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Biomedical subjects

A D Fraser

Publications and source records attributed to A D Fraser.

At least 37 records · Page 2Linked to original sources
PubMed1996

New drugs for the treatment of epilepsy.

OBJECTIVES: This article will review current data on the metabolism, interactions, methods of analysis, and adverse effects observed with the use of new anticonvulsant drugs. The role of the laboratory in the provision of therapeutic drug monitoring for these drugs is discussed. CONCLUSION: Certain of the newer anticonvulsant drugs require therapeutic drug monitoring for their optimal use in the treatment of epileptic seizures. The requirement for therapeutic drug monitoring has not been established for some of these drugs. Many of the newer anticonvulsant drugs, including lamotrigine, felbamate, vigabatrin, and zonisamide, interact clinically with established drugs, such as phenytoin, phenobarbital, carbamazepine, and valproic acid. Introduction of these new drugs will result in the need for more frequent monitoring of the established drugs during polytherapy. The need for a drug-monitoring service for anticonvulsant drugs overall will continue, due to the frequency of drug interactions, the incidence of adverse effects, and concerns about compliance with the dosing regimen in these patients.

Adult↗
PubMed1996

Rapid detection and enumeration of Salmonella in chicken carcass rinses using filtration, enrichment and colony blot immunoassay.

A strategy was developed for 24-h detection and enumeration of Salmonella spp. on processed chicken carcasses. Carcasses were rinsed with saline and the rinses spiked with known numbers of serogroup B, C, D or E Salmonella. The total rinse volume was passed through two filter units of decreasing pore size. These removed most of the extraneous material while permitting rapid passage of more than 77% of the Salmonella. At least 100 ml of the filtrate was passed through a third filter unit containing a nitrocellulose capture membrane. Captured bacteria were selectively enriched by incubating the nitrocellulose membrane on filter pads soaked in Rappaport-Vassiliadis broth and then on pads soaked in brilliant green broth containing sulfadiazine and novobiocin. A colony blot immunoassay using two anti-Salmonella monoclonal antibodies was used to identify and enumerate the captured Salmonella. As few as five Salmonella colony forming units per carcass rinse could be detected. An evaluation of this system with 24 field samples indicated that the specificity was comparable to and the sensitivity higher than that of standard culture procedures.

Animals↗
PubMed1995

Evaluation of the Abbott TDx serum benzodiazepine immunoassay for the analysis of lorazepam, adinazolam, and N-desmethyladinazolam.

This study involved the evaluation of the Abbott TDx serum benzodiazepine assay, a fluorescence polarization immunoassay (FPIA), for the detection of lorazepam, adinazolam, and N-desmethyladinazolam in serum. Precision of the assay was determined by using three control serums containing 75, 300, and 700 ng/mL nordiazepam. Between-run precision studies (N = 22) gave mean values of 76, 306, and 690 ng/mL with coefficients of variation of 6.5, 3.3, and 5.7%, respectively. Percent cross-reactivity of serum lorazepam standards (35-500 ng/mL) ranged from 29 to 69%. The cross-reactivity of serum adinazolam ranged from 40 to 47% between 50 and 150 ng/mL and from 38 to 55% for N-desmethyladinazolam between 50 and 250 ng/mL. Serum specimens (48) collected from individuals known to be receiving lorazepam were analyzed. Twenty-two specimens were positive for benzodiazepines. Serum specimens were collected from 0.25 to 24 h after administering a 15-mg oral dose of adinazolam to six volunteers. The FPIA results were compared with combined high-performance liquid chromatographic (HPLC) results for adinazolam and N-desmethyladinazolam. The FPIA method did not detect benzodiazepines at 0.25 h after administration of adinazolam but did detect benzodiazepines from 0.5 to 24 h after administration. The correlation between HPLC (N-desmethyladinazolam) and FPIA results by regression analysis gave the following: y = 0.937x + 4.449, r = 0.98, n = 15. It was concluded that the Abbott FPIA assay for benzodiazepines can detect lorazepam when prescribed in therapeutic doses and when present at greater than 25 ng/mL and can semiquantitatively detect adinazolam or N-desmethyladinazolam or both when present at concentrations greater than 50 ng/mL.

Anti-Anxiety Agents↗
PubMed1995

Lamotrigine analysis in serum by high-performance liquid chromatography.

Lamotrigine is an anticonvulsant drug soon to be introduced to the North American market. It is chemically unrelated to any currently available antiepileptic drug. The objective of this study was to develop a quantitative high-performance liquid chromatography assay for lamotrigine in serum. Lamotrigine was extracted from serum at alkaline pH into ethyl acetate after addition of the internal standard (BW725C78). After mixing, the organic layer was evaporated to dryness before dissolving the residue in methanol for isocratic separation on a RP-8 column (5 microns) with a mobile phase of water/0.5 M phosphate buffer at pH 6.5/acetonitrile (790/10/200) with eluant monitoring at 306 nm. Calibration was performed with five serum standards (2-32 microM and recovery averaged 88% at 25 microM. Between-run precision was 4.1 and 2.5% C.V. at 13.6 and 31.6 microM, respectively. At room temperature, lamotrigine was stable for a minimum of 7 days. Interference studies were performed on serum specimens containing commonly monitored drugs. The only potentially interfering drug was carbamazepine, which elutes 2.5 times longer than lamotrigine. We conclude that this is a reliable method for quantitation of lamotrigine in serum.

Anticonvulsants↗
PubMed1994

Simple extraction of Campylobacter lipopolysaccharide and protein antigens and production of their antibodies in egg yolk.

Antigens were heat extracted from Campylobacter jejuni (LI04) and C. coli (LI020) in the presence of ethylenediaminetetraacetate (EDTA) and were recovered in the supernatant of a low-speed centrifugation. The method is simpler, safer and more efficient in extracting lipopolysaccharide (LPS) antigens than the hot phenol method. The extracted antigens (LPS plus several proteins) elicited production of antigen-specific antibodies in the egg yolk of immunized hens. Antibodies purified by polyethyleneglycol fractionation were used to detect antigens fractionated on SDS polyacrylamide gel electrophoresis.

Agglutination Tests↗
PubMed1994

Modes of inhibition of foodborne non-Salmonella bacteria by selenite cystine selective broth.

Various cell densities of six common foodborne non-Salmonella bacteria were exposed to selenite cystine (SC) Salmonella selective medium. The insensitivity of Pseudomonas aeruginosa and Proteus vulgaris to SC was confirmed. Selenite cystine selective medium was effective against the sensitive bacteria up to certain cell densities, beyond which the bacteria survived. As judged from the minimum cell number required for survival in SC, Staphylococcus aureus was the most sensitive to SC, followed by Bacillus cereus, Escherichia coli and Citrobacter freundii. When sensitive bacteria were grown in SC, they enriched resistant variants which exhibited no or reduced sensitivity to SC. The change in density of sensitive cells after exposure to SC suggested that bacterial sensitivity to SC depended on the efficiency of killing and growth inhibition by SC as well as the fraction of resistant variants in the bacterial population. Since Salmonella samples generally contain unknown numbers and types of sensitive bacteria, it is difficult to predict the effectiveness of their selective inhibition by SC.

Animals↗
PubMed1993

Evaluation of the toxicity of Salmonella selective media for shortening the enrichment period.

Five Salmonella serotypes recovering from heat injury exhibited different kinetics of resuscitation and growth. Exponential growth was reached before full resuscitation. Fully resuscitated cells and uninjured cells at low cell densities exhibited sensitivity when transferred from non-selective media to selective media, Rappaport-Vassiliadis (RV) and tetrathionate-brilliant green (TBG). The minimum number of cells required to survive in RV and TBG was determined and ranged from 10(2) to 10(5) CFU depending on the serotype. Salmonella grown in RV produced cell populations which exhibited no sensitivity when transferred to fresh RV even at low cell densities. Thus, toxic selective media enriched a resistant population. Selenite cystine exhibited no toxicity to resuscitated or uninjured Salmonella. The significance of these findings was discussed for the purpose of shortening the Salmonella enrichment period.

Anti-Bacterial Agents↗
PubMed1993

The use of antiepileptic drug levels in children: a survey of Canadian pediatric neurologists.

There are 60 pediatric neurologists in Canada. Replies were received from 56 in response to a survey regarding the use and perceived value of antiepileptic drug (AED) levels. AED levels are frequently ordered and influence clinical care. There were, however, discrepancies among pediatric neurologists regarding the upper and lower limits of the "therapeutic ranges" and the clinical application of levels. We suggest that both the value and use of AED levels needs further study.

Adolescent↗
PubMed1993

Colorimetric and gas chromatographic procedures for glycolic acid in serum: the major toxic metabolite of ethylene glycol.

Monitoring of individuals poisoned with ethylene glycol involves analysis of ethylene glycol in serum. The objective of this procedure was to validate a colorimetric and gas chromatographic procedure for glycolic acid in serum. The colorimetric procedure requires no sophisticated instrumentation and has been shown to be specific for glycolic acid. A gas chromatographic procedure has also been developed involving methyl derivatization of glycolic acid and the internal standard (propionic acid). These methods have been used for the analysis of serum specimens from ethylene glycol poisoned patients. Glycolic acid has been recognized as the major toxic agent in ethylene glycol poisoning but current methods available do not allow analysis in a clinically relevant turnaround time. These two procedures allow glycolic acid quantitation by procedures readily set up in most clinical toxicology laboratories.

Chromatography, Gas↗
PubMed1992

Molecular discrimination of Campylobacter coli serogroup 20 biotype I (Lior) strains.

Plasmid, protein and restriction endonuclease analysis (REA) profiles and multilocus enzyme electrophoresis were used to effect a molecular discrimination of twenty-seven Campylobacter coli serogroup 20, biotype 1 (Lior) strains. These strains were not outbreak-associated but were isolated from a number of different countries and different animal and environmental sources. Each of the techniques was able to discriminate, to various degrees, between the serogroup 20, biotype 1 strains. The choice of a particular technique depends to a large extent on the level of discrimination desired, the previous experiences of the investigator and on the laboratory facilities at hand. REA profiles demonstrated the greatest degree of discrimination between these strains. Plasmid and protein profiles could discriminate reasonably well. Multilocus enzyme electrophoresis (allozyme typing) and protein profiles may prove effective in subgrouping serogroup 20, biotype 1 strains.

Animals↗
PubMed1991

Toxicological analysis of a fatal baclofen (Lioresal) ingestion.

A fatality following ingestion of the drug baclofen (Lioresal) is described. Baclofen was identified in urine by gas chromatography/mass spectrometry. After derivatization with trinitrobenzene sulfonic acid, baclofen was quantitated in serum and urine by high-performance liquid chromatography. The concentration of baclofen was 17 mg/L in serum and 760 mg/L in urine collected approximately 12 h after the overdose. To our knowledge, this is only the second reported fatality involving a baclofen overdose. The previous case did not include quantitation of baclofen in any biological fluid.

Adult↗
PubMed1990

Clinical toxicology of drugs used in the treatment of opiate dependency.

Many aspects of the pharmacokinetics of methadone have been evaluated since 1970. Analytic techniques used to monitor urine and serum or plasma concentrations of methadone and its metabolites have improved with advances in chromatography and development of immunoassay techniques. On reviewing the literature on methadone since 1970, however, there were several recurring limitations of the experimental design in a large number of the studies reported. These include: 1. No appreciation for the effect of urinary pH on excretion of methadone 2. Small number of patients enrolled with inadequate control subjects 3. The effect of smoking cigarettes was not evaluated or adequately controlled 4. Urine collections were often obtained without supervision and correcting results to creatinine excretion 5. Blood specimens were generally not collected from 0-15 minutes after intravenous dosing 6. Incomplete excretion data (nonhydrolysis of glucuronide conjugates) in the urine 7. Most studies did not evaluate protein binding of methadone when attempting to correlate therapeutic control or failure with serum concentrations of methadone. In general, the literature supporting the use of naltrexone was more favorable than for methadone, buprenorphine, LAAM, and clonidine. The major limitation on the use of naltrexone, however, is the lack of incentive for the patient to keep taking the medication. If the use of naltrexone, LAAM, buprenorphine, or clonidine becomes widely available, robust analytic techniques must be developed for monitoring of these drugs, their metabolites, or both in the urine to verify patient compliance.

Buprenorphine↗
PubMed1989

Evaluation of the EMIT amitriptyline and nortriptyline assays for the determination of serum clomipramine and desmethylclomipramine.

Homogeneous enzyme immunoassay reagents (EMIT) developed for the measurement of amitriptyline and nortriptyline in serum were modified to allow quantitation of clomipramine and desmethylclomipramine. The method was compared to a high-performance liquid chromatographic method. Between-run precision [coefficient of variation (CV)] for clomipramine in the EMIT assay for amitriptyline ranged from 2.6 to 3.2%. For desmethylclomipramine in the nortriptyline assay, the between-run CV ranged from 1.4 to 1.9%. Serum specimens from 43 patients (desmethylclomipramine) and 59 patients (clomipramine) were analyzed by both methods, with good correlation between methods. For clomipramine, recovery ranged from 100 to 102% (0-600 ng/ml range) and was 95-103% for desmethylclomipramine (0-600 ng/ml). The modified EMIT assays offered sufficient reproducibility, accuracy, and correlation with an established method for routine analysis of clomipramine and desmethylclomipramine.

Amitriptyline↗
PubMed1989

Plasmid transfer and plasmid-mediated genetic exchange in Brucella abortus.

Naturally-occurring plasmids and gene transfer mechanisms have not yet been reported in brucellae. Here we show that Brucella abortus is capable of maintaining and transferring the broad-host-range plasmids pTH10 (IncP), pSa (IncW) and R751 (IncP), and describe pTH10-mediated transfer of B. abortus chromosomal genes to Escherichia coli. All three plasmids transferred by conjugation from E. coli to B. abortus S19, and from B. abortus S19 to B. abortus 292 (biovar 4). They were stably maintained with no effect on biotyping characteristics. Plasmid pTH10 is a Tn1-containing derivative of RP4. It confers temperature-sensitive resistance to kanamycin, tetracycline and ampicillin to E. coli, but its tetracycline resistance and temperature sensitivity were poorly expressed in B. abortus. Plasmids pTH10 and pSa both transferred from B. abortus to E. coli DP50, a strain that is auxotrophic for diaminopimelic acid (DAP) Plasmid pTH10 (but not pSa) mobilized Brucella chromosomal gene(s) for DAP synthesis to DP50, yielding non-DAP-requiring (NDR) transconjugants. Neither plasmid transferred the NDR marker from their original E. coli host strains, nor did pTH10 transfer it from NDR transconjugants. Escherichia coli NDR transconjugant EP8.11 was cured of pTH10 by passage at the nonpermissive temperature, but retained the NDR marker and the Tn1-encoded resistance to ampicillin, indicating Tn1-mediated integration of Brucella chromosomal DNA into the E. coli chromosome.

Brucella abortus↗
PubMed1988

Changes in serum anticonvulsant levels with febrile illness in children with epilepsy.

Changes in anticonvulsant serum levels during intercurrent illness may cause toxicity or decreased seizure control in children with epilepsy. We studied prospectively the effect of intercurrent illness and its treatment in 111 children being treated with AC monotherapy. Free fraction and total serum AC levels were determined when the child was well, on the fifth day of any illness with fever and one month after recovery. There were 55 episodes of febrile illness in 39 children during the study period. Twelve illnesses were associated with significant increases or decreases in serum AC levels; 7 children became clinically toxic; 1 child had increased seizures during illness. The mechanisms of AC level changes appeared to include interaction with antibiotics, with antipyretics or with viral illness. Amoxycillin and acetaminophen did not appear to interact with the AC's used. Physicians caring for children with epilepsy should be aware of the frequency and complexity of potential interactions between intercurrent febrile illness and anticonvulsant medication.

Adolescent↗
PubMed1988

Tissue distribution of ethosuximide and clobazam in a seizure related fatality.

The case of a six-year-old male who died in a hospital while receiving several anticonvulsant drugs is described. Phenytoin, desmethyldiazepam, clobazam (an experimental 1,5 benzodiazepine), and desmethylclobazam were quantitated in serum, liver, and brain tissue by high performance liquid chromatography. Ethosuximide was quantitated by gas chromatography. To our knowledge, this is one of few reports describing tissue concentrations of ethosuximide collected at autopsy and the first report of clobazam/desmethylclobazam tissue distribution in man.

Anti-Anxiety Agents↗