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[PMID]:29377953
[Au] Autor:Waduthantri S; Zhou L; Chee SP
[Ad] Endereço:Singapore Eye Research Institute, Singapore, Singapore.
[Ti] Título:Intra-cameral level of ganciclovir gel, 0.15% following topical application for cytomegalovirus anterior segment infection: A pilot study.
[So] Source:PLoS One;13(1):e0191850, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To investigate the intra-cameral level of ganciclovir following topical application of ganciclovir gel, 0.15% for cytomegalovirus (CMV) anterior segment infection. DESIGN: Non-randomized, prospective, interventional clinical study. METHODS: Patients with active CMV anterior segment infection seen at Singapore National Eye Centre, confirmed by positive CMV real time PCR (RT-PCR) of the aqueous humor, that had not been treated with any form of ganciclovir in the preceding 1 month were recruited. They were treated with ganciclovir gel, 0.15% 1cc 5 times a day. Following 6 weeks of treatment, CMV load in the aqueous humor was measured using CMV RT-PCR and the ganciclovir drug levels in tears and aqueous humor were measured using high-performance liquid chromatography-mass spectrometry. The clinical features of the disease activity and the central corneal thickness (CCT) were recorded at the baseline and post-treatment. RESULTS: There were 29 eyes of 29 patients, of which 23 eyes had CMV anterior uveitis and 6 eyes had CMV endotheliitis. At the end of week 6, 26 eyes had undetectable CMV titre in the aqueous humor and no anterior chamber (AC) activity. Two patients had an increased CMV titre and increased AC inflammation. Both of these patients were non-compliant with the treatment. One patient had a reduced CMV titre in the aqueous humor with minimal AC inflammation. The mean ganciclovir concentration in the aqueous humor and the tears were 17.4 ± 30.6 ng/ml and 20,420.9 ± 33,120.8 ng/ml respectively. Mean CCT was 552.2 ± 42.3 microns. There was a weak correlation between the ganciclovir concentration in the aqueous humor and CCT (Spearmen's r = + 0.42, p = 0.025). There was no significant correlation between the ganiclovir concentration in the tears and CCT (Spearmen's r = + 0.39, p = 0.11). CONCLUSION: Ganciclovir levels in the aqueous humor was below the 50% inhibitory dose (ID50) for CMV replication, following topical application of the ganciclovir gel, 0.15%. TRIAL REGISTRATION: SingHealth Centralized Institutional Review Board, Singapore; R733/17/2010, ClinicalTrials.gov; NCT01647529.
[Mh] Termos MeSH primário: Segmento Anterior do Olho/patologia
Antivirais/administração & dosagem
Infecções por Citomegalovirus/tratamento farmacológico
Ganciclovir/administração & dosagem
[Mh] Termos MeSH secundário: Administração Oftálmica
Adulto
Idoso
Idoso de 80 Anos ou mais
Cromatografia Líquida
Citomegalovirus/genética
Feminino
Seres Humanos
Masculino
Meia-Idade
Projetos Piloto
Estudos Prospectivos
Reação em Cadeia da Polimerase em Tempo Real
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:CLINICAL STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiviral Agents); P9G3CKZ4P5 (Ganciclovir)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191850


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[PMID]:29157621
[Au] Autor:Lurain K; Yarchoan R; Uldrick TS
[Ad] Endereço:HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, 10 Center Drive, Bethesda, MD 20892-1868, USA.
[Ti] Título:Treatment of Kaposi Sarcoma Herpesvirus-Associated Multicentric Castleman Disease.
[So] Source:Hematol Oncol Clin North Am;32(1):75-88, 2018 02.
[Is] ISSN:1558-1977
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Kaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease (MCD) is a rare, polyclonal lymphoproliferative disorder characterized by flares of inflammatory symptoms, edema, cytopenias, lymphadenopathy, and splenomegaly. Diagnosis requires a lymph node biopsy. Pathogenesis is related to dysregulated inflammatory cytokines, including human and viral interleukin-6. Rituximab alone or in combination with chemotherapy, such as liposomal doxorubicin, has led to an overall survival of over 90% at 5 years. Experimental approaches to treatment include virus activated cytotoxic therapy with high-dose zidovudine and valganciclovir and targeting human interleukin-6 activity. Despite successful treatment of KSHV-MCD, patients remain at high risk for developing non-Hodgkin lymphomas.
[Mh] Termos MeSH primário: Doença de Castleman/tratamento farmacológico
Doxorrubicina/uso terapêutico
Ganciclovir/análogos & derivados
Herpesvirus Humano 8
Rituximab/uso terapêutico
Zidovudina/uso terapêutico
[Mh] Termos MeSH secundário: Biópsia
Doença de Castleman/diagnóstico
Doença de Castleman/metabolismo
Doença de Castleman/patologia
Ganciclovir/uso terapêutico
Seres Humanos
Interleucina-6/antagonistas & inibidores
Interleucina-6/metabolismo
Linfonodos/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (IL6 protein, human); 0 (Interleukin-6); 4B9XT59T7S (Zidovudine); 4F4X42SYQ6 (Rituximab); 80168379AG (Doxorubicin); GCU97FKN3R (valganciclovir); P9G3CKZ4P5 (Ganciclovir)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171122
[St] Status:MEDLINE


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[PMID]:29311455
[Au] Autor:Nakagawa H; Matsumaru Y; Nose S; Sasaki H; Kitahara T
[Ad] Endereço:Department of Pharmacy, Nagasaki University Hospital.
[Ti] Título:[Evaluation of the Safety of 2.0% Ganciclovir Eye Drops for Hospital Preparation].
[So] Source:Yakugaku Zasshi;138(1):107-110, 2018.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:The concentration of ganciclovir eye drops for hospital preparation was changed from 0.5% to 2.0% at the Nagasaki University Hospital from March 2015. We investigated the incidence of side effects in 12 patients using 2.0% ganciclovir eye drops and evaluated the cytotoxicity of 2.0% ganciclovir eye drops using cultured rabbit corneal cells in vitro. As a side effect of 2.0% ganciclovir eye drops, three patients exhibited an early feeling of transient stimulation. The 2.0% ganciclovir eye drops did not demonstrate cell cytotoxicity for cultured corneal cells after 5 min, but did after 10 min. These findings suggested that the 2.0% ganciclovir eye drops can be used without corneal epithelium disorder in clinical settings.
[Mh] Termos MeSH primário: Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia
Ganciclovir/efeitos adversos
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Córnea/citologia
Córnea/efeitos dos fármacos
Testes Imunológicos de Citotoxicidade
Relação Dose-Resposta a Droga
Ganciclovir/toxicidade
Hospitais Universitários
Seres Humanos
Incidência
Japão/epidemiologia
Soluções Oftálmicas
Coelhos
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ophthalmic Solutions); P9G3CKZ4P5 (Ganciclovir)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.17-00015


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[PMID]:29422759
[Au] Autor:Parchand S; Barwad A
[Ad] Endereço:Department of Ophthalmology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
[Ti] Título:Cytomegalovirus Retinitis as a Presenting Feature of Multisystem Disorder: Dyskeratosis Congenita.
[So] Source:Middle East Afr J Ophthalmol;24(4):219-221, 2017 Oct-Dec.
[Is] ISSN:0975-1599
[Cp] País de publicação:India
[La] Idioma:eng
[Ab] Resumo:Cytomegalovirus (CMV) retinitis is an opportunistic infection commonly seen in disorders that affect the immune system of the body such as acquired immunodeficiency syndrome and hematological malignancies such as leukemia/lymphoma or organ transplantation. The occurrence of CMV retinitis in the absence of such condition should be thoroughly investigated, as it is a strong indicator of poor immune competence. We here report an interesting case of CMV retinitis as a presenting feature of rare multisystem disorde "Dyskeratosis congenita."
[Mh] Termos MeSH primário: Retinite por Citomegalovirus/diagnóstico
Disceratose Congênita/diagnóstico
[Mh] Termos MeSH secundário: Antivirais/uso terapêutico
Biópsia
Citomegalovirus/isolamento & purificação
Retinite por Citomegalovirus/tratamento farmacológico
Citometria de Fluxo
Ganciclovir/análogos & derivados
Ganciclovir/uso terapêutico
Gastrectomia
Seres Humanos
Hibridização in Situ Fluorescente
Masculino
Meia-Idade
Corpo Vítreo/virologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); GCU97FKN3R (valganciclovir); P9G3CKZ4P5 (Ganciclovir)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180210
[St] Status:MEDLINE
[do] DOI:10.4103/meajo.MEAJO_230_15


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[PMID]:27772620
[Au] Autor:Santos CA
[Ad] Endereço:Rush University Medical Center, Chicago, IL. Electronic address: Carlos_A_Santos@rush.edu.
[Ti] Título:Cytomegalovirus and Other ß-Herpesviruses.
[So] Source:Semin Nephrol;36(5):351-361, 2016 09.
[Is] ISSN:1558-4488
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cytomegalovirus (CMV), human herpes virus (HHV)-6, and HHV-7 are ubiquitous ß-herpesviruses that can cause opportunistic infection and disease in kidney transplant recipients. Active CMV infection and disease are associated with acute allograft failure and death, and HHV-6 and HHV-7 replication are associated with CMV disease. CMV prevention strategies are used commonly after kidney transplantation, and include prophylaxis with antiviral medications and preemptive treatment upon the detection of asymptomatic viral replication in blood. Both approaches decrease CMV disease and allograft rejection, but CMV prophylaxis is preferred for high-risk patients because it is easy to administer and may be more effective in real-world settings. CMV disease commonly occurs even with current preventive strategies, whereas HHV-6 and HHV-7 diseases are rare. The clinical manifestations of CMV, HHV-6, and HHV-7 are nonspecific, and laboratory confirmation is essential to establishing diagnoses. Although nucleic acid testing has supplanted other diagnostic modalities given its high sensitivity and specificity, histopathologic examination sometimes is necessary to identify disease definitively. Ganciclovir and valganciclovir are the treatments of choice for CMV and HHV-6, and foscarnet can be used to treat HHV-7. Treatment duration should be informed by the initial severity of disease, and subsequent clinical and virologic responses.
[Mh] Termos MeSH primário: Infecções por Citomegalovirus/induzido quimicamente
Rejeição de Enxerto/prevenção & controle
Imunossupressores/efeitos adversos
Falência Renal Crônica/cirurgia
Transplante de Rim
Infecções por Roseolovirus/induzido quimicamente
[Mh] Termos MeSH secundário: Antivirais/uso terapêutico
Infecções por Citomegalovirus/diagnóstico
Infecções por Citomegalovirus/tratamento farmacológico
Ganciclovir/análogos & derivados
Ganciclovir/uso terapêutico
Herpesvirus Humano 6
Herpesvirus Humano 7
Seres Humanos
Infecções por Roseolovirus/diagnóstico
Infecções por Roseolovirus/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Immunosuppressive Agents); GCU97FKN3R (valganciclovir); P9G3CKZ4P5 (Ganciclovir)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:29426296
[Au] Autor:Iu LPL; Fan MCY; Lam WC; Wong IYH
[Ad] Endereço:Department of Ophthalmology, The University of Hong Kong, Grantham Hospital, 125 Wong Chuk Hang Road, Aberdeen, Hong Kong, Hong Kong. lawipl@hku.hk.
[Ti] Título:Repeated intraocular crystallization of ganciclovir in one eye after bilateral intravitreal injections: a case report.
[So] Source:BMC Ophthalmol;18(1):36, 2018 Feb 09.
[Is] ISSN:1471-2415
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cytomegalovirus (CMV) retinitis is an opportunistic infection that primarily affects immunocompromised individuals. Intravitreal ganciclovir injection monotherapy or in combination with systemic anti-CMV therapy are effective treatments for CMV retinitis. Crystallization of ganciclovir after intravitreal injection is extremely rare. Only two cases had been reported in literature. Crystallization in only one eye after bilateral injections had not been reported before. We hereby report a case of intraocular ganciclovir crystallization in one eye after bilateral intravitreal injections, and repeated crystallization in the same eye after repeated injections. CASE PRESENTATION: A 79-year-old patient had bilateral cytomegalovirus retinitis and received bilateral intravitreal ganciclovir injections of 2.5 mg in 0.05 ml sterile water. Fundus examination after injection showed formation of needle-shaped, golden-yellow crystals in the vitreous of right eye but not in left eye. The crystals dissolved spontaneously. Repeated bilateral intravitreal ganciclovir injections 4 days later resulted in repeated crystallization of ganciclovir in right eye but not in left eye. The crystals dissolved spontaneously and completely after 5 minutes. Visual acuity remained unchanged and intraocular pressure was normal. CONCLUSIONS: Intraocular ganciclovir crystallization could occur after intravitreal injections. It is important to perform fundus examination after injection. The crystals may dissolve rapidly and vitrectomy may not be necessary. Our case suggested intraocular ganciclovir crystallization is an idiosyncratic phenomenon, subjects to distinctive intraocular environment which could be different between two eyes of the same patient. The susceptible intraocular environment could be persistent leading to repeated crystallization.
[Mh] Termos MeSH primário: Antivirais/química
Precipitação Química
Retinite por Citomegalovirus/tratamento farmacológico
Ganciclovir/química
Corpo Vítreo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Idoso
Antivirais/uso terapêutico
Cristalização
Retinite por Citomegalovirus/diagnóstico
Evolução Fatal
Ganciclovir/uso terapêutico
Seres Humanos
Injeções Intravítreas
Masculino
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); P9G3CKZ4P5 (Ganciclovir)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180211
[St] Status:MEDLINE
[do] DOI:10.1186/s12886-018-0703-8


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[PMID]:29049190
[Au] Autor:Zhong L; Wang W; Ma M; Gou L; Tang X; Song H
[Ad] Endereço:Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
[Ti] Título:Chronic active Epstein-Barr virus infection as the initial symptom in a Janus kinase 3 deficiency child: Case report and literature review.
[So] Source:Medicine (Baltimore);96(42):e7989, 2017 Oct.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: With the progress of sequencing technology, an increasing number of atypical primary immunodeficiency (PID) patients have been discovered, including Janus kinase 3 (JAK3) gene deficiency. PATIENT CONCERNS: We report a patient who presented with chronic active Epstein-Barr virus (CAEBV) infection but responded poorly to treatment with ganciclovir. DIAGNOSES: Next-generation sequencing (NGS) was performed, including all known PID genes, after which Sanger sequencing was performed to verify the results. Genetic analysis revealed that our patient had 2 novel compound heterozygous mutations of JAK3, a gene previously reported to cause a rare form of autosomal recessive severe combined immunodeficiency with recurrent infections. The p.H27Q mutation came from his father, while p. R222H from his mother. Thus, his diagnosis was corrected for JAK3-deficiency PID and CAEBV. INTERVENTIONS: Maintenance treatment of subcutaneous injection of recombinant human interferon α-2a was given to our patient with 2 MU, 3 times a week. OUTCOMES: Interferon alpha was applied and the EBV infection was gradually controlled and his symptoms ameliorated remarkably. Our patient is in good health now and did not have relapses. LESSONS: The diagnoses of PID should be taken into consideration when CAEBV patients respond poorly to conventional treatments. Good results of our patient indicate that interferon α-2a may be an alternative treatment for those who are unwilling to accept hematopoietic stem cell transplantation (HSCT) like our patient. Literature review identified 59 additional cases of JAK3 deficiency with various infections.
[Mh] Termos MeSH primário: Infecções por Vírus Epstein-Barr/genética
Herpesvirus Humano 4
Síndromes de Imunodeficiência/genética
Janus Quinase 3/deficiência
[Mh] Termos MeSH secundário: Antivirais/uso terapêutico
Criança
Doença Crônica
Infecções por Vírus Epstein-Barr/tratamento farmacológico
Infecções por Vírus Epstein-Barr/virologia
Ganciclovir/uso terapêutico
Herpesvirus Humano 4/efeitos dos fármacos
Seres Humanos
Síndromes de Imunodeficiência/tratamento farmacológico
Síndromes de Imunodeficiência/virologia
Interferon-alfa/administração & dosagem
Masculino
Proteínas Recombinantes/administração & dosagem
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Interferon-alpha); 0 (Recombinant Proteins); 47RRR83SK7 (interferon alfa-2a); EC 2.7.10.2 (JAK3 protein, human); EC 2.7.10.2 (Janus Kinase 3); P9G3CKZ4P5 (Ganciclovir)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171122
[Lr] Data última revisão:
171122
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171020
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000007989


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[PMID]:28904689
[Au] Autor:El Hasbaoui B; Bousselamti A; Redouani MA; Barkat A
[Ad] Endereço:Neonatal Medical and Resuscitation Department, Paediatrics V, Children's Hospital, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco.
[Ti] Título:Severe neonatal cytomegalovirus infection: about a case.
[So] Source:Pan Afr Med J;27:161, 2017.
[Is] ISSN:1937-8688
[Cp] País de publicação:Uganda
[La] Idioma:eng
[Ab] Resumo:Maternofoetal infection with Cytomegalovirus (CMV) is the most common congenital infection and a leading cause of mental retardation and sensori-neural hearing loss. Population-based studies indicate that at least 0.5% of all infants born alive have CMV of whom approximately 10% have clinically evident symptomsat birth. The Justification of systematic screening for foetal CMV infection is still controversial and is not recommended in most developed countries. This is mainly justified by the paucity of antenatal prognostic factors and the lack of established intrauterine treatment when foetal infection has been diagnosed. In case of congenital CMV infection, infants can be symptomatic or asymptomatic at birth. Mortality for such infants can reach 30%, and survivors can have mental retardation, sensorineural hearing loss, chorioretinitis, and other significant medical problems. A newborn symptomatic is defined by the existence of clinical and / or biological signs and / or neonatal imaging, the most frequent clinical signs are: hepatosplenomegaly (60%), microcephaly (53%), jaundice (67%), petechiae (76%), at least one neurological abnormality (68%). The frequency of biological abnormalities is as follows: increase in transaminases (83%), thrombocytopenia (77%), hyperbilirubinemia (69%), haemolysis (51%), hyperproteinorrachy (46%). The abnormalities of neonatal imaging are present in 70% of symptomatic newborns; intracerebral calcifications are the most frequent abnormalities. We report a case of newborn who presented a congenital infection by CMV, evoked on the intrauterine growth retardation, organs of the reticulo endothelial and haematological system were reached while nervous system was spared, and CMV PCR was very positive. indicating an antiviral treatment for 6weeks based on ganciclovir.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Infecções por Citomegalovirus/congênito
Retardo do Crescimento Fetal/virologia
Ganciclovir/uso terapêutico
[Mh] Termos MeSH secundário: Infecções por Citomegalovirus/tratamento farmacológico
Infecções por Citomegalovirus/fisiopatologia
Feminino
Seres Humanos
Recém-Nascido
Transmissão Vertical de Doença Infecciosa
Masculino
Gravidez
Complicações Infecciosas na Gravidez/virologia
Índice de Gravidade de Doença
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); P9G3CKZ4P5 (Ganciclovir)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE
[do] DOI:10.11604/pamj.2017.27.161.12004


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[PMID]:28838145
[Au] Autor:Yager JE; Magaret AS; Kuntz SR; Selke S; Huang ML; Corey L; Casper C; Wald A
[Ad] Endereço:Department of Medicine, State University of New York Downstate Medical Center, Brooklyn.
[Ti] Título:Valganciclovir for the Suppression of Epstein-Barr Virus Replication.
[So] Source:J Infect Dis;216(2):198-202, 2017 Jul 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Epstein-Barr virus (EBV) causes infectious mononucleosis and can lead to lymphoproliferative diseases. We evaluated the effects of valganciclovir on oral EBV shedding in a randomized, double-blind, placebo-controlled study. Twenty-six men received oral valganciclovir or daily placebo for 8 weeks, followed by a 2-week "washout period" and then 8 weeks of the alternative treatment. Valganciclovir reduced the proportion of days with EBV detected from 61.3% to 17.8% (relative risk, 0.28; 95% confidence interval [CI], .21-.41; P < .001), and quantity of virus detected by 0.77 logs (95% CI, .62-.91 logs; P < .001). Further investigations into the impact of valganciclovir on EBV-associated diseases are needed.
[Mh] Termos MeSH primário: Antivirais/administração & dosagem
Ganciclovir/análogos & derivados
Mononucleose Infecciosa/tratamento farmacológico
Replicação Viral/efeitos dos fármacos
Eliminação de Partículas Virais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adulto
Idoso
Método Duplo-Cego
Ganciclovir/administração & dosagem
Herpesvirus Humano 4/fisiologia
Seres Humanos
Masculino
Meia-Idade
Carga Viral/efeitos dos fármacos
Washington
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antiviral Agents); GCU97FKN3R (valganciclovir); P9G3CKZ4P5 (Ganciclovir)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170826
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix263


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[PMID]:28829877
[Au] Autor:Limaye AP; Stapleton RD; Peng L; Gunn SR; Kimball LE; Hyzy R; Exline MC; Files DC; Morris PE; Frankel SK; Mikkelsen ME; Hite D; Enfield KB; Steingrub J; O'Brien J; Parsons PE; Cuschieri J; Wunderink RG; Hotchkin DL; Chen YQ; Rubenfeld GD; Boeckh M
[Ad] Endereço:Division of Allergy and Infectious Diseases, University of Washington, Seattle.
[Ti] Título:Effect of Ganciclovir on IL-6 Levels Among Cytomegalovirus-Seropositive Adults With Critical Illness: A Randomized Clinical Trial.
[So] Source:JAMA;318(8):731-740, 2017 08 22.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: The role of cytomegalovirus (CMV) reactivation in mediating adverse clinical outcomes in nonimmunosuppressed adults with critical illness is unknown. Objective: To determine whether ganciclovir prophylaxis reduces plasma interleukin 6 (IL-6) levels in CMV-seropositive adults who are critically ill. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized clinical trial (conducted March 10, 2011-April 29, 2016) with a follow-up of 180 days (November 10, 2016) that included 160 CMV-seropositive adults with either sepsis or trauma and respiratory failure at 14 university intensive care units (ICUs) across the United States. Interventions: Patients were randomized (1:1) to receive either intravenous ganciclovir (5 mg/kg twice daily for 5 days), followed by either intravenous ganciclovir or oral valganciclovir once daily until hospital discharge (n = 84) or to receive matching placebo (n = 76). Main Outcomes and Measures: The primary outcome was change in IL-6 level from day 1 to 14. Secondary outcomes were incidence of CMV reactivation in plasma, mechanical ventilation days, incidence of secondary bacteremia or fungemia, ICU length of stay, mortality, and ventilator-free days (VFDs) at 28 days. Results: Among 160 randomized patients (mean age, 57 years; women, 43%), 156 patients received 1or more dose(s) of study medication, and 132 patients (85%) completed the study. The mean change in plasma IL-6 levels between groups was -0.79 log10 units (-2.06 to 0.48) in the ganciclovir group and -0.79 log10 units (-2.14 to 0.56) in the placebo group (point estimate of difference, 0 [95% CI, -0.3 to 0.3]; P > .99). Among secondary outcomes, CMV reactivation in plasma was significantly lower in the ganciclovir group (12% [10 of 84 patients] vs 39% [28 of 72 patients]); absolute risk difference, -27 (95% CI, -40 to -14), P < .001. The ganciclovir group had more median VFDs in both the intention-to-treat (ITT) group and in the prespecified sepsis subgroup (ITT group: 23 days in ganciclovir group vs 20 days in the placebo group, P = .05; sepsis subgroup, 23 days in the ganciclovir group vs 20 days in the placebo group, P = .03). There were no significant differences between the ganciclovir and placebo groups in duration of mechanical ventilation (5 days for the ganciclovir group vs 6 days for the placebo group, P = .16), incidence of secondary bacteremia or fungemia (15% for the ganciclovir group vs 15% for the placebo group, P = .67), ICU length of stay (8 days for the ganciclovir group vs 8 days for the placebo group, P = .76), or mortality (12% for the ganciclovir group vs 15% for the placebo group, P = .54). Conclusions and Relevance: Among CMV-seropositive adults with critical illness due to sepsis or trauma, ganciclovir did not reduce IL-6 levels and the current study does not support routine clinical use of ganciclovir as a prophylactic agent in patients with sepsis. Additional research is necessary to determine the clinical efficacy and safety of CMV suppression in this setting. Trial Registration: clinicaltrials.gov Identifier: NCT01335932.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Infecções por Citomegalovirus/prevenção & controle
Citomegalovirus/isolamento & purificação
Ganciclovir/uso terapêutico
Interleucina-6/sangue
Sepse/tratamento farmacológico
Ferimentos e Lesões/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Antivirais/farmacologia
Estado Terminal/mortalidade
Citomegalovirus/fisiologia
Infecções por Citomegalovirus/sangue
Método Duplo-Cego
Feminino
Seguimentos
Ganciclovir/análogos & derivados
Ganciclovir/farmacologia
Seres Humanos
Análise de Intenção de Tratamento
Tempo de Internação
Masculino
Meia-Idade
Respiração Artificial/estatística & dados numéricos
Insuficiência Respiratória/etiologia
Insuficiência Respiratória/terapia
Sepse/sangue
Sepse/complicações
Resultado do Tratamento
Ativação Viral/efeitos dos fármacos
Ferimentos e Lesões/sangue
Ferimentos e Lesões/complicações
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (IL6 protein, human); 0 (Interleukin-6); GCU97FKN3R (valganciclovir); P9G3CKZ4P5 (Ganciclovir)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170823
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.10569



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