tbuckley/cabot-search huggingface dataset:
Endocrine Therapy plus Zoledronic Acid in Premenopausal Breast Cancer
Authors: Michael Gnant, Brigitte Mlineritsch, Walter Schippinger, Gero Luschin-Ebengreuth, Sabine Pöstlberger, Christian Menzel, Raimund Jakesz, Michael Seifert, Michael Hubalek, Vesna Bjelic-Radisic, Hellmut Samonigg, Christoph Tausch, Holger Eidtmann, Günther Steger, Werner Kwasny, Peter Dubsky, Michael Fridrik, Florian Fitzal, Michael Stierer, Ernst Rücklinger, Richard Greil
Journal: New England Journal of Medicine (2009)

Ovarian suppression plus tamoxifen is a standard adjuvant treatment in premenopausal women with endocrine-responsive breast cancer. Aromatase inhibitors are superior to tamoxifen in postmenopausal patients, and preclinical data suggest that zoledronic acid has antitumor properties.
Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club
Authors: F Wong
Journal: Gut (2005)

Sepsis is a systemic inflammatory response to the presence of infection, mediated via the production of many cytokines, including tumour necrosis factor a (TNF-a), interleukin (IL)-6, and IL-1, which cause changes in the circulation and in the coagulation cascade.There is stagnation of blood flow and poor oxygenation, subclinical coagulopathy with elevated D-dimers, and increased production of superoxide from nitric oxide synthase.All of these changes favour endothelial apoptosis and necrosis as well as increased oxidant stress.Reduced levels of activated protein C, which is normally anti-inflammatory and antiapoptotic, can lead to further tissue injury.Cirrhotic patients are particularly susceptible to bacterial infections because of increased bacterial translocation, possibly related to liver dysfunction and reduced reticuloendothelial function.Sepsis ensues when there is overactivation of pathways involved in the development of the sepsis syndrome, associated with complications such as renal failure, encephalopathy, gastrointestinal bleed, and shock with decreased survival.Thus the treating physician needs to be vigilant in diagnosing and treating bacterial infections in cirrhosis early, in order to prevent the development and downward spiral of the sepsis syndrome.Recent advances in management strategies of infections in cirrhosis have helped to improve the prognosis of these patients.These include the use of prophylactic antibiotics in patients with gastrointestinal bleed to prevent infection and the use of albumin in patients with spontaneous bacterial peritonitis to reduce the incidence of renal impairment.The use of antibiotics has to be judicious, as their indiscriminate use can lead to antibiotic resistance with potentially disastrous consequences.c Baseline reduced polymorphonuclear count due to hypersplenism c Baseline elevated heart rate because of the hyperdynamic circulatory syndrome c Baseline hyperventilation due to hepatic encephalopathy c Blunted elevation of body temperature that is often observed in cirrhotic patients 719 SEPSIS IN CIRRHOSIS www.gutjnl.com
Impairment of G-protein-mediated signal transduction in the porcine coronary endothelium during rejection after heart transplantation
Authors: L Perrault
Journal: Cardiovascular Research (1999)

Background: Endothelial dysfunction is an early event leading to atherosclerosis. It also occurs after orthotopic heart transplantation and can be used to predict the development of intimal hyperplasia in the coronary artery wall. The present study was designed to assess the time course and specific alterations underlying endothelial dysfunction due to rejection after heart transplantation. Methods: A porcine model of heterotopic heart transplantation was used. Preoperative serum typing for the class I antigen of the swine lymphocyte alloantigen was performed to ensure compatibility for this antigen. This permitted survival of the graft with a low grade rejection without immunosuppression. Rings (with or without endothelium) of epicardial coronary arteries of native and transplanted hearts were studied in organ chambers filled with modified Krebs–Ringer bicarbonate solution and compared 1, 30 and 60 days after transplantation. Results: Myocardial contractility was normal in all grafts studied at 60 days after transplantation and all coronary arteries were patent. Myocardial biopsies showed the progression of rejection from day 1 to day 60 after implantation. All endothelium-dependent relaxations were normal one day after transplantation. Endothelium-dependent relaxations to serotonin and to the α2-adrenergic agonist UK14304 (which both activate receptors coupled to Gi-proteins) and to sodium fluoride (a direct activator of G-proteins) were decreased 30 days after transplantation, while those to the calcium ionophore, A23187, and bradykinin were shifted to the right and those to ADP were normal. At 60 days, endothelium-dependent relaxations mediated by the Gi-protein pathway were decreased further while the concentration–relaxation curves to the other agonists were further shifted to the right. Endothelium-independent relaxations to the nitric oxide donor, Sin-1, were progressively reduced at 30 and 60 days, but maximal relaxations were maintained at 60 days. Histomorphometric studies showed a progressive increase in the percentage of coronary rings with intimal thickening from day 1 to day 60 after transplantation. Conclusions: The progressive endothelial dysfunction reported in this model of accelerated coronary atherosclerosis after transplantation without immunosuppression involves preferentially the pertussis-toxin-sensitive Gi-protein-mediated pathway. Endothelium-independent relaxations are decreased at 60 days, as are all other endothelium-dependent relaxations. Decreased endothelium-dependent vasodilatation may contribute to the development of coronary graft vasculopathy.
A Comparative Evaluation of Amitriptyline and Duloxetine in Painful Diabetic Neuropathy
Authors: Harjot Kaur, Debasish Hota, Anil Bhansali, Pinaki Dutta, Dipika Bansal, Amitava Chakrabarti
Journal: Diabetes Care (2011)

To compare the efficacy and safety of duloxetine and amitriptyline in painful diabetic neuropathy (PDN).In this randomized, double-blind, cross-over, active-control trial, 58 patients received amitriptyline and duloxetine orally once daily at bedtime, each for 6 weeks with optional dose uptitration fortnightly. Single-blinded placebo washout was given for 2 weeks between the two treatments and a single-blinded placebo run-out phase of 4 weeks was given at the end of the treatment period. Pain relief was measured by the patient's global assessment of efficacy, using a visual analog scale (0-100) as a primary end point, and overall improvement and adverse events were assessed as secondary outcome measures. Median pain score reductions of >50%, 25-50%, and <25% were considered good, moderate, and mild responses, respectively.There was a significant improvement in pain with both treatments compared with their baseline values (P < 0.001 for both). Good, moderate, and mild pain relief was achieved in 55, 24, and 15% of patients, respectively, on amitriptyline and 59, 21, and 9% of patients, respectively, on duloxetine. There were no significant differences in various other outcome measures between the groups. Of the reported adverse events, dry mouth was significantly more common with amitriptyline than duloxetine (55 vs. 24%; P < 0.01). Although, numerically, more patients preferred duloxetine, overall this was not statistically significant (48 vs. 36%; P = 0.18).Both duloxetine and amitriptyline demonstrated similar efficacy in PDN. A large, multicentric clinical trial in other populations could possibly demonstrate the superiority of either drug.
Fundamentals of Impact Biomechanics: Part I - Biomechanics of the Head, Neck, and Thorax
Authors: Albert I. King
Journal: Annual Review of Biomedical Engineering (2000)

▪ Abstract This is the first of two chapters dealing with some 60 years of accumulated knowledge in the field of impact biomechanics. The regions covered in this first chapter are the head, neck, and thorax. The next chapter will discuss the abdomen, pelvis, and the lower extremities. Although the principal thrust of the research has been toward the mitigation of injuries sustained by automotive crash victims, the results of this research have applications in aircraft safety, contact sports, and protection of military personnel and civilians from intentional injury, such as in the use of nonlethal weapons. The reader should be keenly aware of the wide variation in human response and tolerance data in the cited results. This is due primarily to the large biological variation among humans and to the effects of aging. Average values are useful in design but cannot be applied to individuals.
Importance of flexible broncoscopy in immunocompromised children with pulmonary infections
Authors: Nesibe Gevher Eroglu Ertugrul, Ebru Yalçin, Nagehan Emiralioglu, Berna Oguz, Aydin Erden, Baris Kuskonmaz, Deniz Dogru, Ugur Özçelik, Ilhan Tezcan, Nural Kiper
Journal: European Respiratory Journal (2014)

INTRODUCTION   Pulmonary infections are frequently seen in immunocomprimised children.   AIMS    1.  To determine the importance of FB and BAL analysis in showing the agent of pulmonary infected immunocompromised children.   2.  To investigate the differences of agents and radiological findings between the pulmonary infections arised after BMT and other immunocompromised cases.   3.  To evaluate the reliability of radiological findings in showing the agent.   METARIALS AND METHODS   FB and BAL analysis for 79 immunocompromised and pulmonary infected children are retrospectively studied and divided into two groups. Children in group I (n=61) are the primary or secondary immunosupressed patients applied FB and BAL because of pulmonary infections. Children in group II (n=18) are the patients applied FB and BAL because of pulmonary infections after BMT.   RESULTS   In BAL sample analysis, the microorganism was shown in 37 (60,6%) patients of group I and 7 (38,8%) patients of group II. When the microbiological agents compared, the bacterial growth in BAL samples was higher in group I (p=0,017). For the other agents there was no significant difference. No relation between HRCT findings and the agents shown in BAL could be found.  After the analysis of all diagnostic tools related with FB, it was determined that 62/79 (78%) of all patients could be diagnosed. In 32/79 (%40) of all patients the agent was exactly shown and therapy changed.   CONCLUSION   Although FB is applied under empirical anti-microbiological therapy, the importance of BAL analysis in showing the agent of pulmonary infection in immunocompromised children and it9s contribution to diagnosis is found to be high.
Training Psychiatrists from Developing Nations
Authors: NEUMAN S. MITTEL
Journal: American Journal of Psychiatry (1970)

Foreign physicians face critical linguistic and cultural barriers to learning American psychiatry. Furthermore, conventional training programs effectively deprive many of them of freedom of choice by forging a professional identity incompatible with medical realities in their own countries. Moral dilemmas complicate the identity crisis. Adequate training for foreign medical school graduates, the author believes, requires working through these conflicts in addition to special emphasis on the social sciences and public health.
Comprehensive analyses of CD8+ T cell responses during longitudinal study of acute human hepatitis C
Authors: Andrea L. Cox, Timothy Mosbruger, Georg M. Lauer, Drew Pardoll, David L. Thomas, Stuart C. Ray
Journal: Hepatology (2005)

Abstract We comprehensively studied the cellular immune response during acute human hepatitis C virus (HCV) infection by monthly prospective sampling of persons at high risk of infection. In 19 of 23 subjects, interferon-gamma–secreting T cells specific for 1 or more peptides spanning the entire HCV polyprotein were detected 1 to 3 months after infection. The median time to development of interferon gamma responses to HCV peptides was 33 days (range, 29-50 days), and these responses peaked between 180 and 360 days. Nineteen subjects had sufficient follow-up to determine outcome, with 15 (79%) developing persistent viremia and 4 (21%) clearing viremia spontaneously. Of those with progression to chronic infection and detectable T cell responses, all lost recognition of one or more antigens recognized during acute infection, and the median reduction in the magnitude of responses was 85%. Most significantly, despite ongoing viremia, those who had persistent infection did not develop new epitope specificities after the first 6 months of infection. In conclusion , in most individuals, the CD8+ T cell responses generated early in HCV infection decline in peripheral blood and are not replaced with new responses. Supplementary material for this article can be found on the Hepatology website ( http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html ). (Hepatology 2005;42:104–112.)
Expression of Inducible Nitric Oxide Synthase Depresses β-Adrenergic–Stimulated Calcium Release From the Sarcoplasmic Reticulum in Intact Ventricular Myocytes
Authors: Mark T. Ziolo, Hideki Katoh, Donald M. Bers
Journal: Circulation (2001)

Background — β-Adrenergic hyporesponsiveness in many cardiomyopathies is linked to expression of inducible nitric oxide synthase (iNOS) and increased production of NO. The purpose of this study was to examine whether iNOS expression alters the function of the sarcoplasmic reticulum (SR) Ca 2+ release channel (ryanodine receptor, RyR) during β-adrenergic stimulation. Methods and Results — Expression of iNOS was induced by lipopolysaccharide (LPS) injection (10 mg/kg) 6 hours before rat myocyte isolation. Confocal microscopy (fluo-3) was used to measure Ca 2+ spark frequency (CaSpF, reflecting resting RyR openings) and Ca 2+ transients. CaSpF was greatly increased by the adenylate cyclase activator forskolin (100 nmol/L) in normal myocytes (iNOS not expressed), but this effect was suppressed (by 77%) in LPS myocytes (iNOS expressed). When NO production by iNOS was inhibited by aminoguanidine (1 mmol/L), there was a further increase in the forskolin-induced CaSpF in LPS myocytes (to levels similar to the forskolin-stimulated CaSpF in normal myocytes). This effect was also seen in myocytes isolated from a failing human heart. There was no effect of aminoguanidine on forskolin-stimulated CaSpF in normal myocytes. ODQ (10 μmol/L), an inhibitor of NO stimulation of guanylate cyclase, did not restore the forskolin-induced rise in CaSpF in LPS myocytes. Aminoguanidine also increased twitch Ca 2+ transient amplitude in LPS myocytes after forskolin application (independent of changes in SR Ca 2+ load). Conclusions — iNOS/NO depresses β-adrenergic–stimulated RyR function through a cGMP-independent pathway (eg, NO- and/or peroxynitrite-dependent redox modification). This mechanism limits β-adrenergic responsiveness and may be an important signaling pathway in cardiomyopathies, including human heart failure.
Fine-Particulate Air Pollution and Life Expectancy in the United States
Authors: C. Arden Pope, Majid Ezzati, Douglas W. Dockery
Journal: New England Journal of Medicine (2009)

Exposure to fine-particulate air pollution has been associated with increased morbidity and mortality, suggesting that sustained reductions in pollution exposure should result in improved life expectancy. This study directly evaluated the changes in life expectancy associated with differential changes in fine particulate air pollution that occurred in the United States during the 1980s and 1990s.We compiled data on life expectancy, socioeconomic status, and demographic characteristics for 211 county units in the 51 U.S. metropolitan areas with matching data on fine-particulate air pollution for the late 1970s and early 1980s and the late 1990s and early 2000s. Regression models were used to estimate the association between reductions in pollution and changes in life expectancy, with adjustment for changes in socioeconomic and demographic variables and in proxy indicators for the prevalence of cigarette smoking.A decrease of 10 microg per cubic meter in the concentration of fine particulate matter was associated with an estimated increase in mean (+/-SE) life expectancy of 0.61+/-0.20 year (P=0.004). The estimated effect of reduced exposure to pollution on life expectancy was not highly sensitive to adjustment for changes in socioeconomic, demographic, or proxy variables for the prevalence of smoking or to the restriction of observations to relatively large counties. Reductions in air pollution accounted for as much as 15% of the overall increase in life expectancy in the study areas.A reduction in exposure to ambient fine-particulate air pollution contributed to significant and measurable improvements in life expectancy in the United States.
Targeted Knockdown of<i>Notch1</i>Inhibits Invasion of Human Prostate Cancer Cells Concomitant with Inhibition of Matrix Metalloproteinase-9 and Urokinase Plasminogen Activator
Authors: Bilal Bin Hafeez, Vaqar Mustafa Adhami, Mohammad Asim, Imtiaz A. Siddiqui, Kumar M. Bhat, Weixiong Zhong, Mohammad Saleem, Maria Din, Vijayasaradhi Setaluri, Hasan Mukhtar
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Notch, a type 1 transmembrane protein, plays a key role in the development of many tissues and organ types. Aberrant Notch signaling, found in a wide variety of human cancers, contributes to tumor development. Because Notch1 was found to be overexpressed in prostate cancer (PCa) cells and human PCa tissue, we therefore tested our hypothesis that overexpression of Notch1 in PCa promotes tumor invasion. Experimental Design: Notch1 expression was evaluated in human PCa cells and human PCa tissues. PCa cells were transiently transfected with Notch1-specific small interfering RNAs in concentrations ranging from 30 to 120 nmol/L and subsequently evaluated for effects on invasion and expression analysis for molecules involved in invasion. Results: Small interfering RNA–mediated knockdown of Notch1 in PC3 and 22Rν1 PCa cells dramatically decreased their invasion. Focused cDNA array revealed that Notch1 knockdown resulted in significant reduction in the expression of urokinase plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP9) gene transcripts. These data were further verified by reverse transcription-PCR, real-time reverse transcription-PCR, and immunoblot analysis. Knockdown of Notch1 was also observed to significantly reduce the mRNA expression and protein levels of uPA and its receptor uPAR. A significant reduction in MMP9 expression in Notch1 knockdown cells suggested a role for Notch1 in augmenting MMP9 transcription. Conclusions: Our data show the involvement of Notch1 in human PCa invasion and that silencing of Notch1 inhibits invasion of human PCa cells by inhibiting the expression of MMP9 and uPA. Thus, targeting of Notch1 could be an effective therapeutic approach against PCa.
Day Care Attendance in Early Life, Maternal History of Asthma, and Asthma at the Age of 6 Years
Authors: Juan C. Celedón, Rosalind J. Wright, Augusto A. Litonjua, Diane Sredl, Louise Ryan, Scott T. Weiss, Diane R. Gold
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Among children not selected on the basis of a parental history of atopy, day care attendance in early life is inversely associated with asthma at school age. We examined the relation between day care in the first year of life and asthma, recurrent wheezing, and eczema at the age of 6 years and wheezing in the first 6 years of life among 453 children with parental history of atopy followed from birth. Among all study participants, day care in the first year of life was inversely associated with eczema (odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.1-0.8). Day care attendance in early life was associated with a decreased risk of asthma (OR = 0.3, 95% CI = 0.1-0.7) and recurrent wheezing (OR = 0.3, 95% CI = 0.1-0.9) at the age of 6 years and with a decreased risk of any wheezing after the age of 4 years only among children without maternal history of asthma. Among children with maternal history of asthma, day care in early life had no protective effect on asthma or recurrent wheezing at the age of 6 years but was instead associated with an increased risk of wheezing in the first 6 years of life. Our findings suggest that maternal history of asthma influences the relation between day care-related exposures and childhood asthma.
Possible protection by inhaled budesonide against ischaemic cardiac events in mild COPD
Authors: C-G. Löfdahl, D. S. Postma, N. B. Pride, J. Boe, A. Thorén
Journal: European Respiratory Journal (2007)

Epidemiological studies have indicated that chronic obstructive pulmonary disease (COPD) may be associated with an increased incidence of ischaemic cardiac events. The current authors performed a post hoc analysis of the European Respiratory Society's study on Chronic Obstructive Pulmonary Disease (EUROSCOP); a 3-yr, placebo-controlled study of an inhaled corticosteroid budesonide 800 microg.day(-1) in smokers (mean age 52 yrs) with mild COPD. The current study evaluates whether long-term budesonide treatment attenuates the incidence of ischaemic cardiac events, including angina pectoris, myocardial infarction, coronary artery disorder and myocardial ischaemia. Among the 1,175 patients evaluated for safety, 49 (4.2%) patients experienced 60 ischaemic cardiac events. Patients treated with budesonide had a significantly lower incidence of ischaemic cardiac events (18 out of 593; 3.0%) than those receiving placebo (31 out of 582; 5.3%). The results of the present study support the hypothesis that treatment with inhaled budesonide reduces ischaemic cardiac events in patients with mild chronic obstructive pulmonary disease.
V617F mutation in JAK2 is associated with poorer survival in idiopathic myelofibrosis
Authors: Peter J Campbell, Martin Griesshammer, Konstanze Döhner, Hartmut Döhner, Rajko Kusec, Hans C Hasselbalch, Thomas Stauffer Larsen, Niels Pallisgaard, Stéphane Giraudier, Marie-Caroline Le Bousse-Kerdilès, Christophe Desterke, Bernadette Guerton, Brigitte Dupriez, Dominique Bordessoule, Pierre P. Fenaux, Jean-Jacques Kiladjian, Jean-François Viallard, Jean Brière, Claire N Harrison, Anthony R Green, John T Reilly
Journal: Blood (2005)