Sudden Death After Febrile Seizure Case Report: Cerebral Suppression Precedes Severe Bradycardia.

A 20-month-old girl with a complex chromosomal disorder had first presentation of febrile status epilepticus and was admitted to the hospital. Two days after her initial seizure, she died suddenly and unexpectedly during a video EEG monitoring study. An advanced analysis of the physiologic changes in the hours and minutes leading up to death was undertaken. The electrocardiography over the last 19 minutes of life was reviewed, and the R-R intervals were manually measured. Heart rate variability was assessed through calculation of the SD of the R-R intervals and the root mean square of successive differences over successive 100 beat periods. Instantaneous heart rate, SD of the R-R intervals, the root mean square of successive differences, and oxygen saturation were plotted against time over the last 19 minutes of life. Diffuse cerebral suppression on EEG was observed 10 minutes before death, followed minutes later by severe bradycardia and increased heart rate variability. Although the child did not meet criteria for a diagnosis of epilepsy, the sequence of physiologic changes leading up to death suggests a pathophysiology similar to sudden unexplained death in epilepsy. A comparable pattern of diffuse cerebral suppression preceding parasympathetic overactivity has been suggested in some rare cases of adults who have experienced sudden unexplained death in epilepsy during video EEG monitoring.

2-aminopurine enhances the oncolytic activity of an E1b-deleted adenovirus in hepatocellular carcinoma cells.

Adenoviruses with deletions of viral genes have been extensively studied as potential cancer therapeutics. Although a high degree of cancer selectivity has been demonstrated with these conditionally replicating adenoviruses, low levels of virus replication can be detected in normal cells. Furthermore, these mutations were also found to reduce the activity of the replicating viruses in certain cancer cells. Recent studies have shown that co-administration of chemotherapeutic drugs may increase the activity of these viruses without affecting their specificity. We constructed an adenovirus with deletions of both the E1b and the VA-RNA genes and found that replication of this virus was selective for human hepatocellular carcinoma (HCC) cell lines when compared to normal cell lines. Furthermore, we show that 2-aminopurine (2'AP) treatment selectively enhanced virus replication and virus-mediated death of HCC cells. 2'AP did not compensate for the loss of VA-RNA activities, but rather the loss of an E1b-55K activity, such as the DNA damage response, suggesting that co-administration of 2'AP derivatives that block host DNA damage response, may increase the oncolytic activity of AdΔE1bΔVA without reducing its selectivity for HCC cells.