tbuckley/cabot-search huggingface dataset:
Mammary Noduligenesis and Tumorigenesis in Pathogen-Free C3Hf Mice2
Authors: Daniel Medina, Jan Vaage, Robert Sedlacek
Journal: JNCI Journal of the National Cancer Institute (1973)

Mammary noduligenesis and tumorigenesis were studied in pathogen-free C3Hf/Sd female mice. The mice experienced a normal breeding regimen for up to 5 pregnancies, then were retired to live out their lifespan. Of 38 mice, 29 died of mammary tumors with a mean latent period of 700 days, 4 died of other neoplasms, and 5 died of non-neoplastic causes. It seemed that mice kept free from accidents or infectious diseases would ultimately develop neoplasms. The rate of mammary tumorigenesis in pathogen-free mice paralleled the rate of tumorigenesis in conventional mice. The high mammary tumor incidence reflected the fact that the whole population of mice survived long enough to develop such tumors. Thus, the low oncogenic potential noted for the nodule-inducing virus was related to the late age of onset of mammary tumors in C3Hf mice, rather than to the ultimate tumor incidence.
Hamburg’s refugee policy is criticised after pregnant woman sent on long train trip miscarries
Authors: Ned Stafford
Journal: BMJ (2015)

The German Medical Association has criticised the state of Hamburg’s refugee policy after a 20 year old, high risk pregnant woman from Guinea had a miscarriage after she, her husband, and their toddler son were sent on a 12 hour train and bus trip from Hamburg to a new refugee centre near Dortmund, in North-Rhine Westphalia.

In a press statement Frank Ulrich Montgomery, president of the German Medical Association, said he was “shocked” to hear of the woman’s miscarriage,1 which occurred on 2 March 2015 and was reported in investigative news reports by the regional public radio and television broadcasters NDR in Hamburg and WDR in Cologne.2 3

The news reports said that shortly before the train trip the woman, in her fifth month of pregnancy, had been in hospital for two days because of vaginal bleeding. Doctors at the hospital labelled her pregnancy as high risk and advised bed rest and as little movement as possible. But she and her family …
Abstract 1844: Novel HER3 neutralizing antibody, patritumab abrogates cetuximab resistance mediated by a heregulin-autocrine loop in colorectal cancer
Authors: Hisato Kawakami, Isamu Okamoto, Kimio Yonesaka, Kunio Okamoto, Kiyoko Kuwata, Yume Morita, Haruka Yamaguchi, Kazuto Nishio, Kazuhiko Nakagawa
Journal: Cancer Research (2014)

Abstract Purpose Acquired resistance to cetuximab is a major problem in the treatment of colorectal cancers. We previously showed that the HER3/HER4 ligand heregulin induced resistance to cetuximab by increasing the association between HER2 and HER3, and subsequent activation of downstream targets. We have now investigated strategies to overcome such resistance, using patritumab, a novel neutralizing HER3 antibody. Experimental design We established DiFi cells that stably express heregulin (DiFi-HRG cells) as a result of retroviral infection, and examined the antitumor effect of cetuximab, patritumab, and the combination of both in these cells in vitro and vivo. Results DiFi-HRG cells secreted large amount of heregulin and exhibited resistance to cetuximab. Cetuximab alone down-regulated ERK phosphorylation, whereas it had no effect on AKT phosphorylation, suggesting that continuous AKT activation underlain underlies resistance to cetuximab in these cells. In contrast, Patritumab in combination with cetuximab markedly reduced the level of phosphorylation of HER2 HER3 and AKT, as well as ERK, and induced apoptosis that was accompanied by upregulation of BIM and by downregulation of survivin in vitro. Furthermore, the combination therapy also markedly inhibited the growth of DiFi-HRG tumors in nude mice to a greater extent than did treatment with either drug alone. Conclusion Our data indicate that HER2/HER3 signaling activated by a heregulin-autocrine loop confers resistance to cetuximab, and that patritumab restored sensitivity to cetuximab by inhibition of HER3 phosphorylation that is stimulated by heregulin. Citation Format: Hisato Kawakami, Isamu Okamoto, Kimio Yonesaka, Kunio Okamoto, Kiyoko Kuwata, Yume Morita, Haruka Yamaguchi, Kazuto Nishio, Kazuhiko Nakagawa. Novel HER3 neutralizing antibody, patritumab abrogates cetuximab resistance mediated by a heregulin-autocrine loop in colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1844. doi:10.1158/1538-7445.AM2014-1844
Combination etanercept and methotrexate provides better disease control in very early (≤4 months) versus early rheumatoid arthritis (&gt;4 months and &lt;2 years): post hoc analyses from the COMET study
Authors: Paul Emery, Tore K Kvien, Bernard Combe, Bruce Freundlich, Deborah Robertson, Tahmina Ferdousi, Eustratios Bananis, Ronald Pedersen, Andrew S Koenig
Journal: Annals of the Rheumatic Diseases (2012)

The objective of this post hoc analysis was to test the benefits of treating very early rheumatoid arthritis (VERA; ≤4 months) using COMET trial data. Treatment response in VERA and early rheumatoid arthritis (ERA; >4 months to 2 years) with combination etanercept+methotrexate (ETN+MTX) or MTX monotherapy was compared.Data assessed at week 52 for baseline disease duration effect included remission (disease activity score (DAS)28 <2.6, SDAI ≤3.3, Boolean), low disease activity (LDA; DAS28 <3.2), Boolean components of remission and radiographic non-progression. Subjects who discontinued because of lack of efficacy were included as non-responders.Higher proportions of VERA subjects achieved LDA (79%) and DAS28 remission (70%) than ERA (62%, 48%, respectively, p<0.05) with ETN+MTX. Such high responses with MTX monotherapy were not observed (VERA, LDA=47%, DAS28 remission=35%; ERA, 47% and 32% respectively, p>0.70 for each). Regardless of disease duration, no radiographic progression was seen in 80% of subjects with ETN+MTX. In contrast, a higher proportion of VERA subjects showed no radiographic progression compared with ERA subjects treated with MTX (73.9% vs 50%, p=0.01).Treatment of VERA with ETN+MTX provides qualitatively improved clinical outcomes not seen with MTX monotherapy, supporting the pivotal role of TNF inhibition in early disease.
Clinical features of pulmonary arterial hypertension in patients receiving dasatinib
Authors: Neil P. Shah, Nicola Wallis, Harrison W. Farber, Michael J. Mauro, Robert A. Wolf, Daniele Mattei, Mausumee Guha, Delphine Rea, Andrew Peacock
Journal: American Journal of Hematology (2015)

The prognosis of most leukemia patients treated with BCR-ABL tyrosine kinase inhibitors (TKIs) is favorable, and a more precise understanding of serious and potentially irreversible treatment-related toxicities is essential to properly inform treatment choice. Few cases of pulmonary arterial hypertension (PAH) have been reported in patients with leukemia treated with dasatinib, a second-generation BCR-ABL TKI. To better understand characteristics and outcomes of dasatinib-treated patients with PAH, all clinical cases of PAH confirmed by right-heart catheterization in the Bristol-Myers Squibb pharmacovigilance database (N = 41), including 22 previously unpublished cases, were examined for previous treatments for leukemia, patient characteristics, time to PAH onset, and outcomes. Our analysis shows that compared with PAH due to other etiologies, dasatinib-related PAH is atypical, in that it is associated with partial to complete reversibility upon treatment discontinuation. The incidence of dasatinib-related PAH appears to be low. Most PAH cases were observed in patients who had received prior treatments for leukemia. No specific patient attributes appear to be associated with an increased risk of developing PAH while receiving dasatinib. Symptoms of PAH in dasatinib-treated leukemia patients should prompt a thorough workup, including consideration of confirmatory right-heart catheterization. In cases of confirmed PAH, dasatinib should be discontinued.
Airway surface dehydration confers susceptibility to allergic airway inflammation in vivo
Authors: Benedikt Fritzsching, Lu Dai, Charlotte van Bodegom, Jolanthe Schatterny, Stephanie Hirtz, Zhe Zhou, Marcus Mall
Journal: European Respiratory Journal (2013)

Introduction:  Recent evidence from mice lacking the epithelial Cl -  channel SLC26A9 and mice with airway specific overexpression of the amiloride-sensitive epithelial Na +  channel (βENaC-Tg) suggests that airway surface dehydration is implicated in the pathogenesis of allergic airway disease (Anagnostopoulou et al., J Clin Invest 2012 and Mall et al., Am J Respir Crit Care Med 2008). We hypothesized that airway surface dehydration and reduced mucociliary clearance may increase the susceptibility for allergic airway inflammation due to reduced allergen clearance.   Results:  We demonstrate that airway surface dehydration in βENaC-Tg mice results into airway hyperresponsiveness as determined by lung function with the Flexivent system. Furthermore, intrapulmonary exposure to Aspergillus fumigatus extract significantly increased airway eosinophils and pulmonary IL-13 in βENaC-Tg mice. 11-color flow cytometry of BAL and lung tissue detected IL-13 secretion from Th2 cells, but also from other cells including recently discovered Lung Natural Helper cells and airway epithelium cells. IL-13 effector functions were further highlighted by introducing a genetic deletion of STAT6, a critical molecule for IL-13 signaling, to βENaC-Tg mice. These βENaC-Tg STAT6 -/-  mice were protected from airway eosinophilia, airway mucus obstruction and elevated IL-13 expression.   Conclusion:  Collectively, our results indicate that airway surface dehydration and impaired mucus clearance constitutes a risk factor for key pathologies in allergic airway disease including increased IL-13 production, eosinophilic inflammation and airway hyperresponsiveness.   Acknowledgements:  DFG (DFG MA 2081/3-2), BMBF (DZL 82DZL00401).
Safety and Efficacy of Nifedipine 20 mg Tablets in Hypertension Using Electronic Data Collection in General Practice
Authors: J E Marley
Journal: Journal of the Royal Society of Medicine (1989)

Electronic data collection was used in this open study to survey the safety and efficacy of nifedipine when used in the treatment of 3972 patients with mild to moderate essential hypertension. The safety and efficacy results are presented and discussed as well as the advantages, disadvantages and reliability of electronic data collection. The validity of data collected electronically has not previously been tested, such data having been assumed to be reliable. The pattern of adverse events reported in this study is compared with the pattern of reports to the Committee on Safety of Medicine (CSM), to Bayer UK and in a large paper-based study of nifedipine, in order to test these assumptions. Reported adverse medical events pre-treatment, prior to entry to the study and noted at visit 1, were compared with reports during treatment in the study at visits 2 and 3. The expected incidence of flushing and headache was seen which diminished with continued treatment. Reductions were seen in dyspnoea and impotence. Ankle oedema was observed and was not reduced by time alone. After one month of treatment with nifedipine 20 mg tablets twice daily, 66.5% of patients had a sitting phase V diastolic blood pressure of 90 mmHg or below and 79% of 95 mmHg or below.
Anaerobic and aerobic bacterial load of childhood non- cystic fibrosis bronchiectasis
Authors: Erkan Cakir, Ahmet Hakan Gedik, Meryem Iraz, Hayrettin Daskaya, Bilge Gultepe, Nurcan Keskin, Tarik Umutoglu
Journal: European Respiratory Journal (2014)

INTRODUCTION:  Non cystic fibrosis (CF) bronchiectasis ( BE) continues to be an issue in developing countries. In these patients, routine sputum culture shows the aerobic culture, and it does not have enough information about the anaerobic load.   MATERIALS-METHODS:    Eighty-eight patients with undergone flexible bronchoscopy (FB) were enrolled to the study. Laringial mask airwaywas used for FB and bronchial fluid while maintaining an anaerobic environment was immediately transported to the laboratory.   RESULTS:  The mean age of the patients was 11 ± 3.4, 53% were men. In the etiology primary ciliary dyskinesia (19 %), post -infectious BE (15 %), bronchiolitis obliterans (9 %), asthma (4 %), immunodeficiency (5 %), and idiopathic BE (47 %) was detected. 57% of the patients had aerobic and / or anaerobic growth. Aerobic growth was seen in 46% of the patients and the most frequently isolated bacteria are S. Pneumonia (27%), H Influenza (11%), P. Auriginosa (5% ), M. Catarrhalis (3% ) and C. Pneumonia (3%). Anaerobic growth was seen 14.3% of the patients and in the most common bacteria are Bacteroides (5%), Prevatella (5% ), Fusobacterium (2%), Clostridum (3%) and Actinomyces (3% ). Two patients were found to be both aerobic and anaerobic growth.   CONCLUSION:  This is the first study revealed anaerobic load of children with non CF-BE. For a discussion of our results of clinical and microbiological studies were presented.
Durability of Treatment Effect Using a Drug-Coated Balloon for Femoropopliteal Lesions
Authors: John R. Laird, Peter A. Schneider, Gunnar Tepe, Marianne Brodmann, Thomas Zeller, Christopher Metzger, Prakash Krishnan, Dierk Scheinert, Antonio Micari, David J. Cohen, Hong Wang, Melissa S. Hasenbank, Michael R. Jaff
Journal: Journal of the American College of Cardiology (2015)

Evidence from large, randomized, controlled peripheral artery disease trials reporting long-term outcomes using drug-coated balloons (DCBs) is limited. Previously, the DCB showed favorable 1-year outcomes compared with conventional percutaneous transluminal angioplasty (PTA), yet durability of the treatment effect with DCBs remains unknown.This study sought to investigate the longer-term outcomes of a paclitaxel-eluting DCB compared to PTA for femoropopliteal lesions.We enrolled 331 patients with symptomatic (Rutherford 2 to 4) femoropopliteal lesions up to 18 cm in length. Patients were randomly assigned in a 2:1 ratio to treatment with DCB or PTA. The 24-month assessments included primary patency, freedom from clinically driven target lesion revascularization (CD-TLR), major adverse events, and quality of life and functional outcomes as assessed by the EuroQOL-5D quality-of-life questionnaire, walking impairment questionnaire, and 6-min walk test.At 24 months, patients treated with DCB showed significantly higher primary patency when compared with PTA (78.9% vs. 50.1%; p < 0.001). The rates of CD-TLR were 9.1% and 28.3% (p < 0.001) for the DCB and PTA groups, respectively. The overall mortality rate in the DCB group was 8.1% versus 0.9% in the PTA group (p = 0.008). There were no device- or procedure-related deaths and no major amputations in either group through 24-month follow-up. The rate of vessel thrombosis was low (1.5% DCB vs. 3.8% PTA; p = 0.243), with no new events reported between 1 and 2 years. Both groups showed similar functional improvement at 2 years, although DCB patients achieved this level of function with 58% fewer reinterventions.The 24-month outcomes from the trial demonstrate a durable and superior treatment effect of DCB versus PTA with significantly higher primary patency, lower CD-TLR, and similar functional status improvement with fewer repeat interventions. (Randomized Trial of IN.PACT Admiral Drug Eluting Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease [INPACT SFA I]; NCT01175850; and IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA] [INPACT SFA II]; NCT01566461).
Clinical Radiosensitization: Why It Does and Does Not Work
Authors: C. Norman Coleman, James B. Mitchell
Journal: Journal of Clinical Oncology (1999)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.1.1 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10458210 Clinical Radiosensitization: Why It Does and Does Not Work C. Norman ColemanxC. Norman ColemanSearch for articles by this author , James B. MitchellxJames B. MitchellSearch for articles by this author Show More *Joint Center for Radiation Therapy Harvard Medical School Boston, MA and †Radiation Biology Branch National Cancer Institute Bethesda, MD https://doi.org/10.1200/JCO.1999.17.1.1 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Hyporeactivity of Rat Diaphragmatic Arterioles after Exposure to Hypoxia <i>In Vivo</i>
Authors: MOURAD TOPORSIAN, MICHAEL E. WARD
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The effect of prior in vivo hypoxia on the in vitro responses to changes in transmural pressure, α -adrenoceptor activation, and depolarization with KCl were evaluated in first-order diaphragmatic arterioles. Rats (n = 14 per group) were exposed to normoxia (controls) or to hypoxia (inspired O2 concentration = 10%) for 12 or 48 h. The arteriolar pressure-diameter relationships were recorded over a pressure range from 10 to 200 mm Hg. In separate groups of arterioles (n = 12 per group), the diaphragmatic arteriolar responses to phenylephrine (10− 8 to 10− 5 M) or KCl (10 to 100 mM) were determined after exposure to either room air or hypoxia for 48 h. In half of the arterioles studied, the endothelium was removed. After 12 h of hypoxia, the pressure-diameter relationship was normal in endothelialized arterioles but was shifted upward in de-endothelialized vessels (p < 0.05). After 48 h of hypoxia, the constrictor response to increasing transmural pressure was severely suppressed in all arterioles. The intraluminal diameters during activation with phenylephrine and KCl were larger in arterioles from rats exposed to hypoxia (103 ± 8 and 81 ± 7 μ m, respectively) than in control arterioles (41 ± 5 and 54 ± 6 μ m, respectively; p < 0.05 for differences). During maximum phenylephrine- and KCl-induced constriction in de-endothelialized arterioles, diameters averaged 125 ± 8 and 105 ± 8 μ m, respectively, for arterioles from hypoxic rats and 32 ± 6 and 40 ± 5 μ m, respectively, for arterioles from control vessels. Exposure to hypoxia results in impairment of diaphragmatic arteriolar smooth muscle reactivity and reversal of the normal inhibitory influence of the endothelium on diaphragmatic arteriolar tone.
Characteristics of cough reported by adolescents with different ENT disorders
Authors: Maja Jurca, Cristian Dogaru, Aniña Pescatore, Ben Spycher, Philipp Latzin, Erol Gaillard, Claudia Kuehni
Journal: European Respiratory Journal (2014)

Introduction   Cough is a frequent symptom in children with upper respiratory tract problems. We do not know whether cough characteristics vary between different ENT (Ear,Nose and Throat) disorders, such as allergic rhinitis, habitual snoring and otitis. This study compares the association of different cough characteristics with these disorders.   Methods   In a population-based cohort in Leicestershire, UK, we analysed self-reported respiratory outcomes in adolescents aged 13-17 years in 2010. We computed symptom scores for allergic rhinitis (0-4), chronic snoring (0-3) and otitis (0-2). We estimated odds ratios (ORs) for cough characteristics (coughing more than peers, night cough, cough of long duration (>3 weeks), cough triggered by aeroallergens and exercise) comparing children with high and low ENT symptom scores using logistic regression.   Results   Among 2,805 children who replied to the questionnaire, 530 reported a high allergic rhinitis score, 217 had severe snoring and 370 had otitis at least once in the last 12 months. Adjusting for age, sex and ethnicity, all ENT disorders showed significant associations with cough, but the results varied between disorders. Severe allergic rhinitis was most strongly associated with cough triggered by aeroallergens (OR 6.4; 95%CI 5.1-7.9), children with a high snoring score reported mainly coughing more than peers (4.1; 3.0-5.7) and cough of long duration (3.6; 2.6-5.1). Otitis was associated with all cough questions with ORs from 1.6 to 2.1.   Conclusion   Characteristics of cough in children vary between different ENT disorders. These results help to distinguish underlying aetiologies of cough in children.  Funding: SNF PDFMP3 137033; SNF 32003B-144068; Asthma UK 07/048.
Selective V2-Receptor Vasopressin Antagonism Decreases Urinary Aquaporin-2 Excretion in Patients with Chronic Heart Failure
Authors: PIERRE-YVES MARTIN, WILLIAM T. ABRAHAM, XU LIEMING, BEATRIZ R. OLSON, RON M. OREN, MAMIKO OHARA, ROBERT W. SCHRIER
Journal: Journal of the American Society of Nephrology (1999)

Aquaporin-2 (AQP-2), a water channel located on the apical membrane of collecting duct cells, regulates water reabsorption under the control of vasopressin (AVP). Using an antibody directed to human AQP-2, a quantitative Western blot analysis was performed to determine the collecting duct responsiveness to an oral, nonpeptide, V2 receptor antagonist (VPA-985) in patients with chronic NYHA II and III heart failure. Standards were derived by conjugating the immunizing peptide to maleimide-activated bovine serum albumin and a standard curve was generated for each blot. Quantification of baseline steady-state AQP-2 excretion was done by collecting urine on the day before study drug administration. The next day patients received either placebo or VPA-985 at one of four different doses and urine was collected every 2 h. Thereafter, urinary AQP-2 excretion was calculated as a ratio of the urine flow and was expressed in pmol/h. During baseline, steady-state excretion did not change significantly (T0-T2, 458 +/- 44; T2-T4, 443 +/- 35; T4-T6, 422 +/- 35; T6-T8, 401 +/- 30). Compared to placebo, urinary AQP-2 excretion decreased significantly and in all groups in a dose-dependent manner during VPA-985 administration. The most impressive decrease was observed in the 250-mg group (T0-T2, 89 +/- 5; T2-T4, 50 +/- 18; T4-T6, 43 +/- 22; T6-T8, 42 +/- 23; P < 0.001 during each period compared with baseline and placebo results). VPA-985 significantly increased solute-free water clearance and urine output and significantly decreased urinary osmolality. Urinary AQP-2 excretion correlated best with solute-free water clearance during T0-T2 and T2-T4 collection, but a correlation with urinary osmolality and urinary output was also found during these periods. In conclusion, AQP-2 urinary excretion, as measured by quantitative Western analysis, is a sensitive biologic marker to assess the short-term responsiveness of the collecting duct to a V2 receptor AVP antagonist in chronic heart failure.