tbuckley/cabot-search huggingface dataset:
Twenty thousand conversations
Authors: T. Delamothe
Journal: BMJ (2002)

Conversation is a meeting of minds with different memories and habits. When minds meet, they don't just exchange facts: they transform them, reshape them, draw different implications from them, and engage in new trains of thought. Conversation doesn't just reshuffle the cards; it creates new cards.1

Four years ago we added a feature to bmj.com, which we called “rapid responses.”2 The feature allows readers to respond to articles directly via the website as they are reading them. We don't regard them as second class letters: they are just as eligible for inclusion in the paper journal as letters received in other forms. In fact, most of the letters to the editor that we now print in the paper journal started life as rapid responses.

Our original intention was to post all but the libellous, gratuitously rude, trivial, irrelevant, or incomprehensible on the website within 72 hours.We hoped that, at the very least, it would solve the problem of receiving far more letters to the editor than we could possibly print in the paper journal. We wondered whether rapid responses marked the most democratic step that the journal had ever taken.

So how has it gone? With 20 000 rapid responses now published on the website we consider the experiment a success. Particularly gratifying has been the participation of readers from outside the United Kingdom; in fact, …
Diagnostic value of hazelnut allergy tests including <scp>rCor</scp> a 1 spiking in double‐blind challenged children
Authors: L. J. Masthoff, S. G. Pasmans, E. van Hoffen, M. J. Knol, C. A. Bruijnzeel‐Koomen, A. E. Flinterman, P. Kentie, A. C. Knulst, Y. Meijer
Journal: Allergy (2011)

Abstract Background The diagnostic value of hazelnut allergy tests in double‐blind challenged children is largely unknown. The aim of this study was to analyze the performance of current diagnostic tests for hazelnut allergy in children and the effect of spiking. Methods Data of 151 children who underwent a double‐blind placebo‐controlled food challenge for hazelnut were analyzed. The positive predictive value and negative predictive value ( PPV / NPV ) of level of specific IgE ( sIgE ) for hazelnut, the influence of rCor a 1 spiking of the I mmuno CAP , and size of the skin prick test ( SPT ) for hazelnut were determined, also in relation to the severity of the hazelnut allergy. Reported accidental ingestion leading to an allergic reaction to hazelnut was also analyzed in relation to hazelnut allergy. Results Specific IgE ≥0.35 kU A /l for hazelnut was a moderate predictor for hazelnut allergy. The spiking decreased the PPV from 41% to 38% and increased the NPV from 91% to 100% for sIgE ≥0.35 kU A /l. The maximum reached PPV was 73% for sIgE cutoff of 26 kU A /l. Level of sIgE before spiking was significantly different between different grades of severity and was lost after spiking. Skin prick test was a better predictor for hazelnut allergy and severity than the level of sIgE . A history of accidental ingestion leading to an allergic reaction to hazelnut had a predictive value of 59% for hazelnut allergy. Conclusions This study showed a good NPV of diagnostic tests for hazelnut allergy in children which further improved by rCor a 1 spiking. However, the PPV s are moderate and decreased by spiking.
ET-70 * COMBINATION OF oHSV WITH INTEGRIN 1 NEUTRALIZING ANTIBODY (OS2966) AUGMENTS oHSV THERAPY
Authors: J. Y. Yoo, Y. Y. Banasavadi-Siddegowda, T. Relation, M. Aghi, B. Kaur
Journal: Neuro-Oncology (2014)

Oncolytic HSV (oHSV) is a biologic therapy currently being tested in patients. We have previously shown that oHSV-induced Cysteine-rich 61 protein (CCN1) binds with integrin α6β1, activating a type 1 IFN-antiviral defense response. oHSV-induced CCN1 induction also increases macrophage infiltration and activation, resulting in increased virus clearance in glioblastoma cells. Integrin β1 is cell surface molecule involved in multiple functions like cellular proliferation, invasion and inflammation. Inhibition of integrin β1 has shown anti-tumor efficacy in preclinical modles of glioma. Furthermore, incorporating the Rembrandt database of the National Cancer Institute, we found integrin β1 expression is negatively associated with glioblastoma patient survival (p value < 0.0001). Interestingly, oHSV infection strongly increased integrin β1 expression (western blot). Based on this, we hypothesized that the combination of oHSV with integrin β1neutralizing antibody (OS2966) will augment oHSV therapy. Combination treatment with OS2966 increased oHSV replication and cell killing. Increased viral replication and cell killing was more obvious in the laminin-coated cells, consistent with integrin β1 signaling pathway. OS2966 treatment strongly inhibited oHSV-induced raw246.7 macrophage cell migration towards infected glioblastoma cells as dose dependent manner (migration assay). Inhibition of integrin β1in glioma cell lines and patient derived primary GSCs significantly increased markers of sensencsence such as enhanced β-gal activity, along with induction of p21, and reduction of phosphorylation of AKT and Rb, indicating that integrin β1 activation is involved in self-renewal, and proliferation. In conclusion, oHSV-induced integrin β1 expression sensitize to OS2966 effect, resulting in enhanced viral replication and inhibition of macrophage migration. Our findings reveal how integrin β1 limits oHSV replication. Our findings also reveal how OS2966, an integrin β1 blocking antibody which has been humanized in anticipation of potential clinical trials, inhibits the innate immune response elicited upon oHSV therapy. The results will lead to the development of a novel oHSV therapeutic strategy.
1006-43 Hirulog™ vs. Heparin During Percutaneous Transluminal Coronary Angioplasty in Patients with Post-Infarction Angina: Results of the Myocardial Infarction Arm of the Hirulog Angioplasty Trial
Authors: John Strony, John A. Bittl, Ezra Deutsch, Russell Ivanhoe, Clyde Meckel, Burt Adelman
Journal: Journal of the American College of Cardiology (1995)
Abstract 1822: Novel potent inhibitor of Bcr-Abl mutated imatinib resistant chronic myeloid leukemia cell lines
Authors: Kalpana S. Joshi, Sonal Manohar, Archana Jalota-Badhwar, Vinay Sonawane, Anagha Damre, Meenakshi Sivakumar, Somesh Sharma
Journal: Cancer Research (2012)

Abstract The hallmark of chronic myeloid leukemia (CML) is the presence of Bcr-Abl oncoprotein that is essential for leukemogenesis and accumulation of neoplastic cells. The Abl tyrosine kinase inhibitor imatinib mesylate (Gleevec) represents the standard treatment for CML. However, a number of CML patients develop imatinib resistance and several mechanisms of resistance have been described. While most mutant forms are sensitive to second-generation tyrosine kinase inhibitors, the T315I mutation remains completely refractory to imatinib, as well as to these agents. Treatment of CML patients harboring T315I mutation is still an unmet medical need in the imatinib and post-imatinib era. We have identified P2745, a novel orally bioavailable small molecule that is effective in imatinib resistant mutations and particularly T315I mutation form to address this unmet medical need. In vitro P2745 showed potent cytotoxicity (IC50 0.8-5 μM) in twelve Bcr-Abl mutated imatinib resistant cell lines including T315I compared to wild type Bcr-Abl cell lines. P2745 did not show cytotoxicity upto 30 μM in normal fibroblasts (MRC-5 and WI-38) and normal human peripheral blood mononuclear cells thus indicating specificity towards cancerous cells. P2745 inhibited pCrkLTyr207 in imatinib-resistant CML cell lines accompanied with down regulation of Bcr-Abl protein levels. Additionally, it up regulated tumor suppressor protein SMAR-1 which resulted in negative regulation TGF-β/SMAD-dependent pathway as demonstrated by low phosphorylated levels of SMAD2 and SMAD3, two key players implicated in the preservation of the malignant progenitor population, and partly responsible for the resistance to treatments targeting Bcr-Abl. P2745 also induced significant apoptosis in imatinib resistant cell lines (Y253F, T315I and E255V) but not in normal MRC-5 cell line. In addition, like imatinib it induced 80-90 % apoptosis in cells derived from CML patients. In vivo studies demonstrated significant (p&amp;lt;0.001), dose dependent efficacy in imatinib resistant T315I cells xenograft in SCID mice. It also demonstrated significant in vivo efficacy in Bcr-Abl wild type imatinib sensitive K-562 (p&amp;lt;0.05) and Ba/F3 (p&amp;lt;0.001) xenografts in SCID mice. PK-PD evaluation in imatinib resistant xenograft experiments indicated that at the efficacious dose, P2745 modulated proteins responsible for CML pathogenesis (60-80 %), which correlates with the levels of P2745 in the tumors. This unique mechanism of action makes P2745 a promising clinical candidate for CML patients harboring T315I mutation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1822. doi:1538-7445.AM2012-1822
Loss of Epidermal Growth Factor Receptor Expression in Lymph Node and Liver Metastases of Colon Carcinoma
Authors: Marie-Pierre Bralet, Bernard Paule, Rene Adam, Catherine Guettier
Journal: Journal of Clinical Oncology (2005)

of the Journal of Clinical Oncology. 1 In their series, epidermal growth factor receptor (EGFR) status was positive in only 53% of colorectal tumors and its status in primary tumors did not correlate with EGFR expression in related metastatic sites.We would like to emphasize that using a different test of EGFR immunohistochemical detection, we also observed this discrepancy between primary colon carcinoma and liver metastases in a series of 40 patients (25 men, 15 women; mean age, 57.5 years).All patients underwent a first hepatectomy for liver metastases; second and third hepatic resections were performed in 14 and three patients, respectively.In addition, seven patients had tumor liver biopsy.Using CONFIRM anti-EGFR (3C6) primary antibody (Ventana Medical Systems; Illkirch, France) on a Ventana NexES immunohistochemistry staining platform (Ventana Medical Systems), we analyzed EGFR expression on 40 surgically resected colon adenocarcinomas, on the 27 metastatic regional lymph nodes, and on the 64 related liver metastases.Membranous EGFR expression was detected in Ն 1% of the tumor cells of 38 colon carcinomas (95%), 23 metastatic lymph nodes (88%), and 51 liver metastases (79%).In our series, both primary tumors and related metastases (lymph node and liver) were positive for EGFR expression in 28 patients (73%).In six patients with a positive EGFR status in colon carcinoma, EGFR expression was detected either in lymph node or in liver metastases, as listed in Table 1.Taken together, these data point out the variability of EGFR detection using different immunohistochemical methods.Even in a series of patients with a high rate of EGFR-positive colon carcinomas, immunohistochemical expression of EGFR could be lost in the related metastases.Which sample-primary or metastic tumor-is the most adequate to determine a therapeutically relevant EGFR status is yet to be solved.
Estimation of Primate Speciation Dates Using Local Molecular Clocks
Authors: Anne D. Yoder, Ziheng Yang
Journal: Molecular Biology and Evolution (2000)

Protein-coding genes of the mitochondrial genomes from 31 mammalian species were analyzed to estimate the speciation dates within primates and also between rats and mice. Three calibration points were used based on paleontological data: one at 20–25 MYA for the hominoid/cercopithecoid divergence, one at 53–57 MYA for the cetacean/artiodactyl divergence, and the third at 110–130 MYA for the metatherian/eutherian divergence. Both the nucleotide and the amino acid sequences were analyzed, producing conflicting results. The global molecular clock was clearly violated for both the nucleotide and the amino acid data. Models of local clocks were implemented using maximum likelihood, allowing different evolutionary rates for some lineages while assuming rate constancy in others. Surprisingly, the highly divergent third codon positions appeared to contain phylogenetic information and produced more sensible estimates of primate divergence dates than did the amino acid sequences. Estimated dates varied considerably depending on the data type, the calibration point, and the substitution model but differed little among the four tree topologies used. We conclude that the calibration derived from the primate fossil record is too recent to be reliable; we also point out a number of problems in date estimation when the molecular clock does not hold. Despite these obstacles, we derived estimates of primate divergence dates that were well supported by the data and were generally consistent with the paleontological record. Estimation of the mouse-rat divergence date, however, was problematic.
Psychoanalysis: Science and Profession
Authors: Leon J. Saul
Journal: JAMA (1974)

Max Gitelson was primarily a therapist and a political leader in his field, becoming president of the American Psychoanalytic Association and later of the International Psychoanalytic Association. I think this was largely because he was an articulate spokesman for the best of the orthodox analysts, identifying with their anxieties about psychoanalysis as they understood it. He was not outstanding as a theoretician, like Heinz Hartmann, or as a clinical investigator, like Margaret Mahler. Rather, he was sensitive to the currents and developments of his times in American society at large as well as within the field of psychoanalysis. His writings, here conveniently collected from diverse sources, reflect his concern with preserving the purity of psychoanalysis as he and the orthodox saw it, and defending it against what they saw as attacks from all sides that they felt tended to dilute, deflect, or otherwise distort it. Thus, defensive polemical elements enter
PYOCYANINE, AN ACCESSORY RESPIRATORY ENZYME
Authors: Ernst A. H. Friedheim
Journal: The Journal of Experimental Medicine (1931)

Pyocyanine, the blue pigment of B. pyocyaneus, can increase the respiration of living cells to a great degree (maximum observed increase 24-fold). The reversibility of its oxidation and reduction is responsible for this. The effect is non-species-specific and has been observed in varying degrees with B. pyocyaneus, Staphylococcus aureus, Pneumococcus Type III, and the red blood corpuscles of rabbits. The effect of pyocyanine is dependent on the presence of another respiratory ferment sensitive to potassium cyanide and carbon monoxide. The increase of respiration induced by pyocyanine is paralleled by an increase in the respiratory quotient. The pyocyanine catalysis is not indiscriminately effective in all oxidations, but only in the oxidation of certain substances closely associated with the bacterial body.
Comparable survival after HLA-well-matched unrelated or matched sibling donor transplantation for acute myeloid leukemia in first remission with unfavorable cytogenetics at diagnosis
Authors: Vikas Gupta, Martin S. Tallman, Wensheng He, Brent R. Logan, Edward Copelan, Robert Peter Gale, Hanna J. Khoury, Thomas Klumpp, John Koreth, Hillard M. Lazarus, David I. Marks, Rodrigo Martino, David A. Rizzieri, Jacob M. Rowe, Mitchell Sabloff, Edmund K. Waller, John F. DiPersio, Donald W. Bunjes, Daniel J. Weisdorf
Journal: Blood (2010)
HCV proteins increase expression of heme oxygenase-1 (HO-1) and decrease expression of Bach1 in human hepatoma cells
Authors: Tahereh Ghaziani, Ying Shan, Richard W. Lambrecht, Susan E. Donohue, Thomas Pietschmann, Ralf Bartenschlager, Herbert L. Bonkovsky
Journal: Journal of Hepatology (2006)
Patient Adherence to Medical Treatment Regimens: Bridging the Gap Between Behavioral Science and Biomedicine
Authors: Emilio J Sanz
Journal: BMJ (2005)

T he first three chapters of this book rather dramatically present the over-whelming evidence that most patients do not usually follow most of their prescriptions and treatment recommendations. In theory this poses serious risks of ineffectiveness and harm—for example, rejection in transplant recipients because of insufficient immunosuppressant treatment. A huge amount of research has failed to find any good indicators for compliance. Perhaps most of the studies were too simple or lacked an adequate theoretical foundation, but the result today is that the expectation that a patient will "comply" is misplaced and that measures to improve compliance are based more on common sense or goodwill than on evidence. Alan J Christensen Yale University Press, £27.50, pp 165 ISBN 0 300 10349 2 yalebooks.com Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Alan Christensen and his … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Readiness Is All: Public Health Experts Draft Plan Outlining Pandemic Influenza Response
Authors: Charles Marwick
Journal: JAMA (1996)

WHILE NEW and exotic viral diseases have occupied much media attention in recent years, among scientists and public health officials a major concern has been to try to deal with one of the oldest viral infections known—influenza. Influenza, with its ability to cause repeated epidemics of respiratory illness, can also be viewed as a new, emerging disease. Periodically the virus rises, phoenixlike, from the genetically reassorted residues of its antecedents to sweep through a susceptible human population, leaving death and destruction in its wake. For many years, these shifts in the antigenic constitution of influenza have been monitored with the goal of developing effective vaccines against the new viral strains that emerge. In most years the antigenic changes are minor, but every now and again the virus undergoes a major change and causes a worldwide epidemic—a pandemic—of sudden and widespread illness. Such an event occurred in 1918-1919 and caused an
On Bedside Teaching
Authors: Colin Powell
Journal: Annals of Internal Medicine (1997)

Letters15 July 1997On Bedside TeachingColin Powell, MD, FRCPColin Powell, MD, FRCPDalhousie University; Halifax, Nova Scotia, CanadaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-2-199707150-00042 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Thank you for publishing “On Bedside Teaching” [1]. LaCombe nicely distinguishes between principles, to which we allegedly adhere, and practice, which readily obscures patients and their informal care givers behind a morass of figures. According to McKnight and Rockwood [2] “house staff readily declaim weeks' worth of serial biochemistry but cannot tell when a patient last walked unaided.” One advantage of practicing and teaching geriatric medicine is that one can take the student to the most relevant bedside-the one in the patient's home.References1. LaCombe MA. On bedside teaching. Ann Intern Med. 1997; 126:217-20. Google Scholar2. McKnight C, Rockwood K. A hierarchical assessment of balance and mobility. Age Aging. 1992; 24:126-30. Google Scholar Author, Article, and Disclosure InformationAffiliations: Dalhousie University; Halifax, Nova Scotia, Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1997Volume 127, Issue 2Page: 172-173KeywordsBiochemistryGeriatrics Issue Published: 15 July 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Heart Disease in Infancy
Authors: Samuel Kaplan
Journal: JAMA (1981)

Infants with heart disease have unique problems that can usually be accurately diagnosed. Furthermore, in the majority of cases, surgical treatment, corrective or palliative, is successful. This text is welcome because it is one of the few dedicated to the problems of the infant. After consideration of the incidence of cardiac malformations, six chapters are devoted to methods of diagnosis. The rest of the text describes specific cardiac anomalies, which are grouped by their hemodynamic abnormalities. These are divided according to the presence or absence of cyanosis in association with the degree of pulmonary blood flow. These four chapters are completed by a section on pulmonary venous obstruction. The authors' style makes the book easy to read, in contradistinction to the usual multiauthored texts. However, the book is uneven in its emphasis and there is uncertainty about the optimum audience. The chapter on cardiac catheterization and angiocardiography is detailed and
Maximizing the Success of Transplantation with Kidneys from Older Donors
Authors: Francis L. Delmonico, James F. Burdick
Journal: New England Journal of Medicine (2006)

In this issue of the Journal, Remuzzi et al.1 report on the important challenge of maximizing success when transplanting kidneys from older donors while minimizing poor outcomes due to the risk of receiving older kidneys. This Italian group reports results that are relevant to increasing the rate of successful kidney transplantation anywhere in the world.In the United States, the incidence of end-stage renal disease has escalated in recent years. There are 60,000 patients currently waiting for a kidney transplant, but of those, only 16,000 per year will receive a transplant. Since the Organ Donation Breakthrough Collaborative was established in . . .
The Effects of a Preassessment Clinic on Nonattendance Rates for Day-Case Colonoscopy
Authors: J. A. Tibble, I. Forgacs, I. Bjarnason, R. Przemioslo
Journal: Endoscopy (2000)

Background and Study Aims:Nonattendance for colonoscopy contributes to an increase in the waiting lists for this procedure. Preassessment clinics routinely run for a number of day-patient surgical procedures have been shown to reduce nonattendance rates by enhancing patient understanding. This study aimed to determine prospectively whether preassessing patients booked for colonoscopy would lead to a reduction in the nonattendance rate.
Hemothorax and Heparin
Authors: Carl F. Schaffer
Journal: JAMA (1969)

<h3>To the Editor:—</h3> The synopsis-abstract of the article, "Hemothorax as a Complication of Anticoagulant Therapy in the Presence of Pulmonary Infarction" (<b>208</b>:1830, 1969), by Simon et al includes the statement, "To our knowledge, this complication has not been previously reported." More than a quarter of a century ago, J. W. Keyes and I, then at Henry Ford Hospital, reported a case of "Hemothorax Complicating Heparin Therapy" (<b>JAMA 119</b>:882, 1942). We wonder how many similar or identical cases of pulmonary infarctions in which heparin sodium therapy led to complications have occurred since our report.