RESUMO
We describe a case of vaccine-associated paralytic poliomyelitis (VAPP) in a 7-month-old infant with perianal abscesses. The infant had suffered from perianal abscesses from 3 weeks after birth. The abscesses repeatedly developed and spontaneously drained through the orifice. Twenty-seven days before admission, a live attenuated oral poliovirus vaccine (OPV) was given to the infant for the first time for routine immunization. His body temperature rose to 38°C 19 days after receiving the OPV and fell 4 days later. Flaccid paralysis of the right leg appeared 26 days after receipt of the OPV. A Sabin type 3 poliovirus was isolated from a stool obtained at admission. The DNA sequences of the VP1 region of the isolated virus were more than 99% identical with those of the vaccine strain. Mild muscle atrophy with moderate motor impairment in the right leg persisted at 18 months of age. One VAPP case provoked by a perianal abscess has been reported from the United Kingdom. Database search revealed that one of nine VAPP cases reported during 2003-2008 in Japan had a perianal abscess. Taken together, these reports and our case imply that we should give OPV with caution to infants with a perianal abscess.
Assuntos
Abscesso/complicações , Doenças do Ânus/complicações , Poliomielite/etiologia , Vacina Antipólio Oral/efeitos adversos , Humanos , Lactente , Masculino , Paraplegia/diagnóstico , Paraplegia/etiologia , Paraplegia/imunologia , Poliomielite/diagnóstico , Poliomielite/imunologiaRESUMO
PURPOSE: We examined the activity of gemcitabine against neuroblastoma in vitro and in vivo. In addition, we investigated the cellular mechanisms of high sensitivity to the agent in neuroblastoma cells. EXPERIMENTAL DESIGN: We examined 11 neuroblastoma cell lines for sensitivity to gemcitabine and other chemotherapeutic agents used clinically for neuroblastoma. The in vivo sensitivity of neuroblastoma to gemcitabine was determined in xenograft models. Furthermore, the major metabolic enzymes of gemcitabine were assessed and compared in leukemia and carcinoma cells. Apoptosis and mitochondrial membrane potentials were also evaluated. RESULTS: The IC50s for gemcitabine in 11 neuroblastoma lines ranged between 3 nmol/L and 4 micromol/L. The high activity of gemcitabine against neuroblastoma was confirmed in animal models. Interestingly, enzymes in neuroblastoma cells involved in the metabolism of deoxycytidine analogue have unique characteristics among solid tumors. The median of deoxycytidine kinase activity in neuroblastoma lines was similar to that in leukemia lines, which have low IC50s for cytarabine. Cytidine deaminase (CDA) activity in neuroblastoma was hardly detectable and significantly lower than that in carcinoma. The defect of CDA activity was associated with negative expression of mRNA. Furthermore, gemcitabine-induced apoptosis was observed irrespective of the caspase-8 status of neuroblastoma cells, which indicates that apoptosis depends on the mitochondrial pathway. CONCLUSIONS: Neuroblastoma is highly sensitive to gemcitabine. Although the cellular mechanism involved in sensitivity to gemcitabine is multifactorial, low CDA activity may contribute high sensitivity in neuroblastoma cells. These results suggest that clinical application of gemcitabine to the treatment of neuroblastoma is warranted.