tbuckley/cabot-search huggingface dataset:
Mechanism by Which Mammalian Target of Rapamycin Inhibitors Sensitize Multiple Myeloma Cells to Dexamethasone-Induced Apoptosis
Authors: Huajun Yan, Patrick Frost, Yijiang Shi, Bao Hoang, Sanjai Sharma, Myrna Fisher, Joseph Gera, Alan Lichtenstein
Journal: Cancer Research (2006)

Abstract Mammalian target of rapamycin (mTOR) inhibitors curtail cap-dependent translation. However, they can also induce post-translational modifications of proteins. We assessed both effects to understand the mechanism by which mTOR inhibitors like rapamycin sensitize multiple myeloma cells to dexamethasone-induced apoptosis. Sensitization was achieved in multiple myeloma cells irrespective of their PTEN or p53 status, enhanced by activation of AKT, and associated with stimulation of both intrinsic and extrinsic pathways of apoptosis. The sensitizing effect was not due to post-translational modifications of the RAFTK kinase, Jun kinase, p38 mitogen-activated protein kinase, or BAD. Sensitization was also not associated with a rapamycin-mediated increase in glucocorticoid receptor reporter expression. However, when cap-dependent translation was prevented by transfection with a mutant 4E-BP1 construct, which is resistant to mTOR-induced phosphorylation, cells responded to dexamethasone with enhanced apoptosis, mirroring the effect of coexposure to rapamycin. Thus, sensitization is mediated by inhibition of cap-dependent translation. A high-throughput screening for translational efficiency identified several antiapoptotic proteins whose translation was inhibited by rapamycin. Immunoblot assay confirmed rapamycin-induced down-regulated expressions of XIAP, CIAP1, HSP-27, and BAG-3, which may play a role in the sensitization to apoptosis. Studies in a xenograft model showed synergistic in vivo antimyeloma effects when dexamethasone was combined with the mTOR inhibitor CCI-779. Synergistic effects were associated with an enhanced multiple myeloma cell apoptosis in vivo. This study supports the strategy of combining dexamethasone with mTOR inhibitors in multiple myeloma and identifies a mechanism by which the synergistic effect is achieved. (Cancer Res 2006; 66(4): 2305-13)
United Kingdom back pain exercise and manipulation (UK BEAM) trial
Authors: Richard Tillett
Journal: BMJ (2005)

Developing primary palliative care Continuity of care is paramount but needs to be tailored individuallyEditor-Riley suggests that completion of a form detailing palliative care management should be mandatory for general practitioners. 1 I have spent a great deal of time promoting palliative medicine in primary care, with variable success.Much depends on the individual practitioner's experience and interest, which probably accounts for the variable success of handover forms to communicate with out of hours services.Making this a compulsory part of general practice might bring all practice to the same level.But the initial answer to the question, "Would I be surprised if my patient died in the next 12 months?"would then make the difference.Cynical practitioners would probably answer no for nearly all of their patients, for the longer you practise the less often you are surprised.But, in truth, for many patients in general practice the answer to this question would be no: many elderly patients who live in nursing or residential homes, nearly all patients with chronic disease, including heart disease, chronic obstructive pulmonary disease, neurological disease, and so on.The workload in handing these patients over to the out of hours service would be huge, more so for the out of hours service than the individual practice.Continuity of care for patients who most need it is paramount, including all those with chronic disease.However, more sophisticated systems are needed to meet patient needs: perhaps different systems for different diseases, possibly different systems for each stage of a disease.Whatever the system, it must meet the needs of the individual patient.This entails dialogue between primary care (including out of hours), secondary care, and tertiary care to thrash out the detail.
Measurement of end-expiratory lung volume in intubated children without interruption of mechanical ventilation
Authors: Ido G. Bikker, Thierry V. Scohy, None Ad J. J. C. Bogers, Jan Bakker, Diederik Gommers
Journal: Intensive Care Medicine (2009)

Monitoring end-expiratory lung volume (EELV) is a valuable tool to optimize respiratory settings that could be of particular importance in mechanically ventilated pediatric patients. We evaluated the feasibility and precision of an intensive care unit (ICU) ventilator with an in-built nitrogen washout/washin technique in mechanically ventilated pediatric patients.Duplicate EELV measurements were performed in 30 patients between 5 kg and 43 kg after cardiac surgery (age, median + range: 26, 3-141 months). All measurements were taken during pressure-controlled ventilation at 0 cm H(2)O of positive end-expiratory pressure (PEEP).Linear regression between duplicate measurements was excellent (R (2) = 0.99). Also, there was good agreement between duplicate measurements, bias +/- SD: -0.3% (-1.5 mL) +/- 5.9% (19.2 mL). Mean EELV +/- SD was 19.6 +/- 5.1 mL/kg at 0 cm H(2)O PEEP. EELV correlated with age (p < 0.001, r = 0.92, R (2) = 0.78), body weight (p < 0.001, r = 0.91, R (2) = 0.82) and height (p < 0.001, r = 0.94, R (2) = 0.75).This ICU ventilator with an in-built nitrogen washout/washin EELV technique can measure EELV with precision, and can easily be used for mechanically ventilated pediatric patients.
Truth Telling: A Cultural or Individual Choice?
Authors: Ralph A. Capone
Journal: JAMA (1993)

<h3>To the Editor.</h3> —The recent article<sup>1</sup>and the accompanying Editorial<sup>2</sup>in<i>JAMA</i>are more about the interaction between the two major principles of deontological ethics (autonomy and beneficence) than about truth telling. Taken together they form an excellent primer on the proper interpretation and function of autonomy and beneficence in the clinical setting. Some clinicians and ethicists dwell too long on the potential conflict between patients' autonomy and physicians' obligations to promote patients' best interests. This may be a reaction to past abuses in clinical decision making, grounded in parentalism (paternalism), in which patients' values were rarely accounted for or completely ignored. Physicians must serve their patients, but they are not servants of their patients. Most patients do not want their physicians to be mere "technological waiters," proffering menus of high-tech items from which they choose their own treatments. Clinical medicine involves two parties with differing perspectives, values,
TUMORS OF THE NECK.Read before the Section of Surgery and Anatomy, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: WM. L. RODMAN
Journal: JAMA (1893)

No region of the body is so prolific in neoplasms as the neck. No region of the body is so important from an anatomical and surgical standpoint, containing as it does many great vessels and nerves, the integrity of which is essential to life. Therefore, the diagnosis and treatment of morbid growths in this situation is of commanding interest. Never passed the time since surgery has been practiced as an art, that its followers everywhere have not approached operations upon the neck with the greatest caution, if not trepidation. While a proper amount of anxiety should attend all operations in so vital a spot, I shall endeavor to show that the danger incurred in the removal of tumors from the neck, varies as widely as the many neoplasms differ histologically. Tumors superficial to the deep cervical fascia are comparatively easy of diagnosis and safely operable, presenting no greater danger than
PMO-019 Evaluation of evidence-based recommendations in current British society of gastroenterology guidelines
Authors: I A Rowe, R Parker, M J Armstrong, D D Houlihan
Journal: Gut (2012)

<h3>Introduction</h3> Clinical practice guidelines aim to improve patient care. They are based on best available evidence and are frequently viewed as “gold-standard” care for the disease or intervention that they address. The aim of this study was to determine the overall quality of the evidence supporting current British Society of Gastroenterology (BSG) guidelines. <h3>Methods</h3> Guidelines were retrieved from the BSG website on 6th January 2012. Those posted after 2006 were considered current. The quality of supporting evidence was graded in accordance with the systems initially used to assess the primary literature. Adherence to the BSG9s advice on guideline writing issued in 2010 was assessed in guidelines published thereafter. <h3>Results</h3> 18 BSG guidelines currently exist addressing topics in endoscopy (n=7), luminal gastroenterology (n=8), and hepatology (n=3). Four guidelines published in the study period were updates of previous guidance. These were published a median of 7.5 years after the initial guidance. Of a total of 434 evidence-based recommendations the quality of evidence was low in 42.8% (range 7.1%–85.7%), that is, from case studies or consensus opinions. High quality evidence-based recommendations (consistent data from randomised controlled trials) accounted for only 14.3% of all recommendations (range 0–45.5%). Overall, there was significant heterogeneity between guidelines. These were developed using four different evidence-grading systems. In those published since 2010 only one out of eight guidelines adhered to the evidence grading system advised by the BSG Clinical Services and Standards Committee. <h3>Conclusion</h3> Evidence-based recommendations in current guidelines are most frequently based on low quality evidence, reflecting a lack of available high quality evidence. There is significant heterogeneity in the current guidelines despite BSG committee advice on guideline writing. These findings risk reducing the utility of these guidelines and highlight important areas of unmet research need that should be addressed as a matter of priority. Studies co-ordinated through loco-regional networks could substantially improve the evidence base and ultimately patient outcomes. <h3>Competing interests</h3> None declared.
Metformin Causing Vitamin B12 Deficiency: A Guilty Verdict Without Sufficient Evidence
Authors: Rima Obeid
Journal: Diabetes Care (2014)

Metformin causing vitamin B12 (B12) deficiency has become a traditional myth in medical literature (1,2). But what evidence do we have? The possibility to measure holotranscobalamin (active B12) and the metabolic marker, methylmalonic acid (MMA), has changed the practice of diagnosing B12 deficiency in recent years. We have learned that not all low plasma B12 means a “deficiency” and not all high plasma B12 mean “sufficiency.” When B12 is internalized and is able to maintain the B12-dependent intercellular enzyme activities (methionine synthase and methylmalonyl-CoA mutase), plasma total homocysteine (tHcy) and MMA will be within the reference range. This revolution in diagnosing B12 deficiency has provided convincing evidence that metformin is not as bad as its reputation.

In the National Health and Nutrition Examination Survey (NHANES), which included 1,621 patients with diabetes (575 were taking …
THE EFFECTS OF ELECTRIC CONVULSIVE THERAPY ON CERTAIN PERSONALITY TRAITS IN PSYCHIATRIC PATIENTS
Authors: B. L. PACELLA, Z. PIOTROWSKI, N. D. C. LEWIS
Journal: American Journal of Psychiatry (1947)

Personality studies were conducted on a group of 75 psychiatric patients classified as psychoneurosis, schizophrenia, manic-depressive psychosis and involutional psychosis, before and after a course of electric convulsive therapy. The personality tests were made by means of the Minnesota Multiphasic Personality Inventory and the Rorschach perceptanalysis. The extent to which these tests may be utilized for evaluating the effects of electric shock therapy upon the personality structure are discussed. The diagnostic and prognostic value of these examinations are commented upon.
Periostitis in Typhoid Fever
Authors: J. O. Affleck
Journal: BMJ (1885)

oaie huadwd4,is,fta1 weavT..This is speciaUy the oswe ii wthm4' emphysenia; aemwia!ad phthisis.It may be asked, Are the effect ever permanent, or are they only temporary?Theshort time th Brompton Hospital bath has been openled precludes my speaking with certainty; but the medical men at the large establishments of Stock- holm, Reichenhalle, and,IlIaris offer strong ttimony to the beneficial influence lasting for years.
The response of flow-triggered infant ventilators.
Authors: M Nishimura, D Hess, R M Kacmarek
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Patient-triggered ventilation (PTV) has not been feasible for infants because of large trigger pressures and long delay times with pressure-triggered systems. Recently, four infant ventilators with flow triggering have become available. We questioned if delay times, trigger pressures, and trigger work with these ventilators would be acceptable for PTV in infants. All ventilators were attached via 3-, 4-, and 5-mm endotracheal tubes to a spontaneously breathing infant lung model. The lung simulator was set at an inspiratory time of 0.65 s, tidal volume of 15, 30, and 45 ml, and 0 and 5 cm H2O positive end-expiratory pressure (PEEP). Delay time, trigger pressure, and trigger work were determined from pressure measured at the proximal airway, trachea, and alveolus. There were significant differences between the endotracheal tube sizes, sites of measurement, ventilatory demand and ventilator brand at each PEEP level for delay time, trigger pressure, and trigger work (p < 0.001). Delay time was greatest with the 3-mm endotracheal tube at high ventilatory drive (maximum 138.2 +/- 2.1 ms). Both trigger pressure (minimum 0.23 +/- 0.02 cm H2O) and trigger work (minimum 0.05 +/- 0.01 g.ml) increased with decreasing endotracheal tube size, increasing ventilatory demand, use of PEEP, and site of measurement: alveolus > trachea > airway (maximum: trigger pressure 5.04 +/- 0.02 cm H2O; trigger work 114.48 +/- 0.88 g.ml). PTV may not be appropriate under conditions of increased ventilatory drive and small endotracheal tube size in infants.
P125 ROLE OF SIALIC-ACID-BINDING IMMUNOGLOBULIN-LIKE LECTIN-7 (SIGLEC-7) AS BIOMARKER OF LIVER DISEASE SEVERITY IN CHRONIC HCV INFECTION
Authors: S. Varchetta, D. Mele, A. Lombardi, M.C. Leoni, M. Spreafico, D. Prati, M.U. Mondelli
Journal: Journal of Hepatology (2014)
Role of free radicals and neutrophils in canine myocardial reperfusion injury: myocardial salvage by a novel free radical scavenger, 2-octadecylascorbic acid
Authors: T. KUZUYA, S. HOSHIDA, M. NISHIDA, Y. KIM, H. FUJI, A. KITABATAKE, T. KAMADA, M. TADA
Journal: Cardiovascular Research (1989)

Journal Article Role of free radicals and neutrophils in canine myocardial reperfusion injury: myocardial salvage by a novel free radical scavenger, 2-octadecylascorbic acid Get access TSUNEHIKO KUZUYA, TSUNEHIKO KUZUYA From the Division of Cardiology, First Department of Medicine, and Department of Pathophysiology, Osaka University School of Medicine, Osaka, Japan Address for correspondence and reprints: Dr Tsunehiko Kuzuya, Division of Cardiology, First Department of Medicine, Osaka University School of Medicine, 1-1-50 Fukushima, Osaka 553, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar SHIRO HOSHIDA, SHIRO HOSHIDA From the Division of Cardiology, First Department of Medicine, and Department of Pathophysiology, Osaka University School of Medicine, Osaka, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar MASASHI NISHIDA, MASASHI NISHIDA From the Division of Cardiology, First Department of Medicine, and Department of Pathophysiology, Osaka University School of Medicine, Osaka, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar YOUNGJOON KIM, YOUNGJOON KIM From the Division of Cardiology, First Department of Medicine, and Department of Pathophysiology, Osaka University School of Medicine, Osaka, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar HISAKAZU FUJI, HISAKAZU FUJI From the Division of Cardiology, First Department of Medicine, and Department of Pathophysiology, Osaka University School of Medicine, Osaka, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar AKIRA KITABATAKE, AKIRA KITABATAKE From the Division of Cardiology, First Department of Medicine, and Department of Pathophysiology, Osaka University School of Medicine, Osaka, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar TAKENOBU KAMADA, TAKENOBU KAMADA From the Division of Cardiology, First Department of Medicine, and Department of Pathophysiology, Osaka University School of Medicine, Osaka, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar MICHIHIKO TADA MICHIHIKO TADA From the Division of Cardiology, First Department of Medicine, and Department of Pathophysiology, Osaka University School of Medicine, Osaka, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 23, Issue 4, April 1989, Pages 323–330, https://doi.org/10.1093/cvr/23.4.323 Published: 01 April 1989 Article history Accepted: 28 October 1988 Published: 01 April 1989
Teenagers, HIV, and AIDS: Insights From Youths Living With the Virus
Authors: Mary Jane Rotheram-Borus
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
INDUCTION OF BRUGADA SYNDROME IN THE CANINE RV WEDGE PREPARATION BY SIMULTANEOUSLY PERFUSION OF PINACIDIL, TERFENADINE AND PILSICAINIDE
Authors: Rong Bai, Han-Xuan Tan, Rong-Hui Yu, Lei Ruan, Yang Liu, Nian Liu, Yan-Fei Ruan, Jian-Zeng Dong, Chang-Sheng Ma
Journal: Journal of the American College of Cardiology (2014)
The Nonapproved Use of Medications
Authors: Paul P. Lee, Joyce C. Yang
Journal: Ophthalmology (1991)

The need for new treatments for both established and recently described disorders has heightened awareness of the drug approval process. In particular, many ophthalmologists have questioned the ramifications of using approved drugs in nonapproved settings (such as apraclonidine) and the means of obtaining investigational drugs for patient use. The authors review the legal structures established to address these concerns and recommend approaches ophthalmologists can take to minimize their exposure to legal complications.
TCT-109 Ischemic Outcomes after Coronary Intervention of Calcified Lesions with Drug-eluting Stent: Insight from ADAPT DES study
Authors: Philippe Genereux, Ajay J. Kirtane, Mayank Yadav, Mahesh V. Madhavan, Marie-Pier Arsenault, Bernhard Witzenbichler, Giora Weisz, Ke Xu, Gary S. Mintz, Roxana Mehran, Akiko Maehara, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2014)
Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease
Authors: Rajarshi Banerjee, Michael Pavlides, Elizabeth M. Tunnicliffe, Stefan K. Piechnik, Nikita Sarania, Rachel Philips, Jane D. Collier, Jonathan C. Booth, Jurgen E. Schneider, Lai Mun Wang, David W. Delaney, Ken A. Fleming, Matthew D. Robson, Eleanor Barnes, Stefan Neubauer
Journal: Journal of Hepatology (2013)

With the increasing prevalence of liver disease worldwide, there is an urgent clinical need for reliable methods to diagnose and stage liver pathology. Liver biopsy, the current gold standard, is invasive and limited by sampling and observer dependent variability. In this study, we aimed to assess the diagnostic accuracy of a novel magnetic resonance protocol for liver tissue characterisation.We conducted a prospective study comparing our magnetic resonance technique against liver biopsy. The individual components of the scanning protocol were T1 mapping, proton spectroscopy and T2* mapping, which quantified liver fibrosis, steatosis and haemosiderosis, respectively. Unselected adult patients referred for liver biopsy as part of their routine care were recruited. Scans performed prior to liver biopsy were analysed by physicians blinded to the histology results. The associations between magnetic resonance and histology variables were assessed. Receiver-operating characteristic analyses were also carried out.Paired magnetic resonance and biopsy data were obtained in 79 patients. Magnetic resonance measures correlated strongly with histology (r(s)=0.68 p<0.0001 for fibrosis; r(s)=0.89 p<0.001 for steatosis; r(s)=-0.69 p<0.0001 for haemosiderosis). The area under the receiver operating characteristic curve was 0.94, 0.93, and 0.94 for the diagnosis of any degree of fibrosis, steatosis and haemosiderosis respectively.The novel scanning method described here provides high diagnostic accuracy for the assessment of liver fibrosis, steatosis and haemosiderosis and could potentially replace liver biopsy for many indications. This is the first demonstration of a non-invasive test to differentiate early stages of fibrosis from normal liver.
The Patient Knows Best
Authors: Lourdes C. Corman
Journal: JAMA (1987)

One of the more difficult situations we clinicians face is evaluating patients whose subjective complaints or assessments do not agree with objective findings or current orthodoxy. Although some of these patients often have clues suggesting associated or underlying psychopathology, there remain a fair number who do not seem to have any emotional problems, but give histories that cannot be confirmed objectively or who perceive various therapies in a much different light from currently held beliefs. As I reflect back on my 20-year career in medicine, I am impressed by how these patients truly know better.  During my senior clerkship, a young woman made her third visit in two days to the emergency department for an asthma attack. As had been done twice before, she was treated with mild sedation in the form of oral diazepam, intravenous aminophylline, and three subcutaneous injections of epinephrine 20 minutes apart. Steroids were withheld, as
Introduction of stearoyl moieties into a biocompatible cationic polyaspartamide derivative, PAsp(DET), with endosomal escaping function for enhanced siRNA-mediated gene knockdown
Authors: Hyun Jin Kim, Atsushi Ishii, Kanjiro Miyata, Yan Lee, Shourong Wu, Makoto Oba, Nobuhiro Nishiyama, Kazunori Kataoka
Journal: Journal of Controlled Release (2010)