tbuckley/cabot-search huggingface dataset:
Abstract C07: Impact of human epidermal-growth-factor receptor-2 (HER2) expression and two BRCA1/2 pathogenic mutations with outcome of the breast cancer patients
Authors: Hamid Fiuji, Bahram Bibak, Mina Maftouh, Reza Mirhafez, Amir Avan
Journal: Cancer Research (2013)

Abstract Background/Aim: Breast cancer is a major unsolved health problem with poor prognosis; thus, identification of prognostic biomarkers is warranted. The aim of present study was to 1) evaluate the prevalence of the common mutations in the BRCA1 (C61G) and BRCA2 (6174delT) genes in Iranian patients with breast cancer, 2) and to investigate the correlation of these mutation and also HER-2, P53 and Ki67 expression with clinical outcome of the patients treated with standard regimen chemotherapy. Patients and methods: 168 patients, including eighty healthy volunteers, were selected for BRCA1/2 mutation screening. DNA was isolated from blood samples and then frequency of 6174delT and C61G were evaluated in the patients using amplication refractory mutation system (ARMS) PCR and also by sequencing of the related site of genes in positive patients. Expressions of HER2, P53 and Pi27 were evaluated by ELISA, and their correlations with clinical outcome were investigated. We also analyzed data on overall survival according to clinicopathological characteristics of the patients. Results: Consistent with previous findings, our analysis resulted in the identification of concomitant germline BRCA1 and BRCA2 mutations in none of the patients. Moreover, the present of the mutations were explored and confirmed by sequencing analysis of the positive and control samples, as well as in none of the patient samples. Furthermore, high expression of HER-2 and Ki67 were found in 42 and 66% of the patients, respectively, and were associated with significantly shorter OS. HER2 expression was associated with risk of death (e.g., hazard ratio= 1.6; 95%CI, 1.1–2.3, P&amp;lt;0.05). Conclusions: our results suggest that Iranian breast cancer patients represent the presence of additional kinds of BRCA1/2 alteration (such as genomic rearrangements/deletion) or by mutations on/different breast cancer related genes. However, ethnic background can also influence on prevalence of the mutations. These results prompt further studies as well as research on the biological role of these mutations in breast cancer. Nevertheless, larger multicenter studies are critical to explore the role of emerging biomarkers before planning of prospective trials. Note: This abstract was not presented at the conference. Citation Format: Hamid Fiuji, Bahram Bibak, Mina Maftouh, Reza Mirhafez, Amir Avan. Impact of human epidermal-growth-factor receptor-2 (HER2) expression and two BRCA1/2 pathogenic mutations with outcome of the breast cancer patients. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C07.
Essential Hypertension and Aldosterone
Authors: ELEANOR H. VENNING, INGE DYRENFURTH, JOHN B. DOSSETOR, JOHN C. BECK
Journal: Circulation (1961)

Serial determinations of the urinary excretion of aldosterone have been made in hypertensive patients. Although the majority of patients with benign essential hypertension excrete amounts of aldosterone within the normal range, the mean excretion of 26 patients was significantly higher than that observed in normotensive individuals. When renal complications were present, the mean excretion was still further increased and in patients with malignant hypertension all the values were above the normal range. The mean excretion of the tetrahydro metabolite of aldosterone was also found to be higher in patients with essential hypertension. These patients have a normal response to adrenocorticotrophic hormone stimulation, urinary and plasma corticosteroids, as well as urinary aldosterone, showing comparable increases. The aldosterone content of adrenal glands obtained post mortem from two patients with malignant hypertension was within the range observed by other investigators in primary aldosteronism.
Local Control Following Breast-Conserving Surgery for Invasive Cancer: Results of Clinical Trials
Authors: M. Morrow, J. R. Harris, S. J. Schnitt
Journal: JNCI Journal of the National Cancer Institute (1995)

Prospective, randomized clinical trials have demonstrated that the alternatives of mastectomy or conservative surgery plus radiation therapy provide equivalent survival for patients with invasive breast cancer. The identification of a subset of women who could undergo conservative surgery without radiotherapy would avoid the costs, inconvenience, and complications of radiotherapy and is an important research goal. Four randomized trials comparing conservative surgery alone with conservative surgery plus radiotherapy have demonstrated an average reduction in the risk of disease recurrence in the breast of 84% with the use of radiotherapy. No significant differences in survival have been observed, although the available studies lack sufficient numbers of patients to demonstrate a potential small, but clinically important, survival advantage for patients treated with radiotherapy. Subset analysis in the randomized trials and prospective studies of highly selected patients have failed to consistently identify a group of patients who do not benefit from radiation therapy. Any recurrence of breast cancer is psychologically devastating, and fewer than one half of the patients who have had disease recurrence after conservative surgery alone have undergone further breast-conserving treatment. At present, a group of patients who do not require radiotherapy has not been reproducibly identified, and radiotherapy should remain a part of breast-conserving therapy for invasive carcinoma. [J Natl Cancer Inst 1995;87:1669–73]
P233 COPD and Me: the development and implementation of an individual patient management plan and hand-held record
Authors: T. Robinson, S. Shires, C. Fletcher, J. Parrington, J. Norell, S. Mabbett
Journal: Thorax (2010)

<h3>Background</h3> People with chronic obstructive pulmonary disease (COPD) face multiple challenges living with a progressive and debilitating disease. It also results in heavy use of medical services and frequent hospital admissions. Patients need information, self care skills, education and training to be able to self manage their condition. Following extensive consultation with local COPD patients and the respiratory multidisciplinary team (MDT), an individualised management plan was formulated and implemented into primary, intermediate and secondary care. <h3>Aims</h3> The aim of the record is to increase the knowledge and control patients have of their disease and provide patients and carers with easily identifiable and accessible sources of support <h3>Methods</h3> Fifty COPD patients completed the Bristol COPD Knowledge Questionnaire. The results highlighted many knowledge gaps, despite the mean length of time from diagnosis being &gt;5 years. COPD patients and carers also attended a focus group, where the same knowledge gaps were highlighted. This group also provided advice on how the information should be presented and the type of language and terminology that should be used. A second focus group consisting of members of the respiratory MDT was then held and the final format for the record agreed. <h3>Discussion</h3> The information found in the hand-held record is based on identified gaps in knowledge in the local COPD population and includes: What COPD is Generic COPD management Individual patient and carer management Goal setting Pharmacological management Exacerbation management End of life supportive care Telehealth The hand-held record has been well received by patients and health care professionals alike. The document is a ‘live’ document and is being further developed. Patient and carer education groups have been run over a 4-week period. <h3>Conclusion</h3> Developing and implementing the COPD hand-held record has highlighted the knowledge gaps in the identification, management and education needs not only in patients with COPD but in health care professionals. Working in an integrated manner with patients, carers and colleagues from primary, intermediate and secondary care has helped bridge the knowledge gaps and led to better outcomes for patients and health care professionals alike.
Cimetidine in the Treatment of Acute Intermittent Porphyria
Authors: E. Baccino
Journal: JAMA (1989)

<h3>To the Editor.—</h3> Horie et al<sup>1</sup>recently reported that oral cimetidine in an 800-mg daily dose decreased urinary excretion of 8-aminolevulinic acid (ALA) in a patient with acute intermittent porphyria who was in remission. This study was based on the inhibitory effect of cimetidine on hepatic cytochrome P-450 synthesis and heme oxidase activity, which results in decreased heme consumption with subsequent inhibition of ALA synthetase through a negative feedback mechanism.<sup>2</sup>The aim of this letter is to confirm these biologic changes observed by Horie et al and furthermore to see if they are associated with clinical improvement. <h3>Report of a Case.—</h3> A 38-year-old white female with a well-documented familial (mother, one sister, and one brother) and personal (two previous attacks) history of acute intermittent porphyria was given 400 mg of cimetidine twice daily from day 0 to day 14. Urinary excretion of ALA and porphobilinogen was measured 7
Involving patients and the public in healthcare operational research
Authors: J. Welsman, A. Gibson, J. Heaton, N. Britten
Journal: BMJ (2014)

We are delighted to see The BMJ leading the promotion of meaningful public and patient involvement (PPI) in research,1 and we support Vayena’s contention that PPI in initiating health research is an underplayed aspect of this “patient revolution.”2 It may seem unrealistic to embed PPI in health research within a major organisation, but since …
Smart pH‐Responsive Nanocarriers Based on Nano‐Graphene Oxide for Combined Chemo‐ and Photothermal Therapy Overcoming Drug Resistance
Authors: Liangzhu Feng, Kunyang Li, Xiaoze Shi, Min Gao, Jian Liu, Zhuang Liu
Journal: Advanced Healthcare Materials (2014)

A pH‐responsive nanocarrier is developed by coating nanoscale graphene oxide (NGO) with dual types of polymers, polyethylene glycol (PEG) and poly(allylamine hydrochloride) (PAH), the latter of which is then modified with 2,3‐dimethylmaleic anhydride (DA) to acquire pH‐dependent charge reversibility. After loading with doxorubicin (DOX), a chemotherapy drug, the obtained NGO‐PEG‐DA/DOX complex exhibits a dual pH‐responsiveness, showing markedly enhanced cellular uptake under the tumor microenvironmental pH, and accelerated DOX release under a further lowered pH inside cell lysosomes. Combining such a unique behavior with subsequently slow efflux of DOX, NGO‐PEG‐DA/DOX offers remarkably improved cell killing for drug‐resistant cancer cells under the tumor microenvironmental pH in comparison with free DOX. Exploiting its excellent photothermal conversion ability, combined chemo‐ and photothermal therapy is further demonstrated using NGO‐PEG‐DA/DOX, realizing a synergistic therapeutic effect. This work presents a novel design of surface chemistry on NGO for the development of smart drug delivery systems responding to the tumor microenvironment and external physical stimulus, with the potential to overcome drug resistance.
Quantification of hemodynamics in primary pulmonary hypertension with magnetic resonance imaging.
Authors: A A Tardivon, E Mousseaux, F Brenot, J Bittoun, O Jolivet, E Bourroul, P Duroux
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The aims of this study were first to analyze pulmonary flow differences between patients with primary pulmonary hypertension (PPH) and volunteers, and second to determine whether magnetic resonance (MR) 3D Fourier encoding velocity imaging is capable of assessing hemodynamics in PPH. Pulmonary and aortic flows were quantified with MR imaging in 13 patients with PPH confirmed by right heart catheterization (RHC) within the same week and in 10 volunteers. MR pulmonary antegrade velocities, acceleration time (defined as the time from the onset of flow to the peak velocity), and arterial distensibility (maximal surface-minimal surface/minimal surface) were significantly different in patients (p < 0.05). MR pulmonary and aortic flow volumes correlated well with each other in the two populations (r = 0.98). Agreement between MR and RHC data was low: for the right cardiac output (mean difference) the 95% confidence interval was -0.88 to -0.22 L/min and for the right stroke volume 2.83 to 9.71 ml. However, the high coefficient correlations found between the two techniques showed that MR data could be used as indicators of right hemodynamics. 3D Fourier encoding-velocity sequence is a reliable noninvasive flow measurement method for the quantification of right hemodynamics in patients with PPH.
Inhaled Corticosteroids in Patients With Chronic Obstructive Pulmonary Disease
Authors: Yoon K. Loke
Journal: JAMA (2009)

To the Editor: We are concerned about possible data discrepancies in the systematic review and meta-analysis of inhaled corticosteroids in patients with stable chronic obstructive pulmonary disease (COPD) by Dr Drummond and colleagues. In the analysis of pneumonia events from the study by Burge et al, Drummond et al reported 87 of 372 events in the inhaled corticosteroid group vs 101 of 370 events in the control group, reflecting a control event rate that is considerably higher than any other trial in the metaanalysis. However, the trial publication actually reports on “lower respiratory serious adverse events” rather than pneumonia events. The company trial report from the GlaxoSmithKline Clinical Trial Register (FLTB3054, the identification number for the study by Burge et al) shows that there were only 18 and 8 pneumonia events in the fluticasone and control groups, respectively. We believe that a substantial proportion of the lower respiratory serious adverse events data in the trial publication were actually COPD exacerbations. We question the inclusion of the trial by Wedzicha et al in this meta-analysis. For an unconfounded comparison to be possible, Drummond et al should have selected trials in which the sole difference between the intervention arms was the use of an inhaled corticosteroid. In the context of a metaanalysis focusing on inhaled corticosteroids, the study by Wedzicha et al represents a confounded comparison of fluticasone/salmeterol combination vs tiotropium. The corticosteroid-treated group differed in 2 important respects from the control tiotropium arm: patients received an inhaled corticosteroid, and patients received salmeterol. Any differences in relative treatment effect could have arisen from the administration of salmeterol rather than from the inhaled corticosteroid. Finally, for the Calverley et al 2007 trial (reference 12 in the study by Drummond et al), we refer to the updated pneumonia data in the UK Medicines and Healthcare Regulatory Authority safety newsletter. Drummond et al appear to have estimated the number of pneumonia events using the percentage probability of pneumonia (based on KaplanMeier analysis) for this trial. However, the percentage probability of pneumonia does not provide an exact estimate of the absolute event rate for pneumonia, as is apparent from the different figures presented within the regulatory agency document. These issues argue for meta-analysis on adverse effects to include data from clinical trial registries as well as those submitted to regulatory agencies to obtain accurate estimates of risk. Moreover, consistent and clear reporting of adverse events is essential. Resolving these discrepancies in the data are likely to remove the substantial heterogeneity that exists in this meta-analysis of pneumonia.
Efficacy and Tolerability of Mirabegron, a β3-Adrenoceptor Agonist, in Patients with Overactive Bladder: Results from a Randomised European–Australian Phase 3 Trial
Authors: Vik Khullar, Gerard Amarenco, Javier C. Angulo, Javier Cambronero, Kjetil Høye, Ian Milsom, Piotr Radziszewski, Tomasz Rechberger, Peter Boerrigter, Ted Drogendijk, Marianne Wooning, Christopher Chapple
Journal: European Urology (2012)
Umbilical Cord Mercury Concentration as Biomarker of Prenatal Exposure to Methylmercury
Authors: Philippe Grandjean, Esben Budtz-Jørgensen, Poul J. Jørgensen, Pál Weihe
Journal: Environmental Health Perspectives (2005)

Biomarkers are often applied to assess prenatal exposure to methylmercury in research and surveillance. In a prospective study in the Faroe Islands, the main exposure biomarkers were the mercury concentrations in cord blood and maternal hair obtained at parturition. We have now supplemented these exposure biomarkers with mercury analyses of umbilical cord tissue from 447 births. In particular, when expressed in relation to the dry weight of the tissue, the cord mercury concentration correlated very well with that in cord blood. Structural equation model analysis showed that these two biomarkers have average total imprecision of about 30%, which is much higher than the laboratory error. The imprecision of the dry-weight-based concentration was lower than that of the wet-weight-based parameter, and it was intermediate between those of the cord blood and the hair biomarkers. In agreement with this finding, regression analyses showed that the dry-weight cord mercury concentration was almost as good a predictor of methylmercury-associated neuropsychologic deficits at 7 years of age as was the cord-blood mercury concentration. Cord mercury analysis can therefore be used as a valid measure of prenatal methylmercury exposure, but appropriate adjustment for the imprecision should be considered.
Chronic lymphocytic leukemia presenting in association with aplastic anemia
Authors: Jeffrey A. Zonder, Michael Keating, Charles A. Schiffer
Journal: American Journal of Hematology (2002)

Abstract An unusual case of chronic lymphocytic leukemia presenting in association with aplastic anemia is discussed, along with a review of the few previously reported cases. Possible humoral and cellular autoimmune mechanisms are examined as possible causes of marrow aplasia in this setting. Am. J. Hematol. 71:323–327, 2002. © 2002 Wiley‐Liss, Inc.
Antileukemic effect of nitrous oxide in a patient with chronic myelogenous leukemia
Authors: Kazuma Ikeda, Toshihiko Aosaki, Yusuke Furukawa, Masatsugu Ohta, Yasuhiko Kano, Akihiko Tsuboyama, Shinobu Sakamoto, Yasusada Miura, Kaori Sakuraya, Nobuo Fuke, Tatsuya Kubota
Journal: American Journal of Hematology (1989)
Phylogenetic Relationships of Class II Fumarase Genes from Trichomonad Species
Authors: Delphine Gerbod, Virginia P. Edgcomb, Christophe Noël, Stepánka Vanacova, René Wintjens, Jan Tachezy, Mitchell L. Sogin, Eric Viscogliosi
Journal: Molecular Biology and Evolution (2001)

Class II fumarase sequences were obtained by polymerase chain reaction from five trichomonad species. All residues known to be highly conserved in this enzyme were present. Nuclear run-on assays showed that one of the two genes identified in Tritrichomonas foetus was expressed, whereas no fumarase transcripts were detected in the related species Trichomonas vaginalis. These findings corroborate previous biochemical data. Fumarase genes were also expressed in Monocercomonas sp. and Tetratrichomonas gallinarum but not in Pentatrichomonas hominis, Trichomonas gallinae, Trichomonas tenax, and Trichomitus batrachorum under the culture conditions used. Molecular trees inferred by likelihood methods reveal that trichomonad sequences have no affinity to described class II fumarase genes from other eukaryotes. The absence of functional mitochondria in protists such as trichomonads suggests that they diverged from other eukaryotes prior to the alpha-proteobacterial symbiosis that led to mitochondria. Furthermore, they are basal to other eukaryotes in rRNA analyses. However, support for the early-branching status of trichomonads and other amitochondriate protists based on phylogenetic analyses of multiple data sets has been equivocal. Although the presence of hydrogenosomes suggests that trichomonads once had mitochondria, their class II iron-independent fumarase sequences differ markedly from those of other mitochondriate eukaryotes. All of the class II fumarase genes described from other eukaryotes are of apparent alpha-proteobacterial origin and hence a marker of mitochondrial evolution. In contrast, the class II fumarase from trichomonads emerges among other eubacterial homologs. This is intriguing evidence for an independent acquisition of these genes in trichomonads apart from the mitochondrial endosymbiosis event that gave rise to the form present in other eukaryotes. The ancestral trichomonad class II fumarase may represent a prokaryotic form that was replaced in other eukaryotes after the divergence of trichomonads with the movement of endosymbiont genes into the nucleus. Alternatively, it may have been acquired via a separate endosymbiotic event or lateral gene transfer.
Futility: Another Way?
Authors: Joanne Lynn
Journal: Annals of Internal Medicine (2014)

Letters17 June 2014Futility: Another Way?Joanne Lynn, MD, MA, MSJoanne Lynn, MD, MA, MSFrom Altarum Institute, Washington, DC.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L14-5012-4 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Having read Shah's essay (1), I believe he might do well to consider a different approach that has often worked well in my interactions with frantic family members. In a situation like the one he described, the physician needs to be clear that adding more interventions is not likely to change the outcome. The additional “treatment” might have changed how Ms. K. died, but it was unlikely to improve her odds (which were not 0% without the added treatment, just very small). The daughter was probably in her 20s or 30s and recently moved nearby with the ...Reference1. Shah SK. Futility. Ann Intern Med. 2014;160:138-9. [PMID: 24592501] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Altarum Institute, Washington, DC.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L14-0194. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoFutility Samir K. Shah Futility Samir K. Shah Futility: Another Way? Steven M. Radwany Futility: Another Way? Simon Kassabian Futility: Another Way? Keyvan Ravakhah Futility: Another Way? Samir K. Shah Futility: Another Way? Keyvan Ravakhah Futility: Another Way? Samir K. Shah Futility: Another Way? Simon Kassabian Futility: Another Way? Steven M. Radwany Metrics 17 June 2014Volume 160, Issue 12Page: 878KeywordsConflicts of interestDisclosureMotivation ePublished: 17 June 2014 Issue Published: 17 June 2014 CopyrightCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...