Read by QxMD icon Read


Alice Laroni, Davide Brogi, Vincenzo Brescia Morra, Leonello Guidi, Carlo Pozzilli, Giancarlo Comi, Alessandra Lugaresi, Renato Turrini, Debora Raimondi, Antonio Uccelli, Giovanni Luigi Mancardi
: The safety profile of fingolimod is well established in clinical trials and post-marketing studies. This study aimed to evaluate the safety and tolerability of fingolimod in a cohort of Italian patients with relapsing-remitting multiple sclerosis (RRMS). This is a non-comparative, open-label, multicentre, interventional study conducted in patients with RRMS with no suitable alternative treatment option. Safety and tolerability of fingolimod 0.5 mg were assessed by recording adverse events (AEs) and serious AEs (SAEs)...
October 18, 2016: Neurological Sciences
Joseph A Carcillo, J Michael Dean, Richard Holubkov, John Berger, Kathleen L Meert, Kanwaljeet J S Anand, Jerry Zimmerman, Christopher J Newth, Rick Harrison, Jeri Burr, Douglas F Willson, Carol Nicholson, Michael J Bell, Robert A Berg, Thomas P Shanley, Sabrina M Heidemann, Heidi Dalton, Tammara L Jenkins, Allan Doctor, Angie Webster
BACKGROUND: Nosocomial infection remains an important health problem in long stay (>3 days) pediatric intensive care unit (PICU) patients. Admission risk factors related to the development of nosocomial infection in long stay immune competent patients in particular are not known. METHODS: Post-hoc analysis of the previously published Critical Illness Stress induced Immune Suppression (CRISIS) prevention trial database, to identify baseline risk factors for nosocomial infection...
November 2016: Pediatric Infectious Disease Journal
Xabier Urra, Carlos Laredo, Yashu Zhao, Sergio Amaro, Salvatore Rudilosso, Arturo Renú, Alberto Prats-Galino, Anna M Planas, Laura Oleaga, Ángel Chamorro
BACKGROUND: Infections represent the most frequent medical complications in stroke patients. Their main determinants are dysphagia and a transient state of immunodepression. We analyzed whether distinct anatomical brain regions were associated with the occurrence of stroke-associated infections or immunodepression. MATERIALS AND METHODS: In 106 patients with acute ischemic stroke, we evaluated the incidence of pneumonia, urinary tract infection, or other infections together with the characterization of biomarkers of immunodepression...
October 11, 2016: Brain, Behavior, and Immunity
Anat Gafter-Gvili, Ronit Gurion, Pia Raanani, Ofer Shpilberg, Liat Vidal
Data in the literature are lacking regarding the infection-related adverse events of bendamustine-containing regimens. Therefore, we aimed to assess this risk. We conducted a systematic review and meta-analysis of all randomized controlled trials including bendamustine-containing regimens and those administered for any lymphoproliferative disorder or plasma cell dyscrasia compared with any other regimens. A comprehensive search was conducted until December 2015. Two reviewers appraised the quality of trials and extracted data...
October 13, 2016: Hematological Oncology
Erez Rechavi, Atar Lev, Eran Eyal, Ortal Barel, Nitzan Kol, Sarit Farage Barhom, Ben Pode-Shakked, Yair Anikster, Raz Somech, Amos J Simon
PURPOSE: Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is an extremely rare autosomal recessive disease. The immune phenotype is characterized by hypogammaglobulinemia in the presence of B cells. T cell lymphopenia also develops in some patients. We sought to further investigate the immune defect in an ICF patient with a novel missense mutation in DNMT3B and a severe phenotype. METHODS: Patient lymphocytes were examined for subset counts, immunoglobulin levels, T and B cell de novo production (via excision circles) and receptor repertoire diversity...
October 12, 2016: Journal of Clinical Immunology
Hai-Yun Xiao, Scott H Watterson, Charles M Langevine, Anurag S Srivastava, Soo S Ko, Yanlei Zhang, Robert Joseph Cherney, Weiwei Guo, John L Gilmore, James E Sheppeck, Dauh-Rurng Wu, Peng Li, Duraisamy Ramasamy, Pirama Nayagam Arunachalam, Arvind Mathur, Tracy L Taylor, David J Shuster, Kim W McIntyre, Ding Ren Shen, Melissa Yarde, Mary Ellen Cvijic, Anthony M Marino, Praveen V Balimane, Zheng Yang, Dana M Banas, Georgia Cornelius, Celia J D Arienzo, Bethanne M Warrack, Lois D Lehman-McKeeman, Luisa M Salter-Cid, Jenny H Xie, Joel C Barrish, Percy H Carter, Alaric J Dyckman, T G Murali Dhar
Fingolimod (1) is the first approved oral therapy for the treatment of relapsing remitting multiple sclerosis. While the phosphorylated metabolite of fingolimod was found to be a non-selective S1P receptor agonist, agonism specifically of S1P1 is responsible for the peripheral blood lymphopenia believed to be key to its efficacy. Identification of modulators that maintain activity on S1P1 while sparing activity on other S1P receptors could offer equivalent efficacy with reduced liabilities. We disclose in this paper a ligand based drug design approach that led to the discovery of a series of potent tricyclic agonists of S1P1 with selectivity over S1P3 and were efficacious in a pharmacodynamic model of suppression of circulating lymphocytes...
October 11, 2016: Journal of Medicinal Chemistry
Kristen Lew, Nishith Mewada, Sahana Ramanujam, Bahareh Hassanzadeh, John E Donahue, Leema Reddy Peddareddygari, Robert Moser, Charles Kososky, Raji P Grewal
We report a 35-year-old healthy male who developed central nervous system inflammatory demyelinating disease consistent with tumefactive multiple sclerosis. About 2 weeks after onset of symptoms and prior to initiation of therapy, the patient had lymphopenia and low CD4 and CD8 levels. His lymphocyte count was 400 cells/µl (850-3,900 cells/µl), CD4 was 193 cells/µl (490-1,740 cells/µl) and CD8 was 103 cells/µl (180-1,170 cells/µl). He was treated with intravenous methylprednisolone followed by therapeutic plasma exchange, the levels of CD4 and CD8 normalized, and ultimately, he recovered completely...
May 2016: Case Reports in Neurology
Thibaut Girardot, Julie Mouillaux, Estellie Idealisoa, Fanny Poujol, Christelle Rouget, Thomas Rimmelé, Guillaume Monneret, Julien Textoris, Fabienne Venet
In several clinical contexts, the measurement of ATP concentration in T lymphocytes has been proposed as a biomarker of immune status, predictive of secondary infections. However, the use of such biomarker in lymphopenic patients requires some adaptations in the ATP dosage protocol. We used blood from healthy volunteers to determine the optimal experimental settings. We investigated technical aspects such as the type of anticoagulant for blood sampling, the effect of freeze and thaw cycles, the reagent and sample mixing sequence, and the optimal dilution buffer...
October 6, 2016: Journal of Immunological Methods
Anthony L Desbien
A clear index for a response to adjuvants is a change in the cellular composition of lymph nodes draining the site of adjuvant injection (Didierlaurent et al., J Immunol 183:6186-6197, 2009; Caproni et al., J Immunol 188:3088-98, 2012; Desbien et al., Eur J Immunol 1-11, 2014). During the steady state, lymph nodes (LNs) are composed of a fixed ratio of innate and adaptive cells awaiting activation signals from tissue draining lymph. Upon exposure to innate stimulants, lymph nodes undergo dramatic changes. The most apparent change to the lymph node is an increase in size...
2017: Methods in Molecular Biology
Kesava A Ramakrishnan, Reuben J Pengelly, Yifang Gao, Mary Morgan, Sanjay V Patel, E Graham Davies, Sarah Ennis, Saul N Faust, Anthony P Williams
BACKGROUND: Methylenetetrahydrofolate dehydrogenase (MTHFD1) deficiency has recently been reported to cause a folate-responsive syndrome displaying a phenotype that includes megaloblastic anemia and severe combined immunodeficiency. OBJECTIVE: To describe our investigative approach to the molecular diagnosis and evaluation of immune dysfunction in a family with MTHFD1 deficiency. METHODS: The methods used were exome sequencing and analysis of variants in genes involved in the folate metabolic pathway in a family with 2 affected siblings...
October 1, 2016: Journal of Allergy and Clinical Immunology in Practice
Nancy F Crum-Cianflone
Background.  Invasive aspergillosis may occur in the setting of severe influenza infections due to viral-induced respiratory epithelium disruption and impaired immune effects, but data are limited. Methods.  A retrospective study was conducted among severe influenza cases requiring medical intensive care unit (ICU) admission at an academic center during the 2015-2016 season. Data collected included respiratory cultures, medical conditions and immunosuppressants, laboratory and radiographic data, and outcomes...
September 2016: Open Forum Infectious Diseases
Hsing-Chuan Tsai, Yingxiang Huang, Christopher S Garris, Monica A Moreno, Christina W Griffin, May H Han
Fingolimod (FTY720, Gilenya), a sphingosine-1-phosphate receptor (S1PR) modulator, is one of the first-line immunomodulatory therapies for treatment of relapsing-remitting multiple sclerosis (MS). Human S1PR1 variants have been reported to have functional heterogeneity in vitro, suggesting that S1PR1 function may influence FTY720 efficacy. In this study, we examined the influence of S1PR1 phosphorylation on response to FTY720 in neuroinflammation. We found that mice carrying a phosphorylation-defective S1pr1 gene [S1PR1(S5A) mice] were refractory to FTY720 treatment in MOG35-55-immunized and Th17-mediated experimental autoimmune encephalomyelitis (EAE) models...
June 16, 2016: JCI Insight
Marcel Doerflinger, Jason Glab, Christina Nedeva, Irvin Jose, Ann Lin, Lorraine O'Reilly, Cody Allison, Marc Pellegrini, Richard S Hotchkiss, Hamsa Puthalakath
Sepsis-induced lymphopenia is a major cause of morbidities in intensive care units and in populations with chronic conditions such as renal failure, diabetes, HIV and alcohol abuse. Currently, other than supportive care and antibiotics, there are no treatments for this condition. We developed an in vitro assay to understand the role of the ER-stress-mediated apoptosis process in lymphocyte death during polymicrobial sepsis, which was reproducible in in vivo mouse models. Modulating ER stress using chemical chaperones significantly reduced the induction of the pro-apoptotic protein Bim both in vitro and in mice...
October 3, 2016: Scientific Reports
L M Ren, Y Li, C F Zhang, X T Zhao, X Liu, Z G Li
Objective: To retrospectively investigate the clinical characteristics, risk factors of Cytomegalovirus (CMV) infection in patients with underlying rheumatic diseases. Methods: Clinical records of 263 rheumatic patients with or without CMV infection, hospitalized from March 2011 to June 2014 in Peking University People's Hospital, were analyzed.Clinical characteristics were summarized and compared in CMV positive and negative groups, to investigate the risk factors for CMV infection.Statistical analyses were conducted with SPSS 20...
September 20, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Nasr Y A Hemdan, Cynthia Weigel, Christina-Maria Reimann, Markus H Gräler
Sepsis is a systemic inflammatory response to pathogens and a leading cause of hospital related mortality worldwide. Sphingosine 1-phosphate (S1P) regulates multiple cellular processes potentially involved in the pathogenesis of sepsis, including antigen presentation, lymphocyte egress, and maintenance of vascular integrity. We thus explored the impact of manipulating S1P signaling in experimental polymicrobial sepsis in mice. Administration of 4-deoxypyridoxine (DOP), an inhibitor of the S1P-degrading enzyme S1P-lyase, or of the sphingosine analogue FTY720 that serves as an S1P receptor agonist after phosphorylation ameliorated morbidity, improved recovery from sepsis in surviving mice, and reduced sepsis-elicited hypothermia and body weight loss...
September 29, 2016: European Journal of Immunology
Vincent Biajoux, Jessica Natt, Christelle Freitas, Nagham Alouche, Antoine Sacquin, Patrice Hemon, Françoise Gaudin, Nicolas Fazilleau, Marion Espéli, Karl Balabanian
CXCR4 plays a central role in B cell immune response, notably by promoting plasma cell (PC) migration and maintenance in the bone marrow (BM). Gain-of-function mutations in CXCR4 affecting receptor desensitization have been reported in the rare immunodeficiency called WHIM syndrome (WS). Despite lymphopenia, patients mount an immune response but fail to maintain it over time. Using a knockin mouse model phenocopying WS, we showed that, counter-intuitively, a gain of Cxcr4 function inhibited the maintenance of antibody titers after immunization...
September 27, 2016: Cell Reports
S Ellsworth, G Rebesco, K Fife, S Grossman
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
R Rahman, P J Catalano, N D Arvold, A A Aizer, S E Weiss, N Pinnell, M C Horvath, L Christianson, D A Reardon, E Q Lee, L Nayak, M Rinne, I F Dunn, A J Golby, M D Johnson, E B Claus, K L Ligon, P Wen, B M Alexander
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Lianwen Zhang, Michael B Steele, Nathan Jenks, Jacquelyn Grell, Marshall Behrens, Rebecca Nace, Shruthi Naik, Mark J Federspiel, Stephen J Russell, Kah-Whye Peng
Tumor selective oncolytic vesicular stomatitis viruses (VSVs) are being evaluated in clinical trials. Here we report that the MPC-11 murine plasmacytoma model is so extraordinarily susceptible to oncolytic VSVs that a low dose of virus leads to extensive intratumoral viral replication, sustained viremia, intravascular coagulation and a rapidly fatal tumor lysis syndrome (TLS). Rapid softening, shrinkage and hemorrhagic necrosis of flank tumors was noted within 1-2 days after virus administration, leading to hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, increase in plasma cell free DNA, lymphopenia, consumptive coagulopathy, increase in fibrinogen degradation products, decreased liver function tests, dehydration, weight loss, and euthanasia or death after 5-8 days...
September 27, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
A Utegenova, B Zhetpisbayev, Yu Semenova, A Kydyrmoldina, A Argynbekova
The study aim was to investigate the combined influence of emotional stress and low doses of ionizing radiation (0.2 Gr) on cellular immunity of laboratory animals in the remote period. One hundred and twenty Wistar rats were divided into 4 groups: 1 group control, 2 group - exposed to gamma-radiation, 3 group - exposed to emotional stress, 4 group was exposed to the combined influence of emotional stress and gamma-radiation. Emotional stress was simulated by tail suspension. Animals from groups 2 and 4 were exposed to a single dose of 0...
July 2016: Georgian Medical News
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"