tbuckley/cabot-search huggingface dataset:
Abstract A8: Fibulin-5 (FBLN5) initiates EMT and induces MMPs expression via β1 integrin/EGFR/ERK pathway
Authors: Yonghun Lee, William P. Schiemann
Journal: Cancer Research (2013)

Abstract Epithelial-mesenchymal transition (EMT) is a normal physiological process that regulates tissue development, remodeling and repair; however, aberrant EMT also elicits disease development in humans, including lung fibrosis, rheumatoid arthritis and cancer cell metastasis. Transforming growth factor-β (TGF-β) is a master regulator of EMT in normal mammary epithelial cells (MECs), wherein this pleiotropic cytokine also functions as a potent suppressor of mammary tumorigenesis. In contrast, malignant MECs typically become resistance to TGF-β-mediated cytostasis and develop the ability to proliferate, invade and metastasize when stimulated by TGF-beta. Therefore, the understanding of how TGF-β promotes EMT may offer new insights into targeting the oncogenic activities of TGF-β in human breast cancers. Previously, we showed that the TGF-β gene target, FBLN5, initiates EMT and enhances that induced by TGF-β. FBLN5 stimulated matrix metalloproteinase (MMP 2,3, and 9) expression and activity, leading to MEC invasion and EMT. While WT FBLN5 induces EMT and MMP expression, RGE mutant (loss of integrin binding activity) of FBLN5 fails to induce EMT and MMP expression. We show here that FBLN5 induces EGFR expression, and the inhibition of EGFR and ERK1/2 MAPK with AG 1478 β3 integrin suppresses FBLN5 induced MMP expression, the expression of D119A mutant β3 integrin fails to suppress FBLN5-induced MMP expression. In addition, knock-down of β1 integrin reverses FBLN5-induced EMT and suppress FBLN5-induced MMPs expression. These results suggest FBLN5 induces EMT and MMP expression in β1 integrin-dependent β1 integrin/EGFR/ERK signaling pathway in MECs. These findings identify a novel EMT and tumor-promoting function for FBLN5 in developing and progressing breast cancers. Citation Format: Yonghun Lee, William P. Schiemann. Fibulin-5 (FBLN5) initiates EMT and induces MMPs expression via β1 integrin/EGFR/ERK pathway. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A8.
Cardiology: An Illustrated Text/Reference, vol 1: Physiology, Pharmacology, Diagnosis, vol 2: Cardiovascular Disease
Authors: Samuel Zoneraich
Journal: JAMA (1992)

This cardiology "Text/Reference" is an impressive opus of magnificent technology and erudition. It is a hardbound edition of the looseleaf<i>Cardiology</i>, edited by W. W. Parmley and K. Chatterjee, published in 1987 and updated yearly. The book's two volumes—<i>Physiology, Pharmacology, Diagnosis and Cardiovascular Disease</i>—are divided into six sections, with an editor responsible for each. Both volumes bring to the reader recent developments in cardiology, presenting the pathophysiology of heart disease, the latest technology, and newer methods of treatment in a simple and concise manner. More than 150 authors, all experts in their fields, have contributed, and the volumes are superbly illustrated with color photographs, tables, and graphs. One of the strengths of the text is the personal approach of each author to a specific topic and the evenhandedness employed in dealing with controversial topics. Take, for example, the usefulness of vasodilator drugs in congestive heart failure. In a
Ardeparin Sodium for Extended Out-of-Hospital Prophylaxis against Venous Thromboembolism after Total Hip or Knee Replacement
Authors: John A. Heit, C. Gregory Elliott, Arthur A. Trowbridge, Bernard F. Morrey, Michael Gent, Jack Hirsh
Journal: Annals of Internal Medicine (2000)

Background: The optimal duration of prophylaxis against venous thromboembolism after total hip or knee replacement is uncertain. Objective: To determine the efficacy and safety of extended out-of-hospital prophylaxis with low-molecular-weight heparin (ardeparin sodium). Design: Randomized, double-blind, placebo-controlled trial. Setting: 33 community, university, or university-affiliated hospitals. Patients: 1195 adults who had elective total hip or knee replacement and completed 4 to 10 days of postoperative ardeparin prophylaxis. Intervention: Daily subcutaneous ardeparin (100 IU/kg of body weight) or placebo from time of hospital discharge to 6 weeks after surgery. Measurements: Symptomatic, objectively documented venous thromboembolism or death, along with major bleeding, from time of hospital discharge to 12 weeks after surgery. Results: Patients who received ardeparin (n = 607) and those who received placebo (n = 588) did not differ significantly in the cumulative incidence of venous thromboembolism or death (9 cases [1.5%] compared with 12 cases [2.0%]; odds ratio, 0.7 [95% CI, 0.3 to 1.7]; P > 0.2; absolute difference, −0.56 percentage points [CI, −2.2 to 1.1 percentage points]) or major bleeding (2 cases [0.3%] compared with 3 cases [0.5%]). Conclusions: Among patients who had total knee or total hip replacement and received 4 to 10 days of postoperative ardeparin prophylaxis, the cumulative incidence of symptomatic venous thromboembolism or death after hospital discharge was not significantly reduced by extended out-of-hospital ardeparin prophylaxis. Extended ardeparin use could provide a maximum 2.2–percentage point true reduction in such events. The benefit of extended ardeparin use is not clinically important for most patients. Future research should identify high-risk patients who would benefit most from extended prophylaxis. *For members of the Ardeparin Arthroplasty Study Group, see Appendix.
Resistance Versus Aerobic Exercise
Authors: Jane E. Yardley, Glen P. Kenny, Bruce A. Perkins, Michael C. Riddell, Nadia Balaa, Janine Malcolm, Pierre Boulay, Farah Khandwala, Ronald J. Sigal
Journal: Diabetes Care (2012)

In type 1 diabetes, small studies have found that resistance exercise (weight lifting) reduces HbA(1c). In the current study, we examined the acute impacts of resistance exercise on glycemia during exercise and in the subsequent 24 h compared with aerobic exercise and no exercise.Twelve physically active individuals with type 1 diabetes (HbA(1c) 7.1 ± 1.0%) performed 45 min of resistance exercise (three sets of seven exercises at eight repetitions maximum), 45 min of aerobic exercise (running at 60% of Vo(2max)), or no exercise on separate days. Plasma glucose was measured during and for 60 min after exercise. Interstitial glucose was measured by continuous glucose monitoring 24 h before, during, and 24 h after exercise.Treatment-by-time interactions (P < 0.001) were found for changes in plasma glucose during and after exercise. Plasma glucose decreased from 8.4 ± 2.7 to 6.8 ± 2.3 mmol/L (P = 0.008) during resistance exercise and from 9.2 ± 3.4 to 5.8 ± 2.0 mmol/L (P = 0.001) during aerobic exercise. No significant changes were seen during the no-exercise control session. During recovery, glucose levels did not change significantly after resistance exercise but increased by 2.2 ± 0.6 mmol/L (P = 0.023) after aerobic exercise. Mean interstitial glucose from 4.5 to 6.0 h postexercise was significantly lower after resistance exercise versus aerobic exercise.Resistance exercise causes less initial decline in blood glucose during the activity but is associated with more prolonged reductions in postexercise glycemia than aerobic exercise. This might account for HbA(1c) reductions found in studies of resistance exercise but not aerobic exercise in type 1 diabetes.
Increased Carbon Monoxide in Exhaled Air of Asthmatic Patients
Authors: KIYOSHI ZAYASU, KIYOHISA SEKIZAWA, SHOJI OKINAGA, MUTSUO YAMAYA, TAKASHI OHRUI, HIDETADA SASAKI
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Exhaled carbon monoxide (CO) concentrations were measured on a CO monitor by vital capacity maneuvers in asthmatic patients receiving or not receiving inhaled corticosteroids and in nonsmoking and smoking healthy control subjects. CO was detectable and measured reproducibly in the exhaled air of all subjects. The exhaled CO concentrations were higher in asthmatic patients not receiving inhaled corticosteroids (5.6 ± 0.6 ppm, p < 0.001) and similar in asthmatic patients receiving inhaled corticosteroids (1.7 ± 0.1 ppm) compared with those in nonsmoking healthy control subjects (1.5 ± 0.1 ppm). Smoking healthy control subjects had the highest levels of exhaled CO concentration among the groups (21.6 ± 2.8 ppm, p < 0.001). To examine whether inhaling corticosteroids reduce exhaled CO concentration in a given asthmatic patient, 12 patients with symptomatic asthma who were being treated by inhaled β2-agonists alone underwent measurements of exhaled CO concentration before and 4 wk after the initiation of inhaled corticosteroid treatment. All patients had reductions in exhaled CO concentration (p < 0.001) and eosinophil cell counts in sputum (p < 0.01) that were accompanied by an improvement in airway obstruction. Changes in exhaled CO concentration were significantly related to those in the eosinophil cell counts in sputum (p < 0.001). The present study shows an elevation of exhaled CO in asthmatic patients that decreases with corticosteroid therapy. Increases in the exhaled CO levels therefore may reflect inflammation in the asthmatic lung.
Ethosuximide in Childhood Absence Epilepsy — Older and Better
Authors: Eileen P.G. Vining
Journal: New England Journal of Medicine (2010)

Where did our wisdom about treating epilepsy originate? The ketogenic diet came from ancient teachings. The mistaken belief that seizures were caused by sexual excess led to bromides. Modern medications are developed through screening processes and, now, by drug design. However, establishing the actual clinical efficacy of a specific treatment is quite difficult. In most seizure disorders, a treatment is assumed to have resulted in optimal control if no seizures occur over a considerable period of observation. The patient and the physician cross their fingers and tick off the seizure-free days, weeks, and months before deeming a treatment successful. But . . .
Case of Complete Obstruction of Inferior Vena Cava
Authors: J. A. Keen
Journal: BMJ (1940)

TRANSFUSION OF RECONSTITUTED DkTED SERUM T aSo 823 'two series is evident.Our thanks are due to Dys. 0. M. Solandt and Janet Vaughan for helpful criticism and to many members of the staffs of-various hospitals in the S.W. and N.W. areas for putting cases
The great medicines scandal: Access is not just about cost
Authors: Brenda J Waning
Journal: BMJ (2006)

Editor—I write with reference to the editorial by Richards.1 In addition to important information on pricing, the World Health Organization/Health Action International report provides vital information on the availability of medicines in low resource settings. The authors report alarmingly low availability of key medicines to treat chronic diseases in both public and private pharmacies across most regions.

For example, hydrochlorothiazide, considered a first line antihypertensive in many countries, had very low availability. In the private sector, median availability for the originator product and the generic product was 0% and 41%, respectively.2 In the public sector, median availability for both products was 0%.2 Hydrochlorothiazide remains one of the most cost effective means of controlling hypertension; but if it is not available it cannot be used. Although campaigns to reduce prices are important, they will not tackle the issue of availability.

The availability of beclometasone inhalers to control asthma was far below acceptable levels. The WHO/HAI report shows that no country had 100% availability of beclometasone inhalers in private sector pharmacies.2 And only five countries showed availability of more than 30% for originator and generic beclometasone inhaler.2 In contrast, availability of salbutamol inhalers was relatively high across most countries.2​2



Figure 1

Hospital pharmacy in the Central African Republic



These findings show that while salbutamol rescue therapy is widely used, beclometasone inhaler to prevent asthma attacks is not. This practice has implications on both outcomes and affordability.

Policies on pricing will not address the insufficient availability of chronic disease medicines. Additional qualitative and quantitative research needs to be conducted to better understand why these key medicines are not available in public and private pharmacies. Only then can interventions be designed and implemented to address availability of medicines for chronic diseases in low resource settings.
P5-19-01: Final Results of a Three-Arm Randomised Phase II Study of Oral Vinorelbine Plus Capecitabine Versus Oral Vinorelbine and Capecitabine in Sequence Versus Docetaxel Plus Capecitabine in Patients with Metastatic Breast Cancer Previously Treated with Anthracyclines.
Authors: M Campone, N Dobrovolskaya, S Tjulandin, S-C Chen, S Fourie, F Mefti, M Konstantinova, F Lefresne, N Meheust, J Jassem
Journal: Cancer Research (2011)

Abstract Purpose: Owing to the increasing number of patients treated with anthracycline-based adjuvant chemotherapy, there is a need for new effective and tolerable non-anthracycline based regimens in metastatic breast cancer. Patients and methods: Patients with HER2−negative metastatic breast cancer previously treated with anthracyclines in (neo) adjuvant setting were randomised to fully oral 3-weekly cycles of the combination of oral vinorelbine with capecitabine (V+C), to the same drugs alternating every 3 cycles (V ⇔ C), or to the combination of docetaxel and capecitabine (D+C). V was given at 80 mg/m2 (after the first cycle at 60 mg/m2) on days 1 and 8 in the V+C arm and weekly in the V ⇔ C arm, C at 1,000 mg/m2 bid from days 1 to 14, and D on day 1 at 75 mg/m2. The primary endpoint was disease control rate (CR+PR+NC ≥ 3 months). Results: A total of 139 patients were randomly assigned to V+C (44 patients), V ⇔ C (47 patients) and D+C (48 patients). After an independent review, the disease control rate in the intent-to-treat population in the V+C, V ⇔ and D+C arms [95% CI] was 70.5% [54.8−83.2], 37.0% [23.2−52.5] and 70.8% [55.9−83.1]. The response rate was 31.8% [18.6−47.6], 8.7% [2.4−20.8] and 35.4% [22.2−50.5], respectively. The median duration of progression-free survival in the V+C, V ⇔ C and D+C arms [95% CI] was 7.2 months [5.3−8.9], 3.4 months [2.6−5.6] and 8.9 months [7.2−12.0]; the median overall survival [95% CI] was 22.2 [18.8; 29.9], 19.4 [12.5; 35.4] and 24.2 [14.2; 38.5] months, respectively. Lower efficacy observed in the sequential arm could be due to higher prevalence of patients with visceral disease in this arm (91.3% in comparison to 65.9% in V+C and 64.6% in D+C arm). Combinations of V+C or D+C showed similar efficacy and a different toxicity profile; V+C induced less neutropenia, infection, hand-foot syndrome, fatigue/asthenia and alopecia, whereas D+C- less gastrointestinal toxicity. Conclusions: V+C combination constitutes a valuable fully oral alternative option to D+C in patients with metastatic breast cancer previously treated with anthracyclines in (neo)adjuvant setting, while offering the advantages of an all-oral treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-01.
Place of a Double-barrelled Ileostomy in Ulcerative Colitis and Crohn's Disease of the Colon: a Preliminary Report
Authors: S. C. Truelove, H. Ellis, C. U. Webster
Journal: BMJ (1965)

ResultsThirty-one cases have been treated with double-barrelled ileostomy, the results being summarized in Tables I andII.We here describe some of the problems associated with our three indications for this procedure together with illustrative examples from each group.
Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood?
Authors: Juliana F. Fernandes, Vanderson Rocha, Myriam Labopin, Benedicte Neven, Despina Moshous, Andrew R. Gennery, Wilhelm Friedrich, Fulvio Porta, Cristina Diaz de Heredia, Donna Wall, Yves Bertrand, Paul Veys, Mary Slatter, Ansgar Schulz, Ka Wah Chan, Michael Grimley, Mouhab Ayas, Tayfun Gungor, Wolfram Ebell, Carmem Bonfim, Krzysztof Kalwak, Pierre Taupin, Stéphane Blanche, H. Bobby Gaspar, Paul Landais, Alain Fischer, Eliane Gluckman, Marina Cavazzana-Calvo
Journal: Blood (2012)
Heat stress preconditioning and delayed myocardial protection: what is new?
Authors: M Joyeux-Faure
Journal: Cardiovascular Research (2003)

As other preconditioning phenomena, heat stress is able to induce a delayed myocardial protection against ischaemia-reperfusion injury by preserving ventricular function, preventing arrhythmia occurrence and reducing cellular necrosis. The development of heat stress response has been extensively studied in order to characterize the different steps of this form of preconditioning. It appears that chemical signals (such as nitric oxide, reactive oxygen species (ROS)) released by sublethal hyperthermic stress trigger a complex cascade of signalling events that include activation of protein kinase C (PKC) and mitogen-activated protein kinases (MAPK) and culminate in increased synthesis of inducible nitric oxide synthase, cyclooxygenase-2, antioxidant enzymes and protective proteins such as heat stress proteins (Hsps). A better understanding of this powerful protective adaptation of the cardiomyocyte is essential for the development of clinical applications and the design of cardioprotective pharmacological agents. The purpose of this letter is to review current information regarding the characteristics of heat stress preconditioning compared to other forms of late preconditioning.
Diagnosis and Subtyping of <i>De Novo</i> and Relapsed Mediastinal Lymphomas by Endobronchial Ultrasound Needle Aspiration
Authors: Mufaddal T. Moonim, Ronan Breen, Paul A. Fields, George Santis
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: The current management of lymphoma requires accurate diagnosis and subtyping of de novo lymphoma and of relapsed or refractory lymphoma in known cases. The role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the clinical management of lymphomas is unclear.Objectives: To investigate the use of EBUS-TBNA in the diagnosis of de novo and relapsed mediastinal lymphomas.Methods: A total of 2,256 consecutive patients who underwent EBUS-TBNA in a tertiary center between February 2008 and April 2013 were prospectively evaluated. The diagnostic accuracy and clinical use of EBUS-TBNA in 100 cases of de novo or suspected relapsed mediastinal lymphoma was investigated by comparing EBUS-TBNA diagnosis with the final diagnosis.Measurements and Main Results: De novo mediastinal lymphoma was correctly diagnosed by EBUS-TBNA in 45 (88%) of 51 and relapsed lymphoma in 15 (100%) of 15 lymphoma cases. EBUS-TBNA accurately established a diagnosis other than lymphoma in 32 (97%) of 33 patients with suspected lymphoma relapse. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBUS-TBNA in the diagnosis of mediastinal lymphoma were 89%, 97%, 98%, 83%, and 91%, respectively. Sensitivity of EBUS-TBNA in subtyping lymphomas into high-grade non-Hodgkin lymphoma, low-grade non-Hodgkin lymphoma, and Hodgkin lymphoma was 90%, 100%, and 79%, respectively. EBUS-TBNA diagnosis was adequate for clinical management in 84 (84%) of 100 cases.Conclusions: Multimodality evaluation of EBUS-TBNA can be successful in the diagnosis of de novo mediastinal lymphomas and is ideally suited in distinguishing lymphoma relapse from alternative pathologies; it is least sensitive in subtyping Hodgkin lymphoma.
Buying cake is our job
Authors: Yolanda S Augustin
Journal: BMJ (2007)

I cried at work yesterday, for the first time in ages. Don't know why—it was probably a culmination of a number of small things, but I'd been spending the whole day running around trying to clerk patients, place cannulas, replace blocked suprapubic catheters, chase blood results, liaise with oncologists, break bad news, and talk to relatives. I should know by now that medicine is stressful and you need to multitask. 

On the ward round that morning we'd seen a man with cancer who had come to us for symptom control, but it now looked as though …
Corticosteroid Therapy in Severe Illness
Authors: Steven W.J. Lamberts, Hajo A. Bruining, Frank H. de Jong
Journal: New England Journal of Medicine (1997)

Severe illnesses, trauma, anesthesia, and surgery are accompanied by activation of the hypothalamic–pituitary–adrenal axis, as demonstrated by increased serum corticotropin and cortisol concentrations.17 This activation is an essential component of the general adaptation to stress and contributes to the maintenance of homeostasis.8 The efficacy of replacement doses or high doses of corticosteroids in patients with severe illness, especially those with multiorgan-system diseases, is uncertain.912 The uncertainty is even greater in patients who are already taking corticosteroids. Standard therapy for the latter patients consists of the administration of high doses of corticosteroids during any severe illness and perioperatively. We . . .
Philippines considers euthanasia bill
Authors: C. Wallerstein
Journal: BMJ (1997)

The Philippine Senate is considering a controversial bill that could make the staunchly Catholic country the first in the world to legalise euthanasia.

The bill–part of a 16 point bill of patients' rights–has already undergone its first reading, and the second reading will start after the Senate session resumes in late July. It must pass three readings with a two thirds majority and then be ratified by President Fidel Ramos before it can be incorporated into law.

Senate health …
Treatment of Chronic Immune Thrombocytopenic Purpura
Authors: Neil L. Kao
Journal: Annals of Internal Medicine (1997)

Letters1 October 1997Treatment of Chronic Immune Thrombocytopenic PurpuraNeil L. Kao, MDNeil L. Kao, MDUniversity Asthma and Allergy Service; Rockford, IL 61107Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-7-199710010-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Dr. McMillan's paper [1] on refractory chronic immune thrombocytopenic purpura was excellent. He stated that “an accessory spleen … should be removed, if present.” In the six references cited, accessory splenectomy was successful in 24 of 42 cases (57%). Is Dr. McMillan aware of any prognostic factors for successful or poor outcomes?References1. McMillan R. Therapy for adults with refractory chronic immune thrombocytopenic purpura. Ann Intern Med. 1997; 126:307-14. Google Scholar Author, Article, and Disclosure InformationAffiliations: University Asthma and Allergy Service; Rockford, IL 61107 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1997Volume 127, Issue 7Page: 572KeywordsIdiopathic thrombocytopenic purpuraSpleenSplenectomy Issue Published: 1 October 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...