tbuckley/cabot-search huggingface dataset:
Cardiac Calcitropes, Myotropes, and Mitotropes
Authors: Mitchell A. Psotka, Stephen S. Gottlieb, Gary S. Francis, Larry A. Allen, John R. Teerlink, Kirkwood F. Adams, Giuseppe M.C. Rosano, Patrizio Lancellotti
Journal: Journal of the American College of Cardiology (2019)

The term “inotrope” is familiar and intimately connected with pharmaceuticals clinically used for treatment of low cardiac output with cardiogenic shock. Traditional inotropic agents exert their effect by modulating calcium signaling in the myocardium. Their use is associated with poor long-term outcomes. Newer molecules in development intend to break from calcium mediation and the associated detrimental long-term effects by targeting distinct mechanisms of action to improve cardiac performance. Thus, “inotropy” does not sufficiently describe the range of potential novel pharmaceutical products. To enhance communication around and evaluation of current, emerging, and potential therapies, this review proposes a novel nuanced and holistic framework to categorize pharmacological agents that improve myocardial performance based on 3 myocardial mechanisms: calcitropes, which alter intracellular calcium concentrations; myotropes, which affect the molecular motor and scaffolding; and mitotropes, which influence energetics. Novel chemical entities can easily be incorporated into this structure, distinguishing themselves based on their mechanisms and clinical outcomes.
From medical student to junior doctor: the night shift
Authors: Geoffrey Robinson, Sharmila Bernau, Sarah Aldington, Richard Beasley
Journal: BMJ (2006)

In the last part of the series, Geoffrey Robinson and colleagues tell us how to make sure that the lights never go out during the night shift Working through an entire night is now a standard part of most junior doctors' rosters. The competing needs of service provision and limited hours has resulted in the widespread introduction of night shift systems; a junior doctor will cover several hospital wards, as well as manage acute admissions, between the hours of 10 pm and 8 am.1 The doctor may be required to work up to seven such shifts in a row, a system that has been designed to reduce the effects of sleep deprivation on clinical decision making and improve patient safety. 12 However, working at night for a week is inherently stressful and may drastically affect the wellbeing of junior medical staff and their patients.13 Photos.com Occupational physicians have long recognised that regular night shifts have a negative impact on physical and psychological wellbeing. Junior doctors work intermittent night shifts only and are therefore not at risk of many of the chronic health effects of regular night work.1 However, intermittent night shift work for doctors is also associated with tiredness, sleep deprivation, low mood, and increased stress.14 Other negative psychological effects of night shifts include a feeling of unwanted, increased clinical responsibility, isolation from medical colleagues, and the stress of covering unfamiliar specialties.1234 Although night shifts are supposed to improve patient care by avoiding 24 hour shifts, working up to seven night shifts in a row often generates serious sleep deprivation.15 Many of the other stressors of night shift are exacerbated by tiredness, so box 146 lists some suggestions to minimise risks while on nights. ### Box 1: Tips for before the night shiftRETURN TO TEXT
First aid: Syncope
Authors: Samena Chaudhry, Magnus Harrison
Journal: BMJ (2005)

In the fourth part of our series, Samena Chaudhry and Magnus Harrison explain the management of syncope Many of us will have fainted or seen someone else faint - in medicine, this is called syncope. Syncope is defined as a transient loss of consciousness associated with a decrease in cerebral blood flow.1 Differentiating true syncope from other “non-syncopal” conditions causing a loss of consciousness is important because the mechanisms of syncope range from nearly normal (physiological) to abnormal and life threatening. In syncope, bradycardia (a slow heart rate), hypotension, and a weak thready pulse are common. Unconsciousness results in muscular relaxation and may cause the tongue to fall into the oropharynx, obstructing or partially obstructing the airway - this itself is life threatening.2 Although many causes of syncope exist, we will briefly focus on the commonest causes seen in the emergency department. Presyncope is the period of time when inadequate cerebral circulation and the resulting lack of nutrition and oxygen start to take effect. Early manifestations include pale skin colour that may be cool and moist (“a cold sweat”). Some people say they feel bad, or that everything is going dark just before losing consciousness. By recognising presyncope, you can prevent a person from falling. The causes of syncope can be grouped into cardiac and non-cardiac causes (box 1). Cardiac syncope is associated with increased mortality and may lead to sudden death. Syncope affects 30% of adults at some point in their lives and is a common problem in people presenting at emergency departments.1 One reason postulated for syncope being so common reflects our incomplete evolutionary adaptation to the upright body position as standing upright requires blood pressure regulation to drive blood against gravity up to the head.3 ### Box 1: Causes of syncope #### Non-cardiac causes of syncope
Gauging the Effectiveness of Medicines Safety Communications From Global Regulatory Agencies
Authors: Gerald J. Dal Pan
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Fyn kinase regulates misfolded α-synuclein uptake and NLRP3 inflammasome activation in microglia
Authors: Nikhil Panicker, Souvarish Sarkar, Dilshan S. Harischandra, Matthew Neal, Tae-In Kam, Huajun Jin, Hariharan Saminathan, Monica Langley, Adhithiya Charli, Manikandan Samidurai, Dharmin Rokad, Shivani Ghaisas, Olga Pletnikova, Valina L. Dawson, Ted M. Dawson, Vellareddy Anantharam, Anumantha G. Kanthasamy, Arthi Kanthasamy
Journal: The Journal of Experimental Medicine (2019)

Persistent microglia-mediated neuroinflammation is a major pathophysiological contributor to the progression of Parkinson’s disease (PD), but the cell-signaling mechanisms governing chronic neuroinflammation are not well understood. Here, we show that Fyn kinase, in conjunction with the class B scavenger receptor CD36, regulates the microglial uptake of aggregated human α-synuclein (αSyn), which is the major component of PD-associated Lewy bodies. αSyn can effectively mediate LPS-independent priming and activation of the microglial NLRP3 inflammasome. Fyn kinase regulates both of these processes; it mediates PKCδ-dependent NF-κB–p65 nuclear translocation, leading to inflammasome priming, and facilitates αSyn import into microglia, contributing to the generation of mitochondrial reactive oxygen species and consequently to inflammasome activation. In vivo experiments using A53T and viral-αSyn overexpression mouse models as well as human PD neuropathological results further confirm the role of Fyn in NLRP3 inflammasome activation. Collectively, our study identifies a novel Fyn-mediated signaling mechanism that amplifies neuroinflammation in PD.
Does the Administration of Sevelamer or Nicotinamide Modify Uremic Toxins or Endotoxemia in Chronic Hemodialysis Patients?
Authors: Aurelie Lenglet, Nicolas Fabresse, Méline Taupin, Cathy Gomila, Sophie Liabeuf, Said Kamel, Jean Claude Alvarez, Tilman B. Drueke, Ziad A. Massy
Journal: Drugs (2019)
Susceptibility gene for germ cell testicular cancer localised
Authors: Nisheeth Rajpal
Journal: BMJ (2000)

Scientists have localised the susceptibility gene for germ cell testicular cancer. A multinational study whose results were published this month (Nature Genetics 2000;24:197200) was set up in an attempt to establish the genetic basis of germ cell testicular cancer, which encompasses seminoma, teratoma, and mixed lesions, and makes up over 80% of testicular cancers.

Testicular germ cell tumours are the most prevalent form of cancer in men aged 15-40 years in western Europe. In the past 30 years, the incidence of testicular germ …
Acute care: Circulatory failure and use of inotropes
Authors: Nicola Cooper
Journal: BMJ (2004)

In the fifth part of our series about acute care, Nicola Cooper discusses circulatory failure and using inotropes I bet you never realised that the dry physiology learnt at medical school would turn out to be so important later on. Let us start with blood pressure: Ohm's law has been adapted to demonstrate that blood pressure (BP) is the product of cardiac output (CO) and systemic vascular resistance (SVR)--that is, BP=CO*SVR. Therefore a low blood pressure can be due to a low cardiac output (low flow) or reduced systemic vascular resistance (vasodilatation) or both. Pressure and flow are not the same thing. There is no “normal” blood pressure. What matters is whether a low blood pressure is causing a problem. Cardiac output in turn depends on the interrelated factors of heart rate (HR) and stroke volume (SV)--that is, CO=HR*SV. Stroke volume, you will remember, is the volume of blood ejected in a single ventricular contraction. This, in turn, depends on three things--contractility, preload, and afterload. Contractility is the amount of mechanical work done for a given preload and afterload. It is increased by sympathetic stimulation and inotropes. It is reduced by parasympathetic stimulation, negative inotropes, ischaemia, hypoxaemia, acidosis, and a low serum calcium. Preload is equivalent to the final diastolic volume--how “loaded” the ventricle is just before contraction. Afterload is the tension developed in the ventricular wall during systole--so vasoconstriction increases this. To go back to the beginning, what if you have a patient with a low blood pressure that is causing hypoperfusion of vital organs, like the kidneys? The heart rate, preload, afterload then contractility need to be considered in that order (box 1). ### Box 1: Case histories 1. A patient on the coronary care unit has developed low blood pressure and poor urine output. You are called to assess him. His vital … RETURN TO TEXT
Strategies to Identify Patient Risks of Prescription Opioid Addiction When Initiating Opioids for Pain
Authors: Jan Klimas, Lauren Gorfinkel, Nadia Fairbairn, Laura Amato, Keith Ahamad, Seonaid Nolan, David L. Simel, Evan Wood
Journal: JAMA Network Open (2019)

Although prescription opioid use disorder is associated with substantial harms, strategies to identify patients with pain among whom prescription opioids can be safely prescribed have not been systematically reviewed.To review the evidence examining factors associated with opioid addiction and screening tools for identifying adult patients at high vs low risk of developing symptoms of prescription opioid addiction when initiating prescription opioids for pain.MEDLINE and Embase (January 1946 to November 2018) were searched for articles investigating risks of prescription opioid addiction.Original studies that were included compared symptoms, signs, risk factors, and screening tools among patients who developed prescription opioid addiction and those who did not.Two investigators independently assessed quality to exclude biased or unreliable study designs and extracted data from higher quality studies. The Preferred Reporting Items for Systematic Reviews and Meta-analyses of Diagnostic Accuracy Studies (PRISMA-DTA) reporting guideline was followed.Likelihood ratios (LRs) for risk factors and screening tools were calculated.Of 1287 identified studies, 6 high-quality studies were included in the qualitative synthesis and 4 were included in the quantitative synthesis. The 4 high-quality studies included in the quantitative synthesis were all retrospective studies including a total of 2 888 346 patients with 4470 cases that met the authors' definitions of prescription opioid addiction. A history of opioid use disorder (LR range, 17-22) or other substance use disorder (LR range, 4.2-17), certain mental health diagnoses (eg, personality disorder: LR, 27; 95% CI, 18-41), and concomitant prescription of certain psychiatric medications (eg, atypical antipsychotics: LR, 17; 95% CI, 15-18) appeared useful for identifying patients at high risk of opioid addiction. Among individual findings, only the absence of a mood disorder (negative LR, 0.50; 95% CI, 0.45-0.52) was associated with a lower risk of opioid addiction. Despite their widespread use, most screening tools involving combinations of questions were based on low-quality studies or, when diagnostic performance was assessed among high-quality studies, demonstrated poor performance in helping to identify patients at high vs low risk.While a history of substance use disorder, certain mental health diagnoses, and concomitant prescription of certain psychiatric medications appeared useful for identifying patients at higher risk, few quality studies were available and no symptoms, signs, or screening tools were particularly useful for identifying those at lower risk.
Film review: 28 Days
Authors: Colin Brewer
Journal: BMJ (2000)

Twenty eight days is apparently how long you normally stay if-after getting disgustingly drunk and wrecking your sister's wedding, not to mention the nuptial limousine-you reluctantly enter an American “rehabilitation” clinic. Rehabilitation is big business in the United States, and remarkably monolithic.

28 Days gives a reasonably accurate impression of life in a typical private rehabilitation facility and of some of its highs and lows. The highs include heart warming insights of the “I guess I never saw it that way” variety and the support and …
Thin women risk infertility
Authors: Kay Brennan
Journal: BMJ (2002)

Women who keep their body fat to a minimum, so they can be fashionably thin, could be putting their fertility at risk, according to a US expert. In Female Fertility and the Body Fat Connection , a new book, Professor Rose Frisch looks at fertility, body fat, and reproductive health; she suggests women who are too lean are risking infertility.

Professor Frisch, associate professor of population sciences emeritus at the Harvard Medical School of Public Health, Boston, has devised a critical fatness …
Attitudes decline in medical school
Authors: Karen Hebert
Journal: BMJ (2004)

Medical students' attitudes towards social issues decline as they progress through medical school, says a new study from the University of Calgary Medical School ( Medical Education 2004;38:522-34).

Preclinical and clinical students from three separate years filled out two questionnaires examining their attitudes towards social issues in medicine on entry to medical school, on completion of preclinical training, and on completion of medical school.

Included in the survey …
Understanding ECGs: Minding your Ps and Qs
Authors: Dominic Cox, Hamish Dougall
Journal: BMJ (2001)

In the second article in our series Dominic Cox and Hamish Dougall discuss what you need to learn and what you need to understand

In this series of articles on electrocardiograms (ECGs) we hope to convey the basic concepts of reading and using this simple clinical tool. We re-emphasise that a grasp of only a few rudimentary concepts will allow all of us, not just the cardiologists, to understand the majority of clinically important ECGs. In the first article we explained how the heart works as an engine and outlined the power supply (coronary arteries), control (electrical supply), and how that in an ECG, the electrical supply is recorded as it moves across the heart by a series of detectors placed strategically around the body.

An ECG is a two dimensional recording of a three dimensional process. A cardiac electrical impulse does not travel in a single direction down a straight line with an arrow on the end. It in fact spreads out in all directions across the heart. The ECG leads allow us to look at this depolarisation wave from different views--that is, in the vertical and horizontal planes. When the wave is heading towards a specific lead we will get the largest positive deflection in that lead. When it is heading directly away from it we will get the opposite: the largest negative response. Leads looking at right angles to the wave front will see smaller biphasic responses as the wave passes them. In this article we will go through the different parts that make up the ECG recording (see figure 1) in turn. We appreciate that the material in this, and the previous, article may seem a little dry. It is, however, worth trying to grasp the basic concepts without getting bogged down too much in the …
Asthma progression and mortality: the role of inhaled corticosteroids
Authors: Paul O'Byrne, Leonardo M. Fabbri, Ian D. Pavord, Alberto Papi, Stefano Petruzzelli, Peter Lange
Journal: European Respiratory Journal (2019)

Overall, asthma mortality rates have declined dramatically in the last 30 years, due to improved diagnosis and to better treatment, particularly in the 1990s following the more widespread use of inhaled corticosteroids (ICSs). The impact of ICS on other long-term outcomes, such as lung function decline, is less certain, in part because the factors associated with these outcomes are incompletely understood. The purpose of this review is to evaluate the effect of pharmacological interventions, particularly ICS, on asthma progression and mortality. Furthermore, we review the potential mechanisms of action of pharmacotherapy on asthma progression and mortality, the effects of ICS on long-term changes in lung function, and the role of ICS in various asthma phenotypes.Overall, there is compelling evidence of the value of ICS in improving asthma control, as measured by improved symptoms, pulmonary function and reduced exacerbations. There is, however, less convincing evidence that ICS prevents the decline in pulmonary function that occurs in some, although not all, patients with asthma. Severe exacerbations are associated with a more rapid decline in pulmonary function, and by reducing the risk of severe exacerbations, it is likely that ICS will, at least partially, prevent this decline. Studies using administrative databases also support an important role for ICS in reducing asthma mortality, but the fact that asthma mortality is, fortunately, an uncommon event makes it highly improbable that this will be demonstrated in prospective trials.
Phaeochromocytoma without hypertension
Authors: Arul Ganeshan, John Baxter
Journal: BMJ (2002)

A 34 year old woman presented with a 10 week history of paroxysmal attacks of headache associated with vomiting, sweating,and palpitations. Her blood pressure always remained normal during these episodes. A 24 hour urine collection showed a mildly elevated level of adrenaline at 180 nmol/24hr (normal < 140nmol/24hr) with normal levels of noradrenaline and dopamine. Abdominal computed tomography (CT) showed the following abnormality (see figure).



Abdominal computed tomography scan showing a cystic lesion arising from the right adrenal gland impinging on the liver capsule and the inferior vena cava



1.  What abnormality is seen on the scan?

2.  What is the likely diagnosis?

1.  A cystic adrenal tumour.

2.  Adrenal phaeochromocytoma.

Phaeochromocytoma is an uncommon tumour with an incidence estimated at 0.8 per 100 000 person years. It is associated with a variety of symptoms …
Abstract 14943: High-Throughput Contactless Optogenetic Assay for Cellular Coupling: Illustration by Chr2-Light-Sensitized Cardiac Fibroblasts and Cardiomyocytes
Authors: Jinzhu Yu, Patrick M Boyle, Christina M Ambrosi, Natalia A Trayanova, Emilia Entcheva
Journal: Circulation (2013)

Cellular coupling is an important determinant of cardiac function. The most direct way to quantify coupling, the dual patch clamp, lacks scalability and applicability in situ; other approaches are indirect and low-throughput, using fluorescent molecule diffusion to infer coupling strength. We demonstrate experimentally and computationally a conceptually new contactless assay for electrical coupling based on selective illumination of inexcitable cells expressing ChR2 (light-sensitive ion channel) and optical sensing of the response of coupled excitable cells, e.g. cardiomyocytes, that are light-insensitive. Cell-cell coupling is quantified by the energy required to elicit an action potential via junctional current from the light-excited cell(s). In vitro, we transduced primary cardiac fibroblasts (FB) with ChR2 using Ad-viral delivery, patterned them in a focal zone, and probed their coupling to a monolayer of neonatal rat cardiomyocytes (CM) by all-optical interrogation of excitability, Fig A-B. Cx43-medi...
Simulated patient centre helps students learn diagnoses
Authors: Samena Chaudhry
Journal: BMJ (2002)

Students at the University of Kentucky's College of Medicine have been learning through a different sort of patient recently.

The college has developed a centre to house patient simulators and a standardised patient program. The Clinical Skills Training And Assessment Center (CSTAC) is home to a number of machines that teach students how to identify a variety of illnesses.

At CSTAC, before working with actual patients, the students have the opportunity to …
One more step to licensure for American medical students
Authors: Sara Mangiardi, Oveys Mansuri
Journal: BMJ (2004)

American medical students will now have one additional examination to pass before being licensed to practise medicine in the United States. The National Board of Medical Examiners (NBME) will begin offering the USMLE (United States Medical Licensure Examination) Step 2 CS (Clinical Skills) examination this summer. A similar exam already exists for foreign medical graduates wishing to practise in the United States.

The NBME believes the Step 2 CS exam will allow students to show fundamental clinical skills that are not covered by the current examinations. The test will consist of medical students examining 12 “standardised patients” for 15 minutes each. After each encounter the student will be expected to …
Paper Plus: Randomised equivalence trial: cancer follow-up
Authors: Alan Rodger
Journal: BMJ (2009)

Alan Rodger looks at a study that compared telephone with traditional follow-up for survivors of breast cancer ### This month's paper “Comparing hospital and telephone follow-up after treatment for breast cancer: randomised equivalence trial” by Kinta Beaver and colleagues ( BMJ 2009;338;a3147, doi:10.1136/bmj.a3147). You can read the paper and see responses to it by going to student.bmj.com and clicking on the link. #### Abstract
A human infection with a novel reassortant H3N2 swine virus in China
Authors: Jing Lu, Lina Yi, Yi Jing, Hanqing Tan, Wei Mai, Yingchao Song, Lirong Zou, Lijun Liang, Hong Xiao, Min Kang, Jie Wu, Tie Song, Changwen Ke
Journal: Journal of Infection (2019)