tbuckley/cabot-search huggingface dataset:
Introducing ‘Critically Appraised Topics’
Authors: J.M. Batchelor, S.M. Langan
Journal: British Journal of Dermatology (2012)

The Putting Papers into Practice Section of the BJD has been running for more than 1 year, and has mostly featured critical appraisals of important randomized controlled trials or epidemiological papers on dermatology topics, published in the dermatological or general medical literature. Our aims have been to highlight particularly interesting papers, as it is difficult to read all of the latest dermatology publications, and also to help readers to develop their skills in critical appraisal of the literature.1 While a critical appraisal of a single study can be useful, practical application of its findings is limited by the fact that it focuses on only one study. If there are several studies on a particular topic, it is more useful to understand the implications of the totality of evidence. The gold standard of medical evidence is the systematic review, in which a rigorous search is made for all possible studies on the topic with strict inclusion and exclusion criteria and the results are, if possible, combined using meta-analysis.2 Such reviews are very time consuming and researchers and clinicians do not have time to perform a systematic review on every clinical question of interest, so many important questions cannot be answered using evidence from systematic reviews. A slightly more pragmatic – albeit ‘quicker and dirtier’– approach to summarizing the evidence on a particular topic is the Critically Appraised Topic (CAT). CATs are short summaries of evidence on a topic of interest, usually focused around a clinical scenario. CATs are created using the following four stages: (i) formulating a precise question based on a real-life clinical scenario, such as ‘In a patient with [condition A], which treatment is more effective, [treatment X] or [treatment Y]?’; (ii) systematically searching for the highest quality evidence to answer the question; (iii) critically appraising the evidence; and (iv) applying the evidence back to the clinical scenario. The advantage of a CAT over a standard literature review is that a CAT involves explicit critical appraisal of the evidence found, which should help to avoid biased conclusions (although CATs are still more prone to bias than a systematic review). CATs are well established3 and have become popular in many medical specialties, including Radiology,4 Neurology,5 Rehabilitation Medicine6 and Dermatology.7 We are very keen for readers to submit CATs to the Putting Papers into Practice section of the BJD. We hope that the CAT published in this issue8 will give readers an idea of what a CAT should look like. There are also freely available resources to help with the creation of CATs, such as the CATMaker, freely downloadable from the website of the Centre for Evidence-Based Medicine (http://www.cebm.net/index.aspx?o=1216). It is our hope that readers will enjoy sharpening their critical appraisal skills as they create CATs and, in doing so, will generate useful evidence-based answers for important clinical questions to share with the BJD readership. None declared.
LXRβ/estrogen receptor-α signaling in lipid rafts preserves endothelial integrity
Authors: Tomonori Ishikawa, Ivan S. Yuhanna, Junko Umetani, Wan-Ru Lee, Kenneth S. Korach, Philip W. Shaul, Michihisa Umetani
Journal: Journal of Clinical Investigation (2013)

Liver X receptors (LXR) are stimulated by cholesterol-derived oxysterols and serve as transcription factors to regulate gene expression in response to alterations in cholesterol. In the present study, we investigated the role of LXRs in vascular endothelial cells (ECs) and discovered that LXRβ has nonnuclear function and stimulates EC migration by activating endothelial NOS (eNOS). This process is mediated by estrogen receptor-α (ERα). LXR activation promoted the direct binding of LXRβ to the ligand-binding domain of ERα and initiated an extranuclear signaling cascade that requires ERα Ser118 phosphorylation by PI3K/AKT. Further studies revealed that LXRβ and ERα are colocalized and functionally coupled in EC plasma membrane caveolae/lipid rafts. In isolated aortic rings, LXR activation of NOS caused relaxation, while in mice, LXR activation stimulated carotid artery reendothelialization via LXRβ- and ERα-dependent processes. These studies demonstrate that LXRβ has nonnuclear function in EC caveolae/lipid rafts that entails crosstalk with ERα, which promotes NO production and maintains endothelial monolayer integrity in vivo.
Growth Hormone and Insulin-Like Growth Factor-I in the Transition from Normal Mammary Development to Preneoplastic Mammary Lesions
Authors: David L. Kleinberg, Teresa L. Wood, Priscilla A. Furth, Adrian V. Lee
Journal: Endocrine Reviews (2008)

Abstract Adult female mammary development starts at puberty and is controlled by tightly regulated cross-talk between a group of hormones and growth factors. Although estrogen is the initial driving force and is joined by luteal phase progesterone, both of these hormones require GH-induced IGF-I in the mammary gland in order to act. The same group of hormones, when experimentally perturbed, can lead to development of hyperplastic lesions and increase the chances, or be precursors, of mammary carcinoma. For example, systemic administration of GH or IGF-I causes mammary hyperplasia, and overproduction of IGF-I in transgenic animals can cause the development of usual or atypical hyperplasias and sometimes carcinoma. Although studies have clearly demonstrated the transforming potential of both GH and IGF-I receptor in cell culture and in animals, debate remains as to whether their main role is actually instructive or permissive in progression to cancer in vivo. Genetic imprinting has been shown to occur in precursor lesions as early as atypical hyperplasia in women. Thus, the concept of progression from normal development to cancer through precursor lesions sensitive to hormones and growth factors discussed above is gaining support in humans as well as in animal models. Indeed, elevation of estrogen receptor, GH, IGF-I, and IGF-I receptor during progression suggests a role for these pathways in this process. New agents targeting the GH/IGF-I axis may provide a novel means to block formation and progression of precursor lesions to overt carcinoma. A novel somatostatin analog has recently been shown to prevent mammary development in rats via targeted IGF-I action inhibition at the mammary gland. Similarly, pegvisomant, a GH antagonist, and other IGF-I antagonists such as IGF binding proteins 1 and 5 also block mammary gland development. It is, therefore, possible that inhibition of IGF-I action, or perhaps GH, in the mammary gland may eventually play a role in breast cancer chemoprevention by preventing actions of both estrogen and progesterone, especially in women at extremely high risk for developing breast cancer such as BRCA gene 1 or 2 mutations.
Cannabis and Cigarettes
Authors: Bridget M. Kuehn
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sample size calculations I
Authors: P. Sedgwick
Journal: BMJ (2010)

A randomised, double blind, placebo controlled trial investigated whether fluvastatin reduced major adverse cardiac events in patients who had undergone successful percutaneous coronary intervention (with or without stenting). The primary outcome was the occurrence of major adverse cardiac events—defined as cardiac death, non-fatal myocardial infarction, or a reintervention procedure—within three years.1 To calculate the sample size needed to compare fluvastatin with placebo, it was assumed that the proportion of patients having major adverse cardiac events at three years without treatment would be 25%. For fluvastatin to be considered clinically superior to placebo, it would be necessary to demonstrate a relative improvement of 25%, with only 18.75% of patients having major adverse cardiac events at three years. To do so, a total sample size of 1828 patients (914 in each treatment arm) would be required to achieve 90% power using a two sided hypothesis test and critical level of significance of 0.05. A total of 1677 patients were subsequently recruited to the trial. Which of the following, if any, are true?
Pulmonary capillary blood volume in women: normal values and the effect of oral contraceptives
Authors: A. Seaton
Journal: Thorax (1972)

Pulmonary capillary blood volume (V<sub>c</sub>) was determined in 30 young women, 14 of whom were taking oral contraceptives. Duplicate estimates of V<sub>c</sub> in the 16 women not taking contraceptives showed a significant increase in the second half of the menstrual cycle. Formulae for prediction of V<sub>c</sub> in women were derived for the first and second halves of the cycle. V<sub>c</sub> was shown to be of the same order in women taking contraceptives containing oestrogen and progestogen as in those in the premenstrual phase of the cycle. Possible causes of these findings and their relevance to the diagnosis of pulmonary thromboembolic disease are discussed.
Is erythrokeratoderma one disorder? A clinical and ultrastructural study of two siblings
Authors: A.W. Macfarlane, S.J. Chapman, J.L. Verbov
Journal: British Journal of Dermatology (1991)

Two sisters with erythrokeratoderma are described. In the younger sister the clinical appearance corresponded to erythrokeratoderma variabilis (EKV). whereas in the older sister it corresponded to progressive symmetrical erythrokeratoderma (PSEK). Ultrastructural findings in both cases were identical. We suggest that EKV and PSEK are different manifestations of a single condition.
Physiological and pathological mechanisms governing fluid accumulation within the pleural space.
Authors: W Leckie
Journal: Thorax (1970)

Much less is known of the lymphatics of the pleura and chest wall.There are two main directions of lymph flow-forwards to the internal mammary chain of nodes and vessels, and backwards to the posterior mediastinum.Some of the lymphatics of the lower intercostal spaces drain downwards, through the diaphragm, to reach the cisterna chyli.Some of the mediastinal lymphatics communicate directly with the thoracic duct while the majority run upwards to join the paratracheal and pulmonary lymphatics and then drain by one or more vessels into the veins at the base of the neck near the thoracic duct.The radiological appearances of the abnormal lymphatics in lymphangitis carcinomatosa, pulmonary oedema, etc., are discussed.Lymphography W. F. WHITE The lymphatics and lymph nodes draining many parts of the body may now be demonstrated by lymphography.
New Portuguese code no longer defines abortion as ethical misconduct
Authors: T. Villanueva
Journal: BMJ (2008)

Abortion is no longer considered an act of serious ethical misconduct in the latest ethical code for doctors in Portugal, which was approved recently by the Portuguese Medical Association.

The previous code stated, “The practices of both abortion and euthanasia are considered acts of serious ethical misconduct.” However, the new code, which was approved at the end of September …
The Hysterectomy Hoax
Authors: Allan G. Charles
Journal: JAMA (1994)

In<i>The Hysterectomy Hoax</i>Dr Stanley West makes the sensational accusation that hysterectomy is a big business and that no more than 10% of hysterectomies are necessary and then only for cancer. Dr West, "a noted infertility specialist and Chief of Reproductive Endocrinology at St Vincent's Hospital," although not board certified in reproductive endocrinology, throughout the book claims expertise in conservative surgery. I was curious as to whether Dr West had published any results of his own approaches to treatment, but a computer search over the last 30 years credits him with only two publications in peer-reviewed journals, neither of which is germane to the book. The book contains outrageous and inaccurate statements, for instance, "up to one half of all patients [who have had hysterectomies] develop complications, some of which can be quite serious." Almost any study on hysterectomies shows a complication rate of 5% to 20%, and most
Absence of Mycobacterium tuberculosis DNA in synovial fluid from patients with rheumatoid arthritis.
Authors: H Jalal, M Millar, C Linton, P Dieppe
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--To determine whether Mycobacterium tuberculosis DNA can be detected in synovial fluid of patients with rheumatoid arthritis (RA). METHODS--The polymerase chain reaction was applied to cellular components of synovial fluid. RESULTS--No evidence of M tuberculosis DNA was found in synovial fluid from 31 patients with RA and 13 control patients. CONCLUSION--The findings do not support a role for persistent M tuberculosis infection in the pathogenesis of RA.
Venereal Disease: Diagnosis and Treatment
Authors: PETER E. DANS
Journal: Annals of Internal Medicine (1976)

Comments and Corrections1 April 1976Venereal Disease: Diagnosis and TreatmentPETER E. DANS, M.D., F.A.C.P.PETER E. DANS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-4-499_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Doctor Jaffe, in his timely and excellent review entitled "The Laboratory Diagnosis of Syphilis" (Ann Intern Med83:846-850, 1975), states that "the combination of a clinically suspicious lesion and a reactive RPR card test is sufficient to initiate therapy during the first visit." The judgment "clinically suspicious" is determined by the experience of the observer as much as by the lesion. Many physicians graduating from medical school in the last 2 decades have never seen a chancre and have little basis for designating a lesion as "typical" or "clinically suspicious." To further complicate matters, physicians are taught...References1. DUNCANKNOXWENDE WJR: The FTA-ABS test in dark-field-positive primary syphilis. JAMA 228:859-860, 1974 CrossrefMedlineGoogle Scholar2. DANS P: Spirochetal infections, in Tice's Principles of Internal Medicine. Hagerstown, Maryland, Harper & Row, Inc., 1974, chapter 18, pp. 1-20 Google Scholar3. DANS P: The establishment of a university-based venereal disease clinic. I. Description of the clinic and its population. J Am Vener Dis Assoc 1:70-78, 1974 MedlineGoogle Scholar4. FLEMINGBROWNDONOHUE WWJ: National survey of venereal disease treated by physicians in 1968. JAMA 211:1827-1830, 1970 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Colorado General Health (VD) Clinic University of Colorado Medical Center Denver, Colorado 80220 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1976Volume 84, Issue 4Page: 491-491KeywordsLesionsRapid plasma reaginResearch laboratoriesSexually transmitted diseasesSyphilis Issue Published: 1 April 1976 PDF DownloadLoading ...
Erratum: Corrigendum: Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy
Authors: Cas Simons, Lachlan D Rash, Joanna Crawford, Linlin Ma, Ben Cristofori-Armstrong, David Miller, Kelin Ru, Gregory J Baillie, Yasemin Alanay, Adeline Jacquinet, François-Guillaume Debray, Alain Verloes, Joseph Shen, Gözde Yesil, Serhat Guler, Adnan Yuksel, John G Cleary, Sean M Grimmond, Julie McGaughran, Glenn F King, Michael T Gabbett, Ryan J Taft
Journal: Nature Genetics (2015)
Effect of hormones on the variation of radiosensitivity in females as measured by induction of chromosomal aberrations.
Authors: C J Roberts, G R Morgan, N Danford
Journal: Environmental Health Perspectives (1997)

The frequency of dicentrics + ring (dic/cell) and total chromosome aberrations (dicentrics, rings and excess acentrics, etc.) per cell (TAb/cell) has been studied in 50 male and female volunteers after high or low dose rate (HDR, LDR) irradiation of peripheral blood lymphocytes. The mean male aberration frequencies per cell after HDR irradiation were 0.38 dic/cell and 0.61 TAb/cell; following LDR irradiation, the mean aberration frequencies were 0.28 dic/cell and 0.45 TAb/cell. Equivalent female values after HDR irradiation were 0.42 dic/cell and 0.71 TAb/cell; after LDR irradiation, the mean aberration frequencies were 0.30 dic/cell and 0.48 TAb/cell. Analysis of variance showed that there was a highly significant difference between males and females have a greater HDR, but not LDR, irradiation It is concluded from this study that females have a greater variability in their radioresponse, and that this variability is related to progesterone, which has a profound effect upon radiosensitivity, as measured by cytogenetic end points.
Effects of Loud Noise Exposure on DNA Integrity in Rat Adrenal Gland
Authors: Giada Frenzilli, Paola Lenzi, Vittoria Scarcelli, Francesco Fornai, Antonio Pellegrini, Paola Soldani, Antonio Paparelli, Marco Nigro
Journal: Environmental Health Perspectives (2004)

Loud noise is generally considered an environmental stressor causing negative effects on acoustic, cardiovascular, nervous, and endocrine systems. In this study, we investigated the effects of noise exposure on DNA integrity in rat adrenal gland evaluated by the comet assay. The exposure to loud noise (100 dBA) for 12 hr caused a significant increase of DNA damage in the adrenal gland. Genetic alterations did not decrease 24 hr after the cessation of the stimulus. We hypothesize that an imbalance of redox cell status is responsible for the induction and persistence of noise-induced cellular damage.
Contribution of Granulocyte Colony-Stimulating Factor to the Acute Mobilization of Endothelial Precursor Cells by Vascular Disrupting Agents
Authors: Yuval Shaked, Terence Tang, Jill Woloszynek, Laura G. Daenen, Shan Man, Ping Xu, Shi-Rong Cai, Jeffrey M. Arbeit, Emile E. Voest, David J. Chaplin, Jon Smythe, Adrian Harris, Paul Nathan, Ian Judson, Gordon Rustin, Francesco Bertolini, Daniel C. Link, Robert S. Kerbel
Journal: Cancer Research (2009)

Vascular disrupting agents (VDA) cause acute shutdown of abnormal established tumor vasculature, followed by massive intratumoral hypoxia and necrosis. However, a viable rim of tumor tissue invariably remains from which tumor regrowth rapidly resumes. We have recently shown that an acute systemic mobilization and homing of bone marrow-derived circulating endothelial precursor (CEP) cells could promote tumor regrowth following treatment with either a VDA or certain chemotherapy drugs. The molecular mediators of this systemic reactive host process are unknown. Here, we show that following treatment of mice with OXi-4503, a second-generation potent prodrug derivative of combretastatin-A4 phosphate, rapid increases in circulating plasma vascular endothelial growth factor, stromal derived factor-1 (SDF-1), and granulocyte colony-stimulating factor (G-CSF) levels are detected. With the aim of determining whether G-CSF is involved in VDA-induced CEP mobilization, mutant G-CSF-R(-/-) mice were treated with OXi-4503. We found that as opposed to wild-type controls, G-CSF-R(-/-) mice failed to mobilize CEPs or show induction of SDF-1 plasma levels. Furthermore, Lewis lung carcinomas grown in such mice treated with OXi-4503 showed greater levels of necrosis compared with tumors treated in wild-type mice. Evidence for rapid elevations in circulating plasma G-CSF, vascular endothelial growth factor, and SDF-1 were also observed in patients with VDA (combretastatin-A4 phosphate)-treated cancer. These results highlight the possible effect of drug-induced G-CSF on tumor regrowth following certain cytotoxic drug therapies, in this case using a VDA, and hence G-CSF as a possible therapeutic target.
From a 16th century monastery to a 21st century orthopaedic hospital
Authors: P Tomba, A Viganò, C Menarini, P Picci
Journal: BMJ (2006)

Taddeo Pepoli,1 abbot of the Olivetan (a suborder of Benedictine monks), wearing his white habit, walks quickly up the hill to the monastery of San Michele in Bosco, in Bologna. He has been yearning to revisit the place where he was the prior at the end of the 17th century, and now he has decided to make his wish come true.⇓ 



Allegory of Asia 



Inside the building, he goes straight upstairs to where he and his brother monks used to study. He opens the heavy door confidently, looking forward to admiring the library that he had rebuilt and frescoed. But, crossing the threshold, the monk is bewildered; the room looks strange; it is no longer the place he had remembered all these years. He looks up and sees the brightly coloured frescoes by Domenico Maria Canuti, a pupil of Guido Reni, and the Swiss painter Enrico Haffner, that he had commissioned2; looking down, he sees the fine, shiny floor—but everything else is different. 

The monk walks timidly on and catches sight of a magnificent globe that was not there before: it is the work of Padre Rosini da Lendinara,3 who finished making it, in that room, in 1762. (Australia is but an outline on the globe.) 

Looking around, he notices that the solid walnut bookshelves, made for him by Martorelli, have gone, replaced by stark shelving. Filled with curiosity, the abbot takes down a few books; they look so different from the hymn books he was used to. He is puzzled by the pictures in the books. His fingers feel the shiny paper of the photographs of people in strange poses. “Where are those fine, hand painted pictures that decorate the precious books I remember on the shelves of my library?” he asks himself. What …