tbuckley/cabot-search huggingface dataset:
Abstract P4-09-18: Triple Negative Breast (TNBC) Cancer in Hispanic Population: Clinicopathological and Recurrence Features
Authors: HL Gómez, RG Velarde, SP Neciosup, WR Cruz, LA Mas, JF Suazo, JA Pinto, CE Vigil, CS. Vallejos
Journal: Cancer Research (2010)

Abstract Background: TNBC is characterized by the lack of hormonal receptors and HER2 expression and occurs most frequently in Black and Hispanic than in Caucasian population. We compare clinicopathological and outcome variables between TNBC and non-TNBC Hispanic patients (pts). Methods: We reviewed 1044 cases of operable breast cancer treated at INEN, Lima-Perú (2000 — 2002). Phenotypes were categorized by IHC into TNBC and non-TNBC. Variables in both groups were compared with the X2 test. We used Kaplan-Meier method for comparing disease free survival (DFS), overall survival (OS), post recurrence survival by phenotype (TNBC v non-TNBC) and the hazard rate (HR) for different times. Results: 212 pts (20.3%) were TNBC and 832 non-TNBC (79.7%); median for age was 48 and 49 years (y), for tumor size 3.5 and 2.9cm; TNBC was more likely to have involved nodes (55.7 v 45.6%; P=0.009), tumors &amp;gt; 5cm (14.2 v 8.1%; P=0.011) and histological grade 3 (62.7 v 29.0%; P&amp;lt;0.001). Recurrence rates (RR) were 25.9 v 22.5% (TNBC v non-TNBC). TNBC and non-TNBC present different RR. Recurrence sites and phenotype Median of follow-up was 7.63 and 7.57y; there was not significant differences for DFS between TNBC and non-TNBC (72.8 v 76.6%;P=0.057), but in OS had differences (73.2 v 79.9%; P=0.014). The HR for recurrence was calculated to 1y (7.9 v 2.7%); 2y (8.8 v 5.8%); 3y (8.0 v 6.5%); 4y (2.7 v 3.3%) and to 5y (3.5 v 3.9%) and the HR for death to 1y (4.3 v 0.8%); 2y (6.7 v 2.6%); 3y (8.4 v 3.8%); 4y (5.5 v 2.8%) and to 5y (2.6 v 4.5%) for TNBC and non-TNBC, respectively. HR for recurrence and death was higher in TNBC until the first 3y and 4y, respectively, then HR were similar for both groups. Post recurrence survival show differences between TNBC and non-TNBC (HR=1.7; 95% IC 1.2 - 2.3; P=0.002). Conclusion: In early breast cancer, TNBC is more aggressive than non-TNBC; present a higher RR in brain, distant nodes and other soft tissues; strongly time-dependent HR for recurrence and death, and a worse Post recurrence survival. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-18.
Safety of Two-Step Graded Challenges to Beta-Lactams Using a Single-Blinded Placebo-Controlled Protocol
Authors: Melissa Iammatteo, Denisa Ferastraoaru, Santiago Alvarez Arango, Niharika Thota, Ayobami Akenroye, Elina Jerschow
Journal: Journal of Allergy and Clinical Immunology (2016)
IMPACT OF LEFT-TO-RIGHT VENTRICULAR SHUNTS ON CIRCULATING MICRORNA EXPRESSION
Authors: Takashi Honda, Keiko Nomoto, Manabu Takanashi, Eri Mineo, Atsushi Kitagawa, Hisashi Ando, Sumito Kimura, Masahiro Ishii
Journal: Journal of the American College of Cardiology (2016)
Stat Bite Colorectal Cancer Mortality Rates
Authors: Brenda K. Edwards
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Stat Bite Colorectal Cancer Mortality Rates Get access Brenda K. Edwards Brenda K. Edwards Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 17, 4 September 1991, Page 1203, https://doi.org/10.1093/jnci/83.17.1203 Published: 04 September 1991
The importance of clinical reasoning in the training of all medical practitioners
Authors: David Levine
Journal: Journal of the Royal Society of Medicine (2014)

Sam Leinster presents a very well-argued case for more generalists and describes clearly some of the barriers in the way of change. He states that ‘All doctors are taught general consultation and clinical reasoning skills’ but, while the first part is true, I wonder about the second. I am happy to be corrected, but my understanding is that only a minority of UKmedical schools have curricula that incorporate formal teaching of clinical reasoning as we now understand it. Its inclusion in postgraduate training may not be much better. Although there is still no consensus on a single best way to teach and learn the cognitive processes and errors that affect our decisions, there is growing recognition that effective clinical reasoning is vital for accurate and safe diagnosis and management. Strangely, the General Medical Council’s key publication ‘Tomorrow’s Doctors’ makes no mention of clinical reasoning in its recommendations for education and training. Acquiring clinical reasoning skills early can help doctors to make the most of the, often limited, clinical experience available in relatively short training programmes. Arguably, it is skill in clinical reasoning that underpins generalist expertise although wide experience is also essential. It may be that some will choose a generalist role before becoming specialists and others will choose the opposite path; ensuring that clinical reasoning is taught properly to all medical students and doctors might help both groups.
Increased 24-Hour Energy Expenditure in Cigarette Smokers
Authors: Angela Hofstetter, Yves Schutz, Eric Jéquier, John Wahren
Journal: New England Journal of Medicine (1986)

We studied the effect of smoking on energy expenditure in eight healthy cigarette smokers who spent 24 hours in a metabolic chamber on two occasions, once without smoking and once while smoking 24 cigarettes per day. Diet and physical exercise (30 minutes of treadmill walking) were standardized on both occasions. Physical activity in the chamber was measured by use of a radar system. Smoking caused an increase in total 24-hour energy expenditure (from a mean value [±SEM] of 2230±115 to 2445±120 kcal per 24 hours; P<0.001), although no changes were observed in physical activity or mean basal metabolic rate (1545±80 vs. 1570±70 kcal per 24 hours). During the smoking period, the mean diurnal urinary excretion of norepinephrine (±SEM) increased from 1.25±0.14 to 1.82±0.28 μg per hour (P<0.025), and mean nocturnal excretion increased from 0.73±0.07 to 0.91±0.08 μg per hour (P<0.001). These short-term observations demonstrate that cigarette smoking increases 24-hour energy expenditure by approximately 10 percent, and that this effect may be mediated in part by the sympathetic nervous system. The findings also indicate that energy expenditure can be expected to decrease when people stop smoking, thereby favoring the gain in body weight that often accompanies the cessation of smoking. (N Engl J Med 1986; 314:79–82.)
The physical basics of magnetic-guided capsule endoscopy of the stomach and results of a feasibility study in the porcine stomach
Authors: T. Rupprecht, C. Rupprecht, S. Mühldorfer, M. Vieth, M. Zapke
Journal: Endoscopy (2012)

We read with interest the gastric capsule paper by Rey et al. [1]. We would like to report on similar investigations that we undertook back in 1999 with a project group from the University of Erlangen-Nürnberg led by T. Rupprecht and M. Zapke. The investigations defined the technical specifications of a prototype for magnetic-guided endoscopy in children and adults, which were mainly to develop a system that did not require external cables and that allows freely adjustable movement of the capsule in three dimensions. These results have not yet been published.
Abstract 4605: Combinatory use of synthetic and natural ER beta modulators in treating hormonal-therapy-resistant breast tumors
Authors: Manonmani Ganapathy, Hareesh Babu Bhaskaran Nair, Nameer Kirma, Naveen Krishnegowda, Ratna Vadlamudi, Tagliaferri Mary, Cohen Isaac, Rajeshwar Tekmal
Journal: Cancer Research (2010)

Abstract Although systemic hormone therapies that either block local estrogen production by aromatase inhibitors (AI) such as letrozole or block actions of estrogen/ER actions by anti-estrogens like tamoxifen are well tolerated, the development of resistance to these agents is still a major concern. We have investigated whether treatment of letrozole resistant breast cancer cells with selective ER beta agonists (synthetic and of natural origin) in combination with letrozole restored sensitivity to this AI. We performed similar combination treatment of tamoxifen resistant cells with ER beta agonists and tamoxifen. To test whether combination therapy restores sensitivity to letrozole, we have treated letrozole resistant breast cancer cells LTLTca, derived from MCF-7-aromatase tumors resistant to letrozole] with either letrozole alone or with a combination of letrozole and DPN. Compared to single agents, combination treatment not only restored sensitivity to letrozole but also resulted in decreased cell proliferation and increased apoptosis as well as increased ERβ and decreased ERα levels in these cells. When we tested the growth of letrozole resistant breast tumors using a postmenopausal xenograft model, combination therapy not only restored sensitivity to letrozole but resulted in decreased tumor growth. Long term treatment using nanoparticle- encapsulated DPN and letrozole resulted in a significant and sustained decrease of tumor growth. On the other hand, nanoparticle-encapsulated letrozole treatment resulted in tumor resistance to therapy in13 weeks. In search for better and safer therapeutic modulators for ER, We have tested Liquiritigenein and Nyasol as selective natural ER beta agonists. Effects of these compounds on cell growth was tested in different breast cancer cells including MCF-7, MDA-MB-231, tamoxifen resistant MCF-7, and LTLT-Ca. In tamoxifen resistant MCF-7 breast cancer cells 15uM of liquiritigenin and Nyasol showed ∼70% and 90% of cell death, respectively. Different biological activities of liquiritigenin have been reported including anti-inflammatory activity. Combination of liquiritigenin and Nyasol with letrozole diminished cell growth in MCF-7, MCF-TAM, MCF-Aro and LTLT-Ca cells. Combination therapy using ER beta agonists like DPN, liquiritigenin and nyasol may offer superior response and restore the sensitivity to the current AI and anti-estrogens. Our study suggest a novel role of ER beta agonists as valuable therapeutic modulators to treat endocrine sensitive as well as resistant tumors. (Supported by NIH/NCI CA 750118 &amp; P30 CA 54174, RRT) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4605.
Abstract 2676: Unusual binding of TMP in two different sites in the binary complex with the Q35S/N64F double mutant of human dihydrofolate reductase
Authors: Vivian Cody, Jennifer Piraino, James Pace, Sherry F. Queener
Journal: Cancer Research (2010)

Abstract In an effort to understand the role of specific active site residues in modulating the binding selectivity of inhibitors against dihydrofolate reductase (DHFR) from different species, a series of single and double mutants of DHFR were made at positions 35 and 64 of human (h) DHFR. To explore sequence differences between human and the pathogenic organisms Pneumocystis carinii (pc) and Pneumocystis jirovecii (pj) DHFR, the causative agent of Pneumocystis pneumonia (PcP) in patients with AIDS, kinetic data were measured for trimethoprim, used for treatment of AIDS-related pneumonia. Crystal structure data are reported for the Q35S/N64F double mutant of hDHFR as a binary complex with trimethoprim (TMP). These substitutions make the human enzyme resemble a cross between pjDHFR which has Ser/Ser at these positions and pcDHFR which has Lys/Phe at these sites. Kinetic data show enhanced affinity for the binding of TMP to this double mutant (Ki 604 nM) compared to wild type hDHFR (Ki 1757 nM). The Ki of TMP is 43 nM for pjDHFR and 222 nM for pcDHFR. Structural data for the binary complex of TMP with this double mutant of hDHFR revealed the unexpected binding of two copies of TMP; one bound in the normal binding site while the other occupies a shallow pocket different from that involved in binding the γ-glutamate of folate substrates or inhibitors. The trimethoxyphenyl ring of the second TMP makes a series of hydrophobic contacts with the trimethoxyphenyl ring of the first TMP and with the phenyl ring of residue F31 and the mutated F64 in this structure. Structural data for the binary complex of wild type hDHFR with TMP does not indicate such binding. The conformation of the two TMP in the double mutant complex differ significantly from each other and from that observed for the wild type hDHFR binary complex. Analysis of all DHFR TMP complexes reveals the bridge torsion angles fall into two broad ranges and the two TMP in the mutant hDHFR complex fall into the less populated group. These data suggest that the combination of hydrophobic contacts from the normal F31 in hDFHR and the mutant F64 provide a unique environment to create sufficient van der Waals contact energy to stabilize binding in this unusual site. Supported in part by NIH GM51670 (VC). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2676.
Surgical and Gynæcological Nursing.
Journal: JAMA (1922)

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TRATAMIENTO ENDOSCOPICO DEL DIVERTICULO DE ZENKER: EFICACIA Y SEGURIDAD EN UNA SERIE DE CASOS
Authors: T Revuelto Artigas, Y Arguedas Lázaro, A Lué, P Lacarta García, Y Ber Nieto, C Aznar, MA Simón Marco, J Ducons García
Journal: Endoscopy (2012)

Introducción: El divertículo de Zenker (DZ) es una enfermedad poco frecuente (prevalencia 0,01–0,11% de la población) que afecta sobretodo a pacientes con edad avanzada. El tratamiento estándar es la cirugía abierta con diverticulotomía asociada a miotomía del cricofaríngeo. En pacientes ancianos o con elevado riesgo quirúrgico, una alternativa es el tratamiento endoscópico. Objetivo: Demostrar la eficacia y la seguridad del tratamiento endoscópico del DZ en pacientes añosos. Metodo: Estudio retrospectivo de serie de casos, recogiendo todos los casos realizados en nuestro servicio desde enero de 2009 a junio de 2012. Se utiliza un endoscopio flexible y diverticuloscopio Wilson -Cook, se procede a la exposición del tabique del divertículo y posteriormente a la sección del mismo con la pinza de Liga-Sure o esfinterótomo de aguja Boston Scientific. Se analizaron las siguientes variables: la eficacia definida como la resolución de los síntomas derivados de DZ y la seguridad, valorando las complicaciones. Resultados: Se realizaron 10 casos (5M y 5H) con una media de edad de 82 años y un rango de seguimiento desde 2 años a 1mes tras la técnica. En 6 de los pacientes se realizó el tratamiento endoscópico con sedación profunda y los restantes precisaron de anestesia general. La sección del musculo se realizó, en la mayoria de los pacientes (6 casos) con Liga-Sure mientras los otros 2 casos se hicieron con esfinterótomo. El tratamiento fue eficaz con una única sesión en el 85,7% de los casos. No hubo ningún fallecimiento por le procedimiento, perforación o hemorragia grave; en 2 casos se produjo hemorragia leve durante el procedimiento que se trató durante el mismo acto, con la colocación de hemoclips. Además los pacientes sólo precisan de un día de hospitalización y con una reintroducción de la nutrición oral precoz disminuyendo asi la morbilidad de estos pacientes ingresados. Conclusiones: El tratamiento endoscópico del Divertículo de Zenker es una alternativa segura y eficaz al tratamiento quirúgico en pacientes añosos o con elevado riesgo de cirugía, con complicaciones mínimas y con menor estancia hospitalaria.
A8.01 Systemic and local MIRNAS expressionin patients with osteoarthritis
Authors: R Shumnalieva, D Kachakova, S Monov, R Kaneva, ZI Kolarov, R Rashkov
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Micro-ribonucleic acids (miRNAs) are a class of small, non-coding RNAs that regulate the gene expression on posttranscriptional level. Abnormal miRNAs expression levels have been described in osteoarthritis (OA)patients – in synovial membrane, joint cartilage, chondrocytes, synovial fluid,&nbsp;peripheral blood. miRNAs control the chondrogenesis, osteoclastogenesis, cartilage homeostasis, catabolism and tissue repair. Recent studies have shown that miRNAs contribute to the development of OA through regulating the mechanotransduction or inflammation. <h3>Objective</h3> The aim of our study was to comparethe systemic and local expression of certain miRNAsin OA patients and to establish a possible local dysregulation in their expression levels. <h3>Materials and methods</h3> miRNAs expression levels were compared between matched peripheral blood (PB) and synovial fluid (SF) samples from 13 OA patients using quantitative real-time polymerase chain reaction (qPCR), SybrGreen technology. Relative changes of gene expression levels of miR-146a, miR-155, miR-223 and miR-193b were calculated by 2<sup>-∆∆Ct</sup> method and &nbsp;SPSS were used for statistical analysis. RNU6B gene was used as a reference control for normalisation. <h3>Results</h3> We found difference in the expression levels of the chosen miRNAsbetween PB and SF inOA. miR-223 were downregulated in SF of all 13 (100%) patients when compared to PB (p &lt; 0.05). Higher SF levels were found for miR-155 and miR-193b when compared to PB (53.85% and 76.92% of the patients, respectively). No statistical significant difference was observed between the systemic and local expression of miR-146a. <h3>Conclusions</h3> Our results show that the differences between the systemic and local expression of certain microRNAs in OA could be used in the clinical practice as possible biomarkers for disease activity and severity. Larger sets and functional analysesare needed to establish if these miRNAs play crucial role in the disease pathogenesis and will reveal the potency of new therapeutic targets.
AB0487 Etanercept increases step activity in patients with active rheumatoid arthritis and short disease duration
Authors: P. Willeke, C. Winter, H. Schotte, H. Becker, J. Marx, M. Gaubitz, D. Rosenbaum
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> There is strong evidence that TNF-alpha inhibitors improve disability and activities of daily living in patients with active rheumatoid arthritis (RA). However, the supporting data have been generated mainly by the health-assessment-questionnaire (HAQ) that is based on subjective variables. It is desirable to add objective parameters reflecting patients’ activities to the outcome parameters in RA. The StepWatch™ activity monitor (SAM) is an ankle worn step counter and an accurate instrument to measure real world activities of daily living. <h3>Objectives</h3> Our purpose was to investigate whether step counts measured with the SAM increase during a therapy with the TNF-alpha inhibitor etanercept (ETN) in patients with active RA and further to correlate the data with the results of the HAQ and the DAS28 in these patients. <h3>Methods</h3> We included 26 patients with active RA who started a therapy with ETN 50 mg subcutaneously/week. Before therapy, after 4 weeks, and after 12 weeks step activity was measured for a period of 7 days with the SAM. The results were also correlated to the HAQ and the DAS28. <h3>Results</h3> 23 patients completed the study. A significant increase of the steps per hour was measured after 12 weeks in patients with shorter disease duration of RA (&lt;5 years, n=10), (407 steps/h ± 161 vs. 512 steps/h ± 134, p≤0.02). The HAQ and the DAS28 improved significantly in this group after 12 weeks (HAQ: 1.49±0.82 at baseline vs. 0.85±0.71 after week 12, p&lt;0.01 and DAS28: 5.21±0.72 vs. 3.2±0.68, p&lt;0.01). In patients with longer disease duration (n=13) no significant increase of step activity was noted after 12 weeks (467 steps/h ± 178 vs. 407 steps/h ± 108, p=0.53) although also in this group a significant improvement of the HAQ or the DAS28 was noted (HAQ: 1.71±0.89 at baseline vs. 1.02±0.56 after week 12, p&lt;0.01 and DAS28: 5.09±0.89 vs. 3.3±1.12, p&lt;0.01). <h3>Conclusions</h3> Measuring the step activity by SAM reveals an objective real life parameter of functional capacity of RA patients. If ETN is initiated in patients with shorter disease duration an increase of step activity could be achieved beside the developments in the DAS28 or the HAQ. However, the increase of step activity could not be achieved in patients with long standing disease duration. This emphasizes the need for an early effective therapy before RA activity leads to potentially irreversible destructions of the joints. <h3>Disclosure of Interest</h3> P. Willeke Grant/Research support from: Pfizer Inc., C. Winter: None Declared, H. Schotte: None Declared, H. Becker: None Declared, J. Marx: None Declared, M. Gaubitz Grant/Research support from: Pfizer Inc., Abbott Immunology Pharmaceuticals, Roche Pharma, Consultant for: Pfizer Inc., D. Rosenbaum: None Declared