tbuckley/cabot-search huggingface dataset:
Provision of Palliative Care and Pain Management Services for Oncology Patients
Authors: Paolo Marchetti, Raymond Voltz, Carmen Rubio, Didier Mayeur, Andreas Kopf
Journal: Journal of the National Comprehensive Cancer Network (2013)

Early initiation of palliative care to address pain and other symptoms offers the potential to improve quality of life for patients with cancer. The approaches to implementing and delivering palliative care and pain management services vary depending on patient needs, available resources, provider training, and clinical setting. This article describes the experiences in developing programs in which the need for early palliative care or pain management services for patients with cancer was recognized. In each case, collaborative efforts, careful planning, administrative support, and ample time were needed to implement such services. To tailor services based on the available resources, different approaches were taken, including structuring of services within oncology units; creation of an integrated partnership between oncology and palliative care departments; establishment of a multidisciplinary comprehensive service; and incorporation of nurse-based pain services to address acute, chronic, and cancer pain. These examples offer insights into how to optimize delivery of services in a variety of settings with varying resources.
Short contact dithranol therapy—twice daily and high concentration regimes
Authors: B.N. Statham, N.R. Rowell
Journal: British Journal of Dermatology (1985)

Journal Article Short contact dithranol therapy—twice daily and high concentration regimes Get access B.N. Statham, B.N. Statham Department of Dermatology, The General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, U.K. Search for other works by this author on: Oxford Academic Google Scholar N.R. Rowell N.R. Rowell Department of Dermatology, The General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue 2, 1 August 1985, Pages 245–246, https://doi.org/10.1111/j.1365-2133.1985.tb02071.x Published: 01 August 1985
Combined Tumor Suppressor Defects Characterize Clinically Defined Aggressive Variant Prostate Cancers
Authors: Ana M. Aparicio, Li Shen, Elsa Li Ning Tapia, Jing-Fang Lu, Hsiang-Chun Chen, Jiexin Zhang, Guanglin Wu, Xuemei Wang, Patricia Troncoso, Paul Corn, Timothy C. Thompson, Bradley Broom, Keith Baggerly, Sankar N. Maity, Christopher J. Logothetis
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Morphologically heterogeneous prostate cancers that behave clinically like small-cell prostate cancers (SCPC) share their chemotherapy responsiveness. We asked whether these clinically defined, morphologically diverse, “aggressive variant prostate cancer (AVPC)” also share molecular features with SCPC. Experimental Design: Fifty-nine prostate cancer samples from 40 clinical trial participants meeting AVPC criteria, and 8 patient-tumor derived xenografts (PDX) from 6 of them, were stained for markers aberrantly expressed in SCPC. DNA from 36 and 8 PDX was analyzed by Oncoscan for copy number gains (CNG) and losses (CNL). We used the AVPC PDX to expand observations and referenced publicly available datasets to arrive at a candidate molecular signature for the AVPC. Results: Irrespective of morphology, Ki67 and Tp53 stained ≥10% cells in 80% and 41% of samples, respectively. RB1 stained &amp;lt;10% cells in 61% of samples and AR in 36%. MYC (surrogate for 8q) CNG and RB1 CNL showed in 54% of 44 samples each and PTEN CNL in 48%. All but 1 of 8 PDX bore Tp53 missense mutations. RB1 CNL was the strongest discriminator between unselected castration-resistant prostate cancer (CRPC) and the AVPC. Combined alterations in RB1, Tp53, and/or PTEN were more frequent in the AVPC than in unselected CRPC and in The Cancer Genome Atlas samples. Conclusions: Clinically defined AVPC share molecular features with SCPC and are characterized by combined alterations in RB1, Tp53, and/or PTEN. Clin Cancer Res; 22(6); 1520–30. ©2015 AACR.
VEGF-A Stimulates ADAM17-Dependent Shedding of VEGFR2 and Crosstalk Between VEGFR2 and ERK Signaling
Authors: Steven Swendeman, Karen Mendelson, Gisela Weskamp, Keisuke Horiuchi, Urban Deutsch, Peggy Scherle, Andrea Hooper, Shahin Rafii, Carl P. Blobel
Journal: Circulation Research (2008)

Vascular endothelial growth factor (VEGF)-A and the VEGF receptors are critical for regulating angiogenesis during development and homeostasis and in pathological conditions, such as cancer and proliferative retinopathies. Most effects of VEGF-A are mediated by the VEGFR2 and its coreceptor, neuropilin (NRP)-1. Here, we show that VEGFR2 is shed from cells by the metalloprotease disintegrin ADAM17, whereas NRP-1 is released by ADAM10. VEGF-A enhances VEGFR2 shedding by ADAM17 but not shedding of NRP-1 by ADAM10. VEGF-A activates ADAM17 via the extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase pathways, thereby also triggering shedding of other ADAM17 substrates, including tumor necrosis factor alpha, transforming growth factor alpha, heparin-binding epidermal growth factor-like growth factor, and Tie-2. Interestingly, an ADAM17-selective inhibitor shortens the duration of VEGF-A-stimulated ERK phosphorylation in human umbilical vein endothelial cells, providing evidence for an ADAM17-dependent crosstalk between the VEGFR2 and ERK signaling. Targeting the sheddases of VEGFR2 or NRP-1 might offer new opportunities to modulate VEGF-A signaling, an already-established target for treatment of pathological neovascularization.
The collagenase of Entamoeba histolytica.
Authors: M L MuÑoz, J Calderón, M Rojkind
Journal: The Journal of Experimental Medicine (1982)

The present work was designed to investigate the capacity of trophozoites of Entamoeba histolytica to adhere to and digest human collagen types I and III in vitro. The time-course of binding of ameba to both human collagen types I and III was similar. However, the kinetics of detachment were different for each collagen type. Trophozoites of E. histolytica cultured on heat-reconstituted type I collagen gels produced a well-defined area of lysis. Quantitative studies using 14C-labeled collagen revealed that after 24 h of incubation, Entamoeba digested three and a half times more type I than type III collagen, thus suggesting the presence of a collagenase with higher specificity for type I collagen. This activity was optimum with trophozoites harvested after 42 h in culture (1.5 X 10(5) trophozoites/ml). The digestion of type I collagen was a function of the number of trophozoites, and was inhibited by EDTA, L-cysteine, and serum, but not by soybean trypsin inhibitor, phenylmethanesulfonyl fluoride, or N-ethylmaleimide (NEM). Electrophoretic analysis of the type I collagen fragments revealed three main classes of polypeptides of 75,000, 50,000, and 25,000 daltons. Subsequent proteolysis of these collagen fragments was probably carried out by other proteases derived from trophozoites. This activity was inhibited with 10 mM NEM. Collagenase activity appeared to be located at the plasma membrane and direct contact of the ameba with the substrate is required for collagen digestion. The results suggest that collagenase activity of E. histolytica may play an important role in tissue invasion.
Annular PIP3 accumulation controls actin architecture and modulates cytotoxicity at the immunological synapse
Authors: Audrey Le Floc’h, Yoshihiko Tanaka, Niels S. Bantilan, Guillaume Voisinne, Grégoire Altan-Bonnet, Yoshinori Fukui, Morgan Huse
Journal: The Journal of Experimental Medicine (2013)

The immunological synapse formed by a T lymphocyte on the surface of a target cell contains a peripheral ring of filamentous actin (F-actin) that promotes adhesion and facilitates the directional secretion of cytokines and cytolytic factors. We show that growth and maintenance of this F-actin ring is dictated by the annular accumulation of phosphatidylinositol trisphosphate (PIP3) in the synaptic membrane. PIP3 functions in this context by recruiting the exchange factor Dock2 to the periphery of the synapse, where it drives actin polymerization through the Rho-family GTPase Rac. We also show that synaptic PIP3 is generated by class IA phosphoinositide 3-kinases that associate with T cell receptor microclusters and are activated by the GTPase Ras. Perturbations that inhibit or promote PIP3-dependent F-actin remodeling dramatically affect T cell cytotoxicity, demonstrating the functional importance of this pathway. These results reveal how T cells use lipid-based signaling to control synaptic architecture and modulate effector responses.
PTU-191 An Audit of Testing for Coeliac Disease – are Patients being Investigated Appropriately
Authors: F Leet, S G J Williams, P Bradley, J Butcher
Journal: Gut (2013)

<h3>Introduction</h3> Coeliac disease is a common condition, affecting up to 1 in 100 individuals in the UK. The average age of diagnosis is now over the age of 40 with 20% of newly diagnosed cases being over 60. In those over 60, the delay in diagnosis may be particularly long. The purpose of this audit was to evaluate the appropriate use of tissue transglutaminase (tTG) and duodenal biopsy in the diagnosis of celiac disease in a cohort of DGH patients analysed retrospectively. <h3>Methods</h3> 114 consecutive patients with a reactive anti tTG &gt; 3 were identified from the Ipswich Hospital Pathology laboratory database between January and June 2011. Those with an anti tTG titre &gt; 7 have positive results in our laboratory. The cohort was divided into positive and negative groups. The duodenal biopsy (DDB) results of the positive group were documented. If the patient had not had a DDB the notes were reviewed or relevant clinician contacted. The negative group’s IgA level was recorded to determine the likelihood of a false negative result. <h3>Results</h3> Of 114 patients identified from the database with an anti tTG ≥ 3, 69 were female and 45 male. There were 63 positives and 51 negatives. In the positive serology group, 48 patients were already known to have coeliac disease, 4 had a negative biopsy and 11 have not had a DDB. Of these 11 patients only 2 had been referred to gastroenterology, 3 had been given a diagnosis of coeliac disease without a DDB and 6 had not been informed of their results. In the negative serology group 19 (16 adult and 3 children) were known to have coeliac disease and were on a gluten free diet. Of the remaining 27 adult patients, only 7 (26%) had had their IgA checked, while only 3 of 5 children had had their IgA tested. 2 of these 3 were IgA deficient. The other 2 had not been tested. None of the IgA deficient cohort had undergone a duodenal biopsy to exclude a false negative result. <h3>Conclusion</h3> The results of this audit demonstrate inconsistent application of the national guidelines(1) for the diagnosis of celiac disease. Of greatest concern was the cohort of adult patients who were labelled as having coeliac disease without a confirmatory biopsy. There was also a significant cohort of IgA deficient patients in the negative group who may have had celiac disease. There is clearly a need for further on-going education of all healthcare professionals regarding appropriate testing to diagnose coeliac disease to ensure appropriate treatment and prior to labelling an individual with a lifelong diagnosis. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Ciclitira P J, Dewar D H, McLaughlin S D, Sanders DS (2010) The Management of Adults with Coeliac Disease, British Society of Gastroenterology
Skiing injuries: the increasing workload.
Authors: R L Williams, D I Sweetnam, M Stanislas
Journal: British Journal of Sports Medicine (1995)

All skiing injuries presenting to a fracture clinic during the period December 1992 to April 1993 were studied. Fifty five patients with 59 injuries were treated during this period. Thirty (54.5%) were male and 25 (45.5%) female. The mean age was 34 years (range 9-61). The anatomical distribution of injuries seen corresponded very closely with those seen in much larger studies abroad. There were 35 upper limb injuries (59.3%), 22 lower limb injuries (37.3%), with only two spine and trunk injuries (3.4%). While only two patients underwent surgery abroad, a further 12 needed surgical intervention on return, requiring a total stay of 61 'inpatient days'. The bulk of the workload was, however, on an outpatient basis, with a total of 172 appointments. Many advances have been made towards improving the safety of skiing. However with skiing becoming increasingly popular we can expect an increasing workload and cost associated with such injuries.
Conditional Expression of a Dominant-Negative c-Myb in Vascular Smooth Muscle Cells Inhibits Arterial Remodeling After Injury
Authors: Xiao-Mang You, Imran N. Mungrue, Waseem Kalair, Talat Afroze, Bheeshma Ravi, Al Muktafi Sadi, Robert Gros, Mansoor Husain
Journal: Circulation Research (2003)

Inhibiting activity of the c-Myb transcription factor attenuates G1 to S phase cell cycle transitions in vascular smooth muscle cells (SMCs) in vitro. To determine the effects of arterial SMC-specific expression of a dominant-negative c-Myb molecule (Myb-Engrailed) on vascular remodeling in vivo, we performed carotid artery wire-denudation in 2 independent lines of binary transgenic mice with SM22alpha promoter-defined Doxycycline-suppressible expression of Myb-Engrailed. Adult mice with arterial SMC-specific expression of Myb-Engrailed were overtly normal in appearance and did not display any changes in cardiovascular structure or physiology. However, bromodeoxyuridine-defined arterial SMC proliferation, neointima formation, medial hyperplasia, and arterial remodeling were markedly decreased in mice expressing arterial SMC-restricted Myb-Engrailed after arterial injury. These data suggest that c-Myb activity in arterial SMCs is not essential for arterial structure or function during development, but is involved in the proliferation of arterial SMCs as occurs in vascular pathology, and that the expression of a dominant-negative c-Myb can dramatically reduce adverse arterial remodeling in an in vivo model of restenosis. As such, this model represents a novel tissue-specific strategy for the potential gene therapy of diseases characterized by arterial SMC proliferation.
Recent Achievements in Studies on Thyroid Hormone-Binding Proteins*
Authors: LUIGI BARTALENA
Journal: Endocrine Reviews (1990)

THYROID hormones circulate in the bloodstream mostly bound to a set of plasma proteins which widely differ in their concentration and affinity for the hormones (1). The three major transport proteins are T4-binding globulin (TBG), T4-binding prealbumin (TBPA), and albumin. TBG carries about 70% of T4 in the circulation and, therefore, represents physiologically the most important T4-binding protein (1). TBPA has been named transthyretin (TTR) for the role it also plays in the transport of the retinol-binding protein. Less important proteins with thyroid hormone-binding activity are lipoproteins (2–4): also the 27 K protein identified in normal human plasma and synthesized by human liver cell in culture (5–7) would appear to be apolipoprotein A-l (8). In the last few years, several papers have provided more precise information concerning TBG biosynthesis, the effects of its interaction with the carbohydrate moieties and with the ligand (T4), factors controlling TBG synthesis, TBG gene structure, and a number of genetic variants of the molecule. The present paper is mainly devoted to a review of these recent achievements, with the exception of inherited TBG abnormalities, which are extensively covered in a previous review by Refetoff (9). Additional sections deal with recent findings providing new information on the other major thyroid hormonebinding proteins, TTR and albumin.
Depression as a Risk Factor for Poor Prognosis Among Patients With Acute Coronary Syndrome: Systematic Review and Recommendations
Authors: Judith H. Lichtman, Erika S. Froelicher, James A. Blumenthal, Robert M. Carney, Lynn V. Doering, Nancy Frasure-Smith, Kenneth E. Freedland, Allan S. Jaffe, Erica C. Leifheit-Limson, David S. Sheps, Viola Vaccarino, Lawson Wulsin
Journal: Circulation (2014)

Background— Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute coronary syndrome by the American Heart Association and other health organizations. The purpose of this scientific statement is to review available evidence and recommend whether depression should be elevated to the status of a risk factor for patients with acute coronary syndrome. Methods and Results— Writing group members were approved by the American Heart Association’s Scientific Statement and Manuscript Oversight Committees. A systematic literature review on depression and adverse medical outcomes after acute coronary syndrome was conducted that included all-cause mortality, cardiac mortality, and composite outcomes for mortality and nonfatal events. The review assessed the strength, consistency, independence, and generalizability of the published studies. A total of 53 individual studies (32 reported on associations with all-cause mortality, 12 on cardiac mortality, and 22 on composite outcomes) and 4 meta-analyses met inclusion criteria. There was heterogeneity across studies in terms of the demographic composition of study samples, definition and measurement of depression, length of follow-up, and covariates included in the multivariable models. Despite limitations in some individual studies, our review identified generally consistent associations between depression and adverse outcomes. Conclusions— Despite the heterogeneity of published studies included in this review, the preponderance of evidence supports the recommendation that the American Heart Association should elevate depression to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome.
The Diagnostic Challenge of Nonburrowing Mite Bites
Authors: E. Dorinda Shelley
Journal: JAMA (1984)

Endemic pruritus in a family of four proved to be caused by the "bite and run" habits of the<i>Cheyletiella yasguri</i>mites that lived on the family dog. The mystery was solved only after the 6-year-old daughter experienced an explosive attack of pruritic papules after taking a nap in the dog's sleeping box. Virtually invisible ectoparasites remain a common cause of endemic pruritus within families. Since these patients show no acarologic, clinical, or laboratory evidence for the cause of their itch, a good rule remains,<i>cherchez le chien</i>. (<i>JAMA</i>1984;251:2690-2691)
<i>Annals</i> Graphic Medicine - Doctor and Patient
Authors: Amrita Mukhopadhyay
Journal: Annals of Internal Medicine (2015)

Web Exclusives1 September 2015Annals Graphic Medicine - Doctor and PatientFREEAmrita Mukhopadhyay, BSAmrita Mukhopadhyay, BSAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G15-0001 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Monica LalandaEM doctor at Spanish Health Service8 October 2015 Fantastic What a great image. Amazing. The vulnerability of the patient and the doctor's God like attitude that it creates. It all feels so so wrong but at the same time, so utterly real.Congratulations HyacinthSimply Hyacinth9 September 2015 Great job! Amrita, It is wonderful to see that you have kept your artistic skills alive. We are so very proud of you! I signed up to read an article that went with it, but I guess it was just the sketch. I know that you write well, perhaps a poetry on the Doctor patient relationship to go with the sketch would be fabulous! Keep it up! Author, Article, and Disclosure InformationAffiliations: Disclosures: The author has disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G15-0001.Author/Illustrator Information: Amrita Mukhopadhyay is a 4th-year medical student at The University of Chicago Pritzker School of Medicine who enjoys the fine arts along with medicine and believes that patient outreach and education can be enhanced through artwork.Corresponding Author: Amrita Mukhopadhyay, BS; e-mail, [email protected]Author Contributions: Conception and design: A. Mukhopadhyay.Drafting of the article: A. Mukhopadhyay.Final approval of the article: A. Mukhopadhyay. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 2015Volume 163, Issue 5Page: W140KeywordsConflicts of interestDisclosureHealth careMedical education ePublished: 1 September 2015 Issue Published: 1 September 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
C-Reactive Protein, but not Low-Density Lipoprotein Cholesterol Levels, Associate With Coronary Atheroma Regression and Cardiovascular Events After Maximally Intensive Statin Therapy
Authors: Rishi Puri, Steven E. Nissen, Peter Libby, Mingyuan Shao, Christie M. Ballantyne, Phillip J. Barter, M. John Chapman, Raimund Erbel, Joel S. Raichlen, Kiyoko Uno, Yu Kataoka, Stephen J. Nicholls
Journal: Circulation (2013)

Background— Baseline C-reactive protein (CRP) levels predict major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, coronary revascularization, and hospitalization for unstable angina). The association between changes in CRP levels with plaque progression and MACE in the setting of maximally intensive statin therapy is unknown. Methods and Results— The Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. The treatment groups did not differ significantly in the change from baseline of percent atheroma volume on intravascular ultrasound, CRP-modulating effects, or MACE rates, thus allowing for a (prespecified) post hoc analysis to test associations between the changes in CRP levels with coronary disease progression and MACE. Patients with nonincreasing CRP levels (n=621) had higher baseline (2.3 [1.1–4.7] versus 1.1 [0.5–1.8] mg/L; P &lt;0.001) and lower follow-up CRP levels (0.8 [0.5–1.7] versus 1.6 [0.7–4.1] mg/L; P &lt;0.001) versus those with increasing CRP levels (n=364). Multivariable analysis revealed a nonincreasing CRP level to independently associate with greater percent atheroma volume regression ( P =0.01). Although the (log) change in CRP did not associate with MACE (hazard ratio, 1.18; 95% confidence interval, 0.93–1.50; P =0.17), the (log) on-treatment CRP associated significantly with MACE (hazard ratio, 1.28; 95% confidence interval, 1.04–1.56; P =0.02). On-treatment low-density lipoprotein cholesterol levels did not correlate with MACE (hazard ratio, 1.09; 95% confidence interval, 0.88–1.35; P =0.45). Conclusions— Following 24 months of potent statin therapy, on-treatment CRP levels associated with MACE. Inflammation may be an important driver of residual cardiovascular risk in patients with coronary artery disease despite aggressive statin therapy. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique identifier: NCT000620542.