Monitoring drug concentrations in a case of combined overdosage with primidone and methsuximide

We describe a case of fatal overdosage with primidone and methsuximide. During the early phase of the patient's hospital course we found concentrations of methsuximide, N-desmethylmethsuximide, and primidone in serum that far exceeded the usual therapeutic concentrations, as determined by gas-liquid chromatography. Determination of N-desmethylmethsuximide in peritoneal fluid demonstrated concentrations comparable to those in serum. This led to the therapeutic decision to manage the patient by dialysis. Subsequently, serum samples collected during the course of hospitalization were analyzed quantitatively by gas-liquid chromatography for methsuximide, N-desmethylmethsuximide, primidone, phenobarbital, and diphenylhydantoin. Selected serum specimens were also analyzed by gas chromatography-mass spectrometry, and N-methyl-2-hydroxymethyl-2-phenylsuccinimide, a metabolite of methsuximide not previously described in human serum, was identified by analysis of its mass spectrum.     

New evidence relating to the nature and origin of the hairy cell of leukaemic reticuloendotheliosis

A procedure is presented for the purification of specific mRNAs, which exploits the ability of antibodies prepared against a native protein to bind to the nascent polypeptide on the polysome. Rather than precipitating these soluble antibody-polysome complexes with anti-antibody, which can lead to nonspecific trapping of polysomes, we have linked the anti-antibody to an insoluble matrix. Thus, the antibody-polysome complex binds to the anti-antibody support and nonspecific polysomes can easily be removed by several washes. We have found para-aminobenzyl cellulose (PAB cellulose), to be a suitable matrix for this purpose. This support can bind large quantities of anti-antibody and it displayed no detectable nonspecific affinity for polysomes or RNA. Using this procedure, we have obtained an apparently homogeneous preparation of ovalbumin mRNA.     

L-735,334, a novel sesquiterpenoid potassium channel-agonist from Trichoderma virens

A novel oleic acid ester of the carotane sesquiterpene 14-hydroxy CAF-603 was isolated from Trichoderma virens grown in a solid brown rice-based medium, a solid millet-based medium, or a mannitol-based liquid medium. Its structure was determined on the basis of ms and nmr analysis. It retains distinct biological activity on the high conductance calcium-activated potassium channel, unlike its analogues 14-hydroxy CAF-603, CAF-603 3-oleate, or CAF-603 3-linoleate.