Histone acetylation and DNA demethylation of B cells result in a Hodgkin-like phenotype.

A unique feature of the tumor cells (Hodgkin/Reed-Sternberg (HRS)) of classical Hodgkin lymphoma (cHL) is the loss of their B-cell phenotype despite their B-cell origin. Several lines of evidence suggest that epigenomic events, especially promoter DNA methylation, are involved in this silencing of many B-cell-associated genes. Here, we show that DNA demethylation alone or in conjunction with histone acetylation is not able to reconstitute the B-cell-gene expression program in cultured HRS cells. Instead, combined DNA demethylation and histone acetylation of B-cell lines induce an almost complete extinction of their B-cell-expression program and a tremendous upregulation of numerous Hodgkin-characteristic genes, including key players such as Id2 known to be involved in the suppression of the B-cell phenotype. Since the upregulation of Hodgkin-characteristic genes and the extinction of the B-cell-expression program occurred simultaneously, epigenetic changes may also be responsible for the malignant transformation of cHL. The epigenetic upregulation of Hodgkin-characteristic genes thus plays--in addition to promoter DNA hypermethylation of B-cell-associated genes--a pivotal role for the reprogramming of HRS cells and explains why DNA demethylation alone is unable to reconstitute the B-cell-expression program in HRS cells.

Serious toxicity in a young child due to ibuprofen.

An 18-month-old male presented to the emergency department (ED) for evaluation of lethargy and apnea. Four hours before presentation, the patient was found with an empty bottle of ibuprofen, an ingestion of as much as 7.2 grams (600 mg/kg). The ED course was remarkable for a 30-second tonic-clonic seizure. Laboratory analysis was notable for metabolic acidosis. Four-hour and 7.5-hour serum ibuprofen levels were 640 and 39 microg/mL, respectively. Following treatment, the patient improved and was extubated the next morning. While metabolic acidosis has been frequently described at doses exceeding 400 mg/kg, seizures occurring early in the course of ibuprofen toxicity have been rarely noted.

Fomepizole treatment of ethylene glycol poisoning in an infant.

The enzyme alcohol dehydrogenase metabolizes ingested ethylene glycol (EG) to the toxic compounds glycolic and oxalic acids. Renal failure, acidosis, hypocalcemia, and death may follow. Traditional treatment of EG poisoning may require ethanol, a competitive substrate of alcohol dehydrogenase, and hemodialysis, that removes both EG and its toxic metabolites. A new alcohol dehydrogenase inhibitor, fomepizole (4-methylpyrazole), was approved in 1997 for patients at least 12 years old with suspected or confirmed EG poisoning. Fomepizole has not been studied adequately in the pediatric population. We present a case of an 8-month-old male infant who drank up to 120 mL of EG and developed acidosis and oxalate crystalluria. He was treated with fomepizole and hemodialysis. Even after the completion of hemodialysis, fomepizole appeared to effectively block the production of EG toxic metabolites and to allow the resolution of acidosis; the patient recovered within 48 hours. This is the first report of fomepizole treatment of EG poisoning in an infant.4-methylpyrazole, fomepizole, poisoning, ethylene glycol, hemodialysis, infant, child, pediatrics.