tbuckley/cabot-search huggingface dataset:
Leukotrienes pathway are involved in the anti-inflammatory effects aerobic exercise on asthma
Authors: Ricardo W.A. Custódio, Flavia R. Greiffo, Nicole C. Rigonato-Oliveira, Adilson S. Andrade-Sousa, Paulo R. Pereira, Ana R. Almeida-Oliveira, Jefferson C. J. Aquino, Nilsa R. Damaceno-Rodrigues, Regiane Albertini, Ana P.L. Oliveira, Rodolfo P. Vieira
Journal: European Respiratory Journal (2014)

Leukotrines are involved in the pathophysiology of asthma, contributing for inflammation, remodeling and hyperresponsiveness. Aerobic physical training (APT) inhibits asthmatic reactions and in animal models were already demonstrated that reduces even the airway inflammation and remodeling, although the mechanisms are only superficially investigated. Therefore, this study aimed to investigate if the leukotrienes are involved in these anti-inflammatory effects of APT in an asthma model induced by ovalbumin (OVA) and house dust mite (HDM). After the establishment of airway inflammation and remodeling, APT was performed in a treadmill, at moderate intensity, 5x/week, during 4 weeks. The results demonstrated that, for both OVA and HDM asthma models, APT reduces the number of total cells (pl0.05) and eosinophils in the bronchoalveolar lavage (BAL) (pl0.05), the levels of IL-5 (pl0.01) in BAL and in serum, increases the levels of IL-10 (pl0.01) in BAL and in serum, reduces the number of macrophages (pl0.05), lymphocytes (pl0.01) and eosinophils (pl0.05) in the airways wall and also the collagen fibers accumulation in the airway wall (pl0.01). APT also decreased the levels of leukotriene B4 in BAL and hyperresponsiveness to methacholine (25 and 50mg/mL). Therefore, we conclude that APT reduces asthma phenotype in OVA and HDM experimental settings and these results seems to have the involvement of leukotriene pathway.
A Virus-Induced Disease of Mice Characterized by Erythrocytopoiesis and Lymphoid Leukemia
Authors: Frank J. Rauscher
Journal: JNCI Journal of the National Cancer Institute (1962)

A newly isolated, highly potent murine leukemogenic virus induced a dual type of disease in 90 to 100 percent of mice of different strains. The disease was characterized by rapid and extreme proliferation of predominantly erythrocytic and leukocytic elements as early as 7 days postparenteral inoculation. Within 15 days after inoculation of newborn or adult mice, 50 to 100 percent developed palpable spleens. Fifty percent of the animals, with spleens weighing 30 to 50 times those of normal mice, died within 25 to 35 days. In mice that survived, the erythrocytopoiesis was followed by the development of lymphocytic leukemia beginning 30 to 45 days after inoculation. Leukemic tissues transplanted with ease and killed 100 percent of the recipients. An intense viremia occurred in infected mice at least as early as 16 days after inoculation. The virus extracted from plasma or from leukemic tissues was of such potency that a 10−7 dilution of the test material induced the disease in 50 percent of the recipients within 95 days. Virus particles measuring 100 mμ were seen in thin sections of plasma pellets and in malignant lymphoblasts from spleen. Osborne-Mendel rats, 8 different inbred strains of mice, and random-bred Swiss mice, were all highly susceptible. The virus was stable to lyophilization, −70° C, formalin, and was not neutralized by antiserum prepared against the murine leukemia viruses of Friend, Moloney, or Schoolman-Schwartz. The ratio of mice responding with erythrocytopoiesis only to those developing erythrocytopoiesis plus lymphoid leukemia was influenced by the infecting dose of virus and by the strain and age of the recipients.
Treatment of Patients With Metastatic Renal Carcinoma With a Combination of Subcutaneous Interleukin-2 and Interferon Alfa With or Without Fluorouracil
Authors: Sylvie Négrier, Armelle Caty, Thierry Lesimple, Jean-Yves Douillard, Bernard Escudier, Jean-François Rossi, Patrice Viens, Frédéric Gomez
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Subcutaneous recombinant interleukin-2 (rIL-2) and recombinant interferon alfa-2a (rIFNα-2a) have been used extensively in the treatment of metastatic renal cancer. Most results, coming from noncontrolled phase II trials, showed inconsistent rates of response. More recently, the addition of fluorouracil (FU) was proposed to improve the efficacy of these regimens. PATIENTS AND METHODS: The role of a subcutaneous combination of rIL-2 and rIFNα-2a with or without FU was investigated. Patients were randomly assigned to receive a combination of rIL-2 and rIFNα-2a at weeks 1, 3, 5, and 7 or the same combination together with a continuous infusion of FU at weeks 1 and 5. The major end points of this multicenter, randomized trial were progression-free survival, response rate, and toxicity. Overall survival was a secondary end point. Tumor responses were reviewed by an independent committee. Analysis of the results was performed on an intention-to-treat basis. RESULTS: One hundred thirty-one patients were enrolled. There was no difference in toxicity between the arms, and no toxic death was observed. One partial response was observed in arm A and five in arm B. Progression-free survival did not differ between the arms, and rates at 1 year were 12% and 15% in arms A and B, respectively. No statistically significant differences were detected in any end point. CONCLUSION: The subcutaneous combination of rIL-2 and rIFNα-2a with or without FU does not benefit patients with metastatic renal carcinoma. Neither of these regimens can be recommended as standard treatment. The results of the subcutaneous cytokine regimen seem disappointing.
Two-compartment modelling of respiratory system mechanics at low frequencies: gas redistribution or tissue rheology?
Authors: T Similowski, JH Bates
Journal: European Respiratory Journal (1991)

The mechanical properties of the respiratory system are generally inferred from measurements of pressure and flow at the airway opening. Traditionally, these measurements have been related through a single-compartment model of the respiratory system. Recently, however, there has been considerable interest in modelling low-frequency respiratory mechanics in terms of two compartments, since this gives a much improved description of experimental data. In this paper we consider two classes of two-compartment models that are compatible with pressure-flow relationships of air measured at the airway opening. One type of model accounts for regional ventilation inhomogeneity in the lung in terms of two alveolar compartments. The other type of model considers pulmonary ventilation to be homogeneous, while the tissues of the respiratory system are modelled as being viscoelastic. In normal dogs, the appropriate two-compartment model has been shown to be the viscoelastic model. In the case of abnormal physiology, however, one must invoke a model having both viscoelastic tissues and ventilation inhomogeneities. Additional experimental data are required in order to identify such a model, and to quantify these two phenomena.
Synthesis and SAR development of PD 0325901, a potent and highly bioavailable MEK inhibitor.
Authors: Michael D. Kaufman, Stephen D. Barrett, Cathlin M. Flamme, Joseph Warmus, Yvonne D. Smith, Manoj Cheriyan, Luyan Zhang, Haile Tecle, Judith Sebolt-Leopold, Heather Valik, Richard Gowan, Keri Van Becelaere, Ronald Merriman, Sally Przybranowski, Jeffrey Ohren, Christopher Whitehead, W. R. Leopold, Ellen Dobrusin, Alexander Bridges
Journal: Cancer Research (2004)

2477  The MAP kinase pathway transmits proliferative signals for a number of growth factors and receptors and plays a central role in the growth of many human cancers. MEK (MAP kinase kinase), a central player in the Ras-MAP kinase pathway, is a critical signaling protein for multiple oncogenic pathways including the ErbB family, VEGF, PDGF, and mutated ras. MEK inhibitors therefore have the potential for a broader spectrum of antitumor activity than agents that inhibit only one portion of a tumor’s redundant proliferative pathways. We have previously described the identification and evaluation of PD 184352 (CI-1040), the first MEK inhibitor reported to modulate phosphorylation of MAP kinase in tumor-bearing animals (Sebolt-Leopold et al, Nature Medicine, 5, 810-816, 1999). CI-1040 was well tolerated in Phase 1 studies and did modulate tumor pERK levels at tolerated doses, although low overall bioavailability of the drug hampered its further development. To increase the bioavailability of CI-1040, we have explored the incorporation of polar, solubilizing substituents into the CI-1040 template. In this presentation, we describe synthesis and structure-activity-relationships (SAR) of a new class of N-aryl anthranilic acid hydroxamates that has led to PD 0325901. A variety of functionalized hydroxamate esters were surveyed and maximal in vitro potency was obtained by the incorporation of hydroxyalkyl esters. Further optimization of three sites on the CI-1040 ring system provided an additional boost in potency. These new sub-nanomolar inhibitors, display exquisite selectivity for MEK, like CI-1040. A recently obtained co-crystal structure of a MEK1 construct with PD 0318088, a PD 0325901 congener, explains the kinase selectivity of Pfizer’s MEK inhibitors and is highlighted here.
Cytotoxic Antibodies to Cultured Melanoma Cells in the Sera of Melanoma Patients23
Authors: S. Ferrone, M. A. Pellegrino
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Cytotoxic Antibodies to Cultured Melanoma Cells in the Sera of Melanoma Patients Get access S. Ferrone, S. Ferrone Search for other works by this author on: Oxford Academic PubMed Google Scholar M. A. Pellegrino M. A. Pellegrino Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 5, May 1977, Pages 1201–1204, https://doi.org/10.1093/jnci/58.5.1201 Published: 01 May 1977 Article history Received: 09 July 1976 Accepted: 15 October 1976 Published: 01 May 1977
Avoiding Implementation Errors in Cancer Survivorship Care Plan Effectiveness Studies
Authors: Deborah K. Mayer, Sarah A. Birken, Ronald C. Chen
Journal: Journal of Clinical Oncology (2015)

Although survivorship care plans (SCPs) have been recommended for the last decade, implementation and dissemination has been slow, low, and sporadic. In the accompanying article, Nicolaije et al report on the longitudinal effectiveness of SCPs. This is the fourth publication from the Registrationsystem Oncological Gynecology (ROGY) program, which electronically generates an SCP for women with gynecologic malignancies in the Netherlands. Previously, Nicolaije et al documented the degree of dissatisfaction of information provided for women with endometrial cancer, concluding that SCPs could address many of these unmet needs. They conducted a pragmatic cluster randomized controlled trial in 12 institutions in which half used the ROGY system to create and deliver an individualized SCP and half received usual care for patients ending treatment between 2011 and 2012. This study contributes to a growing number of randomized controlled trials of SCP effectiveness. These and other studies have primarily assessed the effects of SCPs on distal outcomes, such as patient satisfaction with care. They tend not to address the more proximal, process-related outcomes that we might expect SCPs to influence (eg, knowledge, communication, and care coordination) or how SCPs are implemented. In this sense, the standards to which we hold studies of SCP effectiveness diverge from standards for other innovations in cancer care. For example, studies of the effectiveness of a cancer drug report on its indications, mode of administration, dose, frequency, adverse effects, and response rates; we take these into account when evaluating their results. In contrast, SCP effectiveness studies rarely define the information that SCPs contain, how they are developed and delivered, whether survivors or primary care providers (PCPs) receive and use them, whether and how frequently they are updated, and whether SCPs have any negative effects. Without this information, SCP effectiveness studies cannot be compared or contrasted, and they cannot inform future implementation and dissemination efforts. Moreover, omitting this information exposes SCP effectiveness studies to the possibility that outcomes are the result not of the inherent (in)effectiveness of SCPs but rather of poor or inconsistent SCP implementation (type III error).
Cystatin C and albuminuria as markers of kidney and cardiovascular diseases in obstructive sleep apnoea syndrome (OSAS)
Authors: Luiza Jonczak, Adam Nowinski, Robert Plywaczewski, Damian Korzybski, Anna Czyzak-Gradkowska, Monika Targowska, Dorota Górecka, Pawel Sliwinski
Journal: European Respiratory Journal (2012)

Obstructive sleep apnea (OSA) increases the risk of cardiovascular diseases and has been reported to be associated with a chronic kidney disease (CKD). The aim of our study was to assess the relations between indices of renal function (cystatin C, microalbuminuria, creatinine) and OSA severity and obesity.

We studied 238 OSA pts who had AHI ≥5/h in polysomnography: mean age 56.9±9.9y, AHI 38.9±21.7/h, ODI 44.85±27.85/h, BMI 33.5±5.8 kg/m2. Serum cystatin C levels were measured in all patients, normal values were: under 50y old; CysC<0.92mg/L, over 50y old; CysC<1.02mg/L. CKD was diagnosed when plasma creatinine level was above 1.2 mg/dl.

View this table:



Logistic regression analysis (LRA) revealed that increased CysC level was associated with elevated creatinine (OR=7.6; 95%CL=1.5-39.5, p 30/h (OR=7.97, 95%CL=1.5-41.6, p=0.013) and obesity (OR=3.1, 95%CL=1.2-8.1, p=0.016).

Conclusions: CysC should be considered as a biomarker that reflects clinically latent renal dysfunction. The chronic kidney disease was more frequent in obese subjects with severe OSA.
Inhibition of Human Mammary Carcinoma Cell Proliferation by Retinoids and Intracellular cAMP-Elevating Compounds&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J A Fontana, G Miksis, D M Miranda, J P Durham
Journal: JNCI Journal of the National Cancer Institute (1987)

Retinoids and cAMP-elevating agents markedly inhibited the proliferation of human mammary tumor cells. Their response has been previously correlated with the presence of estrogen receptor (ER) positivity. MDA-MB-231 cells were ER negative and insensitive to the antiproliferative effects of retinoids. However, their growth was markedly inhibited by agents that elevated intracellular cAMP levels, i.e., 8-bromo-cAMP, cholera toxin (CT), forskolin, and the phosphodiesterase inhibitor papaverine. The CT and forskolin inhibition of the ER-positive cells (MCF-7) was associated with an elevation of adenylate cyclase activity and intracellular cAMP levels; however, similar elevations in intracellular cAMP levels were not observed following CT or forskolin inhibition of MDA-MB-231 cells but only following the addition of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine.
Analysis of video-amplified body parameters in pediatric sleep
Authors: Marije Kamphuis, Frans de Jongh, Janneke Hilderink, Ron Vaartjes, Joanne Goorhuis, Boony Thio
Journal: European Respiratory Journal (2014)

Background: Diagnosis of Sleep Disordered Breathing (SDB) in pediatrics is commonly based on subjective findings, and at times validated by over-night poly(somno)graphy. Pediatricians seek for less expensive and more convenient ways to diagnose or screen for SDB.

Objectives: Eulerian Video Magnification (EVM) is a novel method that visualizes subtle changes in videos to extract useful body parameters. This study was focused on exploring the potential of EVM, whereby a proof of principle experiment was set up to extract respiration rate (RR) from chest wall movement under ideal settings. The ultimate goal is to improve diagnostic efficiency in pediatric sleep medicine.

Methods: The test person was asked to lay still on a bed, which we filmed with a web-cam for several minutes and amplified 15X using EVM (Wu et al., SIGGRAPH 2012). Both the original and motion-amplified (MA) video were analyzed, with a respiratory inductance plethysmography belt as reference.

Results: Respiratory effort was most visible in the MA video. Both videos showed similar RRs compared to the reference method with a mean difference in RR of respectively -0.05±0.38 and -0.08±0.46 bpm. The potential of EVM seems diverse. When EVM aims to extract multiple body parameters overnight, there are many obstacles to overcome first (i.e. movement in sleep and visibility of other relevant parameters). A simple visualization tool seems easier to apply (i.e. a representative MA video of the child's typical sleep pattern might give extra, objective information during consultation).

Conclusion: Our data showed acceptable RR values for both video analyses. We foresee promising applications in pediatric sleep medicine using the EVM method.
Peritonitis after Duodenal Stenting
Authors: K Hasan, R Motalleb-Zadeh, K Moorthy, R Chavez
Journal: Journal of the Royal Society of Medicine (2001)

Duodenal obstruction is present at diagnosis in about 5% of patients with adenocarcinoma of the head of the pancreas1. Surgical palliation was until recently the only means of improving their quality of life but duodenal stenting is now an option2,3.
Frequency and prognostic value of cutaneous molecular residual disease in mycosis fungoides: a prospective multicentre trial of the Cutaneous Lymphoma French Study Group
Authors: C. Hurabielle, S. Ingen-Housz-Oro, N. Ortonne, P. Cornillet-Lefèbvre, A. Merah, M. D'Incan, P. Joly, N. Franck, E. Estève, E. Maubec, F. Grange, L. Machet, L. Laroche, S. Barete, S. Dalac, L. Mortier, C. Michel, G. Quereux, P. Saiag, C. Ram-Wolff, B. Lenormand, J. Wechsler, S. Bastuji-Garin, M. Bagot, M.H. Delfau-Larue
Journal: British Journal of Dermatology (2015)

Monoclonal T-cell receptor (TCR) rearrangement is detected in 57-75% of early-stage mycosis fungoides (MF) at diagnosis. A retrospective study showed molecular residual disease (MRD) in 31% of patients in complete clinical remission (CR) after 1 year of treatment.To confirm the frequency of MRD at 1 year and to determine its prognostic value for further relapse.Patients with T1-, T2- or T4-stage MF were prospectively included in this multicentre study. At diagnosis, clinical lesions and healthy skin were biopsied. After 1 year of topical treatment, previously involved skin of patients in CR was biopsied for histology and analysis of TCR-γ gene rearrangement. The results were compared with the clinical status each year for 4 years.We included 214 patients, 133 at T1, 78 at T2 and three at T4 stage. At diagnosis, 126 of 204 cases (61·8%) showed TCR clonality in lesional skin. After 1 year, 83 of 178 patients (46·6%) still being followed up were in CR and 13 of 63 (21%) showed MRD. At 4 years, 55 of 109 patients (50·5%) still being followed up were in CR and 44 of 109 (40·4%) were in T1 stage. MRD did not affect clinical status at 4 years (CR vs. T1/T2, P = 1·0; positive predictive value 36·4%; negative predictive value 67·6%).T-cell clonality at diagnosis and MRD at 1 year are not prognostic factors of clinical status at 4 years.
Efficacy and safety of umeclidinium/vilanterol compared with umeclidinium or tiotropium in COPD
Authors: Marc Decramer, Antonio Anzueto, Edward Kerwin, Nathalie Richard, Glenn Crater, Maggie Tabberer, Stephanie Harris, Alison Church
Journal: European Respiratory Journal (2013)

Rationale: The long-acting muscarinic antagonist (LAMA) umeclidinium (UMEC) and long-acting beta2 agonist vilanterol (VI) are in development as a combination treatment for COPD. Tiotropium (TIO) is a LAMA indicated for COPD.

Objective: To evaluate efficacy and safety of two doses of UMEC/VI vs TIO or UMEC in patients with COPD.

Methods: This was a 24-week, multicentre, double-blind, parallel-group, double-dummy study. Patients (N=869 [ITT]) were randomised 1:1:1:1 to once-daily UMEC/VI 125/25 mcg, UMEC/VI 62.5/25 mcg, UMEC 125 mcg or TIO 18 mcg via a dry powder inhaler. Primary endpoint was trough FEV1 at Day 169. Secondary endpoint was weighted mean (WM) FEV1 over 0–6 hours post-dose at Day 168. Safety evaluations included adverse events (AEs), vital signs, electrocardiography (ECG) and clinical laboratory measurements.

Results: UMEC/VI 125/25 mcg showed statistically significant improvement in LS mean change from baseline in trough FEV1 vs TIO (0.074 L, 95% CI: 0.025–0.123; p=0.003), but not vs UMEC 125 mcg (0.037 L, 95% CI: -0.012–0.087). An improvement was also shown by UMEC/VI 62.5/25 mcg vs TIO (0.060 L, 95% CI: 0.010–0.109) but not vs UMEC 125 mcg (0.022, 95% CI: -0.027–0.072). Both UMEC/VI doses showed larger improvements in LS mean change from baseline in 0–6-hour WM FEV1 vs TIO and UMEC 125 mcg (0.070–0.101 L). The incidence of AEs was similar across treatments and no notable treatment-related changes were reported in vital signs, ECG or clinical measures.

Conclusions: UMEC/VI (125/25 and 62.5/25 mcg) was well tolerated in patients with COPD and provided clinically-meaningful benefits in immediate and 24-hour lung function vs TIO.

Funded by GlaxoSmithKline: DB2113374; [NCT01316913][1].

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01316913&atom=%2Ferj%2F42%2FSuppl_57%2FP3640.atom
State Medicaid Coverage for Tobacco Cessation Treatments and Barriers to Coverage — United States, 2014–2015
Authors: Jennifer Singleterry, Zach Jump, Anne DiGiulio, Stephen Babb, Karla Sneegas, Allison MacNeil, Lei Zhang, Kisha-Ann S. Williams
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Medicaid enrollees have a cigarette smoking prevalence (30.4%) twice as high as that of privately insured Americans (14.7%), placing them at increased risk for smoking-related disease and death. Individual, group, and telephone counseling and seven Food and Drug Administration (FDA)–approved medications are evidence-based, effective treatments for helping tobacco users quit. A Healthy People 2020 objective (TU-8) calls for all state Medicaid programs to adopt comprehensive coverage of these treatments. However, a previous MMWR report indicated that, although state Medicaid coverage of cessation treatments had improved during 2008–2014, this coverage was still limited in most states. To monitor the most recent trends in state Medicaid cessation coverage, the American Lung Association collected data on coverage of, and barriers to, accessing all evidence-based cessation treatments except telephone counseling in state Medicaid programs (for a total of nine treatments) during January 31, 2014–June 30, 2015. As of June 30, 2015, all 50 states covered certain cessation treatments for at least some Medicaid enrollees. During 2014–2015, increases were observed in the number of states covering individual counseling, group counseling, and all seven FDA-approved cessation medications for all Medicaid enrollees; however, only nine states covered all nine treatments for all enrollees. Common barriers to accessing covered treatments included prior authorization requirements, limits on duration, annual limits on quit attempts, and required copayments. Previous research in both Medicaid and other populations indicates that state Medicaid programs could reduce smoking prevalence, smoking-related morbidity, and smoking-related health care costs among Medicaid enrollees by covering all evidence-based cessation treatments, removing all barriers to accessing these treatments, promoting coverage to Medicaid enrollees and health care providers, and monitoring use of covered treatments.