tbuckley/cabot-search huggingface dataset:
Role of Cardiovascular Magnetic Resonance as a Gatekeeper to Invasive Coronary Angiography in Patients Presenting With Heart Failure of Unknown Etiology
Authors: Ravi G. Assomull, Carl Shakespeare, Paul R. Kalra, Guy Lloyd, Ankur Gulati, Julian Strange, William M. Bradlow, Jonathan Lyne, Jennifer Keegan, Philip Poole-Wilson, Martin R. Cowie, Dudley J. Pennell, Sanjay K. Prasad
Journal: Circulation (2011)

Background— In patients presenting with new-onset heart failure of uncertain etiology, the role of coronary angiography (CA) is unclear. Although conventionally performed to differentiate underlying coronary artery disease from dilated cardiomyopathy, CA is associated with a risk of complications and may not detect an ischemic cause resulting from arterial recanalization or an embolic episode. In this study, we assessed the diagnostic accuracy of a cardiovascular magnetic resonance (CMR) protocol incorporating late gadolinium enhancement (LGE) and magnetic resonance CA as a noninvasive gatekeeper to CA in determining the etiology of heart failure in this subset of patients. Methods and Results— One hundred twenty consecutive patients underwent CMR and CA. The etiology was ascribed by a consensus panel that used the results of the CMR scans. Similarly, a separate consensus group ascribed an underlying cause by using the results of CA. The diagnostic accuracy of both strategies was compared against a gold-standard panel that made a definitive judgment by reviewing all clinical data. The study was powered to show noninferiority between the 2 techniques. The sensitivity of 100%, specificity of 96%, and diagnostic accuracy of 97% for LGE-CMR were equivalent to CA (sensitivity, 93%; specificity, 96%; and diagnostic accuracy, 95%). As a gatekeeper to CA, LGE-CMR was also found to be a cheaper diagnostic strategy in a decision tree model when United Kingdom–based costs were assumed. The economic merits of this model would change, depending on the relative costs of LGE-CMR and CA in any specific healthcare system. Conclusion— This study showed that LGE-CMR is a safe, clinically effective, and potentially economical gatekeeper to CA in patients presenting with heart failure of uncertain etiology.
Epigenetics at the Epicenter of Modern Medicine
Authors: Andrew P. Feinberg
Journal: JAMA (2008)

Epigenetics, the study of non-DNA sequence-related heredity, is at the epicenter of modern medicine because it can help to explain the relationship between an individual's genetic background, the environment, aging, and disease. It can do so because the epigenetic state varies among tissues and during a lifetime, whereas the DNA sequence remains essentially the same. As cells adapt to a changing internal and external environment, epigenetic mechanisms can remember these changes in the normal programming and reprogramming of gene activity. The common disease genetic and epigenetic (CDGE) model provides an epidemiologic framework that can incorporate epigenetic with genetic variation in the context of age-related susceptibility to disease. Under CDGE, the epigenetic program can modify the effects of deleterious genes or may be influenced by an adverse environment. Thus, including epigenetics into epidemiologic studies of human disease may help explain the relationship between the genome and the environment and may provide new clues to modifying these effects in disease prevention and therapy.
The Placebo Effect
Authors: David M. Baughan
Journal: JAMA (1985)

To the Editor.—  Drs Kramer and Shapiro 1 give some valuable guidelines to improving the quality of research in their article, Scientific Challenges in the Application of Randomized Trials, in the Nov 16, 1984, issue ofThe Journal. However, I'm afraid they perpetuate some of the misunderstandings concerning the nature of the placebo effect and its role in controlled clinical trials. Two errors are found in their discussion of blinding and unblinding: If the active treatment leads to improvement in the patient's symptoms or signs, he or his physician may become unblinded... although such a bias cannot create an efficacious effect. The two errors are these: (1) The placebo effect is not simply a function of whether the patient or physician knows or correctly guesses whether the patient belongs in the control or active treatment group. (2) A placebo can create an efficacious effect, as has been amply documented. 2
Compensated function in hypertrophied ventricles of Wistar Kyoto and spontaneously hypertensive rats
Authors: R. J Tomanek, M. T Whitaker
Journal: Cardiovascular Research (1990)

The aim of the study was to compare the compensatory nature of left ventricular hypertrophy in models of normal and increased peripheral resistance.Peak left ventricular performance was compared in normotensive Wistar Kyoto (WKY) rats, in a subset of this strain with biventricular hypertrophy associated with volume overload (WKY-CH), and in spontaneously hypertensive rats (SHR), all studied at one year of age (ie, long term hypertrophy).8 WKY-CH rats with biventricular hypertrophy were compared with 8 WKY (normal right and left ventricular weights). These groups were then compared with 9 SHR rats. All were maintained under identical conditions.Left ventricular to body weight ratios (mg:g) were as follows: WKY-CH 2.78(SEM 0.09); SHR 2.90(0.09); WKY 2.10(0.09). Systolic blood pressures (mm Hg) were normal in WKY-CH [104(9)] and WKY [111(9)], but raised in SHR [163(8)]. Left ventricles from WKY and WKY-CH had normal histology and no fibre disorientation, fibrosis, or other morphological abnormalities. Peak cardiac index (ml.min-1.body weight-1) measured during rapid volume expansion with Tyrode's solution was higher in WKY-CH [427(33)] than in WKY [315(33)] and SHR [349(31)] (p less than 0.05). When peak stroke volume was expressed per mg left ventricular weight there were no significant differences between the groups. Peripheral resistance (mean arterial pressure divided by cardiac output) at peak cardiac output was higher in SHR [1.20(0.12)] than in either WKY-CH [0.57(0.08)] or WKY [0.74(0.08)].These data show that both types of hypertrophy enhance peak left ventricular performance. In WKY-CH, which have normal peripheral resistance, the larger ventricle allows a higher peak cardiac index compared to WKY with no left ventricular hypertrophy. In SHR, the higher left ventricular mass is used to overcome an increased peripheral resistance and thereby provide a normal peak cardiac index.
Dabigatran and statins: faith, hype, and transparency
Authors: T. Jackson
Journal: BMJ (2014)

This week we put the spotlight on two drug blockbusters at the heart of one of the major issues The BMJ has campaigned on in recent years: transparency, the focus of our Open Data campaign and an issue of vital importance if modern medicine is to retain the trust of doctors and the public.In the case of dabigatran and statins there has been too much emphasis on faith and hype and not enough on transparency.While The BMJ acknowledges the drugs' therapeutic value, the histories of dabigatran and statins are tales of incomplete evidence, in which people are being expected to take too much on trust.Dabigatran was the first of the new oral anticoagulants licensed to prevent stroke in patients with non-valvular atrial fibrillation.It was approved by the US Food and Drug Administration in 2010 and by the European Medicines Agency for this use a year later.The drug's unique selling point, said its manufacturer, Boehringer Ingelheim, was that it would need no monitoring, unlike warfarin.Once on the market, dabigatran proved a rapid financial success, with global turnover exceeding $1bn by April 2012.But, as sales soared, concerns grew about the reports of fatal bleeds that were beginning to emerge.
Inflammatory Response After Open Heart Surgery
Authors: Brit Dybdahl, Alexander Wahba, Egil Lien, Trude H. Flo, Anders Waage, Nilofer Qureshi, Olav F.M. Sellevold, Terje Espevik, Anders Sundan
Journal: Circulation (2002)

Background — Coronary artery bypass grafting with the use of cardiopulmonary bypass is known to mediate an inflammatory response. The stress-inducible heat-shock protein (HSP) 70 has been detected in myocardial cells after CABG, and toll-like receptors (TLRs) are suggested as putative signaling receptors for the HSPs, mediating synthesis of inflammatory cytokines. The main aims of our study were to explore the release of HSP70 and the regulation of monocyte TLR-2 and TLR-4 expression after CABG. Methods and Results — Twenty patients referred for elective CABG were included in this study. Using immunoassays, we detected HSP70 in plasma after CABG, with peak concentration immediately after surgery. Interleukin-6 in plasma reached peak concentration 5 hours after surgery. Monocyte CD14, TLR-2, and TLR-4 expression, as analyzed by flow cytometry, was initially downregulated. On day 1, CD14 expression normalized, whereas TLR-2 and TLR-4 expression was upregulated. TLR-4 was significantly upregulated even on postoperative day 2. Additional experiments revealed that peritoneal macrophages from control (C3H/HeN) mice responded to HSP70 with release of tumor necrosis factor, whereas macrophages from mutated TLR-4 (C3H/HeJ) mice were unresponsive. In vitro, human adherent monocytes responded to recombinant HSP70 with interleukin-6 and tumor necrosis factor release. CD14 and TLR-4 monoclonal antibodies inhibited the cytokine response. Conclusions — In this study, we observed an immediate release of HSP70 into the circulation and a modulation of monocyte TLR-2 and TLR-4 expression after CABG. TLR-4 and CD14 appear to be involved in an HSP70-mediated activation of innate immunity.
Patients' Satisfaction With HMO Visits
Authors: Robert P. Younes
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The goal of the six-sigma quality program espoused by Motorola Inc, one of the first recipients of the Malcolm Baldridge National Quality Award, is to achieve defect rates of 3.4 parts per million.<sup>1</sup>Rubin et al<sup>2</sup>report that 64% of patients rated their solo practitioner's visit as "excellent." Multispecialty groups and HMOs were rated lower. If one assumes that the specification for an excellent rating is 100%, then clearly even the best-rated practices reported in this study achieve a level of one sigma or less, or a defect rate of 317 400 defects per million. (This is equivalent to 159 misspelled words per page of a book.) When viewed from this perspective, all of the consumer satisfaction ratings reported by Rubin et al were clearly inadequate. The service provided patients even in the best settings in the United States does not come close to achieving
Prognosis after West Nile Virus Infection
Authors: Mark Loeb, Steven Hanna, Lindsay Nicolle, John Eyles, Susan Elliott, Michel Rathbone, Michael Drebot, Binod Neupane, Margaret Fearon, James Mahony
Journal: Annals of Internal Medicine (2008)

Background: The long-term prognosis of patients infected with West Nile virus is not well understood. Objective: To describe the patterns of physical and mental function after infection with West Nile virus and to determine factors associated with recovery. Design: Longitudinal cohort study. Setting: Data were collected during home visits and from ambulatory clinics in 4 Canadian provinces. Participants: 156 persons with West Nile virus infection. Measurements: Scores on the Physical Component Summary and Mental Component Summary of the Short Form-36, Depression Anxiety Stress Scale, and Fatigue Severity Scale. Results: Physical and mental function, as well as mood and fatigue, seemed to return to normal within 1 year of symptom onset. Participants with neuroinvasive disease took slightly longer to recover. Maximum predicted recovery or rate of recovery in any domain did not differ between participants with meningoencephalitis and those with encephalitis. Lack of preexisting comorbid conditions was associated with faster recovery of physical function, whereas lack of comorbid conditions and male sex were associated with faster recovery of mental function. Limitations: The analysis excluded 7 patients who died shortly after diagnosis, so the study's estimates of prognosis may be overoptimistic. The authors did not formally assess neuropsychological difficulties. The estimates of recovery are relative to the U.S. population, not to participants' function levels before West Nile virus infection. Conclusion: Physical and mental outcome measures seem to normalize within approximately 1 year in patients with West Nile virus. The presence of preexisting comorbid conditions is associated with longer recovery.
ENJOYING GARDENING PRODUCES DESIRABLE CARDIOVASCULAR PROGNOSIS BY MAINTAINING FAVORABLE CORONARY ENDOTHELIAL FUNCTION
Authors: Noriko Iwatani, Keishi Saihara, Shuichi Hamasaki, Sanemasa Ishida, Tetsuro Kataoka, Akiko Yoshikawa, Naoya Oketani, Hideki Okui, Takuro Shinsato, Takuro Kubozono, So Kuwahata, Shoji Fujita, Satoshi Yoshino, Takuro Takumi, Daisuke Kanda, Takehiko Matsushita, Chuwa Tei
Journal: Journal of the American College of Cardiology (2011)
SPORTS AND EXERCISE SAFETY IN FINLAND – LIVE: AN IMPLEMENTATION PROGRAM TO SPORT CLUBS AND SCHOOLS
Authors: J Parkkari, AM Jussila, R Oksanen, K Pasanen, P Kannus
Journal: British Journal of Sports Medicine (2014)

Background Number of sports injuries has increased in Finland during the past decades. Today sports injuries are the most common injury type. Especially children and youth are at high risk. Objective The purpose of the LiVE program is to increase safety of sports and exercise in a nationwide setting. Methods Sports specific injury incidence, risk factors and mechanisms were studied. Two prevention RCT's have been carried out, one among female athletes (Pasanen et al. BMJ 2008) and another among army recruits (Parkkari et al. BMC Medicine 2011), and finally a systematic review and meta-analysis was conducted in September 2013 on all randomised controlled intervention trials aiming at the prevention of sports injuries (Leppänen et al. submitted). The effectiveness of following interventions was studied: insoles, external joint supports, training programmes, stretching, protective head equipment, modified shoes, and injury prevention videos. Results Implementation of the findings of the above noted studies is now conducted in two nationwide projects; Healthy Athlete (2006-) and Safety in Schools (2010-). The primary target groups are young athletes, their coaches and parents, elementary school pupils and their teachers. Programs main communication channels are websites: www.terveurheilija.fi and www.tervekoululainen.fi. So far, the prevention program has educated over 80 tutors who work in different organisations (e.g. Finnish Ice Hockey Association and Finnish Gymnastic Federation), built up sport safety networks, introduced itself to projects target groups in numerous events, and organized several seminars to improve safety in sports. LiVE websites have attracted 6000-9000 visitors per month each. RE-AIM analyses will be presented during the conference. Conclusions Successful development and implementation of preventive strategies against sports injuries are likely to result in reduction in the absolute number of health problems in sports, decrease in training, work and school absenteeism, and reduction in medical costs.
Accuracy or Outcome in Suspected Pulmonary Embolism
Authors: Arnaud Perrier, Henri Bounameaux
Journal: New England Journal of Medicine (2006)

Sixteen years ago, the results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study1 were published. That large-scale, multicenter trial definitively established the diagnostic characteristics of ventilation–perfusion scintigraphy of the lung, as compared with pulmonary angiography, for the diagnosis of pulmonary embolism. It was also the first trial to provide direct evidence that clinical assessment has a role beyond merely evoking pulmonary embolism as a diagnostic possibility and allows for the stratification of patients into three pretest categories of probability corresponding to an increasing prevalence of pulmonary embolism.As reported by Stein et al. in this issue of the . . .
Renin/prorenin receptors
Authors: G. Nguyen
Journal: Kidney International (2006)

The existence of a tissue renin-angiotensin (RAS) system independent of the circulating RAS has prompted the search for cellular binding sites for angiotensinogen and for renin in order to explain their tissue uptake. Two receptors that bind with similar affinity mature renin and prorenin were identified, the mannose-6-phosphate receptor (M6P-R) and a specific receptor. The M6P-R is a clearance receptor that binds exclusively the glycosylated forms of renin and prorenin. Binding of renin and prorenin to the M6P-R is followed by internalization and degradation, and the intracellular proteolysis of prorenin in mature renin did not provoke any generation of intracellular angiotensins. In contrast to the M6P-R, (pro)renin bound to the specific receptor was not degraded. Instead, receptor-bound renin showed increased catalytic activity, and receptor-bound prorenin exhibited full catalytic activity. This 'gain of activity' was explained by a conformational change of the (pro)renin molecule upon binding. Furthermore, (pro)renin binding provoked a rapid activation of the mitogen-activated protein kinases p44/p42, indicating that the receptor has mediated specific, angiotensin II-independent effects of (pro)renin. This receptor represents an elegant concept to explain the existence of active prorenin in vivo, and it provides a pathological role for prorenin in situations with paradoxical low renin and high prorenin concentrations such as in diabetes. Experimental models of rats overexpressing the receptor either in vascular smooth muscle cells and developing high blood pressure or with ubiquitous expression associated with glomerulosclerosis and proteinuria confirm a role for the receptor in cardiovascular and renal diseases.
Mediation of fibrin-induced release of von Willebrand factor from cultured endothelial cells by the fibrin beta chain.
Authors: J A Ribes, F Ni, D D Wagner, C W Francis
Journal: Journal of Clinical Investigation (1989)

The exposure of endothelial cells (EC) to fibrin has been shown to stimulate the rapid release of von Willebrand factor (vWf) from storage sites in Weibel-Palade bodies. We have now investigated the fibrin structural features required for stimulation of release. The role of fibrinopeptide cleavage was examined by preparing fibrin with thrombin to remove both fibrinopeptide A (FPA) and fibrinopeptide B (FPB) and with reptilase or Agkistrodon contortrix procoagulant to selectively remove FPA or FPB, respectively. vWf release was found to require FPB cleavage, whereas removal of FPA and Factor XIIIa cross-linking of fibrin were without effect. The dependence of release on FPB cleavage suggested that a site involving the NH2 terminus of the beta chain could mediate vWf secretion. To test this hypothesis, B beta chain derivatives were prepared and examined for their capacity to induce release. Purified B beta chain had no effect on release at a concentration of 20 nM but stimulated release from 26 +/- 6% of cells at 200 nM, the maximum solubility. However, after thrombin cleavage of FPB, release occurred from 36 +/- 9% of cells at 20 nM and from 60 +/- 7% at 200 nM, both significantly greater than before cleavage. FPB and B beta 1-42 showed no activity, whereas beta 15-42, representing the NH2 terminus of the thrombin cleaved beta chain, stimulated significant release at concentrations of 0.1 and 1 mM. We conclude that FPB cleavage from fibrin is required for stimulation of vWf release from EC and that this is mediated by a site that includes the NH2 terminus of the beta chain.
Regulation of mammary differentiation by the extracellular matrix.
Authors: J L Blum, M E Zeigler, M S Wicha
Journal: Environmental Health Perspectives (1989)

In multicellular organisms cell growth and differentiation are influenced by soluble factors, cell-cell interactions and cell-extracellular matrix interactions. We have used the rat mammary gland as a model system to study the role of extracellular matrix components in the regulation of milk protein gene expression. Since mammary epithelial cells differentiate on a basement membrane in vivo, we investigated the effects of basement membrane components on the expression of the milk protein genes, alpha-casein, alpha-lactalbumin, and transferrin. We have demonstrated that a basement membrane gel, as well as its major basement membrane component, laminin, induced alpha-casein and alpha-lactalbumin expression as much as 160-fold compared to tissue culture plastic. We demonstrate that laminin affects mRNA stability as well as having an effect on protein stability and secretion. Laminin interacts with mammary epithelial cells via an 68 kD cell surface receptor which is capable of interacting with the cellular cytoskeleton. In order to provide evidence that laminin affects on mammary differentiation are mediated through this receptor via the cytoskeleton, we examined the effects of cytoskeletal disrupting agents on milk protein gene expression. We demonstrate that cytochalasin D or colchicine selectively block laminin-mediated milk protein gene expression by affecting mRNA stability. Based on these experiments, we propose a model in which laminin affects mammary gene expression through interaction with cell surface receptors which interact with the cytoskeleton resulting in stabilization of mRNAs for milk protein genes.
The use of chitosan as a condensing agent to enhance emulsion-mediated gene transfer
Authors: Mi-Kyung Lee, Soo-Kyung Chun, Woo-Jeong Choi, Jin-Ki Kim, Sung-Hee Choi, Adele Kim, Kwunchit Oungbho, Jeong-Sook Park, Woong Shick Ahn, Chong-Kook Kim
Journal: Biomaterials (2004)
Norah Helen Colquhoun Clarke
Authors: J. Clarke
Journal: BMJ (2008)

Norah Helen Colquhoun Clarke (“Auntie Norah”) had a great zest for life. An excellent listener, she became so absorbed in everything she did that she was invariably late. Described by all who knew her as great fun to be with, her intrepid sense of adventure led her to the Belgian Congo.

Born on the 18 July 1914, she was brought up in Derby, the daughter of a much respected general practitioner in the city. She trained at the Royal Free Hospital, where she was awarded the dean’s medal for “skill with the eye, the ear, and the hand in clinical medicine.”

After qualification in 1937, she carried out various house jobs in London and Birmingham, …