tbuckley/cabot-search huggingface dataset:
Diabetic and Nondiabetic Patients With Left Main and/or 3-Vessel Coronary Artery Disease
Authors: Adrian P. Banning, Stephen Westaby, Marie-Claude Morice, A. Pieter Kappetein, Friedrich W. Mohr, Sergio Berti, Mattia Glauber, Mirle A. Kellett, Robert S. Kramer, Katrin Leadley, Keith D. Dawkins, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2010)

This study was designed to compare contemporary surgical revascularization (coronary artery bypass graft surgery [CABG]) versus TAXUS Express (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stents (PES) in diabetic and nondiabetic patients with left main and/or 3-vessel disease.Although the prevalence of diabetes mellitus is increasing, the optimal coronary revascularization strategy in diabetic patients with complex multivessel disease remains controversial.The SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) study randomly assigned 1,800 patients (452 with medically treated diabetes) to receive PES or CABG.The overall 1-year major adverse cardiac and cerebrovascular event rate was higher among diabetic patients treated with PES compared with CABG, but the revascularization method did not impact the death/stroke/myocardial infarction rate for nondiabetic patients (6.8% CABG vs. 6.8% PES, p = 0.97) or for diabetic patients (10.3% CABG vs. 10.1% PES, p = 0.96). The presence of diabetes was associated with significantly increased mortality after either revascularization treatment. The incidence of stroke was higher among nondiabetic patients after CABG (2.2% vs. PES 0.5%, p = 0.006). Compared with CABG, mortality was higher after PES use for diabetic patients with highly complex lesions (4.1% vs. 13.5%, p = 0.04). Revascularization with PES resulted in higher repeat revascularization for nondiabetic patients (5.7% vs. 11.1%, p < 0.001) and diabetic patients (6.4% vs. 20.3%, p < 0.001).Subgroup analyses suggest that the 1-year major adverse cardiac and cerebrovascular event rate is higher among diabetic patients with left main and/or 3-vessel disease treated with PES compared with CABG, driven by an increase in repeat revascularization. However, the composite safety end point (death/stroke/myocardial infarction) is comparable between the 2 treatment options for diabetic and nondiabetic patients. Although further study is needed, these exploratory results may extend the evidence for PES use in selected patients with less complex left main and/or 3-vessel lesions. (SYNergy Between PCI With TAXus and Cardiac Surgery [SYNTAX]; NCT00114972).
High Expression of ErbB Family Members and Their Ligands in Lung Adenocarcinomas That Are Sensitive to Inhibition of Epidermal Growth Factor Receptor
Authors: Nobukazu Fujimoto, Marie Wislez, Jie Zhang, Kentaro Iwanaga, Jennifer Dackor, Amy E. Hanna, Shailaja Kalyankrishna, Dianna D. Cody, Roger E. Price, Mitsuo Sato, Jerry W. Shay, John D. Minna, Michael Peyton, Ximing Tang, Erminia Massarelli, Roy Herbst, David W. Threadgill, Ignacio I. Wistuba, Jonathan M. Kurie
Journal: Cancer Research (2005)

Recent findings in tumor biopsies from lung adenocarcinoma patients suggest that somatic mutations in the genes encoding epidermal growth factor receptor (EGFR) and Kirsten ras (KRAS) confer sensitivity and resistance, respectively, to EGFR inhibition. Here, we provide evidence that these genetic mutations are not sufficient to modulate the biological response of lung adenocarcinoma cells to EGFR inhibition. We found high expression of ErbB family members, ErbB ligands, or both in three models that were sensitive to EGFR inhibition, including alveolar epithelial neoplastic lesions in mice that develop lung adenocarcinoma by oncogenic KRAS, human lung adenocarcinoma cell lines, and tumor biopsies from lung adenocarcinoma patients. Thus, lung adenocarcinoma cells that depend on EGFR for survival constitutively activate the receptor through a combination of genetic mutations and overexpression of EGFR dimeric partners and their ligands.
Review of Andrea Gillies,<i>Keeper: Living With Nancy, A Journey Into Alzheimer's</i><sup>1</sup>
Authors: Emma Zimmerman
Journal: The American Journal of Bioethics (2010)

Bioethics is in need of contemporary literary metaphors; soma is not so much overused as it is out of date, no longer reflecting our present worries. So it is that the The Wellcome Trust's Book Pri...
Idiopathic Portal Hypertension. Proceedings of the International Symposium on Idiopathic Portal Hypertension, July 15-17, 1982, Tokyo, Japan. Edited by Kunio Okuda and Masao Omata. Tokyo: University of Tokyo Press, 1983
Authors: Edward T. Bynum
Journal: Hepatology (1985)

methods that will serve clinical scientists better as a reference than as background reading.As a whole, the Shapiro-Louis books reads better than Tygstrup et al.However, the greater clinical emphasis in Tygstrup may outweigh that literary advantage in the eyes of physicians.The medical reader will not go wrong with either of these collections.
Intensive Hemodialysis Associates with Improved Pregnancy Outcomes
Authors: Michelle A. Hladunewich, Susan Hou, Ayodele Odutayo, Tom Cornelis, Andreas Pierratos, Marc Goldstein, Karthik Tennankore, Johannes Keunen, Dini Hui, Christopher T. Chan
Journal: Journal of the American Society of Nephrology (2014)

Pregnancy is rare in women with ESRD and when it occurs, it is often accompanied by significant maternal and fetal morbidity and even mortality. Preliminary data from the Toronto Nocturnal Hemodialysis Program suggested that increased clearance of uremic toxins by intensified hemodialysis improves pregnancy outcomes, but small numbers and the absence of a comparator group limited widespread applicability of these findings. We compared pregnancy outcomes from 22 pregnancies in the Toronto Pregnancy and Kidney Disease Clinic and Registry (2000-2013) with outcomes from 70 pregnancies in the American Registry for Pregnancy in Dialysis Patients (1990-2011). The primary outcome was the live birth rate and secondary outcomes included gestational age and birth weight. The live birth rate in the Canadian cohort (86.4%) was significantly higher than the rate in the American cohort (61.4%; P=0.03). Among patients with established ESRD, the median duration of pregnancy in the more intensively dialyzed Toronto cohort was 36 weeks (interquartile range, 32-37) compared with 27 weeks (interquartile range, 21-35) in the American cohort (P=0.002). Furthermore, a dose response between dialysis intensity and pregnancy outcomes emerged, with live birth rates of 48% in women dialyzed ≤20 hours per week and 85% in women dialyzed >36 hours per week (P=0.02), with a longer gestational age and greater infant birth weight for women dialyzed more intensively. Pregnancy complications were few and manageable. We conclude that pregnancy may be safe and feasible in women with ESRD receiving intensive hemodialysis.
American Society of Clinical Oncology Policy Statement: The Role of the Oncologist in Cancer Prevention and Risk Assessment
Authors: Robin T. Zon, Elizabeth Goss, Victor G. Vogel, Rowan T. Chlebowski, Ismail Jatoi, Mark E. Robson, Dana S. Wollins, Judy E. Garber, Powel Brown, Barnett S. Kramer
Journal: Journal of Clinical Oncology (2008)

Oncologists have a critical opportunity to utilize risk assessment and cancer prevention strategies to interrupt the initiation or progression of cancer in cancer survivors and individuals at high risk of developing cancer. Expanding knowledge about the natural history and prognosis of cancers positions oncologists to advise patients regarding the risk of second malignancies and treatment-related cancers. In addition, as recognized experts in the full spectrum of cancer care, oncologists are afforded opportunities for involvement in community-based cancer prevention activities. Although oncologists are currently providing many cancer prevention and risk assessment services to their patients, economic barriers exist, including inadequate or lack of insurance, that may compromise uniform patient access to these services. Additionally, insufficient reimbursement for existing and developing interventions may discourage patient access to these services. The American Society of Clinical Oncology (ASCO), the medical society representing cancer specialists involved in patient care and clinical research, is committed to supporting oncologists in their wide-ranging involvement in cancer prevention. This statement on risk assessment and prevention counseling, although not intended to be a comprehensive overview of cancer prevention describes the current role of oncologists in risk assessment and prevention; provides examples of risk assessment and prevention activities that should be offered by oncologists; identifies potential opportunities for coordination between oncologists and primary care physicians in prevention education and coordination of care for cancer survivors; describes ASCO's involvement in education and training of oncologists regarding prevention; and proposes improvement in the payment environment to encourage patient access to these services.
Architecture of epigenetic reprogramming following Twist1-mediated epithelial-mesenchymal transition
Authors: Gabriel G Malouf, Joseph H Taube, Yue Lu, Tapasree Roysarkar, Shoghag Panjarian, Marcos RH Estecio, Jaroslav Jelinek, Jumpei Yamazaki, Noel J-M Raynal, Hai Long, Tomomitsu Tahara, Agata Tinnirello, Priyanka Ramachandran, Xiu-Ying Zhang, Shoudan Liang, Sendurai A Mani, Jean-Pierre J Issa
Journal: Genome biology (2013)

Epithelial-mesenchymal transition (EMT) is known to impart metastasis and stemness characteristics in breast cancer. To characterize the epigenetic reprogramming following Twist1-induced EMT, we characterized the epigenetic and transcriptome landscapes using whole-genome transcriptome analysis by RNA-seq, DNA methylation by digital restriction enzyme analysis of methylation (DREAM) and histone modifications by CHIP-seq of H3K4me3 and H3K27me3 in immortalized human mammary epithelial cells relative to cells induced to undergo EMT by Twist1.EMT is accompanied by focal hypermethylation and widespread global DNA hypomethylation, predominantly within transcriptionally repressed gene bodies. At the chromatin level, the number of gene promoters marked by H3K4me3 increases by more than one fifth; H3K27me3 undergoes dynamic genomic redistribution characterized by loss at half of gene promoters and overall reduction of peak size by almost half. This is paralleled by increased phosphorylation of EZH2 at serine 21. Among genes with highly altered mRNA expression, 23.1% switch between H3K4me3 and H3K27me3 marks, and those point to the master EMT targets and regulators CDH1, PDGFRα and ESRP1. Strikingly, Twist1 increases the number of bivalent genes by more than two fold. Inhibition of the H3K27 methyltransferases EZH2 and EZH1, which form part of the Polycomb repressive complex 2 (PRC2), blocks EMT and stemness properties.Our findings demonstrate that the EMT program requires epigenetic remodeling by the Polycomb and Trithorax complexes leading to increased cellular plasticity. This suggests that inhibiting epigenetic remodeling and thus decrease plasticity will prevent EMT, and the associated breast cancer metastasis.
Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase 1act/Tubulin Interaction Is an Important Determinant of Mitotic Stability in Cultured HT1080 Human Fibrosarcoma Cells
Authors: Jia-ning Cao, Norazizah Shafee, Larry Vickery, Stefan Kaluz, Ning Ru, Eric J. Stanbridge
Journal: Cancer Research (2010)

Abstract Activation of the mitogen-activated protein kinase (MAPK) pathway plays a major role in neoplastic cell transformation. Using a proteomics approach, we identified α tubulin and β tubulin as proteins that interact with activated MAP/extracellular signal-regulated kinase kinase 1 (MEK1), a central MAPK regulatory kinase. Confocal analysis revealed spatiotemporal control of MEK1-tubulin colocalization that was most prominent in the mitotic spindle apparatus in variant HT1080 human fibrosarcoma cells. Peptide arrays identified the critical role of positively charged amino acids R108, R113, R160, and K157 on the surface of MEK1 for tubulin interaction. Overexpression of activated MEK1 caused defects in spindle arrangement, chromosome segregation, and ploidy. In contrast, chromosome polyploidy was reduced in the presence of an activated MEK1 mutant (R108A, R113A) that disrupted interactions with tubulin. Our findings indicate the importance of signaling by activated MEK1-tubulin in spindle organization and chromosomal instability. Cancer Res; 70(14); 6004–14. ©2010 AACR.
P blood group phenotype, proteus antibody titres, and rheumatoid arthritis.
Authors: C M Deighton, J Gray, D F Roberts, A J Bint, D J Walker
Journal: Annals of the Rheumatic Diseases (1992)

The interrelationships between P blood group phenotype, proteus antibodies and rheumatoid arthritis (RA) were investigated in 140 patients with RA and 114 of their siblings who did not have RA. In the group with RA P2 subjects had significantly higher titres of proteus antibodies than P1 patients. This was not observed in the group without RA, or for antibodies to Escherichia coli. Although C reactive protein was the best predictor of proteus antibodies in the group with RA, the P blood group had an independent and significant influence. These observations suggest a testable model in which asymptomatic carriage of proteus in the urinary tract may lead to antibody production, which in turn may be important in the pathogenesis of RA.
Sequential allergen desensitization of basophils is non‐specific and may involve p38 <scp>MAPK</scp>
Authors: S. K. Witting Christensen, I. Kortekaas Krohn, J. Thuraiaiyah, T. Skjold, J. M. Schmid, H. J. H. Hoffmann
Journal: Allergy (2014)

Abstract Background Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity. Methods We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63 + CD193 + SS Low basophils in a basophil activation test with 8 log‐dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with twofold to 2.5‐fold increasing allergen doses in 10 steps starting at 1 : 1000 of the optimal dose. Involvement of p38 mitogen‐activated protein kinase ( MAPK ) was assessed after 3 min of allergen stimulation ( n = 7). Allergen specificity was investigated by desensitizing cells from multi‐allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti‐IgE ( n = 10). Results Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median ( IQR ) 81.0% (66.3–88.8) to 35.4% (19.8–47.1, P &lt; 0.0001). CD63 MFI expression was reduced from 68 248 (29 336–92 001) to 30 496 (14 046–46 179, P &lt; 0.0001). Basophils from multi‐allergic subjects were desensitized with grass allergen. Challenge with grass allergen resulted in 39.6% activation (15.8–58.3). An unrelated challenge (birch, rDer p2 or anti‐IgE) resulted in 53.4% activation (30.8–66.8, P = 0.16 compared with grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6–92.8) to 26.1% (7.4–71.2, P = 0.047) and correlated with decrease in CD63 upregulation ( n = 7, r &gt; 0.79, P &lt; 0.05). Conclusion Desensitization attenuated basophil response rapidly and non‐specifically at a stage before p38 MAPK phosphorylation.
Replication of Genetic Polymorphisms Reported to Be Associated with Taxane-Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel
Authors: Jean E. Abraham, Qi Guo, Leila Dorling, Jonathan Tyrer, Susan Ingle, Richard Hardy, Anne-Laure Vallier, Louise Hiller, Russell Burns, Linda Jones, Sarah J. Bowden, Janet A. Dunn, Christopher J. Poole, Carlos Caldas, Paul P.D. Pharoah, Helena M. Earl
Journal: Clinical Cancer Research (2014)

Associations between taxane-related sensory neuropathy (TRSN) and single-nucleotide polymorphisms (SNP) have previously been reported, but few have been replicated in large, independent validation studies. This study evaluates the association between previously investigated SNPs and TRSN, using genotype data from a study of chemotherapy-related toxicity in patients with breast cancer.
Sex Chromosome Alterations Associate with Tumor Progression in Sporadic Colorectal Carcinomas
Authors: Lorena Bottarelli, Cinzia Azzoni, Francesca Necchi, Costanza Lagrasta, Elisa Tamburini, Tiziana D'Adda, Silvia Pizzi, Leopoldo Sarli, Guido Rindi, Cesare Bordi
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The X and Y chromosomes have been associated with malignancy in different types of human tumors. This study attempts to determine the involvement of X chromosome and pseudoautosomal regions (PAR) in sporadic colorectal carcinogenesis. Experimental Design: An allelotyping of X chromosome in 20 premalignant and 22 malignant sporadic colorectal tumors (CRC) from female patients and an analysis of losses [loss of heterozygosity (LOH)] on PARs from 44 CRCs and 12 adenomas of male patients were carried out. In male tumors, a fluorescence in situ hybridization analysis was done to identify which sex chromosome was possibly lost. Results: The LOH frequency in female CRCs was 46% with higher incidence in patients with tumor recurrence than in those who were disease-free (P &amp;lt; 0.01) and with a significant difference from adenomas (11%; P &amp;lt; 0.0001). The LOH rate of PARs in male CRCs was 37% with a frequency significantly higher in patients with recurrence (P &amp;lt; 0.03). These results were maintained also when data from PARs of all 66 male and female patients were cumulated (P &amp;lt; 0.05). LOH in PARs was significantly correlated with LOH at 5q (P &amp;lt; 0.01) and 18q (P &amp;lt; 0.01), early and late events, respectively, in colorectal carcinogenesis. Fluorescence in situ hybridization analysis in male patients with extensive PAR LOH revealed a preferential loss of the Y chromosome. Conclusions: Our data suggest a role for sex chromosome deletions in the malignant progression of sporadic CRCs and support the presence in the PARs of putative tumor suppressor genes involved in the progression of human sporadic CRCs.
Malignant Breast Tumors After Radiotherapy for a First Cancer During Childhood
Authors: Catherine Guibout, Elisabeth Adjadj, Carole Rubino, Akthar Shamsaldin, Emmanuel Grimaud, Mike Hawkins, Marie-Christine Mathieu, Odile Oberlin, Jean-Michel Zucker, Xavier Panis, Jean-Léon Lagrange, Nicolas Daly-Schveitzer, Jean Chavaudra, Florent de Vathaire
Journal: Journal of Clinical Oncology (2004)

Purpose To assess the specific role of treatment and type of first cancer (FC) in the risk of long-term subsequent breast cancer (BC) among childhood cancer survivors. Patients and Methods In a cohort of 1,814 3-year female survivors treated between 1946 and 1986 in eight French and English centers, data on chemotherapy and radiotherapy were collected. Individual estimation of radiation dose to each breast was performed for the 1,258 patients treated by external radiotherapy; mean dose to breast was 5.06 Gy (range, 0.0 to 88.0 Gy) delivered in 20 fractions (mean). Results Mean follow-up was 16 years; 16 patients developed a clinical BC, 13 after radiotherapy. The cumulative incidence of BC was 2.8% (95% CI, 1.0% to 4.5%) 30 years after the FC and 5.1% (95% CI, 2.1% to 8.2%) at the age of 40 years. The annual excess incidence increased as age increased, whereas the standardized incidence ratio decreased. On average, each Gray unit received by any breast increased the excess relative risk of BC by 0.13 (&lt; 0.0 to 0.75). After stratification on castration and attained age, and adjusting for radiation dose, FC type, and chemotherapy, a higher risk of a subsequent BC was associated with Hodgkin’s disease (relative risk, 7.0; 95% CI, 1.4 to 30.9). Conclusion The reported high risk of BC after childhood Hodgkin’s disease treatment seems to be due not only to a higher radiation dose to the breasts, but also to a specific susceptibility.
Effect of Taichi and treadmill exercise on quadriceps strength in patients with COPD
Authors: Fang Wang, B.T. He, Zhihui Qiu, Y.M. Luo, M.I. Polkey
Journal: European Respiratory Journal (2013)

Background: Traditionally exercise at 60% of maximum load has been considered necessary for effective rehabilitation. It has recently been reported that patients who develop quadriceps contractile fatigue during exercise training show greater training benefits than those who do not (Burtin ERJ 2012;40:338). It is unknown whether Tai Chi is more likely to produce quadriceps fatigue than conventional exercise. Therefore the purpose of the study was to seek the presence of quadriceps fatigue after Tai Chi exercise as compared to constant rate treadmill exercise at 60% of maximal load.  Methods: Tai Chi exercise and constant treadmill exercise at 60% of maximal load were performed in random order in 11 patients with COPD, mean age 62 years, mean BMI 24.4 kg/m 2  and mean FEV 1  61 % predicted. Both protocols lasted for 60 minutes. Unpotentiated quadriceps twitch tension (TwQ) elicited by magnetic stimulation of the femoral nerve was measured before and 20 and 60 minutes after each task.  Results, TwQ significantly decreased after Tai Chi exercise and were 8.7±1.8 Kg, 7.6±2.0 Kg and 7.8±2.9 Kg, before, 20minutes and 60 minutes after excise respectively (p 0.05). Minute ventilation was not different between the 2 tasks (peak 38.2±9.1 l/min and 41.7±15.5 l/min respectively)  Conclusion: Despite similar exertion, Tai Chi exercise but not treadmill exercise was associated with quadriceps fatigue and so could be an alternative method for pulmonary rehabilitation in patients with COPD.
Treatment of borderline diabetes: controlled trial using carbohydrate restriction and phenformin.
Authors: R J Jarrett, H Keen, J H Fuller, M McCartney
Journal: BMJ (1977)

A five-year therapeutic trial of carbohydrate restriction with or without phenformin (50 mg/day) was performed in men with borderline diabetes. The aim of treatment was to diminish the enhanced risk of cardiovascular disease and deterioration of glucose tolerance. Cardiovascular morbidity and mortality were not significantly affected by any form of treatment, alone or in combination. The predominant risk factor for cardiovascular morbidity and mortality and for overall mortality was the initial blood pressure level. The baseline plasma cholesterol concentration significantly predicted the onset of intermittent claudication. One implication of the results is that hypotensive treatment, supplemented when necessary with hypolipidaemic treatment, may be more effective in preventing the progression of arterial disease in people with mild to moderate glucose intolerance than conventional antidiabetic therapy.
Extension of patient choice is an invitation for private providers, warn critics
Authors: A. O'Dowd
Journal: BMJ (2011)

The government is extending its patient choice programme to include some community and mental health services from next year, but the move has prompted criticism that it will allow more private providers a stake in the NHS.

Health secretary Andrew Lansley has announced that from April of next year patients in England, who have so far been able to choose where to have non-urgent hospital care, will also be able to choose within other types of service.

New guidance from the Department of Health published on 19 July outlines how patients, guided by advice from their GP, will be offered a choice of “qualified” providers who meet NHS quality, prices, and contracts. There will be a phased implementation of …