Smoking as a fire risk in Scottish hospitals; an ASH enquiry.
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Fires↗
Biomedical subjects
A D Fraser
Publications and source records attributed to A D Fraser.
Rehabilitation at Astley Ainslie.
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Chronic Disease↗
Simple and economical culture of Campylobacter jejuni and Campylobacter coli in CO2 in moist air.
Strains of Campylobacter jejuni and C. coli representing the 18 serogroups (Lior) most commonly isolated from humans in Canada were grown on solid media in an atmosphere of 10% CO2 in moist air, 99% relative humidity. When the growth of all 18 serogroups on Mueller Hinton agar in a microaerobic atmosphere (5% O2, 10% CO2 and 85% N2) was compared with the growth of all 18 serogroups on the same media in 10% CO2 in moist air, colony sizes were significantly larger (p less than 0.05) for strains grown in 10% CO2 in moist air. No significant difference in colony numbers was seen between the two atmospheres. The addition of blood to the media significantly enhanced the growth of the campylobacters in both types of atmospheres (p less than 0.05). This simple CO2 atmosphere permitted the use of a common CO2 incubator thereby reducing the cost and difficulty of culturing these organisms.
Bacteriological Techniques↗
Once-daily ethosuximide in the treatment of absence epilepsy.
Once-daily ethosuximide was used to treat 10 consecutive children with typical absence seizures. Three patients had gastrointestinal side effects which resolved when the same total daily dose was divided into 2 doses. Two other patients continued to have seizures on ethosuximide, whether given once or twice daily. Five patients had complete seizure control without adverse effects on once-daily ethosuximide.
Adolescent↗
Distribution of trimipramine and its major metabolites in a fatal overdose case.
A fatality following ingestion of the tricyclic antidepressant trimipramine (Surmontil) is described. Quantitation was performed by high-performance liquid chromatography. Trimipramine and desmethyltrimipramine concentrations were 4.8 and 2.1 mg/L, respectively, in postmortem blood. The concentration of trimipramine, desmethyltrimipramine, and their respective 2-hydroxy metabolites were also measured in liver and urine. Analysis of gastric contents revealed a tricyclic antidepressant drug. These findings are compared to previously published reports of trimipramine-related fatalities.
Adult↗
Urinary screening for alprazolam, triazolam, and their metabolites with the EMIT d.a.u. benzodiazepine metabolite assay.
Alprazolam (Xanax) and triazolam (Halcion) are relatively new triazolobenzodiazepines that are anxiolytic and hypnotic. This study assesses the reactivity of these drugs and their major metabolites in the EMIT d.a.u. benzodiazepine metabolite assay. Analytical standards of drugs and metabolites and urine specimens from patients receiving these drugs were analyzed by EMIT. Alprazolam and alpha-OH alprazolam gave an equivalent response to the EMIT low calibrator between 0.2 and 0.3 microgram/mL. Triazolam and alpha-OH triazolam were reactive between 0.3 and 0.5 microgram/mL. The assay was positive in 24 out of 27 random urine specimens from alprazolam-treated patients and in 8 out of 19 urine specimens from triazolam-treated patients. Positive urine results were confirmed by measuring the major urinary metabolites alpha-OH alprazolam and alpha-OH triazolam by HPLC. The study demonstrates that the EMIT assay can detect significant amounts of alprazolam and metabolites in the urine. The assay was negative in 58% of the specimens from individuals receiving triazolam, however.
Alprazolam↗
Modification of the EMIT tox benzodiazepine assay for screening of alprazolam in serum.
Alprazolam (Xanax) is a relatively new triazolobenzodiazepine which is anxiolytic in man and is also prescribed in the treatment of panic attacks. The objective of this study was to optimize the reactivity of the EMIT tox serum benzodiazepine assay for toxicologic screening of alprazolam. The standard EMIT procedure was extensively modified so that therapeutic concentrations of alprazolam could be detected. Modifications for Methods A and B included a single dilution of specimens, increasing incubation temperature to 37 degrees C, dilution of Reagents A and B, and increasing specimen volume to 100 microL. Method B also included supplementing Reagent A with additional glucose-6-phosphate and beta-nicotinamide adenine dinucleotide. Using serum standards, the modified EMIT assays have detection limits of approximately 25 ng/mL (Method A) and 20 ng/mL (Method B). The patient specimens analyzed were considered positive by Method B and 24/28 positive by Method A. All 28 patient specimens tested by Method B were confirmed positive by gas chromatography/electron capture detection. The day-to-day precision of both methods was less than 2% CV with diluted EMIT calibrators (N = 6). In conclusion, the modified EMIT assay can be used to screen for alprazolam in serum at therapeutic concentrations.
Alprazolam↗
Gas chromatographic analysis of methyl formate and application in methanol poisoning cases.
A modified headspace gas chromatographic method for analysis of formate in biological fluids is described. Serum or whole blood specimens were methylated in the presence of concentrated sulfuric acid and sodium propionate (internal standard) dissolved in methanol. Derivatization was performed at 35 degrees C for 30 min before injection (0.5 mL headspace) onto a Hallcomid-Carbowax packed GLC column. Using serum or aqueous standards, the method was linear from 5 to 100 mg/dL. The limit of detection was 2.5 mg/dL. Day-to-day precision was less than 5% (CV) at 54 mg/dL formate. Formate and methanol were analyzed in 3 methanol poisonings, two of which were fatal. Formate analysis is considered important in any patient with suspected methanol poisoning who presents for medical assistance with metabolic acidosis. The extent of ocular toxicity correlates better with formate concentration than with methanol concentration.
Adult↗
Lack of interference by nabilone in the EMIT d.a.u. cannabinoid assay, Abbott TDx cannabinoid assay, and a sensitive TLC assay for delta 9-THC-carboxylic acid.
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Antiemetics↗
Urinary screening for alprazolam and its major metabolites by the Abbott ADx and TDx analyzers with confirmation by GC/MS.
Alprazolam is a short-acting triazolobenzodiazepine with anxiolytic and antidepressant properties. It has a half-life of 10-15 hours after multiple oral doses. Approximately 20% of an oral dose is excreted unchanged in the urine. The major urinary metabolites are alpha-OH alprazolam glucuronide and 3-HMB benzophenone glucuronide. The objective of this study was to characterize the reactivity of alprazolam and three metabolites in the Abbott ADx and TDx urinary benzodiazepine assays compared with the EMIT d.a.u. benzodiazepine assay. Alprazolam (at 300 ng/mL) gave an equivalent response as the 300 ng/mL low control (nordiazepam). alpha-OH alprazolam gave an equivalent response to this control between 300-500 ng/mL and 4-OH alprazolam between 500-1000 ng/mL. The 3-HMB benzophenone was not positive even at 10,000 ng/mL. The ADx screening assay was positive in 26 of 31 urine specimens collected from alprazolam-treated patients. All 31 of these specimens were confirmed positive for alpha-OH alprazolam by GC/MS after enzymatic hydrolysis and formation of a TMS derivative. For the TDx, 27 of 31 specimens were positive for benzodiazepines and all 31 were confirmed by GC/MS. All 5 of the negative ADx specimens and 4 of 5 TDx specimens contained 150-400 ng/mL of alpha-OH alprazolam. In conclusion, both the ADx and TDx urine benzodiazepine assays are acceptable screening assays for alprazolam use when the alpha-OH alprazolam concentration is greater than 400 ng/mL.
Alprazolam↗
Urinary screening for midazolam and its major metabolites with the Abbott ADx and TDx analyzers and the EMIT d.a.u. benzodiazepine assay with confirmation by GC/MS.
Midazolam is a short-acting 1,4-imidazole benzodiazepine with sedative-hypnotic, anxiolytic, and amnestic properties. It is administered orally for sleeping disorders and intravenously for sedation during surgery. This drug has a short half-life (1.5-3.5 h), with less than 1% of a midazolam dose being excreted unchanged. The major urinary metabolite is alpha-hydroxy midazolam glucuronide. The objective of this study was to characterize the reactivity of midazolam and its two major metabolites in the EMIT d.a.u. benzodiazepine assay and in the Abbott TDx and ADx urine benzodiazepine assays. Midazolam and alpha-OH midazolam gave an equivalent response to the EMIT low calibrator at 200 ng/mL. On both Abbott analyzers, midazolam and alpha-OH midazolam gave an equivalent net polarization at 500 ng/mL to the Abbott low control. All three screening assays were positive in all of 21 random urine specimens collected from midazolam-treated patients. Confirmation testing was performed by analyzing for alpha-OH midazolam after enzymatic hydrolysis and formation of a TMS derivative for GC/MS. All urine specimens were confirmed positive for alpha-OH midazolam. In conclusion, all three immunoassay screening assays are acceptable for detecting the presence of midazolam metabolites in urine.
Autoanalysis↗
Evaluation of the Abbott ADx and TDx serum benzodiazepine immunoassays for analysis of alprazolam.
This study evaluated the Abbott ADx and TDx serum benzodiazepine assays for the analysis of alprazolam in serum. These systems were compared to the EMIT tox serum benzodiazepine assay and a gas chromatographic (GC) method. Six-point calibration curves (nordiazepam concentrations from 50-1,000 ng/mL) were stable on both instruments for at least 14 days. The precision of these assays was determined using three control serums containing 75,300, and 700 ng/mL of nordiazepam. On the ADx, within-run coefficients of variation (CV) for the three controls were 3.9, 3.1, and 2.8%, respectively. Between-run CVs were 2.8, 1.4, and 1.2% on the ADx. For the TDx, within-run CVs were 1.9, 1.4, and 2.6, and between-run CVs were 4.1, 1.3, and 1.9% for the three controls. Percent cross-reactivity of serum alprazolam calibrators (25-100 ng/mL) ranged from 77-88% on the ADx and 60-79% on the TDx. 99 serum specimens containing alprazolam were analyzed with the ADx, TDx, EMIT, and by gas chromatography-electron capture detection (sensitivity of 5 ng/mL). Overall, 48 of 99 specimens on the TDx, 43 of 99 on the ADx (both with a cutoff of 12 ng/mL), and 0 of 99 by EMIT (cutoff of 300 ng/mL) were positive. Of the specimens reading negative on the Abbott systems, 43 of 51 TDx results and 44 of 56 ADx results were obtained in specimens containing less than 25 ng/mL of alprazolam. For specimens with more than 25 ng/mL of alprazolam in serum (by GC), 8 specimens were negative on the TDx and 12 on the ADx.
Alprazolam↗
Urinary screening for alpha-OH triazolam by FPIA and EIA with confirmation by GC/MS.
Triazolam is a very short-acting triazolobenzodiazepine with sedative-hypnotic properties. Approximately 2% of an oral dose is excreted unchanged in the urine. The major urinary metabolite is alpha-hydroxytriazolam glucuronide (70% of the dose). The objective of this study was to characterize the reactivity of alpha-hydroxytriazolam in the urine benzodiazepine assay by fluorescence polarization immunoassay (FPIA; Abbott TDx) in comparison with enzyme immunoassay (EIA; Syva EMIT d.a.u. benzodiazepine assay). alpha-OH triazolam at 300 ng/mL gave a response equivalent to the 200-ng/mL nordiazepam Abbott calibrator. In the EMIT assay, alpha-OH triazolam gave a response equivalent to the 300-ng/mL calibrator (Syva) at 100-200 ng/mL. Both immunoassays gave positive results in 9 out of 9 urine specimens collected from individuals receiving triazolam. Confirmation was performed by analyzing for alpha-OH triazolam after enzymatic hydrolysis and formation of a TMS derivative for GC/MS. All urine specimens were positive for alpha-OH triazolam. In conclusion, both the FPIA and EIA immunoassay screening assays are acceptable for detecting the presence of alpha-OH triazolam in the urine of patients receiving therapeutic doses of triazolam.
Fluorescence Polarization↗
Urinary screening for adinazolam and its major metabolites by the Emit d.a.u. and FPIA benzodiazepine assays with confirmation by HPLC.
Adinazolam is a triazolobenzodiazepine, currently under clinical investigation, that possesses antidepressant and anxiolytic activity. It has a short half-life (less than 3 h), and less than 2% of an oral dose is excreted unchanged. The major urinary metabolite is N-desmethyladinazolam, and minor metabolites are estazolam and alpha-OH-alprazolam. The objective of this study was to characterize the reactivity of adinazolam, N-desmethyladinazolam, and estazolam in the Emit d.a.u. benzodiazepine assay and the Abbott TDx urine (FPIA) benzodiazepine assay. N-desmethyladinazolam and estazolam gave an equivalent response to the Emit cutoff calibrator (300 ng/mL) at 100-200 ng/mL, and adinazolam gave an equivalent response at 200 ng/mL. By FPIA, N-desmethyladinazolam and adinazolam had equivalent net polarization values as the 300-ng/mL low control at 500-1000 ng/mL, and estazolam gave a positive response at 300 ng/mL. Six volunteers received single oral doses of 10, 30, and 50 mg of adinazolam. Urine specimens (N = 7) were collected from 0 to 36 h post-administration. By Emit, all urine specimens at all doses were positive from 2 to 36 h, and all FPIA analyzed specimens were positive from 2 to 24 h. Confirmation testing was performed by HPLC by analyzing for N-desmethyladinazolam. All urine specimens were confirmed positive for N-desmethyladinazolam (greater than 200 ng/mL) except for the blank specimens (time = 0) and 7 of 18 specimens collected 36 h post-administration. In conclusion, both immunoassay screening assays are acceptable for detecting the presence of adinazolam in human urine for up to 24 h after a single oral dose of 10-50 mg.
Alprazolam↗
Analysis of diethyltoluamide (DEET) following intentional oral ingestion of Muscol.
N,N-Diethyl-m-toluamide (DEET) is an effective component of several insect repellent products. A 19-year-old woman was admitted to the emergency department following ingestion of 15-25 mL 95% diethyltoluamide (Muscol). Serum and urine toxicology screening tests were negative except for detection of DEET. DEET was qualitatively identified and quantitated by gas chromatography-mass spectrometry. Concentrations of DEET based on selected ion monitoring (ion at m/z 119) were 63.0, 17.2, 1.9, and less than 0.2 mg/L in serum specimens collected at 2, 5, 24, and 48 h following ingestion, respectively. Serial monitoring of DEET concentrations and the cardiac abnormalities observed in this case following oral ingestion were not reported previously.
Adult↗
Comparative evaluation of five immunoassays for the analysis of alprazolam and triazolam metabolites in urine: effect of lowering the screening and GC-MS cut-off values.
This study included evaluation of five commercially available immunoassays for the detection of alprazolam and triazolam metabolites in urine following single oral doses of these drugs. The products investigated were the EMIT d.a.u. assay, EMIT II assay, Abbott TDx (FPIA) assay, Bio Site TRIAGE device, and the Boehringer Mannheim/Microgenics CEDIA assay for urinary benzodiazepines. Urine specimens were also analyzed quantitatively by gas chromatography-mass spectrometry. Percent cross-reactivity was assessed by analysis of drug free urine containing drug standards at concentrations ranging from 100 to 10,000 ng/mL. The drug standards analyzed were alpha-OH-alprazolam, alpha-OH-triazolam, and alpha-OH-alprazolam glucuronide. The effect of lowering the screening cut-off value to 100 ng/mL, lowering the confirmation cut-off value to 50 and 25 ng/mL and the use of beta-glucuronidase hydrolysis prior to analysis was also studied. Lowering the screening cut-off value and using enzymatic hydrolysis prior to screening increased the positive detection rate for benzodiazepines with the EMIT d.a.u. assay and fluorescence polarization immunoassay (FPIA). The TRIAGE device gave the lowest percent cross-reactivity in the analysis of the drug standards and gave negative results in all urine specimens analyzed following ingestion of alprazolam and triazolam.
Alprazolam↗
Oxaprozin cross-reactivity in three commercial immunoassays for benzodiazepines in urine.
Immunoassay methods are commonly used to screen for drugs of abuse and some prescription drug classes as part of drug-testing programs in clinical and forensic toxicology. Oxaprozin (Daypro) is a new nonsteroidal anti-inflammatory drug that is widely prescribed in North America and has been reported to cross-react for benzodiazepines in several different immunoassay methods. The first objective of this study was to characterize the immunoreactivity of oxaprozin standards over a wide concentration range when analyzed by the EMIT dau, Abbott FPIA, and BMC CEDIA urine benzodiazepine assays. The second objective was to measure the immunoreactivity of urine specimens obtained from 12 subjects after receiving a single oral dose (1200 mg) of oxaprozin. Urine oxaprozin standards were prepared in drug-free urine at seven concentrations ranging from 500 to 100,000 ng/mL. The standards gave presumptive positive benzodiazepine results between 5000 and 10,000 ng/mL (EMIT dau) and approximately 10,000 ng/mL (FPIA, CEDIA). With a 200-ng/mL cutoff for benzodiazepines in these assays, all 36 urine specimens collected from the 12 subjects gave positive results by EMIT and CEDIA, and 35 of 36 urine specimens were positive by FPIA. It was concluded that presumptive positive benzodiazepine results by these immunoassays may be due to the presence of oxaprozin or oxaprozin metabolites. It is recommended that all positive immunoassay screening tests for benzodiazepines be confirmed by another technique based upon a different principle of analysis.
Administration, Oral↗
CEDIA dau Benzodiazepine screening assay: a reformulation.
The CEDIA dau Benzodiazepine assay has been reformulated to include online hydrolysis of urinary benzodiazepine glucuronide conjugates. The new antibody possesses enhanced cross-reactivities toward the low-dose benzodiazepines, which are excreted at low urinary drug-metabolite concentrations. The screening method was evaluated using lorazepam as the probe benzodiazepine. Four subjects each consumed a 1-mg lorazepam tablet. Sequential urine voids over the same time intervals were collected for the next 48 h. Twelve postdose urine samples were collected from each subject. Positive results were obtained from 5-24 h to 2-35 h using a 200-ng/mL nitrazepam calibration cutoff. There was no practical difference between hydrolyzing online with the supplied E. coli beta-glucuronidase or offline with Helix pomatia beta-glucuronidase purchased separately. Without hydrolysis, all urine samples tested negative. The cross-reactivities of lorazepam in terms of nitrazepam calibration equivalents, varied from 108 to 178% for lorazepam concentrations between 50 and 2500 ng/mL. Lorazepam glucuronide gave cross-reactivities (expressed as lorazepam base) between 72 and 136% using the online hydrolysis procedure with E. coli beta-glucuronidase. Offline hydrolysis with Helix pomatia gave cross-reactivities between 84 and 134%. Without hydrolysis, lorazepam glucuronide gave less than 4% cross-reactivity in the assay.
Anti-Anxiety Agents↗