tbuckley/cabot-search huggingface dataset:
Plasma cholesterol concentration and death from coronary heart disease: 10 year results of the Whitehall study.
Authors: G Rose, M Shipley
Journal: BMJ (1986)

Ten year mortality from coronary heart disease in 17,718 middle aged men was related to their initial plasma cholesterol concentrations. The relative risk of death from coronary heart disease declined with age, but the absolute excess risk did not. The risk gradient was continuous over the whole range of cholesterol concentrations, the lowest mortality being among men with concentrations below the lowest decile. It seems that, as with blood pressure, the average cholesterol concentration in the blood pressure, the average cholesterol concentration in the population is too high: lowest concentrations are prognostically the best. A quarter of all deaths from coronary heart disease related to cholesterol occurred among men with concentrations above the top decile, but 55% occurred among men with concentrations in the middle three fifths of the distribution; this figure of 55% could be reduced only by a policy aimed at lowering concentrations in the whole population.
Abstract 1787: ImmTACs: Bi-functional reagents for redirected tumour cell killing
Authors: Samantha J. Paston, Rebecca Ashfield, Nathaniel Liddy, Giovanna Bossi, Katherine Adams, Emmet McCormack, Anna Lissina, Tara Mahon, Namir Hassan, Jessie Gavarret, Frayne Bianchi, Nick Pumphrey, Kristin Ladell, Emma Gostick, Andrew K. Sewell, Nikolai Lissin, Peter Molloy, Yi Li, Brian Cameron, Malkit Sami, Emma Baston, Jane Harper, Andrew Johnson, Annelise Vuidepot, Penio Todorov, Rebecca Dennis, Michael Kalos, Carl June, David A. Price, Daniel Williams, Bent K. Jakobsen
Journal: Cancer Research (2011)

Abstract The human immune system can theoretically identify malignant cells by inspecting cell surface Class I HLA -peptide complexes for the presence of disease-associated epitopes. Indeed, many cancer patients generate CD8 cyto-toxic T cell responses to tumour-associated antigens; the majority of patients, however, fail to clear tumours since T cell avidity for self-antigens tends to be weak, and cancer cells employ escape mechanisms for avoiding destruction by T cells. To overcome these issues, we have engineered novel, bi-functional protein therapeutics termed ImmTACs (Immune Mobilising mTCR Against Cancer) which re-direct the immune system to target and destroy tumour cells with a high degree of potency and specificity. An ImmTAC comprises a high affinity ‘monoclonal’ T cell Receptor (mTCR) targeting a cancer-associated HLA-peptide complex, fused to an anti-CD3 scFv domain which activates an anti-tumour T cell response. We demonstrate that ImmTACs against a number of different cancer-associated antigens can target and kill tumour cells expressing as few as 10-20 epitopes per cell with pico-Molar potency. ImmTACs preferentially activate effector memory CD8 T cells, resulting in secretion of multiple cytokines and tumour cell killing; a single activated T cell can kill multiple antigen positive tumour cells. Furthermore, we demonstrate that the reagents are able to inhibit tumour growth in mouse xenograft models. In vitro ImmTAC potency translates to a dose of less than 1mg in humans, representing a significant advance over existing targeted anti-cancer therapies. Currently we are conducting a phase I dose-escalation trial and Phase 0 exploratory trial using ImmTAC-gp100 in late stage melanoma patients. In summary, ImmTACs offers a novel therapeutic approach for the treatment of various cancers with the potential to provide major benefits over current treatments including reduction in dose to sub-mg quantities and an improved safety profile. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1787. doi:10.1158/1538-7445.AM2011-1787
Testing of drugs on children ruled unlawful by US judge
Authors: S. Gottlieb
Journal: BMJ (2002)

A US federal judge has overruled the Food and Drug Administration's requirement that drug companies test some of their products on children, saying the agency had overstepped its authority in requiring companies to do so.

The rule, promulgated by the FDA in 1998, has been generally accepted by the pharmaceutical industry, and the number of drugs tested …
Promotion of physical activity and fitness in sedentary patients with Parkinson's disease: randomised controlled trial
Authors: M. van Nimwegen, A. D. Speelman, S. Overeem, B. P. van de Warrenburg, K. Smulders, M. L. Dontje, G. F. Borm, F. J. G. Backx, B. R. Bloem, M. Munneke
Journal: BMJ (2013)

<b>Objective</b> To evaluate whether a multifaceted behavioural change programme increases physical activities in patients with Parkinson’s disease. <b>Design</b> Multicentre randomised controlled trial. <b>Setting</b> 32 community hospitals in the Netherlands, collaborating in a nationwide network (ParkinsonNet). <b>Participants</b> 586 sedentary patients with idiopathic Parkinson’s disease aged between 40 and 75 years with mild to moderate disease severity (Hoehn and Yahr stage ≤3). <b>Intervention</b> Patients were randomly assigned to the ParkFit programme or a matched general physiotherapy intervention. ParkFit is a multifaceted behavioural change programme, designed specifically to achieve an enduring increase in the level of physical activity (coaches using motivational strategies; ambulatory feedback). <b>Main outcome measures</b> The primary endpoint was the level of physical activity, measured every six months with a standardised seven day recall (LASA physical activity questionnaire—LAPAQ). Secondary endpoints included two other measures of physical activity (activity diary and ambulatory activity monitor), quality of life (Parkinson’s disease questionnaire—PDQ-39), and fitness (six minute walk test). <b>Results</b> 540 (92.2%) patients completed the primary outcome. During follow-up, overall time spent on physical activities (LAPAQ) was comparable between the groups (adjusted group difference 7%, 95% confidence interval −3 to 17%; P=0.19). Analyses of three secondary outcomes indicated increased physical activity in ParkFit patients, as suggested by the activity diary (difference 30%; P&lt;0.001), the activity monitor (difference 12%; P&lt;0.001), and the six minute walk test (difference 4.8 m; P=0.05). PDQ-39 did not differ between ParkFit patients and controls (difference −0.9 points; P=0.14). The number of fallers was comparable between ParkFit patients (184/299; 62%) and controls (191/287; 67%). <b>Conclusions</b> The ParkFit behavioural change programme did not increase overall physical activity, as measured with the LAPAQ. The analysis of the secondary endpoints justifies further work into the possible merits of behavioural change programmes to increase physical activities in daily life in Parkinson’s disease. <b>Trial registration</b> Clinical trials NCT00748488.
Diffusion of Radioactive Sodium in Normotensive and Pre-eclamptic Pregnancies
Authors: T. Johnson, C. G. Clayton
Journal: BMJ (1957)

MEDICALJORAIn-Vitro Studies.-Theaddition of either laminarin sulphate M or N in vitro to lipaemic serum caused neither visible clearing of the serum nor any significant alteration in the electrophoretic distribution of neutral fats and lipoproteins.Discussion As only small amounts of the two laminarins were avail- able for clinical trial, it was particularly useful that laminarin sulphate N proved to be inert and thus acted as a control for the positive findings following injection of laminarin sulphate M.A single intravenous injection of the lower-sulphated polysaccharide laminarin sulphate M cleared lipaemic serum, increased the electrophoretic mobility of lipoproteins, and altered the distribution of lipoproteins in the same way as heparin.The changes could be demonstrated almost immediately after injection, and persisted for four to six hours.They were not reproduced by the addition of laminarin sulphate M to serum in vitro.It is evident, therefore, that the antilipaemic properties of laminarin sulphate M closely parallel those of heparin, except for the shorter duration of action of the dose used in this study.On the other hand, laminarin sulphate N, a closely related polysaccharide, showed no demonstrable effect on the electro- phoretic mobility or distribution of lipoproteins.No effect was noted when 100 mg. of laminarin sulphate M was injected intramuscularly.It is possible, however, that with larger doses changes may be seen following both intramuscular and subcutanous injections, and that the duration of the changes will be prolonged by slow release from the tissues at the site of injection.No local reaction resulted from intramuscular injection of the polysaccharide, and no reactions were observed in any patient following intravenous laminarin.Since laminarin sulphate M possesses the antilipaemic properties of heparin without the hazards of its anticoagu- lant action, it would appear to be a suitable substance with which to study the effect of prolonged administration of " lipaemia-clearing" substances on the course of athero- sclerosis in man.Following the completion of chronic toxicity trials in animals and further information on the acknowledge the co-operation and assistance of Drs.E. V. B. Morton, Cobb, and Adams, of Boots.Dr. Paul Wood, Director of the Institute of Cardiology, has throughout provided us with invaluable advice
Myocardial opacification at intravenous myocardial contrast echocardiography depends on the depth of focus point: in vivo and in vitro study
Authors: Sachiko Yagura, Kumiko Kiyoshima, Jyuri Okazaki, Hideo Hirayama, Kentaro Ohtani, Yasushi Kashiwagi, Tsutomu Toshida, Akiko Iwata, Hiroyuki Kayano, Toshihiko Asanuma, Fuminobu Ishikura, Shintaro Beppu
Journal: Journal of the American College of Cardiology (2002)
Abstract 4187: Phospho-Akt status as a predictor of disease free interval in patients with muscle invasive transitional cell carcinoma of the bladder
Authors: Victor A. McPherson, Andrew Williams, Susanne Chan, Kamilia Rizkalla, Jonathan Izawa, John Lewis
Journal: Cancer Research (2011)

Abstract Background: Akt is an ubiquitous signaling molecule that is associated with a wide array of biological effects including cell growth and proliferation. The dysregulation of Akt has been associated with cancer cell transformation, invasion and metastasis. While the roles of mutations in FGFR3, p53 and Ras have been the focus of the majority of studies of Transitional cell carcinoma (TCC) of the bladder, recent evidence suggests a link between the Akt pathway and the progression of TCC. Mutations in Akt pathway members have been identified in subsets of bladder TCCs, and Akt activation in TCC cell lines confers resistance to chemotherapeutics and promotes invasion in vitro. This led us to hypothesize that activated Akt may be an important biomarker in the progression of muscle invasive TCC. Methods: Tissue was obtained from 67 patients who had undergone radical cystectomy procedures for treatment of muscle invasive TCC. Tissue sections were taken from paraffin embedded samples and subjected to immunohistochemical analysis with anti Akt antibody to detect the activated form of Akt. A database of patient demographics, disease, treatment and survival parameters was generated and used to correlate 4, 12, 24 and 36 month disease-free intervals (DFI). Results: 53 of the 67 patients had sufficient follow-up to allow for DFI analysis. Of these 53 patients, 48 stained positively for pAkt, while 5 stained negatively. None of the pAkt negative patients had recurrent disease, while the pAkt negative patients suffered cumulative recurrence in 10, 19, 24, and 25 of the 48 patients at 4, 12, 24 and 36 months respectively. Chi square analysis reveals statistically significant differences in recurrence rates between pAkt negative and negative patients at 24 (p=0.0235) and 36 months (p=0.016). Tumor stage and nodal status were also strong predictors of recurrence. Conclusions: pAkt negative patients were found to have a significantly better prognosis for TCC recurrence, which indicates that pAkt status could be useful in helping to determine the prognosis for patients with muscle invasive TCC. These results lead us to speculate that the use of a serine threonine kinase inhibitor may prove to be therapeutically beneficial for TCC patients undergoing concurrent chemotherapy for their disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4187. doi:10.1158/1538-7445.AM2011-4187
A method for evaluating the effects of allograft sterilization procedures on the viability of human fibroblasts
Authors: S. C. W. Chalcroft, J. B. Gavin, R. N. Seelye
Journal: Thorax (1974)

<b>Chalcroft, S. C. W., Gavin, J. B., and Seelye, R. N. (1974).</b><i>Thorax</i>, <b>29</b>, 539-544. <b>A method for evaluating the effects of allograft sterilization procedures on the viability of human fibroblasts.</b> A semiquantitative method for assessing the effects of allograft sterilization procedures on the viability of cultured human fibroblasts is described. The proportions of `viable9, `altered9, and `non-viable9 cells in four groups of fibroblasts on coverslips were estimated using light microscopy and their staining reactions with neutral red and nigrosin. While a control group of fibroblasts remained viable, exposure for one to three weeks to each of three solutions used in allograft preparation produced a progressive transition first to the altered and then to the non-viable category. These findings were confirmed by electron microscopic examination of similarly treated cells grown on millipore filters. Applications of the method are discussed.
Our Parents, Ourselves: How American Health Care Imperils Middle Age and Beyond
Authors: Julie H. Silverstein
Journal: Annals of Internal Medicine (2006)

Medical Writings: Book Notes4 July 2006Our Parents, Ourselves: How American Health Care Imperils Middle Age and BeyondJulie H. Silverstein, MDJulie H. Silverstein, MDFrom Christiana Care Health System, Wilmington, Delaware.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-145-1-200607040-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Steinberg Turiel J. 317 pages. Berkeley, CA: Univ of California Pr; 2005. $21.95. ISBN 0520245245. Order at www.ucpress.edu.Fields of medicine: Primary care, geriatrics, and public health.Format: Softcover book.Audience: Consumers or providers of U.S. health care, specifically "baby boomers" and their parents.Purpose: "To address the personal experience of aging and health care issues and policies that surround individuals" as seen from the vantage point of the elderly, as well as those in midlife who are witnessing and caring for aging family members or friends.Content: The book addresses basic concerns about the care of aging family members. ... Author, Article, and Disclosure InformationAuthors: Julie H. Silverstein, MDAffiliations: From Christiana Care Health System, Wilmington, Delaware. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 July 2006Volume 145, Issue 1Page: 80KeywordsAgingGeriatricsHealth careHealth care policyHealth care providersLong-term careMedicarePrevention, policy, and public healthSoftware toolsSuicide ePublished: 4 July 2006 Issue Published: 4 July 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effect of ethanol and fructose on plasma uridine and purine bases
Authors: Tetsuya Yamamoto, Yuji Moriwaki, Sumio Takahashi, Jun-ichi Yamakita, Zenta Tsutsumi, Hiroyuki Ohata, Keisai Hiroishi, Takashi Nakano, Kazuya Higashino
Journal: Metabolism (1997)
Whipple's Disease — Past, Present, and Future
Authors: Morton N. Swartz
Journal: New England Journal of Medicine (2000)

Knowledge of Whipple's disease started with Whipple's report in 1907 of a medical missionary with an illness that had begun five years earlier with episodes of arthritis but that subsequently included weight loss, cough, fever, diarrhea, hypotension, abdominal swelling, increased skin pigmentation, and severe anemia.1 Findings at autopsy consisted of polyserositis, aortic-valve lesions, and prominent deposition of fat within intestinal mucosa and mesenteric lymph nodes, with marked infiltration by foamy macrophages. The pattern of fat deposition suggested that this disorder was an obscure disease of fat metabolism, and Whipple proposed the name “intestinal lipodystrophy.”Whipple's description represents the ideal single . . .
Alpha Methyldopa and Fortgetfulness
Authors: PETER G. FERNANDEZ
Journal: Annals of Internal Medicine (1976)

Comments and Corrections1 July 1976Alpha Methyldopa and FortgetfulnessPETER G. FERNANDEZ, M.D., M.R.C.P.(GLASG.), M.R.C.P.(U.K.), F.R.C.P.(C)PETER G. FERNANDEZ, M.D., M.R.C.P.(GLASG.), M.R.C.P.(U.K.), F.R.C.P.(C)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-85-1-128_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In view of alpha methyldopa being possibly the most widely used antihypertensive agent after the diuretics, I wish to publicise further forgetfulness as an apparent adverse effect of the drug. This has been documented in five professional people (3 physicians, an engineer, and an accountant) by Adler (1). Recently, an additional case report has been cited by Ghosh (2). In my hypertensive clinic in which alpha methyldopa is extensively used, I have documented three similar cases (unpublished). The true incidence of this adverse effect is not known, and I regret to say that it is not documented...References1. ADLER S: Methyldopa. Induced decrease in mental acuity. JAMA 230:1428-1429, 1974 CrossrefMedlineGoogle Scholar2. GHOSH S: Methyldopa and forgetfulness (letter). Lancet 1: 202-203, 1976 CrossrefMedlineGoogle Scholar3. GOODMANGILMAN LA: The Pharmacological Basis of Therapeutics. 5th ed. New York, Macmillan, 1975 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine Faculty of Medicine Memorial University of Newfoundland St. John's NF, Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAntihypertensive Efficacy of Guanfacine and Methyldopa in Patients with Mild to Moderate Essential HypertensionDrug-Related Cognitive Impairment: Current Progress and Recurrent ProblemsNeuropsychological Effects of Antihypertensive DrugsSelective impairment of paired associate learning after administration of a centrally-acting adrenergic agonist (clonidine)Neurotransmitter Deficits in Alzheimer's Disease: Criteria for SignificanceToxic Effects of Adrenergic Nerve-End Inhibitors, Neural-Transmitter Depleting Agents and False Transmitters 1 July 1976Volume 85, Issue 1Page: 128-128KeywordsDiureticsDrugsEmotionsEngineers Issue Published: 1 July 1976 PDF downloadLoading ...
MULTIMODALITY IMAGING IN TRANSCATHETER AORTIC VALVE IMPLANTATION (TAVI): COMPARISON BETWEEN CARDIOVASCULAR MAGNETIC RESONANCE, CARDIAC COMPUTED TOMOGRAPHY AND ECHOCARDIOGRAPHY
Authors: Andrew Jabbour, Francois Okoroafor, Isabelle Roussin, Bradley Park, Francisco Alpendurada, Tevfik Ismail, Maria N. Paes, Simon Davies, Michael Mullen, Nicola Delahunty, Sanjay Prasad, Michael Rubens, Neil Moat, Raad Mohiaddin
Journal: Journal of the American College of Cardiology (2011)
CONTOUR OF NORMAL AND TUBERCULOUS CHESTS
Authors: S. A. WEISMAN
Journal: JAMA (1927)

The shape of the chest of the tuberculous patient and that of the normal is so strikingly different that a study of the various diameters proves very interesting. It is still a common belief that the flat chest or, rather, the one with a low thoracic index is apparently more prone to tuberculosis than the deep chest with a greater thoracic index. By the thoracic index is meant the ratio of the anteroposterior measurement to the transverse. In 1828, Chomel<sup>1</sup>stated that the normal chest was flatter than the tuberculous. Hutchinson<sup>2</sup>in 1897 and again in 1903<sup>3</sup>showed that the tuberculous chest was absolutely narrower, deeper and more round than the normal; that it was a primitive, undeveloped thorax, one approximating that of the quadruped type. In his study of comparative anatomy he showed that the higher the form of mammal the greater was the transverse diameter
COST EFFECTIVENESS OF TRANSCATHETER VERSUS SURGICAL CLOSURE OF SECUNDUM ATRIAL SEPTAL DEFECT IN ADULTS: A POPULATION-BASED ANALYSIS
Authors: Stéphane P. Quenneville, Xuanqian Xie, James M. Brophy, Mark A. Kotowycz, Louise Pilote, Judith Therrien, Raluca Ionescu-Ittu, Giusseppe Martucci, Ariane J. Marelli
Journal: Journal of the American College of Cardiology (2011)
Comparative efficacy of azelastine nasal spray and terfenadine in seasonal and perennial rhinitis
Authors: H. Gastpar, D. Nolte, R. Aurich, P. Brendt, H. Enzmann, G. Giesemann, G. Kunkel, U. Petzold, W. Renz, M. Schata, M. I. Schiffmann
Journal: Allergy (1994)

The efficacy and tolerability of intranasal azelastine (0.14 mg/nostril twice daily) and oral terfenadine (60 mg twice daily) were compared under double-blind conditions in two 6-week, multicenter, parallel-group studies, including 167 patients suffering from seasonal and 52 patients suffering from perennial allergic rhinitis. In both studies, patients were symptomatic on entry and showed significant improvement on both treatments within the first 8 d of therapy, showing little further improvement with continued treatment. Symptoms most pronounced on entry--nasal itching, rhinorrhea, sneezing, and nasal obstruction--responded best to treatment (response rates 80-90%). Objective signs such as mucosal swelling and conjunctivitis improved in a manner parallel to symptoms. In perennial rhinitis, azelastine showed a trend to a superior relief of rhinorrhea and nasal obstruction, whereas terfenadine showed a trend toward better control of sneezing and nasal itchiness. No clinically relevant or statistically significant differences between treatments could be identified. The incidence of adverse effects of possible causal relationship to therapy was low. The most frequent effects in azelastine-treated patients were related to application site disorders, e.g., nasal irritation. Results indicate that with the dose used azelastine nasal spray is an effective treatment for both seasonal and perennial allergic rhinitis.
Cancer Gene Patent Dispute Settled
Authors: Andrew A. Skolnick
Journal: JAMA (1995)

THREE CONTENDERS for the patent involving a recently identified breast and ovarian cancer susceptibility gene have settled a potentially ugly dispute by agreeing to share credit for the discovery. On February 10, the National Institutes of Health (NIH), Bethesda, Md, and the University of Utah and Myriad Genetics Inc, both in Salt Lake City, signed an agreement naming researchers from all three organizations as joint inventors in patent applications relating to the discovery of the<i>BRCA1</i>gene (<i>Science</i>. 1994;266:66-71 and 120-122). Deleterious mutations in the gene located on chromosome 17 have been shown to greatly increase susceptibility to breast and ovarian cancers. Recent studies suggest that women who inherit certain<i>BRCAl</i>mutations may have nearly a 90% cumulative lifetime (to 80 years of age) risk of developing breast cancer (<i>JAMA</i>. 1995;273:535-541 and 577-585). The identification of this gene was announced in October 1994 by a team of scientists at Myriad