tbuckley/cabot-search huggingface dataset:
Impaired function of salvaged myocardium: two-dimensional echocardiographic quantification of regional wall thickening in the open-chest dog.
Authors: D S Blumenthal, L C Becker, B H Bulkley, G M Hutchins, M L Weisfeldt, J L Weiss
Journal: Circulation (1983)

This study was designed to examine the functional properties of myocardium subjected to acute coronary occlusion but surviving the ischemic insult. Ten conscious mongrel dogs underwent mild-circumflex coronary occlusion and were treated for 6 hours with prostacyclin, 540 ng/kg/min, and ibuprofen, 110 micrograms/kg/min, or dipyridamole (7-9.7 micrograms/kg/min). At 7 days, each dog was anesthetized, the chest was opened, and cross-sectional two-dimensional echocardiograms were obtained through the middle of the occluded vascular bed. A computer-aided contouring system was used to assess percent systolic thickening in 16 equally spaced segments around the left ventricle. Metal markers sewn to the epicardium permitted precise regional correlation of histology, percent systolic thickening, and flow, as measured by radioactive microspheres. Necrosis was minimal, averaging only 2.2 +/- 0.8% (+/- SEM) of the left ventricular ring corresponding to the echocardiographic cross section. Percent systolic thickening was 28.6 +/- 4.7 in the nonischemic anterior wall, but was reduced to -4.5 +/- 3.1 in the occluded bed (p less than 0.01). In individual echo segments, percent systolic thickening correlated with local flow (r = 0.69, p less than 0.001), but was still depressed even when flow was normal. In six segments within the occluded bed that had normal histology and flow, percent systolic thickening was 52% less than that in the nonischemic region (p less than 0.02). Thus, coronary artery occlusion combined with drug treatment results in myocardium that, although histologically normal and supplied by normal myocardial blood flow, remains functionally abnormal 7 days after occlusion.
Hospitals must be child friendly, says report
Authors: Z. Kmietowicz
Journal: BMJ (2003)

The Department of Health for England has announced a radical shake up in the way hospitals are organised to meet the needs of children.

New standards set out in the first part of the national service framework for children will require hospitals to provide child friendly services, including dedicated children's units in emergency departments, separate and private facilities for adolescents, play areas and teachers for children on wards, and the sort of food that children want to eat.

In a direct response to the Laming inquiry into …
Pyrimethamine Induces Apoptosis of Melanoma Cells via a Caspase and Cathepsin Double-Edged Mechanism
Authors: Anna Maria Giammarioli, Angela Maselli, Andrea Casagrande, Lucrezia Gambardella, Angelo Gallina, Massimo Spada, Antonello Giovannetti, Enrico Proietti, Walter Malorni, Marina Pierdominici
Journal: Cancer Research (2008)

Abstract The unresponsiveness of metastatic melanoma to conventional chemotherapeutic and biological agents is largely due to the development of resistance to apoptosis. Pyrimethamine belongs to the group of antifolate drugs, and in addition to antiprotozoan effects, it exerts a strong proapoptotic activity, which we recently characterized in human T lymphocytes. However, no data regarding pyrimethamine anticancer activity are available thus far. To this end, we examined the in vitro effects of pyrimethamine on apoptosis, cell cycle distribution, and cell proliferation of human metastatic melanoma cell lines. The in vivo antitumor potential of pyrimethamine was evaluated in a severe combined immunodeficiency (SCID) mouse xenotransplantation model. Our data indicate that pyrimethamine, when used at a clinically relevant concentration, induced apoptosis in metastatic melanoma cells via the activation of the cathepsin B and the caspase cascade (i.e., caspase-8 and caspase-9) and subsequent mitochondrial depolarization. This occurred independently from CD95/Fas engagement. Moreover, pyrimethamine induced a marked inhibition of cell growth and an S-phase cell cycle arrest. Results obtained in SCID mice, injected s.c. with metastatic melanoma cells and treated with pyrimethamine, indicated a significant inhibitory effect on tumor growth. In conclusion, our results suggest that pyrimethamine-induced apoptosis may be considered as a multifaceted process, in which different inducers or regulators of apoptosis are simultaneously implicated, thus permitting death defects of melanoma cells to be bypassed or overcome. On these bases, we hypothesize that pyrimethamine could represent an interesting candidate for the treatment of metastatic melanoma. [Cancer Res 2008;68(13):5291–300]
Management of Common Problems in Obstetrics and Gynecology
Authors: Allan G. Charles
Journal: JAMA (1984)

Drs Mishell and Brenner are to be congratulated for their efforts in editing Management of Common Problems in Obstetrics and Gynecology . This is an excellent book that should be read by obstetricians and gynecologists whether in practice or in training. There are 116 chapters dealing with all aspects of the practice of obstetrics and gynecology.  This volume in its editor's words consists of concise, clinically oriented chapters that provide the clinician with the latest diagnostic and therapeutic methods for the management of the most commonly encountered obstetric and gynecologic disorders. The vast experience garnered at the Women's Hospital, Los Angeles Center/University of Southern California Medical Center, has enabled the 41 contributors (all current or past members of the faculty of the Department of Obstetrics-Gynecology of USC) to present a great deal of information to the reader. This information has been synthesized into easily readable chapters that will enable the reader
Cholesterol Loading and Ultrastable Protein Interactions Determine the Level of Tumor Marker Required for Optimal Isolation of Cancer Cells
Authors: Jayati Jain, Gianluca Veggiani, Mark Howarth
Journal: Cancer Research (2013)

Cell isolation via antibody-targeted magnetic beads is a powerful tool for research and clinical applications, most recently for isolating circulating tumor cells (CTC). Nonetheless fundamental features of the cell-bead interface are still unknown. Here we apply a clinically relevant antibody against the cancer target HER2 (ErbB2) for magnetic cell isolation. We investigate how many target proteins per cell are sufficient for a cell to be isolated. To understand the importance of primary antibody affinity, we compared a series of point mutants with known affinities and show that even starting with subnanomolar affinity, improving antibody affinity improved cell isolation. To test the importance of the connection between the primary antibody and the magnetic bead, we compared bridging the antibody to the beads with Protein L, secondary antibody, or streptavidin: the high-stability streptavidin-biotin linkage improved sensitivity by an order of magnitude. Cytoskeletal polymerization did not have a major effect on cell isolation, but isolation was inhibited by cholesterol depletion and enhanced by cholesterol loading of cells. Analyzing a panel of human cancer cell lines spanning a wide range of expression showed that the standard approach could only isolate the highest expressing cells. However, our optimization of cholesterol level, primary antibody affinity, and antibody-bead linkage allowed efficient and specific isolation of cells expressing low levels of HER2 or epithelial cell adhesion molecule. These insights should guide future approaches to cell isolation, either magnetically or using other means, and extend the range of cellular antigens and biomarkers that can be targeted for CTC isolation in cancer research and diagnosis.
Somatostatin Inhibition of Insulin and Gastrin Hypersecretion in Pancreatic Islet-Cell Carcinoma
Authors: Randall T. Curnow, Robert M. Carey, Andrea Taylor, Ann Johanson, Ferid Murad
Journal: New England Journal of Medicine (1975)

SOMATOSTATIN has been reported to diminish basal insulin levels1 and to inhibit insulin secretion stimulated by glucose,2 arginine,3 glucagon,4 and tolbutamide4 in normal man. These effects of somatostatin administration have not been associated with serious untoward effects. Therefore, it has been suggested5 that somatostatin might be efficacious in suppressing autonomous hypersecretion of insulin by pancreatic islet-cell adenomas or carcinomas. In the following case, somatostatin was indeed found to be effective in suppressing insulin hypersecretion in a woman with metastatic pancreatic islet-cell carcinoma. Somatostatin also reduced elevated serum gastrin levels.Case ReportA 54-year-old woman was admitted to the University of . . .
Evaluating Expected Costs and Benefits of Granting Access to New Treatments on the Basis of Progression-Free Survival in Non–Small-Cell Lung Cancer
Authors: Darius N. Lakdawalla, Jacquelyn W. Chou, Mark T. Linthicum, Joanna P. MacEwan, Jie Zhang, Dana P. Goldman
Journal: JAMA Oncology (2015)

IMPORTANCE Surrogate end points may be used as proxy for more robust clinical end points.One prominent example is the use of progression-free survival (PFS) as a surrogate for overall survival (OS) in trials for oncologic treatments.Decisions based on surrogate end points may expedite regulatory approval but may not accurately reflect drug efficacy.Payers and clinicians must balance the potential benefits of earlier treatment access based on surrogate end points against the risks of clinical uncertainty.OBJECTIVE To present a framework for evaluating the expected net benefit or cost of providing early access to new treatments on the basis of evidence of PFS benefits before OS results are available, using non-small-cell lung cancer (NSCLC) as an example. DESIGN, SETTING, AND PARTICIPANTSA probabilistic decision model was used to estimate expected incremental social value of the decision to grant access to a new treatment on the basis of PFS evidence.The model analyzed a hypothetical population of patients with NSCLC who could be treated during the period between PFS and OS evidence publication.Estimates for delay in publication of OS evidence following publication of PFS evidence, expected OS benefit given PFS benefit, incremental cost of new treatment, and other parameters were drawn from the literature on treatment of NSCLC. MAIN OUTCOMES AND MEASURES Incremental social value of early access for each additional patient per month (in 2014 US dollars).RESULTS For "medium-value" model parameters, early reimbursement of drugs with any PFS benefit yields an incremental social cost of more than $170 000 per newly treated patient per month.In contrast, granting early access on the basis of PFS benefit between 1 and 3.5 months produces more than $73 000 in incremental social value.Across the full range of model parameter values, granting access for drugs with PFS benefit between 3 and 3.5 months is robustly beneficial, generating incremental social value ranging from $38 000 to more than $1 million per newly treated patient per month, whereas access for all drugs with any PFS benefit is usually not beneficial. CONCLUSIONS AND RELEVANCEThe value of providing access to new treatments on the basis of surrogate end points, and PFS in particular, likely varies considerably.Payers and clinicians should carefully consider how to use PFS data in balancing potential benefits against costs in each particular disease.
AN EXPERIMENTAL STUDY OF THE ADDITIVE AND ANTAGONISTIC ACTIONS OF SODIUM OXALATE, AND SALTS OF MAGNESIUM AND CALCIUM IN THE RABBIT
Authors: F. L. Gates, S. J. Meltzer
Journal: The Journal of Experimental Medicine (1916)

The foregoing experiments establish firmly the following facts. Subcutaneous or intramuscular injections of sodium oxalate in subtoxic doses, when administered to an animal which received a subminimal dose of magnesium sulphate, produce profound anesthesia and paralysis of long duration, although the usual effects of sodium oxalate alone are of a stimulating character. This fact is, in general, in harmony with the results reported by Starkenstein who, however, seems to have used the combination of the two salts in one solution; namely, that of magnesium oxalate. The combined injections of subminimal doses of sodium oxalate and magnesium sulphate produce a strong reduction, or even, at times, a complete abolition of the conductivity of the motor nerve endings. An intravenous injection of calcium salts brings on a recovery from the profound and prolonged effects of the combined action of sodium oxalate and magnesium sulphate, which is as prompt as is observed in experiments in which effective doses of magnesium alone were given. This fact is the more noteworthy, since depressions of long duration produced by prolonged continuous injections of magnesium solutions alone do not respond very promptly and effectively to calcium injections. As will be recalled, the starting point for our investigation was the hypothesis that substances which are capable of precipitating calcium-a biological antagonist of magnesium-ought to be capable of increasing the depressive effect of magnesium. Our experiments proved that this assumption was correct. This would seem, therefore, to justify the interpretation that the augmenting action of sodium oxalate has its cause in the ability of the latter to precipitate calcium and thus increase within the body the amount of unantagonized magnesium. However, we wish to state expressly that this view is, for the present, still no more than a hypothesis and does not exclude other possible interpretations of our facts. As we pointed out it speaks against this hypothesis that oxalates do not produce phenomena of depression; the toxic symptoms produced by oxalates exhibit distinctly signs of increased and not of decreased irritability.
Pulmonary Aspiration of Gastric Acid-Reply
Authors: Hugh A. Johnson
Journal: JAMA (1962)

<h3>To the Editor:—</h3> As always, the diagnosis of any case depends on the marshalling of all facts and matching these with the disease entity that most nearly approximates the case. It can be difficult to prove any diagnosis that is clinical, even one based on laboratory findings, for even these are subject to error. The efficacy of this treatment will have to be proved later in controlled studies. Every new idea must eventually be checked clinically by many investigators. I fervently hope no surgeon is ever remiss enough to collect a series of these!
RUNX Transcription Factor-Mediated Association of Cd4 and Cd8 Enables Coordinate Gene Regulation
Authors: Amélie Collins, Susannah L. Hewitt, Julie Chaumeil, MacLean Sellars, Mariann Micsinai, Jeanne Allinne, Fabio Parisi, Elphège P. Nora, Dan J. Bolland, Anne E. Corcoran, Yuval Kluger, Remy Bosselut, Wilfried Ellmeier, Mark M.W. Chong, Dan R. Littman, Jane A. Skok
Journal: Immunity (2011)
Moderate Alcohol Consumption and Risk of Coronary Heart Disease Among Women With Type 2 Diabetes Mellitus
Authors: Timothy J. Regan
Journal: Circulation (2000)

or much of the last century, a major medical interest in ethanol research has been related to the biological effects of ethanol abuse on the brain, liver, and heart.Focused in urban centers where addiction to this agent was a common phenomenon, little consideration of the doseresponse relationship at the lower end of the scale was provided.Fortunately, there has been a growing interest in this relation over the past 2 to 3 decades.
ABO blood groups and gastrointestinal function.
Authors: M J Langman
Journal: Gut (1970)

ABO blood groups and gastrointestinal function or obstruction.20' 21, 22 An extra dimension was added to the problem by the discovery that an isoenzyme of alkaline phosphatase, which can be identified as of small- intestinal origin by its electrophoretic,23 biochemical,24 and immunological on August 19,
NICE clinical guidelines: Maybe health economists should participate in guideline development
Authors: Peter Littlejohns, Gillian Leng, Tony Culyer, Mike Drummond
Journal: BMJ (2004)

EDITOR—Wailoo et al highlight a fundamental challenge that the National Institute for Clinical Excellence (NICE) faces on a daily basis.1 The government established NICE not only to advise the NHS on the quality of care that individual patients could expect (in terms of appropriateness and effectiveness) but also to address the other important dimensions of healthcare quality (equity, fairness, and efficiency) that society expects.

We agree that being required to address both …
Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C
Authors: Nicole Forestier, Hendrik W. Reesink, Christine J. Weegink, Lindsay McNair, Tara L. Kieffer, Hui-May Chu, Susan Purdy, Peter L.M. Jansen, Stefan Zeuzem
Journal: Hepatology (2007)

Telaprevir (VX-950), an inhibitor of the hepatitis C virus (HCV) NS3/4A protease, substantially decreased plasma HCV RNA levels in a prior clinical study. The present study evaluated viral kinetics and safety during dosing with telaprevir alone and in combination with peginterferon alfa-2a for 14 days. Previously untreated patients with genotype 1 hepatitis C were randomized to receive placebo and peginterferon alfa-2a (n = 4); telaprevir (n = 8); or telaprevir and peginterferon alfa-2a (n = 8). Telaprevir was given as 750 mg oral doses every 8 hours; peginterferon alfa-2a was given as weekly 180 mug subcutaneous injections. The median change in HCV RNA from baseline to day 15 was -1.09 log(10) (range, -2.08 to -0.46) in the placebo and peginterferon alfa-2a group; -3.99 log(10) (range, -5.28 to -1.26) in the telaprevir group, and -5.49 log(10) (range, -6.54 to -4.30) in the telaprevir and peginterferon alfa-2a group. Day 15 HCV RNA levels were undetectable in 4 patients who received telaprevir and peginterferon alfa-2a and in 1 patient who received telaprevir alone. No viral breakthrough occurred in patients who received telaprevir and peginterferon alfa-2a. The majority of adverse events were mild. There were no serious adverse events or premature discontinuations. Twelve weeks after starting off-study standard therapy, HCV RNA was undetectable in all 8 patients in the telaprevir and peginterferon alfa-2a group, 5 patients in the telaprevir group, and 1 patient in the placebo and peginterferon alfa-2a group.This study confirmed the substantial antiviral effects of telaprevir and showed an increased antiviral effect of telaprevir combined with peginterferon alfa-2a.
Nervous Control of Cardiovascular Function
Authors: Peter T. Kuo
Journal: JAMA (1985)

In this book, Dr Walter C. Randall and his collaborating authors have presented to the readers a wealth of new information on the interrelation of the nervous and the cardiovascular systems. The painstaking research of these leading investigators has not only culminated in many new facts on the neural regulation of the cardiovascular system in health and its readjustments in disease, but they have also suggested new directions for acquiring answers to existing questions. Thus, the authors of the 20 chapters in this book have fully achieved their objective in providing students of diverse bioscience disciplines with fresh ideas and approaches to the interaction of the two systems to preserve cardiovascular integrity and function. The book may be broadly divided into the following sections with interlinking references: (1) anatomy of extrinsic efferent autonomic nerves and ganglia, and of selective autonomic innervation of the heart; (2) regulation of cardiac function, cardiac
Prevalence and Trends in Obesity Among US Adults, 1999-2008
Authors: Katherine M. Flegal
Journal: JAMA (2010)

The prevalence of obesity increased in the United States between 1976-1980 and 1988-1994 and again between 1988-1994 and 1999-2000.To examine trends in obesity from 1999 through 2008 and the current prevalence of obesity and overweight for 2007-2008.Analysis of height and weight measurements from 5555 adult men and women aged 20 years or older obtained in 2007-2008 as part of the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US population. Data from the NHANES obtained in 2007-2008 were compared with results obtained from 1999 through 2006.Estimates of the prevalence of overweight and obesity in adults. Overweight was defined as a body mass index (BMI) of 25.0 to 29.9. Obesity was defined as a BMI of 30.0 or higher.In 2007-2008, the age-adjusted prevalence of obesity was 33.8% (95% confidence interval [CI], 31.6%-36.0%) overall, 32.2% (95% CI, 29.5%-35.0%) among men, and 35.5% (95% CI, 33.2%-37.7%) among women. The corresponding prevalence estimates for overweight and obesity combined (BMI > or = 25) were 68.0% (95% CI, 66.3%-69.8%), 72.3% (95% CI, 70.4%-74.1%), and 64.1% (95% CI, 61.3%-66.9%). Obesity prevalence varied by age group and by racial and ethnic group for both men and women. Over the 10-year period, obesity showed no significant trend among women (adjusted odds ratio [AOR] for 2007-2008 vs 1999-2000, 1.12 [95% CI, 0.89-1.32]). For men, there was a significant linear trend (AOR for 2007-2008 vs 1999-2000, 1.32 [95% CI, 1.12-1.58]); however, the 3 most recent data points did not differ significantly from each other.In 2007-2008, the prevalence of obesity was 32.2% among adult men and 35.5% among adult women. The increases in the prevalence of obesity previously observed do not appear to be continuing at the same rate over the past 10 years, particularly for women and possibly for men.
Diabetes prescribing in England consumes nearly 10% of primary care budget
Authors: G. Iacobucci
Journal: BMJ (2014)

The NHS in England spent a daily average of £2.2m (€2.6m; $3.7m) last year on prescriptions for managing diabetes in primary care, and almost 10% of the primary care prescribing budget is now spent on treating the condition.

New figures from the Health and Social Care Information Centre showed that the proportion spent on treating diabetes rose from just 6.6% in 2005-06 to 9.5% in 2013-14, having increased each year. The figures were detailed in Prescribing for Diabetes, 1 a new report that assessed trends …
Down-regulation of BLIMP1α by the EBV oncogene, LMP-1, disrupts the plasma cell differentiation program and prevents viral replication in B cells: implications for the pathogenesis of EBV-associated B-cell lymphomas
Authors: Katerina Vrzalikova, Martina Vockerodt, Sarah Leonard, Andrew Bell, Wenbin Wei, Alexandra Schrader, Kenneth L. Wright, Dieter Kube, Martin Rowe, Ciaran B. Woodman, Paul G. Murray
Journal: Blood (2011)