tbuckley/cabot-search huggingface dataset:
Articles disputing link between HRT and breast cancer are "ridiculous"
Authors: Z. Kmietowicz
Journal: BMJ (2012)

A leading epidemiologist has condemned a group of authors for writing and a journal for publishing a series of articles challenging the well established link between hormone replacement therapy (HRT) and breast cancer, describing their actions as “a disgrace.”

Klim McPherson, visiting professor of Public Health Epidemiology at the Nuffield Department of Obstetrics and Gynaecology at the University of Oxford, described the arguments used by the authors as “tortuous and ridiculous.”

He told the BMJ , “If the scientific consensus can incorporate uncertainty about this relationship then people can market and prescribe HRT and downplay its importance.”

Samuel Shapiro, visiting professor of epidemiology at the University of Cape Town, and colleagues looked at the design of three major pieces of research that prompted a rethink of the long term safety of HRT—the Collaborative Reanalysis ( Lancet 1997;98:498-509), the Women’s Health Initiative ( JAMA 2002;288:321-3; JAMA 2006;295:1647-57), and the Million Women Study ( Lancet 2003;362:419-27). Their articles are published in the Journal of Family Planning and Reproductive Health Care (doi:10.1136/jfprhc.2011.0078; doi:10.1136/jfprhc-2011-0090; doi:10.1136/jfprhc-2011-0091;doi:10.1136/jfprhc-2011-100229).

The studies are littered with design flaws, bias, and “biological implausibility,” say the authors. They conclude that …
Contemporary Management of Lower Urinary Tract Disease With Botulinum Toxin A: A Systematic Review of Botox (OnabotulinumtoxinA) and Dysport (AbobotulinumtoxinA)
Authors: Altaf Mangera, Karl-Erik Andersson, Apostolos Apostolidis, Chris Chapple, Prokar Dasgupta, Antonella Giannantoni, Stavros Gravas, Stephan Madersbacher
Journal: European Urology (2011)
POOR BLOOD PRESSURE RESPONSE TO EXERCISE PREDICTS ADVERSE PROGNOSIS IN PATIENTS WITH NON-ISCHEMIC BUT NOT ISCHEMIC CARDIOMYOPATHY
Authors: Yusuke Sata, Hiroshi Takaki, Rika Kawakami, Michio Nakanishi, Michio Nakanishi, Teruo Noguchi, Yoichi Goto, Masaru Sugimachi
Journal: Journal of the American College of Cardiology (2010)
Improving Adoptive T Cell Therapy by Targeting and Controlling IL-12 Expression to the Tumor Environment
Authors: Ling Zhang, Sid P Kerkar, Zhiya Yu, Zhili Zheng, Shicheng Yang, Nicholas P Restifo, Steven A Rosenberg, Richard A Morgan
Journal: Molecular Therapy (2011)

Interleukin-12 (IL-12) is an important immunostimulatory cytokine, yet its clinical application has been limited by the systemic toxicity associated with its administration. In this work, we developed a strategy to selectively deliver IL-12 to the tumor environment using genetically engineered lymphocytes. However, peripheral blood lymphocytes (PBLs) transduced with a γ-retroviral vector, which constitutively expressed IL-12, failed to expand in culture due to apoptosis. To circumvent this problem, a vector was designed where IL-12 expression was directed by a composite promoter-containing binding motifs for nuclear factor of activated T-cells (NFAT.hIL12.PA2). The NFAT-responsive promoter was activated to drive IL-12 expression upon the recognition of tumor-specific antigen mediated by a T cell receptor (TCR) that was engineered into the same lymphocytes. We tested the efficacy of the inducible IL-12 vector in vivo in a murine melanoma model. Adoptive transfer of pmel-1 T cells genetically engineered with NFAT-murineIL12 (NFAT.mIL12.PA2) significantly enhanced regression of large established B16 melanoma. Notably, this targeted and controlled IL-12 treatment was without toxicity. Taken together, our results suggest that using the NFAT.hIL12.PA2 vector might be a promising approach to enhance adoptive cancer immunotherapy. Interleukin-12 (IL-12) is an important immunostimulatory cytokine, yet its clinical application has been limited by the systemic toxicity associated with its administration. In this work, we developed a strategy to selectively deliver IL-12 to the tumor environment using genetically engineered lymphocytes. However, peripheral blood lymphocytes (PBLs) transduced with a γ-retroviral vector, which constitutively expressed IL-12, failed to expand in culture due to apoptosis. To circumvent this problem, a vector was designed where IL-12 expression was directed by a composite promoter-containing binding motifs for nuclear factor of activated T-cells (NFAT.hIL12.PA2). The NFAT-responsive promoter was activated to drive IL-12 expression upon the recognition of tumor-specific antigen mediated by a T cell receptor (TCR) that was engineered into the same lymphocytes. We tested the efficacy of the inducible IL-12 vector in vivo in a murine melanoma model. Adoptive transfer of pmel-1 T cells genetically engineered with NFAT-murineIL12 (NFAT.mIL12.PA2) significantly enhanced regression of large established B16 melanoma. Notably, this targeted and controlled IL-12 treatment was without toxicity. Taken together, our results suggest that using the NFAT.hIL12.PA2 vector might be a promising approach to enhance adoptive cancer immunotherapy.
Logical debate on problem based learning
Authors: Andrew F Mellon, Jonathan Mellon
Journal: BMJ (2006)

EDITOR—Burke et al deal with an area of importance for medical education.1 They perhaps overstated their case—that students validate problem based learning.

Students on a problem based learning course could reasonably be expected to have had explanations of its aims and hence to respond to questions about course content more in line with that information than other students. This must be a potential source of bias in their responses.

What the “traditional” curriculum represents is not clear, …
Clonal analysis of deletions on chromosome 20q and JAK2-V617F in MPD suggests that del20q acts independently and is not one of the predisposing mutations for JAK2-V617F
Authors: Franz X. Schaub, Roland Jäger, Renate Looser, Hui Hao-Shen, Sylvie Hermouet, François Girodon, Andre Tichelli, Heinz Gisslinger, Robert Kralovics, Radek C. Skoda
Journal: Blood (2008)
We need to stop pretending that everything is OK with the Indian healthcare system
Authors: R. Chauhan
Journal: BMJ (2014)

Corruption, the best kept dirty secret in medicine, has eventually tumbled out into the open.1 It has been reported that question papers, even those for postgraduate entrance examinations and entrance examinations to some of the most reputable Indian medical colleges have been leaked, sold, and answers provided.2 3 4 Perhaps this campaign will be the …
FACTOR 5 DEFICIENCY IN HEMORRHAGIC DIATHESIS (PARAHEMOPHILIA)
Authors: Stuart W. Cosgriff
Journal: JAMA (1952)

Normal plasma has been reported to contain a globulin which is a highly active accelerator of blood clotting. This factor acts by catalyzing the interaction of prothrombin, thromboplastin, and calcium in the formation of thrombin. In the absence of this factor blood clotting is delayed markedly. Owren<sup>1</sup>in 1944 discovered this new factor, which he called the fifth coagulation factor, or Factor 5. Fantl and Nance<sup>2</sup>and Ware, Guest, and Seegers<sup>3</sup>also demonstrated this new factor and its mechanism of action, calling it "accelerator globulin" or Ac-globulin. Quick's labile factor<sup>4</sup>may be very similar to or identical with Factor 5. In vivo deficiency of this factor was reported by Owren<sup>1</sup>as the mechanism of a hemorrhagic diathesis in a 29-year-old woman. This deficiency of Factor 5, considered to be congenital, characteristically was associated with a prolonged clotting time of venous blood and a prolonged one-stage
Beyond the Basics: Designing a Comprehensive Response to Low Health Literacy
Authors: Elisa J. Gordon, Michael S. Wolf
Journal: The American Journal of Bioethics (2007)

Click to increase image sizeClick to decrease image size Acknowledgement This work was supported by The Alden March Bioethics Institute and grant DK063953 from the National Institute of Diabetes and Digestive and Kidney Diseases (to Elisa J. Gordon).
Abstract P4-07-18: PDGFRbeta-induced miR-9 is up-regulated in triple negative breast cancer
Authors: I Plantamura, E D'Ippolito, A Tessari, S Cresta, R Orlandi, A Moliterni, ML Carcangiu, F De Braud, E Tagliabue, MV Iorio
Journal: Cancer Research (2013)

Abstract miR-9 has been described as an oncogenic microRNA associated to a metastatic phenotype and able to induce EMT (epithelial-to-mesenchymal transition) through direct targeting of E-cadherin. However, data available concerning the expression and the role of this microRNA in different subgroups of breast cancer are still not exhaustive. Evaluating miR-9 expression by Real-Time PCR in a series of 92 breast cancer specimens (35 luminal, 36 HER2, 21 triple negative), we found that this microRNA is increasingly higher in HER2 and Triple Negative versus ER positive patients (fold change 3 and 8 respectively). Moreover, preliminary analysis of miR-9 expression in correlation with bio-pathological features and clinical data also indicates a trend in association with disease progression. Triple Negative Breast Cancers represent a very aggressive breast cancer subgroup, still lacking specific markers for an effective targeted therapy; we investigated whether miR-9 might play a role in the biology of this tumor subtype. Preliminary data indicate that miR-9 is activated downstream PDGFRbeta, which represents a crucial player in the aggressive phenotype of Triple Negative Breast Cancer. In summary, here we show that miR-9 is significantly upregulated in triple negative breast cancer in comparison with other breast cancer subgroups and is activated downstream PDGFRbeta. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-07-18.
Conference Report: Fiddling while tobacco burns
Authors: S. Chapman
Journal: BMJ (1988)

Every four years since 1968 sections of the world's community interested in the control of smoking have gathered for a world conference.This year it was the turn ofJapan to be the host country.Previous host countries (the United States, the United Kingdom, Sweden, and Canada) all had important strategies and tactics for controlling smoking or important reports to tell the world.The Swedish and Canadian conferences in particular saw plenary speakers throw gauntlet after gauntlet down to the tobacco industry, calling for political action and using terms like "war" and "enemy."Japan was quite a different story.With a staggering two thirds of Japanese men smoking, a government with a monopoly on tobacco and a growing enthusiasm for export to the vast markets of South East Asia, and the recent start of vigorous marketing targeted at Japanese women, who have a low prevalence of smoking, it seemed clear that the local organising committee was looking to the conference as a means of strengthening the hitherto shaky hand of its domestic health agencies.
Heart Transplantation after 16 Years
Authors: W. Gerald Austen, A. Benedict Cosimi
Journal: New England Journal of Medicine (1984)

Six years ago, one of us (W.G.A.) commented in the Journal on the current status of cardiac transplantation.1 The editorial concluded that the procedure, under certain special conditions, could be considered a rational and socially acceptable therapy for a limited number of patients with irreversible cardiac failure. The extension of transplantation to patients with acute cardiac disease had just been described.2 Intraaortic balloon-pump resuscitation of patients presenting with heart failure had led to situations in which the acute condition was stabilized but weaning from the assistance device could not be accomplished because of the advanced stage of disease. With the . . .
THE ERYTHROPOIETIC ACTION OF GERMANIUM DIOXIDE
Authors: Frederick S. Hammett, Joseph E. Nowrey, John H. Müller
Journal: The Journal of Experimental Medicine (1922)

Injections were made of a sterile 0.4 per cent solution of germanium dioxide into four lots of mature male and female albino rats. Exact conditions of control were maintained. To two lots there was administered in four doses at intervals of 4 days a total of 6.6 mg. of the oxide per kilo of body weight. To two lots there was given in three doses at like intervals a total of 45 mg. of the compound per kilo of body weight. In each lot there was one rat which served as a control and which did not receive any germanium. A preliminary period of observation was maintained as a further control during which two determinations of the erythrocyte and leucocyte counts of the blood were made 7 days apart on all the rats. Weekly counts were made on all the rats during the progress of the investigation which lasted for 4 weeks, during 3 of which the treated animals were under the influence of germanium. In the first group 11 days elapsed between the last injection and the last count. In the second group the interval was 14 days. It was found that without exception all of the test rats responded to the germanium dioxide by a marked and sustained rise in the number of erythrocytes in the blood which ranged from 1 to nearly 5 millions. These results are statistically valid. There was an apparent tendency for the degree of effect to be related to the initial erythrocyte number, in that with a lower initial count there seemed to take place a greater rise, and vice versa. There was no indication that the larger doses of germanium dioxide exerted a greater stimulating effect on the production of the resultant erythrocythemia than the smaller doses. There is evidence that the effect is quick in making its appearance. The rise in the red cell count was found to occur within a week, and after but two injections of the oxide. Indications were obtained that germanium dioxide tends to increase the coagulability of the blood. Autopsy findings showed color changes in the liver and bone marrow. We believe that germanium dioxide is an erythrocytogenic agent and we hope that fruitful results will come from its therapeutic application.
STERILITY FROM USE OF RADIUM
Authors: M. A. Varzhabedian
Journal: JAMA (1923)

To the Editor:  —Within the last few years there have come to my attention cases of sterility caused by handling radium. Nearly all the patients were young and healthy, and attracted by the steady salary promised, without much knowledge as to the action of radium on their future physical condition and without being informed as to that fact by those supposed to know. The employment, as a rule, is steady and practically continuous until these unfortunates come to realize that through the constant handling of radium they have become sterile. Young laymen, even most of the medical men in such employment, do not know and realize the dangers when they first start. It is impossible for men handling especially big dosages of radium to wear heavy enough lead aprons to be protected. Applicants should be informed of all the dangers, and decide their course with full knowledge in advance of
Geospatial mapping to estimate timely access to surgical care in nine low-income and middle-income countries
Authors: Nakul P Raykar, Alexis N Bowder, Charles Liu, Martha Vega, Jong H Kim, Gloria Boye, Sarah L M Greenberg, Johanna N Riesel, Rowan D Gillies, John G Meara, Nobhojit Roy
Journal: The Lancet (2015)
Lineage‐dependent effects of aryl hydrocarbon receptor agonists contribute to liver tumorigenesis
Authors: Joshua A. Harrill, Bethany B Parks, Eliane Wauthier, J. Craig Rowlands, Lola M. Reid, Russell S. Thomas
Journal: Hepatology (2014)

Rodent cancer bioassays indicate that the aryl hydrocarbon receptor (AHR) agonist, 2,3,7,8‐tetracholorodibenzo‐ p ‐dioxin (TCDD), causes increases in both hepatocytic and cholangiocytic tumors. Effects of AHR activation have been evaluated on rodent hepatic stem cells (rHpSCs) versus their descendants, hepatoblasts (rHBs), two lineage stages of multipotent, hepatic precursors with overlapping but also distinct phenotypic traits. This was made possible by defining the first successful culture conditions for ex vivo maintenance of rHpScs consisting of a substratum of hyaluronans and Kubota's medium (KM), a serum‐free medium designed for endodermal stem/progenitor cells. Supplementation of KM with leukemia inhibitory factor elicited lineage restriction to rHBs. Cultures were treated with various AHR agonists including TCDD, 6‐formylindolo‐[3,2‐b]carbazole (FICZ), and 3‐3'‐diindolylmethane (DIM) and then analyzed with a combination of immunocytochemistry, gene expression, and high‐content image analysis. The AHR agonists increased proliferation of rHpSCs at concentrations producing a persistent AHR activation as indicated by induction of Cyp1a1 . By contrast, treatment with TCDD resulted in a rapid loss of viability of rHBs, even though the culture conditions, in the absence of the agonists, were permissive for survival and expansion of rHBs. The effects were not observed with FICZ and at lower concentrations of DIM. Conclusion : Our findings are consistent with a lineage‐dependent mode of action for AHR agonists in rodent liver tumorigenesis through selective expansion of rHpSCs in combination with a toxicity‐induced loss of viability of rHBs. These lineage‐dependent effects correlate with increased frequency of liver tumors. (H epatology 2015;61:548‐560)
Two Important Italian Scientists of the Renaissance and the First Book Ever Devoted to Nevi
Authors: Filippo Pesapane, Antonella Coggi, Raffaele Gianotti
Journal: JAMA Dermatology (2014)

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Quality Indicators for Prevention and Management of Pressure Ulcers
Authors: Thomas E. Finucane
Journal: Annals of Internal Medicine (2002)

Letters15 October 2002Quality Indicators for Prevention and Management of Pressure UlcersThomas E. Finucane, MDThomas E. Finucane, MDJohns Hopkins Bayview Medical Center; Baltimore, MD 21044Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-137-8-200210150-00033-w2 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In the article by Bates-Jensen on quality indicators for prevention and management of pressure ulcers in vulnerable elders (1), the third indicator for prevention concerns nutrition. Bates-Jensen states that since poor diet, particularly low dietary protein intake, is an independent predictor of pressure ulcer development, nutritional intervention or dietary consultation should be instituted if malnutrition is suspected. The sentence concluding this section, however, acknowledges that “no direct evidence shows that adequate nutrition will prevent ulcers.”In fact, there is a good bit of evidence to the contrary, both for dietary consultation (2) and for nutritional intervention, especially ...Reference1. Bates-Jensen BM. Quality indicators for prevention and management of pressure ulcers in vulnerable elders. Ann Intern Med. 2001;135 2 8 744-51. [PMID: 11601958] LinkGoogle Scholar2. Lyder CH, Preston J, Grady JN, Scinto J, Allman R, Bergstrom N, et al . Quality of care for hospitalized medicare patients at risk for pressure ulcers. Arch Intern Med. 2001;161:1549-54. [PMID: 11427104] CrossrefMedlineGoogle Scholar3. Berlowitz DR, Ash AS, Brandeis GH, Brand HK, Halpern JL, Moskowitz MA. Rating long-term care facilities on pressure ulcer development: importance of case-mix adjustment. Ann Intern Med. 1996;124:557-63. [PMID: 8597318] LinkGoogle Scholar4. Finucane TE. Malnutrition, tube feeding and pressure sores: data are incomplete. J Am Geriatr Soc. 1995;43:447-51. [PMID: 7706638] CrossrefMedlineGoogle Scholar5. Finucane TE, Christmas C, Travis K. Tube feeding in patients with advanced dementia: a review of the evidence. JAMA. 1999;282:1365-70. [PMID: 10527184] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Johns Hopkins Bayview Medical Center; Baltimore, MD 21044 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoQuality Indicators for Prevention and Management of Pressure Ulcers in Vulnerable Elders Barbara M. Bates-Jensen Quality Indicators for Prevention and Management of Pressure Ulcers in Vulnerable Elders Barbara M. Bates-Jensen Metrics 15 October 2002Volume 137, Issue 8Page: W2KeywordsEatingFoodMalnutritionNutrientsNutritionPressure ulcersProteinsQuality indicatorsUlcersWeight loss ePublished: 15 October 2002 Issue Published: 15 October 2002 Copyright & PermissionsCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Treating to target matrix metalloproteinase 3 normalisation together with disease activity score below 2.6 yields better effects than each alone in rheumatoid arthritis patients: T-4 Study
Authors: Yukitomo Urata, Ryoko Uesato, Dai Tanaka, Yoshihide Nakamura, Shigeru Motomura
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> To assess whether therapy to achieve both a disease activity score in 28 joints (DAS28) less than 2.6 and matrix metalloproteinase (MMP) 3 normalisation offers better outcomes than either target alone in early rheumatoid arthritis (RA) at 56 weeks: Treating to Twin Targets (T-4) Study. <h3>Methods</h3> 243 early RA patients were randomly allocated to one of four strategy groups: routine care (R group; n=62); DAS28-driven therapy (D group; n=60); MMP-3-driven therapy (M group; n=60); or both DAS28 and MMP-3-driven therapy group (twin; T group; n=61). Medication was started with sulfasalazine (1 g/day) in all intervention groups. Targets were DAS28 less than 2.6 for the D group, MMP-3 normalisation for the M group and both DAS28 less than 2.6 and MMP-3 normalisation for the T group. If the value in question did not fall below the previously measured level, medication was intensified, including methotrexate, other disease-modifying antirheumatic drugs and biological agents. Primary, secondary and outcome measures consisted of the proportions of patients showing clinical remission (DAS28 &lt;2.6), radiographic non-progression (Δmodified total Sharp score ≤0.5), normal physical function (modified health assessment questionnaire score 0), or comprehensive disease remission defined as the combination of clinical remission, radiographic non-progression and normal physical function. <h3>Results</h3> Clinical remission at 56 weeks was achieved by more patients in the T group (56%) than in the R group (p&lt;0.0005) or M group (p&lt;0.0005). <h3>Conclusions</h3> Results of the T-4 Study reveal that a twin target strategy can achieve a high clinical remission rate in early RA.