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https://www.readbyqxmd.com/read/28292662/cytomegalovirus-duodenitis-associated-with-life-threatening-duodenal-hemorrhage-in-an-immunocompetent-patient-a-case-report
#1
Lucy Shen, David Youssef, Suzan Abu-Abed, Sangita K Malhotra, Kenneth Atkinson, Elena Vikis, George Melich, Shawn MacKenzie
INTRODUCTION: Cytomegalovirus (CMV) is known to be opportunistic in immunocompromised patients. However, there have been emerging cases of severe CMV infections found in immunocompetent patients. Gastrointestinal (GI) CMV disease is the most common manifestation affecting immunocompetent patients, with duodenal involvement being exceedingly rare. Presented is a case of an immunocompetent patient with life-threatening bleeding caused by CMV duodenitis, requiring surgical intervention. PRESENTATION OF CASE: A 60-year-old male with history of disseminated Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia and aortic valve infective endocarditis, presented with life-threatening upper GI hemorrhage...
February 21, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28283734/intestinal-perforation-due-to-hemorrhagic-cytomegalovirus-enteritis-in-a-patient-with-severe-uncontrolled-lupus-nephritis-a-case-and-review-of-the-literature
#2
REVIEW
Keigo Ikeda, Shihoko Nakajima, Kana Tanji, Takuya Hirai, Kaori Uomori, Shinji Morimoto, Shigeki Tomita, Masaki Fukunaga, Naoto Tamura, Iwao Sekigawa
A 31-year-old woman with systemic lupus erythematosus and lupus nephritis was treated with prednisone and immunosuppressants. After her lupus nephritis symptoms worsened, both high-dose steroid and cyclophosphamide pulse therapy were administered. The patient developed an intestinal perforation, and laparoscopic Hartmann's surgery was performed on the sigmoid colon. Serum Cytomegalovirus (CMV) antigen C7HRP was detected, and the patient was diagnosed with CMV colitis and underwent a colon resection. Severe hematochezia continued despite ganciclovir administration, and the patient underwent laparoscopic total colectomy and partial ileostomy...
March 11, 2017: Rheumatology International
https://www.readbyqxmd.com/read/28220857/samhd1-enhances-nucleoside-analogue-efficacy-against-hiv-1-in-myeloid-cells
#3
Paula Ordonez, Simone Kunzelmann, Harriet C T Groom, Melvyn W Yap, Simon Weising, Chris Meier, Kate N Bishop, Ian A Taylor, Jonathan P Stoye
SAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates into component nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosphohydrolase activity by reducing the cellular dNTP pool to a level that cannot support productive reverse transcription. We now show that, in addition to this direct effect on virus replication, manipulating cellular SAMHD1 activity can significantly enhance or decrease the anti-HIV-1 efficacy of nucleotide analogue reverse transcription inhibitors presumably as a result of modulating dNTP pools that compete for recruitment by viral polymerases...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28213738/cytomegalovirus-infection-in-patients-with-lupus-nephritis-clinical-and-laboratory-features-and-therapeutic-considerations
#4
Lei Zhang, Jianling Tao, Yubing Wen, Li Li, Xueyi Wu, Xuewang Li, Xuemei Li
To better clarify the clinical features and therapeutic strategy of CMV infection in lupus nephritis patients, we retrospectively surveyed a total of 40 lupus nephritis patients, who had been hospitalized and underwent renal biopsy and diagnosed as having CMV infection during their hospitalization at our institution within the last 10 years. The percentage of CMV infections in the entire hospitalized lupus nephritis population was 5.3% (40/755). The principal clinical features of the 40 CMV-infected patients were hematological disorders (n = 25), fever (n = 21), liver dysfunction (n = 19), and respiratory symptoms (n = 12)...
February 17, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28198039/combined-environmental-risk-assessment-for-the-antiviral-pharmaceuticals-ganciclovir-and-valganciclovir-in-europe
#5
Jürg Oliver Straub
Potential environmental risks of the old antiviral pharmaceuticals ganciclovir (GCV) and valganciclovir (VGCV) were reassessed based on new environmental fate and chronic ecotoxicity tests and on actual use data for Europe. Valganciclovir is hydrolyzed to GCV by intestinal and hepatic esterases, and hence the new environmental tests only refer to GCV. A sorption study showed that GCV will not sorb significantly, excluding the soil as a relevant environmental compartment. Despite earlier data suggesting nondegradability, a new water/sediment fate test showed GCV to be primarily and ultimately degraded and to be nonpersistent...
February 15, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28193173/cytomegalovirus-colitis-in-hospitalized-inflammatory-bowel-disease-patients-in-taiwan-a-referral-center-study
#6
Meng-Tzu Weng, Chien-Chih Tung, Yi-Shuan Lee, Yew-Loong Leong, Ming-Jium Shieh, Chia-Tung Shun, Cheng-Yi Wang, Jau-Min Wong, Shu-Chen Wei
BACKGROUND: Colitis is exacerbated in patients with concurrent cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). We assessed the prevalence and clinical features of CMV colitis in hospitalized IBD patients. METHODS: A retrospective study reviewed the data from January 1, 1998 through December 31, 2013 compiled at the National Taiwan University Hospital. The CMV colitis patients' demographic data, clinical information, treatment regimens, pathologic findings, and outcome were analyzed...
February 13, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28191782/preventing-pluripotent-cell-teratoma-in-regenerative-medicine-applied-to-hematology-disorders
#7
Aurelie Bedel, François Beliveau, Isabelle Lamrissi-Garcia, Benoit Rousseau, Isabelle Moranvillier, Benoit Rucheton, Veronique Guyonnet-Dupérat, Bruno Cardinaud, Hubert de Verneuil, François Moreau-Gaudry, Sandrine Dabernat
Iatrogenic tumorigenesis is a major limitation for the use of human induced pluripotent stem cells (hiPSCs) in hematology. The teratoma risk comes from the persistence of hiPSCs in differentiated cell populations. Our goal was to evaluate the best system to purge residual hiPSCs before graft without compromising hematopoietic repopulation capability. Teratoma risk after systemic injection of hiPSCs expressing the reporter gene luciferase was assessed for the first time. Teratoma formation in immune-deficient mice was tracked by in vivo bioimaging...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28182772/murine-cytomegalovirus-infection-of-mouse-macrophages-stimulates-early-expression-of-suppressor-of-cytokine-signaling-socs-1-and-socs3
#8
Christine I Alston, Richard D Dix
Human cytomegalovirus (HCMV) is a species-specific β-herpesvirus that infects for life up to 80% of the world's population and causes severe morbidity in at-risk immunocompromised populations. Suppressors of cytokine signaling (SOCS)1 and SOCS3 are host proteins that act as inducible negative feedback regulators of cytokine signaling and have been implicated in several ocular diseases and viral infections. We recently found in our mouse model of experimental cytomegalovirus retinitis that subretinally-injected murine cytomegalovirus (MCMV) stimulates ocular SOCS1 and SOCS3 during retrovirus-induced immune suppression of murine AIDS (MAIDS), and that infiltrating macrophages are prominent cellular sources of retinal SOCS1 and SOCS3 expression...
2017: PloS One
https://www.readbyqxmd.com/read/28179375/quantitative-prediction-of-human-renal-clearance-and-drug-drug-interactions-of-organic-anion-transporter-substrates-using-in-vitro-transport-data
#9
Sumathy Mathialagan, Mary A Piotrowski, David A Tess, Bo Feng, John Litchfiled, Manthena V Varma
Organic anion transporters (OATs) play an important role in the renal secretion of drugs, and their functional change can result in pharmacokinetic variability. In this study, we applied transport rates measured using OAT-transfected human embryonic kidney cells to predict human renal secretory and total renal clearance of 31 diverse drugs. Selective substrates to OAT1 (tenofovir), OAT2 (acyclovir and ganciclovir) and OAT3 (benzylpenicillin, oseltamivir acid) were used to obtain relative activity factors (RAFs) for these individual transporters by relating in vitro transport clearance to in vivo secretory clearance...
February 8, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28148846/tumor-homing-cytotoxic-human-induced-neural-stem-cells-for-cancer-therapy
#10
Juli R Bagó, Onyi Okolie, Raluca Dumitru, Matthew G Ewend, Joel S Parker, Ryan Vander Werff, T Michael Underhill, Ralf S Schmid, C Ryan Miller, Shawn D Hingtgen
Engineered neural stem cells (NSCs) are a promising approach to treating glioblastoma (GBM). The ideal NSC drug carrier for clinical use should be easily isolated and autologous to avoid immune rejection. We transdifferentiated (TD) human fibroblasts into tumor-homing early-stage induced NSCs (h-iNSC(TE)), engineered them to express optical reporters and different therapeutic gene products, and assessed the tumor-homing migration and therapeutic efficacy of cytotoxic h-iNSC(TE) in patient-derived GBM models of surgical and nonsurgical disease...
February 1, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28145791/human-plasma-metabolic-profiles-of-benzydamine-a-flavin-containing-monooxygenase-probe-substrate-simulated-with-pharmacokinetic-data-from-control-and-humanized-liver-mice
#11
Miho Yamazaki-Nishioka, Makiko Shimizu, Hiroshi Suemizu, Megumi Nishiwaki, Marina Mitsui, Hiroshi Yamazaki
1. Benzydamine is used clinically as a nonsteroidal anti-inflammatory drug in oral rinses and is employed in preclinical research as a flavin-containing monooxygenase (FMO) probe substrate. In this study, plasma concentrations of benzydamine and its primary N-oxide and N-demethylated metabolites were investigated in control TK-NOG mice, in humanized-liver mice, and in mice whose liver cells had been ablated with ganciclovir. 2. Following oral administration of benzydamine (10 mg/kg) in humanized-liver TK-NOG mice, plasma concentrations of benzydamine N-oxide were slightly higher than those of demethyl benzydamine...
February 1, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28134467/late-cytomegalovirus-infection-in-children-high-incidence-of-allograft-rejection-and-hepatitis-in-donor-negative-and-seropositive-liver-transplant-recipients
#12
A Verma, K Palaniswamy, G Cremonini, N Heaton, A Dhawan
The complications and outcome associated with late CMV infection and disease on the graft are poorly characterized in PLT recipients. We studied the overall incidence, risk factors, and outcome of late CMV infection and disease (infection 6 months after transplant) in 180 PLT recipients admitted between 2008 and 2011 at the King's College Hospital. Antiviral prophylaxis of intravenous ganciclovir was given only to the D+R- group starting at day 7 post-transplant. The remaining groups (D-R+, D+R+, and D-R-) received pre-emptive therapy when they have CMV viremia above cut-off value and treatment for symptomatic CMV infection...
January 30, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28105484/-intravitreal-ganciclovir-as-an-additional-therapy-option-in-acute-retinal-necrosis
#13
M Bischoff-Jung, A Viestenz, M Fiorentzis, L Daas, B Seitz, G Pappas, A Viestenz
Acute retinal necrosis (ARN) is a rare viral inflammatory disease, characterized by uveitis, retinal vasculitis, and necrosis in the late stages. Therapeutic management is based on the clinical findings. The positive outcome in our patient (VA 0.6) indicates that, beside the management of retinal detachment and lens opacification, additional intravitreal injections of 2 mg ganciclovir may achieve better results than systemic/topical antiviral application alone.
January 19, 2017: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
https://www.readbyqxmd.com/read/28102325/viral-micrornas-target-a-gene-network-inhibit-stat-activation-and-suppress-interferon-responses
#14
Dhivya Ramalingam, Joseph M Ziegelbauer
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 12 pre-microRNAs during latency that are processed to yield ~25 mature microRNAs (miRNAs). We were interested in identifying cellular networks that were targeted by KSHV-miRNAs and employed network building strategies using validated KSHV miRNA targets. Here, we report the identification of a gene network centering on the transcription factor- signal transducer and activator of transcription 3 (STAT3) that is targeted by KSHV miRNAs. KSHV miRNAs suppressed STAT3 and STAT5 activation and inhibited STAT3-dependent reporter activation upon IL6-treatment...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28093696/secondary-haemophagocytic-lymphohistiocytosis-triggered-by-postnatally-acquired-cytomegalovirus-infection-in-a-late-preterm-infant
#15
Christine Silwedel, Eric Frieauff, Wolfgang Thomas, Johannes G Liese, Christian P Speer
Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition with impairment of cytotoxic T-cells and natural killer cells. Causes in infants are mostly hereditary immune defects as well as various infectious triggering factors, amongst these cytomegalovirus (CMV). Vertical CMV transmission may occur in utero, during birth, and by breast feeding. Usually, a CMV infection transmitted via breast milk is symptomatic only in very immature preterm infants. We report on a late preterm infant born after 35 + 5 weeks of gestation with a birth weight of 1840 g, being admitted to our intensive care unit at the age of 9 weeks with acute enteritis and severe dehydration...
January 16, 2017: Infection
https://www.readbyqxmd.com/read/28090751/a-safety-checkpoint-to-eliminate-cancer-risk-of-the-immune-evasive-cells-derived-from-human-embryonic-stem-cells
#16
Jingjin He, Zhili Rong, Xuemei Fu, Yang Xu
Human embryonic stem cells (hESCs) hold great promise in the regenerative therapy of many currently untreatable human diseases. One of the key bottlenecks is the immune rejection of hESC-derived allografts by the recipient. To overcome this challenge, we have established new approaches to induce immune protection of hESC-derived allografts through the coexpression of immune suppressive molecules CTLA4-Ig and PD-L1. However, this in turn raises a safety concern of cancer risk because these hESC-derived cells can evade immune surveillance...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28089555/epstein-barr-virus-and-renal-transplantation
#17
REVIEW
Jade Le, Christine M Durand, Irfan Agha, Daniel C Brennan
Epstein-Barr virus (EBV) is a gamma herpesvirus associated with diseases ranging from asymptomatic viremia to post-transplant malignancies in kidney transplant recipients. EBV specifically is associated with post-transplantation lymphoproliferative disorder (PTLD), in kidney transplant recipients, with increased risk in EBV seronegative patients with EBV seropositive donors on intensified immunosuppression. The diagnosis of PTLD relies on clinical suspicion plus tissue biopsy with polymerase chain reaction (PCR) testing of blood currently used for risk determination in high-risk recipients...
January 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28081328/cytomegalovirus-hepatitis-in-49-pediatric-patients-with-normal-immunity
#18
Hasan Tezer, Saliha Kanık Yüksek, Belgin Gülhan, Aslı Nur Özkaya Parlakay, Ceyda Tuna Kırsaçlıoğlu
BACKGROUND/AIM: Cytomegalovirus (CMV) hepatitis is generally asymptomatic or rarely can lead to severe complications in immunocompetent hosts. This study aims to evaluate CMV hepatitis in immunocompetent young children, which is discussed relatively rarely in the literature. MATERIALS AND METHODS: A retrospective review of 49 pediatric patients with CMV hepatitis from January 2005 to December 2010 was performed. RESULTS: The median age of the patients was 5...
December 20, 2016: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28059624/pre-clinical-development-of-gene-modification-of-hematopoietic-stem-cells-with-chimeric-antigen-receptors-for-cancer-immunotherapy
#19
Sarah M Larson, Laurel C Truscott, Tzu-Ting Chiou, Amie Patel, Roy Kao, Andy Tu, Tulika Tyagi, Xiang Lu, David Elashoff, Satiro N De Oliveira
Patients with refractory or recurrent B-lineage hematologic malignancies have less than 50% of chance of cure despite intensive therapy and innovative approaches are needed. We hypothesize that gene modification of hematopoietic stem cells (HSC) with an anti-CD19 chimeric antigen receptor (CAR) will produce a multi-lineage, persistent immunotherapy against B-lineage malignancies that can be controlled by the HSVsr39TK suicide gene. High-titer third-generation self-inactivating lentiviral constructs were developed to deliver a second-generation CD19-specific CAR and the herpes simplex virus thymidine kinase HSVsr39TK to provide a suicide gene to allow ablation of gene-modified cells if necessary...
January 6, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28039960/preventive-strategies-against-cytomegalovirus-and-incidence-of-%C3%AE-herpesvirus-infections-in-solid-organ-transplant-recipients-a-nationwide-cohort-study
#20
C Martin-Gandul, S Stampf, D Héquet, N J Mueller, A Cusini, C van Delden, N Khanna, K Boggian, C Hirzel, P Soccal, H H Hirsch, M Pascual, P Meylan, O Manuel
We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138)...
December 31, 2016: American Journal of Transplantation
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