tbuckley/cabot-search huggingface dataset:
Abstract 3594: Conformational control of FMS kinase for treatment of human malignancies
Authors: Scott C. Wise, Molly M. Hood, Bryan D. Smith, Deanne Lister, Wei-Ping Lu, Michael D. Kaufman, Patrick McConville, Daniel L. Flynn
Journal: Cancer Research (2011)

Abstract FMS kinase is involved in the process of osteoclast maturation. Osteoclasts have been shown to play a role not only in arthritic diseases but also in a cancers ability to metastasize to the bone. This is especially true for breast, lung and prostate cancer. Taken together the ability to prevent osteoclast maturation and accumulation through FMS inhibition should be a good target for small molecule therapy of bone metastasis. Using Deciphera Pharmaceutical's approach to kinase inhibition, compounds have been designed that potently inhibit FMS kinase. These inhibitors can be highly selective with lead compounds inhibiting only a single kinase within 20 fold of FMS activity in a 300 kinase profile. A second class broadens the profile to include anti-angiogenic kinase targets in addition to potent FMS inhibition. This presentation will highlight the attributes and development status of these compounds for treatment of human malignancies. Deciphera's FMS program has afforded potent inhibitors that achieve single digit nanomolar inhibition in biochemical assays of FMS activity. The inhibitors retain this same level of potency in the presence of high (5mM) ATP concentrations. These same compounds are also selective with some inhibiting as few as three kinases within 50 fold of FMS potency. In addition, proliferation and FMS phosphoprotein assays performed with M-NFS-60 and THP-1 cells have demonstrated excellent inhibitory profiles with achieved potencies in the low nanomolar range. In functional osteoclast differentiation models, key compounds have demonstrated single digit nanomolar inhibition as assessed by TRAP assays. In vivo evaluation of the inhibitors produced excellent tolerance in two week MTD studies. Potent and durable efficacy in pharmacokinetic/pharmacodynamic xenograft models was also observed demonstrating on target effects. In vivo models of bone invasion coupled with non-invasive translational image-based biomarkers potentially provide a powerful method for visualization and quantification of osteoclast activity and FMS inhibition. Early results in imaging of bone invasion will be presented using micro CT and fluorescent activateable probes. Deciphera's FMS inhibitors show acceptable ADME properties in cell permeability, cytochrome p450 inhibition, microsomal clearance and are orally bioavailable in rat and dog. Key prototype compounds have been evaluated in a two week rat tolerability study. These data demonstrate that Deciphera's technology has been used to identify potent and selective FMS inhibitors to be developed for treatment of cancers where metastasis to bone is an issue. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3594. doi:10.1158/1538-7445.AM2011-3594
Complications in Patients Undergoing Cardiac Electrophysiologic Procedures
Authors: JOHN P. DIMARCO
Journal: Annals of Internal Medicine (1982)

Complications were seen in 20 of 359 patients having programmed electrical stimulation during 1062 cardiac electrophysiologic procedures. No deaths occurred. Direct current countershock was used to end arrhythmias with serious hemodynamic consequences on 107 occasions. Countershock was effective in all cases and not associated with morbidity. The complications in 20 patients were related to intravascular catheterization and included thromboembolism (nine patients), local or systemic infections (six patients), and pneumothorax (five patients). All 20 patients recovered from these complications without long-term sequelae. Intracardiac electrophysiologic procedures can be done with an acceptably low risk in patients with life-threatening or disabling arrhythmias.
THE RELATIVE EFFECTS OF SEVERAL SUBSTANCES IN MINIMIZING IRRITATION CAUSED BY ADHESIVE PLASTER
Authors: Robert F. Legge
Journal: JAMA (1941)

Feeling that the degree and amount of irritation produced by adhesive plaster might be minimized by attempting to protect the skin before its application with certain substances, I carried out the series of observations presented in this paper. Previously the investigation of this phenomenon had been directed chiefly toward an effort to determine the factors involved in its production. This was done, undoubtedly, with the object of removing from the plaster the irritants which caused the irriitation. Apparently it is impossible to remove these irritants without reducing the effectiveness of the plaster so far as its adhesive properties are concerned. Schwartz and Peck<sup>1</sup>in 1935 concluded as a result of their studies that the chief irritants were resins and smoke-cured wild rubber and that irritation was due partially to hypersensitivity to one of these ingredients. However, they also felt that some irritation resulted from maceration of the skin from
Promotion of Cigarettes in Developing Countries
Authors: Ronald M. Davis
Journal: JAMA (1986)

A recent article<sup>1</sup>and editorial<sup>2</sup>inThe Journalexplored the epidemiology and ethical implications of exporting a hazardous product beyond the borders of the United States. In this case, the product was turtles. Another example of such activity is the marketing and promotion of cigarettes in developing countries by US manufacturers and their foreign subsidiaries. The Surgeon General has called cigarette smoking "the chief, single, avoidable cause of death in our society and the most important public health problem of our time."<sup>3</sup>In addition, cigarette smoking is well on its way to becoming the number one health problem in the Third World.<sup>4</sup> The role of US manufacturers in foreign cigarette consumption may involve the exportation of US-made cigarettes or the exportation of unmanufactured tobacco for cigarette production outside the United States. In 1984, US manufacturers exported 56.5 billion cigarettes and 246,156 tons of unmanufactured tobacco.<sup>5</sup>
Disseminated Intravascular Coagulation in Heat Stroke
Authors: Jacob Fine
Journal: JAMA (1975)

<h3>To the Editor.—</h3> An editorial by Knochel (231:496, 1975) comments on a case report of heat stroke in the same issue (231:480, 1975) that deals with the disseminated intravascular coagulation (DIC) that developed as a complication of the heat stroke. There is no reference in the editorial to a case report published earlier inThe Journal(216:1195,1971) in which this hemorrhagic diathesis, as well as the other complications of heat stroke, were accounted for by an endotoxemia of intestinal origin that is the result of acute hepatic failure. Endotoxemia has since been documented in hepatic damage not only by heat stroke, but also in viral hepatitis, advanced cirrhosis, and drug poisoning. The striking uniformity of the clinical picture in all these disorders (brain damage, congestion and edema of the lungs, and renal failure in addition to DIC), and their resemblance to those produced by endotoxemia in advanced Gram-negative sepsis, points
HIGH TRANSVALVULAR GRADIENT VERSUS LOW TRANSVALVULAR GRADIENT IN PATIENTS WITH SEVERE AORTIC STENOSIS AND POOR LEFT VENTRICULAR FUNCTION
Authors: Itsik Ben-Dor, Michael A. Gaglia, Kohei Wakabayashi, Gabriel Maluenda, Manuel A. Gonzalez, Michael Mahmoudi, Gabriel Sardi, Rafael Romaguera, Ana Laynez-Carnicero, Rebecca Torguson, Petros Okubagzi, Zhenyi Xue, William O. Suddath, Kenneth M. Kent, Joseph Lindsay, Lowell F. Satler, Augusto D. Pichard, Ron Waksman
Journal: Journal of the American College of Cardiology (2011)
To Have Been or Not to Have Been
Authors: Robert B. Failey
Journal: JAMA (1965)

<h3>To the Editor:—</h3> In the editorial "To Have Been or Not to Have Been" (<i>JAMA</i><b>190</b>:849 [Nov 30] 1964) the author discusses certain shortcomings of medical writing. In his second paragraph he refers to "sundry vices such as the utilization of polysyllabic structuralizations on a preferential basis, the use of an elongated verbalization instead of a short word, and even the use of incorrect (but correct-sounding) words, although one would not wish to hypothecate that the latter fault was ever deliberate." The late Dr. W. D. Gatch, who was for many years Dean of the Indiana University School of Medicine, was fond of pointing out that the word hypothecate means to pledge, usually in the sense of pledging a security. The proper word in this situation is hypothesize. This teaching has stuck with me for a good many years, and I pass it on to the author of your
Sports medicine Booster doses are not needed
Authors: F Sim, J C M Sharp, K Hay, R M Monsell
Journal: BMJ (1994)

EDITOR, - J C M Sharp's advice on tetanus immunisation1 is contrary to that specified in the current edition of the “green book.” For immunised adults who have received five doses of tetanus vaccine, either as children or according to the recommended schedule of immunisation for those aged 10 years and over, booster doses are not recommended, other than at time of injury, since they have been shown to be unnecessary and can cause considerable local reactions.2 Sharp's recommendation that people should have booster doses at 10 year intervals and that boosters should be considered at five year intervals for athletes is now out of date. 1. 1.↵1. Sharp JCM. Infections in sport. BMJ 1994;308:1702-6. [OpenUrl][1][FREE Full Text][2] 2. 2.↵Department of Health, Welsh Office, Scottish Home and Health Department, DHSS (Northern Ireland). Immunisation against infectious disease. London: HMSO, 1992:37-43. # Author's reply {#article-title-3} EDITOR, - The Department of Health's recommendation limiting the number of doses of tetanus vaccine for prophylaxis … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DSharp%26rft.auinit1%253DJ%2BC%2BM%26rft.volume%253D308%26rft.issue%253D6945%26rft.spage%253D1702%26rft.epage%253D1706%26rft.atitle%253DABC%2Bof%2BSports%2BMedicine%253A%2BInfections%2Bin%2Bsport%26rft_id%253Dinfo%253Apmid%252F8025471%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=bmj&resid=308/6945/1702&atom=%2Fbmj%2F309%2F6952%2F474.1.atom
Abstract P3-05-05: Classification using dynamic re-discovery of the strongest prognostic features in each analysis outperforms static gene expression signatures for prognostic prediction in breast cancer
Authors: B Györffy, T Karn, Z Sztupinszki, B Weltz, V Müller, L Pusztai
Journal: Cancer Research (2013)

Abstract Introduction: To overcome limitations of previous multigene prognostic classifiers, we propose a new dynamic predictor. Our classifier does not use a single universal training cohort and an identical list of informative genes to predict the prognosis of new cases but a case-specific predictor is developed for each test case. Methods: We analyzed gene expression data from 3,534 breast cancers with clinical annotation including survival. For each test case we select a case-specific training subset including only molecularly similar cases and a case-specific predictor is generated. This method yields different training sets and different predictors for each new patient but preserves the independence of model building and validation. The model performance was assessed in leave-one-out validation and also in 325 independent cases. Results: Prognostic discrimination was high for all cases (n = 3,534, HR = 3.68, p = 1.67E-56). The dynamic predictor showed higher overall accuracy (0.68) than genomic surrogates for the 21-gene predictor (0.64), the 97-gene genomic grade index (0.55) or the 70-gene prognostic signature (0.41). The dynamic predictor was also effective in triple-negative cancers (n = 427, HR = 3.08, p = 0.0093) where the above classifiers all failed. Validation in independent patients yielded similar classification power (HR = 3.57). Discussion: We developed a new method to make personalized prognostic prediction using case-specific training cohorts. The dynamic predictors outperform static models developed from single historical training cohorts and they also predict well in triple-negative cancers. The dynamic classifier is available on line at http://www.recurrenceonline.com/?q = Re_training. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-05-05.
Outcomes After Out-of-Hospital Cardiac Arrest Treated by Basic vs Advanced Life Support
Authors: Prachi Sanghavi, Anupam B. Jena, Joseph P. Newhouse, Alan M. Zaslavsky
Journal: JAMA Internal Medicine (2014)

Most out-of-hospital cardiac arrests receiving emergency medical services in the United States are treated by ambulance service providers trained in advanced life support (ALS), but supporting evidence for the use of ALS over basic life support (BLS) is limited.To compare the effects of BLS and ALS on outcomes after out-of-hospital cardiac arrest.Observational cohort study of a nationally representative sample of traditional Medicare beneficiaries from nonrural counties who experienced out-of-hospital cardiac arrest between January 1, 2009, and October 2, 2011, and for whom ALS or BLS ambulance services were billed to Medicare (31,292 ALS cases and 1643 BLS cases). Propensity score methods were used to compare the effects of ALS and BLS on patient survival, neurological performance, and medical spending after cardiac arrest.Survival to hospital discharge, to 30 days, and to 90 days; neurological performance; and incremental medical spending per additional survivor to 1 year.Survival to hospital discharge was greater among patients receiving BLS (13.1% vs 9.2% for ALS; 4.0 [95% CI, 2.3-5.7] percentage point difference), as was survival to 90 days (8.0% vs 5.4% for ALS; 2.6 [95% CI, 1.2-4.0] percentage point difference). Basic life support was associated with better neurological functioning among hospitalized patients (21.8% vs 44.8% with poor neurological functioning for ALS; 23.0 [95% CI, 18.6-27.4] percentage point difference). Incremental medical spending per additional survivor to 1 year for BLS relative to ALS was $154,333.Patients with out-of-hospital cardiac arrest who received BLS had higher survival at hospital discharge and at 90 days compared with those who received ALS and were less likely to experience poor neurological functioning.
The Legal Limits of AIDS Confidentiality
Authors: Jeff Stryker
Journal: JAMA (1988)

<h3>To the Editor.—</h3> When information regarding a diagnosis of human immunodeficiency virus (HIV) infection falls into the wrong hands the result may be the loss of employment, housing, and insurance coverage and the disruption of relationships with family and friends. Legal protections of confidentiality are the first line of defense in the fight against HIV-related discrimination. Because there are occasional situations in which confidentiality can be breached with moral and legal impunity, Dr Dickens<sup>1</sup>would have us instead fall back on the protections provided by antidiscrimination laws—once the damage is done and the horse is out the barn door and down the road a piece. Dr Dickens beats too hasty a retreat. If the legal protections of confidentiality are "illusory," they should be shored up, not abandoned. It is difficult, but not impossible, to balance duties owed to patients and to third parties and to define in advance the
ANTIGENIC SPECIFICITIES ON MURINE SARCOMA CELLS
Authors: Gerald R. Haywood, Charles F. McKhann
Journal: The Journal of Experimental Medicine (1971)

Five methylcholanthrene-induced sarcomas were compared for their capacity to (a) absorb monospecific H-2 antisera, (b) induce tumor-specific immunity in syngeneic mice, and (c) metastasize early to the lungs. Comparison of the uptakes of monospecific H-2 antisera by the five different tumors showed that each of the tumors had a high, intermediate, or low surface representation of all of the seven specificities tested. No antigenic specificity was completely absent from any tumor, and no tumor had an unusually large or small amount of any individual specificity. The tumors could be placed in the sequence from one to five with respect to their H-2 antigenicity. The same five tumors were also ranked with respect to their capacity to induce a tumor-specific immune response in syngeneic mice. The tumor-specific immunogenicity had an inverse relationship to the H-2 antigenicity in that highly immunogenic tumors were those that had quantitatively less H-2 antigen on their surface and vice versa. Early metastases to the lung was associated with low levels of tumor-specific immunogenicity and high levels of H-2 antigenicity.
Management of anemia induced by triple therapy in patients with chronic hepatitis C: Challenges, opportunities and recommendations
Authors: Manuel Romero-Gómez, Marina Berenguer, Esther Molina, José Luis Calleja
Journal: Journal of Hepatology (2013)

The addition of protease inhibitors, boceprevir or telaprevir, to peginterferon + ribavirin (PegIFN/RBV) increases the frequency as well as the severity, and hence, clinical relevance of anemia, which has now become one of the major complications associated with triple therapy. Most significant factors associated with anemia in patients receiving triple therapy include older age, lower body mass index (BMI), advanced fibrosis, and lower baseline hemoglobin. The variability in inosine triphosphate pyrophosphatase (ITPA) gene, which encodes a protein that hydrolyses inosine triphosphate (ITP), has been identified as an essential genetic factor for anemia both in dual and triple therapy. The correct management of anemia is based on anticipation, characterization and therapeutic management. Basically, anemia can be characterized in 3 types: ferropenic (mostly in fertile women), thalassemic type hemolytic anemia, and anemia from chronic processes. Functional deficit of iron should also be excluded in patients with normal ferritin and lower saturation of transferrin. Ribavirin dose reduction and epoetin, sequentially, are indicated in the management of anemia. Epoetin non-response can be caused by lack of time, type of anemia, functional iron deficit or erythropoietin resistance. In the transplantation setting, adding a protease inhibitor to PegIFN/RBV results in a significant increase in the incidence and severity of anemia and, as a consequence, a greater need for epoetin, transfusions, and ribavirin dose reductions. Packed red cell transfusions are utilized when hemoglobin decreases to less than 7.5 g/dl and/or there are clinical symptoms and/or there is no response to other therapeutic measures.
Norovirus gastroenteritis causes severe and lethal complications after chemotherapy and hematopoietic stem cell transplantation
Authors: Stefan Schwartz, Maria Vergoulidou, Eckart Schreier, Christoph Loddenkemper, Mark Reinwald, Martin Schmidt-Hieber, Willy A. Flegel, Eckhard Thiel, Thomas Schneider
Journal: Blood (2011)
Perfusion Vascularity Mismatch in Liver Hemangiomas
Authors: DOV FRONT, RUTH HARDOFF, ORA ISRAEL, SILVIO O. SCHNECK
Journal: Clinical Nuclear Medicine (1978)

Perfusion defect in the dynamic study and slow filling of the lesion by a blood pool agent were observed in three cases with large cavernous hemangiomas of the liver. This finding is explained by the low perfusion and the large blood volume of cavernous hemangiomas. When such a lesion is suspected a late blood pool study should be performed in order to demonstrate the true vascularity of the lesion.
Percutaneous balloon catheterization. A technique for the control of arterial hemorrhage caused by pelvic trauma
Authors: S. B. Paster
Journal: JAMA (1974)

We have employed balloon catheters to establish hemostasis in two patients with arterial hemorrhage caused by pelvic trauma. The catheters were introduced percutaneously under fluoroscopic guidance with a standard catheter-guidewire system. Within 24 hours, the bleeding had ceased in both patients. No sequelae associated with the therapy developed. Alternative therapy for these patients is surgical arterial ligation or clot embolization. Both of these approaches have inherent hazards that are obviated by balloon obstruction. (<i>JAMA</i>230:573-575, 1974)
Reply to Fabio Camponodico and Alberto Michelazzi’s Letter to the Editor re: Enzo Palminteri, Elisa Berdondini, Fulvio Colombo and Edoardo Austoni. Small Intestinal Submucosa (SIS) Graft Urethroplasty: Short-term Results. Eur Urol 2007;51:1695–701
Authors: Enzo Palminteri
Journal: European Urology (2007)
Report of the President
Authors: Walter G. Phippen
Journal: New England Journal of Medicine (1947)

IT IS an annual custom for the President to inform the fellows of the condition of the Library. It is my pleasant duty to present my first annual report.The status of medical libraries in Boston has been a subject of discussion for some years. In 1941 a survey of this situation was made by Mr. Thomas P. Fleming, medical librarian of Columbia University, and his comprehensive report was studied by a committee consisting of Mr. Fleming and Drs. John F. Fulton and Robert N. Nye. This committee brought out the following points:In general, medical institutions in Boston have . . .
An Unforeseen Complication of Oral Flurazepam Therapy
Authors: R. Düsing, D. Haberland, S.E. Miederer
Journal: Endoscopy (1983)

Accident rare: un malade de 72 ans hospitalise pour differentes affections (fracture du maxillaire, diabete, insuffisance cardiaque) se plaint de douleurs epigastriques et retrosternales depuis plusieurs heures. L'endoscopie montre le blocage au niveau du cardia d'un corps etranger qui n'est autre qu'un comprime de flurazepam encore muni de son emballage d'aluminium dont les 4 coins ont blesse la muqueuse
Polyclonal stimulation of resting B lymphocytes by antigen-specific T lymphocytes.
Authors: A L DeFranco, J D Ashwell, R H Schwartz, W E Paul
Journal: The Journal of Experimental Medicine (1984)

Resting B lymphocytes are activated, proliferate, and differentiate into antibody-secreting cells when cultured with long-term lines of major histocompatibility complex (MHC)-restricted, antigen-specific T cell in the presence of the antigen for which the T cells are specific. Under optimal conditions, essentially all B cells are activated and approximately 35% enter S phase in the absence of antigens for which the B cells are specific. Activation and proliferation are observed in cells from both normal mice and mice with the xid-determined immune defect. Highly purified B cells bearing Ia molecules for which the T cells are "cospecific" can present antigen to T cells with the resulting T cell stimulation leading to the activation and proliferation of the antigen-presenting B cells. However, B cells that do not bear Ia molecules for which the T cells are cospecific are also activated and proliferate if antigen and a source of antigen-presenting B cells or macrophage-rich cells of proper histocompatibility type are present. Thus, resting B cells, both normal and "xid", can be activated by non-MHC restricted factors without receptor cross-linkage. Experiments are presented that support the concept that local production and action of such unrestricted activating factors may be responsible for the MHC-restriction of T cell-B cell interaction seen in many circumstances.
Siliceous Granuloma cause of Peritoneal Adhesion
Authors: W. Walker
Journal: BMJ (1948)

should be noted, however, that in this type of case the irritant is a different compound of silicon from that present in talc.Even then one was hesitant to accept the present case as being siliceous, in view of the short period of five months between the appendicectomy, when presumably the talc was introduced, and the subsequent discovery of a tubal granuloma.Walker (see below) has now shown that in