tbuckley/cabot-search huggingface dataset:
Studies of a patient with recurring thrombotic thrombocytopenic purpura
Authors: Craig S. Kitchens
Journal: American Journal of Hematology (1982)

Abstract A young woman with recurring bouts of thrombotic thrombocytopenic purpura presented an opportunity to study a single patient serially and in depth. This patient underwent 12 remissions in response to fresh frozen plasma, and as little as 250 ml of plasma or plasma from which cryoprecipitate had been extracted was efficacious. Neither the Lian factor nor alterations in either cold‐insoluble globulin or protein C could be demonstrated. Evidence in support of the concept of “exhausted” platelets was generated, in that immediately before a thrombocytopenic relapse, platelet function was altered as manifested by bruising, prolongation of the bleeding time, and decreased platelet aggregation. The in vitro addition of normal plasma to such platelets did not improve aggregation. The antiplatelet agent sulfinpyrazone did not seem to add efficacy. Serial observations support the hypothesis that the progression of pathophysiologic events in this patient is: exhausted platelets, thrombocytopenia, hemolysis, renal perturbations, and central nervous system dysfunction.
Brentuximab Vedotin Combined With Donor Lymphocyte Infusions for Early Relapse of Hodgkin Lymphoma After Allogeneic Stem-Cell Transplantation Induces Tumor-Specific Immunity and Sustained Clinical Remission
Authors: Sebastian Theurich, Joke Malcher, Kerstin Wennhold, Alexander Shimabukuro-Vornhagen, Jens Chemnitz, Udo Holtick, Anke Krause, Carsten Kobe, Deniz Kahraman, Andreas Engert, Christof Scheid, Geothy Chakupurakal, Michael Hallek, Michael von Bergwelt-Baildon
Journal: Journal of Clinical Oncology (2012)
Why I declined an invitation to a drug company seminar
Authors: Murad Moosa Khan
Journal: BMJ (2007)

I was recently invited by a pharmaceutical company to a seminar in a five star hotel in Pakistan, where I live and work. The seminar was on mental health, and the company had invited a “foreign speaker” to talk on the subject.

I declined the invitation. These were the reasons I gave: “Thank you for your invitation which for ethical reasons I have to decline. I consider all interactions of physicians with pharmaceutical companies unethical and a cause of serious conflict of interest. I also do not accept any gifts, large or small, in any shape, form, or size from any drug company. I do not attend pharmaceutical company sponsored seminars (such as …
Dysfunctional B-cell activation in cirrhosis resulting from hepatitis C infection associated with disappearance of CD27-Positive B-cell population
Authors: Hiroyoshi Doi, Tara K. Iyer, Erica Carpenter, Hong Li, Kyong-Mi Chang, Robert H. Vonderheide, David E. Kaplan
Journal: Hepatology (2011)

Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis and hepatocellular carcinoma (HCC). Both advanced solid tumors and HCV have previously been associated with memory B-cell dysfunction. In this study, we sought to dissect the effect of viral infection, cirrhosis, and liver cancer on memory B-cell frequency and function in the spectrum of HCV disease. Peripheral blood from healthy donors, HCV-infected patients with F1-F2 liver fibrosis, HCV-infected patients with cirrhosis, patients with HCV-related HCC, and non-HCV-infected cirrhotics were assessed for B-cell phenotype by flow cytometry. Isolated B cells were stimulated with anti–cluster of differentiation (CD)40 antibodies and Toll-like receptor (TLR)9 agonist for assessment of costimulation marker expression, cytokine production, immunoglobulin (Ig) production, and CD4+ T-cell allostimulatory capacity. CD27+ memory B cells and, more specifically, CD27+IgM+ B cells were markedly less frequent in cirrhotic patients independent of HCV infection. Circulating B cells in cirrhotics were hyporesponsive to CD40/TLR9 activation, as characterized by CD70 up-regulation, tumor necrosis factor beta secretion, IgG production, and T-cell allostimulation. Last, blockade of TLR4 and TLR9 signaling abrogated the activation of healthy donor B cells by cirrhotic plasma, suggesting a role for bacterial translocation in driving B-cell changes in cirrhosis. Conclusion : Profound abnormalities in B-cell phenotype and function occur in cirrhosis independent of HCV infection. These B-cell defects may explain, in part, the vaccine hyporesponsiveness and susceptibility to bacterial infection in this population.
Abstract 11163: Predictors of Abdominal Aortic Calcium Incidence: The Multi-Ethnic Study of Atherosclerosis
Authors: Susan G Lakoski, Joseph A Delaney, Matthew A Allison, Mary Cushman, Dhananjay Vaidya, Roger S Blumenthal, Gregory Burke, Nathan D Wong, Matthew Budoff, Michael H Criqui
Journal: Circulation (2010)

Abdominal aortic calcification (AAC) represents the early stages of subclinical atherosclerosis. AAC can be used to study the interplay between traditional and novel risk factors in development and...
Acute Leukemia in Multiple Myeloma
Authors: FRANCISCO GONZALEZ
Journal: Annals of Internal Medicine (1977)

Of 476 patients with multiple myeloma treated during a 9-year period, 11 developed acute myelogenous leukemia or sideroblastic anemia. In all, the myeloma was in remission from chemotherapy with melphalan-prednisone combinations that had been continued for a median duration of 3 years. The incidence of acute leukemia or sideroblastic anemia was about 100 times higher than found in normal individuals of the same age. In all patients studied, major cytogenetic abnormalities were present, with hypodiploidy and evidence of chromosomal damage being noted most frequently. The frequency and nature of the chromosome changes were attributed to effects resulting from the prolonged drug therapy. These findings supported the long-term follow-up of selected patients with myeloma without any chemotherapy when marked degrees of remission followed the initial treatment courses.
The US Health Care System in the Year 2000
Authors: Jeff C. Goldsmith
Journal: JAMA (1986)

PREDICTING the future in an age of rapid social change is risky business. However, one thing can be confidently said about the American health care system in the year 2000: most of its ingredients—the patients, the professionals, the strains of scientific inquiry and technological development, and much of the capital—are already present. Scientific and technological developments have been extensively reviewed elsewhere<sup>1</sup>; this article will speculate on the impact of demographics, changing financing systems, and medical care organization in shaping the future American health care provision system. <h3>Demographics</h3> Barring a major war or natural catastrophe, approximately three fourths of the population to be served at the dawn of the 21st century is already living (unpublished data, National Center for Health Statistics, 1984).<sup>2</sup>The US population currently alive may account for as much as 90% of the health care demand encountered by the early part of the next century. By
Risk factors associated with the onset of daptomycin non-susceptibility in Staphylococcus aureus infections in critically ill patients
Authors: Matteo Bassetti, Giovanni Villa, Filippo Ansaldi, Daniela De Florentiis, Carlo Tascini, Piergiogio Cojutti, Elda Righi, Assunta Sartor, Massimo Crapis, Francesco Giuseppe De Rosa, Federico Pea, Francesco Menichetti
Journal: Intensive Care Medicine (2014)
Spontaneous tumors in SENCAR mice.
Authors: S Melchionne, I Seidman, B L Van Duuren
Journal: Environmental Health Perspectives (1986)

A total of 305 female and 36 male SENCAR mice in six different groups were observed for 540 to 875 days for tumors as well as nonneoplastic lesions. Three of these groups were observed for their lifespans. The 123 females and 36 males, observed for their lifespans (800 to 875 days) showed median survival times ranging from 730 to 745 days. The average peak body weights were 42.4 g for females and 50.0 g for males. In the animals observed for their lifespans, the total tumor incidence was 65.6% for females and 69.4% for males. Both sexes showed a high incidence of papillary tumors of the lung, 16 to 39%, which was independent of aging. Females showed a 5.1 to 21.0% incidence of mammary tumors, which increased with age. Males showed a high incidence of hyperplastic nodules of the liver, i.e., 12 of 36 animals. Other frequently occurring tumors were leukemia and papillomas of the forestomach.
628 Corticosteroid-Sparing Effects of Mepolizumab, an Anti-Interleukin-5 Monoclonal Antibody, in Patients With Hypereosinophilic Syndrome
Authors: L.J. Rosenwasser, L.B. Schwartz, J. Sheikh, A.D. Klion, M.E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2007)
Standardised packs cut adult smoking as well as discouraging young people, evidence indicates
Authors: I. Torjesen
Journal: BMJ (2015)

Growing evidence indicates that standardised tobacco packaging cuts the prevalence of smoking among existing smokers as well as reducing the number of young people who take up the habit. This is the conclusion of a collection of papers setting out the evidence base for introducing standardised packs, published in Addiction .

England is likely to become the second country in the world to introduce standardised packaging, as parliament is set to vote on regulations for it before the general election in May. The decision to table regulations came after the publication of a government commissioned review by the former paediatrician and past chairman of University College London Partners Cyril Chantler last year that found very strong evidence that children who were exposed to advertising or promotion of tobacco products were more likely to take up smoking.1

Australia introduced standardised packs more than two years ago, …
The Medical Complications of Drug Addiction and the Medical Assessment of the Intravenous Drug User: 25 Years Later
Authors: Charles E. Cherubin
Journal: Annals of Internal Medicine (1993)

Purpose: To review changes in the medical complications of drug abuse that have occurred since the authors reviewed them 25 years ago. Data Source: Manual search of the internal medicine and subspecialty literature of the past three decades that was selected by the authors. Study Selection: Selected studies were of three typesbaseline studies for the period ending in 1968, studies after 1968 that emphasized changes from baseline, and studies after 1968 that emphasized change (or the absence of change) and the manner in which clinicians conceptualized problems. Data Extraction: We extracted data that showed changes in the diseases, the appearance of new diseases, or the disappearance of formerly common diseases. Results of Data Synthesis: The diseases complicating drug abuse are now more widely disseminated than they were in the last 25 years. Some former diseases of addiction such as tetanus and malaria are now rare. Diseases (such as human immunodeficiency virus infection) not known to exist or rare 25 years ago now occur frequently. The drugs of abuse have also changed; for example, cocaine is now much more common. Conclusions: Treating the acute medical problems (mostly infectious diseases) in poor, undereducated, and often noncompliant intravenous drug users is far more complex than previously described. Although some features have remained constant, the emergence of human immunodeficiency virus infection and changes in patterns of drug use have radically altered patient management.
OSMOTIC PRESSURE STUDY OF PROTEIN FRACTIONS IN NORMAL AND IN NEPHROTIC SUBJECTS
Authors: Jaques Bourdillon
Journal: The Journal of Experimental Medicine (1939)

In serum of patients with nephrosis both albumin and globulin showed by osmotic pressure nearly double the molecular weights of normal albumin and globulin. In the urines of such patients, on the other hand, both proteins showed molecular weights lower even than in normal serum. The colloidal osmotic pressures were measured by the author's method at such dilutions that the van't Hoff law relating pressures to molecular concentrations could be directly applied. For the albumin and globulin of normal serum the molecular weights found were 72,000 and 164,000 respectively, in agreement with the weights obtained by other methods.
Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes
Authors: Wendy M. Macfarlane, Timothy M. Frayling, Sian Ellard, Julie C. Evans, Lisa I.S. Allen, Michael P. Bulman, Susan Ayres, Maggie Shepherd, Penny Clark, Ann Millward, Andrew Demaine, Terence Wilkin, Kevin Docherty, Andrew T. Hattersley
Journal: Journal of Clinical Investigation (1999)

The transcription factor insulin promoter factor-1 (IPF-1) plays a central role in both the development of the pancreas and the regulation of insulin gene expression in the mature pancreatic β cell. A dominant-negative frameshift mutation in the IPF-l gene was identified in a single family and shown to cause pancreatic agenesis when homozygous and maturity-onset diabetes of the young (MODY) when heterozygous. We studied the role of IPF-1 in Caucasian diabetic and nondiabetic subjects from the United Kingdom. Three novel IPF-1 missense mutations (C18R, D76N, and R197H) were identified in patients with type 2 diabetes. Functional analyses of these mutations demonstrated decreased binding activity to the human insulin gene promoter and reduced activation of the insulin gene in response to hyperglycemia in the human β-cell line Nes2y. These mutations are present in 1% of the population and predisposed the subject to type 2 diabetes with a relative risk of 3.0. They were not highly penetrant MODY mutations, as there were nondiabetic mutation carriers 25–53 years of age. We conclude that mutations in the IPF-1 gene may predispose to type 2 diabetes and are a rare cause of MODY and pancreatic agenesis, with the phenotype depending upon the severity of the mutation.
Genetic and Environmental Influences on the Familial Transmission of Externalizing Disorders in Adoptive and Twin Offspring
Authors: Brian M. Hicks, Katherine T. Foster, William G. Iacono, Matt McGue
Journal: JAMA Psychiatry (2013)

<h3>Importance</h3> Twin-family studies have shown that parent-child resemblance on substance use disorders and antisocial behavior can be accounted for by the transmission of a general liability to a spectrum of externalizing disorders. Most studies, however, include only biological parents and offspring, which confound genetic and environmental transmission effects. <h3>Objective</h3> To examine the familial transmission of externalizing disorders among both adoptive (genetically unrelated) and biological relatives to better distinguish genetic and environmental mechanisms of transmission. <h3>Design</h3> Family study design wherein each family included the mother, father, and 2 offspring, including monozygotic twin, dizygotic twin, nontwin biological, and adoptive offspring. Structural equation modeling was used to estimate familial transmission effects and their genetic and environmental influences. <h3>Setting</h3> Participants were recruited from the community and assessed at a university laboratory. <h3>Participants</h3> A total of 1590 families with biological offspring and 409 families with adoptive offspring. Offspring participants were young adults (mean age, 26.2 years). <h3>Main Outcomes and Measures</h3> Symptom counts of conduct disorder, adult antisocial behavior, and alcohol, nicotine, and drug dependence. <h3>Results</h3> There was a medium effect for the transmission of the general externalizing liability for biological parents (<i>r</i> = 0.27-0.30) but not for adoptive parents (<i>r</i> = 0.03-0.07). In contrast, adoptive siblings exhibited significant similarity on the general externalizing liability (<i>r</i> = 0.21). Biometric analyses revealed that the general externalizing liability was highly heritable (a<sup>2</sup> = 0.61) but also exhibited significant shared environmental influences (c<sup>2</sup> = 0.20). <h3>Conclusions and Relevance</h3> Parent-child resemblance for substance use disorders and antisocial behavior is primarily due to the genetic transmission of a general liability to a spectrum of externalizing disorders. Including adoptive siblings revealed a greater role of shared environmental influences on the general externalizing liability than previously detected in twin studies and indicates that sibling rather than parent-child similarity indexes important environmental risk factors for externalizing disorders.
Obama Signs Law to Improve Postacute Care for Medicare Patients
Authors: Rita Rubin
Journal: JAMA (2014)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Expressed Anti-HBV Primary MicroRNA Shuttles Inhibit Viral Replication Efficiently In Vitro and In Vivo
Authors: Abdullah Ely, Tanusha Naidoo, Steven Mufamadi, Carol Crowther, Patrick Arbuthnot
Journal: Molecular Therapy (2008)

The use of RNA interference (RNAi) to inhibit gene expression is potentially applicable in the treatment of viral infections such as hepatitis B virus (HBV) persistence. Although efficient HBV gene silencing by short hairpin RNA (shRNA) expressed from RNA polymerase (Pol) III promoters has been reported, constitutive high-level transcription may cause harmful side effects. Here, we report an approach that allows the use of a Pol II promoter to improve transcription regulation of expressed RNAi effecters. Pol II [cytomegalovirus (CMV)] or Pol III (U6) promoter cassettes that transcribe anti-HBV primary microRNA (pri-miR)-122 and pri-miR-31 shuttles were generated. In cultured cells both types of pri-miR-like sequences effected knockdown of markers of viral replication (>80%) and were processed to form intended 21-nucleotide guides. The concentration of CMV-expressed miRs was approximately 85-fold lower than the U6 shRNA-derived guide RNA. When cells were co-transfected with pri-miR expression cassettes, attenuation of independent RNAi-mediated gene silencing was not observed, which is in contrast to the action of U6 shRNA expression cassettes. The efficacy of the anti-HBV pri-miR shuttles in vivo was verified using the murine hydrodynamic injection model. Employing Pol II-expressed pri-miR mimics may be useful in the treatment of HBV infection, and potentially also for generic application in RNAi-based therapy.
PTH-096 The Sensitivity Of Eus Fna Of Solid Pancreatic Lesions, Working From A Regional Mdt And Within A Regional Network: Abstract PTH-096 Table 1
Authors: H Gordon, D Lloyd, A Higginson, R McCrudden, C Bent, F Shek, R Beable, A Al-Badri, B Green, E Jaynes, D Collins, D Poller, B Stacey
Journal: Gut (2014)

<h3>Introduction</h3> Endoscopic ultrasound (EUS) guided sampling of advanced malignant pancreatic lesions is increasingly being performed in order to confirm malignancy prior to chemotherapy and or treatment. Meta-analysis of 33 studies examining solid lesion EUS FNA tissue acquisition in 4984 patients showed a pooled sensitivity of 85%, increasing to 91% if suspicious atypia was included <sup>1</sup>. Higher sensitivities have been demonstrated in large volume single operator centres where sensitivities of 92–97% <sup>2,3</sup> have been reported. The four Wessex EUS centres all work from a regional HPB MDT, where pancreatic cases are discussed and EUS procedures requested. Each centre has two EUS operators, performing between 148 and 214 cases per annum. Additionally the regional EUS endoscopists, pathologists and biomedical technicians meet three times a year for EUS network meetings to audit outcomes and review practice standards. In 3 of the 4 centres cytopathology staff are present in the endoscopy room to provide rapid on site evaluation and confirm adequate sample cellularity and give a preliminary diagnosis. <h3>Methods</h3> Each centre prospectively audited the results of EUS guided biopsy of suspected malignant solid pancreatic lesions over a 6 month period from 1.7.13 to 31.12.13. From this data the true positive rate was calculated to determine if such networking produced results comparable to large volume single centres. <h3>Results</h3> There was a regional sensitivity of 96%. The majority of lesions were adenocarcinoma but other results included: 1 lymphoma, 8 neuroendocrine tumours, 1 renal cell cancer metastasis. <h3>Conclusion</h3> A regional sensitivity of 96% is comparable with results from a single large volume UK EUS centre. This demonstrates that smaller volume centres working within a regional network can achieve similar standards to high volume centres. <h3>References</h3> 1 Hewitt <i>et al.</i><i>GI Endoscopy</i> 2012; 75 (2):319–331 2 Cherian <i>et al.</i><i>HPB</i> 2010; 12 (6):389–395 3 Manzia <i>et al.</i><i>Annals of RC Surgeons England</i> 2010; 92 (4):295–301 <h3>Disclosure of Interest</h3> None Declared.
Structural Basis for Benzothiazinone-Mediated Killing of <i>Mycobacterium tuberculosis</i>
Authors: João Neres, Florence Pojer, Elisabetta Molteni, Laurent R. Chiarelli, Neeraj Dhar, Stefanie Boy-Röttger, Silvia Buroni, Elizabeth Fullam, Giulia Degiacomi, Anna Paola Lucarelli, Randy J. Read, Giuseppe Zanoni, Dale E. Edmondson, Edda De Rossi, Maria Rosalia Pasca, John D. McKinney, Paul J. Dyson, Giovanna Riccardi, Andrea Mattevi, Stewart T. Cole, Claudia Binda
Journal: Science Translational Medicine (2012)

The benzothiazinone BTZ043 is a tuberculosis drug candidate with nanomolar whole-cell activity. BTZ043 targets the DprE1 catalytic component of the essential enzyme decaprenylphosphoryl-β-D-ribofuranose-2'-epimerase, thus blocking biosynthesis of arabinans, vital components of mycobacterial cell walls. Crystal structures of DprE1, in its native form and in a complex with BTZ043, reveal formation of a semimercaptal adduct between the drug and an active-site cysteine, as well as contacts to a neighboring catalytic lysine residue. Kinetic studies confirm that BTZ043 is a mechanism-based, covalent inhibitor. This explains the exquisite potency of BTZ043, which, when fluorescently labeled, localizes DprE1 at the poles of growing bacteria. Menaquinone can reoxidize the flavin adenine dinucleotide cofactor in DprE1 and may be the natural electron acceptor for this reaction in the mycobacterium. Our structural and kinetic analysis provides both insight into a critical epimerization reaction and a platform for structure-based design of improved inhibitors.