tbuckley/cabot-search huggingface dataset:
Abstract P2-10-20: A tumor DNA complexity index is an independent predictor of survival in a dataset of 1950 breast cancers; a METABRIC group study.
Authors: HKM Vollan, OM Rueda, A-L Børresen-Dale, S Aparicio, C Caldas
Journal: Cancer Research (2012)

Abstract Background: Cancer genomes undergo substantial alterations during carcinogenesis. Patterns of such rearrangements differ with respect to cancer subtypes and may affect crucial parts of the genome. DNA based markers would make clinical implementation more feasible as markers based on RNA expression are challenging due to the intrinsic problem of RNA stability and volatility in expression patterns. Complex genomic rearrangements in breast cancer genomes, quantified by the complex arm-wise aberration index (CAAI), have previously been shown to be of prognostic value. However this finding has not been validated in independent large-scale breast cancer cohorts or compared with other molecular predictors. Methods: A total of 1950 breast carcinomas from the METABRIC cohort with log term follow up were included in this study. Microarray based copy number and expression data from fresh frozen primary tumors were available. Cases were classified as CAAI positive if at least one complex event was present in the tumor genome. The clinical end points were breast cancer specific survival (BCSS) and overall survival (OS). Results: A total of 33 % of breast cancer cases were CAAI positive with a Cox proportional hazard ratio (HR) of 1.78 (95% CI, 1.49–2.12) for BCSS. Using multivariate Cox regression the adjusted HR for BCSS of 1.42 (95% CI, 1.12–1.80) and 1.44 (95% CI, 1.02–2.03) in estrogen receptor positive (ER+) and estrogen receptor negative breast cancers, respectively. Gene expression classifiers based on OncotypeDX and MammaPrint were not independently prognostic in the ER− subset. Significant difference in survival was both seen in patients that received systemic treatment, and in patients that did not. Conclusions: DNA based prognostic profiling is a robust method for both fresh frozen and FFPE tumor material. This study shows that complex genomic alterations of tumor DNA, measured as CAAI, is an independent predictor of survival in breast cancer, in both ER+ and ER− disease in a large scale breast cancer cohort with long term follow up. The effect seems unrelated to systemic endocrine treatment or chemotherapy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-20.
Effects of the Antacids in Didanosine Tablets on Dapsone Pharmacokinetics
Authors: Jan Sahai
Journal: Annals of Internal Medicine (1995)

To investigate 1) the effects of the magnesium-aluminum antacids in didanosine tablets on dapsone absorption in healthy volunteers and 2) the effects of the antacid formulation of active didanosine tablets on dapsone pharmacokinetics in patients seropositive for human immunodeficiency virus (HIV).Two separate, randomized, two-period, two-treatment, crossover studies with a 21-day washout period between treatments.Clinical investigation unit of a university hospital.Six healthy men and six HIV-positive men.Serial dapsone plasma concentrations were measured when dapsone, 100 mg, was administered alone and with either the third of four doses of didanosine placebo tablets (group 1) or the 27th of 28 doses of active didanosine tablets (group 2). In each study, pharmacokinetic variables were determined using noncompartmental methods and compared by analysis of variance.When dapsone was administered alone, pharmacokinetic variables did not significantly differ from those with dapsone given in either combination (P > 0.10 for all comparisons).Didanosine, antacids, and other excipients in the currently used didanosine chewable tablets did not significantly affect plasma concentrations of dapsone.
PWE-018 Superiority of actual compared with close (&lt;1 mm) circumferential resection margin involvement in the pathological staging of oesophageal and junctional cancer
Authors: N J O'Farrell, C L Donohoe, J M Costelloe, C Muldoon, N Ravi, J V Reynolds
Journal: Gut (2012)

<h3>Introduction</h3> An involved circumferential resection margin (CRM), defined as tumour cells within 1 mm of the CRM, is of established prognostic significance in rectal cancer. In the oesophagus, which unlike rectum lacks a defined mesentery, controversy exists, with the UK Royal College of Pathologists (RCP) recommending the 1 mm definition, while the College of American Pathologists (CAP) advise that only an involved margin defines an incomplete (R1) resection. <h3>Methods</h3> CAP and RCP CRM status were recorded prospectively in a comprehensive prospective data-base from May 2003 to May 2011. Factors impacting on survival were assessed by univariate and multivariate analysis. Kaplan–Meier survival curves for CRM + compared with CRM- groups by RCP and CAP criteria were computed. <h3>Results</h3> RCP and CAP CRM status was available for 316 patients. Overall, positive margins were recorded in 33% (n=103) and 10% (n=33) using the RCP and CAP criteria, respectively. Specific analysis focused on 143 patients with pT3 tumours. Mean follow-up was 19.8 months (range 1.6–79.5 months). RCP criteria diagnosed 60.8% (n=87) of pT3 tumours as positive; however, by CAP criteria, 18% (n=27) were positive. A significantly higher proportion of CAP positive CRMs were associated with lymph node metastases (p=0.05). Using RCP criteria there was no significant difference in survival in patients with positive and negative CRM margins (p=0.201). However, CRM involvement by CAP criteria was associated with poor survival (p=0.003). Multivariate analysis revealed nodal invasion and CAP CRM positive disease as independent prognostic variables (p=0.047 and p=0.028 respectively). <h3>Conclusion</h3> Comparison of the RCP and CAP criteria indicates that CAP is superior, consistent with recent data.<sup>1</sup> It may be best to include both assessments in prospective data-bases, but this data suggests that actual rather than close CRM involvement significantly impacts outcome, and may be factored into prognostic calculation and possibly the design of future adjuvant trials. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1 <b>Deeter M</b>, Dorer R, Kuppusamy MK, <i>et al.</i> Assessment of criteria and clinical significance of circumferential resection margins in esophageal cancer. <i>Arch Surg</i> 2009;<b>144</b>:618–24.
Hearing Voices — How Should Doctors Respond to Their Calling?
Authors: David Loxterkamp
Journal: New England Journal of Medicine (1996)

Typical damn day. I am running behind, swilling lukewarm coffee, and whittling away at the tower of charts and messages the nurse has stacked on my desk. I peep around the corner to survey the crowded waiting room, and I recognize every dependable name and complaint on the morning roster.A family meeting has been scheduled over the lunch hour so that I can meet a patient's two sons who are visiting from out of town. They have left a list of items for me “to consider” before we gather. Scrawled on the back of a coffee-stained envelope are the . . .
Identification of Therapeutic Covariant MicroRNA Clusters in Hypoxia-Treated Cardiac Progenitor Cell Exosomes Using Systems Biology
Authors: Warren D. Gray, Kristin M. French, Shohini Ghosh-Choudhary, Joshua T. Maxwell, Milton E. Brown, Manu O. Platt, Charles D. Searles, Michael E. Davis
Journal: Circulation Research (2014)

Myocardial infarction is a leading cause of death in developed nations, and there remains a need for cardiac therapeutic systems that mitigate tissue damage. Cardiac progenitor cells (CPCs) and other stem cell types are attractive candidates for treatment of myocardial infarction; however, the benefit of these cells may be as a result of paracrine effects.We tested the hypothesis that CPCs secrete proregenerative exosomes in response to hypoxic conditions.The angiogenic and antifibrotic potential of secreted exosomes on cardiac endothelial cells and cardiac fibroblasts were assessed. We found that CPC exosomes secreted in response to hypoxia enhanced tube formation of endothelial cells and decreased profibrotic gene expression in TGF-β-stimulated fibroblasts, indicating that these exosomes possess therapeutic potential. Microarray analysis of exosomes secreted by hypoxic CPCs identified 11 miRNAs that were upregulated compared with exosomes secreted by CPCs grown under normoxic conditions. Principle component analysis was performed to identify miRNAs that were coregulated in response to distinct exosome-generating conditions. To investigate the cue-signal-response relationships of these miRNA clusters with a physiological outcome of tube formation or fibrotic gene expression, partial least squares regression analysis was applied. The importance of each up- or downregulated miRNA on physiological outcomes was determined. Finally, to validate the model, we delivered exosomes after ischemia-reperfusion injury. Exosomes from hypoxic CPCs improved cardiac function and reduced fibrosis.These data provide a foundation for subsequent research of the use of exosomal miRNA and systems biology as therapeutic strategies for the damaged heart.
Preliminary report: circulating levels of the adipokine vaspin in gestational diabetes mellitus and preeclampsia
Authors: Holger Stepan, Susan Kralisch, Katrin Klostermann, Susanne Schrey, Constanze Reisenbüchler, Michael Verlohren, Hans-Joachim Verlohren, Kathrin Drynda, Matthias Blüher, Michael Stumvoll, Jürgen Kratzsch, Peter Kovacs, Mathias Fasshauer
Journal: Metabolism (2010)
DIFFERENT EFFECTS OF THROMBOXANE SYNTHETASE INHIBITORS ON PLATELETS FROM DIFFERENT INDIVIDUALS
Authors: S Heptinstall, N Bientz, S.R Cockbill, S.P Hanley, I Peacock, I.L Smith, T.J Martin, N.J Dodd, M.J Weston, M.P Gordge
Journal: The Lancet (1982)
Blood Amylase and Diabetic Ketoacidosis
Authors: E. Fritz Schmerl
Journal: JAMA (1977)

<h3>To the Editor.—</h3> In their article on prolonged high blood amylase levels in a case of diabetic ketoacidosis, Drs vanSonnenberg and Pitchumoni discuss a possible causal connection between diabetes and pancreatitis. Since they refer to Somogyi's pioneer work on low serum amylase levels in diabetic ketoacidosis, it may be of more than historic interest that this puzzling altered amylase level in diabetes had intrigued the investigator as early as 1929.<sup>1</sup>At that time it was already known that, in experimental as well as clinical nonketotic diabetes, urinary amylase values can be low. This was explained by diminished renal filtration. Perhaps vanSonnenberg and Pitchumoni, as clinicians, can take comfort in the fact that, in the experimental phlorizin diabetes of the rabbit, the increase in urine amylase had then also been found to be "oddly protracted."
Standard Nomenclature for Primary Hepatic Tumors-Reply
Authors: E. Truman Mays
Journal: JAMA (1977)

These two letters illustrate anew the ways mens' prejudices obscure their comprehension of the written word. I did not impugn the classification of hepatic tumors propagated by Edmonson. I simply observed that multiple synonyms have made it difficult for nonpathologists to follow recent new developments in medicine. A careful reading of my COMMENTARY discloses my utmost recognition of the nomenclature established by Edmonson in the<i>Atlas of Tumor Pathology</i>. This nomenclature (despite profuse synonyms) has served us well in classifying sundry hepatic growths developing in livers damaged by viruses, toxins, chemicals and alcohol; likewise, it has effectively differentiated the various congenital nodules occurring in livers of the very young. But new and perplexing things are happening! In men and women in the prime of life with completely normal livers, hepatic growths are developing, some of which are aggressive hepatocellular cancers. The nomenclature used to describe such hepatic tumors
THE STATE BOARD AND THE COLLEGE DIPLOMA.
Authors: MURRAY GALT MOTTER
Journal: JAMA (1907)

pernicious anemia, in hypertrophie cirrhosis and in syphilis of the liver, not to mention that found in primary malignant disease of the ducts, must account for a number of cases of apparent jaundice, even though the tint in these diseases is, in a measure, characteristic.CANCER.
Adrenal Virilism Treated with Steroids
Authors: A. W. Spence, J. S. Jenkins, A. M. Robinson
Journal: BMJ (1956)

and a half years have been observed.The patient in the early stages of the disease is likely to respond better to treatment, but of three patients (Cases 8, 12, and 15) who had become refractory to radiotherapy, two, including one in the acute terminal stage (Case 8), were benefited by mercaptopurine.No unpleasant side-effects have been observed, and evidence of serious bone-marrow depression has not followed prolonged dosage with mercaptopurine.The need for regular blood examination is, however, stressed.
Choosing the Best Prenatal Screening Protocol
Authors: Joe Leigh Simpson
Journal: New England Journal of Medicine (2005)

Prenatal genetic diagnosis for numerical chromosomal abnormalities (aneuploidy) was once simple. In the 1970s, women who were at least 35 years of age at delivery were offered an invasive procedure, amniocentesis, and 25 to 30 percent of trisomy 21 pregnancies were diagnosed. In the 1980s, the approach to screening changed because of observations that relatively low levels of alpha-fetoprotein and unconjugated estriol and relatively high levels of human chorionic gonadotropin and, later, inhibin A in the maternal serum during the second trimester predicted the risk of fetal trisomy. This information, together with the age-specific risk of trisomy, permitted individual risks . . .
Suppressor Cell Function in Sarcoidosis
Authors: JAMES S. GOODWIN
Journal: Annals of Internal Medicine (1979)

We investigated the role of suppressor cells in the depressed cellular immunity of patients with sarcoidosis. The mean response in 16 patients with active sarcoidosis to three concentrations of phytohemagglutinin was significantly (P < 0.01) less than control values. Passage of the cells over glass wool resulted in a 116% increase in response to phytohemagglutinin in patients and a 39% decrease in control subjects. Addition of indomethacin to phytohemagglutinin cultures increased the response of cells in patients with sarcoidosis by 192% ± 32% versus a 112% ± 18%-increase for control subjects (mean ± SEM, P < 0.05). Patients had an increased percentage of monocytes in peripheral blood mononuclear cell preparations, and the percent monocytes correlated with the percent increase in phytohemagglutinin response after glass wool passage (r = 0.62, P < 0.05). Thus, several factors contribute to the depressed phytohemagglutinin response in sarcoidosis patients: an increased suppression by the prostaglandin-producing suppressor cell, an increased percentage of monocytes, and an as yet undefined factor.
Electrophysiologic mechanisms of functional bundle branch block at onset of induced orthodromic tachycardia in the Wolff-Parkinson-White syndrome. Role of stimulation method.
Authors: M H Lehmann, S Denker, R Mahmud, P Tchou, J Dongas, M Akhtar
Journal: Journal of Clinical Investigation (1985)

The mechanisms of aberrant conduction at the onset of induced orthodromic tachycardia in the Wolff-Parkinson-White syndrome were analyzed in 20 consecutive patients in whom this tachycardia was initiated by the atrial (A2) and/or right ventricular (V2) extrastimulus techniques. Of 13 patients in whom orthodromic tachycardia was induced by the A2 method, functional right bundle branch block occurred at tachycardia onset in four (31%) and left bundle aberrancy in two (15%), one of whom also manifested right bundle aberrancy. The occurrence of bundle branch block at the onset of tachycardia was linked to aberrant conduction of the initiating A2 impulse which, in turn, was associated with attainment of relatively short His1His2 intervals within the tachycardia initiation zone. Aberrant conduction of A2 was also more common in patients without manifest preexcitation. In contrast, of 14 patients in whom orthodromic tachycardia was induced by the V2 method, left bundle aberrancy occurred at the onset of tachycardia in 11 (79%), one of whom manifested right bundle branch block as well. Left bundle aberrancy was more likely to occur when the interval from the initiating V2 (or macro-reentrant V3) impulse to the first anterograde His deflection was less than 300 ms. This suggests that left bundle aberrancy at the onset of orthodromic tachycardia induced by the V2 method results from concealed retrograde penetration of the His-Purkinje system, with the left bundle being last to recover. Our findings provide the conceptual basis for a physiologic approach to the deliberate induction of specific types of aberrant conduction at onset of orthodromic tachycardia in patients with Wolff-Parkinson-White syndrome.
Voltage-gated Na+ channels in glia: properties and possible functions
Authors: Harald Sontheimer, Joel A Black, Stephen G Waxman
Journal: Trends in Neurosciences (1996)

Glial cells are nervous-system cells that have classically been considered to be inexcitable. Despite their lack of electrical excitability, they can express voltage-activated Na+ channels with properties similar to the Na+ channels used by excitable cells to generate action potentials. The functional role that these voltage-activated Na+ channels play in glia is unclear. Three functions have been proposed: (1) glial cells might synthesize Na+ channels and donate them to adjacent neurons, thereby reducing the biosynthetic load of neurons; (2) Na+ channels might endow glial cells with the ability to sense electric activity of neighboring neurons, and might thus play a role in neuro-glial communication; and (3) Na+ influx through voltage-gated Na+ channels could be important to fuel the glial (Na+,K+)-ATPase, thereby facilitating and possibly modulating K+ uptake from the extracellular space. Trends Neurosci. (1996) 19, 325–331
High frequency of contact allergy to gold in patients with endovascular coronary stents
Authors: S. Ekqvist, C. Svedman, H. Möller, M. Kehler, C.M. Pripp, J. Björk, B. Gruvberger, E. Holmström, C.G. Gustavsson, M. Bruze
Journal: British Journal of Dermatology (2007)

Stent implantation is an effective method for treatment of atherosclerotic disease. Factors predisposing to in-stent restenosis are still largely unknown. Contact allergy to metal ions eluted from the stent has been suggested to be a risk factor.To explore whether there is a possible induction of contact allergy to metals used in stents among patients with a stainless steel stent containing nickel (Ni stent) and patients with a gold-plated stent (Au stent).Adults (n = 484) treated with coronary stent implantation participated in the study with patch testing. The study design was retrospective and cross-sectional with no assessment of contact allergy before stenting. Age- and sex-matched patch-tested patients with dermatitis (n = 447) served as controls.Of Au-stented patients, 54 of 146 (37%) were allergic to gold compared with 85 of 447 (19%) controls (P < 0.001). Within the stented population there were no statistically significant differences in contact allergy to gold or nickel between Ni-stented and Au-stented patients. In multivariate models where other risk factors for contact allergy to gold were considered, the Au stent showed a trend towards statistical significance (odds ratio 1.43, 95% confidence interval 0.95-2.16; P = 0.09).As the frequency of contact allergy to gold is higher in stented patients independent of stent type it suggests a previous sensitization. However, several pieces of circumstantial evidence as well as statistical analysis indicate the possibility of sensitization in the coronary vessel by the Au stent. Ni stents and Au stents should not be ruled out as risk factors for induction of contact allergy to these metals.
136 REDOX-SENSITIVE GSK-3BETA INHIBITION AND LATE VEGF RELEASE MEDIATE HYPOXIA-DEPENDENT EPITHELIAL—MESENCHYMAL TRANSITION AND INCREASED INVASIVENESS IN HUMAN HEPG2 CELLS
Authors: S. Cannito, E. Novo, A. Compagnone, L. Valfre' di Bonzo, C. Busletta, E. Zamara, A. Bandino, C. Cravanzola, V. Bravoco, S. Colombatto, M. Parola
Journal: Journal of Hepatology (2008)
Patterns of rheumatoid arthritis and systemic lupus erythematosus in Hong Kong.
Authors: J Woo, R W Wong, S W Wang, P Woo
Journal: Annals of the Rheumatic Diseases (1987)

Patterns of rheumatoid arthritis and systemic lupus erythematosus in Hong Kong SIR, Retrospective and cross sectional surveys have sug- gested a higher prevalence of systemic lupus erythemato- sus (SLE) and lower prevalence of rheumatoid arthritis (RA) in the Oriental races than in Caucasians.Surveys for SLE have been performed in Hawaii.' Auckland.New Zealand, Malaysia, and Beijing, China' and for RA in Japan, Taiwan.6 and China.4None of these studies were population surveys and, being hospital based, were likely to be incomplete since traditional medicine is still practised in these countries.Nevertheless, we would like to report the results of a two year prospective pilot survey of the two diseases in hospitals serving the Chinese living on Hong Kong island.Over 99%X of the population of Hong Kong are Chinese, and this population is relatively stable as there has not been any mass emigration during this period.Patients in Hong Kong may refer themselves to fee paying government clinics of low cost, private general practi- tioners.practitioners of traditional Chinese medicine, or a combination of the above.Most cases of chronic arthritis eventually present in the government sector because of the high cost of private medicine and patients with SLE particularly tend to be referred by private general practi- tioners to Queen Mary University Hospital-the only referral centre for Hong Kong island.This hospital is a fee paying government hospital of low cost, and patients with acute systemic illness will usually refer themselves to the emergency department of government hospitals.The government clinics serve as the equivalent of the NHS casualty departments rather than as general practitioners.There is one major and four minor government hospitals on Hong Kong island.The major hospital receives all complicated medical patients and patients that require assessment and monitoring.Our survey was carried out in the major government hospital-Queen Mary.and in one minor hospital Nethersole.From
Biochemical and haematological variables in vegetarians.
Authors: J S Gear, J I Mann, M Thorogood, R Carter, R Jelfs
Journal: BMJ (1980)

Biochemical and haematological variables in vegetariansRelatively little is known about the long-term consequences of a vegetarian diet.Vegetarians have lower serum cholesterol concentra- tions than non-vegetarians' and Seventh-Day Adventists in the United States of America appear to have a lower prevalence of ischaemic heart disease than the general population.2On the other