tbuckley/cabot-search huggingface dataset:
Abstract 5304: A genetically engineered mouse model for GBM wherein Akt kinase activity can be monitored non-invasively in real-time
Authors: Stefanie Galbán, Benjamin Lemasson, Michael J. Lafferty, Fei Li, Kevin Heist, Craig J. Galban, Brian D. Ross, Alnawaz Rehemtulla
Journal: Cancer Research (2011)

Abstract Approximately 30-40% of human gliomas exhibit mutations in the tumor suppressor gene PTEN resulting in deregulation of the phosphoinositide 3-kinase/Akt survival signaling pathway. In a significant number of GBMs tumor initiation is additionally driven by an oncogenic signal stemming from the gene locus amplification of the Platelet derived growth factor receptor (PDGFR), also leading to Akt and mammalian target of rapamycin (mTOR) activation. Phosphorylated, active Akt controls a plethora of cellular responses by regulating a large number of substrates, such as GSK-3, BAD, Forkhead transcription factors (FOXO), and MDM2. Elevated Akt activity increases tumor cell growth, survival and impairs apoptosis. Thus blocking Akt phosphorylation to treat cancer in particular gliomas has therapeutic potential. Here we demonstrate the pre-clinical use of a bioluminescent molecular reporter to evaluate Akt kinase inhibition in real time in a genetically engineered PDGF-driven PTEN-deficient mouse model of GBM. Glial cell specific delivery of the bioluminescent reporter was achieved by RCAS-TVA technology. In brief, we utilized genetically engineered PTEN loxP/loxP, Ink4a-Arf -/-, nestin-TVA transgenic animals and delivered the Akt reporter along with Cre recombinase and PDGF by intracranial implantation of chicken cells expressing avian virus containing the specific cargo. PTEN deletion in nestin positive cells resulted in increased Akt kinase phosphorylation as demonstrated by western blotting. Tumor growth was monitored by MRI and Bioluminescence imaging (BLI) technology. The design of the previously described Akt reporter allows for detectable bioluminescence only in the absence of Akt kinase activity due to the reconstitution of the wt luciferase enzyme. To evaluate the therapeutic potential of PI3-kinase- and Akt inhibitors in this pre-clinical GBM model, tumors were treated with either perifosine or API-2. Increased bioluminescence activity was observed in gliomas in a time- and dose-dependent manner with both inhibitors. These findings demonstrate that the Akt reporter provided a quantitative surrogate for Akt activity in PTEN-deficient gliomas. In conclusion we have provided a novel approach of pairing molecular imaging with a murine GBM model to investigate targeted agents. This may aid the future identification of most efficacious drug combinations impinging on PI3-kinase/Akt signaling in gliomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5304. doi:10.1158/1538-7445.AM2011-5304
Interference with Bilirubin Excretion by a Gall-Bladder Dye (Bunamiodyl)
Authors: Robert J. Bolt, Richard S. Dillon, H. Marvin Pollard
Journal: New England Journal of Medicine (1961)

PREVIOUS reports have summarized the results of thorough annual physical examinations and have reported on the value of various laboratory procedures in helping to establish diagnoses.1 , 2 As a result of these analyses, changes have been made from time to time in the laboratory procedures of our routine examinations. One of these changes included the addition of routine bilirubin determinations in asymptomatic persons. After the first 7 determinations it became obvious that total bilirubin determinations were above the generally accepted upper limit of normal of 1.0 mg. per 100 ml.3 Table 1 shows that the levels obtained were in the region of 1.1 . . .
Abstract 1999: A targeted exome sequencing platform for routine clinical molecular profiling of advanced thoracic malignancies relevant to targeted therapy.
Authors: Christopher C. Lau, Keith Killian, Yuelin J. Zhu, Yonghong Wang, Marbin Pineda, Anish Thomas, Yisong Wang, Betsy Morrow, Liqiang Xi, Mark Raffeld, Giuseppe Giaccone, Paul S. Meltzer
Journal: Cancer Research (2013)

Abstract Increasing number of oncogenic mutations important to the clinical management of advanced thoracic malignancies is being identified. To translate this into routine clinical testing environment, we developed and validated a targeted exome sequencing method using next generation sequencing (NGS) technology that is designed to detect both single nucleotide variants and short insertions or deletions (indels) by employing a custom designed target selection system. In each individual assay, 197 cancer related genes, including 12 clinically relevant genes (AKT1, AKT2, BRAF, EGFR, ERBB2, HRAS, KIT, KRAS, MEK1, NRAS, PIK3CA, and PTEN) are simultaneously sequenced from 100-500ng of total DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue. To date, we have performed this assay on over 250 FFPE tissues from Non-Small-Cell Lung Cancers (NSCLC), Small-Cell Lung Cancers (SCLC), and thymic malignancies. Mutations in all 12 clinically relevant genes including EGFR L858R, KRAS codon 12 missense mutations as well as EGFR exon 19 deletions, EGFR exon 20 insertions, and ERBB2 exon 20 insertions have been identified and validated with alternate technology in approximately 30% of all samples tested. Compared with conventional capillary sequencing, which typically requires in excess of 25% mutant DNA, this assay can detect mutations with 5% - 10% mutant allele frequency. This is a robust, reliable and cost effective assay that not only is suitable for prospective molecular profiling of clinically relevant targets, but also provides a powerful tool for retrospective analysis of existing FFPE tissues from clinical trials. Citation Format: Christopher C. Lau, Keith Killian, Yuelin J. Zhu, Yonghong Wang, Marbin Pineda, Anish Thomas, Yisong Wang, Betsy Morrow, Liqiang Xi, Mark Raffeld, Giuseppe Giaccone, Paul S. Meltzer. A targeted exome sequencing platform for routine clinical molecular profiling of advanced thoracic malignancies relevant to targeted therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1999. doi:10.1158/1538-7445.AM2013-1999
AB0863 Prevalence of sexual dysfunction in patients with ankylosing spondylitis
Authors: A. Akdag, B.S. Budak, N. Samanci Karaman, N. Balci
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Ankylosing Spondylitis (AS) is a chronic, systemic and inflammatory disease affecting spine, peripheral joints and periarticular area causing movement restriction in axial joints. AS itself does not affect sexual functions but it can lead to sexual problems due to pain and stiffness in active stages, movement restriction and disability in advanced stages. Also psychological problems caused by its chronic nature can lead to sexual problems. In this study, we investigated sexual disfunctions in AS patients. <h3>Methods</h3> Patients were divided into two groups - each involving 100 patients – as AS group and control group. AS group consisted of patients diagnosed according to Modified New York Criteria for AS. In control group, patients with extremity pain evaluated in physical medicine polyclinic and diagnosed as tendinitis, bursitis and epicondylitis were included. Patients having waist and back pain and patiens with a history of rheumatologic inflammatory disease were excluded. Demographic data of patients were recorded. All patients filled ASEX and BDI forms. In AS group, patients were also asked for disease duration and medication history and they were asked to fill BASDAI and BASFI forms. <h3>Results</h3> Sexsual function disorder was detected in 66% and 30% patients in AS and control group, respectively. In AS group, statistically significant correlation was detected between sexsual function disorder and BASDAI and BASFI scores. So that it was suggested that disease activity could affect sexual function. According to BDI, depression was detected in 33% of AS group and in 5% of control group. This difference between two groups was thought to be related to disease activity and functional movement restriction. In AS group, no statistically correlation between sexual function disorder and disease duration and anti-TNF therapy was detected. <h3>Conclusions</h3> In this study, it was detected that prevalence of sexual function disorder is statistically higher in AS patients when it is compared with normal population. Also prevalance of depression was higher in AS group suggesting that psychological problems related to disease could affect the frequency and severity of sexual function disorder. <h3>Disclosure of Interest</h3> None Declared
SP0028 Are Guidelines Really Changing Outcomes?
Authors: C. Bombardier
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Improving health outcomes in patients requires the timely and effective integration of research evidence into clinical practice. However, transfer of evidence into routine care can be slow and unpredictable. A number of clinical practice guidelines have been published linking specific practice recommendations to improved patient outcomes. We now recognize that guidelines alone do not necessarily result in a change in practice. To accelerate practice changes, Quality Indicators have been proposed to measure whether specific practice guidelines have been adhered to in routine practice. Indeed examination of the quality of arthritis care suggests that patients may still not be getting the right care at the right time: there remains significant variations in care, delays to treatments and slow uptake of therapeutic advances. These findings suggest that, to improve patient outcomes, clinical practice guidelines must be supplemented with strategies that measure and evaluate if care provided in daily clinical settings adheres to current recommendations for best practices. <h3>Disclosure of Interest</h3> None Declared
Mass Drug Administration for Scabies Control in a Population with Endemic Disease
Authors: Lucia Romani, Margot J. Whitfeld, Josefa Koroivueta, Mike Kama, Handan Wand, Lisi Tikoduadua, Meciusela Tuicakau, Aminiasi Koroi, Ross Andrews, John M. Kaldor, Andrew C. Steer
Journal: New England Journal of Medicine (2015)

Scabies is an underrecognized cause of illness in many developing countries. It is associated with impetigo, which can lead to serious systemic complications. We conducted a trial of mass drug administration for scabies control in Fiji.
Atrial Fibrillation in Heart Failure
Authors: William G. Stevenson, Lynne Warner Stevenson
Journal: New England Journal of Medicine (1999)

In 1920 Sir James Mackenzie reported that atrial fibrillation was present in 80 to 90 percent of patients who had congestive heart failure, which at that time was called “dropsy.”1 In patients with symptomatic heart failure today, the prevalence of atrial fibrillation ranges from 10 to 30 percent, with the highest incidence among those with the most severe heart failure.2,3 Although there are conflicting data as to whether atrial fibrillation is associated with an adverse outcome,24 this perception has long been common. A recent analysis revealed that the mortality rate was 34 percent higher among patients with atrial . . .
Discovery of New Infectious Diseases — Bartonella Species
Authors: Gary P. Wormser
Journal: New England Journal of Medicine (2007)

Careful microbiologic evaluation of patients with various illnesses has led to the discovery of many important pathogens in recent decades, including human immunodeficiency virus (HIV), legionella species, Borrelia burgdorferi (the agent of Lyme disease), human herpesvirus 8 (HHV-8), and numerous others. Success in these endeavors, however, was critically dependent on the availability of the appropriate technology for both the detection of the microorganism and its characterization to the level necessary to permit clear differentiation from already recognized pathogens. The delay between the recognition of a particular clinical syndrome and the identification of its causative agent has been highly variable. Whereas . . .
A Longitudinal Study of Respiratory Viruses and Bacteria in the Etiology of Acute Otitis Media with Effusion
Authors: Frederick W. Henderson, Albert M. Collier, Margaret A. Sanyal, Jessie M. Watkins, Diane L. Fairclough, Wallace A. Clyde, Floyd W. Denny
Journal: New England Journal of Medicine (1982)

We analyzed data from a 14-year longitudinal study of respiratory infections in young children to determine the relative importance of viral respiratory infection and nasopharyngeal colonization with Streptococcus pneumoniae and Haemophilus influenzae as factors influencing the occurrence of acute otitis media with effusion. The incidence of this disorder was increased in children with viral respiratory infections (average relative risk, 3.2; P<0.0001). Infection with respiratory syncytial virus, influenza virus (type A or B), and adenovirus conferred a greater risk of otitis media than did infection with parainfluenza virus, enterovirus, or rhinovirus. Colonization of the nasopharynx with Str. pneumoniae or H. influenzae had a lesser effect on the incidence of the disease (average relative risk, 1.5; P<0.01). Infections with the viruses more closely associated with acute otitis media (respiratory syncytial virus, adenovirus, and influenza A or B) were correlated with an increased risk of recurrent disease. Prevention of selected otitis-associated viral infections should reduce the incidence of this disease. (N Engl J Med. 1982; 306:1377–83.)
Abstract ES2-1: DNA Repair Pathways and Tumorigenesis
Authors: JM Ford
Journal: Cancer Research (2010)

Abstract The genome is constantly undergoing DNA damage from endogenous and environmental sources. DNA damage response pathways detect and repair DNA damage and signal to cell cycle checkpoints to allow repair to take place, thus promoting genomic stability. Multiple DNA repair pathways exist: single-strand damage or base errors are repaired by base excision repair, nucleotide excision repair or mismatch repair, while DNA doublestrand breaks are repaired by nonhomologous end joining or homologous recombination repair. These pathways may be used to repair damage caused by anticancer chemotherapy and radiotherapy. Some defects in DNA damage responses are associated with the genomic instability that is a characteristic of cancer. Targeting the remaining DNA damage response pathways could potentially result in tumor selective therapies. Poly(ADP-ribose) polymerase (PARP) inhibitors have shown great promise in this respect, and early clinical data are beginning to emerge. PARP inhibitors enhance the activity of several DNA damaging and crosslinking chemotherapeutic agents and ionizing radiation. An exciting aspect is the selective toxicity of PARP inhibitors in DNA defective tumors, such as those associated with BRCA mutations or breast cancers exhibiting the triple-negative phenotype. This discovery has led to a paradigm shift in cancer therapy representing a targeted, tumor-specific, nontoxic therapy that is supported by emerging clinical data. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES2-1.
Parathyroid Adenoma Visualization on Octreotide Scintigraphy
Authors: Hatem Boulahdour, Anne-Marie Bertrand, Sébastien Klingelschmitt, Boris Rudenko, Andres Loboguerrero, Anny-Claude Bidet, Georges Mantion, Jean-Claude Cardot
Journal: Clinical Nuclear Medicine (2002)

BOULAHDOUR, HATEM M.D., Ph.D.; BERTRAND, ANNE-MARIE M.D.; KLINGELSCHMITT, SÉBASTIEN M.D.; RUDENKO, BORIS M.D.; LOBOGUERRERO, ANDRES M.D., Ph.D.; BIDET, ANNY-CLAUDE M.D.; MANTION, GEORGES M.D., Ph.D.; CARDOT, JEAN-CLAUDE M.D., Ph.D. Author Information
Internal Ventricular Defibrillation
Authors: A J Moss, J P Daubert
Journal: New England Journal of Medicine (2000)

Figure 1. A 12-year-old boy with the familial long-QT syndrome had an automatic cardioverter–defibrillator implanted after resuscitation from cardiac arrest. The device was programmed to wait 7.5 seconds before discharging in response to ventricular tachycardia or ventricular fibrillation. The boy took 120 mg of nadolol daily. Three months later, he suddenly collapsed while answering a question in school. Analysis of the cardioverter–defibrillator revealed the following sequence of events: normal sinus rhythm with a corrected QT interval of 0.66 second (top tracing) was followed by torsade de pointes (middle tracing) and ventricular fibrillation (bottom tracing), prompting discharge of the cardioverter–defibrillator (arrow) . . .
RISK-TREATMENT PARADOX IN PREVALENCE AND DETERMINANTS OF POTENT P2Y12 INHIBITOR USE IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION: RESULTS FROM A LARGE SINGLE-CENTER REGISTRY
Authors: Raman Sharma, Usman Baber, Melissa Aquino, Jason Kovacic, Joseph Sweeny, Pooja Vijay, Srushti Shah, George Dangas, Roxana Mehran, Annapoorna Kini, Samin Sharma
Journal: Journal of the American College of Cardiology (2016)
MULTIMODALITY IMAGING TO ASSESS DETERMINANTS OF EXERCISE CAPACITY IN HYPERTROPHIC CARDIOMYOPATHY
Authors: Anna Axelsson, Kasper Iversen, Niels Vejlstrup, Lasse Langhoff, Jakob B. Norsk, Anna F. Thomsen, Morten Jensen, Henning Bundgaard
Journal: Journal of the American College of Cardiology (2015)
AB1454-HPR Quality of life in patients with behÇet’s disease: the effects of disease severity and duration
Authors: R.N. Demirtas, S. Yasar Bilge, C. Korkmaz
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Behçet’s disease (BD) is a chronic, inflammatory, multisystemic vasculitic disorder with a wide spectrum of clinical presentations, BD may deteriorate of quality of life. <h3>Objectives</h3> This study aimed to investigate effects of disease severity and duration on general health related quality of life in patients with Behçet’s Disease (BD) <h3>Methods</h3> Patients fulfilling the International Study Group criteria for BD (ISGc) participated in our study. Disease severity was determined by related criteria.The quality of life was assessed by Short Form-36 (SF-36) questionnaire in 8 domains: physical function, role physical, bodily pain, general health, vitality, social function, role emotional, mental health. For usual clinical assessment, the routine assessment of patient index data (RAPID3) which is an index of three patient self-report measures-physical function, pain, and patient global estimate of status, was administered. <h3>Results</h3> Thirty BD patients (15 female, 15 male) with a median age of 39,7±8,23 years were investigated in our study. The duration of BH was correlated to the scores of mental health domain of SF-36 (r = -,419, p&lt;0,05) and RAPID3-pain (r =,374, p&lt;0,05). The severity of BH was correlated to the body weight (r = -,389, p&lt;0,05), the scores of physical function (r = -,401, p&lt;0,05), bodily pain (r = -,406, p&lt;0,05) domains of SF-36 and RAPID3-global status (r =,387, p&lt;0,05). The correlations of severity and duration of BH and other scores of SF-36 and RAPID3 were poor (p&gt;0,05). There were relationships between the domains scores of SF-36 and RAPID3 (p&gt;0,05-p&lt;0,001). <h3>Conclusions</h3> In the light of these results, the severity and duration of BD negatively affect both physical and mental components of health related quality of life in patients with BD. <h3>References</h3> Pincus T, Bergman MJ, Yazici YRAPID3-an index of physical function, pain, and global status as “vital signs” to improve care for people with chronic rheumatic diseases. Bull NYU Hosp Jt Dis. 2009;67(2):211-25. Bernabé E, Marcenes W, Mather J, Phillips C, Fortune F. Impact of Behçet’s syndrome on health-related quality of life: influence of the type and number of symptoms. Rheumatology (Oxford). 2010 Nov;49(11):2165-71. Epub 2010 Jul 30. Ertam I, Kitapcioglu G, Aksu K, Keser G, Ozaksar A, Elbi H, Unal I, Alper SQuality of life and its relation with disease severity in Behçet’s disease. Clin Exp Rheumatol. 2009 Mar-Apr;27(2 Suppl 53):S18-22. <h3>Disclosure of Interest</h3> None Declared
Case 14-1996
Authors: S.J. Thaler, E.M. Bailey
Journal: New England Journal of Medicine (1996)

Presentation of CaseA 66-year-old woman was admitted to the hospital because of possible toxic epidermal necrolysis.Her medical history included primary hypothyroidism, allergy to penicillin, long-standing hypertension, inflammatory arthritis with a positive test for antinuclear antibodies, and progressive, idiopathic chronic renal failure. The arthritis had been treated for several years with prednisone. Eight months before admission, acute renal tubular necrosis developed during a urinary tract infection, and insulin was prescribed for adult-onset diabetes mellitus that had responded for six years to oral hypoglycemic agents. Four months before admission, extracorporeal hemodialysis was initiated. Six weeks before admission, methotrexate was begun; . . .
238 EXTRACORPOREAL LIVER SUPPORT USING UCL-ARSENEL REDUCES INFLAMMATION, IMPROVES HAEMODYNAMIC FUNCTION AND INCREASE SURVIVAL TIME IN A PORCINE PARACETAMOL-INDUCED ACUTE LIVER FAILURE MODEL
Authors: N.A. Davies, P. Leckie, A. Proven, C. Thiel, K. Thiel, M. Schenk, R. Flieg, M. Storr, R. Jalan
Journal: Journal of Hepatology (2012)
Free needles for drug addicts: dont forget the syringe [letter]
Authors: Walterspiel Jn
Journal: New England Journal of Medicine (1988)

The recent New York City program to distribute free needles received wide media attention.  Unfortunately the press spoke of needles only without mentioning their counterpart--the syringe.  Each change of a used needle contaminates the contents of the syringe.  The mechanism for this is a short-lived buildup of negative pressure between the needle hub and the syringe nozzle.  This causes the needles contents to be propelled into the syringe and to contaminate the syringes contents.  Drug addicts health care workers and the press should be aware of this.  (full text)