tbuckley/cabot-search huggingface dataset:
Patients with crohn's disease report high levels of fatigue during a symptomatic disease flare
Authors: C. A. Lamb, M. Price, D. E. Jones, J. C. Mansfield
Journal: Gut (2011)

<h3>Introduction</h3> The symptom of fatigue can have a major impact on quality of life and is often overlooked by physicians. Previous research has indicated a significant link between fatigue and a number of chronic inflammatory conditions including primary biliary cirrhosis and multiple sclerosis. Patients with fatigue often experience sleep disturbance and autonomic nervous system dysregulation. This patient survey aimed to investigate the perceived severity of fatigue and other non-gastrointestinal systemic symptoms during a flare of Crohn9s disease. <h3>Methods</h3> Patients with Crohn9s disease attending the Inflammatory Bowel Disease clinic were asked to complete a questionnaire scoring the severity of gastrointestinal, fatigue-related and autonomic symptoms during a flare of Crohn9s disease. As a hypothesised negative comparator they were also asked to score on urinary incontinence, not typically associated with Crohn9s disease. Score 1 = not affected by Crohn9s disease flare, Score 10 = severely affected by Crohn9s disease flare. The results are summarised in table 1. <h3>Results</h3> 17 patients (7 male and 10 female) completed the survey. The mean patient age was 32.4 years (range 19–53 years), with a mean duration of disease of 9.5 years (range 1–32 years) and a mean of 1.3 prior operative interventions (range 0–5). Seven patients (41.2%) had either a current or previous history of anti-TNF antibody use. <h3>Conclusion</h3> Predictably, patients score abdominal pain and diarrhoea as severely affected by a flare of Crohn9s disease. Interestingly fatigue and sleep disturbance were also perceived by patients to be highly affected by Crohn9s disease activity. Interventions in Crohn9s disease are often designed to impact on symptoms of abdominal pain and diarrhoea. Development of strategies to improve non-gastrointestinal symptoms including fatigue and sleep disturbance in active Crohn9s disease may lead to a positive effect on quality of life. This data supports further investigation into the prevalence, biological causes and consequences of fatigue in Crohn9s disease.
Kidney transplantation in Fabry's disease.
Authors: F R Buhler, G Thiel, U C Dubach, F Enderlin, F Gloor, H Tholen
Journal: BMJ (1973)

The right abducens nerve palsy gradually improved.Six weeks after discharge lateral movement of the right eye was apparently full but the diplopia persisted and he complained of blurring in the left eye.Prednisolone was then given, but a week later vision in the right eye became blurred.The left carotid and the left radial pulses were absent and the right carotid pulse was weak.A short, soft systolic bruit was audible over the right carotid artery.Visual impairment was believed to be due to retinal ischaemia.Three months after discharge the patient still had headache and intermittent blurring of vision.The left auriculotemporal arterial pulsation was absent.Nicotinic acid added to the treatment gave no benefit.Four months after dischage he developed another crop of papulonecrotic eruptions over the back, buttocks, arms, legs, and face.The headache was intense and there was polyarthralgia involving the wrists, ankles, and knees.These symptoms persisted for over a month despite prednisolone in doses of up to 60 mg/day.Prednisolone was stopped and cyclophosphamide by mouth 150 mg/day gradually reducing to 100 mg/day was given instead.The headache became less frequent and less severe.Aortography nine months later showed the state of the extra- cranial cerebral vessels to be unchanged.
Standard forward-viewing colonoscopy versus full-spectrum endoscopy: an international, multicentre, randomised, tandem colonoscopy trial
Authors: Ian M Gralnek, Peter D Siersema, Zamir Halpern, Ori Segol, Alaa Melhem, Alain Suissa, Erwin Santo, Alan Sloyer, Jay Fenster, Leon M G Moons, Vincent K Dik, Ralph B D'Agostino, Douglas K Rex
Journal: The Lancet Oncology (2014)
Total Anomalous Pulmonary Venous Drainage
Authors: ERIC D. SILOVE, DOUGLAS M. BEHRENDT, EOIN ABERDEEN, RICHARD E. BONHAM-CARTER
Journal: Circulation (1972)

The spontaneous functional closure of the interatrial communication in total anomalous pulmonary venous drainage (TAPVD) subsequent to surgical correction of the TAPVD in infants is reported. Three cases are documented with descriptions of clinical features, cardiac catheterization data, thermodilution curves, and angiography. This evidence suggests that it might be unnecessary in infants to close the interatrial communication at the time of correction of the TAPVD. It also suggests that balloon atrial septostomy may sometimes be unwise before the first-stage correction.
An increase of C-reactive protein is associated with enhanced activation of endogenous fibrinolysis at baseline but an impaired endothelial fibrinolytic response after venous occlusion
Authors: Walter Stefan Speidl, Andrea Zeiner, Mariam Nikfardjam, Alexander Geppert, Nelli Jordanova, Alexander Niessner, Gerlinde Zorn, Gerald Maurer, Wolfgang Schreiber, Johann Wojta, Kurt Huber
Journal: Journal of the American College of Cardiology (2004)
Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection
Authors: Sjoerd Repping, Helen Skaletsky, Laura Brown, Saskia K M van Daalen, Cindy M Korver, Tatyana Pyntikova, Tomoko Kuroda-Kawaguchi, Jan W A de Vries, Robert D Oates, Sherman Silber, Fulco van der Veen, David C Page, Steve Rozen
Journal: Nature Genetics (2003)
Book Review Luckiest Man: The Life and Death of Lou Gehrig By Jonathan Eig. 420 pp., illustrated. New York, Simon &amp; Schuster, 2005. $26. 0-7432-4591-1 Lou Gehrig: A Biography (Baseball's All-Time Greatest Hitters.) By William C. Kashatus. 148 pp., illustrated. Westport, Conn., Greenwood Press, 2004. $29.95. 0-313-32866-8
Authors: Lewis P. Rowland
Journal: New England Journal of Medicine (2005)
Clonazepam: A New Anticonvulsant
Authors: Hugh H. Hussey
Journal: JAMA (1976)

This editorial is abstracted in large part from an article by Browne that soon will be published in<i>Archives of Neurology</i>. The editorial is intended to alert physicians to the article and to bring their attention to the recent approval of clonazepam (Clonopin) by the Food and Drug Administration (FDA) for marketing in the United States. Clonazepam is a benzodiazepine anticonvulsant structurally related to chlordiazepoxide hydrochloride (Librium) and diazepam (Valium). Browne's article reviews in some detail the drug's effects on the electroencephalogram, and, more importantly, presents the facts known from what has been published about clonazepam. The drug is rapidly absorbed by the oral route and appears to pass quickly from blood to brain. Preliminary results indicate a biological half-life of 22 to 32 hours, and the therapeutic serum concentration is 5 to 50 ng/ml. Major side effects of the drug are drowsiness, ataxia, and behavioral changes. They tend to
Genome-Wide Activity-Dependent MeCP2 Phosphorylation Regulates Nervous System Development and Function
Authors: Sonia Cohen, Harrison W. Gabel, Martin Hemberg, Ashley N. Hutchinson, L. Amanda Sadacca, Daniel H. Ebert, David A. Harmin, Rachel S. Greenberg, Vanessa K. Verdine, Zhaolan Zhou, William C. Wetsel, Anne E. West, Michael E. Greenberg
Journal: Neuron (2011)
The Oriented Emergence of Axons from Retinal Ganglion Cells Is Directed by Laminin Contact In Vivo
Authors: Owen Randlett, Lucia Poggi, Flavio R. Zolessi, William A. Harris
Journal: Neuron (2011)

How the site of axon emergence is specified during neural development is not understood. Previous studies disagree on the relative importance of intrinsic and extrinsic mechanisms. The axons of retinal ganglion cells (RGCs) emerge basally in vivo, yet because RGCs develop from polarized neuroepithelial cells within a polarized environment, disentangling intrinsic and extrinsic influences is a challenge. We use time-lapse imaging to demonstrate that Laminin acting directly on RGCs is necessary and sufficient to orient axon emergence in vivo. Laminin contact with the basal processes of newborn RGCs prevents the cells from entering a stochastic Stage 2 phase, directs the rapid accumulation of the early axonal marker Kif5c560-YFP, and leads to the formation of axonal growth cones. These results suggest that contact-mediated cues may be critical for the site of axon emergence and account for the differences in cellular behavior observed in vitro and in vivo.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI3MWNjY2JhZTFjMmMxZWIyZTU1NDlmNmY4MzU5MjJjYyIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjcyMzUyMjgwfQ.soGq8o9QwHunWKPokVBaGbO4aiL2IdH8KCPedCELesfuUo2DWXLEkTdwJ5LCOaUJtsyEVEtMZ14kz_L3vot_1TVggok4Q8AiTG8VhsaHF-4ZAvmpdG0eTNF77PZiVBTRq1hcgtmtg8JMbIvuTtPopBtfqNnbAsmy4OwM6jvhiqbWRCxtMcWbvzjMLlXNKhfBfLm68NFUyfDwHgyOitBf6iqL63kAiw6Pw83Ag4zp12r725lggIhQ6_AtUGT8E1-fyYzI1dKUH-URQQCCiUhu68JXcSWsa0NlTxxbn29NwBg8nYNHDMDJYhyEmwyxTiC1xkNz1QJnLC51VkVYJEUahw(mp4, (15.99 MB) Download video
Great Cases in Psychoanalysis
Authors: Alfred B. Flarsheim
Journal: JAMA (1974)

The strength and weakness of this book lies in the heterogeneity of the articles it contains. Dr. Greenwald's objective is to portray the history of the development of psychoanalysis through the presentation of representative case histories by famous authors. "For the professional therapist or student, whether he be psychiatrist, psychologist, or social worker, these cases will illustrate the therapeutic methods employed by the masters in our field." Exposure to the heterogeneous collection of case histories might expose the reader to points of view other than those with which he may be familiar. Theories that differed on personality development and structure, and on the origin and rational treatment of emotional disorder divided psychoanalysis into various schools in the early part of the century. Many of the case histories in this book were originally reported to support the theoretical position of proponents of one or another of the schools. A single report
Loss of leucocyte common antigen (CD45) on atypical lymphocytes in the localized but not disseminated type of Pagetoid reticulosis
Authors: W. STERRY, A. HAUSCHILD
Journal: British Journal of Dermatology (1991)

Atypical intraepidermal T cells in Pagetoid reticulosis did not express CD45RO, the low molecular isoform of CD45. These cells did express other CD45 isoforms in the disseminated aggressive variant (Ketron‐Goodman type). The complete CD45 family was lost from the cell surface in the henign localized variant (Woringer‐Kolopp type). Because the presence of CD4S is crucial for the function of the lymphocyte‐specific tyrosine kinase p56lck, which is associated with lymphocyte growth and transformation, this may be the molecular basis for the non‐aggressive nature of this clonal T‐cell proliferation.
The Association Among Autonomic Nervous System Function, Incident Diabetes, and Intervention Arm in the Diabetes Prevention Program
Authors: Mercedes R. Carnethon, Ronald J. Prineas, Marinella Temprosa, Zhu-Ming Zhang, Gabriel Uwaifo, Mark E. Molitch
Journal: Diabetes Care (2006)

Autonomic nervous system dysfunction, a correlate of obesity and poor cardiorespiratory fitness, is associated with the development of diabetes. We tested whether estimates of autonomic nervous system function improved in the intensive lifestyle versus metformin or placebo arms of the Diabetes Prevention Program (DPP) and whether baseline or a change in autonomic nervous system function was associated with the development of diabetes over 3.2 years.In 2,980 DPP participants, 12-lead electrocardiograms were measured at baseline and annually. Heart rate, heart rate variability (HRV), and QT duration were used to estimate fitness and autonomic nervous system function.In the lifestyle arm, heart rate and QT indexes decreased, and HRV increased over time. The magnitude of decline in heart rate and QT duration was substantially smaller in the other arms, whereas HRV did not increase. Baseline heart rate was the only index significantly (P < 0.05) associated with incident diabetes after adjustment for demographics and weight change (hazard ratio for lifestyle and metformin arms = 1.19 and 1.17 per 10.6 beats/min, respectively). Decreases in heart rate and QT indexes and increases in HRV over time were associated with a lower risk of developing diabetes. The protective association between decreased heart rate and incident diabetes in the lifestyle arm remained significant after accounting for change in weight and physical activity.Indexes that reflect autonomic function and fitness improved (i.e., heart rate decreased and HRV increased) in the lifestyle modification arm of the DPP. Improvements in these indexes are inversely associated with the development of diabetes independent of weight change.
A potential role for hydrocortisone in the positive regulation of IL-15–activated NK-cell proliferation and survival
Authors: Sonia A. Perez, Louisa G. Mahaira, Fillio J. Demirtzoglou, Panagiota A. Sotiropoulou, Panayotis Ioannidis, Eleni G. Iliopoulou, Angelos D. Gritzapis, Nectaria N. Sotiriadou, Constantin N. Baxevanis, Michael Papamichail
Journal: Blood (2005)
Morbidity and Mortality Associated With Nosocomial Transmission of Oseltamivir- Resistant Influenza A(H1N1) Virus
Authors: Jairo Gooskens
Journal: JAMA (2009)

The sudden emergence and rapid spread of oseltamivir-resistant influenza A(H1N1) viruses with neuraminidase (NA) gene H274Y amino acid substitution is the hallmark of global seasonal influenza since January 2008. Viruses carrying this mutation are widely presumed to exhibit attenuated pathogenicity, compromised transmission, and reduced lethality.To investigate nosocomial viral transmission in a cluster of patients with influenza A(H1N1) virus infection.Descriptive outbreak investigation of 2 hematopoietic stem cell transplant recipients and an elderly patient who developed hospital-acquired influenza A virus infection following exposure to an index patient with community-acquired H274Y-mutated influenza A(H1N1) virus infection in a medical ward at a Dutch university hospital in February 2008. The investigation included a review of the medical records, influenza virus polymerase chain reaction and culture, phenotypic oseltamivir and zanamivir susceptibility determination, and hemagglutinin chain 1 (HA(1)) gene and NA gene sequence analysis.Phylogenetic relationship of patient cluster influenza A(H1N1) viruses and other 2007-2008 seasonal influenza A(H1N1) viruses.Viral HA(1) and NA gene sequence analysis from the 4 patients revealed indistinguishable nucleotide sequences and phylogenetic clustering of H274Y-mutated, oseltamivir-resistant influenza A(H1N1) virus, confirming nosocomial transmission. Influenza virus pneumonia (3 patients) and attributable mortality (2 patients) during active infection was observed in patients with lymphocytopenia at onset.Seasonal oseltamivir-resistant influenza A(H1N1) viruses with NA gene H274Y mutation are transmitted and retain significant pathogenicity and lethality in high-risk patients.
The effect of clobetasone butyrate and other topical steriods on skin thickness of the domestic pig
Authors: GEORGE D. WINTER, LYN WILSON
Journal: British Journal of Dermatology (1976)

A new glucocorticoid, clobetasone butyrate, has been shown in patients to have good topical anti‐inflammatory activity and a minimal effect on hypothalamic–pituitary–adrenal function. Among a group of topically active corticosteroids, compared in a controlled study in the domestic pig, clobetasone butyrate is shown to cause less epidermal thinning than any of the others except only 1% hydrocortisone. This evidence of a lesser atrophogenic effect may indicate further dissociation of unwanted from wanted properties in clobetasone butyrate.
SOME PHYSICAL SIGNS IN INFANTS AND CHILDREN NOT SUFFICIENTLY EMPHASIZED.
Authors: SAMUEL McC. HAMILL
Journal: JAMA (1905)

Several years ago we began a systematic examination of the heart and lungs of infants and children in our out-patient services in the Howard and Polyclinic Hospitals, with a view to confirming certain observations which we had made, some of which had not been sufficiently emphasized in the literature, and others of which were at variance with the results reported. <h3>CONDITIONS IN THE LUNGS.</h3> Our observations relate exclusively to normal or functional conditions. In relation to the lungs, they are three in number: First, an area of impaired resonance under the left clavicle. Second, the area of transmission of the bronchial type of breathing as heard over the root of the lung. Third, the influence of position on the percussion note in infants. An Area of Impaired Resonance Under the Left Clavicle.—This sign was first noted accidentally by one of us in a child convalescent from bronchopneumonia. In this instance, owing to the absence of all other signs
Inhibiting Tankyrases Sensitizes KRAS-Mutant Cancer Cells to MEK Inhibitors via FGFR2 Feedback Signaling
Authors: Marie Schoumacher, Kristen E. Hurov, Joseph Lehár, Yan Yan-Neale, Yuji Mishina, Dmitriy Sonkin, Joshua M. Korn, Daisy Flemming, Michael D. Jones, Brandon Antonakos, Vesselina G. Cooke, Janine Steiger, Jebediah Ledell, Mark D. Stump, William R. Sellers, Nika N. Danial, Wenlin Shao
Journal: Cancer Research (2014)

Tankyrases (TNKS) play roles in Wnt signaling, telomere homeostasis, and mitosis, offering attractive targets for anticancer treatment. Using unbiased combination screening in a large panel of cancer cell lines, we have identified a strong synergy between TNKS and MEK inhibitors (MEKi) in KRAS-mutant cancer cells. Our study uncovers a novel function of TNKS in the relief of a feedback loop induced by MEK inhibition on FGFR2 signaling pathway. Moreover, dual inhibition of TNKS and MEK leads to more robust apoptosis and antitumor activity both in vitro and in vivo than effects observed by previously reported MEKi combinations. Altogether, our results show how a novel combination of TNKS and MEK inhibitors can be highly effective in targeting KRAS-mutant cancers by suppressing a newly discovered resistance mechanism.
Abstract 3150: Epithelial mesenchymal transition (EMT) and IGF-2 expression as determinants of sensitivity to the dual IGF-1R/IR inhibitor OSI-906 in hepatocellular carcinoma
Authors: Hui Zhao, Vidhi Desai, Jian Wang, David Epstein, Mark Miglarese, Elizabeth Rizzo
Journal: Cancer Research (2011)

Abstract Hepatocellular carcinoma (HCC) affects over 600,000 patients worldwide and is the third leading cause of cancer-related death. Understanding signaling pathways that may be targeted for the treatment of HCC has been a major goal. A growing body of data indicates that inhibiting the type 1 insulin-like growth factor receptor (IGF-1R) might be an especially effective treatment strategy for HCC. Increased expression of IGF-2 as well as phospho-IGF-1R is observed in a subset of HCC tumors, and blockade of IGF-1R results in inhibition of proliferation for preclinical HCC cell models. OSI-906 is a small molecule dual IGF-1R/IR inhibitor currently in advanced clinical development. In this report we sought to determine the effect of OSI-906 on proliferation for a panel of 21 HCC tumor cell lines as well as to investigate molecular determinants of responsiveness to OSI-906. A subset of HCC tumor cell lines was sensitive to OSI-906 in proliferation assays. Sensitivity to OSI-906 correlated with epithelial-mesenchymal-transition (EMT) status where the majority of epithelial HCC cell lines, but none of mesenchymal cell lines, were sensitive to OSI-906. We also found differential expression of IGF axis components, including IGF-2, in epithelial and mesenchymal tumor cell lines, which correlated with sensitivity to OSI-906. Induction of EMT upon treatment with TGFβ reduced sensitivity to OSI-906. Within a human HCC tumor database, epithelial tumors were identified to be enriched in one subgroup with higher IGF2 expression. We have previously shown that both IGF-1R and IR can maintain tumor growth in a mouse mammary tumor model, and co-inhibition of both receptors is required for maximal inhibition of tumor growth. Herein, we find that OSI-906 sensitive HCC tumor cell lines expressed both phosphorylated IGF-1R and IR, and dual targeting of both receptors appears to be important for maximal inhibition of proliferation. Treatment of HuH-7 tumor cells with an IGF-1R neutralizing antibody was associated with increased IR signaling. In contrast OSI-906 fully inhibited both phosphorylated IR and IGF-1R and achieved greater inhibition of the IRS-AKT pathway compared to the IGF-1R antibody. Collectively, these data support the concept for dual IGF-1R/IR targeting HCC, where EMT status and expression of IGF-2 could be utilized to identify those patients most likely to benefit from treatment. A phase 2 clinical study evaluating OSI-906 in HCC is currently ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3150. doi:10.1158/1538-7445.AM2011-3150
R &amp; D in Health Care
Authors: F.J. Ingelfinger
Journal: New England Journal of Medicine (1972)

Some wag who writes for the Annals of Internal Medicine doesn't like the initials COLD,1 but he would hardly dare lampoon R & D. These letters, with their connecting ampersand, are of superior essence, far loftier than the mere words research and development. R & D is the acronymic banner held on high by the many who belittle the scientific idea unless it can be exploited. Thus, to most of us, R & D connotes research designed to create something that is useful in a big way — i.e., a product, process, or system that will either protect us or . . .
Drug-Induced Vessel Remodeling in Bone Metastases as Assessed by Dynamic Contrast Enhanced Magnetic Resonance Imaging and Vessel Size Imaging: A Longitudinal<i>In vivo</i>Study
Authors: Tobias Bäuerle, Maximilian Merz, Dorde Komljenovic, Stefan Zwick, Wolfhard Semmler
Journal: Clinical Cancer Research (2010)

The aim of this study was to assess the antiangiogenic treatment effects of zoledronic acid (ZA) and sunitinib malate (SM) noninvasively in experimental breast cancer bone metastases by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and vessel size imaging.Nude rats bearing bone metastases after inoculation of MDA-MB-231 breast cancer cells were treated with ZA (40 microg/kg weekly; n = 8 rats), SM (20 mg/kg daily; n = 8 rats), or their combination (ZA and SM; n = 8 rats) and compared with sham-treated controls (n = 10 rats). Vascular changes in bone metastases were longitudinally imaged in vivo using DCE-MRI [amplitude (A) and exchange rate coefficient (k(ep))] and vessel size imaging [blood volume (BV) and vessel size index (VI)]. In addition, antiresorptive and antitumor changes were assessed in these lesions by flat-panel volumetric computed tomography as well as morphologic MRI and diffusion-weighted imaging.In bone metastases, significant changes in A, k(ep), BV, and VI in accordance with decreased blood volume and vessel permeability as well as with increased mean vessel diameters were observed after application of ZA and SM as compared with controls. In this longitudinal study, antiangiogenic changes preceded the inhibition of osteolysis and antitumor effects after treatment.These results indicate vessel remodeling in breast cancer bone metastases on ZA and SM treatment and implicate substantial effects on imaging and treatment of malignant bone lesions.