tbuckley/cabot-search huggingface dataset:
Canadian tobacco firms are ordered to pay 8bn for damage from smoking
Authors: O. Dyer
Journal: BMJ (2015)

Canada’s three major tobacco firms suffered a heavy defeat when the Quebec Superior Court awarded $C15.6bn (£8bn; €11bn; $US13bn) to smokers in what could be a forerunner of further awards in other provinces.

The country’s biggest and longest running class action suit involved a million current, former, and deceased smokers, of whom 99 957 had contracted serious smoking related diseases and sought punitive damages. Their cases were represented by the suit of Jean-Yves Blais, who died from lung cancer in 2012. A further 918 218 sued for addiction, represented by the suit of Cecilia Letourneau. Both suits were filed 17 years ago.

The defendants, Imperial Tobacco Canada, JTI-Macdonald, and …
Complete nucleotide sequence analysis of the VP1 genomic region of Echoviruses 6 isolated from sewage in Greece revealed 98% similarity with Echoviruses 6 that were characterized from an aseptic meningitis outbreak 1 year later
Authors: Z. Kyriakopoulou, E. Dedepsidis, V. Pliaka, D. Tsakogiannis, I.G.A. Ruether, A. Krikelis, P. Markoulatos
Journal: Clinical Microbiology and Infection (2010)
Carboplatin and etoposide chemotherapy regimen for recurrent malignant glioma: a phase II study.
Authors: B Jeremic, D Grujicic, S Jevremovic, B Stanisavljevic, L Milojevic, L Djuric, L Mijatovic
Journal: Journal of Clinical Oncology (1992)

PURPOSE A phase II study that used combination chemotherapy with carboplatin (CBDCA) and etoposide (VP 16) (CE) was performed on patients with recurrent malignant glioma to investigate tumor control and toxicity. PATIENTS AND METHODS Thirty-eight patients were treated with CBDCA 300 mg/m2 on days 1 to 3 and VP 16 100 mg/m2 on days 1 to 5. A minimum of three courses were required unless the patient had a rapid progression of disease (PD). Courses were repeated every 4 weeks. RESULTS We observed partial responses (PRs) in eight of 38 patients (21%), stable disease (SD) in 12 of 38 (32%), whereas 18 of 38 (47%) patients had PD. The median time to tumor progression (TTP) for PR and SD patients was 42.5 weeks, whereas the median survival time (MST) for PR and SD patients was 47.5 weeks. Three groups of toxicities were observed: hematologic, gastrointestinal, and hepatic. No grade 4 Eastern Cooperative Oncology Group toxicity was observed. CONCLUSIONS This regimen has shown at least comparable results with other series that used platinum-based agents. Further studies that use these agents in various-dose schedules and drug combinations are warranted.
Treatment of Anemia in Patients With Heart Disease: A Clinical Practice Guideline From the American College of Physicians
Authors: Amir Qaseem, Linda L. Humphrey, Nick Fitterman, Melissa Starkey, Paul Shekelle
Journal: Annals of Internal Medicine (2013)

This article has been corrected. The original version (PDF) is appended to this article as a supplement. Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the treatment of anemia and iron deficiency in adult patients with heart disease. Methods: This guideline is based on published literature in the English language on anemia and iron deficiency from 1947 to July 2012 that was identified using MEDLINE and the Cochrane Library. Literature was reassessed in April 2013, and additional studies were included. Outcomes evaluated for this guideline included mortality; hospitalization; exercise tolerance; quality of life; and cardiovascular events (defined as myocardial infarction, congestive heart failure exacerbation, arrhythmia, or cardiac death) and harms, including hypertension, venous thromboembolic events, and ischemic cerebrovascular events. The target audience for this guideline includes all clinicians, and the target patient population is anemic or iron-deficient adult patients with heart disease. This guideline grades the evidence and recommendations using the ACP's clinical practice guidelines grading system. Recommendation 1: ACP recommends using a restrictive red blood cell transfusion strategy (trigger hemoglobin threshold of 7 to 8 g/dL compared with higher hemoglobin levels) in hospitalized patients with coronary heart disease. (Grade: weak recommendation; low-quality evidence) Recommendation 2: ACP recommends against the use of erythropoiesis-stimulating agents in patients with mild to moderate anemia and congestive heart failure or coronary heart disease. (Grade: strong recommendation; moderate-quality evidence)
High-dose chemotherapy without autologous bone marrow transplantation in melanoma.
Authors: N S Tchekmedyian, N Tait, D Van Echo, J Aisner
Journal: Journal of Clinical Oncology (1986)

High-dose chemotherapy with BCNU, melphalan, or both, followed by autologous bone marrow transplantation (ABMT) has been reported to produce response rates in excess of 60% in patients with advanced melanoma. We tested doses of BCNU associated with reversible bone marrow toxicity and acceptable extramedullary toxicity without the use of ABMT in 19 patients with a diagnosis of advanced malignant melanoma. All patients were evaluable for toxicity and 18 were evaluable for response; one patient had a new primary tumor. The patient population had a median age of 44 years (range, 16 to 71) and a median Karnofsky performance status of 80 (range, 50 to 100). Ten were women and nine were men, all had visceral dominant disease, and none had received previous chemotherapy. Our purpose was to test the feasibility of treatment without ABMT, its toxicity and efficacy, and the possibility of administering sequential repeated courses of therapy. Vincristine was added to the regimen to potentially increase efficacy. Treatment consisted of BCNU (750 mg/m2) and vincristine (2 mg days 1 and 8). Six patients who recovered bone marrow function received melphalan (60 mg/m2) and vincristine (2 mg days 1 and 8). Twenty-two percent (95% confidence limits, 3% to 39%) of patients had remissions (all partial) and these were of short duration. Toxicity was substantial with 16% early lethality and 29% incidence of lethal drug-related complications. Two patients (11%) died toxic after a second course of BCNU. Our results suggest that there is no practical role for high-dose BCNU in the treatment of melanoma.
CEACAM1: A Marker With a Difference or More of the Same?
Authors: Timothy A. Plunkett, Paul A. Ellis
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.21.4273 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12409323 CEACAM1: A Marker With a Difference or More of the Same? Timothy A. PlunkettxTimothy A. PlunkettSearch for articles by this author , Paul A. EllisxPaul A. EllisSearch for articles by this author Show More Guy’s Hospital, London, United Kingdom https://doi.org/10.1200/JCO.2002.20.21.4273 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
The relation of comorbidities with the exacerbation severity in patients with COPD
Authors: Eylem Özgür, Sibel Atis Nayci, Cengiz Özge, Yasin Duman, Gamze Çavusoglu, Ahmet Ilvan
Journal: European Respiratory Journal (2013)

Comorbidities are common in patients with COPD, but there is a few study investigating the relation of comorbidities with the exacerbation. We aimed to compare the comorbidities according to exacerbation severity in COPD patients.  We recruited 157 COPD patients. They were divided into four groups according to exacerbation severity: patients hospitalized in ICU(n=21,group 1), patients hospitalized in the pulmonary service(n=51, group 2), patients with non-hospitalized(n=42, group 3), and without exacerbation in the previous year(n=43, group 4).  Mean FEV1 46.3±17.27%, and Charlson score 1.87±1.38. The most frequent comorbidities were: hypertension (43.3%), ischemic heart disease (29.3%), diabetes (17.2%), chronic heart failure(17.8%), cachexia(15.9%), obesity(25.5%), anemia(12.7%), dyslipidemia (19.7%), chronic kidney disease (10.8%), and depression (11.5%). The patients of hospitalized in ICU had higher charlson score(2.4 vs. 2.1, 1.3, 1.8 respectively; p=0.007) than the other groups. This group had a greater proportion of cor-pulmonale(100% vs 72.5%, 7.1%, 20.9%, p  In conclusion, this study showed that higher incidence and more severe degree of respiratory and other comorbidities in COPD patients with severe exacerbation. It was thought that comorbidities contribute to the severity of exacerbation in COPD patients.
CARESS: The Canadian registry of palivizumab (2005-2010)
Authors: Ian Mitchell, Bosco Paes, Abby Li, Krista Lanctot
Journal: European Respiratory Journal (2011)

Objective:  To evaluate the current management of children at high-risk of RSV infection who received palivizumab prophylaxis in tertiary care centers and community settings using a Canadian Registry Database.   Methods:  A prospective, observational, registry of infants who received ≥1 dose of palivizumab during the 2005-2010 RSV seasons across 29 sites. Data on palivizumab utilization and compliance, and outcomes related to a respiratory infection were collected monthly until the full course of palivizumab was completed.   Results:  7699 infants were enrolled, with an average age of 5.4±6.0 months. Participants were typically male (56.4%), Caucasians (71.5%), with an average gestational age (GA) of 32.2 (SD 6.0) completed weeks. 5237 (68.0%) infants received palivizumab for prematurity (35 completed weeks GA) only, 766 (9.9%) for congenital heart disease, 646 (8.4%) for chronic lung disease and 1050 (13.6%) for other risk factors (e.g., CNS disorders, airway anomalies and cystic fibrosis). Patients received an average of 3.9 (SD 1.6) injections, with 30,040 doses given overall. 5.5% of patients withdrew from the study. No direct, drug related serious adverse events were identified. 460 infants had a total of 541 hospitalizations for a spectrum of respiratory tract illnesses resulting in a hospitalization rate of 6.0%.The overall RSV positive hospitalization rate was 1.47% with no mortality. Living with siblings was significantly correlated with a shorter time to first RSV-positive hospitalization (B=0.615, df=1, p=0.046).   Conclusions:  The RSV hospitalization rate observed in the 2005-2010 RSV seasons was similar to that found in several published reports of infants receiving prophylaxis (range 1.3%-5.3%).
Biochemical modulation of fluorouracil: evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma.
Authors: M A Poon, M J O'Connell, C G Moertel, H S Wieand, S A Cullinan, L K Everson, J E Krook, J A Mailliard, J A Laurie, L K Tschetter
Journal: Journal of Clinical Oncology (1989)

The purpose of this study was to evaluate the effectiveness of several new approaches designed to enhance the activity of fluorouracil (5-FU) in the management of advanced colorectal cancer. A total of 429 patients were randomized to one of the following regimens: single-agent 5-FU, given by standard 5-day, intensive-course intravenous bolus technique; 5-FU plus high-dose folinic acid (leucovorin) or 5-FU plus low-dose leucovorin; 5-FU plus high-dose methotrexate (MTX) with oral leucovorin rescue; 5-FU plus low-dose MTX; and 5-FU plus cisplatin (CDDP). The median survival for patients receiving 5-FU alone was 7.7 months. The high- and low-dose leucovorin plus 5-FU regimens had median survivals of 12.2 and 12.0 months, respectively, and offered a significant survival advantage over 5-FU alone with one-sided P values of .037 and .050, respectively (P = .051 for each treatment after correction for prognostic variables). The only other regimen possibly associated with improved survival was high-dose MTX plus 5-FU, with a median survival of 10.5 months (P = .21, P = .076 corrected). In addition, both high- and low-dose leucovorin plus 5-FU regimens were associated with significantly improved tumor response rates (P = .04 and .001) and significantly improved interval-to-tumor-progression rates (P = .015 and .007) when compared with 5-FU alone. Only the low-dose leucovorin plus 5-FU regimen was associated with significant (P less than .05) superiority in each of the following parameters of quality of life: performance status, weight gain, and symptomatic relief. The overall most therapeutically favorable regimen in this trial was 5-FU given with low-dose leucovorin; fortuitously, this regimen is associated with very low drug cost. Whereas this is the first study to demonstrate both improved palliation and survival for any regimen compared with 5-FU given by rapid intravenous (IV) injection for 5 consecutive days at a dose of 500 mg/m2/d in patients with advanced colorectal cancer, the magnitude of the gain is still relatively small. Our low-dose leucovorin plus 5-FU regimen is currently being studied in a national trial with the hope that this increased advanced disease activity may produce more substantive gains in the surgical adjuvant setting.
Th1 and Th17 Cytokines Drive Inflammation in Takayasu Arteritis
Authors: D. Saadoun, M. Garrido, C. Comarmond, A. C. Desbois, F. Domont, L. Savey, B. Terrier, G. Geri, M. Rosenzwajg, D. Klatzmann, P. Fourret, P. Cluzel, L. Chiche, J. Gaudric, F. Koskas, P. Cacoub
Journal: Arthritis & Rheumatology (2015)

Takayasu arteritis (TAK) is a large-vessel vasculitis that induces damage to the aorta and its branches. Glucocorticoids remain the gold standard of therapy for TAK. The nature of the T cells driving vascular inflammation and the effects of glucocorticoids on the systemic components of TAK are not understood. The aim of this study was to analyze T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta in patients with TAK.T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta were analyzed using Luminex analysis, flow cytometry, and immunohistochemical analysis. The study included 41 patients fulfilling the American College of Rheumatology 1990 criteria for the classification of TAK (17 patients with active TAK and 24 patients with disease in remission), 30 patients with giant cell arteritis and 39 patients with Behçet's disease (disease controls), and 20 age- and sex-matched healthy control subjects.We observed a marked increase in the expression of Th1 and Th17 cells, which correlated with TAK disease activity. The addition of serum from patients with active TAK to sorted CD4+ T cells from healthy donors in culture medium induced significant production of interferon-γ (IFNγ) and interleukin-17A (IL-17A). We demonstrated the presence of IFNγ-, IL-6-, and IL-17A-producing T cells in vascular inflammatory infiltrates in patients with TAK. Corticosteroid therapy was associated with decreased levels of circulating Th1 cytokines in corticosteroid-treated patients with TAK compared with steroid-free patients with TAK (for IL-2, mean ± SD 5,079 ± 5,300 versus 7,359 ± 3,197 pg/ml; for IFNγ, 2,592 ± 3,072 versus 8,393 ± 3,392 pg/ml; for tumor necrosis factor α, 847 ± 724 versus 1,491 ± 392 pg/ml). However, glucocorticoids had essentially no effect on the frequency of Th17 cytokines (IL-1 receptor, IL-17, and IL-23).The Th17 and Th1 pathways contribute to the systemic and vascular manifestations of TAK. Glucocorticoid treatment suppresses Th1 cytokines but spares Th17 cytokines in patients with TAK.
Abstract 35: Diacylglycerol kinase zeta-mediated regulation of mTOR and SREBP-1 offers new opportunities for cancer management
Authors: PEDRO Torres-Ayuso, David Jones, Maria Tello-Lafoz, Antonia Avila-Flores, Isabel Merida
Journal: Cancer Research (2015)

Abstract Diacylglycerol (DAG) and phosphatidic acid (PA) are two lipids that lie at the core of several metabolic and signaling pathways, which allows integrated control of cell growth and nutrient sensing with cell metabolism. Diacylglycerol kinases (DGK) are a family of enzymes that balance the levels of both lipids. Some DGK isoforms, mainly DGKα, have been recently suggested as potential targets for cancer treatment (Dominguez et al, 2013; Torres-Ayuso et al, 2014). Previous observations from us indicate that the DGKζ isoform contributes the most to DGK activity in cancer cells, and DGKζ-derived PA is required for mTOR activation, a master regulator of cell growth and metabolism (Avila-Flores et al, 2005). To address the potential of DGKζ as new therapeutic target for cancer treatment, we used several breast and colon cancer cell lines, and analyzed the effect of its pharmacological inhibition or siRNA-mediated knock down in the proliferation, survival and metabolism of these cells. We found that DGKζ protein levels where higher in malignant cells compared to their non-transformed counterparts, and its depletion abrogated cancer cell growth in colony assays. DGKζ was prominent over other PA sources to activate mTOR, and its activity was induced by rapamycin. We also investigated whether DGKζ-derived PA functions were coordinated with DAG metabolism and signaling. We observed that DGKζ-dependent DAG consumption was crucial for cell homeostasis via control of the SREBP-1 transcription factor, which was negatively regulated by DAG. Our data provide new evidence of the crosstalk between mTOR and lipid metabolism, and suggest that DGKζ represents an effective target for cancer control. References Avila-Flores A, Santos T, Rincon E, Merida I (2005) Modulation of the mammalian target of rapamycin pathway by diacylglycerol kinase-produced phosphatidic acid. The Journal of biological chemistry 280: 10091-10099 Dominguez CL, Floyd DH, Xiao A, Mullins GR, Kefas BA, Xin W, Yacur MN, Abounader R, Lee JK, Wilson GM, Harris TE, Purow BW (2013) Diacylglycerol kinase alpha is a critical signaling node and novel therapeutic target in glioblastoma and other cancers. Cancer discovery 3: 782-797 Torres-Ayuso P, Daza-Martin M, Martin-Perez J, Avila-Flores A, Merida I (2014) Diacylglycerol kinase alpha promotes 3D cancer cell growth and limits drug sensitivity through functional interaction with Src. Oncotarget 5: 9710-9726 Citation Format: PEDRO Torres-Ayuso, David Jones, Maria Tello-Lafoz, Antonia Avila-Flores, Isabel Merida. Diacylglycerol kinase zeta-mediated regulation of mTOR and SREBP-1 offers new opportunities for cancer management. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 35. doi:10.1158/1538-7445.AM2015-35
Reference values for cardiorespiratory fitness in a 20 - 85 year old population
Authors: Elisabeth Edvardsen, Bjørge H. Hansen, Ingar M. Holme, Sindre M. Dyrstad, Sigmund A. Anderssen
Journal: European Respiratory Journal (2012)

Background: Existing reference values used during clinical exercise testing have been obtained with rather small none randomly sample sizes, lack of women and elderly or poor maximal end-criteria. The aim was to establish reference values during maximal exercise in a representative sample of men and women.

Methods: 904 randomly sampled healthy men and women (20 – 85 yr old) exercised on a treadmill using a modified Balke protocol to exhaustion.

Results: 759 participants met the criteria for an acceptable VO2max based on RER≥1.10 or BORG≥17. In the age group 20-29, the VO2max (ml•kg-1•min-1) was 40.3 (SD 7.1) and 48.6 (SD 9.6) in women and men, respectively. A linear decline (8 % per decade) was observed after the age of 30 in both genders.

View this table:

Physiological responses at maximal exercise, mean (SD)





Conclusions: The present study establishes VO2max and other typical cardiorespiratory variables during maximal exercise and may be used as reference values.
Sleep-disordered Breathing and Incident Heart Failure in Older Men
Authors: Sogol Javaheri, Terri Blackwell, Sonia Ancoli-Israel, Kristine E. Ensrud, Katie L. Stone, Susan Redline
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: The directionality of the relationship between sleep-disordered breathing and heart failure is controversial.Objectives: We assessed whether elevations in the obstructive or central sleep apnea index or the presence of Cheyne-Stokes breathing are associated with decompensated and/or incident heart failure.Methods: We conducted a prospective, longitudinal study of 2,865 participants derived from the Osteoporotic Fractures in Men Study, a prospective multicenter observational study of community-dwelling older men. Participants underwent baseline polysomnography and were followed for a mean 7.3 years for development of incident or decompensated heart failure. Our main exposures were the obstructive apnea–hypopnea index (AHI), central apnea index (CAI ≥5), and Cheyne-Stokes breathing. Covariates included age, race, clinic site, comorbidities, physical activity, and alcohol and tobacco use.Measurements and Main Results: CAI greater than or equal to five and presence of Cheyne-Stokes breathing but not obstructive AHI were significant predictors of incident heart failure (adjusted hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.16–2.77 for CAI ≥5) (HR, 2.23; 95% CI, 1.45–3.43 for Cheyne-Stokes breathing). After excluding those with baseline heart failure, the incident risk of heart failure was attenuated for those with CAI greater than or equal to five (HR, 1.57; 95% CI, 0.92–2.66) but remained significantly elevated for those with Cheyne-Stokes breathing (HR, 1.90; 95% CI, 1.10–3.30).Conclusions: An elevated CAI/Cheyne-Stokes breathing, but not an elevated obstructive AHI, is significantly associated with increased risk of decompensated heart failure and/or development of clinical heart failure in a community-based cohort of older men.
A Factor in the Serum of Irradiated Rats Stimulating Lymphoid Tissue Mitosis
Authors: Yoichiro Ito, Fay B. Weinstein
Journal: JNCI Journal of the National Cancer Institute (1962)

A new technique is described, with which it has been possible to demonstrate a factor in the sera of lymphopenic irradiated rats which appears to act directly upon lymphoid tissue to stimulate mitosis. The method involves compari-son of the mitosis density in the popliteal lymph node draining the site of injection of test material with that in the contralateral node. It is felt that this may be a valuable technique for the further investigation of the mechanisms of lymphocyte homeostasis. (auth)