tbuckley/cabot-search huggingface dataset:
The RADAR Project and the FDA—Reply
Authors: Charles L. Bennett, Jonathan R. Nebeker, Dennis W. Raisch
Journal: JAMA (2005)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
THE HEMODYNAMIC EFFECTS OF SYMPATHECTOMY IN ESSENTIAL HYPERTENSION
Authors: R W WILKINS, J W CULBERTSON, M H HALPERIN
Journal: Annals of Internal Medicine (1949)

Excerpt Surgical sympathectomy has been employed so extensively for the treatment of essential hypertension that one might assume its hemodynamic effects to be completely understood. Quite to the contrary, however, very little is known concerning its direct vascular or indirect metabolic effects that will explain its success in some cases and its failure in others. Until these matters are fully understood the rationale for surgical treatment, and indeed for medical management, of essential hypertension must remain on an empirical basis. For this reason these problems have been and will continue to be the subject of long-term investigation in this laboratory. MATERIALS
Investigation of the Combination Effects of Andrographis Paniculata With Chemotherapeutics for Esophageal Cancer Treatment
Authors: L. Li, G.G.L. Yue, J.M.K. Lee, E.C.W. Wong, K.M. Chan, K.P. Fung, J. Yu, C.B.S. Lau, P.W.Y. Chiu
Journal: Clinical Gastroenterology and Hepatology (2015)
ABC of Transfusion
Authors: Marcela Contreras
Journal: Annals of Internal Medicine (1991)

Contributors, v Introduction, vii 1 The Blood Donor: Demographics, Donor Selection and Tests on Donor Blood, 1 Liz Caffrey, Patricia Hewitt and John Barbara 2 Supply and Demand for Blood and Blood Components and Stock Management, 6 Judith Chapman, Peter Garwood and Sue Knowles 3 Compatibility Testing Before Transfusion Blood Ordering and Administration, 10 Marcela Contreras and Aleksandar Mijovic 4 Red Cell Transfusion, 15 Mike Murphy and Jonathan Wallis 5 Platelet and Granulocyte Transfusions, 22 Modupe Elebute, Simon Stanworth and Cristina Navarrete 6 Haemolytic Disease of the Newborn and its Prevention, 27 Fiona Regan, Sailesh Kumar and Marcela Contreras 7 Fetal and Neonatal Transfusion, 33 Helen V. New and Sailesh Kumar 8 Plasma Products and Indications for Their Use, 40 Hannah Cohen and Trevor Baglin 9 Human Albumin Solutions and the Controversy of Crystalloids Versus Colloids , 48 Neil Soni 10 Treatment of Massive Haemorrhage in Surgery and Trauma, 54 Tim Walsh 11 Immunological Complications of Blood Transfusion, 61 Marcela Contreras and Cristina Navarrete 12 Infectious Complications of Blood Transfusion: Bacteria and Parasites, 69 John Barbara and Marcela Contreras 13 Infectious Complications of Blood Transfusion: Viruses, 74 John Barbara and Marcela Contreras 14 Variant Creutzfeldt--Jakob Disease and its Impact on the UK Blood Supply, 79 Patricia Hewitt, James Ironside and Marcela Contreras 15 Risks of Transfusion in the Context of Haemovigilance: SHOT -- the UK Haemovigilance System, 83 Dorothy Stainsby, Hannah Cohen and Brian McClelland 16 Alternatives to Allogeneic Blood Transfusion, 89 Dafydd Thomas and Beverley Hunt 17 Blood Substitutes and Oxygen Therapeutics, 95 Kenneth C. Lowe 18 Appropriate Use of Blood and Better Blood Transfusion, 99 Mike Murphy 19 Stem Cell Transplantation and Cellular Therapies, 104 Aleksandar Mijovic, Derwood Pamphilon and Suzanne Watt 20 Blood Transfusion in a Regulatory Environment and the EU Directives, 110 Shubha Allard, Clare Taylor and Angela Robinson Index, 117
DIVERTICULA OF THE GASTROINTESTINAL TRACT
Authors: M. A. GOLD, M.D., J. G. SAWYER, M.D.
Journal: Annals of Internal Medicine (1952)

ExcerptThe subject of diverticula and their attending complications is one which is usually without drama and therefore usually without great interest to the average physician. The great majority of cases are not diagnosed clinically but are discovered during surgical procedures or, what is more common, during an examination by the roentgenologist searching for some other condition. It has been stated that "the average practitioner still fails to recognize it as one of the daily recurrent important diseases, or to include the search for its diagnosis among his routine examinations."1It is our hope that this review will reawaken an interest...
Development and characterization of EGFR inhibitor resistant lines; A model to study acquired resistance to EGFR blockade
Authors: Deric L. Wheeler, Tim J. Kruser, Shymin Huang, Vinai Gondi, Eric A. Armstrong, Paul M. Harari
Journal: Clinical Cancer Research (2006)

B60   Inhibition of Epidermal Growth Factor Receptor (EGFR) signaling has emerged as a promising cancer therapy. The first major Phase III clinical trial in head and neck cancer combining EGFR inhibition (Cetuximab) with radiation confirmed a strong survival advantage. However, many patients still manifested tumor recurrence suggesting acquired resistance to EGFR inhibition when coupled to radiation. Therefore the development of both in vitro and in vivo models of cetuximab resistance is highly desired to elucidate the mechanisms leading to resistance and to identify biomarkers that can be used clinically to predict response to EGFR blockade. In addition, identifying targets that may be potential candidates for combinatorial therapy will play an important role in defining future therapeutic regimens.To understand mechanisms of acquired resistance to EGFR inhibition we established stable EGFR inhibitor-resistant clones from the NSCLC (H226) cell line. The IC50 dose for cetuximab was placed on H226 sensitive lines and the cetuximab dose was doubled every 10-14 days for 8 dose doublings (10nM-1280nM cetuximab). We utilized this heterogeneous population of resistant cells to perform protein array-based identification of intracellular signaling proteins as well as phosphoRTK (receptor tyrosine kinases) arrays to investigate putative RTKs involved in conferring resistance to EGFR inhibition. The results of this work indicated that pErk1/2, p-AKT, p-Stat1, STAT5, catenin, pJNK and GSK-38 were all upregulated whereas Stat3, Caveolin1 and p53 were dramatically down regulated. The phosphoRTK array indicated that the RTKs MET, EGFR, ErbB2 and ErbB3 were significantly upregulated in the resistant lines as compared to the cetuximab-sensitive parental line. Once stable resistant lines were generated and characterized we subcloned out seven single cell clones for further characterization. Further analysis of individual resistant clones revealed striking homogeneity in regards to intracellular signaling molecules and their pathways. Most notable was the gain of active MET, EGFR, ErbB2, ErbB3 and the down regulation of p53, Bax and p21 in all seven cetuximab-resistant clones. Furthermore the cetuximab-resistant clones have constitutively active MAPK and AKT as compared to the cetuximab- sensitive parental line.In summary we have generated seven cetuximab-resistant lines and these lines show remarkable homogeneity in terms of altered protein expression. These findings suggest that these pathways may be critical for conferring resistance to EGFR blockade. We aim to characterize these specific molecular targets and their pathways and determine if they are directly or indirectly involved in regulating resistance to EGFR blockade.
Abstract 39: Atropine for Patients with Out-Of-Hospital Cardiac Arrest
Authors: Ken Nagao, Tetsuya Sakamoto, Masaki Igarashi, Shinichi Ishimatsu, Akira Sato, Shingo Hori, Shigeru Kanesaka, Yuichi Hamabe, Kimio Kikushima
Journal: Circulation (2007)

BACKGROUND AHA guidelines for cardiopulmonary resuscitation (CPR) have recommended that administration of atropine can be considered for asystole or pulseless electrical activity (PEA), because atropine has improved survival to hospital admission in a retrospective review (Ann Emerg Med, 1984), and is inexpensive, easy to administer, and has few side effects. However, there are insufficient data in humans. METHODS We assessed the effects of atropine in 7,443 adults patients with asystole or PEA arrest from the SOS-KANTO study: a prospective, multicenter, observational trial. The medications for asystole or PEA arrest were managed according to the advanced cardiovascular life support algorithm of the CPR guidelines (i.e. a 1-mg dose of epinephrine was administered intravenously every 3 to 5 minutes and a1-mg dose of atropine was administered intravenously every 3 to 5 minutes; maximum total of 3 doses). The primary endpoint was a favorable neurological outcome 30 days after cardiac arrest. RESULTS Of the 7,443 adult patients who had out-of-hospital cardiac arrest with asystole or PEA, I,708(23%) were treated with epinephrine and atropine and 5,735(77%) were treated with epinephrine. At baseline, the epinephrine and atropine group had significantly higher proportions of cardiac cause, witnessed arrest, and bystander CPR attempt than the epinephrine group. However, the two groups had a similar frequency of the favorable neurological outcome (0.3% in each group, p=0.805). Multiple logistic-regression analysis showed that the adjusted odds ratio for the favorable neurological outcome was 0.6 (95% CI 0.2–1.7, p=0.37) after epinephrine and atropine (compared with epinephrine). On the other hand, the epinephrine and atropine group had significantly higher rate of return of spontaneous circulation (ROSC) than the epinephrine group (35% vs. 23%, p&lt;0.0001), and the adjusted odds ratio for ROSC was 1.6 (95% CI 1.4 –1.7, p&lt;0.0001) after epinephrine and atropine (compared with epinephrine). CONCLUSIONS We demonstrated that administration of atropine during management of asystole or PEA arrest did not increase the frequency of favorable neurological outcome, although the atropine favored initial ROSC.
How to Read a Paper: The Basics of Evidence Based Medicine, by Trisha Greenhalgh
Authors: D. C Slawson
Journal: BMJ (1997)

Trisha Greenhalgh, BMJ Publishing Group, £14.95, pp 196 ISBN 0 7279 1139 2

Evidence based medicine is clearly a major medical “buzz-phrase” of the 1990s. Much work has already been published on “How to do it,” and, no doubt, clinicians will continue to see much more in the future. Greenhalgh's book is intended for people wishing to “find their way into the medical literature, assess the scientific validity and practical relevance of the articles … and … put the results into practice.” Her extensive experience in teaching evidence based medicine is clearly evident, and her humorous and conversational no-nonsense style is refreshing and delightful.

The …
Abstract 821: Fusogenic liposomes: A novel therapeutic strategy to efficiently target and destroy prostate cancer
Authors: Jihane Mriouah, Rae-Lynn Nesbitt, Desmond Pink, Roy Duncan, Andries Zijlstra, John D. Lewis
Journal: Cancer Research (2014)

Abstract Prostate cancer is the most common malignancy in North American men. While patients have benefited from advances in androgen deprivation therapy, prostate cancer ultimately evolves to a metastatic or castrate-resistant state that makes it the second-leading cause of cancer mortality in males. In the past 3 years, new chemotherapeutic drugs with efficacy in advanced disease have been introduced. Yet their efficacy is limited by dose-limiting toxicities and side effects due primarily to suboptimal biodistribution - they do not target tumors directly. To overcome these limitations, we have developed a novel drug encapsulation system for efficient and specific delivery of chemotherapeutic agents to prostate tumors. The reptilian reovirus-derived fusion-associated small transmembrane (FAST) protein (p14) increases the fusion of liposomes to cell membranes. In this study, we combine these fusogenic liposomes with peptides targeted to gastrin-releasing peptide receptors (GRPR) to improve the delivery of chemotherapeutic payloads specifically to prostate cancer cells while sparing normal tissue. A fusion protein containing p14 and a C-terminal bombesin peptide was produced in a baculovirus expression system and incorporated into liposomes. The targeting and fusogenic properties of the p14-bombesin protein-containing liposomes were confirmed using flow cytometry. These experiments demonstrated improved delivery to cancer cells in vitro (PC3, LNCaP), compared to non-tumoral cells (BPH). The specificity of targeted fusogenic liposomes was confirmed by knockdown of GRPR and by blocking with free bombesin peptides. We then used intravital imaging in an avian xenograft model to measure the accumulation and specific uptake of the fusogenic targeted liposomes in prostate tumors compared to benign (BPH) and normal tissue, and found a significant increase in uptake in GRPR-expressing prostate cancer tumors using the bombesin-targeted fusogenic liposomes compared to controls. As a further proof of principle, we modified a commercial formulation of Doxil to incorporate our p14-bombesin fusion protein. This formulation showed significantly enhanced cancer-specific cytotoxicity in vitro and increased efficacy in xenograft models. Taken together, these studies demonstrate that molecular-targeted fusogenic FAST liposomes are a promising platform for improving the efficacy of chemotherapies that should show enhanced activity in advanced and metastatic prostate cancers. Citation Format: Jihane Mriouah, Rae-Lynn Nesbitt, Desmond Pink, Roy Duncan, Andries Zijlstra, John D. Lewis. Fusogenic liposomes: A novel therapeutic strategy to efficiently target and destroy prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 821. doi:10.1158/1538-7445.AM2014-821
64. Bioluminescence Imaging of Regulated Gene Expression Using HSV-1 Amplicon Vectors in Rodent Brain
Authors: Sam Wang, Jeremy Petravicz, Xandra O. Breakefield
Journal: Molecular Therapy (2004)

For many applications, it may be necessary to regulate gene expression in a dose-dependent manner to attain the most efficacious dose of gene product. Using the pantropic HSV-1 amplicon vector, regulatory components can be incorporated into its genome and delivered in multiple copies via the concatermizeration of amplicon sequences during virion packaging. An earlier version of the regulated amplicon vector was previously shown to express dsRed when treated with 20 nM rapamycin. More notable was the basal expression level of dsRed mRNA in an uninduced state. In the present experiments, the parental HSV-1 amplicon vector has been modified to contain both an improved activation fusion protein domain (from pC4N2-RHS3H/ZF3, ARIAD Pharmaceuticals), which has been reported to possess a broader induction range, and insulator elements derived from the b-globin gene (from pJC13.1, Dr. Gary Felsenfeld, NIH), which flank the inducible promoter, to minimize basal promoter expression. The inducible cassette has also been modified to express luciferase (luc) to permit real time imaging and includes a human growth hormone intron sequence (from pZ12-I-PL5, ARIAD) to promote message stability. A RSV-driven enhanced green fluorescent protein (eGFP) was incorporated for vector titration and identification of infected cells. 293T/17 cells infected at a m.o.i. = 1 resulted in up to 70% eGFP+ cells, and demonstrated a graded luc response to rapamycin (0–20 nM), with no detectable luc expression in an uninduced state. Induction of luc expression was also evident after injection of vector (2 × 105 tu) into the cortex of nude mice and i.p. injection of rapamycin (1 mg/kg) 24 hr later. By bioluminescence imaging, no luc was detectable prior to rapamycin administration, and luc expression was observed four days after induction with rapamycin. Luc expression was not detectable three days later. Experiments are currently in progress to assess repeated induction, as well as to correlate bioluminescence expression with luc histology.
A “body armor” of leukemia cutis
Authors: Nico A.F. Janssen, Konnie M. Hebeda, Wendy B.C. Stevens, Walter J.F.M. van der Velden
Journal: American Journal of Hematology (2015)

A 25-year old female was diagnosed with an acute myeloid leukemia (AML: FAB classification M2) with very poor-risk cytogenetic abnormalities i.e. monosomal karyotype (including monosomy 17p resulting in loss of the tumor suppressor gene p53). At presentation, she had enlarged lymph nodes and tonsils that were at that time designated reactive to infection. After remission-induction and consolidation chemotherapy, which contained cytarabine and an anthracycline (idarubicin and daunorubicin, respectively), she achieved a complete morphological and cytogenetic remission on bone marrow evaluation. During consolidation chemotherapy, she had experienced an episode of fluctuating skin changes mainly consisting of a bluish discoloration and no particular suspicion was raised. Two weeks later and prior to the start of conditioning treatment for an allogeneic hematopoietic stem cell transplantation (HSCT), she again reported skin changes that consisted of cyanotic discoloration and progressive thickening which gave her the feeling that she was getting stuck in some kind of body armor. The skin changes were most pronounced at her forehead, cheeks, and upper body (Image 1). On physical examination, there was hardening and roughness of the skin and also cervical and axillary lymphadenopathy was noticed. Histological examination of a skin biopsy showed dermal infiltration by leukemic blasts (Image 2) with immunophenotypical evaluation expression of CD34, CD43, CD68, and myeloperoxidase. Therefore, she was diagnosed with an extramedullary relapse of the AML, also designated leukemia cutis or myeloid sarcoma. Positron-emission tomography (Image 3) revealed extensive skin (red arrow) and regional lymph node enhancement (green arrow). Examination of cerebrospinal fluid revealed myeloblasts confirming central nervous system involvement. Shortly thereafter salvage, high-dose chemotherapy was initiated with normalization of her face and resolution of lymphadenopathy. Unfortunately after a myeloablative T cell replete allogeneic HSCT, she experienced an early relapse and died. In retrospect at initial diagnosis, the AML already had extramedullary manifestations, which might have had increased the vigilance for extramedullary relapse and initiation of prophylactic intrathecal chemotherapy.
Lymphocyte subsets in healthy children from birth through 18 years of age
Authors: William T. Shearer, Howard M. Rosenblatt, Rebecca S. Gelman, Rebecca Oyomopito, Susan Plaeger, E.Richard Stiehm, Diane W. Wara, Steven D. Douglas, Katherine Luzuriaga, Elizabeth J. McFarland, Ram Yogev, Mobeen H. Rathore, Wende Levy, Bobbie L. Graham, Stephen A. Spector
Journal: Journal of Allergy and Clinical Immunology (2003)
The Biologic Basis of Clinical Heterogeneity in Juvenile Idiopathic Arthritis
Authors: Simon W. M. Eng, Trang T. Duong, Alan M. Rosenberg, Quaid Morris, Rae S. M. Yeung
Journal: Arthritis & Rheumatology (2014)

Childhood arthritis encompasses a heterogeneous family of diseases. Significant variation in clinical presentation remains despite consensus-driven diagnostic classifications. Developments in data analysis provide powerful tools for interrogating large heterogeneous data sets. We report a novel approach to integrating biologic and clinical data toward a new classification for childhood arthritis, using computational biology for data-driven pattern recognition.Probabilistic principal components analysis was used to transform a large set of data into 4 interpretable indicators or composite variables on which patients were grouped by cluster analysis. Sensitivity analysis was conducted to determine key variables in determining indicators and cluster assignment. Results were validated against an independent validation cohort.Meaningful biologic and clinical characteristics, including levels of proinflammatory cytokines and measures of disease activity, defined axes/indicators that identified homogeneous patient subgroups by cluster analysis. The new patient classifications resolved major differences between patient subpopulations better than International League of Associations for Rheumatology subtypes. Fourteen variables were identified by sensitivity analysis to crucially determine indicators and clusters. This new schema was conserved in an independent validation cohort.Data-driven unsupervised machine learning is a powerful approach for interrogating clinical and biologic data toward disease classification, providing insight into the biology underlying clinical heterogeneity in childhood arthritis. Our analytical framework enabled the recovery of unique patterns from small cohorts and addresses a major challenge, patient numbers, in studying rare diseases.
The neuropsychiatric phenotype in Darier disease
Authors: K. Gordon-Smith, L.A. Jones, S.M. Burge, C.S. Munro, S. Tavadia, N. Craddock
Journal: British Journal of Dermatology (2010)

Darier disease (DD) is a rare autosomal dominantly inherited skin disorder in which co-occurrence of neuropsychiatric abnormalities has been frequently reported by dermatologists. It is caused by mutations in a single gene, ATP2A2, which is expressed in the skin and brain.To conduct the first systematic investigation of the neuropsychiatric phenotype in DD.One hundred unrelated individuals with DD were assessed using a battery of standardized neuropsychiatric measures. Data were also obtained on a number of clinical features of DD.Individuals with DD were found to have high lifetime rates of mood disorders (50%), specifically major depression (30%) and bipolar disorder (4%), and suicide attempts (13%) and suicidal thoughts (31%). These were more common in DD when compared with general population data. The prevalence of epilepsy (3%) in the sample was also higher than the prevalence in the general population. There was no consistent association of specific dermatological features of DD and presence of psychiatric features.These findings highlight the need for clinicians to assess and recognize neuropsychiatric symptoms in DD. The results do not suggest that neuropsychiatric symptoms are simply a psychological reaction to having a skin disease, but are consistent with the pleiotropy hypothesis that mutations in the ATP2A2 gene, in addition to causing DD, confer susceptibility to neuropsychiatric features. Further research is needed to investigate genotype-phenotype correlations between the types and/or locations of pathogenic mutations within ATP2A2 and the expressed neuropsychiatric phenotypes.