tbuckley/cabot-search huggingface dataset:
Superiority of Docetaxel + Capecitabine Compared to Docetaxel + Epirubicin as First-Line Therapy for Metastatic Breast Cancer – Final Results of the ERASME-4 Study.
Authors: T. Bachelot, A. Bajard, I. Ray-Coquard, J. Provencal, D. Coeffic, D. Dramais, R. Ferri-Dessens, J. Guastalla, D. Perol
Journal: Cancer Research (2009)

Abstract Background: Docetaxel plus capecitabine (DC) combination therapy improves both time to disease progression and overall survival over docetaxel alone in metastatic breast cancer (MBC). The aim of the ERASME-4 trials was to assess the efficacy of DC vs. docetaxel plus epirubicin (DE) combination regimens as first-line therapy for MBC.Material and Methods: Patients with MBC, previously untreated with chemotherapy were randomly assigned to receive either DC (docetaxel 75 mg/m² on day 1 and oral capecitabine 1,000 mg/m² twice daily on days 1 to 14 every 3 weeks) or DE (docetaxel 75 mg/m² and epirubicin 75 mg/m² on day 1 every 3 weeks). The primary endpoint was progression-free rate 6 months after randomization. The planned sample sizes were 106 patients (pts), based on a randomized phase II selection design. The main secondary endpoints were progression-free survival (PFS) and overall survival (OS).Results: Between June 2004 and April 2006, 68 pts were randomized. Slow accrual led to premature termination the study. Final analysis included 33 pts randomized to DC and 35 pts to DE. This sample size allowed to effectively selecting the best arm for non-progression rate with a power of 82%. Patient characteristics were well balanced between the two treatment arms, except for pleural metastasis, alkaline phosphatase and SBR III more present in DE arm or adjuvant hormonotherapy given in more DC patients. Toxicity has been mild or moderate; 62% of patients reported at least one grade 3-4 episode. Hand-foot syndrome grade 3-4 was reported for 18% of DC arm patients, vs. none in the DE arm (p=0.008).Complete/partial response rates were 20/44% in DC and 7/41% in DE (p=0.3). Six months after randomization, 75.8% (95%CI: 57.7-88.9) of pts in the DC arm vs. 65.7% (95%CI: 47.8-80.9) in the DE arm were progression-free (p=0.36). After a median follow-up of 42 months, (95%CI: 32.5-21.1), median PFS was 12 months and 7 months in the DC and DE groups, respectively (p=.004). Median OS was 27 and 37 months for DE and DC respectively (p=0.49).Conclusion: Despite our low accrual, these results show that DC combination therapy is associated with a superior progression-free rate at 6 months and a longer PFS than DE.DC provides a highly active, non-anthracycline-containing, first-line treatment option for MBC patients previously exposed to anthracycline in the adjuvant setting. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2099.
Physical Activity and Primary Cardiac Arrest
Authors: David S. Siscovick, Noel S. Weiss, Alfred P. Hallstrom, Thomas S. Inui, Donald R. Peterson
Journal: JAMA (1982)

To explore the relationship between vigorous physical activity and primary cardiac arrest (PCA), we identified, through emergency service incident reports, 163 cases of PCA aged 25 to 75 years. Control subjects matched for age, sex, residence, and the absence of prior clinical heart disease or major comorbidity were identified from the community. Spouses of subjects were interviewed to quantify leisure-time activity (LTA) during the prior year. Energy expended in high-intensity LTA, requiring 60% of maximum oxygen intake, was determined. The risk of PCA was 55% to 65% lower in persons in the two upper quartiles of high-intensity LTA than in persons without high-intensity LTA (95% confidence interval of relative risk, 0.22 to 0.85). Because this association was demonstrated in a clinically healthy population without prior morbidity, our data support the hypothesis that high-intensity LTA protects against PCA. (<i>JAMA</i>1982;248:3113-3117)
Long Term Results of Neuromodulation by Sacral Nerve Stimulation for Lower Urinary Tract Symptoms: A Retrospective Single Center Study
Authors: A.C. van Voskuilen, D.J.A.J. Oerlemans, E.H.J. Weil, R.A. de Bie, Ph.E.V.A. van Kerrebroeck
Journal: European Urology (2006)
Successful Gene Therapy in the RPGRIP1-deficient Dog: a Large Model of Cone–Rod Dystrophy
Authors: Elsa Lhériteau, Lolita Petit, Michel Weber, Guylène Le Meur, Jack-Yves Deschamps, Lyse Libeau, Alexandra Mendes-Madeira, Caroline Guihal, Achille François, Richard Guyon, Nathalie Provost, Françoise Lemoine, Samantha Papal, Aziz El-Amraoui, Marie-Anne Colle, Philippe Moullier, Fabienne Rolling
Journal: Molecular Therapy (2013)

For the development of new therapies, proof-of-concept studies in large animal models that share clinical features with their human counterparts represent a pivotal step. For inherited retinal dystrophies primarily involving photoreceptor cells, the efficacy of gene therapy has been demonstrated in canine models of stationary cone dystrophies and progressive rod–cone dystrophies but not in large models of progressive cone–rod dystrophies, another important cause of blindness. To address the last issue, we evaluated gene therapy in the retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1)-deficient dog, a model exhibiting a severe cone–rod dystrophy similar to that seen in humans. Subretinal injection of AAV5 (n = 5) or AAV8 (n = 2) encoding the canine Rpgrip1 improved photoreceptor survival in transduced areas of treated retinas. Cone function was significantly and stably rescued in all treated eyes (18–72% of those recorded in normal eyes) up to 24 months postinjection. Rod function was also preserved (22–29% of baseline function) in four of the five treated dogs up to 24 months postinjection. No detectable rod function remained in untreated contralateral eyes. More importantly, treatment preserved bright- and dim-light vision. Efficacy of gene therapy in this large animal model of cone–rod dystrophy provides great promise for human treatment. For the development of new therapies, proof-of-concept studies in large animal models that share clinical features with their human counterparts represent a pivotal step. For inherited retinal dystrophies primarily involving photoreceptor cells, the efficacy of gene therapy has been demonstrated in canine models of stationary cone dystrophies and progressive rod–cone dystrophies but not in large models of progressive cone–rod dystrophies, another important cause of blindness. To address the last issue, we evaluated gene therapy in the retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1)-deficient dog, a model exhibiting a severe cone–rod dystrophy similar to that seen in humans. Subretinal injection of AAV5 (n = 5) or AAV8 (n = 2) encoding the canine Rpgrip1 improved photoreceptor survival in transduced areas of treated retinas. Cone function was significantly and stably rescued in all treated eyes (18–72% of those recorded in normal eyes) up to 24 months postinjection. Rod function was also preserved (22–29% of baseline function) in four of the five treated dogs up to 24 months postinjection. No detectable rod function remained in untreated contralateral eyes. More importantly, treatment preserved bright- and dim-light vision. Efficacy of gene therapy in this large animal model of cone–rod dystrophy provides great promise for human treatment.
A CASE OF TRUE ALLERGY ESTABLISHED BY PATCH TESTING AND REPORTED BY SIR KENELME DIGBY IN 1645.
Authors: IDA MACALPINE, RICHARD A. HUNTER
Journal: British Journal of Dermatology (1956)

Journal Article A CASE OF TRUE ALLERGY ESTABLISHED BY PATCH TESTING AND REPORTED BY SIR KENELME DIGBY IN 1645. Get access IDA MACALPINE, IDA MACALPINE Search for other works by this author on: Oxford Academic Google Scholar RICHARD A. HUNTER RICHARD A. HUNTER Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 68, Issue 2, 1 February 1956, Pages 61–62, https://doi.org/10.1111/j.1365-2133.1956.tb12784.x Published: 01 February 1956
Safer prescribing for children
Authors: Harvey Marcovitch
Journal: BMJ (2005)

Will be boosted by European and US laws and the new British national formulary for children 

P aediatric prescribing can be precise, beneficial, and safe. It can also be confusing, based on little or no evidence of effectiveness, and can put children at risk. The nature of marketing authorisations (formerly product licences) for drugs merely enhances the paradox. They were designed as a means of obtaining approval for use by an appropriate regulatory body, usually a government agency; so the decision to apply for authorisation is influenced more by commercial than clinical considerations.1 One result is that unlicensed and “off label” prescribing is common. Paediatricians, general practitioners, and others are torn between providing treatment which their experience and reason have deemed suitable and denying it because of the lack of research data underpinning indications, dosages, or formulations. …
COMPARISON OF TWO POPULATIONS TO OBTAIN THE NORMAL LIMITS USED IN THE QUANTIFICATION OF MYOCARDIAL THALLIUM-201 SCINTIGRAMS
Authors: K Van Train, E Garcia, J Maddahi, D Brown, A Waxman, J Areeda, D Berman
Journal: Clinical Nuclear Medicine (1982)

Train, K Van; Garcia, E; Maddahi, J; Brown, D; Waxman, A; Areeda, J; Berman, D Author Information
SELECTIVE "STAINING" FOR ELECTRON MICROGRAPHY
Authors: Stuart Mudd, Thomas F. Anderson
Journal: The Journal of Experimental Medicine (1942)

The physical basis of contrast and image formation in electron micrography is considered in relation to the possibility of recording selective chemical effects on cell components. A technology of selective microchemical analysis, equivalent to differential staining, is suggested as practicable in electron micrography. Electron pictures of bacteria after exposure to salts of heavy metals have shown the bacterial inner protoplasm, but not the cell walls, to be selectively darkened; shrinkage, coagulation, or escape of protoplasm from the injured cells may result and be recorded in the electron micrographs. Recording of the action of germicidal agents on individual bacterial cells is indicated as one promising field of application of microchemical analysis with the aid of the electron microscope.
Dexamethasone in the treatment of meningeal leukemia
Authors: David Gómez‐Almaguer, Oscar González‐Llano, Jorge Montemayor, José C. Jaime‐Pérez, Cesar Galindo
Journal: American Journal of Hematology (1995)

Abstract To determine if dexamethasone has a role in the treatment of meningeal leukemia, 8 consecutive patients with acute lymphoblastic and signs or symptoms of CNS were included in the study. After the confirmation of leukemic blast cells on cerebrospinal fluid, they received intrathecal and IV dexamethasone; 3 days later the patients received “triple” intrathecal chemotherapy with dexamethasone, methotrexate and cytarabine, and the spinal fluid was studied again. All patients had good clinical response and 7 out of the 8 patients showed reduction on the CSF cell count after the use of dexamethasone alone. The results suggest that dexamethasone is a lympholytic agent that could play a more active role in the prevention and therapy of meningeal leukemia and should be preferred over hydrocortisone in the so called “triple” intrathecal chemotherapy for the prevention and treatment of CNS leukemia. © 1995 Wiley‐Liss, Inc.
Scientists in Search of Their Conscience
Authors: Marjorie C. Meehan
Journal: JAMA (1973)

Is all scientific investigation good? Are scientists responsible for the application of their findings? How much should society pay for pure science, for task-oriented science? Who will decide which research will be pursued? Can the real results be measured and evaluated? Most scientists might prefer to ignore these questions and be left alone to pursue their special ends with a minimum of interference and a maximum of support from the community. But increasing criticism and reluctance to pay for research has led some scientists to question their values. In 1971, the European Committee of the Weizmann Institute of Israel organized a symposium in Brussels and invited ten distinguished European and Israeli scientists to discuss "The Impact of Science on Society." Their presentation, together with remarks by several discussants constitute this volume. All the contributors are mature, successful, thoughtful scientists who express their ideas clearly and forcefully. Some refer to specific
Plain Film Interpretation in Congenital Heart Disease
Authors: Jeremiah Kelleher
Journal: JAMA (1980)

Some books understate their objectives, but most make relatively extravagant claims. Dr Swischuk, in the preface to this, the second edition of his book on plain film interpretation in congenital heart disease, states his objective to be "to provide a primer for the interpretation and understanding of the plain film roentgenographic findings in congenital heart disease." I think he is too modest. This is a fine comprehensive review of the subject and contains a large amount of useful information. There is a nice brief review of the relevant embryology of cardiovascular development that serves to make some of the more complex malformations a little more understandable. He divides the plain film findings in congenital heart disease according to the basic pulmonary vascular patterns. Though not a new approach, it makes for much easier classification for the student of congenital heart disease. Thus, discussion according to the patterns of increased pulmonary
Massively parallel sequencing identifies a previously unrecognized X-linked disorder resulting in lethality in male infants owing to amino-terminal acetyltransferase deficiency
Authors: Alan F Rope, Kai Wang, Rune Evjenth, Jinchuan Xing, Jennifer J Johnston, Jeffrey J Swensen, W Evan Johnson, Barry Moore, Chad D Huff, Lynne M Bird, John C Carey, John M Opitz, Cathy A Stevens, Christa Schank, Heidi Deborah Fain, Reid Robison, Brian Dalley, Steven Chin, Sarah T South, Theodore J Pysher, Lynn B Jorde, Hakon Hakonarson, Johan R Lillehaug, Leslie G Biesecker, Mark Yandell, Thomas Arnesen, Gholson J Lyon
Journal: Genome biology (2011)

Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations.We analyzed exome data from 2,440 individuals of European and African ancestry as part of the National Heart, Lung, and Blood Institute's Exome Project, the aim of which is to discover novel genes and mechanisms that contribute to heart, lung and blood disorders.Each exome was sequenced to a mean coverage of 116×, allowing detailed inferences about the population genomic patterns of both common variation and rare coding variation.We identifi ed more than 500,000 single nucleotide variations, the majority of which were novel and rare (76% of variants had a minor allele frequency of less than 0.1%), refl ecting the recent dramatic increase in the size of the human population.The unprecedented magnitude of this dataset allowed us to rigorously characterize the large variation in nucleotide diversity among genes (ranging from 0 to 1.32%), as well as the role of positive and purifying selection in shaping patterns of proteincoding variation and the diff erential signatures of population structure from rare and common variation.This dataset provides a framework for personal genomics and is an important resource that will allow inferences of broad importance to human evolution and health.
INTERVENTIONAL MITRAL VALVE REPAIR USING THE MITRACLIP SYSTEM AFTER PRIOR SURGICAL MITRAL ANNULOPLASTY
Authors: Johannes Schirmer, Volker Rudolph, Britta Goldmann, Lenard Conradi, Moritz Seiffert, Michael Schlueter, Edith Lubos, Hendrik Treede, Stefan Blankenberg, Hermann Reichenspurner, Stephan Baldus
Journal: Journal of the American College of Cardiology (2013)
Pollen NADPH Oxidases Increase Intracellular ROS (iROS) And IL5 Production From PBMC Of Ragweed Allergic Patients With Late Phase Symptoms To Intranasal Ragweed Challenge
Authors: H. Murai, D. Redding, K.A. Gonzalez, B. Singh, A. Kalita, H. Qi, V.J. Cardenas Jr., S. Sur
Journal: Journal of Allergy and Clinical Immunology (2009)
THE ASSAULT ON TROPICAL DISEASE.
Authors: LEWELLYS F. BARKER
Journal: JAMA (1906)

<h3>INTRODUCTION.</h3> Tropical pathology is rapidly becoming recognized as a special field in medicine, a field worthy of cultivation by itself and for its own sake. Indeed a number of the energetic and able men of our profession have already made the decision to devote themselves to it as a life work. Though it was my rare good fortune some years ago to travel as a member of a commission for the special study of tropical diseases, and I had the opportunity in Hongkong, in the Philippines and in India to observe some of the more prevalent maladies occurring there, it was less this fleeting experience, I imagine, which prompted you to ask me to speak on the subject allotted to me, than, in the first place, a desire to extend a courtesy to the appointee to a dignified office, and, in the second place, the conviction that one whose life
Melanoma molecular classes and prognosis in the postgenomic era
Authors: Elisa Tremante, Agnese Ginebri, Elisa Lo Monaco, Pasquale Frascione, Franco Di Filippo, Irene Terrenato, Maria Benevolo, Marcella Mottolese, Edoardo Pescarmona, Paolo Visca, Pier Giorgio Natali, Patrizio Giacomini
Journal: The Lancet Oncology (2012)
Defibrillating shocks delivered to the heart impair efferent sympathetic responsiveness.
Authors: M Ito, H P Pride, D P Zipes
Journal: Circulation (1993)

BACKGROUND Functional studies indicate that sympathetic efferents are located in the superficial subepicardium and vagal efferents are located in the subendocardium. It is possible that electrical shocks applied directly to the heart might affect the function of these autonomic nerves. METHODS AND RESULTS Low- (&lt; or = 1 J), medium- (6 to 16 J), or high- (30 to 35 J) energy truncated monophasic exponential shocks, synchronized to the R wave during sinus rhythm, were delivered over implantable patches sutured inside the pericardium in anesthetized open-chest dogs. Shortening of ventricular effective refractory period (ERP), produced by bilateral ansae subclaviae stimulation (SS), was measured before and after shock delivery. High-energy shocks shifted the SS frequency-ERP response curves downward and to the right (P &lt; .001) for sites beneath and apical to the patches; ERP shortening at basal sites remained unchanged. Such sympathetic attenuation occurred with shocks &gt; 10 J but not with shocks &lt; or = 10 J, was noted 15 minutes after the shock, and showed incomplete return to control values at 3 hours. Neither low- nor high-energy shocks affected norepinephrine dose-ERP response curves, indicating normal myocardial responsiveness. Low- and high-energy shocks did not attenuate bilateral cervical vagal stimulation-induced ERP prolongation. High-energy shocks delivered over patches sutured to the outside of the pericardium showed no effects on sympathetic response, suggesting a protective effect of the pericardium against shock-induced sympathetic attenuation. CONCLUSIONS DC shocks &gt; 10 J delivered directly to the epicardium attenuated efferent sympathetic neural function. Such changes may affect electrophysiological, as well as hemodynamic, responses to sympathetic neural stimulation after cardioversion-defibrillation.
Differences in antigen-specific T-cell responses between infants with atopic dermatitis with and without cow’s milk allergy: Relevance of TH2 cytokines
Authors: Rogier P. Schade, Adrie G. Van Ieperen-Van Dijk, Frank C. Van Reijsen, Coraline Versluis, Jan L.L. Kimpen, Edward F. Knol, Carla A.F.M. Bruijnzeel-Koomen, Els Van Hoffen
Journal: Journal of Allergy and Clinical Immunology (2000)
A Practical Guide to Fundholding
Authors: U. Freudenstein
Journal: BMJ (1995)

Rod Smith, Shaun Brogan, Richard, Stephenson, Janet Fitzgerald, Lesley Withers, Blackwell Science, pounds sterling16.95, pp 287 ISBN 0 63203869 1

Are you on the verge of fundholding? Is your practice manager or newly appointed fundholding manager desperate for an introduction to the practicalities of fundholding? If your answer to any of these questions is yes this review is for you.

What data do you have to collect? What plans do you submit when? How detailed do your contracts with providers have to be? I vividly remember our search for answers to such questions. …
Endoscopic treatment of early oesophageal or gastric cancer.
Authors: K Takeshita, M Tani, H Inoue, I Saeki, S Hayashi, T Honda, F Kando, N Saito, M Endo
Journal: Gut (1997)

BACKGROUND AND AIMS: Endoscopic treatment has become increasingly popular in recent years as an alternative to surgical treatment with the hope of offering superior quality of life (QOL) for the patient. The results of endoscopic treatment of mucosal lesions of mostly early oesophageal or gastric cancer performed in 145 patients (155 lesions) over the past eight years were reviewed from the standpoint of QOL. RESULTS: In 56 patients who underwent radical resection of the oesophageal mucosa, no serious complications and symptoms occurred, with epithelialisation completed within about a month. Patients also showed good results regarding dietary intake and performance status (PS), and all are currently alive without any sign of recurrence. One time fractionated endoscopic resection was carried out in about 40% of the 57 patients who underwent gastric mucosal resection. In these 57 patients, an artificial ulcer measuring 3 cm or more was formed, resulting in a favourable outcome after healing. An overwhelming proportion of these subjects had no symptoms and good PS after the treatment. CONCLUSIONS: The introduction of this method, endoscopic mucosal resection using a cap fitted panendoscope, is expected to permit additional indications for endoscopic treatment. Endoscopic Nd-YAG laser irradiation was applied mainly to early gastric cancer lesions (32 patients), usually for relative indications for endoscopic treatment. This procedure is safe and advantageous in that it requires no hospitalisation, permits fractionated irradiation, and secures good QOL.
A novel stealth liposomal topotecan with amlodipine: Apoptotic effect is associated with deletion of intracellular Ca2+ by amlodipine thus leading to an enhanced antitumor activity in leukemia
Authors: Xing Li, Guo-Rui Ruan, Wan-Liang Lu, Hai-Yan Hong, Gong-Wen Liang, Yu-Teng Zhang, Yang Liu, Chuan Long, Xi Ma, Lan Yuan, Jian-Cheng Wang, Xuan Zhang, Qiang Zhang
Journal: Journal of Controlled Release (2006)
Target-Independent EphrinA/EphA-Mediated Axon-Axon Repulsion as a Novel Element in Retinocollicular Mapping
Authors: Philipp Suetterlin, Uwe Drescher
Journal: Neuron (2014)

EphrinAs and EphAs play critical roles during topographic map formation in the retinocollicular projection; however, their complex expression patterns in both the retina and superior colliculus (SC) have made it difficult to uncover their precise mechanisms of action. We demonstrate here that growth cones of temporal axons collapse when contacting nasal axons in vitro, and removing ephrinAs from axonal membranes by PI-PLC treatment abolishes this response. In conditional knockout mice, temporal axons display no major targeting defects when ephrinA5 is removed only from the SC, but substantial mapping defects were observed when ephrinA5 expression was removed from both the SC and from the retina, with temporal axons invading the target areas of nasal axons. Together, these data indicate that ephrinA5 drives repellent interactions between temporal and nasal axons within the SC, and demonstrates for the first time that target-independent mechanisms play an essential role in retinocollicular map formation in vivo.