tbuckley/cabot-search huggingface dataset:
Disseminated Intravascular Coagulation: An Intermediary Mechanism of Disease
Authors: Oscar D. Ratnoff
Journal: JAMA (1965)

As its title states, the thesis of Dr. McKay's monograph is that diffuse intravascular coagulation is important in the pathogenesis of a number of different disease states. It has been known since Woolridge's experiments in the 1880's that the intravenous injection of clot-promoting agents may be followed by diffuse intravascular coagulation. As a consequence, the animal's plasma is depleted of fibrinogen. Paradoxically, then, the induction of intravascular clotting leads to a bleeding tendency. Dr. McKay reviews the voluminous clinical literature in which various clinical syndromes are attributed to the process of thrombosis in small blood vessels. These disorders include such apparently diverse processes as snake bite, amniotic fluid embolism, and intravascular hemolysis. Moreover, he summarizes some of the studies in which attempts have been made to produce experimental counterparts of human disease. To my knowledge, this is the first time anyone has tried to assemble information about these important processes
Enhanced Local Control by Radiation Boost in Breast Cancer: Back Side of the Coin?
Authors: Céline Bourgier, Marie-Catherine Vozenin-Brotons, Rodrigo Arriagada
Journal: Journal of Clinical Oncology (2007)

et al 1 reported the impact of higher radiation dose on local control and survival in patients who underwent breast conservation therapy for early breast cancer.They used 10-year results of the randomized boost versus no boost European Organisation for Research and Treatment of Cancer 22881-10882 trial.A total of 5,318 patients with microscopically complete excision followed by whole-breast irradiation of 50 Gy were randomly assigned to receive either a boost dose of 16 Gy (2,661 patients) or no boost dose (2,657 patients), with a median follow-up of 10.8 years.The major purpose of this report was to find out the long-term impact of a boost irradiation of 16 Gy on local control, fibrosis, and overall survival for patients with stage I and II breast cancer who underwent breastconserving therapy.They reported that severe fibrosis was statistically significantly increased in the boost group, with a 10-year rate of 4.4% v 1.6% in the no-boost group.It is well known in the literature that higher radiation doses significantly increase severe fibrosis that resulted in poor cosmetic results. 2,3However, in Bartelink et al, 1 there is no information about the percentage of patients within the boost or no-boost group that received tamoxifen (TAM) treatment.In addition, the differences between TAM treatment versus no TAM treatment in the boost group must be explained (if any).Apart from its (anti)hormonal properties, TAM also has a number of nonhormonal effects.The induction of transforming growth factor ␤ (TGF-␤) is one of the documented nonhormonal effects of TAM. 4 It generally inhibits the growth of epithelial cells, but induces chemotaxis of fibroblasts.6][7] Nonhormonal effects of TAM can cause fibrosis of liver, skin, muscle, lungs, and mammary gland, most likely by the induction of TGF-␤ secretion.Johansen et al 8 also recently reported that TAM was significantly associated with breast fibrosis.I believe that in the article by Bartelink et al, 1 if the impact of TAM on fibrosis were analyzed in subgroups of boost versus no-boost groups in a study with a large sample size (ie, 5,318 patients) and 10-year period, the contribution to the literature would be enormous.
Comparison of bronchoconstriction induced by cycling and running
Authors: S. D. Anderson, N. M. Connolly, S. Godfrey
Journal: Thorax (1971)

Bicycle ergometer, treadmill, and free range running exercise have been used to induce bronchoconstriction in 10 asthmatic subjects who were relatively well and free from symptoms at the time of study. Comparisons have been made with normal subjects under similar laboratory conditions. Bronchoconstriction was measured by peak expiratory flow rate before, during, and after each test. Ventilation, pulse rate, and gas exchange were also measured. The work involved in the different types of exercise was matched to produce similar ventilation and pulse rates for any one subject. Exercise-induced bronchoconstriction was significantly less on the bicycle ergometer than on running (treadmill or free range). The normal subjects showed less than one quarter the bronchial lability of the asthmatic subjects in any one test. All subjects had lower respiratory exchange ratios during running compared with cycling and this appeared to correlate with the bronchial lability in the asthmatics, who also had rather higher pulse rates during running. Running involves a proportion of high-efficiency negative work which might partly account for the observed differences.
The Impact of Overseas Medical Graduates on Service and Training in the United Kingdom
Authors: John Lister
Journal: New England Journal of Medicine (1986)

The United Kingdom, like the United States, has a long tradition of welcoming overseas medical graduates for postgraduate studies. Many come with the intention of taking examinations for specialty diplomas, and they seek to prepare themselves for such examinations either by attending specific courses of instruction or by taking hospital posts that they hope will provide them with suitable practical experience.Before World War II the numbers involved were not large, but after the war they rose steadily, the majority of foreign medical graduates coming from the Indian subcontinent. At that time the rules governing medical immigration were liberal, and . . .
Use of Selective Serotonin Reuptake Inhibitors and Myocardial Infarction
Authors: Pal Pacher, Zoltan Ungvari
Journal: Circulation (2002)

To the Editor:In a recent study, Sauer et al 1 showed that the use of selective serotonin reuptake inhibitor antidepressants (SSRIs) may confer a protective effect against myocardial infarction (MI) in smokers.They hypothesized that this beneficial effect of SSRIs in reducing the risk of MI could mainly be attributed to the inhibitory effect on serotonin-mediated platelet activation in addition to treatment of depression itself.In contrast to these results, in a recent larger population-based case-control study, Meier et al 2 found that SSRI exposure adjusted for age, sex, geography, calendar time, smoking status, and body mass index was not associated with altered risk of developing first-time MI.MI risk estimates were also not influenced by timing, duration, and dosing of SSRIs.In addition, this analysis yielded no difference between patients using SSRIs or non-SSRIs, including tricyclic antidepressants (TCAs), with regard to MI.The reason for the discrepancy between results of the two aforementioned studies 1,2 is not clear.The proposed mechanism underlying the putative cardioprotective effect of SSRIs is an interference with serotonin handling decreasing platelet aggregability.Indeed, there are case reports extant associating use of SSRIs with abnormal platelet aggregation.Although inhibition of platelet aggregation may also result in bleeding disorders, a recent study provided weak, if any, evidence for a link between SSRIs and precipitation of bleeding events at a population level. 3owever, in addition to their putative effect on platelet function, SSRIs are thought to have clinically important cardiac and vascular effects as well.Surprisingly, in a recently study, the use of SSRIs similarly to TCAs was associated with cases of first-degree atrioventricular block, prolonged QTc interval and orthostatic hypotension in patients lacking cardiovascular disorders, raising new concerns about the putative cardiovascular safety of these compounds. 4Importantly, SSRI antidepressants,
EFFECT OF ACUTE INTENSE EXERCISE ON ARTERIAL STIFFNESS
Authors: Despina Kardara, Charalambos Vlachopoulos, Aris Anastasakis, Katerina Baou, Ioanna Dima, Dimitrios Terentes-Printzios, Georgios Antoniou, Athanasios Gravos, Grigorios Aggelidis, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2010)
Local Television News Coverage of President Clinton's Introduction of the Health Security Act
Authors: Lori Dorfman
Journal: JAMA (1996)

To investigate how local television news reported on health system reform during the week President Clinton presented his health system reform bill.Retrospective content analysis of the 1342-page Health Security Act of 1993, the printed text of President Clinton's speech before Congress on September 22, 1993, and a sample of local television news stories on health system reform broadcast during the week of September 19 through 25, 1993.The state of California.During the week, 316 television news stories on health system reform were aired during the 166 local news broadcasts sampled. Health system reform was the second most frequently reported topic, second to stories on violent crime. News stories on health system reform averaged 1 minute 38 seconds in length, compared with 57 seconds for violent crime. Fifty-seven percent of the local news stories focused on interest group politics. Compared with the content of the Health Security Act, local news broadcasts devoted a significantly greater portion of their stories to financing, eligibility, and preventive services. Local news stories gave significantly less attention to cost-saving mechanisms, long-term care benefits, and changes in Medicare and Medicaid, and less than 2% of stories mentioned quality assurance mechanisms, malpractice reform, or new public health initiatives. Of the 316 televised news stories, 53 reported on the president's speech, covering many of the same topics emphasized in the speech (financing, organization and administration, and eligibility) and de-emphasizing many of the same topics (Medicare and Medicaid, quality assurance, and malpractice reform). Two percent of the president's speech covered partisan politics; 45% of the local news stories on the speech featured challenges from partisan politicians.Although health system reform was the focus of a large number of local television news stories during the week, in-depth explanation was scarce. In general, the news stories provided superficial coverage framed largely in terms of the risks and costs of reform to specific stakeholders.
Induction of neostriatal neurogenesis slows disease progression in a transgenic murine model of Huntington disease
Authors: Sung-Rae Cho, Abdellatif Benraiss, Eva Chmielnicki, Amer Samdani, Aris Economides, Steven A. Goldman
Journal: Journal of Clinical Investigation (2007)

Ependymal overexpression of brain-derived neurotrophic factor (BDNF) stimulates neuronal addition to the adult striatum, from subependymal progenitor cells. Noggin, by suppressing subependymal gliogenesis and increasing progenitor availability, potentiates this process. We asked whether BDNF/Noggin overexpression might be used to recruit new striatal neurons in R6/2 huntingtin transgenic mice. R6/2 mice injected with adenoviral BDNF and adenoviral Noggin (AdBDNF/AdNoggin) recruited BrdU(+)betaIII-tubulin(+) neurons, which developed as DARPP-32(+) and GABAergic medium spiny neurons that expressed either enkephalin or substance P and extended fibers to the globus pallidus. Only AdBDNF/AdNoggin-treated R6/2 mice harbored migrating doublecortin-defined neuroblasts in their striata, and the new neurons expressed p27 as a marker of mitotic quiescence after parenchymal integration. AdBDNF/AdNoggin-treated R6/2 mice sustained their rotarod performance and open-field activity and survived longer than did AdNull-treated and untreated controls. Neither motor performance nor survival improved in R6/2 mice treated only with AdBDNF, and intraventricular infusion of the mitotic inhibitor Ara-C completely blocked the performance and survival effects of AdBDNF/AdNoggin, suggesting that the benefits of AdBDNF/AdNoggin derived from neuronal addition. Thus, BDNF and Noggin induced striatal neuronal regeneration, delayed motor impairment, and extended survival in R6/2 mice, suggesting a new therapeutic strategy in Huntington disease.
Familial predisposition of left ventricular hypertrophy
Authors: Heribert Schunkert, Ulrich Bröckel, Christian Hengstenberg, Andreas Luchner, Michael W Muscholl, Klaus Kurzidim, Bernhard Kuch, Angela Döring, Günter A.J Riegger, Hans-Werner Hense
Journal: Journal of the American College of Cardiology (1999)
Deciphering the tête-à-tête between the microbiota and the immune system
Authors: Neeraj K. Surana, Dennis L. Kasper
Journal: Journal of Clinical Investigation (2014)

The past decade has witnessed an explosion in studies — both clinical and basic science — examining the relationship between the microbiota and human health, and it is now clear that the effects of commensal organisms are much broader than previously believed. Among the microbiota's major contributions to host physiology is regulation of the development and maintenance of the immune system. There are now a handful of examples of intestinal commensal bacteria with defined immunomodulatory properties, but our mechanistic understanding of how microbes influence the immune system is still in its infancy. Nevertheless, several themes have emerged that provide a framework for appreciating microbe-induced immunoregulation. In this Review, we discuss the current state of knowledge regarding the role of the intestinal microbiota in immunologic development, highlighting mechanistic principles that can guide future work.
Vitamin A Absorption From Plastic IV Bags
Authors: R. L. Nedich
Journal: JAMA (1973)

To the Editor.—  The LETTER TO THE EDITOR by Chiou and Moorhatch (223:328, 1973) regarding the apparent sorption of polysorbate 80 solubilized vitamin A acetate in polyvinyl chloride parenteral containers was read with great interest. It was noted that the study design was not representative of usual parenteral administration practices.  In order to assess the extent of this sorption phenomenon under simulated use conditions, liter polyvinyl chloride (Viaflex PL-146) and rubberstoppered glass infusion containers were filled with vitamin A acetate solubilized in 0.01% polysorbate 80. The concentration of vitamin A utilized was 10 units/ml of solution thus yielding the frequently administered concentration of 10,000 units/liter. Typical polyvinyl chloride administration sets were attached to the containers, and the containers were wrapped in aluminum foil to protect the photosensitive vitamin from light. Drip rates were monitored and controlled at 100 ml/hour to deliver the total volume in ten hours. Aliquots were periodically
Campaign to revitalise academic medicine: Direction of academic medicine is worrying
Authors: Margaret S Terpenning
Journal: BMJ (2004)

EDITOR—Three things concern me about the direction of academic medicine.1

Firstly, coordination of global concerns seems to be lacking in academic medicine. Diverse groups advocate for their causes, but there is no central organisation. For example, does a central group try to keep track of sanitation and public health data for various areas of the world? Does …
Business, Trades, and Professions-Reply
Authors: Lester S. King
Journal: JAMA (1985)

<h3>In Reply.—</h3> The question is not, can we, by defining the term "profession," construct an ideal behavioral pattern to which physicians ought to adhere? The answer is clearly "yes." Rather let us ask, is any such idealized statement reflected in reality? The answer, I think, is clearly "no." In the last 500 years there has been massive documentation on the grasping and selfish behavior of physicians, ranging from Chaucer's Doctour of Phisyk, who "lovede gold in special," through guilds and colleges that devoted themselves to securing monopolies, to present-day political action committees. The general principle seems to be, what is good for the doctors is good for the country. To this I have no objection. It is a fine capitalist principle. I do object, however, to self-deception that confuses mythology with reality. I maintain, as a point of fact, that present-day usage of the term "professions" is so diluted that
Abstract 2373: Deep computational analysis of human and mouse specific next-generation sequencing data generated from PDX specimen
Authors: Roopika Menon, Petra Schneider, Martin Peifer, Frauke Leenders, Johannes M. Heuckmann
Journal: Cancer Research (2014)

Abstract Patient derived xenograft (PDX) samples are powerful tools to analyze tumor biology and drug sensitivity of primary tumors in animal models. However, sequencing studies on those samples face the challenge of mouse stromal contamination, which varies in each of the explanted tumor specimen. Thus, without applying mouse and human specific filters on sequencing data, species specific genomic alterations and differences in expression are impossible to detect. To allow mouse and human specific transcriptome/genome analyses, we adapted our NGS data analysis pipelines to filter for mouse and human specific reads. By applying the analysis algorithms on hybrid-capture and transcriptome sequencing data from 60 lung cancer PDX samples, we were able to generate a comprehensive overview on tumor specific alterations, including point mutations, deletions and insertions, copy number alterations, gene fusions and isoform specific expression levels, as well as species specific genomic alterations and transcriptome wide expression levels. From 5781 nonsynonymous substitutions which were detected by hybrid-capture sequencing of 333 cancer relevant genes (CAGE-Rx Scanner), 863 human specific nonsynonymous substitutions were detected after filtering for mouse specific variations. The mean sequencing coverage of the CAGE analysis across all targeted bases in all 60 samples was 662x. An integrated analysis of this data set and corresponding transcriptome sequencing data revealed TP53 and KRAS as the most frequently mutated genes which were expressed. As expected, due to the relative high tumor content in all samples (ranging from 30 to 90% with a median of 90% as determined by pathological review), 80% of all mutations called from transcriptome sequencing in an unfiltered fashion were human specific and called after species specific filtering. In addition, the detection of mouse specific transcriptome sequencing reads identified several growth factors expressed by tumor surrounding tissue, which would have been discarded as unmapped reads in the normal analysis setting. Thus, our analysis alorithms not only enable to remove mouse specific false positive single nucleotide variants (SNVs), but also a detailed analysis of mouse specific expression patterns which might strongly influence tumor growth via the tumor microenvironment. Citation Format: Roopika Menon, Petra Schneider, Martin Peifer, Frauke Leenders, Johannes M. Heuckmann. Deep computational analysis of human and mouse specific next-generation sequencing data generated from PDX specimen. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2373. doi:10.1158/1538-7445.AM2014-2373
MPs call for safeguards for people with personality disorder
Authors: L. Beecham
Journal: BMJ (2000)

UK government proposals to detain dangerous people who have a severe personality disorder but no criminal conviction should be applied to individuals only when an assessment predicts that it is almost certain that they will commit a very serious criminal offence, a report from a cross party committee of MPs said this week.

New powers to detain such people should be accompanied by the most stringent safeguards—to satisfy the requirements of the European Convention on Human Rights and the liberties traditionally protected by parliament, the report adds.

Substantial extra funds …
Biological Basis for Cancer Treatment
Authors: Bruce A. Chabner
Journal: Annals of Internal Medicine (1993)

The new knowledge of the regulation of cell growth and the genetic and biochemical changes that lead to malignancy have created many new opportunities for cancer drug discovery. These new targets include oncogenes, growth factors and their receptors, signal transduction pathways, and cell differentiation signals. Attempts to identify new therapies based on these targets can complement traditional drug discovery efforts that rely on high-volume screening of candidate natural products and synthetic chemicals against human tumor cell lines and against defined molecular reactions. Through modern computer-based data analysis, drug screening data can be used to establish mechanisms of drug action of new agents; these analyses shed light on patterns of cross-resistance of new compounds and their interactions with defined molecular targets as well as allow selection of chemically and biologically unique agents as candidates for clinical development.
Compulsory Health Insurance: The Continuing American Debate
Authors: Odin W. Anderson
Journal: JAMA (1983)

There is persistent interest among proponents of some form of universal health insurance under government auspices in this country as to   United States is  only remaining large industrial nation without such insurance. The question of why is freighted with  implication that  United States is, thus, an anomaly. Maybe so, but there is more than one road to universality than a national system, and  United States may well back into universality according to its own genius, predilections, and ignorance, as expressed in this book by Poen writing about  Truman era and Cohen, former secretary of  Department of Health, Education, and Welfare, and architect of  Medicare Act, in a short Postscript for  Future, where he predicts that at some time the cause of national health insurance will reappear.  The compilation of essays is largely a result of papers given at a symposium