tbuckley/cabot-search huggingface dataset:
Temperature Management and Modern Post–Cardiac Arrest Care
Authors: Jon C. Rittenberger, Clifton W. Callaway
Journal: New England Journal of Medicine (2013)

Modern cardiopulmonary resuscitation (CPR) began in 1960, when clinicians translated observations about external chest compressions from the laboratory to patients.1 CPR increased survival for patients who had cardiopulmonary collapse outside of the operating room from none to a few. Incremental improvements in the survivorship from CPR occurred as more persons were trained in CPR and as defibrillators became portable and were deployed in more locations. Unfortunately, a cascade of brain injury begins within minutes after cardiac arrest, with the consequence that most patients who had return of cardiac activity did not survive to leave the hospital or did so in . . .
The TD50: a proposed general convention for the numerical description of the carcinogenic potency of chemicals in chronic-exposure animal experiments.
Authors: R Peto, M C Pike, L Bernstein, L S Gold, B N Ames
Journal: Environmental Health Perspectives (1984)

A generally accepted format for the numerical description of the carcinogenic potency of a particular chemical in a particular strain of animals is desirable so that statements from different sources about potency and attempts by different authors to correlate potency with particular laboratory measurements will be comparable. The choice of an appropriate standard format is to a certain extent arbitrary. In this paper we recommend that the TD50 (tumorigenic dose rate 50) be used. TD50 can be calculated for a single target site or combination of sites. The TD50, in analogy with the LD50, is defined as that chronic dose rate (in mg/kg body weight/day) which would halve the actuarially adjusted percentage of tumor-free animals at the end of a standard experiment time--the
Prediction of rodent carcinogenicity using the DEREK system for 30 chemicals currently being tested by the National Toxicology Program. The DEREK Collaborative Group.
Authors: C A Marchant
Journal: Environmental Health Perspectives (1996)

DEREK is a knowledge-based expert system for the qualitative prediction of toxicity. The DEREK system has been used to predict the carcinogenicity in rodents of the 30 chemicals in the second National Toxicology Program (NTP) carcinogenicity prediction exercise. Seven of the chemicals were predicted to be carcinogens. For 23 chemicals, there was no evidence in the DEREK knowledge base to suggest carcinogenic activity. Supplementary data from a variety of sources have been evaluated by human experts to assess confidence in each DEREK prediction. These sources included standard toxicology reference texts, genotoxicity and subchronic toxicity assay results for each chemical, as well as Salmonella mutagenicity and carcinogenicity data for close structural analogues. This process has led to the proposal of a number of improvements to the DEREK carcinogenicity knowledge base.
Pralatrexate Is Synergistic with the Proteasome Inhibitor Bortezomib in<i>In vitro</i>and<i>In vivo</i>Models of T-Cell Lymphoid Malignancies
Authors: Enrica Marchi, Luca Paoluzzi, Luigi Scotto, Venkatraman E. Seshan, Jasmine M. Zain, Pier Luigi Zinzani, Owen A. O'Connor
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Pralatrexate (10-propargyl-10-deazaaminopterin) is an antifolate with improved cellular uptake and retention due to greater affinity for the reduced folate carrier (RFC-1) and folyl-polyglutamyl synthase. Based on the PROPEL data, pralatrexate was the first drug approved for patients with relapsed and refractory peripheral T-cell lymphoma. Bortezomib is a proteasome inhibitor that has shown some activity in patients with T-cell lymphoma. Experimental Design: Assays for cytotoxicity including mathematical analysis for synergism, flow cytometry, immunoblotting, and a xenograft severe combined immunodeficient-beige mouse model were used to explore the in vitro and in vivo activities of pralatrexate alone and in combination with bortezomib in T-cell lymphoid malignancies. Results: In vitro, pralatrexate and bortezomib exhibited concentration- and time-dependent cytotoxicity against a broad panel of T-lymphoma cell lines. Pralatrexate showed synergism when combined with bortezomib in all cell lines studied. Pralatrexate also induced potent apoptosis and caspase activation when combined with bortezomib across the panel. Cytotoxicity studies on normal peripheral blood mononuclear cells showed that the combination was not more toxic than the single agents. Western blot assays for proteins involved in broad growth and survival pathways showed that p27, NOXA, HH3, and RFC-1 were all significantly modulated by the combination. In a severe combined immunodeficient-beige mouse model of transformed cutaneous T-cell lymphoma, the addition of pralatrexate to bortezomib enhanced efficacy compared with either drug alone. Conclusion: Collectively, these data suggest that pralatrexate in combination with bortezomib represents a novel and potentially important platform for the treatment of T-cell malignancies. Clin Cancer Res; 16(14); 3648–58. ©2010 AACR.
Abstract A53: Genome-wide profile of somatic copy number alterations in Wilms tumor: Comparison between samples derived from patients with and without relapse
Authors: Ana C.V. Krepischi, Mariana Maschietto, Silvia S. Costa, Tales A. Abreu, Amanda Gonçalves, Beatriz de Camargo, Paul E. Grundy, Carla Rosenberg, Dirce M. Carraro
Journal: Cancer Research (2011)

Abstract Wilms tumor (WT) is the most common kidney malignancy of childhood; nevertheless, its pathogenesis remains largely unknown. Although the majority of the WT occur sporadically, a strong genetic component is present at least in the many cases which are related to underlying syndromes. Tumor relapse occurs at a rate of approximately 15%, and molecular studies are focused in identifying markers to define the minimal therapy for limiting the late effects of treatment while maintaining high survival rate. Loss of heterozygosity of both 1p and 16q was already associated to an increased risk of relapse and death although detected in a very small subset of WT patients, making this feature a less sensitive prognostic factor. Somatic DNA copy number alterations (CNAs) are common genetic mutations in cancer, and often define key pathogenic events. This study was designed to assess the genome profile of CNAs in WT, aiming to identify genetic markers associated to relapse that could be of clinical and prognostic importance. We performed an array-CGH based survey of 48 WT samples, mainly tumors in stages III and IV, derived from patients with (17) and without (31) relapse in at least three years. Data was obtained using a high resolution oligoarray platform (180K - Agilent), with an average resolution &amp;gt;70 Kb, and analysis was performed on the software Nexus 6 (Biodiscovery). The analysis revealed high frequency of arm/whole chromosome alterations at 1q, 7q, and chromosomes 6 and 12 (gains), while losses were recurrent at 7p, 11 q, and 16q chromosome regions. WT derived from patients with relapse exhibited a distinctive pattern of genomic alterations, mainly characterized for an increased frequency of proximal 1q gain and low amplitude gain of chromosome 6. Additionally, analysis of small regions affected by recurrent focal alterations disclosed new genes that can be relevant for Wilms tumorigenesis and relapse. Financial support: FAPESP/CNPq Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A53.
Drugs, secrecy, and society.
Authors: C Medawar
Journal: BMJ (1993)

Health promotion and children and teenagersWhy it is mainly the government's responsibilityThe Health of the Nation contains several targets directly affecting the health of present children and teenagers and future adults.'These include reducing smoking in 1 1-15 year olds by one third, reducing the proportion of energy derived from fats to 35%, reducing deaths from accidents by one third
Sir Thomas Browne
Authors: Jerome M. Schneck
Journal: JAMA (1983)

<h3>To the Editor.—</h3> I read the informative and erudite article on Sir Thomas Browne (1982;248:1845) by John H. Dirckx, MD, noting the 300th anniversary of Browne's death and observing, among other assessments, that his<i>Religio Medici</i>and<i>Christian Morals</i>were not in any sense scientific works. <i>Religio Medici</i>transcends dimensions of a religious, spiritual, philosophical, and literary work. I believe it can be viewed, with<i>A Letter to A Friend</i>and<i>Christian Morals</i>, at least in part, as psychological in the modern sense when studied from the vantage point of contemporary psychiatric knowledge and concepts. Discerning insights into psychological experience and functioning and awareness about mental derangements appear clearly. The variety of psychodynamics of which Browne was cognizant and wrote would, in 20th-century terms, be designated compensation, repression, reaction formation, identification, introjection, rationalization, and displacement. He was certainly aware of unconscious components in human behavior and deserves a niche in
Utility of a standard allergen series alone in the evaluation of allergic contact dermatitis: A retrospective study of 732 patients
Authors: David E. Cohen, Ronald Brancaccio, Dina Andersen, Donald V. Belsito
Journal: Journal of the American Academy of Dermatology (1997)

Background: Patch testing remains the standard for the diagnosis of allergic contact dermatitis. The validity and usefulness of a standard patch test allergen series has not been addressed adequately by previous studies. Objective: We sought to examine the utility of the standard allergen series as a sole screening tool in the diagnosis of allergic contact dermatitis. Methods: The charts of 732 patients referred for patch testing were reviewed for positive patch test results. The group of patients with positive reactions was stratified into two groups based on the clinical relevance of their reactions. These groups were subsequently analyzed to determine whether the reactions were to part of the standard series of allergens or to part of a supplementary group. Results: Of patients tested, 50% had a positive patch test. Of those, 221 (30%) had reactions deemed clinically relevant. Only 23% of patients with positive patch tests reacted to an allergen(s) in the standard series exclusively. When adjusted for clinical relevance, only 15.7% of patients were completely evaluated with the standard series of 20 allergens. Conclusion: The standard allergen series of 20 allergens available in the United States is limited as a screening tool when used alone in the evaluation of patients with allergic contact dermatitis. Patch testing remains the standard for the diagnosis of allergic contact dermatitis. The validity and usefulness of a standard patch test allergen series has not been addressed adequately by previous studies. We sought to examine the utility of the standard allergen series as a sole screening tool in the diagnosis of allergic contact dermatitis. The charts of 732 patients referred for patch testing were reviewed for positive patch test results. The group of patients with positive reactions was stratified into two groups based on the clinical relevance of their reactions. These groups were subsequently analyzed to determine whether the reactions were to part of the standard series of allergens or to part of a supplementary group. Of patients tested, 50% had a positive patch test. Of those, 221 (30%) had reactions deemed clinically relevant. Only 23% of patients with positive patch tests reacted to an allergen(s) in the standard series exclusively. When adjusted for clinical relevance, only 15.7% of patients were completely evaluated with the standard series of 20 allergens. The standard allergen series of 20 allergens available in the United States is limited as a screening tool when used alone in the evaluation of patients with allergic contact dermatitis.
In vivo modulation of CD1 and MHC class II expression by sheep afferent lymph dendritic cells. Comparison of primary and secondary immune responses.
Authors: J Hopkins, B M Dutia, R Bujdoso, I McConnell
Journal: The Journal of Experimental Medicine (1989)

The experiments described in this article characterize the phenotypic and functional changes in afferent lymph cell populations that occur as a result of in vivo immune stimulation. During the primary immune response (in antigen-naive sheep) there are very transient increases in level of CD1 expression by subpopulations of dendritic cells (DC) but no alterations in cell kinetics or MHC class II expression. In contrast, secondary antigenic challenge (in primed sheep) into the drainage area of an afferent lymphatic causes profound changes in the cell output, characterized by a greater than threefold drop in total cell output on days 1-3 followed by an approximate fivefold rise on day 5. There is also a substantial increase in both the proportion of MHC class II-positive T lymphocytes (from 28 to 54%) and in the quantitative expression of class II by both DC and lymphocytes. Class II expression by DC increases five- to sixfold by day 5, while the level of expression of class II on lymphocytes approximately doubles. The increase in CD1 expression during the secondary response is more prolonged than during the primary response, being detectable between days 2 and 6 after challenge. The rise in class II affects the whole DC population, in contrast to CD1 where the increase affects only a subpopulation of cells. In terms of functional properties, afferent lymph DC isolated during a primary response show no alteration of their activity, whereas DC taken 4-5 d after secondary challenge are up to fivefold more active in their ability to present soluble antigen to primed autologous T cells and to antigen-specific cell lines as well as to stimulate in the MLR. The relative expression of class II correlates temporally with an increased capacity of DC to present antigen. Monoclonal anti-class II antibodies totally inhibit the in vitro assays but anti-CD1 antibodies have no effect. The previous paper has demonstrated that afferent DC can associate with antigen in vivo and can present that antigen to antigen-specific T cells. This article extends our knowledge of DC biology and demonstrates that DC, activated during secondary in vivo immune responses, have an enhanced ability to present an antigen, unrelated to that used for challenge, to specific T cell lines. This enhancement correlates directly with quantitative variation of expressed class II and not CD1 and suggests that this variation in class II expression plays a physiological role in in vivo immune regulation.
Reduction in IgG galactose in juvenile and adult onset rheumatoid arthritis measured by a lectin binding method and its relation to rheumatoid factor.
Authors: N Sumar, D A Isenberg, K B Bodman, A Soltys, A Young, A M Leak, J Round, F C Hay, I M Roitt
Journal: Annals of the Rheumatic Diseases (1991)

Glycosylation changes in patients with juvenile chronic and adult onset rheumatoid arthritis have been studied using a novel binding method. Both these major types of arthritis showed decreased galactosylation of serum IgG, which confirms earlier studies using a different, more complex chemical method. No significant correlation between serum IgG, IgM, and IgA rheumatoid factors and age corrected G(o) (percentage of oligosaccharide chains lacking galactose) was found. The possibility that the less glycosylated IgG is preferentially confined to circulating IgM/IgG immune complexes cannot be excluded, however.
Primary and secondary care management of women with early breast cancer from affluent and deprived areas: retrospective review of hospital and general practice records
Authors: U. Macleod
Journal: BMJ (2000)

To investigate whether poorer survival of breast cancer among deprived women compared with affluent women is related to their NHS care.Retrospective review of hospital and general practice case records.Greater Glasgow Health Board area.Women diagnosed with breast cancer in 1992-3 who lived in the most affluent (deprivation categories 1 and 2) and the most deprived areas (deprivation categories 6 and 7) of Glasgow (Carstairs and Morris deprivation index).Breast cancer treatment, time from general practice consultation to clinic visit and surgery, and details of hospital admissions and follow up in primary and secondary care.The access to care and surgical and oncological treatment of women from affluent and deprived areas were similar. Admissions to hospital for problems not related to breast cancer were more common in those living in deprived areas (number admitted once or more: 51 (24%) v 13 (10%), P=0.001). Consultation patterns in general practice by the second year after diagnosis showed women in deprived areas consulting more frequently than women in affluent areas (median (interquartile range) number of consultations (5 (2-10) v 7 (4-13), P=0.01).Women living in affluent areas did not receive better NHS care for breast cancer than women in deprived areas. However, women from deprived areas seem to have greater comorbidity, and poorer outcomes from breast cancer among these women is probably due to factors which result in deprived communities having poorer health outcomes rather than to management of their breast cancer.
Radiological and clinical relationship between idiopathic carpal tunnel syndrome, humeral epicondylitis, and cervical spine changes
Authors: C. Murray-Leslie, V. Wright
Journal: Annals of the Rheumatic Diseases (1976)

Antibodies to ds (native) DNA in chronic active hepatitis (CAH).P. Davis and A. E. A. Read (Department of Medicine, Bristol) Recent studies have suggested that antibodies to DNA have a high degree of specificity for systemic lupus erythematosus (Tan et al., 1966).These antibodies have, however, also been described in discoid LE (Mandel et al., 1972).Chronic active hepatitis is an immune liver disease which has many clinical and serological similarities to SLE (Read et al., 1963).In particular antinuclear antibodies and evidence of complement conversion are common (Gitnick et al., 1973).The aim of this study was to determine the incidence of antibodies to ds DNA in CAH.Sera from 36 patients with CAH were studied using the Farr ammonium precipitation test and the filter radioimmunoassay technique. 15of the 36 cases (42 %) had levels of antibody previously only seen in patients with active SLE.These antibodies were detected despite steroid therapy in the majority.Antibodies to ds DNA were not found in 22 cases of other liver disease, including alcoholic cirrhosis and primary biliary cirrhosis, nor in a number of control sera.Serial studies showed that levels of DNA antibody rise and fall with disease activity as determined by liver function tests and clinical parameters.There was an inverse relationship between the height of DNA antibody and serum complement levels and a direct relationship between the height of DNA antibody and the presence of C3 breakdown products.This study suggests that DNA antibodies may not be as specific for SLE as was previously thought or, that CAH and SLE have further immunological similarities.These antibodies may have diagnostic and therapeutic value in the study of immunological liver disease.
Medicine Man: A Young Doctor on the Brink of the 21st Century
Authors: Sylvia M. Ramos
Journal: JAMA (1986)

Few physicians may be examining the moral consequences of the changes being brought about in medicine by the growth of technology. These changes will affect not only physicians but everyone who comes in contact with them. This book will function as a sextant by means of which we can check our present position and examine those consequences. The points of reference are a narrative of the life of a third-year medical student, Aaron Kenigsberg (the present), including family vignettes used to highlight his physician father (the past), and two essays that examine the humanist revolution in medicine (the future). Those, in brief, are the premise and content of this book, which is at various times, but not consistently, witty, interesting, repetitious, disconcerting, and, probably, more likely to appeal to the lay public than to physicians. Many of the important yet timeworn ethical issues in medicine are raised, although without further
Association of HLA-DRw2 with autoimmune thrombocytopenic purpura.
Authors: S Karpatkin, M Fotino, A Gibofsky, R J Winchester
Journal: Journal of Clinical Investigation (1979)

Peripheral blood lymphocytes from 38 patients with autoimmune thrombocytopenic purpura (AITP) were tested for HLA-A, -B, and -C alloantigens. Isolated B lymphocytes from 20 of these patients were tested for HLA-DRw (Ia) alloantigens. The profile of HLA alloantigens in the patients with AITP was significantly different from that of a matched control population. The most significant finding was the presence of the HLA-DRw2 alloantigen in 75% of patients as compared with 23% in the control population, P less than 0.001, relative risk 10.0 (A relative risk of 1 would indicate no association between the presence of the antigen and the disease.) The co-occurrence of either A3 and B7 (known to be in linkage disequilibrium with DRw2) or A26 and Bw38 was significantly increased as compared with the control population (P less than 0.001). Of the patients positive for DRw2, 47% had the association A26 and Bw38 as compared with the control population association incidence of 21% (P less than 0.1). Thus, in the patient population, A26-Bw38 appears to be a haplotype that is in linkage disequilibrium with DRw2 (as presumably is the case with A3-B7). These data indicate that a predisposition to AITP is inherited with a DRw2 gene of the major histocompatibility system.
IMPACT OF EPOETIN ALFA ON LV STRUCTURE, FUNCTION, AND PRESSURE-VOLUME RELATIONS AS ASSESSED BY CARDIAC MAGNETIC RESONANCE &amp;ndash; THE HEART FAILURE PRESERVED EJECTION FRACTION (HFPEF) ANEMIA TRIAL
Authors: Philip Green, Benson Babu, Sergio Teruya, Stephen Helmke, Jonathan Weinsaft, Mathew Maurer
Journal: Journal of the American College of Cardiology (2012)
Atypical Hyperplasia of the Breast — Risk Assessment and Management Options
Authors: Lynn C. Hartmann, Amy C. Degnim, Richard J. Santen, William D. Dupont, Karthik Ghosh
Journal: New England Journal of Medicine (2014)

The criteria for inclusion in the table were a central pathological review and the use of the criteria of David Page and colleagues for the diagnosis of atypical hyperplasia. 9CI denotes confidence interval.† The study was a retrospective cohort study involving women who had excisional biopsies performed during the period 1950 -1968.The median duration of follow-up was 17 years.Risk estimates are for invasive breast cancer only.‡ The study was a retrospective cohort study involving women who had excisional biopsies, core biopsies, or both performed during the period 1967-2001.The median duration of follow-up was 12.1 years.Risk estimates are for both invasive and in situ breast cancer (19% of cases were in situ).The numbers of patients in subcategories may not add to the total because information was missing for some patients.§ A strong family history was defined as at least one first-degree relative with breast cancer before 50 years of age or two or more relatives with breast cancer, with at least one being a first-degree relative.A weak family history was defined as any lesser degree of family history.¶ The study was a retrospective cohort study involving women who had biopsies performed during the period 1981-1994.The duration of follow-up was not specified.Risk estimates are for both invasive and in situ breast cancer (20% of cases were in situ).‖ The study was a nested case-control study.The type of breast cancer (i.e., invasive or in situ) evaluated for the risk estimates was not specified.** The study was a nested case-control study; risk estimates are for both invasive and in situ breast cancer.