tbuckley/cabot-search huggingface dataset:
P4-07-12: Identification of p53 Mutation in Whole Genome DNA from Single Circulating Tumor Cells (CTCs) and Primary Breast Cancers (BC) from Patients (pts) with Metastatic Breast Cancer (MBC).
Authors: L Yang, Y Wang, P Chu, Q Liu, B Hsieh, X Liu, Y Yen, R Bruce, G Somlo
Journal: Cancer Research (2011)

Abstract Background: CTCs represent the source of distant metastases, and are also implied in the growth/re-growth of primary BC. Molecular/gene-level characterization of similarities and discordances between CTCs and BCs in pts with MBC may provide useful information for individualized treatment. Since somatic p53 mutations are frequently observed in primary BCs, we set out to assess the feasibility of identifying such mutations in CTCs from pts with MBCs, and compare the findings with those of the primary BCs from the same pts. Material and Method: Fiber-optic Array Scanning Technology (FAST) was used for identification and location of CTCs on large glass substrates. CTCs were identified after blood samples (10 ml) from MBC pts were stained to detect CTCs via automated digital microscopy by morphology, based on immunofuorescence staining for cytokeratin and nucleus, and the absence of CD45. Single CTCs from 10 pts with MBC were identified and removed from the glass substrates. DNA was extracted, and the whole genome of isolated CTCs was amplified by using whole genome amplification method (Sigma). P53 mutations in exon 5, exon 6, exon 7 and exon 8 were assessed. As comparison, genomic DNA from formalin-fixed and paraffin-embedded (FFPE) from primary BCs of the same pts, was amplified using the same method. Results: p53 mutations were found in 8 out of 10 CTCs, and in 4 out of 10 in primary BC samples. Of 8 mutations detected in CTCs, one silent mutation and 7 missense mutations were seen. One particular point mutation, R181L, previously assessed as functional mutation, was observed in 4 out of 8 CTCs. None of the 4 mutations (a silent mutation, one missense mutation and two different deletions) detected in tumor samples were found in CTCs. We validated that the mutations detected in CTCs were not artifacts occurring during genome amplification, by comparing p53 mutations between unamplified tumor genomic DNA vs. amplified samples. Conclusion: Whole genome amplification based on extracting DNA from single CTCs using FAST, and identification of mutations such as those in p53, is feasible. The quantitative and qualitative discordance in detecting p53 mutations between CTCs and primary BCs may be due to CTCs acquiring new -possibly epithelial-mesenchymal transition-like-characteristics with metastatic potential as they evolve from the primary tumors or metastatic sites, or, technical issues (analyzing FFPE-preserved vs. CTCs, tumor heterogeneity) may contribute to our findings. Further assessment of the functionality of high frequent functional mutations such as R181L is warranted. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-12.
Prevalence of Silent Cerebral Ischemia in Paroxysmal and Persistent Atrial Fibrillation and Correlation With Cognitive Function
Authors: Fiorenzo Gaita, Laura Corsinovi, Matteo Anselmino, Cristina Raimondo, Martina Pianelli, Elisabetta Toso, Laura Bergamasco, Carlo Boffano, Maria Consuelo Valentini, Federico Cesarani, Marco Scaglione
Journal: Journal of the American College of Cardiology (2013)
A SERIES OF CASES OF APPENDICITIS IN CHILDREN
Authors: H. M. W. Gray, A. Mitchell
Journal: BMJ (1914)

IN submiitting for your consideration a series of cases of appendicitis occurring in children, we wish to draw attention to certain points which lhave appealed to us as being of special itmnportance and to the conclusions we have drawn therefrom.All the patients were children under 13 years of age, and all were treated in the Aberdeen Royal Hospital for Sick Children.Out of a total of 20( cases, 126 were admitted and operated on during an acute attack.Table showin1g the Condition in 200 Cases of Appendicitis in Childreni.Chronic and recurrent .. ... ...
Review: Evidence for the effectiveness of surgery for low back pain, radiculopathy, and spinal stenosis is limited
Authors: Bruce Rothschild
Journal: Annals of Internal Medicine (2009)

ACP Journal Club20 October 2009Review: Evidence for the effectiveness of surgery for low back pain, radiculopathy, and spinal stenosis is limitedBruce Rothschild, MDBruce Rothschild, MDNortheastern Ohio Universities College of Medicine, Rootstown, Ohio, USA (B.R.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-151-8-200910200-02011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationChou R, Baisden J, Carragee EJ, et al. Surgery for low back pain: a review of the evidence for an American Pain Society clinical practice guideline. Spine. 2009;34:1094-109. https://pubmed.ncbi.nlm.nih.gov/19363455Clinical Impact RatingsGIM/FP/GP: Neurology: Phys Med & Rehab: Rheumatology: References1 Rothschild BM. Safety measures, but what about measures to assure education/training/experience? J Rheumatol. (In press) Google Scholar2 Rothschild BM. Lumbar spondylosis. eMedicine: Neurosurgery: Spine. www.emedicine.com/med/topic2901.htm (updated 9 Apr 2009). Google Scholar3 Rothschild BM. Rheumatology: A primary care approach. New York: Yorke Medical Books; 1982. Google Scholar4 Weinstein JN, Lurie JD, Tosteson TD, et al. Surgical versus nonsurgical treatment for lumbar degenerative spondylolisthesis. N Engl J Med. 2007;356:2257-70. [PMID: 17538085] Google Scholar5 Weinstein JN, Tosteson TD, Lurie JD, et al. Surgical versus nonsurgical therapy for lumbar spinal stenosis. N Engl J Med. 2008;358:794-810. [PMID: 18287602] Google Scholar Author, Article, and Disclosure InformationAffiliations: Northeastern Ohio Universities College of Medicine, Rootstown, Ohio, USA (B.R.)This article was published at Annals.org on 6 October 2009. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoReview: Evidence for the effectiveness of nonsurgical interventions for low back pain and radiculopathy is limited Bruce Rothschild Metrics 20 October 2009Volume 151, Issue 8Page: JC4-11KeywordsEtiologyExerciseFibromyalgiaLower back painNervesOsteoporosisStenosisSurgerySystematic reviewsTreatment guidelines ePublished: 20 October 2009 Issue Published: 20 October 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Concordance of sustained virological response 4, 12, and 24 weeks post‐treatment with sofosbuvir‐containing regimens for hepatitis C virus
Authors: Eric M. Yoshida, Mark S. Sulkowski, Edward J. Gane, Robert W. Herring, Vlad Ratziu, Xiao Ding, Jing Wang, Shu‐Min Chuang, Julie Ma, John McNally, Luisa M. Stamm, Diana M. Brainard, William T. Symonds, John G. McHutchison, Kimberly L. Beavers, Ira M. Jacobson, K. Rajender Reddy, Eric Lawitz
Journal: Hepatology (2014)

Historically, clinical trials of regimens to treat chronic infection with hepatitis C virus (HCV) have used, as their primary efficacy endpoint, a sustained virological response (SVR)—defined as HCV RNA levels below a designated threshold of quantification—24 weeks after the end of treatment (SVR24). More recently, regulatory authorities have begun to accept SVR at 12 weeks post‐treatment (SVR12) as a valid efficacy endpoint because of its high rate of concordance with SVR24. However, the concordance between SVR12 and SVR24 has not been systematically assessed with new regimens of recently approved direct‐acting antiviral agents. The aim of this study was to assess the concordance between SVR at various post‐treatment time points in phase III clinical trials of sofosbuvir (SOF)‐containing regimens. We conducted a retrospective analysis of five trials enrolling 863 patients infected with HCV genotypes 1‐6. The concordance between SVR at 4 weeks post‐treatment (SVR4) and SVR12, and between SVR12 and SVR24, were determined, as well as positive predictive values (PPVs) and negative predictive values (NPVs). Overall, 779 of 796 patients (98.0%) with an SVR4 also achieved an SVR12, making the PPV of SVR4 for SVR12 98% and the NPV 100%. Of the 779 patients with an SVR12, 777 (99.7%) also achieved an SVR24, making the PPV of SVR12 for SVR24 &gt;99% and the NPV 100%. Of patients who relapsed post‐therapy, 77.6% did so within 4 weeks of completing therapy. Conclusion : Data from phase III studies demonstrate that with SOF‐based regimens, with or without interferon, SVR12 and SVR24 correlate closely. Thus, SVR12 can be used effectively to determine “cure” rates in trials and in clinical practice. (H epatology 2015;61:41–45)
P3-135: Results of an open-label, Phase II trial of nanoparticle albumin bound paclitaxel (nab-paclitaxel), carboplatin, and bevacizumab as first-line therapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC)
Authors: Craig Reynolds, David Barrera, Duy Quoc Vu, Robert Jotte, Alexander I. Spira, Charles Weissman, Kristi A. Boehm, Sharon Pritchard, Lina Asmar
Journal: Journal of Thoracic Oncology (2007)
Long-term immune reconstitution after anti-CD52–treated or anti-CD34–treated hematopoietic stem cell transplantation for severe T-lymphocyte immunodeficiency
Authors: Mary A. Slatter, Kenneth Brigham, Anne M. Dickinson, Helen L. Harvey, Dawn Barge, Antony Jackson, Nicholas Bown, Terence J. Flood, Andrew J. Cant, Mario Abinun, Andrew R. Gennery
Journal: Journal of Allergy and Clinical Immunology (2007)
Chronic blockade of AT2-subtype receptors prevents the effect of angiotensin II on the rat vascular structure.
Authors: B I Levy, J Benessiano, D Henrion, L Caputo, C Heymes, M Duriez, P Poitevin, J L Samuel
Journal: Journal of Clinical Investigation (1996)

Angiotensin II (Ang II) is both a vasoactive and a potent growth-promoting factor for vascular smooth muscle cells. Little is known about the in vivo contribution of AT1 and AT2 receptor activation to the biological action of Ang II. Therefore, we investigated the effect of AT1 or AT2 subtype receptor chronic blockade by losartan or PD123319 on the vascular hypertrophy in rats with Ang II-induced hypertension. Normotensive rats received for 3 wk subcutaneous infusions of Ang II (120 ng/kg per min), or Ang II + PD 123319 (30 mg/kg per d), or Ang II + losartan (10 mg/kg per d) or PD 123319 alone, and were compared with control animals. In normotensive animals, chronic blockade of AT2 receptors did not affect the plasma level of angiotensin II and the vascular reactivity to angiotensin II mediated by the AT1 receptor. Chronic blockade of AT1I in rats receiving Ang II resulted in normal arterial pressure, but it induced significant aortic hypertrophy and fibrosis. Chronic blockade of AT2 receptors in Ang II-induced hypertensive rats had no effect on arterial pressure, but antagonized the effect of Ang II on arterial hypertrophy and fibrosis, suggesting that in vivo vasotrophic effects of Ang II are at least partially mediated via AT2 subtype receptors.
Restenosis and clinical outcome in patients treated with amlodipine after angioplasty: results from the coronary AngioPlasty Amlodipine REStenosis Study (CAPARES)
Authors: Bjørn Jørgensen, Svein Simonsen, Knut Endresen, Kolbjørn Forfang, Karleif Vatne, James Hansen, John Webb, Christopher Buller, Gilles Goulet, Jan Erikssen, Erik Thaulow
Journal: Journal of the American College of Cardiology (2000)
Analysis of Ventricular Activation Using Surface Electrocardiography to Predict Left Ventricular Reverse Volumetric Remodeling During Cardiac Resynchronization Therapy
Authors: Michael O. Sweeney, Rutger J. van Bommel, Martin J. Schalij, C. Jan Willem Borleffs, Anne S. Hellkamp, Jeroen J. Bax
Journal: Circulation (2010)

Cardiac resynchronization therapy for heart failure with left bundle branch block reduces left ventricular (LV) conduction delay, contraction asynchrony, and LV end-systolic volume ("reverse remodeling"). Up to one third of patients do not improve, and the electric requirements for reverse remodeling are unclear. We hypothesized that reverse remodeling is predicted by the left bundle branch block ventricular activation sequence, the paced activation sequence, and interactions between these 2 conditions.Twelve-lead ECGs during left bundle branch block and cardiac resynchronization therapy were analyzed in 202 consecutive patients (New York Heart Association class III to IV heart failure, ejection fraction < or =35%) for predictors of reverse remodeling (> or =10% reduction in end-systolic volume) at 6 months. Greater longest baseline LV activation time predicted increased odds of reverse remodeling (odds ratio [confidence interval]=1.30 [1.11, 1.52] per 10-ms increase), whereas higher QRS scores for LV scar predicted reduced reverse remodeling (odds ratio [confidence interval]=0.49 [0.27, 0.88] for each 1-point increase from 0 to 4; 0.92 [0.83, 1.01] for each 1-point increase >4). After cardiac resynchronization therapy, increasing R amplitudes in leads V(1) through V(2) (odds ratio [confidence interval]=2.76 [1.01, 7.51] for each 1x increase over [baseline Rx4.5]) and left-->right frontal axis shift (odds ratio [confidence interval]=2.00 [0.99, 4.02]), indicators of ventricular activation wavefront fusion, were positive predictors of reverse remodeling. Predicted probability of reverse remodeling ranged from <20% for patients with adverse predictors to 99% for those with positive predictors.Ventricular activation with the use of the ECG accurately predicts LV reverse remodeling during cardiac resynchronization therapy. Greater longest baseline LV activation time and smaller scar volume combined with wavefront fusion on the paced ECG, anticipate higher probability of reverse remodeling.
Detection of Effects of Ionizing Radiation by Population Studies
Authors: G. Hems
Journal: BMJ (1966)

The development and use of atomic energy have led to an increase in man's exposure to ionizing radiation, and there is general concern over the possible damage which might result from this increased exposure.Situations which give rise to large individual doses are extremely rare, and the major exposure is to low doses at very low dose rates.Large numbers of the general population are exposed to fallout at dose rates which average a few hundreths of a rad per year.A small section of the population are radiation workers and are exposed, occupationally, to higher doses; these amount, on average, to 11 rad per year, or less.So far, harmful effects of low doses of radiation at low dose rates have not been detected, and the possible risks are estimated by extrapolating from the effects of high doses, delivered at high dose rates, and observed in studies of atomic-bomb survivors, and ankylosing-spondylitis patients who have been treated with ionizing radiation.This extrapolation introduces considerable uncertainty, which might be avoided by attempting to detect directly the effects of exposures
The Dawn Phenomenon, an Early Morning Glucose Rise: Implications for Diabetic Intraday Blood Glucose Variation
Authors: Maria Ines Schmidt, Angeliki Hadji-Georgopoulos, Marc Rendell, Simeon Margolis, Avinoam Kowarski
Journal: Diabetes Care (1981)

Eleven insulin-dependent (type I) diabetic subjects were studied during a 24-h period to assess intraday blood glucose (BG) variation and related free insulin (FI) levels. Ten patients exhibited the dawn phenomenon, a rise in early morning fasting blood glucose (123 +/- 81.1 m/dl; mean +/- SD). This increase was positively and significantly correlated with the morning postprandial BG peak (r = 0.723; P = 0.012). FI/BG ratios were highest during the night (0.717 and 0.666 at 2200 and 0400 h, respectively) and lowest during the early morning (0.294 at 0800 h) (P less than 0.01). Three of the four observed hypoglycemic episodes occurred during the period when free insulin levels were high relative to BG. We conclude that the dawn phenomenon contributed directly and significantly to the BG maximum and indirectly, in some cases, to nocturnal hypoglycemia. It thus played an important role in the intraday blood glucose variation of such patients.
The ileal brake--inhibition of jejunal motility after ileal fat perfusion in man.
Authors: R C Spiller, I F Trotman, B E Higgins, M A Ghatei, G K Grimble, Y C Lee, S R Bloom, J J Misiewicz, D B Silk
Journal: Gut (1984)

The possibility that malabsorbed fat passing through the human ileum exerts an inhibitory feedback control on jejunal motility has been investigated in 24 normal subjects by perfusing the ileum with a fat containing solution designed to produce ileal luminal fat concentrations similar to those in steatorrhoea (30-40 mg/ml). Mean transit times through a 30 cm saline perfused jejunal segment were measured by a dye dilution technique. Thirty minutes after ileal fat perfusion, mean transit times rose markedly to 18.9 +/- 2.5 minutes from a control value of 7.5 +/- 0.9 minutes (n = 5; p less than 0.05). This was associated with an increase in volume of the perfused segment which rose to 175.1 +/- 22.9 ml (control 97.6 +/- 10.3 ml, n = 5; p less than 0.05). Transit times and segmental volumes had returned towards basal values 90 minutes after completing the fat perfusion. Further studies showed that ileal fat perfusion produced a pronounced inhibition of jejunal pressure wave activity, percentage duration of activity falling from a control level of 40.3 +/- 5.0% to 14.9 +/- 2.8% in the hour after ileal perfusion (p less than 0.01). Ileal fat perfusion was associated with marked rises in plasma enteroglucagon and neurotensin, the peak values (218 +/- 37 and 68 +/- 13.1 pmol/l) being comparable with those observed postprandially in coeliac disease. These observations show the existence in man of an inhibitory intestinal control mechanism, whereby ileal fat perfusion inhibits jejunal motility and delays caudal transit of jejunal contents.
Progression of borderline abnormalities on cervical smear testing.
Authors: M. A. Ratcliffe, A. A. Dawson, G. Flannelly
Journal: BMJ (1992)

sampling error (probably the most important single cause of lack of correlation between histo- logical and cytological findings).Negative results ofsmear tests in women with cervical intraepithelial neoplasia grade III have also been attributed to sampling error.We believe that the argument of progression and sampling error also applies to many cases of mild dyskaryosis in which biopsy specimens taken after some follow up period or at the time of the smear test show cervical intra- epithelial neoplasia grade III.
Access to some NICE approved drugs varies hugely across England
Authors: I. Torjesen
Journal: BMJ (2014)

A “postcode lottery” still exists in access to the latest drugs in England, show figures in a report by the NHS Health and Social Care Information Centre.

For the first time the centre’s annual analysis of actual versus expected use of drugs recently approved by the National Institute for Health and Care Excellence (NICE) also looked at use by local area.1 It found wide variation, including a 28-fold difference in use of the newer anticoagulants rivaroxaban and dabigatran for stroke prevention in atrial fibrillation and a more than nine-fold variation in use of denosumab for osteoporosis.

The analysis looked at the actual versus expected use in England of 18 drugs in 10 categories. It found lower than expected …
Hepatic Arterial Chemotherapy for Colorectal Cancer Metastatic to the Liver
Authors: ROBERT J. STAGG
Journal: Annals of Internal Medicine (1984)

Hepatic metastases of colorectal origin are resistant to radiation and immunotherapy. Traditional intravenous chemotherapy produces responses in 10% to 30% of patients, and surgical resection is feasible in approximately 20% of patients who have a solitary or unilobar lesion. Infusion of cytotoxic agents into the hepatic artery, introduced 2 decades ago, is the most promising form of therapy for unresectable hepatic metastases. Fluorouracil, floxuridine, and mitomycin have been most commonly administered by hepatic arterial infusion. The recent development of a totally implantable pump has allowed prolonged ambulatory infusion of chemotherapeutic agents into the hepatic artery. We review the recent data on the pharmacology, therapeutic outcome, administration techniques, and complications of hepatic arterial chemotherapy. Future trials in this area should use uniform stratification variables and standardized criteria for evaluating response, time to progression, and survival.
THE DIAGNOSIS OF CANCER
Authors: FRANCIS CARTER WOOD
Journal: JAMA (1930)

The extensive education of the lay public which has been conducted in the past fifteen years by the American Society for the Control of Cancer has created a situation not without interest to the medical profession as a whole. The fact is that while it is perfectly possible to have the lay public absorb a certain amount of information concerning the symptoms of cancer, after such absorption has taken place and the desired reaction occurred the profession is not in a position, speaking generally, to render efficient service to those who apply for it. In other words, the medical profession as a whole is not yet prepared accurately to diagnose the disease which it is called on to treat, at a stage which permits of effective therapeutic attack, nor are all surgeons or radiologists prepared to offer the proper therapy.<sup>1</sup> This failure is not confined to the internal group
239. Histological Measurement of Myocardial Infarct Area Does Not Provide a Sensitive Assessment of Infarct Size in a Mouse Chronic Infarct Model
Authors: Junya Takagawa, Yan Zhang, Richard E. Sievers, Neel K. Kapasi, Maelene L. Wong, Yerem Yeghiazarians, Randall J. Lee, William Grossman, Matthew L. Springer
Journal: Molecular Therapy (2006)

Assessment of severity of a myocardial infarction (MI) is an important measure of success after experimental delivery of potentially therapeutic genes or cells in rodent MI models. In experiments involving an acute MI setting, histological measurement of the area of the infarcted region in tissue sections of the left ventricle (LV) is a standard assessment of "infarct size." This approach is also used by numerous investigators in a chronic infarct setting, taking infarct area measurements several weeks post_MI.
Importance of Tumor Necrosis Factor-α Cleavage Process in Post-Transplantation Lung Injury in Rats
Authors: Taichiro Goto, Akitoshi Ishizaka, Fujio Kobayashi, Mitsutomo Kohno, Makoto Sawafuji, Sadatomo Tasaka, Eiji Ikeda, Yasunori Okada, Ikuro Maruyama, Koichi Kobayashi
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Tumor necrosis factor-alpha (TNF-alpha) has two forms with apparently different biological activities: a membrane-associated form and a soluble form. TNF-alpha-converting enzyme (TACE) mediates a cleavage of membrane-associated TNF-alpha to induce its bioactive soluble form. We hypothesized that inhibition of TACE might prevent TNF-alpha-induced tissue injury while preserving the benefits of TNF-alpha. In this study, we evaluated the role of TACE in acute inflammation using an inhibitor of the enzyme in a rat model of lung transplantation. Inbred Lewis rats underwent left lung isotransplantation, and the donor lungs were kept in Euro-Collins solution with or without the inhibitor. After 6 hours of ischemia, the left lung was transplanted into the recipient rat and reperfused for 4 hours. Inhibition of TACE significantly attenuated endothelial and alveolar septal damage, as assessed by radiolabeled albumin leakage after transplantation. The inhibition also attenuated neutrophil accumulation in the alveolar space and other histopathologic findings, including intercellular adhesion molecule-1 expression. In addition, significantly lower levels of monocyte chemotactic protein-1, cytokine-induced neutrophil chemoattractant-1, high mobility group box-1, and soluble epithelial cadherin and decreased neutrophil elastase activity were observed in bronchoalveolar lavage fluid from the rats treated with the inhibitor. We conclude that TACE mediates a critical step in the development of post-transplantation lung injury.