tbuckley/cabot-search huggingface dataset:
Mechanisms of adverse effects of -agonists in asthma
Authors: S. L Johnston, M. R Edwards
Journal: Thorax (2009)

asthma, can improve BHR when administered chronically to patients with mild asthma. 19 This research has many parallels with the use of b-blockers in the treatment of patients with heart failure where this class of drug was once contraindicated as acute dosing produced adverse effects in such patients. 20 It was then subsequently recognised that chronic dosing with b-blockers was beneficial in patients with heart failure, and the use of this drug class is now considered a central part of standard treatment guidelines.So-called ''paradoxical pharmacology'', 21 where there may be differential effects of acute versus chronic dosing of a given class of drug, would seem to be a very important issue when considering the use of drugs that recognize the b 2 receptor.Furthermore, given that it has been recently suggested that some b-blockers act as inverse agonists at the b 2 receptor and activate novel signalling pathways that are required for the full asthma phenotype in mice, 22 it would seem time to challenge the dogma that activation of b 2 receptors chronically is a good thing.If nothing else, the study by Virchow and colleagues provides further support for why monotherapy with b 2 receptor agonists has no role in the treatment of patients with asthma.Competing interests: CP is a co-founder of Verona Pharma which has an interest in developing novel drugs for treating respiratory diseases.
Consciousness and control: The argument from developmental psychology
Authors: Philip David Zelazo, Douglas Frye
Journal: Behavioral and Brain Sciences (1999)

Limitations of Dienes &amp; Perner's (D&amp;P's) theory are traced to the assumption that the higher-order thought (HOT) theory of consciousness is true. D&amp;P claim that 18-month-old children are capable of explicitly representing factuality, from which it follows (on D&amp;P's theory) that they are capable of explicitly representing content, attitude, and self. D&amp;P then attempt to explain 3-year-olds' failures on tests of voluntary control such as the dimensional change card sort by suggesting that at this age children cannot represent content and attitude explicitly. We provide a better levels-of-consciousness account for age-related abulic dissociations between knowledge and action.
Beyond Autonomy -- Physicians' Refusal to Use Life-Prolonging Extracorporeal Membrane Oxygenation
Authors: J J Paris, M D Schreiber, M Statter, R Arensman, M Siegler
Journal: New England Journal of Medicine (1993)

Three years ago we noted that the literature on physicians' refusal to provide requested treatment was sparse1. Since that time the issue has fueled an intense, two-pronged debate -- on futility and on the limits of patient autonomy. The debate over patient autonomy is a genuinely philosophical dispute; that over futility seems to be a relapse into nominalism. It is not the meaning of a word but the moral basis for the actions of the participants that ought to be the focus of our attention. The fractious debate on the meaning of futility, evidenced in a spate of recent . . .
Pulmonary Insufficiency and Hypercapnia Complicated by Potassium-Responsive Alkalosis
Authors: Robert T. Cochran
Journal: New England Journal of Medicine (1963)

TWO patients seen recently at the University of Texas Medical Branch Hospitals presented severe chronic pulmonary insufficiency and hypercapnia complicated by systemic alkalosis. The alkalosis was rapidly corrected in both by the administration of large amounts of potassium salts. A strongly positive potassium balance was effected during this interim, suggesting that potassium depletion was causally related to the alkalosis.This unique association has not previously been reported. The purpose of this article is to point out its occurrence and to discuss the mechanisms where-by it might develop. Although any conclusions obtained from a necessarily retrospective study will be inferential, the . . .
SOME MEDICO-LEGAL EXPERIENCES IN RAILWAY CASES.Read before the Section of Neurology and Medical Jurisprudence, at the Forty fourth Annual Meeting of the American Medical Association.
Authors: THOMAS G. MORTON
Journal: JAMA (1893)

Railroad injuries, from a surgical point of view, possess many features of interest; not the least of which is the medico-legal question concerning the gravity or reality of alleged injuries for which pecuniary compensation is demanded.  At a time when he least expects it, in these days of rapid transit and frequent travel, any individual may be obliged to witness, participate in or be the victim of a railroad accident attended by loss of life or by various degrees of traumatism—maiming, contusion or concussion, and every surgeon is liable to be called upon to render assistance to those injured or claiming to have been injured by such an occurrence. Experience, however, has taught us to exercise special caution and to express a very guarded opinion as to the prognosis or gravity of a traumatism occurring under such circumstances. Suits for damages are so common that the surgeon or physician almost
131. Design and Construction of an Adenovirus Vector Containing Fiber Fibritin/Canine CD40L Fibers Directed to Canine CD40-Expressing Cells
Authors: Masaharu Nakayama, Joel N. Glasgow, Bruce F. Smith, Jing Li, Nikolay Korokhov, Natalya Belousova, Kenzaburo Tani, David T. Curiel
Journal: Molecular Therapy (2006)

Dendritic cells (DCs) are a central element in the development of antigen-specific immune responses. On this basis, antigen loading of dendritic cells via transduction with viral vectors in vivo has been proposed as a standardized and easily clinically applicable approach for tumor vaccination strategies. For genetic vaccine approaches to be effective, it is of vital importance to achieve a selective and high transduction efficiency of the DC present in situ, while also ensuring their effective activation and migration. Towards this goal, we have reported that an adenovirus (Ad) serotype 5 vector targeted to human (hCD40) via genetic capsid incorporation of human CD40 ligand (hCD40L) achieves selective transduction of DC in vitro (Belousova et al. Journal of Virology, 2003). We have sought further evaluation of this CD40-targeted vector system in vivo. Of note, certain dog breeds are subject to spontaneous cancers such as osteosarcoma and lymphoma, thereby providing large animal models as stringent in vivo models of human immunotherapy. We have therefore adapted our CD40 targeting system for use in canine systems. We have constructed an E1-deleted, luciferase transgene Ad5 vector encoding a genetically modified fiber that displays canine CD40L, utilizing similar technique as our hCD40L-incorporating Ad5 vector. Viral particles were harvested from Ad5 fiber included- 293F28 cells and 293 cells, purified by standard cesium chloride gradient centrifugation and yielded titers in excess of 3.0 × 10e12 vp/ mL. Characterization of AdFFcCD40L vector infectivity in canine CD40-positive 293 cells (293cCD40) showed 6.9-to-14.6 fold greater luciferase reporter gene activities versus cCD40-negative 293 cells. Herein, we have demonstrated the construction, purification, and initial infectivity characterization of a novel Ad vector that exploits the native canine CD40-CD40L pathway. These data support our use of our cCD40-targeted Ad vectors in novel canine models of immunotherapy.
Near Misses in Anesthesia: Lessons Learned
Authors: E. S. Siker
Journal: JAMA (1989)

This 98-page paperback contains a litany of anesthetic nightmares. The authors have collected 45 critical incidents from "actual experiences in nine different hospitals scattered over several states" and have presented them in brief, comprehensive, narrative formats, each of which challenges the reader to diagnose the problem before turning the page and learning the answer. Each narrative is followed by a brief description of the causative factors under the heading "Resolution." Each incident concludes with a discussion, and pertinent references are appended. Episodes, from first—"The Case of the Tilted Timebomb"—to last—"The Case of the Sluggish Stream"—are alliteratively titled. As an example of the style and format used by the authors, the issue to be resolved in "Tilted Timebomb" is the postoperative hypertension/tachycardia that occurs in an elderly patient who, following vascular surgery, is treated for hypotension with head-down positioning while undergoing pressure-cycled mechanical ventilation. The lesson to be learned is that
Quality Assurance in Endoscopy Should Include Data on Sedation
Authors: L. T. Heuss, C. Beglinger
Journal: Endoscopy (2004)

We read with great interest the recent article by Naylor et al. on ”Setting up a quality assurance program in endoscopy” [1] and we strongly agree with the authors that major improvements should be made in assessing the quality and outcome of endoscopy.
Treatment of ankylosing spondylitis with pamidronate: an open label study
Authors: R Grover
Journal: Annals of the Rheumatic Diseases (2006)

<h3>Background</h3> Motorcycle one-wheeling (MOW) is one of the burgeoning factors in motorcycle crashes in Pakistan. Young One-wheelers (YOW) perform dangerous stunts such as riding motorcycle while laying flat, lifting front-wheel and their backs facing motorcycle handles. Consequently, they put themselves and others at risk. A newspaper reported that over 200 YOW died and around 1,300 other road users were injured or killed in MOW crashes during 2011–2013. Current research is the first in Pakistan that presents the most recent epidemiology of MOW crashes. <h3>Methods</h3> Retrospective analysis was conducted on crash data for last two years collected by Rescue 1122 (an emergency service in Pakistan) from 37 major cities of Province Punjab. <h3>Results</h3> Rescue 1122 attended 389 MOW crashes during the study period. Of them, maximum MOW crashes were reported in Kasur (<i>n</i> = 88), followed by Lahore (<i>n</i> = 69) and Rawalpindi (<i>n</i> = 41). In all 351 injuries and 16 fatalities were reported among YOW. Of the 351 injuries, about 70% were critical (head, spinal &amp; fractures). All 16 fatalities were aged between 16 and 25 years. Most (19%) were aged 21 years, followed by 13% amongst aged 18, 19 and 22 years respectively. None of fatalities/injured YOW were wearing helmet. Most MOW crashes were reported on Pakistan Independence Day (14 August) and Chand Rat—a night before Eid, whilst some of them were also reported on normal week-days. <h3>Conclusions</h3> Prevalence of MOW crashes across Punjab is alarming, as initially this dangerous venture was only confined to large cities. In addition to major cities, MOW crashes are mostly reported from Kasur, which is a suburban city. Though MOW crashes constitute only 1% of reported crashes, their outcomes are very severe, as all MOW fatalities/injured included youngsters have devastating psycho-social impacts on the society. A serious effort is required on part of all the stakeholders. School road safety education with parents partaking is also very important in this view.
SUBSEQUENT HISTORIES OF ONE HUNDRED AND SIXTY "ARRESTED CASES" OF TUBERCULOSIS TREATED AT THE SHARON SANATORIUM, 1891-1906.
Authors: VINCENT Y. BOWDITCH
Journal: JAMA (1907)

In offering you the results of work of over fifteen years at the Sharon Sanatorium, this time with the invaluable assistance of Dr. Griffin, neither he nor I offer any apology for what may seem an unnecessary harping on a subject which has become familiar in the past few years since the crusade against tuberculosis has assumed such great proportions. It must be remembered that in certain respects, so far as climate, altitude and proximity to the sea and a large city are concerned, the Sharon Sanatorium was for several years unique. The results of treatment, therefore, should be kept before you that you may judge whether that which was begun sixteen years ago as an experiment has proved a success or otherwise. As shown by the title of the paper, I still adhere to the term "arrested" in speaking of cases in which the most important symptoms (chiefly cough,
THE PROTEIN POISON AND ITS RELATION TO DISEASE
Authors: VICTOR C. VAUGHAN
Journal: JAMA (1913)

In 1903, Vaughan and Wheeler found that the cellular substance of the colon bacillus contains a highly active poison. This was obtained by extracting the dried, dead cells with a 2 per cent. solution of sodium hydroxid in absolute alcohol at 78 C. (172.4 F.). This poison was partially purified by repeated precipitation from alcoholic solution with either mercuric or cupric chlorid and removal of the base with hydrogen sulphid. This poison kills guinea-pigs when injected intravenously in doses of 0.5 mg. When given intra-abdominally this dose must be multiplied by 16 and when given subcutaneously by 32 in order to cause death. Subsequently the same, or a closely related, poison was obtained from other pathogenic and from non-pathogenic bacteria, and then from vegetable and animal proteins. This work has been repeated and confirmed by others in this country and abroad. It is now known as "the protein poison" and
IMMUNIZATION OF DISSOCIATED SPLEEN CELL CULTURES FROM NORMAL MICE
Authors: Robert I. Mishell, Richard W. Dutton
Journal: The Journal of Experimental Medicine (1967)

A culture system for cell suspensions from mouse spleens has been described. The system provides adequate conditions for in vitro immunization on initial exposure to heterologous erythrocytes. The in vitro response closely parallels that observed in vivo with respect to size, early kinetics, antigen dose, and the inhibitory effect of passive antibody. The response of cultured cells differs in two respects from that seen in vivo. There is an increase in the ability to discriminate between different varieties of homologous erythrocytes and the in vitro response does not appear to be limited by whatever mechanisms regulate the in vivo response.
Article omitted to mention victims of left wing revolutionary politics
Authors: D. Steinberg
Journal: BMJ (1996)

<h3>Objective</h3> To analyse the expression of SIRT1 in synovial tissues and cells of patients with rheumatoid arthritis (RA) and to study the function of SIRT1 in inflammation and apoptosis in RA. <h3>Methods</h3> Levels of SIRT1 expression were analysed in synovial tissues and cells from patients with RA by real-time PCR and western blotting before and after stimulation with toll-like receptor ligands, tumour necrosis factor α (TNFα) and interleukin 1β (IL-1β). Immunohistochemistry was used to study the localisation of SIRT1. Fluorescence activated cell sorting analysis was performed to investigate the effect of SIRT1 on apoptosis. Peripheral blood monocytes and rheumatoid arthritis synovial fibroblasts (RASFs) were transfected with wild-type or enzymatically inactive SIRT1 expression vectors or with siRNA targeting SIRT1. Cytokine analysis of IL-6, IL-8 and TNFα were performed by ELISA to study the role of SIRT1 on proinflammatory mediators of RA. <h3>Results</h3> SIRT1 was found to be constitutively upregulated in synovial tissues and cells from patients with RA compared to osteoarthritis. TNFα stimulation of RASFs and monocytes resulted in further induced expression levels of SIRT1. Silencing of SIRT1 promoted apoptosis in RASFs, whereas SIRT1 overexpression protected cells from apoptosis. Inhibition of SIRT1 enzymatic activity by inhibitors, siRNA and overexpression of an enzymatically inactive form of SIRT1 reduced lipopolysaccharide-induced levels of TNFα in monocytes. Similarly, knockdown of SIRT1 resulted in a reduction of proinflammatory IL-6 and IL-8 in RASFs. <h3>Conclusion</h3> The TNFα-induced overexpression of SIRT1 in RA synovial cells contributes to chronic inflammation by promoting proinflammatory cytokine production and inhibiting apoptosis.
Screening Misses High LDL in Many Youths
Authors: Mike Mitka
Journal: JAMA (2010)

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Bleeding Risk with Dabigatran in the Frail Elderly
Authors: Paul Harper, Laura Young, Eileen Merriman
Journal: New England Journal of Medicine (2012)

In response to Eikelboom and Weitz: when prescribing a drug with side effects that include life-threatening hemorrhage, reversal is not "desirable," it is essential.Our letter to the Editor never mentioned prothrombin complex concentrates.Rapid reversal is indeed associated with reduced morbidity and mortality. [1]][3] Thromboelastography detects the effects of dabigatran within minutes (and the values for activated clotting time were markedly prolonged in all the patients described in our letter).Partialthromboplastin times were normal.The dilutethrombin-time assay with dabigatran calibrators is currently labeled for research use only.Eikelboom and Weitz state the deaths could not be attributed to "lack of an antidote."These patients were receiving dabigatran and presented with coagulopathy, and the multidisciplinary team caring for them could not control their hemorrhages.Next, although an absolute reduction of 0.2 percentage points in intracranial hemorrhage may be statistically significant (in 18,000 patients), this may not be clinically meaningful. 4 Finally, they state that a lack of an antidote should not deter physicians from prescribing dabigatran.We hope all prescribers will take note of the Food and Drug Administration alert re-garding dabigatran and, in doing so, expand the risk-benefit conversation with their patients. 5
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
Authors: Rene Dubos, Chi-Jen Lee, Richard Costello
Journal: The Journal of Experimental Medicine (1969)

The effects of neonatal influences on the growth and longevity of mice were studied by using animals derived from a highly inbred germfree colony that had been reassociated with a microbial flora free of known pathogens. The size of the animals at weaning time could be conditioned predictably by manipulating the diet of their mothers during gestation and lactation or by shortening or lengthening the period of lactation. A deficient diet during gestation or during lactation decreased the metabolic efficiency of the adult animal, even if it was fed an optimum diet after weaning. The effect was greatest when malnutrition occurred during both pregnancy and lactation. In contrast, an optimum diet during gestation and lactation rendered the animal less susceptible to the depressing effects of nutritional deficiency during adult life. A marked and lasting growth depression could be reproducibly achieved by contaminating newborn mice orally with an unidentified enterovirus. But neonatal infection with enterobacteria or mycobacteria even though severe, did not significantly alter the growth rate. Regardless of its initial cause, the depression of the growth rate during the preweaning period persisted throughout the whole life span of the animals, even when they were placed under optimum sanitary and nutritional conditions after weaning. Agencies (nutritional or infectious) which brought about a depression of whole body weight also affected the absolute and relative sizes of the various organs, especially of the brain. By manipulating neonatal influences, it was possible to produce at will in a given colony of highly inbred mice a family of strikingly different growth curves. This could be done without causing the death of any animal or affecting longevity.
Physical control and coordination in childhood and adult obesity: longitudinal birth cohort study
Authors: W. Osika, S. M Montgomery
Journal: BMJ (2008)

To identify whether measures of childhood physical control and coordination as markers of neurological function are associated with obesity in adults.Longitudinal birth cohort study.National child development study in Great Britain.11,042 people born during one week in 1958.Obesity at age 33 years defined as body mass index >or=30.Among 7990 cohort members at age 7 years, teachers reported that poor hand control, poor coordination, and clumsiness "certainly applied" more often among those who would be obese adults, producing adjusted odds ratios of 1.57 (95% confidence interval 1.13 to 2.20; P=0.008) for poor hand control, 2.30 (1.52 to 3.46; P<0.001) for poor coordination, and 3.91 (2.61 to 5.87; P<0.001) for clumsiness. Among 6875 participants who had doctor administered assessments with continuous scores at age 11 years, poorer function was associated with later obesity, indicated by adjusted odds ratios (change in risk per unit increase in score) of 0.88 (0.81 to 0.96; P=0.003) for copying designs, 0.84 (0.78 to 0.91; P<0.001) for marking squares, and 1.14 (1.06 to 1.24; P<0.001) for picking up matches (a higher score indicates poor function in this test). Further adjustment for contemporaneous body mass index at age 7 or 11 years did not eliminate statistical significance for any of the associations.Some aspects of poorer neurological function associated with adult obesity may have their origins in childhood.
Fish acute toxicity syndromes and their use in the QSAR approach to hazard assessment.
Authors: J M McKim, S P Bradbury, G J Niemi
Journal: Environmental Health Perspectives (1987)

Implementation of the Toxic Substances Control Act of 1977 creates the need to reliably establish testing priorities because laboratory resources are limited and the number of industrial chemicals requiring evaluation is overwhelming. The use of quantitative structure activity relationship (QSAR) models as rapid and predictive screening tools to select more potentially hazardous chemicals for in-depth laboratory evaluation has been proposed. Further implementation and refinement of quantitative structure-toxicity relationships in aquatic toxicology and hazard assessment requires the development of a
15 OPEN-LABEL PROSPECTIVE RANDOMIZED 48 WEEK CLINICAL TRIAL: ROSIGLITAZONE VERSUS ROSIGLITAZONE AND METFORMIN (AVANDAMET) VERSUS ROSIGLITAZONE AND LOSARTAN IN THE TREATMENT OF NON-ALCOHOLIC STEATOHEPATITIS (NASH)
Authors: D. Torres, F.J. Jones, J. Shaw, C. Williams, J.A. Ward, S.A. Harrison
Journal: Journal of Hepatology (2011)
Bypass Enteropathy
Authors: Ernst J. Drenick
Journal: JAMA (1976)

Many manifestations following jejunoileal bypass are due to chronic inflammation of the excluded bowel rather than short bowel malabsorption. Diarrhea, abdominal distention, and gas-fluid levels were common diagnostic features of "bypass enteropathy." Exploration showed the bypassed bowel to be dilated, with serosal inflammation and pneumatosis cystoides intestinalis. The bypassed loops contained a fecal flora and the mucosa demonstrated nonspecific chronic inflammatory changes. Exudative protein losses were noted. Systemic complications of bypass enteropathy were similar to other inflammatory diseases of the bowel. Improvement following treatment with metronidazole or after dismantling of the bypass suggested that bacterial byproducts originating in the excluded bowel were causally related. (<i>JAMA</i>236:269-272, 1976)