tbuckley/cabot-search huggingface dataset:
Saturnine Gout among Roman Aristocrats
Authors: Jerome O. Nriagu
Journal: New England Journal of Medicine (1983)

Although Musgrave is generally credited with the first report of coexistent gout and plumbism,1 it was Sir Alfred Garrod who clearly demonstrated the high incidence of plumbism in subjects with gout and adduced a causal relation between the two disorders.2 The effect of lead on renal tubular function is well known; damaged tubules apparently cause retention of uric acid, which many clinicians believe is responsible for gout.3 Saturnine gout can also be attributed to the accretions of guanine (a highly insoluble purine) resulting from the inhibition by lead of guanase (guanine aminohydrolase) activity.4 Indeed, gout is now widely regarded as . . .
Aging and the alimentary tract
Authors: MICHAEL FARTHING, OLIVER JAMES
Journal: Gut (1997)

Although at some point in our lives most of us finally accept that we are not going to live forever, few enjoy the process of getting old, particularly when it involves loss of function. However, improved living standards and the continuing progress in the quality and availability of healthcare, particularly in westernised countries, is resulting in populations being skewed towards the elderly. In these communities, provision for the aged will become one of the major challenges for the next century.

The editors of more than 100 international medical journals decided last year to sponsor a world wide movement to bring healthcare problems of the elderly to the fore in October 1997. Gut decided to join the initiative by dedicating part of this issue to aging with focused leading articles and original papers on gastrointestinal and liver topics as they relate to the elderly. We took …
Chemical interaction: enhancement and inhibition of clastogenicity.
Authors: W A Anwar
Journal: Environmental Health Perspectives (1993)

Most environmental exposures involve concurrent or sequential exposure to multiple chemicals in air, water, and food. Interactive effects in carcinogenesis have been described for certain combinations of agents. They are described in terms of enhancement or inhibition of carcinogenesis. Enhancement effects have been documented for cigarette smoking in combination with exposure to asbestos, radon, alcohol, or other exposures. A variety of inhibitors of carcinogenesis have also been described. They are classified into agents preventing formation of carcinogens; blocking agents; and suppressing agents. Assessment of risk from exposure to multiple agents can be derived either from epidemiological studies in relation to actual exposure or from laboratory studies after controlled exposure to different agents. Prediction of how toxic components of mixtures will interact should be based on an understanding of the mechanisms of such interactions. Compounds may interact chemically, yielding new toxic components or causing a change in the biological availability of the existing components or metabolites. In humans, great individual variability in response is to be expected because of genetic heterogeneity or acquired host susceptibility factors. Interaction is thus a key component in the risk assessment process. In this paper, the definition of interaction and the theoretical basis for different types of interaction in cancer causation are reviewed. Epidemiological and experimental studies showing interactive effects of two chemical carcinogens are also presented.
Small joint ankylosis in rheumatoid arthritis: a vanishing phenomenon or a pathogenetic clue, or both?
Authors: I Leden, J Theander, B Svensson
Journal: Annals of the Rheumatic Diseases (2008)

The main pathological feature of rheumatoid arthritis (RA) is synovitis, which may become erosive and extend to cartilage and bone and cause bone resorption with subsequent joint instability. In contrast, the spondyloarthropathies are characterised by enthesitis, which may bring about new bone formation with osteophytes and ankylosis.

Only recently these important differences in pathogenesis have become elucidated.1 Earlier, ankylosis had been accepted as a part of RA.2 Interestingly, in palaeopathological publications the existence of ankylosis in RA has for a long time been a matter of dispute and even denied.3–5

To examine this subject further, the occurrence of spontaneous ankylosis was studied in patients attending the rheumatology unit at Kristianstad County Hospital in southern Sweden …
UNIFORMITY IN DEFINITION AND APPLICATION OF THE TERMS POSITION AND PRESENTATION.
Authors: FRANK A. STAHL
Journal: JAMA (1900)

Ambiguity in definition and application of terms, more especially of terms of importance, is still a method of expression unfortunately of too frequent recurrence in descriptive obstetrics. Nor are these infelicities of expression of recent date, for, the need of uniformity in definition and nomenclature has long been recognized. Repeatedly, in monograph, in discussion, and in medical congresses, efforts have been made to overcome these and to establish greater clearness in definition and application of term and a more simple, yet accurate nomenclature.  Among the last to treat of this subject was Prof. A. R. Simpson of Edinburgh, with a committee of American obstetric teachers. Preparatory to its consideration, he had sent out the following question to various teachers of obstetrics throughout the world: Do you consider it desirable to try to attain uniformity in obstetrical nomenclature? The replies varied from eminently so to certainly, but very difficult. At the
More evidence that folic acid reduces risk of ischaemic stroke
Authors: S. Gottlieb
Journal: BMJ (2004)

Men who consume relatively large amounts of folic acid have a significantly reduced risk of developing ischaemic stroke, concludes a newly reported study.

The study's lead author, Dr Ka He of Northwestern University in Illinois, and colleagues investigated a total of 725 incident strokes—455 ischaemic, 125 haemorrhagic, and 145 unknown types of stroke—that were documented during 14 years of follow up between 1986 and 2000.

The participants were part of the health professional follow up study, which was established in 1986 when 51 529 male US health professionals aged 40-75 answered …
The first wave of NHS foundation trusts
Authors: Rudolf Klein
Journal: BMJ (2004)

Low turnout in elections sends a warning signal 

On 1 April 2004 the first 10 NHS foundation trusts came into being while another 14 remain on the starting line, awaiting the approval of the independent regulator.1 So begins an experiment that has the potential to transform the NHS, but in which formidable obstacles remain in the way of translating ambitions into reality. In launching the experiment the government set out two linked aims—decentralisation and democratisation.2 Firstly, foundation trust status would give providers “freedom from Whitehall control.” Secondly, it would introduce “a new form of social ownership where health services are owned by and accountable to local people rather than to central government.”2 We do not know how much freedom from Whitehall control will exist in practice and how much scope foundation trusts will have to develop new ways of working. During the passage of the legislation through parliament, the government was forced to appease backbench opposition by introducing a series of restrictions on the way in which foundation trusts can run their affairs. …
Models of the Physician-Patient Relationship
Authors: Larry Tibbles
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Although the labels are different, Emanuel and Emanuel's models of the physician-patient relationship<sup>1</sup>are almost identical to Hersey and Blanchard's situational leadership styles: telling, selling, participating, and delegating.<sup>2</sup>The similarity is not just a coincidence. When analyzing any categorization of human behavior, one finds that each model or style is supported by a school of philosophy.<sup>3</sup>One of the three basic questions of philosophy is, "What is true?" Epistemology is the study of the various answers and the models of human behavior are restatements of those answers. Idealism and the related classical school neo-Thomism (derived from the writings of Saint Thomas Aquinas) both contend that truth or knowledge exists apart from our perceptions. Since one acquires knowledge through memorization, drill, and reasoning, there is little need to seek input from others.<sup>4</sup>Physicians who hold these philosophies are authoritarian, parental, and "paternalistic." They "tell"
Galectin‐9 induced by dietary synbiotics is involved in suppression of allergic symptoms in mice and humans
Authors: S. de Kivit, E. Saeland, A. D. Kraneveld, H. J. G. van de Kant, B. Schouten, B. C. A. M. van Esch, J. Knol, A. B. Sprikkelman, L. B. van der Aa, L. M. J. Knippels, J. Garssen, Y. van Kooyk, L. E. M. Willemsen
Journal: Allergy (2012)

Abstract: Background: Prebiotic galacto‐ and fructo‐oligosaccharides (sc GOS /lc FOS ) resembling non‐digestible oligosaccharides in human milk reduce the development of atopic disorders. However, the underlying mechanisms are still unclear. Galectins are soluble‐type lectins recognizing β‐galactoside containing glycans. Galectin‐9 has been shown to regulate mast cell degranulation and T ‐cell differentiation. In this study, the involvement of galectin‐9 as a mechanism by which sc GOS /lc FOS in combination with Bifidobacterium breve M ‐16 V protects against acute allergic symptoms was investigated. Methods: Mice were sensitized orally to whey, while being fed with a diet containing sc GOS /lc FOS and Bifidobacterium breve M ‐16 V ( GF / Bb ) or a control diet. Galectin‐9 expression was determined by immunohistochemistry in the intestine and measured in the serum by ELISA . T ‐cell differentiation was investigated in the mesenteric lymph nodes ( MLN ) as well as in galectin‐9‐exposed peripheral blood mononuclear cells ( PBMC ) cultures. Sera of the mice were evaluated for the capacity to suppress mast cell degranulation using a RBL ‐2 H 3 degranulation assay. In addition, in a double‐blind, placebo‐controlled multicenter trial, galectin‐9 levels were measured in the sera of 90 infants with atopic dermatitis who received hydrolyzed formulae with or without GF / Bb . Results: Galectin‐9 expression by intestinal epithelial cells and serum galectin‐9 levels were increased in mice and humans following dietary intervention with GF / Bb and correlated with reduced acute allergic skin reaction and mast cell degranulation. In addition, GF / Bb enhanced T h 1‐ and T reg ‐cell differentiation in MLN and in PBMC cultures exposed to galectin‐9. Conclusions: Dietary supplementation with GF / Bb enhances serum galectin‐9 levels, which associates with the prevention of allergic symptoms.
Intralesional 5-fluorouracil in the treatment of keloids: An open clinical and histopathologic study
Authors: George Kontochristopoulos, Christina Stefanaki, Antonios Panagiotopoulos, Kalliopi Stefanaki, Theodoros Argyrakos, Athanasios Petridis, Andreas Katsambas
Journal: Journal of the American Academy of Dermatology (2005)
Comparative Effectiveness and Cost-Effectiveness of Computed Tomography Screening for Coronary Artery Calcium in Asymptomatic Individuals
Authors: Bob J.H. van Kempen, Sandra Spronk, Michael T. Koller, Suzette E. Elias-Smale, Kirsten E. Fleischmann, M. Arfan Ikram, Gabriel P. Krestin, Albert Hofman, Jacqueline C.M. Witteman, M.G. Myriam Hunink
Journal: Journal of the American College of Cardiology (2011)
Impact of Autonomic Neuropathy on Left Ventricular Function in Normotensive Type 1 Diabetic Patients: a Tissue Doppler Echocardiographic Study
Authors: Per M. Humpert, Dimitrios Oikonomou, Michael Morcos, Helmut Kuecherer, Tobias Schilling, Angelika Bierhaus, Peter P. Nawroth, Hugo A. Katus, Grigorios Korosoglou
Journal: Diabetes Care (2008)

Data from a recent study (1) suggest that autonomic cardiovascular function (ANF) influences left ventricular (LV) diastolic function in patients with type 1 diabetes. Utilizing similar methods, including tissue Doppler imaging (TDI) and echocardiographic phase imaging (EPI) as described (2), we studied 49 type 2 diabetic patients (33 men, 16 women) with normal renal function and LV wall thickness. Five patients had a history of coronary artery disease (CAD), and none had previous myocardial infarction. Patients were screened for ANF as described (3) utilizing a standardized protocol and were divided into groups by tertiles of expiration-to-inspiration ratio (E/I) of heart rate variability (4 …
Osteoprotegerin inhibits prostate cancer–induced osteoclastogenesis and prevents prostate tumor growth in the bone
Authors: Jian Zhang, Jinlu Dai, Yinghua Qi, Din-Lii Lin, Peter Smith, Chris Strayhorn, Atsushi Mizokami, Zheng Fu, John Westman, Evan T. Keller
Journal: Journal of Clinical Investigation (2001)

Prostate cancer (CaP) forms osteoblastic skeletal metastases with an underlying osteoclastic component. However, the importance of osteoclastogenesis in the development of CaP skeletal lesions is unknown. In the present study, we demonstrate that CaP cells directly induce osteoclastogenesis from osteoclast precursors in the absence of underlying stroma in vitro. CaP cells produced a soluble form of receptor activator of NF-κB ligand (RANKL), which accounted for the CaP-mediated osteoclastogenesis. To evaluate for the importance of osteoclastogenesis on CaP tumor development in vivo, CaP cells were injected both intratibially and subcutaneously in the same mice, followed by administration of the decoy receptor for RANKL, osteoprotegerin (OPG). OPG completely prevented the establishment of mixed osteolytic/osteoblastic tibial tumors, as were observed in vehicle-treated animals, but it had no effect on subcutaneous tumor growth. Consistent with the role of osteoclasts in tumor development, osteoclast numbers were elevated at the bone/tumor interface in the vehicle-treated mice compared with the normal values in the OPG-treated mice. Furthermore, OPG had no effect on CaP cell viability, proliferation, or basal apoptotic rate in vitro. These results emphasize the important role that osteoclast activity plays in the establishment of CaP skeletal metastases, including those with an osteoblastic component.
Cholecystectomy and Abdominal Hysterectomy
Authors: James M. Murray
Journal: JAMA (1980)

Cholelithiasis is a common disease in women and can lead to serious complications. At Wilford Hall USAF Medical Center, we have performed 21 cholecystectomies at the time of abdominal hysterectomy. All patients had been asymptomatic with regard to gallbladder disease, but showed either preoperative or intraoperative evidence of gallbladder disease. The mean surgical time was 3.3 hours, mean blood loss was 474 mL, and only one patient had febrile morbidity (&gt;38.3<sup>°</sup>C). Because of the low morbidity, we recommend that this combined surgical approach be considered by both the gynecologist and general surgeon. (<i>JAMA</i>244:2305-2306, 1980)
Effect of 20, 25 Diazacholestenol on Serum Cholesterol.
Authors: J. M. Martt
Journal: Annals of Internal Medicine (1964)

s1 October 1964Effect of 20, 25 Diazacholestenol on Serum Cholesterol.J. M. Martt, M.D., F.A.C.P., C. Talbert Jr., M.D., G. E. Lee, M.D.J. M. Martt, M.D., F.A.C.P.Search for more papers by this author, C. Talbert Jr., M.D.Search for more papers by this author, G. E. Lee, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-61-4-810_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe drug 20, 25 diazacholestenol, a potent inhibitor of cholesterol biosynthesis, was administered to 42 subjects with hypercholesterolemia and coronary atherosclerosis in doses of 25 mg/100 ml/day for up to 20 months. Serum cholesterol was determined every 2 to 3 weeks and serum lactescence, liptoproteins, and phospholipids every 6 to 9 weeks. Photographs of the arcus senilis in the cornea and of xanthelasma and xanthomata were made every 3 months. Serum cholesterol fell in 41 of the subjects with a mean reduction of 78mg/100 ml (30%) from pretreatment levels. A less predictable but favorable response was also seen in the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Columbia, Mo. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByWege zur Totalsynthese heterocyclischer SteroidsystemeApproaches to Total Synthesis of Heterocyclic Steroidal Systems 1 October 1964Volume 61, Issue 4Page: 810-810KeywordsBiosynthesisCholesterolCorneaDrugsPhospholipidsStable coronary artery disease Issue Published: 1 October 1964 PDF DownloadLoading ...
Community acquired pneumonia: severity scores as an adjunct to clinical judgement
Authors: P.J. Marcos, M.I. Restrepo, H. Verea
Journal: European Respiratory Journal (2012)

We read with interest the article by CHOUDHURY et al. [1] in a recent issue of the European Respiratory Journal.The authors investigated the reasons for hospital admission in pneumonia patients with a CURB-65 (confusion, urea .7 mmol?L -1 , respiratory frequency o30 breaths?min -1 , systolic blood pressure ,90 mmHg or diastolic blood pressure f60 mmHg and age o65 yrs) score of 0-1, in order to identify the potential for improving outpatient management.However, the conclusion of the study is discordant with the objectives.The authors conclude that their study supports the recommendation from international guidelines that pneumonia severity scores should be used as an adjunct to clinical judgment when determining the need for hospitalisation.However, there are several issues regarding this study that should be mentioned.First, in order to avoid selection bias when recording the causes of admission, a prospective cohort study design should be applied and not a retrospective review by independent reviewers as mentioned by the authors.Secondly, in order to arrive at the authors conclusion that international guidelines should be used as an adjunct to clinical judgment when deciding on hospitalisation, the authors should have a priori strict criteria according to the severity of illness (CURB-65) as to which patients with community-acquired pneumonia need to be admitted and which do not.Therefore, strict admission criteria may facilitate the identification of variables that may be important for clinicians at the time of admission, in order to overrule CURB-65.Thirdly, we believe that clinical judgement is not equivalent, generalisable and infallible for every physician caring for patients with pneumonia.As suggested previously, certain physicians are more likely to appropriately manage patients with community-acquired pneumonia compared with others, and this may influence the results of the authors' observations [2,3].Finally, we agree with the authors that a prospective cohort design is desirable in order to appropriately address these questions.
Ordinary and extraordinary means.
Authors: R Gillon
Journal: BMJ (1986)

The Roman Catholic doctrine of ordinary and extraordinary means in patient care decisions is the subject of this essay in Gillon's series on medical ethics. He briefly traces the Church history of this doctrine, which holds that saving life is not obligatory if doing so would be excessively burdensome or disproportionate in relation to the expected benefits. The burdens and benefits are to be weighed in the context of "circumstances of persons, places, times, and cultures," and factors such as the costs and risks of undergoing a proposed treatment may be considered. Gillon also notes the disagreement among Roman Catholic commentators over whether it is ever permissible to discontinue feeding as a burdensome, extraordinary treatment. He concludes that, despite different weightings of harms and benefits, Roman Catholic and non-Catholic thinkers are in accord over the appropriate moral approach to deciding when treatment is not obligatory.
Treatment of Psoriasis with Azathioprine
Authors: A. du Vivier, D. D. Munro, J. Verbov
Journal: BMJ (1974)

Azathioprine treatment benefited 19 (66%) out of 29 patients suffering from severe psoriasis. Haematological complications were not troublesome and results of biochemical liver function tests remained normal. Minimal cholestasis was seen in two cases and portal fibrosis of a reversible degree in eight. Liver biopsies should be undertaken at regular intervals if azathioprine therapy is continued so that structural liver damage may be detected at an early and reversible stage.
Abstract 3790: Preclinical profile of LGX818: A potent and selective RAF kinase inhibitor
Authors: Darrin D. Stuart, Nanxin Li, Daniel J. Poon, Kimberly Aardalen, Susan Kaufman, Hanne Merritt, Fernando Salangsang, Edward Lorenzana, Allen Li, Majid Ghoddusi, Giordano Caponigro, Frank Sun, Swarupa Kulkarni, Shefali Kakar, Nancy Turner, Richard Zang, John Tellew, Nancy Pryer
Journal: Cancer Research (2012)

Abstract Selective RAF inhibitors have significant activity in patients with metastatic melanoma whose tumors express BRAFV600E. However, not all patients respond equally well to treatment and the duration of response is often limited to less than 6 months. LGX818 was developed with the hypothesis that a more potent inhibitor with excellent pharmacological properties would maximize the degree and duration of patient response. LGX818 is a highly potent RAF inhibitor with selective anti-proliferative and apoptotic activity in cells expressing BRAFV600E. In the A375 (BRAFV600E) human melanoma cell line LGX818 suppresses phospho-ERK (EC50 = 3 nM) leading to potent inhibition of proliferation (EC50 = 4 nM). No significant activity was observed against a panel of 100 kinases (IC50 &amp;gt; 900 nM) and LGX818 did not inhibit proliferation of &amp;gt; 400 cell lines expressing wild-type BRAF. Contributing to the high potency of LGX818 is the extremely slow off-rate from BRAFV600E which is not observed with other RAF inhibitors. In biochemical assays the dissociation half-life was &amp;gt;24 hours which translated into sustained target inhibition in cells following drug wash-out. Single dose PK/PD studies in human melanoma xenograft models (BRAFV600E) indicated that LGX818 treatment at oral doses as low as 6 mg/kg resulted in strong (75%) and sustained (&amp;gt;24 hours) decrease in phospho-MEK, even following clearance of drug from circulation. Decreases in phospho-ERK were consistent with phospho-MEK but markers of downstream transcriptional output (DUSP6 and SPRY4) appeared to provide a more sensitive measure of pathway activation. LGX818 induced tumor regression in multiple BRAF mutant human tumor xenograft models grown in immune compromised mice and rats at doses as low as 1 mg/kg. Consistent with the in vitro data, LGX818 was inactive against BRAF wild-type tumors at doses up to 300 mg/kg bid, with good tolerability and linear increase in exposure. Efficacy was also achieved in a more disease-relevant spontaneous metastatic melanoma and a model of melanoma brain metastasis. LGX818 is a potent and selective RAF kinase inhibitor with unique biochemical properties that contribute to an excellent pharmacological profile. A Phase I clinical trial in patients with BRAF mutant tumors is ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3790. doi:1538-7445.AM2012-3790
Evaluation of protein-N-(2-hydroxypropyl) methacrylamide copolymer conjugates as targetable drug-carriers. 2. Body distribution of conjugates containing transferrin, antitransferrin receptor antibody or anti-Thy 1.2 antibody and effectiveness of transferrin-containing daunomycin conjugates against mouse L1210 leukaemia in vivo
Authors: Pauline A. Flanagan, Ruth Duncan, Vladimir Šubr, Karel Ulbrich, Pavla Kopec⌣ková, Jindřich Kopec⌣ek
Journal: Journal of Controlled Release (1992)