tbuckley/cabot-search huggingface dataset:
Campaign seeks to increase US 'cholesterol consciousness'
Authors: Charles Marwick
Journal: JAMA (1986)

A major national campaign is being mounted to alert both the medical profession and the public to the hazards that most investigators associate with elevated cholesterol levels. As a result, more people may be seeing physicians to have their cholesterol levels checked and to seek counseling about avoiding problems associated with high cholesterol levels. A number of organizations already are considering or even undertaking professional educational programs that might help to prepare physicians to respond to these heightened public concerns about cholesterol. Most physicians are aware that, currently, those persons older than 40 years of age with serum cholesterol levels of 240 mg/dL or above are at an increased risk of coronary heart disease, while those with levels 260 mg/dL or above are at especially high risk. As in hypertension, the "borderline risk" area still is in debate. One view, that cholesterol levels should be no more than 200 mg/dL,
GP2, the homologue to the renal cast protein uromodulin, is a major component of intraductal plugs in chronic pancreatitis.
Authors: S D Freedman, K Sakamoto, R P Venu
Journal: Journal of Clinical Investigation (1993)

Protein plug obstruction of the pancreatic duct is one of the early events in chronic pancreatitis yet little is known about its pathogenesis. GP2, a protein in the exocrine pancreas, is a glycosyl phosphatidylinositol-anchored protein that is cleaved from the zymogen granule membrane and secreted into pancreatic juice. Since its homologue, uromodulin, is involved in renal cast formation, we asked the question whether GP2 might play a similar role in plug formation in chronic pancreatitis. The protein composition of intraductal plugs from patients with noncalcific chronic pancreatitis was examined. Plugs purified from pancreatic juice obtained by endoscopic cannulation were analyzed by SDS-PAGE. A 97-kD protein was found not only to be a reproducible constituent but also enriched within intraductal plugs. This protein was confirmed as GP2 by its localization to zymogen granule membranes, its isoelectric point, and by Western blotting. Although the pancreatic stone protein was identified in plugs, it was not a major reproducible component. These results demonstrate that GP2 is an integral component of plugs in pancreatic juice and suggest that GP2 may play a role in pancreatic plug formation that is analogous to the role played by uromodulin in the pathogenesis of renal casts.
ERASION, EXCISION AND AMPUTATION IN JOINT DISEASE.
Authors: De FOREST WILLARD
Journal: JAMA (1895)

From failure of early diagnosis, from lack of early treatment, and from the neglect of early protection and fixation of inflamed joint surfaces, or on account of the intensity of the tubercular process, a large number of cases of tubercular joint disease still require operative procedures for the safety of the limb or the life of the affected individual. Fortunately, owing to a better appreciation of the conditions, these cases are becoming rare; it being more generally recognized that destructive results are preventable by early treatment; that is, by long-continued protection secured by rest and by effective mechanical devices. Proper management of these cases will result in the saving of a large number of these joints, even if the tubercular bacillus has secured a foothold in the osseous structures adjacent to the joint itself. Much will depend upon the joint invaded; but the same principles of treatment will apply to
Politicians may not have same goals as clinicians with regard to mergers
Authors: T. Sheldon, A. Maynard
Journal: BMJ (1999)

EDITOR—Garside's editorial on evidence based mergers confuses outcomes and process.1 She wants to collect evidence on “how to manage the process of merging” as well as to assemble “evidence on the benefits of NHS merged organisations.”

International evidence on the benefits of mergers and the influence of hospital size on the quality of, cost …
Scientists fear that libel ruling will inhibit debate
Authors: D. Cohen
Journal: BMJ (2009)

Leading academics, journalists, science writers, libel lawyers, and MPs have spoken out in support of the science broadcaster and writer Simon Singh—against whom the British Chiropractic Association has launched a libel action—at a public meeting hosted by the Index on Censorship on Monday 18 May.

Writing in the Guardian on 19 April 2008 during chiropractic awareness week, Dr Singh made various claims about the treatments offered by chiropractors. The claims also appeared in a book he coauthored with Edzard Ernst, professor of complementary medicine at Exeter University, Trick or Treatment? Alternative Medicine on Trial. 

In his article (which the Guardian has removed from its website) Dr Singh said that the British Chiropractic Association “claims that their members can help treat children with colic, sleeping and feeding problems, frequent ear infections, asthma and prolonged crying, even though there is not a jot of evidence. This organisation is the respectable face of the chiropractic profession and yet it happily promotes bogus treatments.”

The association, which represents between about 1300 …
Abstract A92: Tumor suppressive function of human macrophage-derived ADAM15 exosomes.
Authors: Hee Doo Lee, Yeon Hyang Kim, Doo-Sik Kim
Journal: Cancer Research (2013)

Abstract A disintegrin and metalloproteinase (ADAM) 15, the only ADAM protein containing an Arg-Gly-Asp (RGD) motif in its disintegrin-like domain, is a widely expressed, human membrane protein. The present study demonstrates that macrophages derived from monocytes actively release ADAM15 into the extracellular space as an exosomal component. The exosomal ADAM15 release is further elevated by lipopolysaccharide stimulation, indicating that the exosome release is closely associated with immune cell differentiation and activation. ADAM15-rich exosomes display enhanced binding affinity for integrin alpha v beta 3, thereby interfering with the interaction between integrin alpha v beta 3 and vitronectin. ADAM15 exosomes significantly suppress vitronectin- and fibronectin-induced proliferation and migration of various tumor cells as well as tumor growth in vivo. Tumor suppressive function of exosomal ADAM15 is effectively blocked by monoclonal antibody specific for the extracellular domain of ADAM15. Experimental evidence shows that RGD-containing disintegrin-like domain, but not metalloproteinase activity, of ADAM15 is the responsible element for the tumor suppressive activity. Notably, proliferation and migration of macrophages are stimulated by the exosomes, indicating anti-tumor immunity. This work strongly suggests that a novel tumor suppressive mechanism is mediated by macrophage-derived ADAM15 exosomes. Citation Format: Hee Doo Lee, Yeon Hyang Kim, Doo-Sik Kim. Tumor suppressive function of human macrophage-derived ADAM15 exosomes. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A92.
Anti–IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial
Authors: James G. Krueger, Laura K. Ferris, Alan Menter, Frank Wagner, Alexander White, Sudha Visvanathan, Bojan Lalovic, Stella Aslanyan, Elaine E.L. Wang, David Hall, Alan Solinger, Steven Padula, Paul Scholl
Journal: Journal of Allergy and Clinical Immunology (2015)
The High—Monounsaturated Fat Diet as a Practical Alternative for NIPPM
Authors: Lesley V Campbell, Priscilla E Marmot, Jenny A Dyer, Mark Borkman, Len H Storlien
Journal: Diabetes Care (1994)

To examine the dietary preferences of and metabolic effects in patients with non-insulin-dependent diabetes mellitus (NIDDM) of a home-prepared high-monounsaturated fat (HM) diet compared with the recommended high-carbohydrate (CHO) diet.Ten men with mild NIDDM prepared HM and high-CHO diets at home alternately and in random order for 2 weeks each with a minimum 1-week washout. Before and after each diet, 24-h urine glucose, fasting lipids, fructosamine, and 6-h profiles of glucose, insulin, and triglycerides were measured. Dietary preferences were assessed by questionnaire.In the HM diet, patients consumed 40% of energy intake as CHO and 38% as fat (21% monounsaturated) compared with 52 and 24%, respectively, in the high-CHO diet, with equal dietary fiber content. Body weight and total energy intake were similar in both. The HM diet resulted in significantly lower 24-h urinary glucose excretion, fasting triglyceride, and mean profile glucose levels. The fructosamine levels, the fasting total, low-density lipoprotein, and high-density lipoprotein cholesterol, and the prandial triglyceride concentrations did not differ significantly as a result of the diets. The two diets did not differ in ratings for overall acceptance, taste, cost, ease of preparation, variety, or satiety.Prepared at home, the HM diet was, in the short-term, metabolically better in some aspects than the currently recommended diet for NIDDM. It also provided a palatable alternative.
547 CHOLANGIOCARCINOMA IN ITALY: A NATIONAL SURVEY ON DEMOGRAPHIC AND CLINICAL CHARACTERISTICS, DIAGNOSTIC MODALITIES AND TREATMENT
Authors: M.C. Bragazzi, D. Alvaro, A. Benedetti, R. Capocaccia, E. Crocetti, L. Fabris, G. Fava, S. Ferretti, A. Floreani, G.L. Grazi, P. Invernizzi, A. Laghi, M.G. Mancino, M. Marzioni, M. Mutignani, P. Paoloantonio, A. Sonzogni, M. Strazzabosco, T. Stroffolini
Journal: Journal of Hepatology (2010)
Letter: Temperature change and multiple sclerosis.
Authors: F A Davis
Journal: BMJ (1974)

this risk-and at the least avoid prolonged pregnancy.The second item concerns our doubleblind trial of chlorpropamide 100 mg a day in the treatment of gestational chemical diab_tes in women of average body weight.We do know that such a dose of ohlorpropamide is effective in reversing chemical diabetes in the mother in pregnancy-without apparent harm to the fetus4-though we do not recommend this form of treatmenit for diabetes of a more severe degree, wh-ich seems to require more delicate oDntrol during pregnancy.5-Weare, etc.,
Echo-wave termination of ventricular tachycardia. A common mechanism of termination of reentrant arrhythmias by various pharmacological interventions.
Authors: J Brugada, L Boersma, H Abdollah, C Kirchhof, M Allessie
Journal: Circulation (1992)

BACKGROUND Based on epicardial mapping, different mechanisms of termination of reentrant ventricular tachycardia by various pharmacological interventions are described. METHODS AND RESULTS In 40 Langendorff-perfused rabbit hearts, rings of anisotropic left ventricular epicardium were made by a cryoprocedure. Sustained monomorphic ventricular tachycardia based on continuous circus movement of the impulse around the ring was induced by programmed stimulation. Increasing doses of heptanol (n = 10), potassium (n = 10), tetrodotoxin (n = 6), RP62719 (a new class III drug) (n = 4), flecainide (n = 5), and propafenone (n = 5) were administered to terminate ventricular tachycardia. Epicardial mapping (248 points) was used to study the mechanism of termination of ventricular tachycardia. In 28 of 40 hearts, ventricular tachycardia terminated because the drugs produced complete conduction block of the impulse in a segment of the reentrant pathway. In the remaining 12 hearts (heptanol, n = 2; potassium, n = 3; tetrodotoxin, n = 2; RP62719, n = 2; flecainide, n = 1; and propafenone, n = 2), termination of ventricular tachycardia occurred by collision of the circulating impulse with a spontaneous antidromic wave front reflected within the circuit. This phenomenon occurred when the circulating impulse encountered an arc of functional conduction block that did not extend along the whole width of the ring. As a result, the impulse dissociated into a continuing orthodromic circulating wave and a returning antidromic echo-wave caused by microreentry within the ring. CONCLUSIONS Independent of their mechanisms of action, sodium channel blockers, electrical uncouplers, and class III drugs terminate reentrant ventricular tachycardia either by complete conduction block or by collision of the impulse with an echo-wave.
Relationships among the composition of mucus, epithelial lining liquid, and adhesion of microorganisms.
Authors: J Widdicombe
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Airway surface liquid (ASL) is complex and comes from many sources, in particular glands and epithelium. The mucoglycoproteins present bind to bacteria. Bacterial membranes contain adhesins that bind to receptors on the mucus. The bound bacteria multiply and release toxins that diffuse to the epithelium and damage or destroy it, inhibiting mucociliary transport. The damaged epithelium releases products such as phospholipids into the ASL. These change the physical properties of the mucus and also promote mucus secretion, which may block smaller airways. Airway surface liquid contains constituents such as immunoglobulins, lysozyme, and lactoferrin and neutrophil products such as proteases that act on bacteria. Few bacteria adhere to healthy epithelium. To adhere, most require damaged tissue with membrane receptors that encourage bacterial invasion. If the epithelium is destroyed, bacteria adhere to the basement membrane or extracellular matrix. A damaged epithelium can also cause hyperresponsiveness of airway secretory mechanisms, with increased gland secretion that in turn interacts with the bacteria.
Mexico conference considers pre-exposure prophylaxis for AIDS
Authors: B. Roehr
Journal: BMJ (2008)

The possible use of a daily pre-exposure prophylactic pill against AIDS raised interest at last week’s 17th international AIDS conference because of the recent failures of trials of vaccines and microbicides.

Several studies of pre-exposure prophylaxis are being launched in different parts of the world. Most involve a combination of two popular anti-HIV drugs, tenofovir and emtricitabine, in one pill, marketed as Truvada. The combination has amassed millions of people years of use. It seems to be safe, well tolerated, and holds the virus in check.

There are biological reasons to think that pre-exposure prophylaxis can work, and trials in monkeys are …
Retargeting Sleeping Beauty Transposon Insertions by Engineered Zinc Finger DNA-binding Domains
Authors: Katrin Voigt, Andreas Gogol-Döring, Csaba Miskey, Wei Chen, Toni Cathomen, Zsuzsanna Izsvák, Zoltán Ivics
Journal: Molecular Therapy (2012)

The Sleeping Beauty (SB) transposon is a nonviral, integrating vector system with proven efficacy in preclinical animal models, and thus holds promise for future clinical applications. However, SB has a close-to-random insertion profile that could lead to genotoxic effects, thereby presenting a potential safety issue. We evaluated zinc finger (ZF) DNA-binding domains (DBDs) for their abilities to introduce a bias into SB's insertion profile. E2C, that binds a unique site in the erbB-2 gene, mediated locus-specific transposon insertions at low frequencies. A novel ZF targeting LINE1 repeats, ZF-B, showed specific binding to an 18-bp site represented by ~12,000 copies in the human genome. We mapped SB insertions using linear-amplification (LAM)-PCR and Illumina sequencing. Targeted insertions with ZF-B peaked at approximately fourfold enrichment of transposition around ZF-B binding sites yielding ~45% overall frequency of insertion into LINE1. A decrease in the ZF-B dataset with respect to transposon insertions in genes was found, suggesting that LINE1 repeats act as a sponge that "soak up" a fraction of SB insertions and thereby redirect them away from genes. Improvements in ZF technology and a careful choice of targeted genomic regions may improve the safety profile of SB for future clinical applications. The Sleeping Beauty (SB) transposon is a nonviral, integrating vector system with proven efficacy in preclinical animal models, and thus holds promise for future clinical applications. However, SB has a close-to-random insertion profile that could lead to genotoxic effects, thereby presenting a potential safety issue. We evaluated zinc finger (ZF) DNA-binding domains (DBDs) for their abilities to introduce a bias into SB's insertion profile. E2C, that binds a unique site in the erbB-2 gene, mediated locus-specific transposon insertions at low frequencies. A novel ZF targeting LINE1 repeats, ZF-B, showed specific binding to an 18-bp site represented by ~12,000 copies in the human genome. We mapped SB insertions using linear-amplification (LAM)-PCR and Illumina sequencing. Targeted insertions with ZF-B peaked at approximately fourfold enrichment of transposition around ZF-B binding sites yielding ~45% overall frequency of insertion into LINE1. A decrease in the ZF-B dataset with respect to transposon insertions in genes was found, suggesting that LINE1 repeats act as a sponge that "soak up" a fraction of SB insertions and thereby redirect them away from genes. Improvements in ZF technology and a careful choice of targeted genomic regions may improve the safety profile of SB for future clinical applications.
The place of botulinum toxin type A in the treatment of focal hyperhidrosis: reply from authors
Authors: N.J. Lowe
Journal: British Journal of Dermatology (2005)

Journal Article The place of botulinum toxin type A in the treatment of focal hyperhidrosis: reply from authors Get access N.J. Lowe, N.J. Lowe Cranley Clinic, 3 Harcourt House, 19a Cavendish Square, London W1G 0PN, U.K E‐mail: cranleyuk@aol.com Search for other works by this author on: Oxford Academic Google Scholar For the European Hyperhidrosis Group For the European Hyperhidrosis Group Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 2, 1 August 2005, Page 461, https://doi.org/10.1111/j.1365-2133.2005.06789.x Published: 01 August 2005
Guide to the Internet: The world wide web
Authors: M. Pallen
Journal: BMJ (1995)

The world wide web provides a uniform, user friendly interface to the Internet. Web pages can contain text and pictures and are interconnected by hypertext links. The addresses of web pages are recorded as uniform resource locators (URLs), transmitted by hypertext transfer protocol (HTTP), and written in hypertext markup language (HTML). Programs that allow you to use the web are available for most operating systems. Powerful on line search engines make it relatively easy to find information on the web. Browsing through the web--"net surfing"--is both easy and enjoyable. Contributing to the web is not difficult, and the web opens up new possibilities for electronic publishing and electronic journals.
Randomised controlled trial of antibiotics in patients with cough and purulent sputum.
Authors: N C Stott, R R West
Journal: BMJ (1976)

Two hundred and twelve adults with cough and purulent sputum of up to one week9s duration were allocated randomly to treatment with doxycycline or placebo capsules for up to 10 days. Cough, purulent sputum, feeling "off colour," and time off work lasted as long in treatment and control groups, but running nose persisted for a shorter time in the doxycycline group. The number of new episodes of lower respiratory tract infections, vaginal infections, gastrointestinal upsets, and otitis media over the next six months were the same in both groups, but fewer new upper respiratory infections were experienced by the doxycycline-treated patients. There is no consensus among doctors about using antibiotics in patients with cough and purulent sputum, and these results indicate that otherwise healthy people with these symptoms will usually get better without antibiotic treatment.
Traumatic Aneurysm of the Ulnar Artery in the Palm Cured by Tying the Ulnar Artery above the Wrist
Authors: Wm. Robertson
Journal: BMJ (1897)

Tii;=1637 optic neuritis was present.By the perimeter he was found to have well-marked bitemporal hemianopia, the nasal half of the field of vision being perfect.He did not suffer from headaches, but if he stooped he felt as though his head was swelling and would burst.The ribs were quite twice the thickness of normal ones, and markedly thickened at the sternal ends.The sternum was enlarged to a considerable degree, and projects forward.The heart was normal.The spleen and liver were not examined.There was no apparent enlargement of the thyroid.He perspired very freely, and suffered much from thirst.He constantly felt drowsy.Memory for recent events was very bad, but he remembered things that happened years ago well.His gait was slow, measured, with a pronounced stoop, and he had difficulty in getting up and down stairs.Both knees and shoulders were affected with rheumatoid arthritis.In the nineteen days he was under my observation he lost 4 lbs.RE,MARKS.Since August 24th, 1897, the patient has been taking tabloids of "pituitary gland substance," gr.ii (B.WV. and Co)., three times a day, with the following result, which I give in his own words, his letter to me being
Next Influenza Vaccine Set
Authors: Charles Marwick
Journal: JAMA (1988)

AS THE CURRENT influenza season winds down (see accompanying article), infectious disease experts are preparing for future outbreaks. For example, two new isolates will be in the vaccine prepared in this country for the late 1988 and early 1989 influenza season. The Centers for Disease Control, Atlanta, says the decision has been made to include A/Sichuan/2/87 for the H3N2—that is, the antigenic hemagglutinin and neuraminidase glycoproteins of the viral coat—component and a Victoria-like isolate for the B component (<i>JAMA</i>1988;259:977). The H1N1 component will remain the Taiwan isolate that is in the current vaccine (<i>JAMA</i>1988;259:1131). The isolates have been prepared for the large-scale vaccine effort that must be undertaken between now and the next influenza season, and the strains sent to the manufacturers. This involves making mutant strains of the virus that have growth potential, yet possess antigenicity. At the same time, the United Nations' World Health Organization (WHO)
Sexual contact between doctors and patients.
Authors: T. Fahy, N. Fisher
Journal: BMJ (1992)

<h3>Summary</h3> DNA double-strand breaks (DSBs) are a feature of many acute and long-term neurological disorders, including neurodegeneration<sup>1,2</sup>, following neurotrauma<sup>3</sup> and after stroke<sup>4</sup>. Persistent activation of the DNA damage response (DDR) in response to DSBs contributes to neural dysfunction and pathology as it can force post-mitotic neurons to re-enter the cell cycle leading to senescence or apoptosis<sup>5–8</sup>. Mature, non-dividing neurons may tolerate low levels of DNA damage, in which case muting the DDR might be neuroprotective. Here, we show that attenuating the DDR by targeting the MRN complex, which is responsible for recognition of DSBs, is neuroprotective in three neurodegeneration models in <i>Drosophila</i> and prevents Aβ-induced loss of synapses in hippocampal neurons. Attenuating the DDR after optic nerve injury is also neuroprotective to retinal ganglion cells (RGC) and promotes dramatic regeneration of their neurites both <i>in vitro</i> and <i>in vivo</i>. Dorsal root ganglion neurons similarly regenerate when the DDR is targeted <i>in vitro</i> and this strategy also induces a full restoration of lost function after spinal cord injury <i>in vivo</i>. We conclude that muting the DDR in the nervous system is neuroprotective in multiple neurological disorders. Our results point to new therapies to maintain or repair the nervous system.