Adverse events, including death, associated with the use of 1,4-butanediol.

BACKGROUND: 1,4-Butanediol is an industrial solvent that, when ingested, is converted to gamma-hydroxybutyrate, a drug of abuse with depressant effects, primarily on the central nervous system. After reports of toxic effects of gamma-hydroxybutyrate and its resultant regulation by the federal government, 1,4-butanediol and gamma-butyrolactone, another precursor of gamma-hydroxybutyrate and an industrial solvent, began to be marketed as dietary supplements. We investigated reports of toxic effects due to the ingestion of 1,4-butanediol and reviewed the related health risks. METHODS: From June 1999 through December 1999, we identified cases of toxic effects of 1,4-butanediol involving patients who presented to our emergency departments with a clinical syndrome suggesting toxic effects of gamma-hydroxybutyrate and a history of ingesting 1,4-butanediol and patients discovered through public health officials and family members. We used gas chromatography-mass spectrometry to measure 1,4-butanediol or its metabolite, gamma-hydroxybutyrate, in urine, serum, or blood. RESULTS: We identified nine episodes of toxic effects in eight patients who had ingested 1,4-butanediol recreationally, to enhance bodybuilding, or to treat depression or insomnia. One patient presented twice with toxic effects and had withdrawal symptoms after her second presentation. Clinical findings and adverse events included vomiting, urinary and fecal incontinence, agitation, combativeness, a labile level of consciousness, respiratory depression, and death. No additional intoxicants were identified in six patients, including the two who died. The doses of 1,4-butanediol ingested ranged from 5.4 to 20 g in the patients who died and ranged from 1 to 14 g in the nonfatal cases. CONCLUSIONS: The health risks of 1,4-butanediol are similar to those of its counterparts, gamma-hydroxybutyrate and gamma-butyrolactone. These include acute toxic effects, which may be fatal, and addiction and withdrawal.

Choline acetyltransferase activity and histopathology of frontal neocortex from biopsies of demented patients.

Cortical biopsies were taken from the frontal lobe of 25 patients with presenile dementia. Choline acetyltransferase (ChAT) activity, and in some specimens the high affinity uptake of choline, was used to estimate loss of cholinergic nerve terminals. Of the 15 samples with varying degrees of histological evidence of Alzheimer's disease (AD) 14 were from clinically suspected examples of the disease. There was significant loss of ChAT in 10 of the 15 compared with control and the mean activity was also highly significantly reduced (to 41% of control). The deficit was found in patients examined within a year of onset of symptoms. In 6 biopsies from clinically suspected cases of AD without diagnostic histological features there was loss of activity in only one, subsequently shown to have Jakob-Creutzfeldt disease. The remaining samples were two of vascular dementia (no loss of ChAT), one probable disorder of white matter (no loss of activity) and one undiagnosed disorder (with loss of ChAT activity). Thus most patients without histologically demonstrated AD had no evidence of a presynaptic cholinergic defect. It was concluded that suspected cases of AD particularly suitable for putative cholinergic therapy were those with an onset of the disease at 55 to 65 and an absence of family history.