tbuckley/cabot-search huggingface dataset:
Britain needs a national cancer institute
Authors: J. Waxman, I. Gibson
Journal: BMJ (1998)

Within the past few months five potential new cures for cancer have been announced. These announcements have increased the sales of newspapers, boosted the share prices of certain biotechnology companies by 600%, and raised hopes in the hearts of the 278 000 people a year who develop cancer in England and Wales. Such pronouncements have been a constant media feature since 1980 when the Imperial Cancer Research Fund announced that it was going to spend £1m on interferon, the wonder drug of the time, for treating cancer.

You could cynically comment that such announcements represent the devious attempts of snappily dressed public relations consultants to bolster share prices and promote fund raising for cancer charities. But are they? Although there is no doubt that financial public relations consultants do attempt to manipulate the media, the cancer charities have an ever present and …
Myocardial Fibrosis and Stiffness With Hypertrophy and Heart Failure in the Spontaneously Hypertensive Rat
Authors: Chester H. Conrad, Wesley W. Brooks, John A. Hayes, Subha Sen, Kathleen G. Robinson, Oscar H. L. Bing
Journal: Circulation (1995)

Background Fibrosis is commonly found in association with cardiac hypertrophy and failure, but the relation of the connective tissue response to the development of impaired cardiac function remains unclear. We examined passive myocardial stiffness, active contractile function, and fibrosis in the spontaneously hypertensive rat (SHR), a model of chronic pressure overload in which impaired cardiac function follows a long period of stable hypertrophy. Methods and Results We studied the passive and active mechanical properties of left ventricular (LV) papillary muscles isolated from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at the ages of 12 months and 20 to 23 months. Seven of 15 SHR between 20 and 23 months of age had findings consistent with heart failure (SHR-F). In comparison to preparations from WKY rats and nonfailing SHR (SHR-NF), papillary muscles from the SHR-F group demonstrated increased passive stiffness (central segment exponential stiffness constant, k cs : SHR-F 95.6±19.8, SHR-NF 42.1±9.7, WKY rats 39.5±9.5 (mean±SD); SHR-F P &lt;.01 versus SHR-NF, WKY rats). The increase in stiffness was associated with an increase in LV collagen concentration (SHR-F 8.71±3.14, SHR-NF 5.83±1.20, WKY rats 4.78±0.70 mg hydroxyproline/g dry LV wt; SHR-F P &lt;.01 versus SHR-NF, WKY rats); an increase in interstitial fibrosis, as determined histologically (SHR-F 13.5±8.0%, SHR-NF 4.9±2.1%, WKY rats 3.6±0.8%; SHR-F P &lt;.01 versus SHR-NF, WKY rats); and impaired tension development (SHR-F 3.18±1.27, SHR-NF 4.41±1.04, WKY rats 4.64±0.85 kdyne/mm 2 ; SHR-F P &lt;.05 versus SHR-NF; P &lt;.01 versus WKY rats). Conclusions The development of heart failure in the aging SHR is associated with marked myocardial fibrosis, increased passive stiffness, and impaired contractile function relative to age-matched nonfailing SHR and nonhypertensive control animals. These data suggest that fibrosis or events underlying the connective tissue response are important in the transition from compensated hypertrophy to failure in the SHR.
Why New Psychotherapies for Posttraumatic Stress Disorder?
Authors: Ulrich Schnyder
Journal: Psychotherapy and Psychosomatics (2005)

Editorials| June 07 2005 Why New Psychotherapies for Posttraumatic Stress Disorder? Subject Area: Psychiatry and Psychology Ulrich Schnyder Ulrich Schnyder Department of Psychiatry, University Hospital, Zürich, Switzerland Search for other works by this author on: This Site PubMed Google Scholar Psychother Psychosom (2005) 74 (4): 199–201. https://doi.org/10.1159/000085142 Article history Published Online: June 07 2005 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Ulrich Schnyder; Why New Psychotherapies for Posttraumatic Stress Disorder?. Psychother Psychosom 1 June 2005; 74 (4): 199–201. https://doi.org/10.1159/000085142 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsPsychotherapy and Psychosomatics Search Advanced Search Article PDF first page preview Close Modal This content is only available via PDF. © 2005 S. Karger AG, Basel2005Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.
TRAVELLING DELEGATES OF DIVISIONS
Authors: J. H. Churchill
Journal: BMJ (1912)

Neuronal firing patterns are crucial to underpin circuit level behaviors. In cerebellar Purkinje cells (PCs), both spike rates and pauses are used for behavioral coding, but the cellular mechanisms causing code transitions remain unknown. We use a well-validated PC model to explore the coding strategy that individual PCs use to process parallel fiber (PF) inputs. We find increasing input intensity shifts PCs from linear rate-coders to burst-pause timing-coders by triggering localized dendritic spikes. We validate dendritic spike properties with experimental data, elucidate spiking mechanisms, and predict spiking thresholds with and without inhibition. Both linear and burst-pause computations use individual branches as computational units, which challenges the traditional view of PCs as linear point neurons. Dendritic spike thresholds can be regulated by voltage state, compartmentalized channel modulation, between-branch interaction and synaptic inhibition to expand the dynamic range of linear computation or burst-pause computation. In addition, co-activated PF inputs between branches can modify somatic maximum spike rates and pause durations to make them carry analogue signals. Our results provide new insights into the strategies used by individual neurons to expand their capacity of information processing. <b>SIGNIFICANCE STATEMENT</b>:Understanding how neurons process information is a fundamental question in neuroscience. Purkinje cells were traditionally regarded as linear point neurons. We used computational modeling to unveil their electrophysiological properties underlying the multiplexed coding strategy that is observed during behaviors. We demonstrate that increasing input intensity triggers localized dendritic spikes, shifting Purkinje cells from linear rate-coders to burst-pause timing-coders. Both coding strategies work at the level of individual dendritic branches. Our work suggests that Purkinje cells have the ability to implement branch-specific multiplexed coding at the cellular level, thereby increasing the capacity of cerebellar coding and learning.
Abnormal signal-averaged electrocardiograms in patients with nonischemic congestive cardiomyopathy: relationship to sustained ventricular tachyarrhythmias.
Authors: D S Poll, F E Marchlinski, R A Falcone, M E Josephson, M B Simson
Journal: Circulation (1985)

We assessed whether signal-averaged electrocardiography could identify patients with sustained ventricular arrhythmias in 41 patients with non-ischemic cardiomyopathy. Twelve of these patients presented with sustained ventricular arrhythmia and 29 patients had no history of sustained ventricular arrhythmias. The mean ejection fractions in the groups were 30 +/- 9% and 24 +/- 9%, respectively. Results were compared with signal-averaged electrocardiograms in 55 normal individuals. The filtered QRS duration was longest in patients with sustained ventricular arrhythmias (130.2 +/- 19.5 vs 105.0 +/- 13.1 msec in the group without sustained ventricular arrhythmia, p less than .001 and 95.9 +/- 9.1 in the normal group, p less than .001). The voltage in the last 40 msec of the filtered QRS was lower in the sustained ventricular arrhythmia group (11.3 +/- 9.3 microV) than the group without sustained ventricular arrhythmia (53.5 +/- 28.3 microV; p less than .001) or the normal group (53.7 +/- 25.2 microV; p less than .001). Eighty-three percent of patients in the sustained ventricular arrhythmia group had an abnormal signal-averaged electrocardiogram characterized by both a long filtered QRS duration and a late potential of low voltage level; only 2% of normal subjects and 14% of patients without sustained ventricular arrhythmias had an abnormal signal-averaged electrocardiogram. The signal-averaged electrocardiogram can identify patients with nonischemic congestive cardiomyopathy and sustained ventricular arrhythmias.
Case 38-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Lawrence M. Miller, James J. Galdabini
Journal: New England Journal of Medicine (1973)

Presentation of CaseA 75-year-old woman was admitted to the hospital because of weakness.She was well until three months previously, when she began to complain of headaches and tenderness in the temporal region. Two months before admission she was admitted to another hospital, where physical examination was negative. The urine gave a + + test for protein. The hemoglobin was 8.2 g per 100 ml, and the red cells appeared macrocytic. The creatinine was 1.8 mg, and the protein 6.3 g (the albumin 1.8 g, and the globulin 4.5 g) per 100 ml. The vitamin B12 was 36 . . .
Diagnostic Decision: Biochemical Profiles: Applications in Ambulatory Screening and Preadmission Testing of Adults
Authors: RANDALL D. CEBUL
Journal: Annals of Internal Medicine (1987)

Evidence bearing on the utility of biochemical profiles for ambulatory care screening and preadmission testing was reviewed, and recommendations were formulated. Certain biostatistical principles relevant to this analysis include the concepts of regression to the mean, the meaning of biochemical "normality" (particularly as it relates to multiple testing), and the effects of disease prevalence on the post-test probability of disease for individual test results. Applying these principles to a typical 12-test battery in asymptomatic adults, one would expect a low yield of unanticipated diagnoses and a high proportion of false-positive results. For the typical test battery, the empirical evidence supports these expectations in ambulatory care screening. In addition, routine preadmission use of biochemical profiles is not supported by studies examining their impact on patient care, hospital costs, or lengths of stay. Whereas components of these profiles can be endorsed for screening or preadmission testing, we recommend that the routine use of the entire profile be abandoned in these settings.
Abstract 442: Down-regulation of MET/RON receptor tyrosine kinases in colon cancer cells under chronic hypoxia as a mechanism for resistance towards targeted therapy
Authors: Sunny Guin, Qi Ma, Snehal Padhye, Hong-Ying Zhang, Ming-Hai Wang
Journal: Cancer Research (2010)

Abstract Hypoxia is a pathogenic factor observed in solid tumors, which plays a critical role in tumor malignancy and drug resistance. The MET and RON receptor tyrosine kinases belong to a unique proto-oncogene family and contribute to tumorigenic progression and malignant phenotypes in various epithelial cancers. To address their pathogenic significance under chronic hypoxic condition (1% O2, 5% CO2 for 5 days), functional analysis of MET and RON were conducted using colon cancer HCT116 and HT29 cells as models. Contrary to previous reports, we consistently observed that levels of MET and RON were significantly decreased over a period of 5 days under chronic hypoxic condition as documented by Western blot and cell-surface fluorescent analysis. The reduction was also accompanied with decreased in both spontaneous and ligand (HGF/MSP)-induced tyrosine phosphorylation manners, which affected the downstream signaling cascades. Moreover, we observed that hypoxia-induced HIF-1α expression (known as a positive regulator for both receptors) is unable to sustain MET or RON expression, suggesting that the receptor down-regulation is mediated through a HIF-1α-independent mechanism. RT-PCR analysis revealed that diminished MET and RON expression occurs at the mRNA transcription level. However, increase in protein degradation also contributed to the observed reduction. Functional studies further demonstrated that chronic hypoxia facilitates colon cancer cells to develop a unique pathogenic phenotype. This phenotype was featured by reduced cell migration, decreased cell proliferation, and lack of S phase in cell cycle profile. Tumor cells were also insensitive in response towards HGF or MSP-induced cell movement and replication. These cancer cells were resistant to cytotoxic effects induced by MET-RON duel small molecule inhibitors such as PHA665752 and compound I. As shown by cytotoxicity assay, the IC50 values of these inhibitors in cell survival were significantly increased in cancer cells under chronic hypoxic treatment compared to normoxic cells. In conclusion, our results demonstrate that under chronic hypoxia colon cancer cells developed a pathogenic phenotype characterized by diminished expression of MET and RON. Such a change contributes to the insensitivity of tumor cells towards cytotoxic activities of specifically targeted drugs. Thus, diminished expression of MET and RON under chronic hypoxia is a potential mechanism that affects the effectiveness of targeted therapy in the treatment colon cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 442.
Utilization and outcomes of enoxaparin treatment for deep-vein thrombosis in a tertiary-care hospital
Authors: Kristine B. Gilbert, George M. Rodgers
Journal: American Journal of Hematology (2000)

The availability of a low-molecular-weight heparin, enoxaparin, to treat deep-vein thrombosis (DVT) offers the option for outpatient therapy for certain DVT patients. We monitored the utilization and outcomes of enoxaparin treatment for DVT in our tertiary-care hospital. A retrospective chart survey was performed for all DVT patients treated at our facility between October 1998 and September 1999. We tracked treatment received (unfractionated heparin or enoxaparin), clinical outcomes (recurrent thromboembolism or bleeding), and whether the patient would have met practice guideline criteria for outpatient enoxaparin therapy. A total of 266 patients were either admitted to the hospital for DVT or experienced DVT during their hospitalization. Of 266 DVT patients, 73 (27%) received enoxaparin. Sixty-four (88%) patients receiving enoxaparin met practice guideline criteria. Nine patients (12%) who did not meet criteria also received the drug. Major bleeding occurred in 3 patients (4%) receiving enoxaparin; one patient had a life-threatening hemorrhage. Two of the three patients with major bleeding had contraindications to enoxaparin use. Only 45% of our DVT patients were appropriate candidates for outpatient enoxaparin therapy. We conclude that in tertiary-care hospitals with acutely ill patients, most DVT patients will not be candidates for outpatient therapy with enoxaparin. Limitations to enoxaparin use are not widely appreciated.
Atherosclerosis Complicating Chronic Hypertension
Authors: HARRIET P. DUSTAN
Journal: Circulation (1974)

The accelerating effect of hypertension on atherogenesis in the aorta and iliofemoral and coronary arteries is presented here as a graded function of elevated intraarterial pressure. Predilection of the abdominal aorta and iliofemoral arteries for atherosclerosis can be explained on the basis of pressure augmentation by reflected pressure pulse waves and the increase in hydrostatic pressure that is produced by standing. Wave reflection is intensified by vasoconstriction, which is a characteristic not only of hypertension but also occurs with upright posture. Standing also raises the hydrostatic pressure of blood in vessels below heart level. Coronary atherosclerosis seems likely to relate to the fact that the coronary vessels are located in an area of high pressure in the arterial system and that their intramyocardial branches are normally completely occluded during systole — a condition which could be accompanied by subtle differences in the pressure-volume characteristics of the epicardial vessels. Evidence is presented from actuarial statistics, epidemiologic studies, and laboratory experiments to indicate that the level of arterial pressure has a measurable effect on the metabolism of arterial smooth muscle cells. Thus arterial pressure is viewed as having a metabolic determinant role in addition to its vital role in the circulation of blood.
ACCREDITATION IS PERCEIVED TO IMPROVE THE QUALITY OF VASCULAR TESTING FACILITIES: RESULTS OF AN INTERSOCIETAL ACCREDITATION COMMISSION (IAC) SURVEY
Authors: Linda Zhu, Mary Farrell, Louis Bezold, John Choi, Kevin Cockroft, Gary Heller, Scott Jerome, Sandra Katanick, Warren Manning, Laurence Needleman, Heather Gornik
Journal: Journal of the American College of Cardiology (2014)
Antileukemic Effect of Graft-versus-Host Disease in Human Recipients of Allogeneic-Marrow Grafts
Authors: P L Weiden, N Flournoy, E D Thomas, R Prentice, A Fefer, C D Buckner, R Storb
Journal: New England Journal of Medicine (1979)

To determine whether allogeneic bone-marrow transplantation is associated with a graft-versus-leukemia effect, we examined the relation between relapse of leukemia and graft-versus-host disease in 46 recipients of identical-twin (syngeneic) marrow, 117 recipients of HLA-identical-sibling (allogeneic) marrow with no or minimal graft-versus-host disease, and 79 recipients of allogeneic marrow with moderate to severe or chronic disease. The relative relapse rate was 2.5 times less in allogeneic-marrow recipients with graft-versus-host disease than in recipients without it (P less than 0.01). This apparent antileukemic effect was more marked in patients with lymphoblastic than nonlymphoblastic leukemia, and in those who received transplants during relapse rather than during remission, and was most evident during the first 130 days after transplantation. Survival of all patients was comparable since the lesser probability of recurrent leukemia in patients with graft-versus-host disease was offset by a greater probability of other causes of death.
THE LETHAL AGENT IN ACUTE INTESTINAL OBSTRUCTION
Authors: R. W. GERARD
Journal: JAMA (1922)

The continuous appearance in clinical journals of papers which purport to discuss the cause of death in acute intestinal obstruction, but which entirely ignore or misconstrue the important experimental work carried on in the last few years, especially by L. R. Dragstedt and his co-workers, suggests the desirability of a brief review of this field. Particularly vexed have been the questions of the nature of the poison (for all workers agree that a poison taken up from the obstructed intestine is the lethal agent) and its source.  Whipple and his collaborators 1 have shown that the formation of a closed loop of the upper intestine, by double section, infolding the cut ends of the isolated segment after thorough washing, and reestablishing continuity of the remaining intestine by anastomosis, is equivalent to a simple obstruction. An animal on which such an operation has been performed dies in a manner typical of
Vital Capacity as a Predictor of Premature Death
Authors: David B. Pryor
Journal: Annals of Internal Medicine (1993)

Letters15 September 1993Vital Capacity as a Predictor of Premature DeathDavid B. Pryor, MDDavid B. Pryor, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-6-199309150-00032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate Dr. Petty's interest in and support of our article [1]. Before rushing out to equip every primary care physician's office with a spirometer, however, we would point out the differences between our study and those cited by Dr. Petty.All our patients reported chest pain thought to require subsequent diagnostic testing. Studies cited by Dr. Petty [2, 3] focused on a healthy, asymptomatic population. The distinction is important for two reasons. First, the independent prognostic value of characteristics in healthy asymptomatic patients may be substantially lower in symptomatic patients after adjusting for known prognostic characteristics. For ...References1. Pryor DB, Shaw L, McCants CB, Lee KL, Mark DB, Harrell FE Jr, et al. Value of the history and physical in identifying patients at increased risk for coronary artery disease. Ann Intern Med. 1993; 118:81-90. Google Scholar2. Kannel WB, Lew EA, Hubert HB, Castelli WP. The value of measuring vital capacity for prognostic purposes. Trans Assoc Life Insur Med Dir Am. 1980; 64:66-83. Google Scholar3. Beaty TH, Newill CA, Cohen BH, Tockman MS, Bryant SH, Spurgeon HA. Effects of pulmonary function on mortality. J Chronic Dis. 1985; 38:703-10. Google Scholar Author, Article, and Disclosure InformationAuthors: David B. Pryor, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 1993Volume 119, Issue 6Page: 538-539KeywordsAnginaCoronary heart diseaseHeart failureIschemiaMedical risk factors ePublished: 15 August 2000 Issue Published: 15 September 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Urbanization — An Emerging Humanitarian Disaster
Authors: Ronak B. Patel, Thomas F. Burke
Journal: New England Journal of Medicine (2009)

In 2008, the proportion of the world's population living in urban areas crossed the 50% mark. Drs. Ronak Patel and Thomas Burke write that urbanization is a health hazard for certain vulnerable populations, and this demographic shift threatens to create a humanitarian disaster.