet, A. Magnan, L Garbe, M-J Payan, D. Vervloet
Journal: European Respiratory Journal (1999)

Epithelioid haemangioendotheliomas are rare tumours of endothelial origin. They can develop in any tissue but occur principally in the lung and liver. Their usual course is a slow progression, so that they can be treated by surgery. In aggressive forms, no treatment has proved efficient to date. This study, describes a case of bilateral pleural epithelioid haemangioendothelioma that extended to the peritoneum. The histological diagnosis was confirmed by both conventional examination and immunohistochemistry. After six courses of carboplatine plus etoposide, a complete response was obtained. The complete remission is still lasting at 18 months after the diagnosis and the patient is healthy.
A Randomized Trial of Dialectical Behavior Therapy Versus General Psychiatric Management for Borderline Personality Disorder
Authors: Shelley F. McMain, Paul S. Links, William H. Gnam, Tim Guimond, Robert J. Cardish, Lorne Korman, David L. Streiner
Journal: American Journal of Psychiatry (2009)

Objective: The authors sought to evaluate the clinical efficacy of dialectical behavior therapy compared with general psychiatric management, including a combination of psychodynamically informed therapy and symptom-targeted medication management derived from specific recommendations in APA guidelines for borderline personality disorder. Method: This was a single-blind trial in which 180 patients diagnosed with borderline personality disorder who had at least two suicidal or nonsuicidal self-injurious episodes in the past 5 years were randomly assigned to receive 1 year of dialectical behavior therapy or general psychiatric management. The primary outcome measures, assessed at baseline and every 4 months over the treatment period, were frequency and severity of suicidal and nonsuicidal self-harm episodes. Results: Both groups showed improvement on the majority of clinical outcome measures after 1 year of treatment, including significant reductions in the frequency and severity of suicidal and nonsuicidal self-injurious episodes and significant improvements in most secondary clinical outcomes. Both groups had a reduction in general health care utilization, including emergency visits and psychiatric hospital days, as well as significant improvements in borderline personality disorder symptoms, symptom distress, depression, anger, and interpersonal functioning. No significant differences across any outcomes were found between groups. Conclusions: These results suggest that individuals with borderline personality disorder benefited equally from dialectical behavior therapy and a well-specified treatment delivered by psychiatrists with expertise in the treatment of borderline personality disorder.
Non-fatal injuries sustained by seatbelt wearers: a comparative study.
Authors: M S Christian
Journal: BMJ (1976)

The injuries sustained by 969 drivers and front-seat passengers in road-traffic accidents were studied. Altogether 196 (20-2%) of the drivers and passengers were wearing seat belts and 773 (79-8%) were not. The injuries among the two groups differed greatly in both severity and distribution. A total of 54 (27-6%) of the seatbelt wearers sustained one or more fractures compared with 300 (38-8%) of the non-wearers, and 18 (9-2%) of the seatbelt wearers were severely injured compared with 300 (38-8%) of the non-wearers. Soft-tissue injuries to the face were sustained by only 29 (14-8%) of the seatbelt wearers compared with 425 (55%) of the non-wearers. Since wearing seatbelts may become compulsory, the type and pattern of injuries to be expected in wearers should be appreciated.
Granulocyte Colony-Stimulating Factor (G-CSF) Treatment of Childhood Acute Myeloid Leukemias That Overexpress the Differentiation-Defective<i>G-CSF</i>Receptor Isoform IV Is Associated With a Higher Incidence of Relapse
Authors: Stephanie Ehlers, Christin Herbst, Martin Zimmermann, Nicole Scharn, Manuela Germeshausen, Nils von Neuhoff, Christian Michel Zwaan, Katarina Reinhardt, Iris H. Hollink, Jan-Henning Klusmann, Thomas Lehrnbecher, Silja Roettgers, Jan Stary, Michael Dworzak, Karl Welte, Ursula Creutzig, Dirk Reinhardt
Journal: Journal of Clinical Oncology (2010)

This prospective, multicenter Acute Myeloid Leukemia Berlin-Frankfurt-Muenster (AML-BFM) 98 study randomly tested the ability of granulocyte colony-stimulating factor (G-CSF) to reduce infectious complications and to improve outcomes in children and adolescents with acute myeloid leukemia (AML). However, a trend toward an increased incidence of relapses in the standard-risk (SR) group after G-CSF treatment was observed.Of 154 SR patients in the AML-BFM 98 cohort, 50 patients were tested for G-CSF receptor (G-CSFR) RNA isoform I and IV expression, G-CSFR cell surface expression, and acquired mutations in the G-CSFR gene.In patients randomly assigned to receive G-CSF after induction, 16 patients overexpressing the G-CSFR isoform IV showed an increased 5-year cumulative incidence of relapse (50% +/- 13%) compared with 14 patients with low-level isoform IV expression (14% +/- 10%; log-rank P = .04). The level of G-CSFR isoform IV had no significant effect in patients not receiving G-CSF (P = .19). Multivariate analyses of the G-CSF-treated subgroup, including the parameters G-CSFR isoform IV overexpression, sex, and favorable cytogenetics as covariables, revealed the prognostic relevance of G-CSFR isoform IV overexpression for 5-year event-free survival (P = .031) and the 5-year cumulative incidence of relapse (P = .049).Our results demonstrate that children and adolescents with AMLs that overexpress the differentiation-defective G-CSFR isoform IV respond to G-CSF administration after induction, but with a significantly higher incidence of relapse.
Red blood cell membrane α-linolenic acid and the risk of sudden cardiac arrest
Authors: Rozenn N. Lemaitre, Irena B. King, Nona Sotoodehnia, Thomas D. Rea, Trivellore E. Raghunathan, Kenneth M. Rice, Thomas S. Lumley, Robert H. Knopp, Leonard A. Cobb, Michael K. Copass, David S. Siscovick
Journal: Metabolism (2009)
Sildenafil Induces Delayed Preconditioning Through Inducible Nitric Oxide Synthase–Dependent Pathway in Mouse Heart
Authors: Fadi Salloum, Chang Yin, Lei Xi, Rakesh C. Kukreja
Journal: Circulation Research (2003)

Sildenafil citrate (Viagra) is the most widely used drug for treating erectile dysfunction in men. We recently demonstrated that it induces potent protective effects against ischemia-reperfusion (I-R) injury in rabbit hearts through the opening of mitochondrial ATP-dependent K + channels. In the present study, we investigated the role of the NO-dependent signaling pathway in delayed cardioprotection by sildenafil. Adult male ICR mice were treated with saline or sildenafil (0.7 mg/kg IP) 24 hours before global I-R in the Langendorff mode. Infarct size was reduced from 27.6±3.3% in saline-treated control mice to 6.9±1.2% in sildenafil-treated mice (mean±SEM, P &lt;0.05) without compromising cardiac function. Reverse transcription–polymerase chain reaction revealed a transient increase in endothelial and inducible NO synthase (eNOS and iNOS, respectively) mRNA in sildenafil-treated mice, peaking at 45 minutes (eNOS) and 2 hours (iNOS) after sildenafil injection. The magnitude of mRNA increase was more pronounced for iNOS than for eNOS. In addition, a significant increase in both iNOS and eNOS protein was detected 24 hours after sildenafil treatment. A selective inhibitor of iNOS, 1400W (10 mg/kg IP given 30 minutes before I-R), abolished sildenafil-induced protection (23.7±2.8%, P &lt;0.05 versus sildenafil). These data suggest that the induction of NO synthase isoforms is an essential component of the signaling mechanism for sildenafil-induced delayed preconditioning. However, iNOS appears to be the primary isoform that mediates the robust cardioprotection.
Point-of-care HIV testing in primary care and early detection of HIV (RHIVA2): a cluster randomised controlled trial
Authors: W Leber, H McMullen, N Marlin, S Bremner, AC Santos, F Terris-Prestholt, K Boomla, R Ashcroft, S Kerry, A Martineau, D Millett, S Mguni, S Creighton, G Hart, J Figueroa, J Anderson, C Griffiths
Journal: The Lancet (2013)
Anti-citrullinated protein antibodies in rheumatoid arthritis: a functional role for mast cells and basophils?
Authors: J. Suurmond, A. J. M. Schuerwegh, R. E. M. Toes
Journal: Annals of the Rheumatic Diseases (2011)

Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation of the joints. Anti-citrullinated protein antibodies (ACPA) are highly specific for RA and are associated with a more severe disease progression. ACPA have also been shown to have a pathological role in RA. In animal models of RA, ACPA enhances arthritis. Furthermore, in vitro generated immune complexes with ACPA can activate macrophages and the complement system in the human system. Recently, a direct functional and specific response of FcεRI+ immune cells towards citrullinated proteins was demonstrated. Basophils of ACPA+ RA patients are activated by citrullinated proteins that cross link the FcεRI receptor via IgE-ACPA, physiologically bound to the receptor. In addition, synovial mast cells from ACPA+ RA patients show a more activated phenotype than mast cells from ACPA- patients. These findings underline the suggestion that ACPA+ and ACPA- RA are two different disease entities and point to a possible functional role of ACPA and FcεRI+ cells in the pathogenesis of RA.
Safety and Feasibility of Autologous Myoblast Transplantation in Patients With Ischemic Cardiomyopathy
Authors: Nabil Dib, Robert E. Michler, Francis D. Pagani, Susan Wright, Dean J. Kereiakes, Rose Lengerich, Philip Binkley, Diane Buchele, Inder Anand, Cory Swingen, Marcelo F. Di Carli, James D. Thomas, Wael A. Jaber, Shaun R. Opie, Ann Campbell, Patrick McCarthy, Michael Yeager, Vasken Dilsizian, Bartley P. Griffith, Ronald Korn, Steven K. Kreuger, Marwan Ghazoul, W. Robb MacLellan, Gregg Fonarow, Howard J. Eisen, Jonathan Dinsmore, Edward Diethrich
Journal: Circulation (2005)

Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device (LVAD) implantation. In addition, we sought to gain preliminary information on graft survival and any associated changes in cardiac function.Thirty patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twenty-four patients with a history of previous myocardial infarction and a left ventricular ejection fraction <40% were enrolled in the CABG arm. In a second arm, 6 patients underwent LVAD implantation as a bridge to heart transplantation, and patients donated their explanted native hearts for testing at the time of heart transplantation. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term, unexpected adverse events. Follow-up positron emission tomography scans showed new areas of glucose uptake within the infarct scar in CABG patients. Echocardiography measured an average change in left ventricular ejection fraction from 28% to 35% at 1 year and of 36% at 2 years. Histological evaluation in 4 of 6 patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium.These results demonstrate the survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality offers a potential therapeutic treatment for end-stage heart disease.
Elastin expression in very severe human COPD
Authors: G. Deslee, J. C. Woods, C. M. Moore, L. Liu, S. H. Conradi, M. Milne, D. S. Gierada, J. Pierce, A. Patterson, R. A. Lewit, J. T. Battaile, M. J. Holtzman, J. C. Hogg, R. A. Pierce
Journal: European Respiratory Journal (2009)

Alveolar elastic fibres are key targets of proteases during the pathogenesis of chronic obstructive pulmonary disease (COPD). In the current study, we hypothesised that a response to injury leads to enhanced alveolar elastin gene expression in very severe COPD. Lung samples obtained from 43 patients, including 11 with very severe COPD (stage 4), 10 donors, 10 with moderate/severe COPD (stage 2–3) and 12 non-COPD subjects, were analysed for elastin mRNA expression by real-time RT-PCR and in situ hybridisation. Alveolar elastic fibres were visualised using Hart's staining of sections of frozen inflated lungs obtained from 11 COPD stage 4 patients and three donor lungs. Compared with donors, non-COPD and stage 2–3 COPD, elastin mRNA expression was significantly increased in very severe COPD lungs (12-fold change), and localised in situ hybridisation induced elastin expression to alveolar walls. Compared with donors, alveolar elastic fibres also comprised a greater volume fraction of total lung tissue in very severe COPD lungs (p&lt;0.01), but elastic fibre content was not increased per lung volume, and desmosine content was not increased. The present study demonstrates enhanced alveolar elastin expression in very severe COPD. The efficiency of this potential repair mechanism and its regulation remain to be demonstrated.
Birth Spacing and Adverse Perinatal Outcomes
Authors: H. C. J. Scheepers, Didi Braat
Journal: JAMA (2006)

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