tbuckley/cabot-search huggingface dataset:
Molecular Modulation of Estrogen-Induced Apoptosis by Synthetic Progestins in Hormone Replacement Therapy: An Insight into the Women's Health Initiative Study
Authors: Elizabeth E. Sweeney, Ping Fan, V. Craig Jordan
Journal: Cancer Research (2014)

Abstract Hormone replacement therapy (HRT) is widely used to manage menopausal symptoms in women and can be comprised of an estrogen alone or an estrogen combined with a progestin. The Women's Health Initiative demonstrated in their randomized trials that estrogen alone HRT decreases the risk of breast cancer in postmenopausal women, whereas combined estrogen plus a progestin (medroxyprogesterone acetate, MPA) HRT increases this risk. Long-term estrogen-deprived MCF-7:5C cells were used to model the postmenopausal breast cancer cell environment. MPA is able to modify E2-induced apoptosis in MCF-7:5C cells. MPA, similar to dexamethasone, increases glucocorticoid receptor (GR) transcriptional activity, increases SGK1, a GR target gene, and can be blocked by RU486 (an antiglucocorticoid), suggesting that it functions through the GR. Norethindrone acetate (NETA), another progestin used in HRT, acts like an estrogen at high doses, upregulating estrogen receptor target genes and generating apoptosis in MCF-7:5C cells. The data suggest that women taking HRT comprising an estrogen plus MPA may have an increased risk of breast cancer due to MPA acting as a glucocorticoid and blunting E2-induced apoptosis in this environment. Therefore, perhaps other approved progestins (e.g., NETA) should be considered as alternatives to MPA. Cancer Res; 74(23); 7060–8. ©2014 AACR.
IODINE AS A DRESSING FOR OPERATION WOUNDS
Authors: F. C. Madden
Journal: BMJ (1912)

MTwDAAM= 765 fected pieces of catgut were then dipped into the spirit and perchloride solution for A, 2, 3, or 5 minutes.They were then soaked in sterile water for twenty-four hours to remove the perchloride, and finally cLultivated in broth tubes.Minutes in Spirit Solution: | 2 3 5Stapzhylococcus albuts (catgut) .
Accuracy of Molecular Data Generated with FFPE Biospecimens: Lessons from the Literature
Authors: Sarah R. Greytak, Kelly B. Engel, B. Paige Bass, Helen M. Moore
Journal: Cancer Research (2015)

Formalin-fixed and paraffin-embedded (FFPE) tissue biospecimens are a valuable resource for molecular cancer research. Although much can be gained from their use, it remains unclear whether the genomic and expression profiles obtained from FFPE biospecimens accurately reflect the physiologic condition of the patient from which they were procured, or if such profiles are confounded by biologic effects from formalin fixation and processing. To assess the physiologic accuracy of genomic and expression data generated with FFPE specimens, we surveyed the literature for articles investigating genomic and expression endpoints in case-matched FFPE and fresh or frozen human biospecimens using the National Cancer Institute's Biospecimen Research Database (http://biospecimens.cancer.gov/brd). Results of the survey revealed that the level of concordance between differentially preserved biospecimens varied among analytical parameters and platforms but also among reports, genes/transcripts of interest, and tumor status. The identified analytical techniques and parameters that resulted in strong correlations between FFPE and frozen biospecimens may provide guidance when optimizing molecular protocols for FFPE use; however, discrepancies reported for similar assays also illustrate the importance of validating protocols optimized for use with FFPE specimens with a case-matched fresh or frozen cohort for each platform, gene or transcript, and FFPE processing regime. On the basis of evidence published to date, validation of analytical parameters with a properly handled frozen cohort is necessary to ensure a high degree of concordance and confidence in the results obtained with FFPE biospecimens.
Haemophilus biotypes in respiratory disease.
Authors: G B Rhind, G A Gould, F Ahmad, M J Croughan, M A Calder
Journal: Thorax (1987)

<b>Objectives:</b> To describe children with pertussis who require intensive care. <b>Design, setting and patients:</b> An audit in Auckland, New Zealand, of pertussis admissions to the national paediatric intensive care unit (PICU) from 1991 to 2003. <b>Results:</b> 72 children, 97% &lt; 12 months old. The annual number of cases increased with time (p = 0.04). Forty (56%) were coughing for less than eight days before admission. Apnoea or paroxysmal cough were present in 33 (83%) of these children. 19% were readmitted to PICU. Those readmitted presented with more atypical disease, had a shorter first admission but longer total PICU admission (9 versus 5 days, p = 0.009). Thirty five (49%) received assisted ventilation. Four died. Of the 58 children from Auckland 9 either died (3), or had subsequent respiratory or neurodevelopmental problems (6). There was an increased risk (relative risk, 95% CI) of death or disability associated with having a co-morbidity (RR = 5.56, 1.50-8.15), an elevated lymphocyte count (RR = 5.75, 1.54-13.65), presenting with seizures/encephalopathy (4.87, 1.18-8.34 ) or shock (6.50, 1.89-8.94), having a PIM score of 1% or more (RR = 6.20, 1.22-21.72 ), any abnormal neurological signs (RR = 9.65, 3.32-15.23), or being readmitted to PICU (RR = 4.63, 1.44-8.82 ). <b>Conclusions:</b> Apnoea and paroxysmal cough are key symptoms of pertussis in those with shorter cough duration. Death or disability are frequent. Clinical factors define children at increased risk of these poor outcomes. Early discharge from PICU is associated with an increased risk of readmission and poor outcome.
Assessment of CD24 expression on bone marrow neutrophilic granulocytes: CD24 Is a marker for the myelocytic stage of development
Authors: M. Tarek Elghetany, Jyoti Patel
Journal: American Journal of Hematology (2002)

The understanding of normal surface maturation pattern of granulocytes plays an essential role in identifying abnormal patterns, which may be of diagnostic or pathogenetic significance in some disorders, such as myclodysplastic syndromes. CD24, which is expressed only on granulocytes and not on monocytes, has not been adequately studied. Surface marker studies on eight control marrows indicate that CD24 is expressed on bone marrow granulocytes in a pattern that is similar to CD11b while much different than the more mature markers, CD16b and CD35. Three sorting experiments show that the majority of CD24(-) cells are promyelocytes. We conclude that CD24 is expressed on the neutrophilic granulocytes at the stage of myelocytes, and hence it could potentially be used to study normal and abnormal maturation of granulocytes.
A Call for More With a Desire for Less: Pelvic Radiotherapy With Androgen Deprivation in the Treatment of Prostate Cancer
Authors: Alan Pollack
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.01.129 Journal of Clinical Oncology - published online before print November 1, 2016 PMID: 12743140 A Call for More With a Desire for Less: Pelvic Radiotherapy With Androgen Deprivation in the Treatment of Prostate Cancer Alan PollackxAlan PollackSearch for articles by this author Show More Fox Chase Cancer Center, Philadelphia, PA https://doi.org/10.1200/JCO.2003.01.129 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Magnetic Resonance Imaging Findings in Temporal Arteritis
Authors: T.A. Bley, O. Wieben, J. Leupold, M. Uhl
Journal: Circulation (2005)

investigated the use of MRI with a gadolinium- based contrast agent (Magnevist, Schering-Plough) for the noninvasive evaluation of temporal arteritis.In contrast-enhanced MRI, arteritis is revealed by increased signal intensity of the inflamed vessel wall.Thickening of an inflamed vessel wall as well as perivascular edema also can be demonstrated and potential aneurysms of the inflamed vessel can be excluded.A dedicated 8-channel phase-array head coil was used on a 1.5-T scanner (Sonata, Siemens Medical Solutions) to produce a stack of highresolution images with an in-plane resolution of 0.3 mm ϫ 0.2 mm and a slice thickness of 3 mm.Characteristic
Media hype? It's not as bad as it seems
Authors: David Spurgeon
Journal: BMJ (2004)

Researchers are often quick to blame the media for inaccuracies and distortions in reporting on health matters ( BMJ 2003;327: 688). But what if it turns out that newspapers are being unfairly criticised? A Canadian study of media coverage of genetic research shows that the charges are not well founded and that in most cases the media gets it right ( CMAJ 2004;170: 1399-407).

“Our data suggest that the majority of newspaper articles accurately convey the results and reflect the claims made in scientific journal articles,” say the report s authors, Tania M Bubela and Timothy A Caulfield of the University of Alberta s …
Basal cell adhesion molecule/lutheran protein. The receptor critical for sickle cell adhesion to laminin.
Authors: M Udani, Q Zen, M Cottman, N Leonard, S Jefferson, C Daymont, G Truskey, M J Telen
Journal: Journal of Clinical Investigation (1998)

Sickle red cells bind significant amounts of soluble laminin, whereas normal red cells do not. Solid phase assays demonstrate that B-CAM/LU binds laminin on intact sickle red cells and that red cell B-CAM/LU binds immobilized laminin, whereas another putative laminin binding protein, CD44, does not. Ligand blots also identify B-CAM/LU as the only erythrocyte membrane protein(s) that binds laminin. Finally, transfection of murine erythroleukemia cells with human B-CAM cDNA induces binding of both soluble and immobilized laminin. Thus, B-CAM/LU appears to be the major laminin-binding protein of sickle red cells. Previously reported overexpression of B-CAM/LU by epithelial cancer cells suggests that this protein may also serve as a laminin receptor in malignant tumors.
Propoxyphene and Friends
Authors: Fergus Fergusson
Journal: JAMA (1970)

To the Editor.—  The critical review of propoxyphene hydrochloride literature (213:996, 1970) states in its synopsis-abstract that a literature review was undertaken to determine if the widepopularityof the drug is justified. Fortunately, most of the study was not of popularity, whatever that may be, but a review of the effects of this drug compared with those of aspirin and codeine especially.  The authors find it ... reasonable to conclude, on the basis of our review, that propoxyphene is no more effective than aspirin or codeine and may even be inferior to these analgesics... Evidence for an inferiority is circuitous, external, statistically undocumented, and contingent upon that thin red line of patient definition of the empire of pain, which is never objective.  The statement, several times repeated, that propoxyphene is the most-prescribed drug is flattened by the probability that it is far from the most used drug—aspirin and its
Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2)
Authors: Lewis J. Rubin, Nazzareno Galiè, Friedrich Grimminger, Ekkehard Grünig, Marc Humbert, Zhi-Cheng Jing, Anne Keogh, David Langleben, Arno Fritsch, Flavia Menezes, Neil Davie, Hossein-Ardeschir Ghofrani
Journal: European Respiratory Journal (2015)

Riociguat is a soluble, guanylate cyclase stimulator, approved for pulmonary arterial hypertension. In the 12-week PATENT-1 study, riociguat was well tolerated and improved several clinically relevant end-points in patients with pulmonary arterial hypertension who were treatment naïve or had been pretreated with endothelin-receptor antagonists or prostanoids. The PATENT-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from the PATENT-1 study received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was to assess the safety and tolerability of riociguat; exploratory efficacy assessments included 6-min walking distance and World Health Organization (WHO) functional class. Overall, 396 patients entered the PATENT-2 study and 324 (82%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in PATENT-2 was similar to that observed in PATENT-1, with cases of haemoptysis and pulmonary haemorrhage also being observed in PATENT-2. Improvements in the patients', 6-min walking distance and WHO functional class observed in PATENT-1 persisted for up to 1 year in PATENT-2. In the observed population at the 1-year time point, mean± sd 6-min walking distance had changed by 51±74 m and WHO functional class had improved in 33%, stabilised in 61% and worsened in 6% of the patients versus the PATENT-1 baseline. Long-term riociguat was well tolerated in patients with pulmonary arterial hypertension, and led to sustained improvements in exercise capacity and functional capacity for up to 1 year.
Structural Conservation Despite Huge Sequence Diversity Allows EPCR Binding by the PfEMP1 Family Implicated in Severe Childhood Malaria
Authors: Clinton K Y Lau, Louise Turner, Jakob S Jespersen, Edward D Lowe, Bent Petersen, Christian W Wang, Jens E V Petersen, John Lusingu, Thor G Theander, Thomas Lavstsen, Matthew K Higgins
Journal: Cell Host & Microbe (2014)

The PfEMP1 family of surface proteins is central for Plasmodium falciparum virulence and must retain the ability to bind to host receptors while also diversifying to aid immune evasion. The interaction between CIDRα1 domains of PfEMP1 and endothelial protein C receptor (EPCR) is associated with severe childhood malaria. We combine crystal structures of CIDRα1:EPCR complexes with analysis of 885 CIDRα1 sequences, showing that the EPCR-binding surfaces of CIDRα1 domains are conserved in shape and bonding potential, despite dramatic sequence diversity. Additionally, these domains mimic features of the natural EPCR ligand and can block this ligand interaction. Using peptides corresponding to the EPCR-binding region, antibodies can be purified from individuals in malaria-endemic regions that block EPCR binding of diverse CIDRα1 variants. This highlights the extent to which such a surface protein family can diversify while maintaining ligand-binding capacity and identifies features that should be mimicked in immunogens to prevent EPCR binding.
Periodicity of Thalamic Synchronized Oscillations: the Role of Ca2+-Mediated Upregulation of Ih
Authors: Anita Lüthi, David A McCormick
Journal: Neuron (1998)

Thalamocortical networks can generate both normal and abnormal patterns of synchronized network activity, such as spindle waves and spike-and-wave seizures. These periods of synchronized discharge are often separated by a silent, refractory phase of between 5 and 20 s. In vitro investigations have demonstrated that this refractory period is due in large part to the persistent activation of the hyperpolarization-activated cation current Ih in thalamocortical cells. Here, we show that increases in [Ca2+]i due to rebound Ca2+ bursts result in persistent activation of Ih resulting from a positive shift in the activation curve of this current. The dynamical upregulation and persistent activation of Ih is the critical determinant of the time course of the refractory period. These findings demonstrate that periodicity in neural network oscillations may be generated through an interaction between the electrophysiological properties and intracellular signaling pathways of the constituent neurons.
PVL positive Staphylococcus aureus skin infections
Authors: A. Fogo, N. Kemp, R. Morris-Jones
Journal: BMJ (2011)

Patients presenting with recurrent skin abscesses may be infected with the rapidly emerging and highly pathogenic strains of Staphylococcus aureus that carry the virulence factor Panton-Valentine leukocidin (PVL). PVL positive S aureus can be acquired in the community and lead to recurrent and potentially serious infections of the skin and necrotising pneumonia. #### Case scenario A 39 year old woman presented with recurrent deep painful abscesses (figure⇓) and was one of 30 similar patients referred to our dermatology unit over the past 12 months. She was otherwise well with no intercurrent illness. Routine skin swabs taken by her general practitioner grew meticillin sensitive S aureus , but the abscesses did not resolve after several weeks of oral flucloxacillin. Further swabs were therefore taken and the S aureus isolate was sent to the national staphylococcal reference unit for typing. This confirmed PVL positive S aureus , which is not easily eradicated from skin infections with conventional courses of flucloxacillin or erythromycin. The patient subsequently required a four week course of rifampicin and clindamycin, plus five days of chlorhexidine wash and nasal mupirocin, to clear the lesions completely. No relapse was seen six months later. Top: Necrotising abscesses typical of PVL positive S aureus infection. Bottom: Cutaneous abscess with purulent discharge, central ulceration, and severe soft tissue inflammation #### How common is PVL positive S aureus skin infection?
Increased Carotid Wall Elastic Modulus and Fibronectin in Aldosterone-Salt–Treated Rats
Authors: Patrick Lacolley, Carlos Labat, Alex Pujol, Claude Delcayre, Athanase Benetos, Michel Safar
Journal: Circulation (2002)

Previous studies have demonstrated the development of cardiac fibrosis in aldosterone (Aldo)-salt hypertensive rats. Our aim was to determine the effects of Aldo and the Aldo receptor antagonist eplerenone (Epl) on in vivo mechanical properties of the carotid artery using echo-tracking system.Aldo was administered (1 microg/h) in uninephrectomized Sprague-Dawley rats (SD) receiving a high-salt diet from 8 to 12 weeks of age. Uninephrectomized control SD rats received a normal salt diet without Aldo. Three groups of Aldo-salt rats were treated with 1, 10, or 30 mg/kg(-1) x d(-1) of Epl by gavage. Elasticity was measured by elastic modulus (Einc)-wall stress curves using medial cross-sectional area (MCSA). The structure of the arterial wall was analyzed by histomorphometry (elastin and collagen), immunohistochemistry (EIIIA fibronectin, Fn), and Northern blot (collagens I and III). Aldo produced increased systolic arterial pressure, pulse pressure, Einc, MCSA, and EIIIA Fn with no change in wall stress or elastin and collagen densities compared with controls without Aldo. No differences in collagen mRNA levels were detected between groups. Epl blunted the increase in pulse pressure in Aldo rats and normalized Einc-wall stress curves, MCSA, and EIIIA Fn. These effects were dose dependent and not accompanied by a reduction in wall stress.Aldo is able to increase arterial stiffness associated with Fn accumulation, independently of wall stress. The preventive effects of Epl suggest a direct role for mineralocorticoid receptors in mechanical and structural alterations of large vessels in rat hyperaldosteronism.
Fats and atheroma: a retrial.
Authors: J I Mann
Journal: BMJ (1979)

The controversy over medical endorsement of dietary measures to reduce cholesterol intake has been reconsidered. The results of several published reports that apparently do not confirm the association between diet, cholesterol concentrations, and ischaemic heart disease (IHD) were found to be largely inapplicable to the argument. Results of primary prevention trials, however, suggested that lowering the cholesterol concentration had a beneficial effect in reducing morbidity from IHD. The "average Western diet" is particularly associated with accelerated or premature atherosclerotic disease, yet the saturated fatty acid component of the diet may be only one of several factors relevant to IHD. Such diets are usually high in refined carbohydrate and total energy intake. Disordered nutrition generally, and other environmental and constitutional factors seem to be important in the aetiology of IHD. A prudent diet, incorporating decreased intake of fats, simple sugars, and refined carbohydrate, with polyunsaturated fats comprising less than 25% of total energy intake, may be the best method of reducing the incidence of IHD and other diseases of overnutrition.
Ammonia in the eye.
Authors: A. G. Cross
Journal: BMJ (1969)

lion Act.She said that these fell into three categories: " To know and understand its provisions; to apply the knowledge objec- tively ; and to avoid using it if at all pos- sible."What an extraordinary statement !The Abortion Act is the law of the land and 'has already proved of immense benefit to many of my patients.It is there to be used and to be applied uniformly throughout the country.It is the antagonism to abortion reform of many doctorse particularly N.H.S. consultants in certain parts of the country, that creates long queues for abortion.It is only necessary for two doctors, a general practitioner and his colleague, to sign certi- ficate A-the patient is then ready for opera- tion.A great deal of valuable time is now being wasted in referring these unfortunate patients to psychiatrists, and the gynaeco- logist could perform three abortions in the time that he takes, unnecessarily, to investigate one case.Some psychiatrists will not approve termination under the Act but will admit the patient to a mental hospital for supportive therapy.What nonsense !If all doctors, general practitioners and consultants, put their patient's welfare before their own religious and biased cobwebbed ideas on abortion, then the new Act would present no problems at all.A patient for termination of pregnancy would appear in hospital as an acute appendix does today, and would be dealt with as quickly and without question.-Iam, etc.,
ACP Library on Disk 2
Authors: Eric A. Pifer
Journal: Annals of Internal Medicine (1998)

Medical Writings1 May 1998ACP Library on Disk 2Eric A. Pifer, MD and Chris Dwyer, BAEric A. Pifer, MDUniversity of Pennsylvania, Philadelphia, PennsylvaniaAmerican College of Physicians, Philadelphia, PennsylvaniaSearch for more papers by this author and Chris Dwyer, BAUniversity of Pennsylvania, Philadelphia, PennsylvaniaAmerican College of Physicians, Philadelphia, PennsylvaniaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-9-199805010-00046 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ACP Library on Disk 2; Philadelphia: American Coll Physicians; 1997. Single-user price, $195.00 for ACP members, $275.00 for non-members. Multi-user version also available. Order phone 800-523-1546, ext. 2600.Field of medicine: General internal medicine.Format: CD-ROM software program.System requirements: Windows 3.1, 95, or NT; Macintosh 6.7 or above.Audience: Internal medicine practitioners, house officers, medical students rotating through clinical clerkships, physicians in specialties other than internal medicine, and allied health professionals with primary care knowledge needs.Purpose: To provide an electronic archive of information sources from the American College of Physicians and the U.S. government.Content: The CD-ROM contains ... Author, Article, and Disclosure InformationAuthors: Eric A. Pifer, MD; Chris Dwyer, BAAffiliations: University of Pennsylvania, Philadelphia, PennsylvaniaAmerican College of Physicians, Philadelphia, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1998Volume 128, Issue 9Page: 791KeywordsAllied health care professionalsArchivesDrug informationEvidence based medicineForecastingHealth care policyLibrariesSub-specialty careTreatment guidelines ePublished: 15 August 2000 Issue Published: 1 May 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...