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Biomedical subjects

J E Manno

Publications and source records attributed to J E Manno.

13 recordsLinked to original sources

The effects of temazepam and ethanol on human psychomotor performance.

We have studied the effects of temazepam, alone and in combination with ethanol, on psychomotor performance in six healthy men and women using a battery of five microcomputer-based tasks before and 30, 90, and 150 min after treatment. The tests were pursuit tracking, divided attention, two four-choice reaction time tests and tapping rate. The entire battery required 25 min. The subjects also reported their mood at each testing time using a computerized bipolar mood scales test. Temazepam (15 mg) plus ethanol (peak blood concentration of 11 mmol.l-1) significantly impaired divided attention, tracking, and reaction time over a 3 h period. There was significant impairment versus placebo for each drug alone on some of the tests. Plasma and urine concentrations of temazepam and temazepam glucuronide were measured, but there was no significant temporal correlation between impairment and drug or metabolite concentration in either plasma or urine. The subjects knew when they had taken ethanol, but could not discriminate temazepam from ethanol whether alone or in combination. The subjects rated their performance similarly after each of the four treatment conditions. The performance on the tracking, divided attention, and PAB reaction time tasks used in this study was impaired by a combination of temazepam and ethanol in doses which may not cause impairment when each is given alone.

Adult

Lack of effect of respiratory syncytial virus infection on theophylline disposition in children.

Conflicting reports raise a question about decreased plasma clearance (Clp) of theophylline in man during viral infections. Thus a dilemma exists concerning requisite dose adjustments. We examined this issue by retrospectively evaluating theophylline Clp in children infected with respiratory syncytial virus (RSV). Two pharmacokinetic approaches were applied to a one-compartment open model to fit theophylline concentrations during 83 hospitalizations of 76 children, 6 to 48 months of age, who received intravenous theophylline therapy and were tested for RSV infection. Iterative linear regression analyses of all theophylline data were used to estimate apparent volume of distribution, elimination rate constant, plasma half-life, and Clp in 39 of the hospitalizations. When insufficient data were available to distinguish apparent volume of distribution and elimination rate constant (n = 44), steady-state estimates of Clp were calculated. An age-matched and percentile body weight-matched cohort design presented RSV as the primary covariate. Theophylline Clp was similar in 29 matched RSV-infected and -uninfected pairs (1.32 +/- 0.14 and 1.25 +/- 0.05 ml/kg per minute, respectively), as were other pharmacokinetic values. Unexpectedly, a significant, inverse linear relationship was found for Clp and percentile body weight. Additionally, children born prematurely and hospitalized in the neonatal intensive care unit had significantly higher theophylline Clp; this did not affect findings regarding RSV infection. Theophylline Clp was not decreased in RSV-infected children. Current theophylline dosing recommendations for young children infected with RSV should not be altered, but careful monitoring of plasma theophylline levels should be continued.

Case-Control Studies

The use of microcomputer-based psychomotor tests for the evaluation of benzodiazepine effects on human performance: a review with emphasis on temazepam.

1. The literature relating to the effects of benzodiazepines in general, and temazepam in particular, on human psychomotor performance as assessed using microcomputer-based testing batteries is surveyed. 2. The adverse effects of central nervous system depressants on performance is an important mediocolegal issue and frequently comes into question in on-the-road and on-the-job accidents. The use of microcomputer-based testing batteries allows for performance evaluation both in the laboratory and at-the-scene, as well as providing the opportunity to model a large number of different behaviours required in routine yet complex psychomotor tasks. 3. The conclusions in general are: (1) The benzodiazepines as a class of drugs impair both cognitive and motor performance. These effects are often subtle when low doses are involved or when testing occurs the morning following evening administration of the medication. (2) No single psychomotor task adequately simulates complex daily tasks such as automobile driving. A battery of tests that evaluates a number of the components of such tasks is necessary to determine adequately the full range of effects of these medications.

Benzodiazepines

Determination of temazepam and temazepam glucuronide by reversed-phase high-performance liquid chromatography.

A rapid and sensitive method for extracting temazepam from human serum and urine is presented. Free temazepam is extracted from plasma and urine samples using n-butyl chloride with nitrazepam as the internal standard. Temazepam glucuronide is analyzed as free temazepam after incubating extracts with beta-glucuronidase. Separation is achieved using a C8 reversed-phase column with a methanol-water-phosphate buffer mobile phase. An ultraviolet detector operated at 230 nm is used and a linear response is observed from 20 ng/ml to 10 micrograms/ml. The limit of detection is 15.5 ng/ml and the limit of quantitation is 46.5 ng/ml. Coefficients of variation are less than 10% for concentrations greater than 50 ng/ml. Application of the methodology is demonstrated in a pharmacokinetic study using eight healthy male subjects.

Chromatography, High Pressure Liquid

Validation of two devices for evaluation of human psychomotor performance.

The Pursuit Meter III (PM III) and the Simultaneous Hand and Foot Tracking (SHAFT) task are microcomputer-based devices for the evaluation of human psychomotor performance. Both devices are pursuit-tracking tasks. The primary task (PM III) requires a subject superimpose a line over a computer-generated sine wave. The computer wave is black and the subject's wave is red. The vertical position of the subject's wave is determined by a joystick controller. The SHAFT adds a second simultaneous tracking task (FTT) that is operated by means of a foot control. Ten naive subjects performed either device for 5 sessions/day over a three-day period. Each session consisted of 5 sweeps of the sine wave pattern. Mean performance on both tasks generally improved over the assessment period, and differential stability was reached within 10 sweeps for each device.

Adolescent

ESTRIP, a BASIC computer program for obtaining initial polyexponential parameter estimates.

A new BASIC exponential stripping program, ESTRIP, allows the relatively rapid calculation of initial polyexponential parameter estimates, as does the previously published FORTRAN IV program, CSTRIP. The potential advantages of the new program are that it can be run on microcomputers and minicomputers with BASIC capability and a relatively small core and that it can be easily modified by the user.

Computers

Toxicology of ipecac: a review.

The general effectiveness and safety of Ipecac syrup, per se, has not been questioned, but rather an attempt has been made to consolidate pertinent literature dealing with the toxic manifestations of Ipecac fluid extract. Ipecac contains both emetine and cephaeline and the toxicity of Ipecac fluid extract is consistent with reports on the toxicity of both compounds. The majority of the work has involved emetine since it is in higher concentration in Ipecac fluid extract than is cephaeline. Comparison of the clinical picture presented in syrup or fluid extract of Ipecac overdose and emetine toxicity in amebiasis treatment permits us to summarize the general characteristics of Ipecac alkaloid toxicity as involving primarily gastrointestinal, cardiovascular, and neuromuscular foci.

Adult

Pancreatic inclusions and its relation to boric acid poisoning: review of the literature and report of a case.

It is known among forensic and pediatric pathologists that the demonstration of pancreatic inclusions is considered to have diagnostic significance in cases of boric acid poisoning. Fisher was the first to suggest a causal relationship between the inclusions and boric acid toxicity. Valdes-Dapena and Arey paid particular attention to the pancreatic inclusions in reviewing the literature of cases of boric acid poisoning. They found the inclusions in 6 of the 55 autopsies. This paper describes the finding of pancreatic inclusions in a fatal case of gastro-enteritis not associated with boric acid intoxication. The nature of the inclusion bodies was studied by light and electron microscopy. Ultrastructurally, the cytoplasmic inclusions represent a non-specific autophagic cell degenerative process. Toxicological examination of postmortem blood and viscera showed no evidence of boric acid toxicity. The desirability of toxicological analysis in cases of boric acid poisoning and the restricted value of pancreatic inclusions as a diagnostic tool are emphasised.

Boric Acids

Identification of flurazepam (Dalmane) and a primary metabolite in urine by thin-layer chromatography.

A relatively simple, routine method has been described for the qualitative identification of flurazepam and its primary metabolite 7-chloro-1-(2-hydroxyethyl)-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one in urine. We have described two extractions and several identification procedures by which flurazepam and its primary urinary metabolite can be identified by TLC.

Anti-Anxiety Agents

Application of the Syva EMIT and Abbott TDx amphetamine immunoassays to the detection of 3,4-methylene-dioxymethamphetamine (MDMA) and 3,4-methylene-dioxyethamphetamine (MDEA) in urine.

MDMA and MDEA are hallucinogenic analogs of amphetamine. The need for laboratory monitoring of these substances has developed as a result of their increased recreational use. Since the Abbott TDx and Syva EMIT-d.a.u. immunoassays are commonly used tests for urine monitoring of drugs-of-abuse, the amphetamine assay of each manufacturer was assessed to determine the degree of cross-reactivity with MDMA and MDEA. Cross-reactivity was evaluated using a series of MDMA- and MDEA-spiked urine samples. Testing was performed over a two-day period with 3 runs/day and each sample run in duplicate. The Syva EMIT d.a.u. amphetamine assay was positive only at the highest concentration standard (10.0 micrograms/mL) for both MDMA and MDEA. Consequently, no further testing was performed with this assay. Calibration curves were generated for the TDx runs and percent cross-reactivity determinations were made. Precision for the TDx data was evaluated based on within-day and between-day coefficients of variation (CV). CVs for MDMA runs were below 6% for within-day and below 5% for between-day runs. Values of CV for MDEA were below 16% for both within-day and between runs; CVs were less than 2.5% for positive values. Cross-reactivity for MDMA ranged from 18% (10.00 micrograms/mL) to 118% (0.15 microgram/mL). Cross-reactivity for the MDEA standards ranged from 12% (10.00 micrograms/mL) to 47% (0.15 micrograms/mL). The presence of MDMA and/or MDEA in samples resulting in a negative EMIT-d.a.u. test and a positive TDx test was confirmed by GC/MS analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Methylenedioxyamphetamine

A modification and validation of two urine ethanol procedures for use with the Monarch 2000 Chemistry System.

A modification of two commercially available enzymatic ethanol urine assays for use with the Monarch 2000 Chemistry System (Instrumentation Laboratory) is described. Both the Syva EMIT st Urine Ethyl Alcohol Assay and the Sigma Diagnostics Alcohol in Urine Assay, which utilize the reduction of nicotinamide adenine dinucleotide (NAD) to NADH associated with the oxidation of ethanol in the presence of alcohol dehydrogenase (ADH), were adapted to spectrophotometrically determine ethanol concentration. Precision was evaluated over a 3-day period. Within-day (n = 9) and total (n = 27) coefficients of variation (CV) were less than 7% for the controls greater than or equal to 200 mg/L (20 mg/dL). Enzymatic assay results utilizing the Monarch procedure were compared to a gas chromatographic (GC) reference method (n = 100 samples). Regression analysis of assay data with each reagent compared to the reference method resulted in correlation coefficients r = 0.972 (Syva) and 0.948 (Sigma). Both methods exhibited nonlinear results and therefore quantitative applications cannot be made. No false positive or negative results were encountered with either reagent, indicating that the assay is acceptable as a positive/negative screen for urine ethanol for a threshold less than or equal to 20 mg/dL.

Chromatography, Gas

Evaluation of the Abbott ADx Amphetamine/Methamphetamine II abused drug assay: comparison to TDx, EMIT, and GC/MS methods.

Although the legitimate clinical use of amphetamine and amphetamine congeners is declining, the illicit use of these drugs remains high. There is a need for a rapid and conclusive method for detecting these compounds in routine urine drug testing, drug screening in drug rehabilitation centers, and as an aid in the diagnosis and treatment of potential overdoses. The Abbott ADx Amphetamine/Methamphetamine II assay (A/M II), a fluorescence polarization Immunoassay (FPIA), was compared to the Abbott TDx Amphetamine/Methamphetamine II assay (FPIA), the Syva enzyme-multiplied immunoassay technique (EMIT) and a gas chromatograph/mass spectrometry (GC/MS) method. Precision of the A/M II assay was evaluated on the ADx analyzer over a 14-day period in each of three modes of operation (batch, combination, and panel) and was based on within-run and between-run coefficients of variation (CVs). Within-run CVs for all three controls (low [L], medium [M], and high [H]) ranged from 0.40% to 10.60% and between run CVs ranged from 3.96% to 7.92%. Data indicated that the calibration curve was stable for 16 days. Each of the six calibrators and three controls were within 10% of their labeled concentrations when analyzed by GC/MS. Fifty routine clinical specimens from our laboratory and 74 specimens screened as positive for amphetamine or related compounds from a rehabilitation center were screened by ADx, TDx, and EMIT. Any specimen yielding a positive result by any of these three methods was confirmed by GC/MS. In-house controls, as well as clinical samples, which contained both amphetamine and methamphetamine in the same sample produced results greater than two times the expected response on the ADx and TDx.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine