tbuckley/cabot-search huggingface dataset:
The definition of exertion-related cardiac events
Authors: M Rai, P D Thompson
Journal: British Journal of Sports Medicine (2010)

Vigorous physical activity increases the risk of sudden cardiac death (SCD) and acute myocardial infarction (AMI) but there is no standard definition as to what constitutes an exertion-related cardiac event, specifically the time interval between physical exertion and cardiac event. A systematic review of studies related to exertion-related cardiac events was performed and the time interval between exertion and the event or the symptoms leading to the event was looked for in all the articles selected for inclusion. A total of 12 of 26 articles "suggested" or "defined" exertion-related events as those events whose symptoms started during or within 1 h of exertion. Others used definitions of 0.5 h, 2 h, "during exertion", "during or immediately post exertion" and "during or within several hours after exertion". It is suggested, therefore, that the definition of an exertion-related cardiac event be established as a cardiac event in which symptoms started during or within 1 h of physical exertion.
Heparins Increase Endothelial Nitric Oxide Bioavailability by Liberating Vessel-Immobilized Myeloperoxidase
Authors: Stephan Baldus, Volker Rudolph, Mika Roiss, Wulf D. Ito, Tanja K. Rudolph, Jason P. Eiserich, Karsten Sydow, Denise Lau, Katalin Szöcs, Anna Klinke, Lukas Kubala, Lars Berglund, Sonja Schrepfer, Tobias Deuse, Munif Haddad, Tim Risius, Hanno Klemm, Hermann C. Reichenspurner, Thomas Meinertz, Thomas Heitzer
Journal: Circulation (2006)

Neutrophils and monocytes are centrally linked to vascular inflammatory disease, and leukocyte-derived myeloperoxidase (MPO) has emerged as an important mechanistic participant in impaired vasomotor function. MPO binds to and transcytoses endothelial cells in a glycosaminoglycan-dependent manner, and MPO binding to the vessel wall is a prerequisite for MPO-dependent oxidation of endothelium-derived nitric oxide (NO) and impairment of endothelial function in animal models. In the present study, we investigated whether heparin mobilizes MPO from vascular compartments in humans and defined whether this translates into increased vascular NO bioavailability and function.Plasma MPO levels before and after heparin administration were assessed by ELISA in 109 patients undergoing coronary angiography. Whereas baseline plasma MPO levels did not differ between patients with or without angiographically detectable coronary artery disease (CAD), the increase in MPO plasma content on bolus heparin administration was higher in patients with CAD (P=0.01). Heparin treatment also improved endothelial NO bioavailability, as evidenced by flow-mediated dilation (P<0.01) and by acetylcholine-induced changes in forearm blood flow (P<0.01). The extent of heparin-induced MPO release was correlated with improvement in endothelial function (r=0.69, P<0.01). Moreover, and consistent with this tenet, ex vivo heparin treatment of extracellular matrix proteins, cultured endothelial cells, and saphenous vein graft specimens from CAD patients decreased MPO burden.Mobilization of vessel-associated MPO may represent an important mechanism by which heparins exert antiinflammatory effects and increase vascular NO bioavailability. These data add to the growing body of evidence for a causal role of MPO in compromised vascular NO signaling in humans.
A 44-yr-old male with progressive dyspnoea and dry cough
Authors: P. Rodrigues Genta, C. Bastos Valeri, R. Adib Kairalla, V.L. Capelozzi, C.R. Ribeiro de Carvalho
Journal: European Respiratory Journal (2002)

A 44-yr-old male carpenter presented to the outpatient clinic complaining of progressive dyspnoea and dry cough for the last 7 yrs. The patient's symptoms had worsened in the last 2 yrs and at the time of presentation he had dyspnoea at rest. He used intravenous amphetamine but stopped 12 yrs before presentation. The patient denied smoking or other previous illnesses.

Physical examination revealed an increased anteroposterior chest diameter. Auscultation disclosed diminished breath sounds and fine crackles at the lower lung fields. Respiratory rate was 24 beats per minute and pulse oximetry in room air and at rest was 90%.

A chest radiograph (fig. 1⇓) and, later, a high-resolution computed tomography were performed (figs. 2a and b⇓). Pulmonary function tests showed: forced vital capacity (FVC) 1.23 L (25%), forced expiratory volume in one second (FEV1) 0.46 L (13%), FEV1/FVC 0.37 (46%), total lung capacity 7.56 L (110%), functional residual capacity 6.31 L (166%), residual volume 6.03 …
Importance of Testes in Induction of Hyperplastic Nodules, Carcinomas, and Cirrhosis of Liver in A × C Male Rats Ingesting 0.025% N-2-Fluorenyldiacetamide
Authors: Melvin D. Reuber
Journal: JNCI Journal of the National Cancer Institute (1974)

The dependence of hepatic carcinogenesis on the testes was studied in inbred A × C male rats ingesting 0.025% N-2-fluorenyldiacetamide (F-diAA). The experimental groups consisted of intact rats with normal testes, rats with 1 normal testis, rats with 1 atrophic testis related to a congenital defect, and rats without testes. The incidence of carcinomas and the number of rats with large carcinomas, multiple carcinomas, and metastases were highest in intact rats. The incidence and size not only decreased in animals with 1 or both testes removed, but also the decrease was directly related to the bulk and weight of the testis in rats in the other groups. The incidence was lowest in rats with both testes removed. This experiment confirmed the importance of the testes in F-diAA hepatic carcinogenesis, and also demonstrated the extreme sensitivity of the liver to the level of male sex hormone.
Randomized, Placebo-Controlled Study of Ethyl-Eicosapentaenoic Acid as Supplemental Treatment in Schizophrenia
Authors: Robin Emsley, Christo Myburgh, Pieter Oosthuizen, Susan J. van Rensburg
Journal: American Journal of Psychiatry (2002)

The study investigated the efficacy and tolerability of ethyl-eicosapentaenoic acid (E-EPA) as add-on treatment in chronic, severe schizophrenia.A randomized, parallel-group, double-blind, placebo-controlled, fixed-dose, add-on study was conducted over 12 weeks. Forty patients with persistent symptoms after at least 6 months of stable antipsychotic treatment received E-EPA or placebo, in addition to their existing treatment.At 12 weeks, the E-EPA group had significantly greater reduction of Positive and Negative Syndrome Scale total scores and of dyskinesia scores than the placebo group.EPA may be an effective and well-tolerated add-on treatment in schizophrenia.
Role of nitric oxide and platelet-activating factor in cardiac alterations induced by tumor necrosis factor-α in the guinea-pig papillary muscle
Authors: Giuseppe Alloatti, Claudia Penna, Antonella De Martino, Giuseppe Montrucchio, Giovanni Camussi
Journal: Cardiovascular Research (1999)

Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine with negative inotropic properties, is implicated in several pathophysiological events. To clarify the mechanism of action of TNF-alpha on myocardium, we investigated the possible role of platelet-activating factor (PAF) and nitric oxide (NO) as secondary mediators of the depressant effect of this cytokine.Isometric twitches and intracellular action potentials were recorded from guinea pig papillary muscles. The effects of TNF-alpha (1-10 ng/ml) were studied in controlled conditions and after treatment with 0.5% Triton X-100, to destroy the endocardial endothelium NG-nitro-L-arginine methyl ester (L-NAME), D-NAME (1 mM) and the two different PAF-receptor antagonists WEB 2170 (3 microM) and CV 3988 (5 microM) were used to study the role of NO and PAF in cardiac depression induced by TNF-alpha. To study the role of NO in cardiac alterations induced by PAF, papillary muscles were pretreated with L-NAME or D-NAME and then challenged with PAF (0.1-1 microM). Nitrite production by papillary muscles challenged with TNF-alpha alone. TNF-alpha in the presence of WEB 2170 or CV 3988, or PAF was studied with the Greiss reagent method. PAF production by papillary muscles stimulated by TNF-alpha was studied by a bioassay method.TNF-alpha induced an initial, transient positive inotropic effect, then reduced the contractility and the action potential duration in a concentration-dependent manner. Treatment of papillary muscle with Triton X-100 did not modify the response to TNF-alpha, suggesting that the effect of TNF-alpha is not mediated by endocardial endothelial cells. Pretreatment with indomethacin reduced the negative effect of TNF-alpha, while propranolol abolished the initial increase of contractility. The role of PAF and NO as mediators of TNF-alpha was suggested by: (1) the protective effect of L-NAME, but not of D-NAME, on electrical and mechanical alterations; (2) the stimulatory effect of TNF-alpha on nitrite production; (3) the inhibitory effect of WEB 2170 and CV 3988, on both the electromechanical alterations and the nitrite production; (4) the synthesis of PAF induced by TNF-alpha. L-NAME blocked the negative effect of PAF and PAF enhanced nitrite production by papillary muscle.The present results suggest that in cardiac muscle: (1) the release of PAF triggered by TNF-alpha may account for the stimulation of NO production; (2) both PAF and NO contribute to the development of the electrical and mechanical alterations induced by TNF-alpha; (3) NO production was down-stream to the synthesis of PAF.
Schistosoma mansoni shares a protective carbohydrate epitope with keyhole limpet hemocyanin.
Authors: J M Grzych, C Dissous, M Capron, S Torres, P H Lambert, A Capron
Journal: The Journal of Experimental Medicine (1987)

The glycanic epitope of the 38,000 Mr Schistosoma mansoni schistosomula major immunogen defined by the IPLSm1 protective mAb was identified in the hemocyanin of the marine mollusc Megathura crenulata, better known as KLH. This antigenic community was exploited to investigate further the biological properties of this epitope. KLH was shown to strongly inhibit the binding of IPLSm1 mAb to its 38,000 Mr target antigen. Immunization of naive LOU rats with KLH elicited the production of anti-S. mansoni antibodies capable of immunoprecipitating the 38,000 Mr schistosomulum antigen. Antibodies to KLH mediated a marked eosinophil-dependent cytotoxicity and passively transferred immunity towards S. mansoni infection. Finally, rats immunized with KLH were significantly protected against a challenge with S. mansoni cercariae. The deglycosylation of KLH completely abolishes its immunological and functional KLH properties, indicating the participation of an oligosaccharidic epitope of the native KLH that is also recognized by the sera of S. mansoni-infected patients. These observations provide new opportunities of access to the well-defined structure of a glycanic epitope potentially available for the immunoprophylaxis and seroepidemiology of schistosomiasis, and a new approach to the isotypic response towards a well-chemically defined epitope.
Essential fatty acids in the plasma phospholipids of patients with atopic eczema
Authors: M.S. MANKU, D.F. HORROBIN, N.L. MORSE, S. WRIGHT, J.L. BURTON
Journal: British Journal of Dermatology (1984)

Journal Article Essential fatty acids in the plasma phospholipids of patients with atopic eczema Get access M.S. MANKU, M.S. MANKU Efamol Research Institute, P.O. Box 818, Kentville, Nova Scotia, B4N 4H8, Canda Search for other works by this author on: Oxford Academic Google Scholar D.F. HORROBIN, D.F. HORROBIN Efamol Research Institute, P.O. Box 818, Kentville, Nova Scotia, B4N 4H8, Canda Search for other works by this author on: Oxford Academic Google Scholar N.L. MORSE, N.L. MORSE Efamol Research Institute, P.O. Box 818, Kentville, Nova Scotia, B4N 4H8, Canda Search for other works by this author on: Oxford Academic Google Scholar S. WRIGHT, S. WRIGHT Department of Dermatology, Bristol Royal Infirmary, Bristol, England Search for other works by this author on: Oxford Academic Google Scholar J.L. BURTON J.L. BURTON Department of Dermatology, Bristol Royal Infirmary, Bristol, England Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 110, Issue 6, 1 June 1984, Pages 643–648, https://doi.org/10.1111/j.1365-2133.1984.tb04698.x Published: 01 June 1984 Article history Accepted: 20 December 1983 Published: 01 June 1984
Bridging the gap between epigenetics research and nutritional public health interventions
Authors: Graham C Burdge, Karen A Lillycrop
Journal: Genome Medicine (2010)

Epigenetic processes, primarily DNA methylation and covalent modifications of histones, regulate the transcriptional activity of genes in a manner that can be modified by environmental cues. This allows variation in the expression of the transcriptome without changes in the genome. Constraint in the early life environment, such as poor early nutrition, is associated with increased risk of non-communicable diseases, including cardio-metabolic disease and cancer in later life. Such induced phenotypic change involves environmental signals acting through developmental plasticity. Recent studies in humans and in animal models show that epigenetic processes, in particular DNA methylation, have a central role in the induction and stability of novel phenotypes and in increased disease risk. Identification of such processes suggests the potential for developing biomarkers of disease risk and for interventions to prevent or reverse the adverse effects of a poor early life environment. At present, knowledge in this area is limited to proof-of-principle studies in animal models and some initial studies in humans. Before such findings can be translated into reliable biomarkers and safe, effective interventions, several fundamental questions need to be answered. In order to achieve this, new technologies will be needed to support large cohort studies. Despite the early stage of knowledge in this field and the intellectual, technological and financial challenges, epigenetic research has substantial potential for public health benefits.
Maintenance of the cellobiose utilization genes of Escherichia coli in a cryptic state.
Authors: B G Hall, P W Betts, M Kricker
Journal: Molecular Biology and Evolution (1986)

The genes for cellobiose utilization are normally cryptic in Escherichia coli. The cellobiose system was used as a model to understand the process by which silent genes are maintained in microbial populations. Previously reported was (1) the isolation of a mutant strain that expresses the cellobiose-utilization (Cel) genes and (2) that expression of those genes allows utilization of three beta-glucoside sugars: cellobiose, arbutin, and salicin. The Cel gene cluster has now been cloned from that mutant strain. In the course of locating the Cel genes within the cloned DNA segment, it was discovered that inactivation of the Cel-encoded hydrolase rendered the host strain sensitive to all three beta-glucosides as potent inhibitors. This sensitivity arises from the accumulation of the phosphorylated beta-glucosides. Because even the fully active genes conferred some degree of beta-glucoside sensitivity, the effects of cellobiose on a series of five Cel+ mutants of independent origin were investigated. Although each of those strains utilizes cellobiose as a sole carbon and energy source, cellobiose also acts as a potent inhibitor that reduces the growth rate on glycerol 2.5-16.5-fold. On the other hand, wild-type strains that cannot utilize cellobiose are not inhibited. The observation that the same compound can serve either as a nutrient or as an inhibitor suggests that, under most conditions in which cellobiose will be present together with other resources, there is a strong selective advantage to having the cryptic (Cel0) allele. In those environments in which cellobiose is the sole, or the best, resource, mutants that express the genes (Cel+) will have a strong selective advantage. It is suggested that temporal alternation between these two conditions is a major factor in the maintenance of these genes in E. coli populations. This alternation of environments and fitnesses was predicted by the model for cryptic-gene maintenance that was previously published.
Melanoma patients in a phase I clinic: molecular aberrations, targeted therapy and outcomes
Authors: H. Henary, D.S. Hong, G.S. Falchook, A. Tsimberidou, G.C. George, S. Wen, J. Wheler, S. Fu, A. Naing, S. Piha-Paul, F. Janku, K.B. Kim, P. Hwu, R. Kurzrock
Journal: Annals of Oncology (2013)
Purchasing Power in Health: Business, the State, and Health Care Politics
Authors: David J. Shulkin
Journal: JAMA (1990)

For the past two decades, Business has been at war with Medicine. Medicine has lost crucial battles and is still retreating. This book recounts the underlying causes of the conflict and adds an understanding of past and present strategies of the warfare. In what reads more like a doctoral dissertation than a flowing narrative, the author examines the impact of corporate America on medical care between 1969 and 1988. With extensive interviews requiring 30 pages of footnotes, she recounts the events leading to business' entrance into the health policy forum. The myriad of facts makes for slow reading. Nonetheless, it's an interesting story. Dwindling corporate profits in the late 1960s set the stage for change in health policy. While the general economy faltered, the health care industry was undergoing a growth spurt. With declining revenues and rising medical care benefits, industrial leaders felt compelled to act. By the early 1970s,
Blocking EphB1 Receptor Forward Signaling in Spinal Cord Relieves Bone Cancer Pain and Rescues Analgesic Effect of Morphine Treatment in Rodents
Authors: Su Liu, Wen-Tao Liu, Yue-Peng Liu, Hai-Long Dong, Mark Henkemeyer, Li-Ze Xiong, Xue-Jun Song
Journal: Cancer Research (2011)

Treating bone cancer pain continues to be a clinical challenge and underlying mechanisms of bone cancer pain remain elusive. Here, we report that EphB1 receptor forward signaling in the spinal cord is critical to the development of bone cancer pain and morphine tolerance in treating bone cancer pain. Tibia bone cavity tumor cell implantation (TCI) produces bone cancer-related thermal hyperalgesia, mechanical allodynia, spontaneous and movement-evoked pain behaviors, and bone destruction. Production and persistence of these pain behaviors are well correlated with TCI-induced upregulation of EphB1 receptor and its ligand ephrinB2 in the dorsal horn and primary sensory neurons. Spinal administration of an EphB1 receptor blocking reagent EphB2-Fc prevents and reverses bone cancer pain behaviors and the associated induction of c-Fos and activation of astrocytes and microglial cells, NR1 and NR2B receptors, Src within the N-methyl-D-aspartate receptor complex, and the subsequent Ca(2+)-dependent signals. The exogenous ligand ephrinB2-Fc upregulates level of phosphorylation of NR1 and NR2B receptors depending on the activation of EphB1 receptor. Spinal administration of EphB2-Fc and ephrinB2-Fc induces downregulation of EphB1 and ephrinB2, respectively, accompanied with increased activity of matrix metalloproteinase (MMP)-2/9. Blocking MMP-2 or MMP-9 reverses EphB1-Fc treatment-induced downregulation of EphB1 receptor. In addition, spinal blocking or targeted mutation of EphB1 receptor reverses morphine tolerance in treating bone cancer pain in rats and defensive pain in mice. These findings show a critical mechanism underlying the pathogenesis of bone cancer pain and suggest a potential target for treating bone cancer pain and improving analgesic effect of morphine clinically.
End-Stage Renal Disease in the United States
Authors: Robert N. Foley, Allan J. Collins
Journal: Journal of the American Society of Nephrology (2007)

Patients with ESRD consume a vastly disproportionate amount of financial and human resources. Approximately 0.03% of the US population began renal replacement therapy in 2004, an adjusted incidence rate of 339 per million. Declining incidence rates were observed for most primary causes of ESRD and in most major demographic categories; the worry is that rates of diabetic ESRD continue to rise in younger black adults. Although diabetes and hypertension remain the most commonly reported cause of ESRD, rates of end-stage atherosclerotic renovascular disease seem to be on the rise in older patients. Although clinical care indicators, such as the proportion of hemodialysis patients using fistulas, continue to improve gradually, the proportion of patients overshooting target hemoglobin levels under epoetin therapy may be a source of concern. Survival probabilities have improved steadily in the US ESRD population since the late 1980s, which is remarkable when one considers the ever-expanding burden of comorbidity in incident patients. However, although first-year dialysis mortality rates have clearly improved since 1987, meaningful improvements do not seem to have accrued since 1993, in contrast to steady annual improvements in years 2 through 5. Although most of these findings are grounds for cautious optimism, the same cannot be said for issues of cost; reflecting the growth in the size of the ESRD population, associated costs grew by 57% between 1999 and 2004 and now account for 6.7% of total Medicare expenditures.
Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stage I and II Invasive Breast Cancer: American Society of Clinical Oncology Endorsement of the Society of Surgical Oncology/American Society for Radiation Oncology Consensus Guideline
Authors: Thomas A. Buchholz, Mark R. Somerfield, Jennifer J. Griggs, Souzan El-Eid, M. Elizabeth H. Hammond, Gary H. Lyman, Ginny Mason, Lisa A. Newman
Journal: Journal of Clinical Oncology (2014)

The Society of Surgical Oncology (SSO)/American Society for Radiation Oncology (ASTRO) guideline on surgical margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer was considered for endorsement.The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing practice guidelines developed by other organizations. ASCO staff reviewed the SSO/ASTRO guideline for developmental rigor; an ASCO ad hoc review panel of experts reviewed the guideline content.The ASCO ad hoc guideline review panel concurred that the recommendations are clear, thorough, and based on the most relevant scientific evidence in this content area and that they present options acceptable to patients. According to the SSO/ASTRO guideline, the use of no ink on tumor (ie, no cancer cells adjacent to any inked edge/surface of specimen) as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of ipsilateral breast tumor recurrence and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.The ASCO review panel endorses the SSO/ASTRO recommendations with qualifications, as follows. The panel reinforces and amplifies the guideline authors' call for the monitoring of outcomes of the guideline at the institutional level, as institutions transition to adopting the SSO/ASTRO recommendations; would place greater emphasis on the importance of postlumpectomy mammography for cases involving microcalcifications; and calls for flexibility in the application of the guideline in light of the generally weak evidence supporting the recommendations.