tbuckley/cabot-search huggingface dataset:
The economy of science
Authors: Andrew R. Marks
Journal: Journal of Clinical Investigation (2004)

We are in the midst of an era of plummeting pay lines at the NIH. History shows that when the federal deficit is high, NIH pay lines tend to fall, and the impact on biomedical research can be disastrous. Equally bad is the disincentive for the future generations of biomedical researchers who observe their mentors struggling to get adequate funding. How many bright young people will be turned away from careers in biomedical research? How much innovative science will be delayed or never initiated, how many new cures never realized? At a time of unprecedented challenges and remarkable technological advances that enable us to address those challenges, lack of funding is a threat to our society.
Training and the latest reorganisation of the NHS
Authors: J A G Bremner, K Edelman
Journal: BMJ (1994)

EDITOR, - Both Chris Ham1 and John Warden2 discuss the impending abolition of regional health authorities without referring to the implications for clinical training. At present the allocation of training posts is assessed in the regional health authority's strategic plan for medical and dental staffing,3 and the provision of training is safeguarded …
Clinically and Statistically Significant Differences
Authors: Paul D. Fuchs
Journal: JAMA (1986)

To the Editor.—  Keeler et al 1 in their article state that  of 1.9 mm Hg in diastolic blood pressure... are important—they translate into differences of 5% to 8% in the probability of dying in the next year. As a clinician, I am very skeptical that a reduction in diastolic blood pressure of approximately 0.5 mm Hg per year (1.9 mm Hg achieved over a three- to five-year period) in the free group is clinically significant. Could this be another case of confusing statistical significance with clinical significance?  If indeed the reduction in diastolic blood pressure was clinically significant, it seems that a difference in the number of deaths in the hypertensive subgroup of 856 patients should have been noted over the three- to five-year period of follow-up. Was such a difference noted? (It has already been reported that the total numbers of deaths in the free vs cost-sharing
Psoriasis: the future
Authors: B. Kirby, C.E.M. Griffiths
Journal: British Journal of Dermatology (2001)

The aetiology of psoriasis is still unclear but our knowledge of the psoriatic process has grown substantially over the last two decades. The future will undoubtedly bring advances in our understanding of the pathogenesis of psoriasis and, as a consequence, new therapies. Defining the molecular genetics of psoriasis will enhance our understanding of the disease process and hopefully facilitate the development of a representative animal model. This in itself will be a key step in the development and testing of new therapies. Precise identification of the immunological events involved in psoriasis will allow specific T-cell- and cytokine-targeted, and perhaps less toxic, immunotherapies. Anti-angiogenic agents that are in development for use in oncology may also be effective in psoriasis. The adaptation of current topical therapies such as retinoids and vitamin D analogues to produce more effective and better-tolerated formulations will also play a significant role in our future first-line management of patients. The increased recognition and better management of environmental trigger factors such as psychological distress will become an important factor in future psoriasis care. The development of physical therapies including photodynamic therapy and excimer lasers has the potential to expand the remit of psoriasis therapy. There is little doubt that the future for our patients with psoriasis is bright. However, this will only be achievable by a concerted research effort to understand all facets of this enigmatic disease ranging from the molecular to the environmental.
Serum fructosamine concentration as measure of blood glucose control in type I (insulin dependent) diabetes mellitus.
Authors: J R Baker, P A Metcalf, I M Holdaway, R N Johnson
Journal: BMJ (1985)

Serum fructosamine activity was studied in 42 patients with type I (insulin dependent) diabetes mellitus and 30 non-diabetic volunteers as an index of blood glucose control. There was a significant correlation both between fructosamine and glycosylated haemoglobin values (r = 0.82) and between fructosamine and the fasting C peptide concentration (r = -0.81). Test results in 14 of the diabetics reflected the mean plasma glucose concentration calculated from 25 serial estimations in a single 24 hour period (r = 0.75; p less than 0.01) but not the mean amplitude of glycaemic excursion (r = 0.23; p greater than 0.05). Fructosamine concentrations measured in these multiple blood specimens did not change significantly throughout the day (mean coefficient of variation 4.1%) despite wide variability of the respective plasma glucose concentrations (mean coefficient of variation 36.2%). It is concluded that a single random serum sample analysed for fructosamine concentration provides a simple and reliable assessment of glucose homoeostasis in patients with type I diabetes mellitus.
Care for Chronic Pain
Authors: TIMOTHY E. QUILL
Journal: Annals of Internal Medicine (1981)

Letters1 January 1981Care for Chronic PainTIMOTHY E. QUILL, M.D.TIMOTHY E. QUILL, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-94-1-134 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I was glad to see Reuler and his associates (1) address the thorny issue of chronic pain; they have clarified the false distinction between organic and psychogenic pain, the use and abuse of placebos, and the need for a regular schedule of analgesic medication rather than "prn pain" in the treatment of patients with chronic pain. The remainder of their article considers medications, procedures, and behavioral techniques that have been useful in some patients with chronic pain. Many pain patients, however, have "tried it all" and are unwilling to submit themselves to the complex controls needed for...References1. REULERGIRARDNARDONE JDD. The chronic pain syndrome: misconceptions and management. Ann Intern Med. 1980;93:588-96. LinkGoogle Scholar2. STERNBACK R. Varities of pain games. Adv Neurol. 1974;4:423-30. Google Scholar3. LESHAN L. The world of the patient in severe pain of long duration. J Chronic Dis. 1964;17:119-26. CrossrefMedlineGoogle Scholar1. REULERGIRARDNARDONE JDD. The chronic pain syndrome: misconceptions and management. Ann Intern Med. 1980;93:588-96. LinkGoogle Scholar2. VON RECHENBERGZEERLEDER HR. Klinische Enfahrungen mit Dromoran [(-)-2-oxy-n-methyl-morphinen tartrat], einen neuen synthetischen Analgeticum. Schweiz Med Wochenschr. 1951;81:44-7. Google Scholar3. BROWN A. Levorphanol in anesthesia. Br Med J. 1954;2:967-70. CrossrefMedlineGoogle Scholar4. LIPMANBROOKS AK. Clinical considerations in analgesic surgery. PA. 1976;6:68-71. MedlineGoogle Scholar5. BONICAPROCACCIPAGNI JPC eds. Recent Advances on Pain: Pathophysiology and Clinical Aspects. Springfield, Illinois: Charles C Thomas; 1974:168-88. Google Scholar1. REULERGIRARDNARDONE JDD. The chronic pain syndrome: misconceptions and management. Ann Intern Med. 1980;3:588-96. LinkGoogle Scholar2. PIRCIOGYLYSCAVANAGH AJR. The pharmacology of butorphanol, a 3, 14-dihydroxymorphinan narcotic antagonist analgesic. Arch Int Pharmacodyn Ther. 1976;220:231-57. MedlineGoogle Scholar3. JASINSKIGRIFFITHPENVICK DJJ. Progress Report on Studies from the Clinical Pharmacology Section of the Addiction Research Center. National Institute on Drug Abuse; Lexington, Kentucky: 1975:121-61. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Genesee Hospital Medical/Psychiatric Liaison Division Rochester, NY 14607 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1981Volume 94, Issue 1Page: 134-135KeywordsAnalgesicsPatients Issue Published: 1 January 1981 PDF downloadLoading ...
Medical Student-Faculty Ratios
Authors: J. R. Harnes
Journal: JAMA (1979)

<h3>To the Editor.—</h3> In commenting on the drop in the medical student-faculty ratio (240:2819, 1978) from 1.5 in 1970 to 1971 (40,487/26,504) to 1.3 in 1977 to 1978 (59,950/44,762), the article states the change suggests "that the impact of economic restrictions on faculty hiring and increases in enrollment is becoming evident." The authors have drawn a totally incorrect conclusion from these figures, which indicate a proportionate increase in the faculty rather than a decrease. If a student-faculty ratio of 1.5 is calculated for 1977 to 1978 enrolled students, the faculty would consist of 39,967 members. Thus, there has been an increase of 4,795 faculty members in proportion to the student body since 1970 to 1971. Assuming a conservative cost of $30,000 per year for salary, fringe benefits, and office expenses for each faculty member, the cost of medical education has risen $143,850,000 or $2,400 per student per year. At a
Remission of arthritis and radiological improvement after combination therapy for non-Hodgkin's lymphoma in a patient with rheumatoid arthritis undergoing treatment with D-penicillamine
Authors: P Sheldon, J K Wood
Journal: Annals of the Rheumatic Diseases (1985)

A patient receiving d-penicillamine for rheumatoid arthritis developed a lymphoma, therapy for which resulted not only in haematological resolution but marked remission of rheumatoid disease activity, including radiological improvement.
Identification of monoclonal B-cell lymphocytosis among sibling transplant donors for chronic lymphocytic leukemia patients
Authors: Ilaria Del Giudice, Francesca Romana Mauro, Maria Stefania De Propris, Irene Della Starza, Daniele Armiento, Anna Paola Iori, Giovanni Fernando Torelli, Anna Guarini, Robin Foà
Journal: Blood (2009)
Fluorouracil as an Adjuvant to Colorectal Cancer Surgery; The Breakthrough That Never Was
Authors: Charles G. Moertel
Journal: JAMA (1976)

To the Editor.—  In an article published inThe Journal(235:2825, 1976) that was endorsed by an editorial,  and Ross claimed  significant improvement of five-year cure rate for patients with type B and C Dukes colorectal cancer through the use of fluorouracil as a surgical adjuvant.The Journaleditorial would appear to offer enthusiastic concurrence: Li and Ross show clearly the benefit from two postoperative courses of fluorouracil in patients with colorectal carcinoma, and One of the striking features... is the exceptionally short duration of treatment with fluorouracil necessary to achieve the impressive results. It is scarcely surprising that such outspoken claims made breakthrough headlines in the news media. These claims have no foundation in fact.   and Ross have attempted to demonstrate the effectiveness of fluorouracil as a surgical adjuvant by comparing survivorship in patients so treated from 1965 to 1970 with survivorship in patients treated with
On the Affections of the Joints, Which Complicate or follow Scarlet Fever
Authors: H. Ashby
Journal: BMJ (1886)

<h3>Objective:</h3> Analyse the efficiency of Visual Restoration therapy as a tool in the management of visual field defects. <h3>Background:</h3> Visual field deficits have a poor response to medications and complete spontaneous recovery of vision is rare. In spite of recent advances in biotechnology, there currently exists no consensus on rehabilitative therapy. <h3>Design/Methods:</h3> A prospective follow up study. Inclusion criteria:Participants above 18 years of age and willing to participate.Visual field defects resulting from lesion of visual pathway beginning at retina to the occipital cortex.Exclusion criteria:Ocular pathology – either a primary ocular disease or secondary to any systemic disease like Diabetes/Hypertension, etc. Method: Patients presenting with visual field defects are assessed with automated perimetry and optical Coherence Tomography, prior and post 3 months of therapy. An image (face) unveils itself in a sectoral fashion by both clockwise and anticlockwise direction corresponding to the visual field defect in patient. The video is calibrated to 3 different speeds of 30, 60 and 120 seconds with an enhancing colour contrast background of either Red, Green or Blue as the video progresses. Patient is instructed to focus at the centre of the video as the image unveils. The visual task is to be performed 1 hour a day for 3 months. Assessment of Visual field Index was used to measure the outcome of therapy. <h3>Results:</h3> A total of 25 patients with visual field defect were enrolled to the study. Totally 14 male and 11 female participants, median age being 43 years. On an average, the visual field index improved by an 8%. <h3>Conclusions:</h3> Our study was found to be beneficial in the management of visual field defects. Marginal improvement demonstrated in the visual field is tantamount to a huge clinical translation, aiding in daily activity and opens up a new avenue in Visual Field rehabilitation. <b>Disclosure:</b> Mr. Sankaranarayanan has nothing to disclose. Dr. Ramamurthy has nothing to disclose. Dr. Ranganathan has nothing to disclose.
Human Immunoglobulin A
Authors: Thomas B. Tomasi
Journal: New England Journal of Medicine (1968)

ONE of the important recent advances in modern immunology is the recognition that antibody activity is associated with a group of multichain proteins of varying mobility and molecular size. Normal serum probably contains hundreds of different antibodies, each being individually specific in its sequence of amino acids. This extensive heterogeneity of antibodies has been simplified somewhat since antibodies can be grouped into five major immunoglobulin classes as outlined in Table 1. This classification is based on chemical and physical, as well as immunologic, differences in these groups of proteins. Each of the major classes can be further subdivided into various subclasses . . .
A2.24 IL23/TH17-mediated Regulation of Antibody Glycosylation Controls Autoimmune-Induced Arthritis
Authors: René Pfeifle, Iryna Magorivska, Ulrich Scherer, Ulrike Harre, Tobias Rothe, Sybille Böhm, Martin Herrmann, Stephan Blüml, Falk Nimmerjahn, Georg Schett, Gerhard Krönke
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Both rheumatoid arthritis (RA) and the murine models of collagen-induced arthritis (CIA) and of K/BxN arthritis are characterised by an initial break in self-tolerance, the appearance of specific autoantibodies and an autoantibody-mediated effector phase resulting in chronic inflammation and joint destruction. The IL23-dependent Th17 T-cell response has been identified as a major driving force during the pathogenesis of these disorders. The exact contribution of the IL23/Th17 axis to autoimmune-triggered inflammation, however, has remained incompletely understood. In this study, we aimed to further elucidate the role of IL23 and Th17 T-cells during murine autoimmune arthritis. <h3>Materials and Methods</h3> To study and dissect the contribution of Th17 T cells to the initiation and effector phase of autoimmune arthritis, we performed the CIA as well as the K/BxN serum transfer model of arthritis in both wild-type (WT) mice and in mice lacking the IL23-specific subunit p19. Subsequently we determined the clinical course of disease as well as the serum levels, the avidity and the glycosylation pattern of antibodies in the sera of the respective mice. <h3>Results</h3> While IL23<sup>-/-</sup> mice, which lack functional Th17 T-cells, developed a full-blown arthritis after passive transfer of autoantibodies in the K/BxN model, these mice were resistant to collagen-induced arthritis. These data indicated that the IL-23/Th17 axis is dispensable during the autoantibody-mediated effector phase of arthritis, whereas it is crucially involved in mounting an autoimmune response during CIA. Despite being protected from CIA, IL23<sup>-/-</sup> mice displayed regular levels of anti-collagen antibodies, which also showed a regular avidity. Likewise, we observed no difference in the IgG subclasses between the two genotypes. Analysis of the glycosylation pattern of antibodies in the sera of WT and IL23<sup>-/-</sup> mice, however, revealed major differences in the content of sialic-acid and fucose residues at the Fc part of the IgGs resulting in an anti-inflammatory IgG profile in the sera of IL23<sup>-/-</sup> mice. The changes in the IgG glycosylation, in turn, correlated with changes in the expression pattern of glycosyltransferases in plasmablasts and plasmacells of WT and IL23-deficient mice. <h3>Conclusions</h3> Together, these data show that the IL23/Th17 axis controls the degree of antibody glycosylation and, in turn, indicate that this regulation of the glycosylation of autoantibodies is a critical step in the pathogenesis of Th17-mediated autoimmune diseases such as RA.
Textbook of the Rheumatic Diseases
Authors: John H. Talbott
Journal: JAMA (1965)

It is not customary to comment at length on each new edition of a standard text or monograph. Copeman's treatise, however, is one of the exceptions because of the subject matter and the incidence of the diseases discussed. A complete rewriting every seven years is frequent enough to incorporate new items of significance and, at the same time, is less of a chore to the senior author than would be a more frequent revision. In this current edition Copeman was assisted by 24 of the best-informed and clinically wise physicians in the United Kingdom who concern themselves with bones and joints. We may mention a few, even at the expense of apparent favoritism: Lord Cohen of Liverpool, Bywaters of Taplow, Kellgren of Manchester, Kersley of Bath, and Sir Reginald Watson-Jones of London, all of them teachers, investigators, and clinicians who insure quality without compromise. The discussions will interest American physicians,
Alternatives to Toxicity Testing in Animals: Challenges and Opportunities
Authors: George P. Daston, Pauline McNamee
Journal: Environmental Health Perspectives (2005)

We have learned over time that the development of successful alternative methods in toxicology testing requires the successful integration of three elements: First, there must be a solid foundation of understanding the basic biology and toxicology of the tissues and organs being studied. Second, in vitro platforms must be available that can be modified to make them amenable for toxicity testing. Third, one needs to convince the scientific community, which is skeptical by nature and training (and rightfully so), that the alternative methods fulfill their intended purpose and have been rigorously validated. In vitro mutagenicity screening methods have been used for many years and are a good illustration of these three points. Initially, the basic biology that needed to be understood was that DNA is the molecular basis for heredity and that mutations are, in fact, manifestations of damage to the DNA. Furthermore, several types of mutations (e.g., point mutations, insertions, deletions) require the development of different in vitro models. In vitro platforms, the second element, were adapted from extensive research into the molecular biology of prokaryotes, and later, eukaryotic cells. The third element involved years of assay standardization, replication of results in multiple laboratories, and comparisons with in vivo results. For more complex end points, the development of alternatives has been a daunting task. Even supposedly simple targets for replacement, such as the Draize test for eye irritation, have proved difficult to model in vitro and progress through successful external validation despite major efforts by the European Centre for the Validation of Alternatives (ECVAM), industry trade associations, individual companies, and academia. An extensive list of in vitro models that have been proposed as alternatives to the Draize test has been published E s s a y o n Toxicity Testing in Animals
Abstract 1987: The role of lipolysis-stimulated lipoprotein receptor in directing breast cancer cell behavior and subtype
Authors: Jodie M. Fleming, Denise K. Reaves, Katerina D. Fagan-Solis, Karen Dunphy, Shannon D. Oliver
Journal: Cancer Research (2014)

Abstract The claudin-low molecular subtype of breast cancer is of particular interest for clinically the majority of these tumors are poor prognosis, triple negative, invasive ductal carcinomas. Claudin-low tumors are characterized by low gene expression of cell junction and adhesion proteins, and de-regulation of tight junction proteins is often been implicated in tumorigenesis. Herein, we sought to define the role of tricellular tight junction (tTJ) proteins in breast cancer and cancer cell behavior with a focus on lipolysis-stimulated lipoprotein receptor (LSR). LSR was expressed in epithelium, endothelium, adipose and stromal cells within the healthy breast tissue, as well as in tumor epithelium. LSR expression was significantly correlated with invasive ductal carcinomas compared to invasive lobular carcinomas, and ERα positive tumors and breast cancer cell lines. Consistent with the role of LSR in tTJs, LSR levels were significantly reduced in claudin-low breast cancer cell lines. Functional studies illustrated that that re-introduction of LSR into a claudin-low cell line suppressed the EMT phenotype and reduced individual cell migration. However, our data suggest that LSR may direct collective cell migration. Moreover, re-introduction of LSR in claudin-low breast cancer cell lines reestablished a family of TJ expression, thereby reverting claudin-low lines to other molecular subtypes. Overexpression of LSR enhanced proliferation and survival in anchorage independent conditions, suggesting that reestablishment of tight junctions is not sufficient to inhibit aggressive cell behaviors in vitro. Collectively, these data highlight an unanticipated role for the tTJ protein, LSR in directing aggressive breast cancer behavior. Citation Format: Jodie M. Fleming, Denise K. Reaves, Katerina D. Fagan-Solis, Karen Dunphy, Shannon D. Oliver. The role of lipolysis-stimulated lipoprotein receptor in directing breast cancer cell behavior and subtype. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1987. doi:10.1158/1538-7445.AM2014-1987
A New Ventilator Utilizing Fluid Logic
Authors: Stanley W. Weitzner
Journal: JAMA (1969)

The coming of age of "fluidics" (fluid amplifiers, fluid logic) has resulted in the application of this new technology to the construction of mechanical ventilators. The most sophisticated fluidic apparatus presently available weighs less than 5 kg and is 6 × 14 × 24 cm in size. Basically, it consists of six fluid-logic cells which permit tidal volume and respiratory frequency to be adjusted independently. The unit is driven by compressed gas, and only 500 ml/min in excess of the desired minute volume are consumed during operation. This unit has been readily adapted to the clinical requirements of humidification, adjustment of inspired oxygen concentration, and monitoring of expired volume and airway pressure. Tested under rigorous laboratory control, during normal use and under stress conditions, this ventilator performed as well as other conventional, well-accepted machines.
Cost of anaesthetic agents.
Authors: J A Thornton, C J Levy
Journal: BMJ (1970)

matter, and perfume.'It has been found that both the quaternary ammonium compounds and the amido-amines give positive results with tests for proteinuria using tetrabromo- phenolphthalein and tetrabromophenol blue (Albustix).Since our health visitors have advised the mothers to place the filter- paper in nappies not treated with fabric softeners the incidence of false positive tests has markedly fallen.