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Firas El Chaer, Dimpy P Shah, Roy F Chemaly
Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy...
October 19, 2016: Blood
Malik Y Ghannam, Mohammed Naseemuddin, Peter Weiser, John O Mason
BACKGROUND: Acute Multifocal Hemorrhagic Retinal Vasculitis (AMHRV) is a rare disease with unknown incidence that presents with abrupt onset of visual loss associated with retinal vasculitis, retinal hemorrhage, non-confluent posterior retinal infiltrates, vitreous cellular inflammation and papillitis in, otherwise, healthy adult individuals. The reported treatment options for Acute Multifocal Hemorrhagic Retinal Vasculitis are oral corticosteroids, intravitreal ganciclovir and laser photocoagulation or vitrectomy...
October 18, 2016: BMC Ophthalmology
Emanuele Nicastro, Sara Giovannozzi, Paola Stroppa, Anna Paola Callegaro, Alessandra Tebaldi, Claudio Farina, Michele Colledan, Lorenzo DʼAntiga
BACKGROUND: Most pediatric liver transplantation (LT) centers administer long courses of prophylaxis against Cytomegalovirus (CMV) without evidence of benefit and with significant drug exposure and costs. We aimed at evaluating overall outcomes, direct and putative indirect effects of CMV, possible impact of viremia and risk factors for CMV infection in pediatric LT recipients managed with ganciclovir-based preemptive therapy (PET). METHODS: The records of all the children who underwent LT between 2008 and 2014 were retrospectively analyzed...
October 17, 2016: Transplantation
Majid Sohrabi, Farida Behzadian, Seied Mohammad Javad Hosseini, Hadi Lashini
BACKGROUND: Gancyclovir-resistant (GanR) cytomegalovirus (CMV) remains an issue, especially in solid organ transplant (SOT) recipients. Some mutations in UL54 and UL97 confer this resistance. Long-lasting high-dose drug exposure, high viral load, together with lack of sufficient compliance with treatment may account for these mutations. The aim of this study was to detect UL97 and UL54 putative mutations conferring ganciclovir-resistance in renal organ transplant recipients with high CMV load...
October 2016: Archives of Iranian Medicine
Yaoping Shi, Jianfeng Wang, Zhibin Bai, Yonggang Li, Longhua Qiu, Bo Zhai, Feng Zhang, Xiaoming Yang
Despite recent advances in surgical technique and treatment strategies for esophageal cancer (EC), to effectively manage the advanced (metastatic or disseminated) and recurrent EC still remain a great challenge. The aim of this study was to determine the feasibility of using intra-esophagus radiofrequency hyperthermia to enhance local HSV-TK/ganciclovir-mediated suicide gene therapy of an innovative animal models with orthotopic esophageal squamous cancers. Human esophageal squamous cancer (ESCa) cells were labeled with lentivirus/luciferase...
2016: American Journal of Cancer Research
De Gui Wang, Mei-Jun Zhao, Yong-Qiang Liu, Xiang-Wen Liu, Hai-Tao Niu, Yan-Feng Song, Ying-Xia Tian
Adenovirus-mediated gene therapy is a promising strategy for bladder cancer treatment. However, the loss of the coxsackie and adenovirus receptor (CAR) in bladder cancer cells decreases the infection efficiency of the therapeutic adenovirus. In this study, we constructed an Arg-Gly-Asp (RGD)-modified adenovirus, RGDAd-UPII-TK, that carries a suicide gene called HSV-TK that is driven by a human UPII promoter. Then, we tested the bladder cancer specificity of the UPII promotor and the expression of the HSV-TK protein...
September 28, 2016: Oncotarget
Elisabeth A Pitt, Pranay Dogra, Ravi S Patel, Angela Williams, Jonathan S Wall, Tim E Sparer
Human cytomegalovirus (HCMV) infection in utero can lead to congenital sensory neural hearing loss and mental retardation. Reactivation or primary infection can increase the morbidity and mortality in immune suppressed transplant recipients and AIDS patients. The current standard of care for HCMV disease is nucleoside analogs, which can be nephrotoxic. In addition resistance to current treatments is becoming increasingly common. In an effort to develop novel CMV treatments, we tested the effectiveness of the D-form of a novel heparan sulfate binding peptide, p5RD, at reducing infection of ganciclovir (GCV) resistant HCMVs in vitro and MCMV in vivo...
September 25, 2016: Antiviral Research
William J Muller
Viral infections in the fetus or newborn often involve the central nervous system (CNS) and can lead to significant morbidity and mortality. Substantial progress has been made in identifying interventions decreasing adverse neurodevelopmental outcomes in this population. This review highlights progress in treatment of important viruses affecting the CNS in these susceptible hosts, focusing on herpes simplex (HSV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), and enteroviruses. The observation that high-dose acyclovir improves mortality in neonatal HSV disease culminated decades of antiviral research for this disease...
September 27, 2016: Pediatric Research
Charlotte J Houldcroft, Josephine M Bryant, Daniel P Depledge, Ben K Margetts, Jacob Simmonds, Stephanos Nicolaou, Helena J Tutill, Rachel Williams, Austen J J Worth, Stephen D Marks, Paul Veys, Elizabeth Whittaker, Judith Breuer
Human cytomegalovirus (HCMV) is a significant pathogen in immunocompromised individuals, with the potential to cause fatal pneumonitis and colitis, as well as increasing the risk of organ rejection in transplant patients. With the advent of new anti-HCMV drugs there is therefore considerable interest in using virus sequence data to monitor emerging resistance to antiviral drugs in HCMV viraemia and disease, including the identification of putative new mutations. We used target-enrichment to deep sequence HCMV DNA from 11 immunosuppressed pediatric patients receiving single or combination anti-HCMV treatment, serially sampled over 1-27 weeks...
2016: Frontiers in Microbiology
Ester Fernández López, Elsie Chan
PURPOSE: There is currently limited information regarding the outcomes of endothelial keratoplasty in eyes with cytomegalovirus (CMV) endotheliitis. We report the results of Descemet stripping automated endothelial keratoplasty (DSAEK) for endothelial failure secondary to CMV. METHODS: This is a retrospective review of 4 eyes of 4 patients with CMV endotheliitis and DSAEK. CMV was confirmed in each case by a positive aqueous tap on qualitative polymerase chain reaction...
September 21, 2016: Cornea
Noriko Mitsuiki, Keita Tamanuki, Kenshi Sei, Jun Ito, Aiko Kishi, Kenji Kobayashi, Yoshiho Hatai, Masayuki Nagasawa
We report a neonate of severe cytomegalovirus (CMV) infection who presented vomiting, severe thrombocytopenia and thrombotic microangiopathy (TMA). He showed occasional vomiting at 3 weeks of age and visited us with systemic petechiae at 29 days old. Platelet was markedly decreased to 18,000/μL and fragmented red blood cells were increased in the peripheral blood. Intravenous ganciclovir (GCV) administration was started at 35 days old after detection of CMV in the peripheral blood. His normal values of T-cell receptor excision circles (TREC) and signal joint kappa-deleting recombination excision circles (sjKREC) excluded the possibility of severe immunodeficiency...
September 11, 2016: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
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...
September 7, 2016: Stem Cells Translational Medicine
Danielle El-Haddad, Firas El Chaer, Jackapat Vanichanan, Dimpy P Shah, Ella J Ariza-Heredia, Victor E Mulanovich, Alison M Gulbis, Elizabeth J Shpall, Roy F Chemaly
BACKGROUND: The emergence of resistance to available antiviral drugs may cause higher Cytomegalovirus (CMV)-associated morbidity and mortality in hematopoietic cell transplant (HCT) recipients. Few novel antiviral drugs are being developed with potential effect against refractory or resistant CMV infections. Brincidofovir, an oral nucleotide analog and prodrug of cidofovir, has shown in vitro activity against CMV. METHODS: We reviewed data of 4 cancer patients with resistant CMV or herpes simplex virus (HSV) infections and were treated with brincidofovir under emergency IND application...
October 2016: Antiviral Research
Denise Bradley, Sebastian Moreira, Vishak Subramoney, Clifford Chin, Jane Ives, Ka Wang
BACKGROUND: Valganciclovir (VGCV) effectively prevents cytomegalovirus disease in adult and pediatric solid organ transplant (SOT) recipients. A dosing algorithm for VGCV for pediatric patients, based on body surface area and renal function, provides a personalized dose using age-appropriate formulations. The suitability of this dosing algorithm has not been assessed specifically in infants and neonates 4 months of age and younger receiving a SOT. METHODS: This multicenter prospective study evaluated the pharmacokinetics (PK) and safety of VGCV oral solution in 17 heart transplant recipients 4 months of age and younger who received two doses of VGCV on consecutive days using the pediatric dosing algorithm...
August 30, 2016: Pediatric Infectious Disease Journal
Jianfeng Wang, Yaoping Shi, Zhibin Bai, Yonggang Li, Longhua Qiu, Guy Johnson, Feng Zhang, Xiaoming Yang
PURPOSE: To determine the feasibility of using radiofrequency hyperthermia (RFH) to enhance the therapeutic effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Human HCC cells (HepG2) were first transfected with lentivirus/luciferase. For both in-vitro confirmation and in-vivo validation, luciferase-labeled HCC cells and HCC tumor xenografts on mice received different treatments: (i) combination therapy of intratumoral HSV-TK/GCV-mediated gene therapy plus MR imaging-heating-guidewire (MRIHG)-mediated RFH; (ii) gene therapy only; (iii) RFH only; and (iv) phosphate-buffered saline (PBS) as control...
August 28, 2016: International Journal of Hyperthermia
Mariko Sunada, Daisuke Kinoshita, Naoko Furukawa, Minako Kihara, Akira Nishimura, Masako Moriuchi, Hiroyuki Moriuchi
BACKGROUND: Ganciclovir is a therapeutic choice for extremely premature infants with severe postnatal cytomegalovirus disease, but little is known about its optimal dose size and dosing interval for them. CASE PRESENTATION: We treated an extremely premature female infant with postnatal cytomegalovirus infection with intravenous administration of ganciclovir since 49 days of life (postmenstrual age of 31 weeks). After ganciclovir treatment was initiated at a dose of 5 mg/kg every 12 h, cytomegalovirus loads in the peripheral blood were markedly decreased...
2016: BMC Pediatrics
Jayant Venkatramani Iyer, Rupesh Agrawal, Tun Kuan Yeo, Dinesh V Gunasekeran, Praveen Kumar Balne, Bernett Lee, Veonice Bijin Au, John Connolly, Stephen C B Teoh
The data shows the aqueous humor cytokine profiling results acquired in a small cohort of 17 HIV patients clinically diagnosed with Cytomegalovirus retinitis using the FlexMAP 3D (Luminex®) platform using the Milliplex Human Cytokine® kit. Aqueous humor samples were collected from these patients at different time points (pre-treatment and at 4-weekly intervals through the 12-week course of intravitreal ganciclovir treatment) and 41 cytokine levels were analyzed at each time point. CMV DNA viral load was assessed in 8 patients at different time points throughout the course of ganciclovir treatment...
September 2016: Data in Brief
Tetsu Akimoto, Tomoyuki Yamazaki, Osamu Saito, Shigeaki Muto, Eiji Kusano, Daisuke Nagata
Several viral infections may occasionally induce supraglottic mass lesions, resulting in an obstructive airway emergency. We herein report one such case in a 63-year-old male immunocompromised patient with nephrotic syndrome due to membranous nephropathy who also had ophthalmic herpes zoster with a laryngeal mass, which required urgent intubation and mechanical ventilation. The patient was initially treated with acyclovir; however, because a serological analysis revealed a concurrent cytomegalovirus infection, we discontinued the administration of acyclovir and gave priority to the simultaneous treatment of the cytomegalovirus and varicella-zoster virus infections with ganciclovir...
2016: Clinical Medicine Insights. Case Reports
M A AlDabbagh, M R Gitman, D Kumar, A Humar, C Rotstein, S Husain
The role of antiviral prophylaxis for the prevention of posttransplant lymphoproliferative disease (PTLD) remains controversial for solid organ transplantation (SOT) recipients who are seronegative for Epstein-Barr virus (EBV) but who received organs from seropositive donors. We performed a systematic review and meta-analysis to address this issue. Two independent assessors extracted data from studies after determining patient eligibility and completing quality assessments. Overall, 31 studies were identified and included in the quantitative synthesis...
August 22, 2016: American Journal of Transplantation
Hossein Keyvani, Sedigheh Taghinezhad Saroukalaei, Amir Hossein Mohseni
BACKGROUND: Human cytomegalovirus (HCMV) infections are a major cause of morbidity and mortality among immunocompromised patients. Prolonged antiviral therapy is a cause of mutation and drug resistance in the HCMV genome. OBJECTIVES: The aim of this study was to identify resistance to ganciclovir (GCV) in Iranian immunosuppressed patients at two different stages of the disease: early (before GCV is initiated) and late (after six months of GCV therapy). PATIENTS AND METHODS: In this study, 87 specimens from Iranian patients were amplified using nested PCR amplification of the UL97 gene...
May 2016: Jundishapur Journal of Microbiology
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