tbuckley/cabot-search huggingface dataset:
Comparison of pentamidine inhaled dose with two different nebulizers
Authors: Nicolas Audag, Etienne Sokal, Françoise Smets, Dimitri Van der Linden, Xavier Stéphenne, Giuseppe Liistro, Gregory Reychler
Journal: European Respiratory Journal (2014)

Body: INTRODUCTION: Nebulized pentamidine is used in the prevention of pneumocystis carinii pneumonia in immunosuppressed patients. A specific nebulizer with characteristics to ensure deep lung deposition is required. It must include a circuit with expiratory filter preventing the dissemination of droplets into the environment. The reference nebulizer for pentamidine delivery is the Respirgard II®. All nebulizers with comparable properties could be used for the nebulization. AIMS AND OBJECTIVES: The aim of this work was to evaluate and to compare the inhaled dose between the Respirgard II® and the Isoneb®. METHODS: The nebulizers were connected to a dual chamber lung model (5600i Dual Adult Training/Test Lung®,Michigan Instrument Inc.) simulating usual breathing pattern of an adult patient. A solution of pentamidine (300mg/6mL sterile water) was nebulized during 20 minutes. We measured in triplicate the inhaled dose by weighting the filter positioned between the nebulizer and the test lung. We measured also the residual solution by weighting the cup of nebulizers before and directly after nebulization. The residual dose was obtained by subtracting the inhaled dose from the nominal dose. RESULTS: There is no significant difference in the inhaled dose (p = 0.611). The residual solution in the nebulizer cup is greater with Respirgard II® (p= 0.0363) but we find no significant difference in residual dose (p= 0.611). CONCLUSION: We observed that the inhaled dose is similar with the two nebulizers
Trichotillomania, Skin Picking, and Other Body-Focused Repetitive Behaviorsby GrantJon E., M.D., M.P.H., J.D., SteinDan J., M.D., Ph.D., WoodsDouglas, Ph.D., and KeuthenNancy J., Ph.D. Washington, DC, American Psychiatric Publishing, 2012, 268 pp., $59.00.
Authors: Joseph Zohar, Oded Ben-Arush
Journal: American Journal of Psychiatry (2012)
Deep Sequencing Reveals Oligoclonality At The Immunoglobulin Locus In Multiple Myeloma Patients
Authors: Joaquin Martinez-Lopez, Mariateresa Fulciniti, Santiago Barrio, Victoria Carlton, Martin Moorhead, Juan Jose Lahuerta, Kenneth C. Anderson, Florence Magrangeas, Stephane Minvielle, Herve Avet-loiseau, Malek Faham, Nikhil C. Munshi
Journal: Blood (2013)
ErbB3–ErbB2 Complexes as a Therapeutic Target in a Subset of Wild-type BRAF/NRAS Cutaneous Melanomas
Authors: Claudia Capparelli, Sheera Rosenbaum, Lisa D. Berman-Booty, Amel Salhi, Nadège Gaborit, Tingting Zhan, Inna Chervoneva, Jason Roszik, Scott E. Woodman, Michael A. Davies, Yulius Y. Setiady, Iman Osman, Yosef Yarden, Andrew E. Aplin
Journal: Cancer Research (2015)

The treatment options remain limited for patients with melanoma who are wild-type for both BRAF and NRAS (WT/WT). We demonstrate that a subgroup of WT/WT melanomas display high basal phosphorylation of ErbB3 that is associated with autocrine production of the ErbB3 ligand neuregulin-1 (NRG1). In WT/WT melanoma cells displaying high levels of phospho-ErbB3, knockdown of NRG1 reduced cell viability and was associated with decreased phosphorylation of ErbB3, its coreceptor ErbB2, and its downstream target, AKT. Similar effects were observed by targeting ErbB3 with either siRNAs or the neutralizing ErbB3 monoclonal antibodies huHER3-8 and NG33. In addition, pertuzumab-mediated inhibition of ErbB2 heterodimerization decreased AKT phosphorylation, cell growth in vitro, and xenograft growth in vivo. Pertuzumab also potentiated the effects of MEK inhibitor on WT/WT melanoma growth in vitro and in vivo. These findings demonstrate that targeting ErbB3-ErbB2 signaling in a cohort of WT/WT melanomas leads to tumor growth reduction. Together, these studies support the rationale to target the NRG1-ErbB3-ErbB2 axis as a novel treatment strategy in a subset of cutaneous melanomas.
Cigarette smoke exposure facilitates allergic sensitization to house dust mite and aggravates the asthmatic phenotype in mice
Authors: Ellen Lanckacker, Kurt Tournoy, Gabriele Holtappels, Hamida Hammad, Bart Lambrecht, Guy Joos, Tania Maes
Journal: European Respiratory Journal (2012)

Background: Cigarette smoke (CS) exposure has been associated with increased sensitization and asthma development in children and adults.  Aims and objectives: We wanted to design a novel mouse model to unravel the impact of CS on the different stages of asthma pathogenesis, specifically during the initial sensitization and acute asthma development.  Methods: Mice were exposed to 25µg house dust mite (HDM) extract (intranasaly, 1/week) for 3 consecutive weeks, combined with air or CS exposure (3 times/day, 5 days/week) during 3 weeks or only during the first week.  Results: Mice concomitantly exposed to HDM and CS for 3 weeks, showed a significant increase in eosinophils, goblet cells, airway hyperresponsiveness and HDM-specific serum IgG1, compared to sole HDM or CS exposure. Interestingly, exposure to CS only during the first week was sufficient to induce an aggravated asthmatic phenotype after rechallenge with HDM allergens. To further investigate the effect of CS during mucosal sensitization, mice were exposed to HDM (just once) and 3 days of CS, followed by the assessment of DC trafficking and early Th2 responses in the lymph nodes. This short CS exposure amplified DC-mediated transport of HDM allergens to the lymph nodes and was sufficient to generate a Th2 response, characterized by IL-4, IL-5 and IL-13 production in the draining lymph nodes.  Conclusions: CS facilitates the development of HDM-induced allergic asthma. Only a few days of smoke exposure are sufficient to facilitate allergic sensitization to common aeroallergens.  Funding: IUAP - Belgian Science Policy P6/35 and BOF/GOA 01251504.
Changes in Protein C and Free Protein S during Pregnancy and following Hysterectomy
Authors: R Warwick, R A Hutton, L Goff, E Letsky, M Heard
Journal: Journal of the Royal Society of Medicine (1989)

Two longitudinal studies were undertaken to measure the naturally occurring coagulation inhibitors, protein C and protein S, in females who were either pregnant or who were undergoing hysterectomy. Functional and immunological protein C and free protein S were assayed. During pregnancy, protein C levels remained unchanged except for a small increase in protein C antigen at 28-32 weeks gestation. The free protein S fell significantly and progressively during pregnancy, although only in about one-third of patients did the level fall below the normal range. In the hysterectomy study, a significant fall in protein C occurred on days one and three after surgery but had returned to normal by the time of discharge (days 7-10). A small rise in free protein S was observed at time of discharge, but this factor was otherwise unchanged. We conclude that the changes observed may contribute to the hypercoagulable state which is associated with pregnancy or major surgery.
Lenalidomide is safe and active in <scp>W</scp>aldenström macroglobulinemia
Authors: Guillemette Fouquet, Stéphanie Guidez, Marie‐Odile Petillon, Chanaz Louni, Bella Ohyba, Malek Dib, Stéphanie Poulain, Charles Herbaux, Audrey Martin, Béatrice Thielemans, Pauline Brice, Sylvain Choquet, Jana Bakala, Claire Bories, Hélène Demarquette, Morgane Nudel, Olivier Tournilhac, Bertrand Arnulf, Steven LeGouill, Pierre Morel, Anne Banos, Lionel Karlin, Gilles Salles, Véronique Leblond, Xavier Leleu
Journal: American Journal of Hematology (2015)

Lenalidomide is manageable and effective in multiple myeloma, particularly in elderly patients. Surprisingly, the combination of lenalidomide with rituximab produced clinically significant anemia at 25 mg/day for 21/28 days, the highest possible dose, in Waldenström's Macroglobulinemia (WM). We aimed to determine the maximum tolerated dose (MTD) of single agent lenalidomide and determine its impact on WM. RV-WM-0426 is a multicenter dose escalation open label phase 1/2 study of lenalidomide in relapsed/refractory WM (RRWM). Lenalidomide was given orally 21/28 days per cycle for 1 year, at escalated dose of 15 to 20 mg during phase 1 to determine the MTD; the phase 2 part was conducted at the MTD. Seventeen RRWM patients were included. The MTD was established at 15 mg/day 21/28. By ITT analysis, the overall response rate was 29%. With a median follow-up of 36 months, median TTP was 16 months (95% CI 5.5-26), the 5-year OS was 91%. The most frequent adverse events ≥ grade 3 at 15 mg were 14% anemia and 43% neutropenia. The MTD of lenalidomide is 15 mg/day 21/28 days in RRWM. Lenalidomide is active in the treatment of RRWM and the safety profile appears manageable. Future studies may look into combinations of lenalidomide and continuous dosing.
Intravenous Glycopyrrolate and Atropine at Induction of Anaesthesia: A Comparison<sup>1</sup>
Authors: M Dewar, J Greenan, C J Jones
Journal: Journal of the Royal Society of Medicine (1983)

In unpremedicated patients presenting for general anaesthesia for electroconvulsive therapy (ECT), the use of atropine combined with methohexitone as an intravenous induction agent was found to produce a significantly greater increase in heart rate than glycopyrrolate in similar combination. There was no difference in the antisialogogue effect of the two drugs at the doses used, and both drugs provided similar protection against the effects of suxamethonium and ECT on heart rate.
Red blood cell transfusion is associated with increased hemolysis and an acute phase response in a subset of critically ill children
Authors: Camilla L'Acqua, Sheila Bandyopadhyay, Richard O. Francis, Donald J. McMahon, Marianne Nellis, Sujit Sheth, Steven G. Kernie, Gary M. Brittenham, Steven L. Spitalnik, Eldad A. Hod
Journal: American Journal of Hematology (2015)

In healthy adults, transfusion of older stored red blood cells (RBCs) produces extravascular hemolysis and circulating non–transferrin‐bound iron. In a prospective, observational study of critically ill children, we examined the effect of RBC storage duration on the extent of hemolysis by comparing laboratory measurements obtained before, and 4 hr after, RBC transfusion ( N = 100) or saline/albumin infusion ( N = 20). Transfusion of RBCs stored for longer than 4 weeks significantly increased plasma free hemoglobin ( P &lt; 0.05), indirect bilirubin ( P &lt; 0.05), serum iron ( P &lt; 0.001), and non‐transferrin‐bound iron ( P &lt; 0.01). However, days of storage duration poorly correlated (R 2 &lt;0.10) with all measured indicators of hemolysis and inflammation. These results suggest that, in critically ill children, most effects of RBC storage duration on post‐transfusion hemolysis are overwhelmed by recipient and/or donor factors. Nonetheless, we identified a subset of patients ( N = 21) with evidence of considerable extravascular hemolysis (i.e., increased indirect bilirubin ≥0.4 mg/dL). In these patients, transfusion‐associated hemolysis was accompanied by increases in circulating non‐transferrin‐bound iron and free hemoglobin and by an acute phase response, as assessed by an increase in median C‐reactive protein levels of 21.2 mg/L ( P &lt; 0.05). In summary, RBC transfusions were associated with an acute phase response and both extravascular and intravascular hemolysis, which were independent of RBC storage duration. The 21% of transfusions that were associated with substantial hemolysis conferred an increased risk of inducing an acute phase response. Am. J. Hematol. 90:915–920, 2015. © 2015 Wiley Periodicals, Inc.
Primary Low-Grade Lymphomas of the Intestine
Authors: C. S. Chim, C. Choy, G. C. Ooi, R. Liang
Journal: Journal of Clinical Oncology (1999)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.11.3684 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10550168 Primary Low-Grade Lymphomas of the Intestine C. S. ChimxC. S. ChimSearch for articles by this author , C. ChoyxC. ChoySearch for articles by this author , G. C. OoixG. C. OoiSearch for articles by this author , R. LiangxR. LiangSearch for articles by this author Show More University Departments of Medicine, Pathology, and Radiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong https://doi.org/10.1200/JCO.1999.17.11.3684 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Bcl11a (Ctip1) Controls Migration of Cortical Projection Neurons through Regulation of Sema3c
Authors: Christoph Wiegreffe, Ruth Simon, Katharina Peschkes, Carolin Kling, Michael Strehle, Jin Cheng, Swathi Srivatsa, Pentao Liu, Nancy A. Jenkins, Neal G. Copeland, Victor Tarabykin, Stefan Britsch
Journal: Neuron (2015)
The features of high resolution CT (HRCT) in patients with respiratory symptom due to gastroesophageal reflux disease (GERD)
Authors: Miho Ikura, Hirohiko Ikura, Hisayuki Abe, Seiichirou Watanabe, Shin Kimoto
Journal: European Respiratory Journal (2012)

GERD is well known as one of cause for chronic cough. Gastric acid refluxed stimulates the esophagus and airways, then it induce cough with or without inflammation. This study aimed to evaluate the features of HRCT in patients with GERD.     Ten consecutive patients (6 males and 4 females) with various symptoms, 7 of cough, 3 of sputum, 2 of heart burn, and one of sore throat. They underwent HRCT using a MDCT. Eight of them underwent gastrointestinal fiberscopy and were diagnosed, 4 of GERD with reflux esophagitis, one of sliding hernia, and 3 of normal findings. All of patients were medicated with proton pump inhibitor, H2 blocker, and mosapride citrate hydrate, and improved with their symptom after two weeks.  Two radiologist (H.I. and M.I.), who were board-certified by Japan Radiological Society, diagnosed and estimated image quality with their consultation. They observed some findings, ground glass opacity (GGO), bronchial wall thickening (BWT), centrilobular nodule (CLN), consolidation, and esophageal sliding herniation (ESH), expected definitely old inflammatory change.     One of the patients was observed a finding as normal in HRCT. HRCT depicted the features, 6 of GGO, 5 of CLN, 2 of BWT, one of consolidation, one of SH in 9 patients. GGO were frequently observed in 5 of 7 patients with chronic cough. The findings of GGO existed in bilateral in all of 5, in lower lobe in 4, in upper lobe in 2, and in middle lobe in one.     The HRCT findings of GGO were frequently observed in patients with chronic cough due to GERD.
Investigation of doxorubicin on the skin: A spectroscopic study to understand the pathogenesis of PPE
Authors: J. Lademann, A. Martschick, U. Jacobi, H. Richter, M. Darvin, J. Sehouli, G. Oskay-Oezcelik, J.-U. Blohmer, W. Lichtenegger, W. Sterry
Journal: Journal of Clinical Oncology (2005)

5093 Background: Pegylated liposomal doxorubicin has showed its efficacy against solid and angiomatous tumors. Nevertheless, severe and dose-limiting mucocutaneous reactions occur, mostly the palmar-plantar erythrodysesthesia syndrome (PPE) located on the palms and plantae and also intertrigeneous sites.No prophylactic therapy for PPE is known. Therefore, a better understanding of the pathogenesis of PPE could be the basis for the development of prevention and effective treatment. Methods: In the first part of the study, the penetration of Doxorubicin from inside out onto the skin was studied by laser scanning microscopy on different anatomic sites of 12 patients. Results: It was found that Doxorubicin was excreted by the sweat glands onto the skin surface between 1 and 2 hours after injection. Subsequently, it was distributed homogeneously onto the skin surface and afterwards penetrated into the stratum corneum. Intensive fluorescent signals were detected on the palm and the plantae of the patients, where the density of sweat glands is highest. In addition, this thick stratum corneum represents an effective reservoir for drugs, where they can be stored for a long period of time and converted into free radicals, which destroy the tissue resulting in PPE. In the second part of the study, several attempts failed to stop sweat production during the injection. Antioxidant substances were applied onto the skin surface of the palm to neutralize the free radicals. An interaction of the free radicals of Doxorubicin with the antioxidants was observed by Raman spectroscopy. Conclusions: The topical application of antioxidant substances seems to be an efficient way to prevent PPE. No significant financial relationships to disclose.
Abstract 4830: The Effects of Stem Cells on C-Kit Up-Regulation and Cell-Cycle Reentry of Neonatal Cardiomyocytes are Mediated by IGF-1 Receptor Activation
Authors: Xi-Yong Yu, Yong-Jian Geng, Xiao-Hong Li, Chun-Yu Deng, Shu-Guang Lin, Tong Yang, Yao-Hua Song, Yangxin Li
Journal: Circulation (2008)

Mesenchymal stem cells (MSCs) contribute myocardial regeneration, and the beneficial effects may be mediated by paracrine factors produced by MSCs. C-kit positive neonatal cardiomyocytes (NCMs) contribute to myocardial regeneration, but they do not give a robust regenerative response since low expression of c-kit. Cell-cycle reentry of NCMs and insulin-like growth factor (IGF-1) improve myocardial function in infarcted hearts. MSCs and NCMs were prepared from Lewis rats, and cocultured in two chambers which allowed the diffusion of secreted factors from upper chamber to lower chamber, but prevented cell contacts. MSCs secreted significant amount of IGF-1 (159.6 ± 34.4 pg/ug DNA at 24 h, 285.3 ± 28.5 pg/ug DNA at 48 h, and 358.3 ± 39.9 pg/ug DNA at 72 h), whereas the amount of IGF-1 in conditioned medium from NCMs was undetectable assessed by IGF-1 ELISA. Using flow cytometry, we found that the secreted factors by MSCs increased c-kit protein expression, which was attenuated by IGF-1 receptor neutralizing antibody (IGF-1R Ab) and phosphatidylinositol 3 (PI3) kinase inhibitor LY 294002 (NCM vs MSC/NCM vs MSC/NCM+IGF-1R Ab vs MSC/NCM+ LY294002= 1.5 ± 0.6 % vs 5.5 ± 0.3 % vs 1.9 ± 0.6% vs 2.1 ± 0.5%) assessed by flow cytometry. The cytokinesis of NCMs was increased when cocultured with MSC analyzed by calcein fluorescence intensity (3.1 ± 0.5 fold increase, p&lt;0.02). As determined by BrdU assay, the DNA synthesis of NCMs was significantly increased when cocultured with MSC compared to NCM alone (1.8 ± 0.3 fold increase at 48 h, 2.6 ± 0.2 fold increae at 72 h), which was attenuated by IGF-1R Ab and by PI3 kinase inhibitor. To confirm the paracrine effects of MSCs are mediated by IGF-1 signaling and PI3/Akt pathway, we performed in vitro Akt kinase assay using GSK-3 fusion protein as substrate, and found that co-culture system increased the activity of Akt kinase in NCMs, and the IGF-1R Ab and PI3 kinase inhibitor dose-dependent blocked the ability of co-culture system to increase Akt kinase activity. Our results demonstrate that the paracrine effects of MSC on c-kit up-regulation and cell-cycle reentry of NCM are mediated by IGF-1R activation through PI3 kinase/Akt - mediated pathway. These findings provide a new paradigm for the biological effects of IGF-1 on myocardial regeneration. This research has received full or partial funding support from the American Heart Association, AHA South Central Affiliate (Arkansas, New Mexico, Oklahoma &amp; Texas).
Global evaluation of treatment effectiveness (GETE) is an accurate predictor of response to omalizumab in patients with severe allergic asthma: A pooled analysis
Authors: Jean Bousquet, Shashidhar Rao, Volkan Manga
Journal: European Respiratory Journal (2014)

Introduction   Global evaluation of treatment effectiveness is a validated tool, and has been used to evaluate the clinical response to omalizumab at 16 weeks of therapy, in patients with moderate-severe allergic asthma. The relationship of investigator GETE with response to omalizumab was further explored in recent studies of severe allergic asthma.   Methods   Data from three omalizumab studies (INNOVATE, EXALT & EXTRA) in severe allergic asthma patients were pooled to explore the association of the investigator GETE score at 16 weeks of therapy with the response to the omalizumab treatment vs placebo. A negative binomial model was used to measure the association of the post treatment exacerbation with investigator GETE adjusted for baseline percentage predicted FEV 1 , treatment received (omalizumab vs placebo), baseline peripheral blood eosinophil count, baseline total IgE level, history of exacerbation, body mass index, age, smoking status & gender.   Results   In the negative binomial regression model investigator GETE was an accurate predictor of exacerbations (p   Conclusion   GETE is an accurate predictor of response to omalizumab and can be used as an effective tool to identify omalizumab responders at 16 weeks of therapy. The tool also discriminates between the treatment and placebo responders.
The pattern of lymphocyte subpopulations including Fas positive cells in patients with obstructive sleep apnea (OSA)
Authors: Aleksandra Piechuta, Tomasz Skirecki, Iwona Osinska, Anna Kaszuba, Barbara Moszczuk, Piotr Bielicki, Joanna Domagala-Kulawik
Journal: European Respiratory Journal (2013)

Recurrent pauses in respiration during sleep have its consequences in deteriorations of immune system functions in patients with OSA that may lead to systemic inflammation.  This study was to analyze the proportion of lymphocyte subpopulations in the blood of patients with OSA with special relation to receptor of apoptosis - Fas on these cells. The results were compared regarding to polysomnographic parameters (AHI, ODI) and BMI.  The main lymphocyte subpopulations and Fas receptor on CD4 and CD8 cells were examined by flow cytometry in the blood of 42 patients with confirmed OSA.  30 of all 42 patients (mean age 58 years, 13 female) were obese (BMI>30kg/m^2; mean BMI=33.5 kg/m^2). The polysomnographic study showed that 40 patients had severe OSA (AHI per hour>30; mean AHI per hour=55, mean ODI per hour=31).  The median proportion of CD3 (75.7%), CD3HLADR (7.5%), CD4 (41.9%), CD8 (34.5%), the CD4/CD8 ratio (1.3), CD19 (7.4%), NK (14.5%) cells did not differ between patients and reference data. The median Fas positive CD4 and Fas positive CD8 cells were respectively 31.7% and 20.3%, which also did not differ from reference data.  The severity of OSA, determined by AHI and ODI, was negatively related to Fas positive CD4 and CD8 subsets (ns). These correlations were statistically significant among obese patients with severe OSA and those with low Hb concentration (lower than 14.7g/dl), p  In conclusion, the number of dyspnea and desaturation episodes during sleeping may be involved in lower rate of lymphocyte apoptosis thus promotes systemic inflammation.