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Biomedical subjects

D B Smith

Publications and source records attributed to D B Smith.

At least 235 records · Page 13Linked to original sources
PubMed1983

Scalp and depth recordings of induced deep cerebral potentials.

A balanced square wave was introduced between two adjacent depth electrodes implanted in the course of studying patients with intractable epilepsy and who were being considered for surgery. The stimulus current was designed so that charge density loading was well within limits of safety to avoid tissue damage. No neuronal activation was seen, and the stimulus intensity was significantly less than that used in subsequent stimulation session for the purpose of eliciting a clinical response and after-discharges. Averaging techniques were used to record the stimulus at distant electrodes both within the cerebrum and on the scalp. The recorded voltage decrement from the source was nearly identical with the theoretical voltage decrement predicted using principles of electric field theory in which the brain was assumed to be a homogeneous conductive medium. When the voltage recorded on the scalp was compared with the voltages recorded from depth electrodes, it was found that the effect of the highly resistive skull on voltage decrement was relatively less the more centric the source. This result also confirmed predictions based on electric field theory. Most significantly, voltages well within the physiologic range introduced in deep mesial temporal lobe structures were recorded from the scalp.

Brain↗
PubMed1983

The effect of chronic phenytoin treatment on tissue folate concentrations and on the activities of the methyl synthetic enzymes in the rat.

The folacin-depleting effect of phenytoin has been known clinically for many years, but a systematic investigation of this effect in animals has never been undertaken. In this study we found that chronic oral phenytoin treatment (100 mg/kg every 12 hours for 8 weeks) in rats significantly affected concentrations of folates in both liver and brain. Concentration of liver folates dropped to one-third the normal level even though concentration of plasma folates was not affected. Concentration of brain folates increased over the first 2 weeks of treatment and then declined to a level approximately three-fourths the normal concentration. The apparent activity of 5,10-methylenetetrahydrofolate reductase (MTR) increased as a function of the length of treatment in both brain and liver, but when phenytoin was added to the MTR assay in vitro, the activity was inhibited. No significant effects of phenytoin on the activities of serine hydroxymethyltransferase (SHMT), 5-methyltetrahydrofolate:homocysteine methyltransferase (MHMT) or methionine adenosyltransferase (MAT) were observed either in vivo or in vitro. These data are consistent with the hypothesis that phenytoin interacts with the metabolism of folates at the enzymatic level.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed1983

Interaction of phenytoin and folate in the rat.

The interactions between folate and phenytoin were studied in the rat using a model in which constant, nontoxic, and continuously protective levels of phenytoin were maintained. After 10 days of treatment with phenytoin, liver folate concentration was decreased while brain, plasma, and adrenal folate concentrations remained unaffected. Oral folate supplementation (20 mg/kg) increased folate concentrations in all tissues examined in phenytoin-treated animals, but had no effect on phenytoin levels. Folate supplementation did, however, increase the recovery time after maximal electroshock seizures in phenytoin-treated rats, but did not influence phenytoin's ability to protect against tonic hindlimb extension. Oral folate supplementation in animals not treated with phenytoin also significantly increased folate concentrations in all tissues examined except brain.

Animals↗
PubMed1983

A design for the prospective evaluation of the efficacy and toxicity of antiepileptic drugs in adults.

The design for the comparative evaluation of the efficacy and toxicity of phenobarbital, phenytoin, primidone, and carbamazepine is outlined. A double-blind prospective study of a sufficient number of patients can determine the optimum drug to use initially for partial and generalized tonic-clonic seizures in adults. The rationale for methods defines the major parameters that should be addressed in order to determine optimum drug for longterm seizure therapy. Major problems in the function of such a project include aspects of sample size attainment, screening/recruitment, non-drug-related losses, and adjustments to the ongoing protocol. The design, with modifications, can be used to study other antiepileptic drugs and other types of seizures.

Adult↗
PubMed1982

Fluorescent immunoassay for determining antiepileptic drug concentrations: clinical usefulness.

The need for rapid and accurate antiepileptic drug measurement in blood is well established. A substrate-labeled fluorescent immunoassay (FIA) has been developed that can measure phenobarbital, phenytoin, primidone, and carbamazepine in serum. To our knowledge, the primidone and carbamazepine assays have not previously been tested in a field trial. We compared FIA and the well-established antiepileptic drug immunoassay technique EMIT for the quantitation of both carbamazepine and primidone. In our hands, the FIA method compared favorably with the EMIT method for accuracy and reliability but is somewhat more time consuming. This method has the advantage of being more sensitive, however, and requires only a finger-stick blood sample. Because of this and the simplicity of the equipment required, the FIA system should also be relatively inexpensive to set up and to operate.

Anticonvulsants↗
PubMed1982

Comparison of fluorescent immunoassay (FIA) and enzyme-multiplied immunoassay technique (EMIT) for measurement of serum carbamazepine concentration.

The recently developed fluorescent immunoassay (FIA) for measuring serum carbamazepine concentration is compared to the established enzyme-multiplied-immunoassay-technique (EMIT). The Accuracy, precision and simplicity of these methods are comparable. The sensitivity of FIA is approximately eight times greater than the EMIT but the assay time required for FIA is longer. Potential improvements of the FIA technique are discussed.

Carbamazepine↗
PubMed1982

Comparison of fluorescent immunoassay and EMIT for assay of serum primidone concentration.

A fluorescent immunoassay procedure (FIA) for the assay of serum of plasma primidone concentrations that was developed by Ames Laboratories is compared to the established enzyme-multiplied immunoassay technique (EMIT) developed by Syva. The FIA compares favorably with the established EMIT system for accuracy, and the FIA is eight times more sensitive but requires a greater turnover time.

Fluorescent Antibody Technique↗
PubMed1982

The cross-linking of tubulin with imidoesters.

Tubulin was reacted with a monofunctional imidoester, ethyl acetimidate, and three bifunctional imidoesters ranging in extension from 5 to 10 A. Extensive cross-linking was found to occur with the three bifunctional reagents resulting in the formation of dimers, trimers, tetramers, pentamers, and hexamers. In addition, a similar cross-linking patterns was observed with the monofunctional reagent. This type of cross-linking is rarely seen when proteins are reacted with imidoesters. Given that the cross-linking span of ethyl acetimidate is only 3 A it is reasonable to infer that there are nucleophilic groups in close proximity within the tubulin dimer. Amidinated tubulin is still capable of assembling into microtubules.

Amino Acids↗
PubMed1982

Pseudoseizures: diagnostic evaluation.

A prospective study of pseudoseizures using prolonged video-electroencephalographic (EEG) recording was carried out in 60 patients. Of 33 patients with episodes of uncertain mechanism, a diagnosis based on recorded episodes was made in 18 (55%). Twelve (36%) had pseudoseizures; 6 (18%) had epileptic seizures. Ten additional patients had epileptiform EEGs compatible with epilepsy. Of 27 patients with presumably uncontrolled epileptic seizures, 4 (15%) had recorded pseudoseizures. Prediction of the nature of the episode by the admitting neurologist was accurate in 67% of cases. Determination from observations of unit personnel and neurologists was correct in less than 80% of episodes. These data suggest that pseudoseizures occur frequently in patients being evaluated for epilepsy or suspected epilepsy. The clinical differentiation between epileptic seizures and pseudoseizures is often inaccurate. This differentiation is facilitated by prolonged video-EEG recording.

Adolescent↗
PubMed1982

Interactions between folates and carbamazepine or valproate in the rat.

Carbamazepine and valproate each afforded protection against seizures induced by electroshock or by inhalation of hexafluorodiethyl ether (HFDE). After injections of either anticonvulsant for 10 days, plasma folate concentration decreased, but brain folate concentration did not change. Folinic acid administration had no effect on the concentration of either anticonvulsant in plasma or brain. These findings are in contrast with the demonstrated effects of other anticonvulsants on folate biochemistry.

Animals↗
PubMed1981

The role of constituency groups in policy formulation: items for a health services research agenda.

The Veterans Administration medical care system functions within a larger VA services program that has as its direct constituency many organized veterans' groups. The VA system is viewed from the larger perspective of consumer representation in its direction through three effective functions of consumer representation: ownership, control, and oversight. In the VA the Congress and the veterans' groups perform these functions with varying levels of impact on the system. While veterans feel a measure of ownership of the medical care system, they have little voice in its actual operation. Research is needed to describe more fully fully the actual role of the veterans-client in the system and to explore the possibility that aspects of the system may be adopted outside.

Community Participation↗