tbuckley/cabot-search huggingface dataset:
Are persistent throat symptoms atypical features of gastric reflux and should they be treated with proton pump inhibitors?
Authors: J. Powell, J. O'Hara, J. A. Wilson
Journal: BMJ (2014)

Persistent throat symptoms are common in adults. Globus pharyngeus (a feeling of a lump in the throat), dysphonia, throat clearing, cough, excessive phlegm, throat pain, and postnasal secretions are present in up to 25% of primary care attenders, and more than 60 000 people are referred to secondary otolaryngological care annually.1 Treating persistent throat symptoms with gastric acid suppression has been in vogue for more than a decade, on the basis that they represent “atypical” manifestations of gastro-oesophageal reflux disease (GORD).2 So called extraoesophageal reflux or laryngopharyngeal reflux is internationally acknowledged as a separate GORD subcategory from “typical” oesophageal reflux disease.3 However, the relation between gastric reflux and persistent throat symptoms, and the role of proton pump inhibitor (PPI) treatment remains controversial.4 5 More than half of UK otolaryngologists prescribe PPIs for persistent throat symptoms.6 The message has also filtered through to primary care that PPIs are a reasonable “empirical” treatment. PPI treatment is a substantial expense for healthcare systems and increasingly treatment of persistent throat symptoms is adding to this. The cost of PPI treatment to the National Health Service in England for all conditions, including persistent throat symptoms, was £425m (€540m; $694m) in 2006 and the global bill was £7bn.7

On 25 June 2014 we searched Medline and Embase databases and the Cochrane Library for studies dealing with persistent throat symptoms, gastric reflux, and treatment with PPIs. We used the search terms “throat symptoms” or “laryngopharyngeal reflux” or “extra-oesophageal reflux” or “extra-esophageal reflux” or “gastro-oesophageal reflux disease” or “gastro-esophageal reflux disease” or “proton pump inhibitors”.

### Are persistent throat symptoms atypical features of gastric reflux?

The pathogenesis of persistent throat symptoms in gastric reflux is hypothesised to be through retrograde flow of gastric contents (particularly acid, bile, and pepsin) that affect the laryngopharynx by direct mucosal contact, or by a secondary mechanism.8 …
Hemoglobin Indianapolis (beta 112[G14] arginine). An unstable beta-chain variant producing the phenotype of severe beta-thalassemia.
Authors: J G Adams, L A Boxer, R L Baehner, B G Forget, G A Tsistrakis, M H Steinberg
Journal: Journal of Clinical Investigation (1979)

Hemoglobin (Hb) Indianapolis is an extremely labile beta-chain variant, present in such small amounts that it was undetectable by usual techniques. Clinically, it produces the phenotype of severe beta-thalassemia. Biosynthetic studies showed a beta:alpha ratio of 0.5 in reticulocytes and about 1.0 in marrow after a 1-h incubation. These results, similar to those seen in typical heterozygous beta-thalassemia, suggested that betaIndianapolis was destroyed so rapidly that its net synthesis was essentially zero. To examine the kinetics of globin synthesis, reticulocyte incubations of 1.25--20 min were performed with [3H]leucine. The betaIndianapolis:beta A ratio at 1.25 min was 0.80 suggesting that beta Indianapolis was synthesized at a near normal rate. At 20 min, this ratio was 0.46 reflecting rapid turnover of beta Indianapolis. The erythrocyte ghosts from these incubations contained only betaIndianapolis and alpha-chains, and the proportion of betaIndianapolis decreased with time, indicating loss of betaIndianapolis. Pulse-chase studies showed little change in beta A:alpha ratio and decreasing betaIndianapolis:alpha and betaIndianapolis:beta A with time. The half-life of betaIndianapolis in the soluble hemoglobin was approximately equal to 7 min. There was also rapid loss of beta Indianapolis from the erythrocyte membrane. From these results, it may be inferred that betaIndianapolis is rapidly precipitated from the soluble cell phase to the membrane, where it is catabolized. Heterozygotes for beta 0-thalassemia usually have minimal hematologic abnormalities, whereas heterozygotes with betaIndianapolis, having a similar net content of beta-chain, have severe disease. The extremely rapid precipitation and catabolism of betaIndianapolis and the resulting excess of alpha-chains, both causing membrane damage, may be responsible for the severe clinical manifestations associated with this variant. It seems likely that other, similar disturbances in the primary sequence of globin polypeptide chains may produce clinical findings similar to those seen with hemoglobin Indianapolis and thus produce the phenotype of severe beta-thalassemia.
Tamoxifen Induces Heparanase Expression in Estrogen Receptor–Positive Breast Cancer
Authors: Irit Cohen, Bella Maly, Itamar Simon, Amichay Meirovitz, Eli Pikarsky, Eyal Zcharia, Tamar Peretz, Israel Vlodavsky, Michael Elkin
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Mammalian heparanase degrades heparan sulfate, the main polysaccharide of the basement membrane. Heparanase is an important determinant in cancer progression, acting via the breakdown of extracellular barriers for invasion, as well as release of heparan sulfate–bound angiogenic and growth-promoting factors. The present study was undertaken to elucidate molecular mechanisms responsible for heparanase overexpression in breast cancer. Experimental Design: To characterize heparanase regulation by estrogen and tamoxifen and its clinical relevance for breast tumorigenesis, we applied immunohistochemical analysis of tissue microarray combined with chromatin immunoprecipitation assay, reverse transcription-PCR, and Western blot analysis. Results: A highly significant correlation (P &amp;lt; 0.0001) between estrogen receptor (ER) positivity and heparanase overexpression was found in breast cancer. Binding of ER to heparanase promoter accompanied estrogen-induced increase in heparanase expression by breast carcinoma cells. Surprisingly, heparanase transcription was also stimulated by tamoxifen, conferring a proliferation advantage to breast carcinoma cells grown on a naturally produced extracellular matrix. Heparanase overexpression was invariably detected in ER-positive second primary breast tumors, developed in patients receiving tamoxifen for the initial breast carcinoma. The molecular mechanism of the estrogenlike effect of tamoxifen on heparanase expression involves recruitment of transcription coactivator AIB1 to the heparanase promoter. Conclusions: Heparanase induction by ligand-bound ER represents an important pathway in breast tumorigenesis and may be responsible, at least in part, for the failure of tamoxifen therapy in some patients. Our study provides new insights on breast cancer progression and endocrine therapy resistance, offering future strategies for delaying or reversing this process.
A Special JAMA Theme Issue on Caring for the Uninsured and the Underinsured
Authors: George D. Lundberg
Journal: JAMA (1990)

The Journalof the American Medical Association plans to publish a special theme issue dedicated to Caring for the Uninsured and the Underinsured in the spring of 1991. The more than 30 million uninsured and more than 25 million seriously underinsured among us represent a tragedy of such vast proportions for a rich developed country as to demand a solution. We wish to place many serious, well-documented, and well-argued papers about how to solve this problem side by side for comparison and contrast.  We, as coeditors of this project, invite you, the readers, to submit original articles describing your personal or your organization's best proposals on this subject. The articles should contain the elements of major reform and include a description of financing methods and sources of new revenue, where necessary. Depending on the type of paper submitted, the length can run from 1800 to 4000 words. The paper should
A PATIENT WHO CHANGED MY PRACTICE
Authors: A. Martin
Journal: BMJ (1996)

Mobile health (mHealth) approaches for medical education in developing countries may be particularly useful given the number of mobile phone subscription rates and the challenges faced by medical educators. The evidence to support its effectiveness has not been critically reviewed. The electronic databases PubMed, Scopus and MEDLINE were searched to retrieve English language articles published in international academic journals between January 2007 and September 2014. Two reviewers independently reviewed citations using predetermined inclusion and exclusion criteria. Only articles addressing the use of mobile or tablet technologies and that met a prespecified keyword strategy were selected for review. The original search returned 583 results, of which only seven pertained to medical education in developing countries and had full text available. There was significant variation between the studies reviewed, in terms of intended audience, intervention design, assessment method and outcome. Three studies assessed the integration of mHealth solutions into the training of allied healthcare professionals, three assessed resident doctors, and another assessed undergraduate medical students. Six of the seven studies used mobile phones as the intervention tool. The majority of studies pointed towards mHealth as a promising tool for education and training of healthcare professionals, yet due to the limited size of the studies definite conclusions were limited. The results of this review suggest that more studies with larger sample sizes and more quantitative methods of evaluation are needed in order to demonstrate that mHealth holds more than mere potential.
Serotonin Rising — The Bone, Brain, Bowel Connection
Authors: Clifford J. Rosen
Journal: New England Journal of Medicine (2009)

In a recent article, Yadav et al.1 elucidated the regulation of gut-produced serotonin by low-density lipoprotein receptor–related protein 5 (Lrp5) and the deleterious effect of serotonin on bone mass. This discovery reflects the rapid advances taking place in bone biology and lends support to three newly understood facts about skeletal physiology.The first fact relates to the preeminence, in skeletal acquisition and maintenance, of a signaling pathway consisting of the mammalian homologue of wingless in drosophila (Wnt), Lrp5 or Lrp 6, and β-catenin. This pathway's importance was firmly established through clinical observations from gain-of-function and loss-of-function mutations in the LRP5 . . .
Verification of the susceptibility loci on 7p12.2, 10q21.2, and 14q11.2 in precursor B-cell acute lymphoblastic leukemia of childhood
Authors: Rashmi B. Prasad, Fay J. Hosking, Jayaram Vijayakrishnan, Elli Papaemmanuil, Rolf Koehler, Mel Greaves, Eamonn Sheridan, Andreas Gast, Sally E. Kinsey, Tracy Lightfoot, Eve Roman, Malcolm Taylor, Kathy Pritchard-Jones, Martin Stanulla, Martin Schrappe, Claus R. Bartram, Richard S. Houlston, Rajiv Kumar, Kari Hemminki
Journal: Blood (2009)
Gene therapy enhances chemotherapy tolerance and efficacy in glioblastoma patients
Authors: Jennifer E. Adair, Sandra K. Johnston, Maciej M. Mrugala, Brian C. Beard, Laura A. Guyman, Anne L. Baldock, Carly A. Bridge, Andrea Hawkins-Daarud, Jennifer L. Gori, Donald E. Born, Luis F. Gonzalez-Cuyar, Daniel L. Silbergeld, Russell C. Rockne, Barry E. Storer, Jason K. Rockhill, Kristin R. Swanson, Hans-Peter Kiem
Journal: Journal of Clinical Investigation (2014)

BACKGROUND. Temozolomide (TMZ) is one of the most potent chemotherapy agents for the treatment of glioblastoma. Unfortunately, almost half of glioblastoma tumors are TMZ resistant due to overexpression of methylguanine methyltransferase (MGMThi). Coadministration of O6-benzylguanine (O6BG) can restore TMZ sensitivity, but causes off-target myelosuppression. Here, we conducted a prospective clinical trial to test whether gene therapy to confer O6BG resistance in hematopoietic stem cells (HSCs) improves chemotherapy tolerance and outcome.
THE STRATEGY OF CATHETER ABLATION FOR PERSISTENT/PERMANENT ATRIAL FIBRILLATION IN THE PATIENTS WITH IMMEDIATE RECURRENCE AFTER CARDIOVERSION
Authors: Koichi Inoue, Toshiya Kurotobi, Ryusuke Kimura, Yuko Toyoshima, Norihisa Ito, Katsuomi Iwakura
Journal: Journal of the American College of Cardiology (2010)
The Obstetrical Society of London and the Midwives Question: Being an Abstract of the Inaugural Address delivered before the Society on March 6th, 1895
Authors: F. H. Champneys
Journal: BMJ (1895)

result followed paracentesis now, I should hold the operator, and not the operation, to blame.4. The deliberate opening of the side for a simple serous effusion has, I believe, been rarely practised, and rightly, for do what we will it is practically impossible, I believe, to prevent the effusion becoming purulent.That certainly happened at any rate in this case, in spite of the strictest antiseptic precautions.In this case, with so strong a tuberculous history in the family and with the strong presumption that the disease was of tuberculous nature, it seemed especially desirable to do nothing which might lead to an empyema.So I resisted the pressure put upon me to open the side as long as I could, and it was only after putting the whole case before the family and insisting that they should share in the responsibility of the decision that I at last consented.My fears were fully confirmed, for although I did not confess it I felt many times tempted to despair of her recovery and to reproach myself for having yielded to the pressure put upon me.So far as the operation was concerned it was a complete success.The anxiety was caused, not by the condition of the pleura, but by the general condition of the patient, and this still remains a puzzle to me, for I can- not see any plausible explanation of the fever and rapid failure of health.There was not enough discharge to account
Regulation of endocytosis via the oxygen-sensing pathway
Authors: Yi Wang, Olga Roche, Mathew S Yan, Greg Finak, Andrew J Evans, Julie L Metcalf, Bridgid E Hast, Sara C Hanna, Bill Wondergem, Kyle A Furge, Meredith S Irwin, William Y Kim, Bin T Teh, Sergio Grinstein, Morag Park, Philip A Marsden, Michael Ohh
Journal: Nature Medicine (2009)
A Vaccine against Rotavirus — When is Too Much Too Much?
Authors: Gerald T. Keusch, Richard A. Cash
Journal: New England Journal of Medicine (1997)

The development of the quadrivalent rotavirus vaccine evaluated in the study by Pérez-Schael et al., reported in this issue of the Journal, 1 represents the culmination of a long and highly creative process of research and development at the National Institutes of Health.2 Today, just 25 years after rotavirus was discovered,3 the use of a modified Jennerian approach has resulted in a quadrivalent vaccine that combines a naturally attenuated serotype 3 rhesus rotavirus with reassortants composed of 10 genomic segments of rhesus rotavirus RNA plus 1 of human origin encoding the VP7 neutralization specificity of serotype 1, 2, or 4 rotavirus. . . .
Monoclonal antibody against lymphocyte function-associated antigen 1 inhibits the formation of primary biliary cirrhosis-like lesions induced by murine graft-versus-host reaction
Authors: T Kimura, K Suzuki, S Inada, A Hayashi, M Isobe, Y Matsuzaki, N Tanaka, T Osuga, M Fujiwara
Journal: Hepatology (1996)

Interaction between intercellular adhesion molecule 1 (ICAM–1) and lymphocyte function–associated antigen 1 (LFA–1) might be involved in the pathogenesis of liver diseases. We investigated whether monoclonal antibodies (mAbs) against these two adhesion molecules could inhibit the formation of primary biliary cirrhosis (PBC)–like lesions in an animal model using graft–versus–host reaction (GVHR) with major histocompatibility complex class II disparity. PBC–like hepatic lesions such as cellular infiltration of portal area and nonsupprative destructive cholangitis (NSDC) were generated by injecting spleen T cells of C57BL/6 (B6) mice into (B6. C–H–2bm12 X B6) F1 mice. In the liver of these mice, increased number of LFA–1–positive cells and enhanced expression of ICAM–1 on sinusoidal endothelial cells and bile duct epithelial cells were observed immunohistochemically, when compared with F1 mice without GVHR. Hepatic lesions of these mAb–treated mice were almost completely inhibited in these mice compared with GVHR mice. Furthermore, we studied to determine which anti–LFA–1 mAb or anti–ICAM–1 mAb was essential to inhibit the hepatic lesions. Mice solely treated with anti–LFA–1 mAb showed significant inhibition of hepatic lesions, whereas treatment with anti–ICAM–1 mAb could not inhibit the lesions. Despite the inhibition of hepatic lesions, induction of GVHR and production of antimitochondrial antibodies were not impaired in mAb–treated mice. We conclude that LFA–1 mediates cell infiltration into the liver in this murine model of GVHR and suggest a possible therapeutic role of mAbs to this adhesion molecule in selective autoimmune liver diseases.
India plans to expand private sector in healthcare review
Authors: G. Mudur
Journal: BMJ (2003)

The Indian government has announced fiscal incentives to boost private investment in health care, promote India as an inexpensive health destination for foreign patients, and expand health insurance coverage.

The federal budget for 2003-4, unveiled last week, has a package of measures for health that includes tax benefits to financial institutions that provide loans to hospitals with more than 100 beds.

Private investments have fuelled the growth of corporate hospitals in several Indian cities in recent years, and the new incentives are expected to encourage private …
Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes.
Authors: G Argyropoulos, A M Brown, S M Willi, J Zhu, Y He, M Reitman, S M Gevao, I Spruill, W T Garvey
Journal: Journal of Clinical Investigation (1998)

Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that uncouples oxidative ATP phosphorylation. With the capacity to participate in thermogenesis and energy balance, UCP3 is an important obesity candidate gene. A missense polymorphism in exon 3 (V102I) was identified in an obese and diabetic proband. A mutation introducing a stop codon in exon 4 (R143X) and a terminal polymorphism in the splice donor junction of exon 6 were also identified in a compound heterozygote that was morbidly obese and diabetic. Allele frequencies of the exon 3 and exon 6 splice junction polymorphisms were determined and found to be similar in Gullah-speaking African Americans and the Mende tribe of Sierra Leone, but absent in Caucasians. Moreover, in exon 6-splice donor heterozygotes, basal fat oxidation rates were reduced by 50%, and the respiratory quotient was markedly increased compared with wild-type individuals, implicating a role for UCP3 in metabolic fuel partitioning.
Combination Delivery of Antigens and CpG by Lanthanides‐Based Core‐Shell Nanoparticles for Enhanced Immune Response and Dual‐Mode Imaging
Authors: Zhenhua Li, Zhen Liu, Meili Yin, Xinjian Yang, Jinsong Ren, Xiaogang Qu
Journal: Advanced Healthcare Materials (2013)

Europium-doped GdPO4 hollow spheres/polymer core-shell nanoparticles are functionalized with ovalbumin (OVA) as a model antigen and an oligonucleotide (CpG) that stimulates the immune response. These functionalized core-shell nanoparticles are used as vaccines, where they enable efficient delivery of an antigen to target sites, tracking of the vaccines using non-invasive clinical imaging technology.
Upper Panes Replaced With Double Panes.
Authors: S. J. Fort
Journal: JAMA (1899)

Ellicott City, Md., May 18, 1899. <h3>To the Editor:</h3> —I note in theJournalof April 29, under "Public Health," that a prize has been awarded Dr. Caslaing "by the French Academy of Science, for his suggestion that two upper panes in each window be replaced with double panes a short distance apart, the outer pane leaving a narrow opening at the bottom, as it does not reach quite to the sash below, and the inner pane leaving a similar opening at the top, as it does not reach quite up to the top of the sash." This seems a curious thing, when we read in Parkes' "Hygiene" (Edition 1883, Wood's Library, p. 174, Vol. i), in speaking of natural ventilation and its practical application: "Various plans have been proposed by different persons. The panes of glass may be made double, spaces being left at the<i>bottom</i>of the outside
THE EFFECT OF POLYSACCHARIDES ON THE REACTION BETWEEN ERYTHROCYTES AND VIRUSES, WITH PARTICULAR REFERENCE TO MUMPS VIRUS
Authors: Harold S. Ginsberg, Walther F. Goebel, Frank L. Horsfall
Journal: The Journal of Experimental Medicine (1948)

Polysaccharides which cause inhibition of the multiplication of mumps virus in the allantoic sac may or may not cause inhibition of hemagglutination by the virus. Moreover, such substances may or may not prevent adsorption of the virus by erythrocytes. The available evidence indicates that polysaccharides active as inhibitors do not block adsorption of mumps virus by cells of the living allantoic membrane. With influenza A, influenza B, and Newcastle disease viruses, as well as with PVM, there also appears to be a lack of correlation between the in vitro and in vivo inhibiting activity of polysaccharides.
Access and Exposure in Abdominal Surgery
Authors: Arthur B. Voorhees
Journal: JAMA (1965)

The authors have presented an excellent, orderly dissertation on the fundamentals of surgical techniques usually encountered in the operating room. The text has been divided into three convenient sections dealing separately with general considerations, individual incisions, and the choice of an incision. Under general considerations is a comprehensive discussion of many obvious, practical points concerned with the position and the responsibilities of the surgical team, the preparation of the operative field, and the use of the basic surgical tools. The points made are usually taken for granted by the trained surgeon and either initially go unnoticed by the neophyte or remain obscure in embarrassed silence. The section on the practical aspects of wound healing and wound closure, based on experience objectively appraised, is of particular and practical interest even though it is brief.  The section devoted to individual incisions takes up each of the common abdominal and combined thoracicoabdominal incisions
Their lordships on medical research
Authors: R. Smith
Journal: BMJ (1995)

Historically research policy swings between two poles. One pole is research driven by researchers pursuing what makes them curious and the opposite pole is research directed by politicians and managers to solve the problems that most concern them. The 1988 House of Lords report on medical research (produced with advice from Walter Holland, a professor with a particular interest in health services research) identified the fact that most medical research in Britain bore little relation to the needs of the NHS.1 From that House of Lords report grew the NHS research and development programme. But this week their lordships (advised this time by Keith Peters, regius professor of physics in Cambridge and a biomedical researcher to his fingertips) have produced a report in which they are worried that things have gone to far (p 1555).2 3 Now they are concerned that hospital based clinical research is losing out to health services research and research inprimary care and nursing. Their fears may be exaggerated.

Most BMJ readers are probably bewildered by the proliferation of reports on research, so I will summarise the story so far. The first House of Lords report was born into the ferment of the debate that preceded the NHS changes, and the government …