tbuckley/cabot-search huggingface dataset:
Intracranial Hemorrhage: Cerebral Amyloid Angiopathy or Nasal Decongestants?
Authors: Michael I. Weintraub
Journal: JAMA (1990)

<h3>To the Editor.—</h3> I would like the physicians who were involved in the recent Questions and Answers discussion of the accountant with massive hemorrhage without apparent cause to reconsider their analysis.<sup>1</sup>They are obviously overlooking an important issue that I believe represents the cause for this patient's sudden massive hemorrhage. According to the history, this 61-year-old man was taking nasal decongestants for 1 week prior to the hemorrhagic event. A number of reports document the association of intracerebral hemorrage with the use of nasal decongestants and similar over-the-counter products.<sup>2-4</sup>Phenylpropanolamine, a synthetic sympathomimetic drug, is available in over-the-counter nasal decongestants and cold preparations. The mechanism of the hypertensive effect of phenylpropanolamine is thought to be related to a combination of α-adrenergic receptor stimulation and release of norepinephrine from nerve terminals. Brain infarction, vasculitis, headaches, seizures, and psychosis are additional neurological complications that have been confirmed as caused
Sickle-Cell Anemia — High Prevalence and Low Priority
Authors: Robert B. Scott
Journal: New England Journal of Medicine (1970)

IN the United States sickle-cell anemia occurs in about one of 500 Negro births and causes progressive disability and shortened life expectancy. Despite its prevalence it is little known by the general public. In a recent survey in Richmond, Virginia, only three of 10 adult Negroes had heard of sickle-cell anemia.1 Yet sickle-cell anemia is more prevalent among Negroes than many highly publicized disorders of children such as cystic fibrosis,2 childhood leukemia3 and phenylketonuria,4 which are principally recognized in white children. In any city with 30 per cent Negro population, more than twice as many children are born with sickle-cell . . .
Role of Industry Representatives in Providing Assistance to Certified Diabetes Educators
Authors: Sue B Daughtry, Kevin F O'Brien, Stuart D Long, Daniel R Scharf
Journal: Diabetes Care (1992)

Objectives As diabetes educators have become more frequently involved in decisions regarding medications, equipment, and supplies, industry representatives have increasingly provided various types of assistance. The major objectives of this survey were to determine 1) the types of assistance being provided to certified diabetes educators (CDEs) by industry representatives, 2) whether product recommendations are based on assistance provided, and 3) the types of assistance that CDEs consider appropriate. Research Design and Methods We developed the survey instrument and it was mailed to every fifth person listed in the 1989 directory of CDEs. Three hundred twenty-five (51%) of the active surveys were returned. Results Those responding indicated that 1) the types of support provided most frequently by industry representatives include instructional materials, samples, supplies, and equipment for patient care and education; 2) the number of types of support provided is directly related to the number of industry representatives seen on a regular basis and the frequency of interaction; 3) 22% of the educators state that they make product recommendations based on support provided; and 4) the role of the industry reps should be to continue support for patient care and education, to provide more support for public and professional education, and to minimize support for personal items, e.g., gifts or meals. Conclusions The survey indicates that CDEs are receiving many types of assistance from industry representatives and that they prefer that such assistance be targeted toward patient and professional education.
Primary lymphoblastic non-Hodgkin's lymphoma of the skin
Authors: R. WILLEMZE, W.A. VLOTEN, E.M. LOO, C.J.L.M. MEYER
Journal: British Journal of Dermatology (1981)

The clinical, histological, and ultrastructural features of a patient with a primary lymphoblastic non‐Hodgkin's lymphoma of the skin are described. Four months after the onset of the disease the patient died with extracutaneous involvement of lymph nodes, spleen, liver, kidneys and lungs. The rapidly fatal outcome without the development of leukaemia or involvement of the bone marrow and the mediastinum is uncommon.
Structure-activity correlations for interactions of bicyclophosphorus esters and some polychlorocycloalkane and pyrethroid insecticides with the brain-specific t-butylbicyclophosphorothionate receptor.
Authors: J E Casida, L J Lawrence
Journal: Environmental Health Perspectives (1985)

[35S]t-Butylbicyclophosphorothionate or [35S]TBPS is an improved radioligand for the picrotoxinin binding site in rat brain synaptic membranes. The toxic isomers of the hexachlorocyclohexanes, polychlorobornanes, and chlorinated cyclodienes displace [35S]TBPS with a stereospecificity and potency generally correlated with their mammalian toxicity. In a few cases this correlation is improved by correction for metabolic activation or detoxification on using a coupled brain receptor/liver microsomal oxidase system. The alpha-cyano-3-phenoxybenzyl pyrethroids, although less potent, inhibit [35S]TBPS binding in a stereospecific manner correlated with their toxicity. Scatchard analyses indicate that these three classes of polychlorocycloalkane insecticides act at the TBPS binding site within the gamma-aminobutyric acid (GABA) receptor-ionophore complex whereas the alpha-cyano pyrethroids interact with a closely associated site. These insecticides and TBPS analogs may serve as useful probes further to elucidate the topography of the TBPS binding site and its relationship to the chloride channel.
Assessing small airways disease
Authors: J. Hansen
Journal: European Respiratory Journal (2008)

The manifestations of the sickling disorders are becoming increasingly familiar to clinicians in Great Britain. One of these disorders, sickle-cell haemoglobin disease, has hitherto received little attention, being regarded as a relatively mild condition. This paper describes some of the distinctive clinical features of the disease as seen in a series of nine cases which have recently presented in London, two of which were fatal. The special hazards of the condition in relation to pregnancy, air travel, and general anaesthesia are discussed.
Abstract 2521: Targeting CD44 in head and neck squamous cell carcinoma (HNSCC) with a new humanized antibody RO5429083
Authors: Aymee Perez, David M. Neskey, Judy Wen, Jarrard W. Goodwin, Joyce Slingerland, Lutecia Pereira, Stefan Weigand, Elizabeth J. Franzmann
Journal: Cancer Research (2012)

Abstract Introduction: HNSCC is a debilitating and deadly disease for which current treatments are extremely toxic and ineffective. Increasing data suggest that persistent cancer stem cells (CSC), resistant to standard chemo and radiation therapy, give rise to disease recurrence. Thus, poor outcomes may reflect ineffective CSC killing. CD44 is a promising therapeutic target that has two defined roles in tumorigenesis: it is a putative cancer initiating cell or CSC marker and it promotes migration and proliferation through interaction with EGFR, Rho and Ras signaling. Therefore therapies that target CD44 may destroy the CSC population, which is resistant to therapy while precisely eradicating the proliferating population of cancer cells. Methods: RO5429083 is a novel functional monoclonal antibody, developed by Roche, that targets a glycosylated, conformation dependent epitope of CD44. To evaluate CD44 as a therapeutic target in vivo, we established CAL 27 (HNSCC cell line) xenografts in nude mice and treated them with RO5429083 (Roche) in comparison to cisplatin (DPP), a conventional drug used in HNSCC treatment. After treatment, the mice were sacrificed, and the tumors were embedded in paraffin for IHC analysis. We also analyzed the effect of RO5429083 in vitro on peripheral blood lymphocytes (PBMCs). Results: RO5429083 treatment displayed a remarkable tumor growth inhibition in CAL 27 xenografts compared to DPP or control (P&amp;lt;0.005). Moreover, treatment with this new humanized antibody inhibited constitutive EGFR phosphorylation on CAL 27 xenografts. In addition, treatment of PBMCs from healthy donors with RO5429083 produced an expansion of cytolytic natural killer (NK) cells. Conclusion: Based on our studies the anti-CD44 antibody RO5429083 effectively inhibits tumor growth in the CAL 27 model of HNSCC. In addition to decreasing EGFR signaling, RO5429083 appears to have a protective effect on PBMCs and expands the NK cell population. In conclusion, we anticipate that anti-CD44 therapy will effectively target the stem cell population while boosting the number of NK cells, and thus may synergize with drugs that work via antibody-dependent cell-mediated cytotoxicity (ADCC) such as Cetuximab. 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 2521. doi:1538-7445.AM2012-2521
Protective Role of Angiopoietin-1 in Endotoxic Shock
Authors: Bernhard Witzenbichler, Dirk Westermann, Sabine Knueppel, Heinz-Peter Schultheiss, Carsten Tschope
Journal: Circulation (2004)

Angiopoietin-1 (Ang1) plays an essential role in embryonic vasculature development, protects the adult peripheral vasculature from leakage, and has antiinflammatory properties. Because endotoxin-induced shock is a condition with microvascular leakage resulting from inflammation, we examined the potential therapeutic benefit of Ang1 in a murine model of lipopolysaccharide (LPS)-induced endotoxic shock.To induce endotoxic shock, LPS was injected intraperitoneally into C57BL/6 mice. Half of the mice received an intravenous application of 1.0x10(9) plaque-forming units of an adenoviral construct expressing human Ang1 (AdhAng1); in the other half an identical vector expressing green fluorescent protein (AdGFP) was injected as a control. In the AdhAng1-treated mice, hepatic transfection and high expression of circulating Ang1 protein were observed. Whereas in LPS-treated control mice, hemodynamic function was severely depressed 12 hours after LPS injection (decrease of blood pressure from 91+/-3 to 49+/-7 mm Hg, dP/dt(max) from 7284+/-550 to 2699+/-233 mm Hg/s, cardiac output from 11.3+/-1.2 to 2.8+/-0.8 mL/min; P<0.0005), in LPS-treated AdhAng1 mice blood pressure fell only to 76+/-3 mm Hg, dP/dt(max) to 5091+/-489 mm Hg/s, and cardiac output to 6.7+/-1.4 mL/min (P<0.05). This resistance to LPS-induced hemodynamic changes was reflected by an improved Kaplan-Meier survival rate of the AdhAng1 mice. Histological analysis revealed that lung injury after LPS injection was markedly attenuated in AdhAng1 mice. In addition, LPS-induced increase in lung water content and pulmonary myeloperoxidase activity was significantly reduced. Furthermore, LPS-induced increases in the expression level of vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin protein in the lungs were markedly lower in AdhAng1 mice than in control mice. Finally, in the mice overexpressing Ang1, pulmonary endothelial NO synthase (eNOS) expression and activity remained preserved after LPS challenge, providing evidence that the beneficial effect of Ang1 in endotoxic shock is mediated by eNOS-derived NO.Our study demonstrates an improved mortality rate in mice with endotoxic shock pretreated with an adenoviral construct encoding Ang1. The enhanced survival rate induced by Ang1 was accompanied by an improvement in hemodynamic function, reduced lung injury, a lower expression of inflammatory adhesion molecules, and preserved eNOS activity in the lung tissue. Ang1 may therefore have utility as an adjunctive agent for the treatment of septic shock condition.
Atropine Inhibits the Increase in Gastric Emptying During Hypoglycemia in Humans
Authors: Erik Schvarcz, Mats Palmér, Jan Åman, Christian Berne
Journal: Diabetes Care (1995)

OBJECTIVE To study the effect of a cholinergic muscarinic blockade on the gastric emptying rate during insulin-induced hypoglycemia in healthy subjects. RESEARCH DESIGN AND METHODS In eight healthy subjects, the rate of gastric emptying of an isotope-labeled meal was assessed by a scintigraphic technique during normoglycemia and hypoglycemia with simultaneous infusion of either atropine or saline. Blood glucose concentrations were controlled by an insulin-glucose clamp. RESULTS The median time for emptying 50% of the liquid phase from the stomach (T50) was 24.9 min (range 13.9−120.0) during normoglycemia compared with 8.1 min (range 3.6−16.5) during hypoglycemia without atropine infusion (P = 0.0005). The T50 for the solid phase was 26.8 min (range 9.7−74.0) and 43.1 min (range 29−57.8), respectively (P = 0.007). During hypoglycemia with atropine infusion, T50 was 40.7 min (range 10.0−120.0) for the liquid phase and 111.4 min (range 38.9−120.0) for the solid phase, not statistically different from normoglycemic examinations. CONCLUSIONS Cholinergic muscarinic blockade with atropine inhibits the increase in gastric emptying during hypoglycemia. Vagal activity seems to be an important determinant of gastric emptying during hypoglycemia.
IS MERCANTILE HEALTH SERVICE A DANGER OR AN ASSET TO MEDICAL PRACTICE?
Authors: A. B. Emmons
Journal: JAMA (1927)

<h3>To the Editor:</h3> —InThe Journal, Dec. 25, 1926, p. 2180, is a review of "Health Control in Mercantile Life." The reviewer says: "Many physicians view with anxiety, if not with dread and alarm, present trends toward contract medical practice.... Is it for the good of the patients that they be treated with this type of service or is it preferable... that they be advised to select good physicians?" Kindly allow me to point out a few facts disclosed by this six year demonstration in store health work: An average of from six to twelve visits a year was voluntarily made by each person in at least a dozen stores where records were kept. The cost of each visit averaged about 50 cents because the work was organized to use effectively the time of the physician, the nurse, the dentist, the dental hygienist and sometimes the physical educator. Part of
A Pain in the Neck
Authors: Sandra J. Bliss, Scott A. Flanders, Sanjay Saint
Journal: New England Journal of Medicine (2004)

A previously healthy 16-year-old girl presented to her physician because of a two-day history of sore throat, fatigue, fever, headache, and vomiting. On examination, her temperature was 36.7°C. She had mild erythema and white plaques on her tonsillar pillars and mild tenderness of the anterior neck, without lymphadenopathy.
Automatic Washer Disinfector for Flexible Endoscopes: A New Evaluation Process
Authors: L. Pineau, C. Roques, J. Luc, G. Michel
Journal: Endoscopy (1997)

Many automatic washer disinfectors for flexible endoscopes have been marketed and offered as an alternative method of preventing infections, but they are frequently unsatisfactory. There is therefore clearly a need to test prototypes prior to marketing, following an evaluation process that is sufficiently reliable and rigorous to guarantee the efficacy of the decontamination processes.The present study describes an experimental method based on the follow-up of the decontamination of a Tygon tube, the internal surface of which was contaminated by a bacterial biofilm. This method is proposed as a preliminary test for evaluating washer disinfectors.An analysis of the results obtained after technical modifications of the first prototype of the Fibro-Cleaner showed that complementary activities of each successive cycle phase allow a reduction in the number of adherent bacteria of more than 8 log per cm2 of support. With the three different biofilms tested (Escherichia coli, Pseudomonas aeruginosa mucoid and Staphylococcus aureus), no microorganisms were recovered from the support at the end of the decontamination process.The experimental protocol suggested here seems to be well suited for assessing washer disinfectors during the development phase of the prototype, as well as for comparative studies.
Deciphering the Molecular Events Necessary for Synergistic Tumor Cell Apoptosis Mediated by the Histone Deacetylase Inhibitor Vorinostat and the BH3 Mimetic ABT-737
Authors: Adrian P. Wiegmans, Amber E. Alsop, Michael Bots, Leonie A. Cluse, Steven P. Williams, Kellie-Marie Banks, Rachael Ralli, Clare L. Scott, Anna Frenzel, Andreas Villunger, Ricky W. Johnstone
Journal: Cancer Research (2011)

The concept of personalized anticancer therapy is based on the use of targeted therapeutics through in-depth knowledge of the molecular mechanisms of action of these agents when used alone and in combination. We have identified the apoptotic proteins and pathways necessary for synergistic tumor cell apoptosis and in vivo antitumor responses seen when the HDAC inhibitor vorinostat is combined with the BH3-mimetic ABT-737 in lymphomas overexpressing Bcl-2. Vorinostat "primes" tumors overexpressing Bcl-2 for rapid ABT-737-mediated apoptosis by inducing expression of the BH3-only gene bmf. Moreover, these synergistic effects of vorinostat/ABT-737 were blunted in cells with an inactive p53 pathway or in cells lacking expression of the p53 target gene, noxa. These studies show the important and complex functional interaction between specific proapoptotic BH3-only proteins and the BH3-mimetic compound ABT-737 and provide the most comprehensive functional link between tumor genotype and the apoptotic and therapeutic effects of HDACi combined with ABT-737.
A Clinical Prediction Model to Assess Risk for Chemotherapy-Related Hospitalization in Patients Initiating Palliative Chemotherapy
Authors: Gabriel A. Brooks, Ankit J. Kansagra, Sowmya R. Rao, James I. Weitzman, Erica A. Linden, Joseph O. Jacobson
Journal: JAMA Oncology (2015)

Chemotherapy-related hospitalizations in patients with advanced cancer are common, distressing, and costly. Methods to identify patients at high risk of chemotherapy toxic effects will permit development of targeted strategies to prevent chemotherapy-related hospitalizations.To demonstrate the feasibility of using readily available clinical data to assess patient-specific risk of chemotherapy-related hospitalization.Nested case-control study conducted from January 2003 through December 2011 at the Mass General/North Shore Cancer Center, a community-based cancer center in northeastern Massachusetts. The parent cohort included 1579 consecutive patients with advanced solid-tumor cancer receiving palliative-intent chemotherapy. Case patients (n = 146) included all patients from the parent cohort who experienced a chemotherapy-related hospitalization. Controls (n = 292) were randomly selected from 1433 patients who did not experience a chemotherapy-related hospitalization.Putative risk factors for chemotherapy-related hospitalization-including patient characteristics, treatment characteristics, and pretreatment laboratory values-were abstracted from medical records. Multivariable logistic regression was used to model the patient-specific risk of chemotherapy-related hospitalization.Chemotherapy-related hospitalization, as adjudicated by the oncology clinical care team within a systematic quality-assessment program.A total of 146 (9.2%) of 1579 patients from the parent cohort experienced a chemotherapy-related hospitalization. In multivariate regression, 7 variables were significantly associated with chemotherapy-related hospitalization: age, Charlson comorbidity score, creatinine clearance, calcium level, below-normal white blood cell and/or platelet count, polychemotherapy (vs monotherapy), and receipt of camptothecin chemotherapy. The median predicted risk of chemotherapy-related hospitalization was 6.0% (interquartile range [IQR], 3.6%-11.4%) in control patients and 14.7% (IQR, 6.8%-22.5%) in case patients. The bootstrap-adjusted C statistic was 0.71 (95% CI, 0.66-0.75). At a risk threshold of 15%, the model exhibited a sensitivity of 49% (95% CI, 41%-57%) and a specificity of 85% (95% CI, 81%-89%) for predicting chemotherapy-related hospitalization.In patients initiating palliative chemotherapy for cancer, readily available clinical data were associated with the patient-specific risk of chemotherapy-related hospitalization. External validation and evaluation in the context of a clinical decision support tool are warranted.
Cardiac Neural Crest Expression of Hand2 Regulates Outflow and Second Heart Field Development
Authors: Yuka Morikawa, Peter Cserjesi
Journal: Circulation Research (2008)

The cardiac neural crest (cNC) lineage plays key roles in heart development by directly contributing to heart structures and regulating development of other heart lineages. The basic helix-loop-helix factor Hand2 regulates development of cardiovascular structures and NC-derived tissues including those that contribute to face and peripheral nervous system. Although Hand2 is expressed in cNC, its role has not been examined because of an early embryonic lethality when Hand2 is deleted in the NC lineage. We find that the lethality is attributable to loss of norepinephrine synthesis that can be overcome by activating adrenergic receptors. In rescued embryos, loss of Hand2 in the NC lineage leads to the misalignment of the outflow tract and aortic arch arteries. Defects include pulmonary stenosis, interrupted aortic artery, retroesophageal right subclavian artery, and ventricular septum defect, which resemble congenital heart defects attributed to defects in the NC. Hand2 functions in part by regulating signaling from the cNC to other cardiac lineages but not by regulating migration or survival of the cNC. Loss of Hand2 in NC also uncovered a novel role for the cNC in regulating proliferation and differentiation of the second heart field-derived myocardium that persists late into development. These results show that the cNC functions as a major signaling center for heart development and Hand2 plays a pivotal role in regulating both cell-autonomous and -nonautonomous functions of the cNC.