tbuckley/cabot-search huggingface dataset:
Abstract 5368: Igf +hgf Enhance Sca-1 <sup>+</sup> /cd31 <sup>−</sup> Cell Therapy in Hearts with Postinfarction Lv Remodeling
Authors: Xiaohong Wang, Elizabeth Braunlin, Qingsong Hu, Joseph Lee, Qinglu Li, Qiang Xiong, Mohammad N Jameel, Jianyi Zhang
Journal: Circulation (2008)

Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are two potent cell survival factors in response to hypoxia and oxidative stress. We have previously shown that transplantation of Sca-1 + /CD31 − cells can improve LV function in hearts with acute myocardial infarction (AMI) although the engraftment rate was low. We hypothesized that supplementation of IGF-1 and HGF at delivery of cellular therapy can enhance the beneficial effects of Sca-1 + /CD31 − cells in the injured heart by increasing engraftment rate and endogenous cardiac cell survival. Adenovirus nuclear LacZ-labeled Sca-1 + /CD31 − cells (1x10 6 ) were injected into the ischemic area after LAD ligation in BalbC mice. Recombinant mouse IGF-1+HGF (100ng) was added to the cell suspension prior to the injection. The LV function (ECHO) and in vivo myocardial bioenergetics ( 31 P-NMR spectroscopy) were assessed 4 weeks after AMI and cell transplantation. Normal mice (Normal, n=6), and 2 control groups of LAD ligation (MI, n=6), and MI plus Sca-1 + /CD31 − cell transplantation (Cell, n=6), were compared to AMI mice with Sca-1 + /CD31 − cells transplantation plus IGF-1+HGF (Cell+IGF-1+HGF, n=6). Sca-1 + /CD31 − cells formed viable grafts and improved LV contractile function (EF: Control, 53.3+/−3.2; MI, 18.9+/−3.9; Cell, 29.1+/−5.1, p&lt;0.05) and myocardial bioenergetics (PCr/ATP: Control, 2.13+/−0.09; MI, 1.21+/−0.09; Cell, 1.72+/−0.12; p&lt;0.01). IGF+HGF significantly further enhanced the benefits of the cell transplantation as evidenced by significantly increased EF to 38.3+/−3.1% (p&lt;0.05), which was accompanied by a higher cell engraftment rate (p&lt;0.05). Using the in vitro co culture of Sca-1 + /CD31 − cells with HL-1 cells labeled by Vybrant CFDA SE cell tracer kit, we observed both IGF+HGF and Sca-1 + /CD31 − cells can inhibit TNFα and hypoxia induced HL-1 cell apoptosis (Control, 7+/−1%; TNFα, 24+/−1%; IGF+HGF+TNFα, 10+/−1%; n=6, P&lt;0.001) and caspase 3 expression. These data demonstrate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial restoration.
hs-Troponin I Followed by CT Angiography Improves Acute Coronary Syndrome Risk Stratification Accuracy and Work-Up in Acute Chest Pain Patients
Authors: Maros Ferencik, Ting Liu, Thomas Mayrhofer, Stefan B. Puchner, Michael T. Lu, Pal Maurovich-Horvat, J. Hector Pope, Quynh A. Truong, James E. Udelson, W. Frank Peacock, Charles S. White, Pamela K. Woodard, Jerome L. Fleg, John T. Nagurney, James L. Januzzi, Udo Hoffmann
Journal: JACC. Cardiovascular imaging (2015)
Enhancement of cell adhesion, retention, and survival of HUVEC/cbMSC aggregates that are transplanted in ischemic tissues by concurrent delivery of an antioxidant for therapeutic angiogenesis
Authors: Chieh-Cheng Huang, Wen-Yu Pan, Michael T. Tseng, Kun-Ju Lin, Yi-Pei Yang, Hung-Wen Tsai, Shiaw-Min Hwang, Yen Chang, Hao-Ji Wei, Hsing-Wen Sung
Journal: Biomaterials (2015)
Effects of nasal positive expiratory pressure on dynamic hyperinflation during exercise in patients with COPD
Authors: Thomas Wibmer, Stefan Ruediger, Claudia Heitner, Cornelia Kropf-Sanchen, Kathrin M. Stoiber, Wolfgang Rottbauer, Christian Schumann
Journal: European Respiratory Journal (2013)

Introduction: Dynamic hyperinflation is an important target in the treatment of COPD. There is increasing evidence that positive expiratory pressure (PEP) could reduce dynamic hyperinflation during exercise. PEP application through a nasal mask and a flow resistance device might have the potential to be used during daily physical activities as an auxiliary strategy of ventilatory assistance.  Aims: To analyze the effects of nasal PEP on lung volumes during physical exercise in patients with COPD.  Methods: 20 patients (mean age 69.4 ± 6.4 years) with stable, mild-to-severe COPD were randomized to complete a six-minute walk test (6MWT) with nasal PEP breathing, followed by a second 6MWT with normal breathing, or vice versa. Lung function tests were performed immediately pre- and post-exercise. PEP was applied by means of a silicone nasal mask loaded with a fixed-orifice resistor expiratory valve.  Results: Differences in mean pre- to post-exercise changes in TLC (-0.63 +/- 0.80 L; p = 0.002), FRC (-0.48 +/- 0.86 L; p = 0.021), RV (-0.56 +/- 0.75 L; p = 0.004), SpO2 (-1.7 +/- 3.4 %; p = 0.041) and 6MWT-distance (-30.8 +/- 30.0 m; p = 0.001) were statistically significant between the experimental and the control interventions.  Conclusions: The use of flow-dependent expiratory pressure, applied with a nasal mask and a PEP valve, promotes significant reduction of dynamic hyperinflation during walking exercise. Further studies are warranted addressing improvements in exercise capacity under regular application of nasal PEP during physical activities.
Phase II multicentric uncontrolled national trial assessing the efficacy of nilotinib in the treatment of advanced melanomas with c-KIT mutation or amplification.
Authors: Celeste Lebbe, Sylvie Chevret, Thomas Jouary, Sophie Dalac, Stephane Dalle, Bernard Guillot, Jean-Philippe Arnault, Marie-Françoise Avril, Christophe Bedane, Guido Bens, Marie- Beylot-Barry, Sandrine Mansard, Florent Grange, Nicolas Meyer, Laurent Machet, Laurent Misery, Philippe Saiag, Maxime Battistella, Samia Mourah, Nicolas Dumaz
Journal: Journal of Clinical Oncology (2014)

9032 Background: Three phase II trials have shown an overall response rate (ORR) around 20% with imatinib in melanoma carrying KIT mutations. The aim of this study was to study the interest of nilotinib a Kit inhibitor with pharmacological advantages compared to imatinib. Methods: this multicenter uncontrolled open Hern's single-stage Phase II study enrolled patients with advanced melanoma and KIT amplifications and/or mutations and no BRAF and NRAS mutation, nor previous Kit targeted therapy or active brain metastasis.Patients received Nilotinib 400 mg bid. ORR was the primary endpoint. Secondary endpoints included disease control, metabolic response rate and biomarkers associated to response . Based on type I and II error rates fixed at 0.05 and 0.10, respectively, a sample size of 25 patients was required to test the level of response, p≤ 7.5% against > 30%, with at least 5 successes tindicating that the treatment was effective. Analysis was based on intent to treat. Results: 25 patients were enrolled from 2010-07-27 to 2012-08-27: 13 females (52%); median age 70 years(range, 43-87); 23 (92%) tumors with KIT mutations, 5 (20%) KIT amplifications, and 3 (12%) both. One patient (4%) had primary unresectable melanoma, 3(12%) unresectable stage III melanoma, 21 (84%) stage IV melanoma .13 (52%) patients were chemotherapy naive, 12 (48%) had previously received dacarbazine or fotemustine, 1 immunotherapy . Median follow-up was 3 months ([IQR: 2-7], range 0.3-12).One patient reached CR and 4 partial responses, concluding to treatment effectiveness with an ORR of 20% (95%CI: 6.8-40.7) all in patients with KIT mutation . Six patients died and 1-year overall survival was 68.3% (95%CI: 46.5-1.00).The 25 patients experienced a total of 236 adverse events , 2/3 imputed to the drug mostly of grade 1 (n=146 in 21 patients) and grade 2 (47 in 13 pts), and less frequently of grade 3 (39 in 18 pts) or grade 4 (3 in 3 pts: 2 dyspnea, 1 renal failure) and 1 death. Five patients had drug withdrawal because of toxicity. Conclusions: According to our hypothesis, nilotinib is an effective drug in KIT mutated melanoma in the absence of BRAF and NRAS mutations and should be added to our armamentarium. Clinical trial information: NCT01168050.
MMR vaccine debate
Authors: R. Fry
Journal: BMJ (2002)

Editor—Tom Heller articulates the dilemma facing doctors in many medical disciplines in his article in the ethical debate on measles, mumps, and rubella (MMR) vaccine, a debate that is being stifled because of the overwhelming evidence base in favour of immunisation.1 He reaches the core of the debate when he refers to the balance to be struck between informed consent and the right of the state to control an infectious disease. He may feel uncomfortable because he is caught between two roles: that of the agent of the state, which doctors are often unwittingly asked to be, and that of protecting the best interest of his patients.

After Alder Hey and Bristol a lot of noise has been made centrally about the need to put patients first and reverse what is seen as the historical imbalance in power between doctors and clients, as Pattison points out in the final paragraph of his contribution to the debate.1 The need for a power differential between experts and clients and for an implicit contract between the parties in terms of who delivers the expertise is currently out of vogue.

If the profession is to be shaken into putting patients first, how does it also put evidence or central government directives first? Doing it surreptitiously by payments for immunisation targets helps no one. Therefore, in its attempt to put patients first the government will presumably now revoke immunisation targets and reincorporate the monies into general practitioners' basic remuneration—still time to include this in the new contractual arrangements.

If not, then it will presumably support giving doctors time to prepare their own leaflets on the available evidence, individualise their patient care, and then state that once informed it is entirely up to parents to decide on the best course of action for their child.

The only other way to extract clinicians from this mire would be to separate the functions of patient advocacy and protection from central pronouncements and evidence based medicine. This might lead to the evolution of new professions: those of expert (remunerated) patient advocates accompanying patients to consultations. It could also lead to two types of doctors: those trained in evidence based medicine and those trained in person centred medicine. They would work in pairs and debate issues in front of patients, who would then decide. This already happens in the postmodern world of family therapy, in the “reflecting team” approach.2 It would cost more, but it might allow people to reoccupy positions of expertise that are reconcilable and put patients where the government wants them: in the driving seat. Of course they might have to take responsibility for their decisions, and what would that do to the system in which people sue for negligence?
Late-breaking abstract: Changes in cortisol levels in the plasma of asthmatic individuals undergoing allergen inhalation challenge differentiate isolated early from dual responders
Authors: Scott Tebbutt, Sarah Kam, Amrit Singh, Louis-Philippe Boulet, Mark FitzGerald, Gail Gauvreau, Paul O'Byrne
Journal: European Respiratory Journal (2011)

Allergen inhalation challenge in mild asthmatic subjects induces airflow obstruction, airway hyperresponsiveness and inflammation, and provides a model for hypothesis-generating experiments to understand molecular regulation of these responses. Adult asthmatic subjects (18-55 years of age, with stable, mild allergic asthma, n=14) underwent cat allergen inhalation challenges. All subjects had an early asthmatic response of ≥20% fall in FEV1, and six individuals also had a late phase response of ≥15% fall in FEV1 (dual responders). Blood samples were collected just prior to, and two hours after allergen challenge. We have evaluated the differential changes in genome-wide gene expression in peripheral blood cells and changes in the plasma metabolome, post-challenge compared to pre-challenge. Amongst other findings, we have demonstrated significantly reduced cortisol levels in the plasma of mild asthmatic subjects post-challenge, compared to pre-challenge (p=0.013). Importantly, this reduction in plasma cortisol was only significant in subjects who had an isolated early asthmatic reaction, rather than in subjects who also went on to develop a late phase asthmatic reaction. Interestingly, this is consistent with gene expression data demonstrating that in isolated early responders only, there is a significant increase in RNA transcript levels for the hydroxysteroid (11-beta) dehydrogenase 2 gene (HSD11B2), post-challenge compared to pre- (p=0.026). The HSD11B2 enzyme converts cortisol to inactive cortisone. Thus, allergen inhalation challenge may improve understanding of pathways and underlying genes associated with asthma.
Abstract 6283: Obstructive Sleep Apnea Syndrome Associated with Major Cardiovascular Events in Male Diabetic Patients
Authors: Michel P Hermans, Sylvie A Ahn, Michel F Rousseau
Journal: Circulation (2008)

Obstructive sleep apnea syndrome (OSAS), an obesity comorbidity, is an independent risk factor for diabetes (T2DM) and major cardiovascular events (MACE). While OSAS prevalence and association with MACE are well documented in the general population, such information is not available in T2DM. We analyzed 467 consecutive male T2DM outpatients in whom OSAS was diagnosed through Epworth’s Sleepiness Scale (ESS), overnight oximetry and polysomnography. OSAS (+) (n=43) were compared to OSAS (−) (n=424) regarding cardiovascular (CV) risk factors and MACE. Mean (1SD) age was 64 (12) years, diabetes duration 13 (9) years. Metabolic syndrome prevalence was 77%, HbA1c 7.6 (1.6) %. OSAS prevalence was 9%. There were no differences in age, diabetes duration, smoking, blood pressure and lipids between OSAS (+) and (−). There were significant differences in ESS score, ethanol intake, hypertension, BMI, waist, relative/absolute fat, conicity index, and visceral fat, all higher in OSAS (+) p&lt;0.05. Nasal continuous positive airway pressure was used by 37% of OSAS (+). OSAS (+) were less often in primary prevention (PP) for CV disease than OSAS (−) (43 vs. 66%; p&lt;0.003), with MACE and coronary artery disease (CAD) prevalence 61 and 63% higher (61 vs. 38%; p&lt;0.01 and 44 vs. 27%; p&lt;0.03), as well as much higher stroke prevalence (15 vs. 8%; NS) (see Figure ). OSAS is frequent in male T2DM patients (9%) and associated with a marked increase in MACE and CAD. With gender and diabetes ruled out as confounders, this increase is related to classical and emerging risk factors such as hypertension, BMI, waist, relative/absolute fat, conicity index, and visceral fat.
Hyperfunctioning Intrathyroid Parathyroid Gland: A Potential Cause of Failure in Parathyroid Surgery<sup>1</sup>
Authors: Chiu-an Wang
Journal: Journal of the Royal Society of Medicine (1981)

Four patients with hyperfunctioning intrathyroid parathyroid are reported. In each case the intrathyroid parathyroid was embedded within the thyroid parenchyma and appeared as a solitary ‘cold’ thyroid nodule by radioactive iodine scanning. It is believed that the intrathyroid parathyroid evolves as the lateral lobe of the thyroid fuses with the isthmus in the early development of the thyroid. Embryologically, an intrathyroid parathyroid is thus likely to be the superior gland. When the superior parathyroid gland is missing at the time of exploration, a nodule within the ipsilateral lobe of the thyroid may well be an intrathyroid parathyroid. Under these conditions, lobectomy for the exclusion of such a gland is mandatory.
Nucleus to Synapse Nesprin1 Railroad Tracks Direct Synapse Maturation through RNA Localization
Authors: Mary Packard, Vahbiz Jokhi, Baojin Ding, Catalina Ruiz-Cañada, James Ashley, Vivian Budnik
Journal: Neuron (2015)

An important mechanism underlying synapse development and plasticity is the localization of mRNAs that travel from the nucleus to synaptic sites. Here we demonstrate that the giant nuclear-associated Nesprin1 (dNesp1) forms striated F-actin-based filaments, which we dubbed "railroad tracks," that span from muscle nuclei to postsynaptic sites at the neuromuscular junction in Drosophila. These railroad tracks specifically wrap around immature boutons formed during development and in response to electrical activity. In the absence of dNesp1, mRNAs normally localized at postsynaptic sites are lacking and synaptic maturation is inhibited. This dNesp1 function does not depend on direct association of dNesp1 isoforms with the nuclear envelope. We also show that dNesp1 functions with an unconventional myosin, Myo1D, and that both dNesp1 and Myo1D are mutually required for their localization to immature boutons. These studies unravel a novel pathway directing the transport of mRNAs from the nucleus to postsynaptic sites during synaptic maturation. VIDEO ABSTRACT.
Multiple Myeloma: Most Common End-Organ Damage and Management
Authors: Mohamad A. Hussein
Journal: Journal of the National Comprehensive Cancer Network (2007)

End-organ damage is the factor that differentiates plasma cell dyscrasia requiring therapy (active multiple myeloma [MM]) from disease that does not require therapy (monoclonal gammopathy of undetermined significance and smoldering [asymptomatic] MM). Progressive skeletal destruction is the hallmark of MM and responsible for principle morbidity in the disease. The spine is the most afflicted skeletal organ, and vertebral fractures have significantly contributed to its poor prognosis. Early mortality in MM is usually attributed to the combined effects of active disease and comorbid factors. Infection and renal failure are the main direct causes of early mortality. Using bisphosphonates to manage skeletal events mainly by preventing or slowing the destructive process has become an important adjunctive treatment in MM. Advances in minimally invasive surgical techniques, such as percutaneous vertebroplasty and kyphoplasty, offer these patients less-invasive options for treating vertebral collapse and restoring function. The aggressive management of other complications of the disease through more effective and less toxic therapy that targets the primary disease, in addition to supportive care, is resulting in patients experiencing less morbidity and probably lower mortality. This article reviews recent advances in the understanding of bone disease in MM, the role of bisphosphonates in preventing skeletal events, and available data on percutaneous vertebroplasty and kyphoplasty, and discusses the management of infection and renal failure, which seem to be responsible for high initial mortality and thereby compromise the current advances in therapy.
Dissociation of locomotor and cerebellar deficits in a murine Angelman syndrome model
Authors: Caroline F. Bruinsma, Martijn Schonewille, Zhenyu Gao, Eleonora M.A. Aronica, Matthew C. Judson, Benjamin D. Philpot, Freek E. Hoebeek, Geeske M. van Woerden, Chris I. De Zeeuw, Ype Elgersma
Journal: Journal of Clinical Investigation (2015)

Angelman syndrome (AS) is a severe neurological disorder that is associated with prominent movement and balance impairments that are widely considered to be due to defects of cerebellar origin. Here, using the cerebellar-specific vestibulo-ocular reflex (VOR) paradigm, we determined that cerebellar function is only mildly impaired in the Ube3am–/p+ mouse model of AS. VOR phase-reversal learning was singularly impaired in these animals and correlated with reduced tonic inhibition between Golgi cells and granule cells. Purkinje cell physiology, in contrast, was normal in AS mice as shown by synaptic plasticity and spontaneous firing properties that resembled those of controls. Accordingly, neither VOR phase-reversal learning nor locomotion was impaired following selective deletion of Ube3a in Purkinje cells. However, genetic normalization of αCaMKII inhibitory phosphorylation fully rescued locomotor deficits despite failing to improve cerebellar learning in AS mice, suggesting extracerebellar circuit involvement in locomotor learning. We confirmed this hypothesis through cerebellum-specific reinstatement of Ube3a, which ameliorated cerebellar learning deficits but did not rescue locomotor deficits. This double dissociation of locomotion and cerebellar phenotypes strongly suggests that the locomotor deficits of AS mice do not arise from impaired cerebellar cortex function. Our results provide important insights into the etiology of the motor deficits associated with AS.
Infected Abdominal Aortic Aneurysm Attributable to <i>Haemophilus influenzae</i>
Authors: Jessie Risse, Nicla Settembre, Damien Mandry, Haroun Benayad, Camille Lemarié, Corentine Alauzet, Stéphane Zuily, Alix Bertaux, Sergueï Malikov, Michel Claudon, Denis Wahl
Journal: Circulation (2015)
2008 European Football Championship - ECDC epidemic intelligence support
Authors: P Kreidl, P Buxbaum, F Santos-O’Connor, L Payne, R Strauss, H Hrabcik, H. C. Matter, A Dreyfus, P Arias
Journal: Eurosurveillance (2008)

Mass gathering events may pose an increased risk for outbreak of infectious diseases, and a potential for rapid international spread [1,2]. Even events not considered relevant from the public health point of view can have a big media impact. The European Centre for Disease Prevention and Control (ECDC) has on several occasions given support to the European Union Member States (EU MS) during sporting events such as the Olympic Games and football championships to ensure the rapid detection of possible public health risks [3-6].
Neurological Examination of the Unconscious Patient
Authors: M C Walker, M D O'brien
Journal: Journal of the Royal Society of Medicine (1999)

All unconscious patients should have neurological examinations to help determine the site and nature of the lesion, to monitor progress, and to determine prognosis. The examination consists of observing the patient and eliciting reflexes. We have provided a scheme for the bedside neurological examination of the unconscious patient that can be easily and quickly executed and is easy to interpret. We have not tried to provide a comprehensive pathophysiology of coma; for a more detailed discussion see Plum and Posnert. The Glasgow coma scale should be completed (Table 1) and a coma chart initiated to monitor pupillary reactions, pulse, temperature and blood pressure. Neurological examination is most useful in the well-oxygenated, normotensive, normoglycaemic patient with no sedation, since hypoxia, hypotension, hypoglycaemia and sedating drugs profoundly affect the signs elicited.
BMA calls for 20% sugar tax to subsidise cost of fruit and vegetables
Authors: Ingrid Torjesen
Journal: BMJ (2015)

The British Medical Association is calling on the government to introduce a 20% tax on sugary drinks to help tackle the increasing prevalence of obesity and diet related health problems in the United Kingdom by using the money to subsidise the cost of fruit and vegetables.1

The BMA also wants the government to make it mandatory for all the 3500 independently run academy schools and 200 free schools in England to adhere to the same food standards as set for state schools, such as not serving soft drinks and providing at least …