tbuckley/cabot-search huggingface dataset:
Shared decision making is not always a priority for patients, website finds
Authors: J. Feinmann
Journal: BMJ (2011)

Doctors should recognise that there is no “one size fits all” approach to breaking bad news or to sharing decision making, especially when caring for people with life threatening or terminal illness. That was the view of some of the 32 patients and eight carers who were interviewed about the experience of being treated for pancreatic cancer for the latest section of the Healthtalkonline.org website, launched last week (www.healthtalkonline.org/Cancer/Pancreatic_Cancer).

The website’s cofounder, the former GP Ann McPherson, is one of those patients, having been given a diagnosis of pancreatic cancer four years ago and then having a relapse, with the cancer spreading to her lungs, two years ago.

At the launch event at the Museum of London she was joined by the actor Hugh Grant, who donated £100 000 (€115 000; $164 000) to fund the pancreatic cancer site and contributes personally to it. He described his “great admiration” for the NHS in providing the “marvellous” care that his mother received in the months leading …
Abstract 861: Selective small-molecule kinase inhibitors of the c-Src:FAK complex
Authors: Jamie A. Moroco, Nathanael S. Gray, Thomas E. Smithgall
Journal: Cancer Research (2012)

Abstract The c-Src protein-tyrosine kinase is the prototype of a large non-receptor kinase family involved in a variety of signaling pathways in virtually every cell type. In normal cells, c-Src controls cell-cell adhesion, cell-matrix adhesion, and cell motility by interacting with and phosphorylating focal adhesion and extracellular matrix (ECM) proteins. Focal adhesion kinase (FAK), a key component of focal adhesions, activates c-Src by binding to its SH2 and SH3 domains and disrupting their negative regulatory influence on the kinase domain. The c-Src:FAK complex plays a major role in the migration and invasion of both normal and cancer cells. Both c-Src and FAK are over-expressed and constitutively active in many tumor types, enhancing focal adhesion turnover, cell migration and metastatic potential. The goal of our project is to determine whether distinct conformational changes occur in the c-Src kinase domain as a function of binding to FAK that can be selectively targeted with small molecule inhibitors. Using the FRET-based Z’-Lyte in vitro kinase assay, we first identified assay conditions where recombinant, downregulated c-Src activation was dependent on a synthetic phosphopeptide based on the FAK SH3- and SH2-binding motifs for c-Src. We then screened a chemical library of about 600 kinase-biased inhibitors for compounds that preferentially inhibited FAK-peptide-dependent c-Src activation compared to c-Src alone. Remarkably, 13 compounds showed at least five-fold selectivity for the FAK peptide:Src complex in the primary screen. Several of these compounds are of the Type II kinase inhibitor class and may exploit unique conformations of c-Src that are induced by FAK peptide binding to the SH3 and SH2 region of c-Src. These compounds are currently being evaluated for their impact on cell growth, invasion and migration in both fibroblasts and epithelial tumor cell lines. Discovery and development of selective inhibitors for a unique FAK-induced c-Src conformation may provide a new approach to targeted therapy for metastatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 861. doi:1538-7445.AM2012-861
Dosage of angiotensin converting enzyme inhibitors
Authors: J. Mcmurray
Journal: BMJ (1995)

Dosage ofangiotensin converting enzyme inhibitorsEDrrOR,-A L Clark and A J S Coats highlight the common problem of suboptimal doses of angio- tensin converting enzyme inhibitors being pre- scribed for patients with impaired left ventricular function.'Their paper, however, contains an important error, and when this is corrected the situation is seen to be even worse than they state.Clark and Coats suggest that the optimum dose of captopril to reduce mortality is 25 mg twice daily.This is not the case.The study they cite in support of this dose did not show a significant reduction in mortality.The dose of captopril most clearly shown to reduce mortality is 50 mg three times daily, and most studies of heart failure show- ing an improvement in symptoms and exercise tolerance with captopril have used doses at least as large as this.23
Relation between coronary artery stenosis assessed by visual, caliper, and computer methods and exercise capacity in patients with single-vessel coronary artery disease. The Veterans Affairs ACME Investigators.
Authors: E D Folland, R A Vogel, P Hartigan, E R Bates, G J Beauman, T Fortin, C Boucher, A F Parisi
Journal: Circulation (1994)

BACKGROUND Practitioners often assume a close relation between angiographic coronary artery stenosis and patient functional capacity. To test this unproven hypothesis, we analyzed the relation between coronary artery stenosis measured by different methods and maximal treadmill exercise tolerance in patients with single-vessel disease before and after intervention by percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS Coronary angiography and maximal exercise testing off anti-ischemic medication were performed before random assignment of 227 patients with single-vessel coronary artery disease to PTCA or drug therapy. Six months later, angiography and exercise testing were repeated with patients assigned to PTCA off anti-ischemic therapy so that the altered coronary stenosis was the only consistent variable. Patients assigned to drug therapy were exercised on drug therapy. Coronary stenosis was assessed visually by the local investigator and quantitatively by blinded caliper and computer methods in central laboratories. Variabilities of caliper and computer measurements were established in a subset read twice. Visually estimated stenosis &gt; or = 90% at baseline was associated with shorter exercise duration (7.9 versus 9.2 minutes, P &lt; .04). Similar segregation at baseline was not observed with caliper or computer methods. Regardless of the method of measurement used, correlation between changes of lesion severity and exercise duration from baseline to follow-up was poor. Patients were angiographically classified as "better," "unchanged," or "worse" if follow-up stenosis was below, within, or above 2 SD of mean technical variability from baseline (+/- 18.8%, caliper, +/- 14.6%, computer). Exercise duration for PTCA patients improved among those with better lesions (+2.4 minutes, n = 50, P = .001) but also among those with unchanged lesions (+1.9 minutes, n = 41, P &lt; or = .001). Unchanged medically treated patients improved less (+0.5 minutes, n = 86, P = .04). Results were similar when patients were angiographically classified by minimum lumen diameter. CONCLUSIONS Handheld calipers and quantitative coronary angiography are equivalent techniques for making anatomic measurements. Neither method identified patients having reduced exercise capacity at baseline as well as visual estimation. The relation between changes of coronary stenosis and exercise duration is highly variable, at least in part because of the insensitivity of angiographic methods for detecting small but potentially important changes. Minimal anatomic improvement 6 months after PTCA does not preclude a good functional outcome. Contrary to common belief, angiographic stenosis does not correlate well with functional capacity, even in patients with single-vessel disease.
714-1 Interaction Between Strong Electrical Stimulation and Reentrant Wavefronts in Canine Ventricular Fibrillation
Authors: Claudio Bonometti, Chun Hwang, Dustan Hough, John J. Lee, Michael C. Fishbein, Hrayr S. Karagueuzian, Peng-Sheng Chen
Journal: Journal of the American College of Cardiology (1995)
Differential role of the low affinity neurotrophin receptor (p75) in retrograde axonal transport of the neurotrophins
Authors: Rory Curtis, Krystyna M Adryan, Jennifer L Stark, John S Park, Debra L Compton, Gisela Weskamp, L.Julie Huber, Moses V Chao, Rudolf Jaenisch, Kuo-Fen Lee, Ronald M Lindsay, Peter S DiStefano
Journal: Neuron (1995)

The receptor mechanisms mediating the retrograde axonal transport of the neurotrophins have been investigated in adult rats. We show that transport of the TrkB ligands NT-4 and BDNF to peripheral neurons is dependent on the low affinity neurotrophin receptor (LNR). Pharmacological manipulation of LNR in vivo using either an anti-LNR antibody or a soluble recombinant LNR extracellular domain completely blocked retrograde transport of NT-4 and BDNF to sensory neurons, while having minimal effects on the transport of NGF in either sensory or sympathetic neurons. Furthermore, in mice with a null mutation of LNR, the transport of NT-4 and BDNF, but not NGF, was dramatically reduced. These observations demonstrate a selective role for LNR in retrograde transport of the various neurotrophins from distinct target regions in vivo.
Radiation-Induced Myelomatosis
Authors: Jack Cuzick
Journal: New England Journal of Medicine (1981)

Abstract It is well known that radiation can cause myeloid leukemia. However, no excess of chronic lymphocytic leukemia has been observed. Myelomatosis, like chronic lymphocytic leukemia, is a tumor of B lymphocytes. To determine whether this disease has a radiogenic origin, we surveyed all cohorts of persons exposed to radiation for which data on cancer-related mortality are available. An excess of myeloma was found in most cohorts. However, a striking deficit was found in two groups irradiated intensely for uterine neoplasms (three cases observed, 10.71 expected; P = 0.012). All other groups combined had a highly significant excess (50 observed, 22.21 expected; P = 2×10-7). The largest relative risk appeared among persons receiving internal doses of α-particles (14 observed, 3.24 expected; P = 2×10-5), but a significant excess (13 observed, 6.33 expected; P = 0.026) was also found in patients receiving only therapeutic or diagnostic γ-rays or x-rays. Most cases occurred 15 to 25 years after exposure. (N Engl J Med. 1981; 304: 204–10.)
PMO-214 Double balloon colonoscopy: single centre experience in patients with previously failed colonoscopy
Authors: E G Alexandridis, A Koulaouzidis, K Trimble, J N Plevris
Journal: Gut (2012)

<h3>Introduction</h3> Double balloon endoscopy is considered a technique for the investigation of the small-bowel. Recently, Double balloon colonoscopy (DBC) using dedicated colonoscopes has been shown to be associated with very high rates of caecal intubation. In this study we report the DBC experience in our centre as second line endoscopic investigation in patients who failed conventional colonoscopy. <h3>Methods</h3> Retrospective review of patients referred for DBC to our Centre from July 2009 to January 2012. <h3>Results</h3> Twenty-three consecutive patients (12 male/11 female mean age 60.2±16 years) underwent DBC. The sedation used was midazolam/fentanyl (mean: 3.5/75 mg). 19/23 had a DBC due to previously failed colonoscopies. In four, DBC was first choice test as they had unpleasant experiences from conventional colonoscopy in the past. In 7/23 (30.4%), there was evidence of previous abdominal surgery. In 4/23 (17.4%) a fixed and/or acutely angulated sigmoid was the cause of failure. In the remaining 12 patients, significant patient discomfort was the principal cause of failure. Nine patients (39.1%) had one failed colonoscopy, six (26.1%) had two failed colonoscopies, while four (17.4%) had more than two failed colonoscopies. In 22/23 DBC (95.7%) was successful; the entire colon and terminal ileum DBC were examined in all cases. No immediate or delayed complications were recorded. Patient tolerability was very good. <h3>Conclusion</h3> DBC is a safe and reliable method for complete colon examination and it is an important alternative technique in cases where a conventional colonoscopy has failed. Patient groups that are more likely to benefit are those with adhesions due abdominal surgery or fixed and angulated sigmoid colon. The technique is currently limited to few centers only, but the success rate and the very good patient tolerability suggest that it should be considered as an alternative in challenging cases. <h3>Competing interests</h3> E. Alexandridis Grant/Research Support from: Fujifilm, Imotech, A. Koulaouzidis: None Declared, K. Trimble: None Declared, J. Plevris Grant/Research Support from: Fujinon, Imotech.
Up-regulation of L1CAM in Pancreatic Duct Cells Is Transforming Growth Factor β1– and Slug-Dependent: Role in Malignant Transformation of Pancreatic Cancer
Authors: Claudia Geismann, Mascha Morscheck, Dorothee Koch, Frank Bergmann, Hendrik Ungefroren, Alexander Arlt, Ming-Sound Tsao, Max G. Bachem, Peter Altevogt, Bence Sipos, Ulrich R. Fölsch, Heiner Schäfer, Susanne Sebens Müerköster
Journal: Cancer Research (2009)

Pancreatic ductal adenocarcinoma (PDAC) is thought to originate from ductal structures, exhibiting strong desmoplastic reaction with stromal pancreatic myofibroblasts (PMF), which are supposed to drive PDAC tumorigenesis. Previously, we observed high expression of the adhesion molecule L1CAM (CD171) in PDAC cells accounting for chemoresistance. Thus, this study aimed to investigate whether PMFs are involved in the induction of tumoral L1CAM and whether this contributes to malignant transformation of pancreatic ductal cells and PDAC tumorigenesis. Immunohistochemistry of tissues from chronic pancreatitis specimens revealed considerable L1CAM expression in ductal structures surrounded by dense fibrotic tissue, whereas no L1CAM staining was seen in normal pancreatic tissues. Using the human pancreatic duct cell line H6c7, we show that coculture with PMFs led to a transforming growth factor-beta1 (TGF-beta1)-dependent up-regulation of L1CAM expression. Similarly, L1CAM expression increased in monocultured H6c7 cells after administration of exogenous TGF-beta1. Both TGF-beta1- and PMF-induced L1CAM expression were independent of Smad proteins but required c-Jun NH(2)-terminal kinase activation leading to the induction of the transcription factor Slug. Moreover, Slug interacted with the L1CAM promoter, and its knockdown abrogated the TGF-beta1- and PMF-induced L1CAM expression. As a result of L1CAM expression, H6c7 cells acquired a chemoresistant and migratory phenotype. This mechanism of TGF-beta1-induced L1CAM expression and the resulting phenotype could be verified in the TGF-beta1-responsive PDAC cell lines Colo357 and Panc1. Our data provide new insights into the mechanisms of tumoral L1CAM induction and how PMFs contribute to malignant transformation of pancreatic duct cells early in PDAC tumorigenesis.
PRELIMINARY NOTE ON THE DEVELOPMENT OF PIROPLASMA CANIS IN THE TICK
Authors: S. R. Christophers
Journal: BMJ (1907)

nonp.We see here, again, the presence of endocomplements in the guinea-pig corpuscles, and we have a slightly greater action with the presence of heated serum than with unheated serum.A similar experiment was made with sheep's blood.In this case, with 5 per cent.emulsion and two drops of 50 per cent.weever poison, there was advanced haemolysis, and with the same quantity of poison, with both normal serum and serum heated for an hour at 620 C., there was complete haemolysis after two hours in the incabator at 370 0. We have here a very marked example of tke amboceptor of weever poison combining with the endocomplement of the sheep corpuscles, resulting in rapid haemolysis.The increased haemolysis with the added serum was not affected by heating to 620 C.With human blood we also find that there is haemo-Jysis of the washed corpuscles without the addition of serum.But unless the venom is quite fresh 1 drop of the 50 per cent.solution is not sufficient to produce hlaemo- lysis, although 2 drops suffice.It seemed important, in the light of Briot's investigations previously referred to, to be quite sure of this.I have made seven separate experiments with human blood.Thc following experiment was very conclusive:Six tubes, each containing 1 c.cm. of 5 per cent.washed human corpuscles, were numbered 0, 1, 2, 3, 4, and 5; 0 was the control. 1 contained 1 drop of 50 per cent.weever poison. ,,,, 2 drops + 0.1 c.cm. normal serum.0 underwent no change after two hours at 370 C. 1 showed medium haemolysis with dark red sediment.2 showed well-marked haemolysis with dark pink sediment.3 ditto.4 showed very marked haemolysis, almost complete, the sediment being merely a faint pink.5 showed complete haemolysis; sediment yellow.
Review of cases of nosocomial Lassa fever in Nigeria: the high price of poor medical practice
Authors: S P Fisher-Hoch, O Tomori, A Nasidi, G I Perez-Oronoz, Y Fakile, L Hutwagner, J B McCormick
Journal: BMJ (1995)

To investigate two hospital outbreaks of Lassa fever in southern central Nigeria.Hospitals and clinics in urban and rural areas of Imo State, Nigeria.Medical records were reviewed in hospitals and clinics in both areas. Patients with presumed and laboratory confirmed Lassa fever were identified and contracts traced. Hospital staff, patients, and local residents were questioned, records were carefully reviewed, and serum samples were taken. Serum samples were assayed for antibody specific to Lassa virus, and isolates of Lassa virus were obtained.Among 34 patients with Lassa fever, including 20 patients, six nurses, two surgeons, one physician, and the son of a patient, there were 22 deaths (65% fatality rate). Eleven cases were laboratory confirmed, five by isolation of virus. Most patients had been exposed in hospitals (attack rate in patients in one hospital 55%). Both outbreak hospitals were inadequately equipped and staffed, with poor medical practice. Compelling, indirect evidence revealed that parenteral drug rounds with sharing of syringes, conducted by minimally educated and supervised staff, fuelled the epidemic among patients. Staff were subsequently infected during emergency surgery and while caring for nosocomially infected patients.This outbreak illustrates the high price exacted by the practice of modern medicine, particularly use of parenteral injections and surgery, without due attention to good medical practice. High priority must be given to education of medical staff in developing countries and to guidelines for safe operation of clinics and hospitals. Failure to do so will have far reaching, costly, and ultimately devastating consequences.
Studies on the mechanism of benzene toxicity.
Authors: R Snyder, E Dimitriadis, R Guy, P Hu, K Cooper, H Bauer, G Witz, B D Goldstein
Journal: Environmental Health Perspectives (1989)

Using the 59Fe uptake method of Lee et al. it was shown that erythropoiesis in female mice was inhibited following IP administration of benzene, hydroquinone, p-benzoquinone, and muconaldehyde. Toluene protected against the effects of benzene. Coadministration of phenol plus either hydroquinone or catechol resulted in greatly increased toxicity. The combination of metabolites most effective in reducing iron uptake was hydroquinone plus muconaldehyde. We have also shown that treating animals with benzene leads to the formation of adducts of bone marrow DNA as measured by the 32P-postlabeling technique.
Clinical impact of DNMT3A mutations in younger adult patients with acute myeloid leukemia: results of the AML Study Group (AMLSG)
Authors: Verena I. Gaidzik, Richard F. Schlenk, Peter Paschka, Anja Stölzle, Daniela Späth, Andrea Kuendgen, Marie von Lilienfeld-Toal, Wolfram Brugger, Hans Günter Derigs, Stephan Kremers, Richard Greil, Aruna Raghavachar, Mark Ringhoffer, Helmut R. Salih, Mohammed Wattad, Heinz G. Kirchen, Volker Runde, Gerhard Heil, Andreas L. Petzer, Michael Girschikofsky, Michael Heuser, Sabine Kayser, Gudrun Goehring, Maria-Veronica Teleanu, Brigitte Schlegelberger, Arnold Ganser, Jürgen Krauter, Lars Bullinger, Hartmut Döhner, Konstanze Döhner
Journal: Blood (2013)
Expired hydrogen peroxide in breath condensate of cystic fibrosis patients
Authors: LP Ho, J Faccenda, JA Innes, AP Greening
Journal: European Respiratory Journal (1999)

Stimulated inflammatory cells release large amounts of hydrogen peroxide (H2O2). Breath condensate H2O2 has been shown to be elevated in stable asthmatic children, chronic obstructive pulmonary disease and intubated adult respiratory distress syndrome. In cystic fibrosis airways, where neutrophilic inflammation dominates, it is postulated that H2O2 in breath condensate would be elevated and may be used as a marker of airways inflammation. Expired breath condensate was collected from 16 clinically stable cystic fibrosis (CF) patients (mean age 25.3 yrs, mean forced expiratory volume in one second (FEV1) 50.2%) and 14 normal subjects (mean age 29.9 yrs). Total plasma leukocyte, neutrophil, monocyte and eosinophil counts and lung function were also measured on the day of collection. A method of breath condensate collection excluding the confounding factors of nasal air and saliva contamination was validated and used and H2O2 measured fluorometrically using an optimized assay. The median level of H2O2 concentration in breath condensate of CF patients was lower than that in normal subjects (0.064 versus 0.089 microM), but this did not reach statistical significance (p = 0.20, Mann-Whitney rank sum test). Within the CF group, there was no correlation between H2O2 concentration and lung function. Expired breath condensate H2O2 is not elevated in patients with cystic fibrosis, and is thus not a suitable marker of airways inflammation in these patients. Possible explanations include physical barriers to its detection caused by viscous airways secretions, reaction with other reactive species or increased antioxidant activity caused by trapping of positively charged antioxidants in negatively charged airways secretions.
Thank You, Doctor
Authors: Lori Levy
Journal: Annals of Internal Medicine (2000)

Ad Libitum6 June 2000Thank You, DoctorLori LevyLori LevySherman Oaks, CA 91401 (Levy)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-11-200006060-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail For Dr. Richard SobelYou are a fixture in the living room—man reading medical journal—while the TV stands silent in the den.But you know it's not the textsthat make you a good doctor; it's “Aïda” and “Madama Butterfly,”Dannie Abse and William Carlos Williams; it's the winter walk in the desertwith your wife and childrenand red anemones.It's the words you choose,the way you dangle them, sparkling,before the eyesof a dying patient,an aspiring medical student,or me—your daughter. Author, Article, and Disclosure InformationAffiliations: Sherman Oaks, CA 91401 (Levy)Corresponding Author: Lori Levy, 13913 Chandler Boulevard, Sherman Oaks, CA 91401. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 June 2000Volume 132, Issue 11Page: 920KeywordsChildren ePublished: 15 August 2000 Issue Published: 6 June 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The effect of lovastanin on intimal hyperplasia following balloon angioplasty: An angiographic and morphometric study of the artery in the atherosclerotic rabbit
Authors: Joel Gellman, Michael D. Ezekowitz, Ian J. Sarembock, Emanuel Lerner, Michael A. Azrin, Lucien E. Nochomovitz, Christian Raudenschild
Journal: Journal of the American College of Cardiology (1990)