RESUMO
A 60-year-old myelodysplastic syndrome patient underwent tandem cord blood transplantation. The primary cord blood graft was rejected, and human herpesvirus 6 (HHV6) encephalitis developed after engraftment of secondary cord blood. Polyuria and adipsic hypernatremia were observed during treatment of the encephalitis. The patient died of bacteremia caused by methicillin-resistant Streptococcus epidermis. HHV6 infection in the posterior pituitary was confirmed on autopsy, as was infection of the hippocampus, but not of the hypothalamus. This is the first case report of central diabetes insipidus caused by an HHV6 posterior pituitary infection demonstrated on a pathological examination.
Assuntos
Anemia Refratária com Excesso de Blastos/cirurgia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Diabetes Insípido Neurogênico/etiologia , Encefalite Viral/complicações , Herpesvirus Humano 6/isolamento & purificação , Doenças da Hipófise/complicações , Neuro-Hipófise/virologia , Complicações Pós-Operatórias/etiologia , Infecções por Roseolovirus/complicações , Aloenxertos , Antivirais/uso terapêutico , Bacteriemia/etiologia , Bacteriemia/microbiologia , Encefalite Viral/tratamento farmacológico , Encefalite Viral/virologia , Evolução Fatal , Feminino , Rejeição de Enxerto , Humanos , Hospedeiro Imunocomprometido , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Neutropenia/induzido quimicamente , Neutropenia/complicações , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/virologia , Neuro-Hipófise/fisiopatologia , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/virologia , Reoperação , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/microbiologia , Microangiopatias Trombóticas/etiologia , Condicionamento Pré-Transplante/efeitos adversosRESUMO
The objective of the present study was to define the optimum conditions for using replication-defective adenovirus (Ad) to transfer the gene for the green fluorescent protein (GFP) to the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei and cells of the neurohypophysis (NH). As indicated by characterizing cell survival over 15 days in culture and in electrophysiological whole cell patch-clamp studies, viral concentrations up to 2 x 10(7) pfu/coverslip did not affect viability of transfected PVN and NH cultured cells from preweanling rats. At 2 x 10(7) pfu, GFP gene expression was higher (40% of GFP-positive cells) and more sustained (up to 15 days). Using a stereotaxic approach in adult rats, we were able to directly transduce the PVN, SON, and NH and visualize gene expression in coronal brain slices and in the pituitary 4 days after injection of Ad. In animals receiving NH injections of Ad, the virus was retrogradely transported to PVN and SON neurons as indicated by the appearance of GFP-positive neurons in cultures of dissociated cells from those brain nuclei and by polymerase chain reaction and Western blot analyses of PVN and SON tissues. Adenoviral concentrations of up to 8 x 10(6) pfu injected into the NH did not affect cell viability and did not cause inflammatory responses. Adenoviral injection into the pituitary enabled the selective delivery of genes to the soma of magnocellular neurons. The experimental approaches described here provide potentially useful strategies for the treatment of disordered expression of the hormones vasopressin or oxytocin.