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Biomedical subjects

B K Logan

Publications and source records attributed to B K Logan.

50 records · Page 3Linked to original sources
PubMed1986

Sedation in intensive care: morphine and renal function.

Intravenous morphine infusions have been administered to 12 critically-ill patients during controlled ventilation. Acute oliguric renal failure was present in 4 patients, who were treated with a combination of haemofiltration and haemodialysis. Severity of physiological disturbance was assessed using a modified APACHE Score, level of sedation by a linear-analogue scale, and blood morphine levels by high-pressure liquid chromatography. Morphine clearance was impaired in renal failure, and was dependent on haemofiltration volumes; accumulation of morphine did not occur during this form of treatment. Conscious level was clearly more closely related to the degree of physiological disturbance than blood morphine levels; and for a given blood morphine level, depression of consciousness was more pronounced the greater the degree of physiological disturbance. Use of a physiological sickness score may help to clarify some of the factors influencing cerebral function during critical illness. Careful clinical monitoring of level of sedation is important in patients with oliguric renal failure receiving morphine, and haemofiltration appears to reduce the risk of morphine accumulation in these patients.

Acute Kidney Injury↗
PubMedDate not supplied

The measurement and interpretation of morphine in blood.

A method for the determination of morphine is post-mortem blood by HPLC with electrochemical detection is described. Blood morphine levels in post-mortem cases are reported and the importance of these in causing death is discussed. These post-mortem levels are compared further with morphine levels in the blood of patients receiving morphine as an analgesic.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Direct analysis of anticonvulsant drugs in vitreous humour by HPLC using a column switching technique.

A method is described for the rapid HPLC analysis of a number of anticonvulsant drugs in vitreous humour by injection directly onto a preconcentration column without the need for prior extraction. The conditions for optimum precision and accuracy were investigated and the method was subsequently applied to the analysis of phenytoin in a number of overdose cases. Sensitivity was 0.05 microgram/ml on a 0.5 ml vitreous sample. The mean blood/vitreous ratio for phenytoin was found to be 2.8 (range: 1.4-5.1). The relationship between blood and vitreous levels had a correlation coefficient of 0.85. Vitreous was found to be a very clean, stable sample, ideally suited to this technique.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Rapid screening for 100 basic drugs and metabolites in urine using cation exchange solid-phase extraction and high-performance liquid chromatography with diode array detection.

A system involving the combination of cation exchange solid-phase extraction and gradient elution HPLC with diode array detection was developed for the isolation and identification of basic drugs in urine. At least 100 basic drugs commonly encountered in urinary drug screening and many popular illicit drugs could be identified. Detailed study of 30 of these compounds showed that in addition to the procedure's simplicity and convenience, recoveries were close to 100% in most cases. The method was compared with an existing liquid-liquid extraction/capillary gas chromatography procedure and was at least as effective for extracting and identifying basic drugs, and especially effective at extracting problematic compounds including morphine, benzoylecgonine, temazepam, and oxazepam. Additional advantages of solid-phase extraction technology include the elimination of time-consuming shaking and centrifugation steps, elimination of reusable glassware, and reduced sample-operator contact with potentially infectious samples.

Cations↗
PubMedDate not supplied

Identification of laudanosine, an atracurium metabolite, following a fatal drug-related shooting.

In a case involving a fatal shooting, toxicology tests on blood and urine demonstrated the presence of cocaine metabolites and a large amount of an unidentified compound. This compound was subsequently identified by mass spectral, gas chromatographic, and thin layer chromatographic tests as laudanosine, a metabolite of the skeletal muscle relaxant atracurium which was administered during emergency surgery. Identification was confirmed by comparison with commercially available standards. Because of the difficulty associated with isolating and chromatographing highly water-soluble compounds, recognition of this artifact is a useful tool in identifying these cases.

Adult↗
PubMedDate not supplied

Three fatal drug overdoses involving bupropion.

Bupropion is a "second generation" antidepressant agent structurally related to the phenethylamines. Postmortem toxicology data are presented from three suicidal drug overdoses in which bupropion was detected. In two cases in which bupropion was the major toxicology finding, peripheral blood levels of the parent drug were 4.0 and 4.2 mg/L and total metabolite levels were 15 and 16.6 mg/L. Lethal doses in both cases were estimated by history to be less than 10 g.

Adolescent↗
PubMedDate not supplied

Analysis of sertraline (Zoloft) and its major metabolite in postmortem specimens by gas and liquid chromatography.

We report methods for the analysis of sertraline and desmethylsertraline in postmortem biological fluids. The extraction method is based on a widely used procedure employing n-butyl chloride, and instrumental analysis is performed using GC/MS and HPLC with photodiode array detection. We report retention index, mass spectral, and UV-vis properties of the drug and its metabolite. Samples from three sertraline-related deaths were analyzed and revealed concentrations up to 10 times greater than the normal therapeutic levels, although two of the deaths were obviously the result of other causes. We also noted in one case that the drug concentrations in central and peripheral blood were very similar, suggesting that postmortem distribution may be uniform.

1-Naphthylamine↗
PubMedDate not supplied

Analysis of ketorolac in postmortem blood.

This paper describes analytical methods using high-performance liquid chromatography and gas chromatography-mass spectrometry (GC-MS) for the isolation of the nonsteroidal anti-inflammatory drug, ketorolac. The drug is isolated from postmortem blood using a batched solid-phase extraction method on Amberlite XAD-2 resin. Derivatization of ketorolac using diazopropane was necessary prior to GC-MS analysis. The methods were applied in the investigation of a death occurring shortly after the administration of an intramuscular injection of ketorolac tromethamine. Death was attributed to an adverse reaction to the drug, resulting in anaphylaxis and cardiac arrest.

Adult↗
PubMedDate not supplied

Lack of predictable site-dependent differences and time-dependent changes in postmortem concentrations of cocaine, benzoylecgonine, and cocaethylene in humans.

This study evaluated the stability of cocaine, benzoylecgonine, and cocaethylene in postmortem fluids in cases of cocaine-related death. Femoral and ventricular blood and cisternal cerebrospinal fluid were collected soon after death and again at the time of autopsy. In addition, iliac blood was collected at autopsy. There were no consistent patterns of site-specific differences for any of the analytes, and the central compartment showed both higher and lower concentrations than the peripheral. There was no consistent pattern of direction or magnitude of change in the concentrations with respect to time for any of the analytes. This is consistent with anecdotal reports from other workers and is believed to be a result of competing processes of tissue release and chemical and enzymatic degradation of the analytes. Postmortem cocaine and metabolite concentrations in blood are not necessarily reflective of the perimortem concentrations and should not be the primary consideration in determining the cause of death in suspected cocaine-related deaths.

Adult↗
PubMedDate not supplied

Identification of tramadol and its metabolites in blood from drug-related deaths and drug-impaired drivers.

Tramadol is a centrally acting, binary analgesic that is neither an opiate-derived nor a nonsteroidal anti-inflammatory drug and that was approved for use in the United States in 1995. It is used to control moderate pain in chronic pain settings such as osteoarthritis and postoperative cases. Used in therapy as a racemic mixture, the (+)-enantiomer weakly binds to the mu-opioid receptor, and both enantiomers inhibit serotonin and norepinephrine reuptake. Tramadol's major active metabolite, O-desmethyltramadol (ODT), shows higher affinity for the mu-opioid receptor and has twice the analgesic potency of the parent drug. The synergism of these effects contributes to tramadol's analgesic properties with the (+)-enantiomer exhibiting 10-fold higher analgesic activity than the (-)-enantiomer. Although tramadol was initially thought to exhibit low abuse potential, Ortho-McNeil, the drug's manufacturer, recently reported a large number of adverse events attributed to tramadol including abuse by opioid-dependent patients, allergic reactions, and seizures. The high number of adverse reactions has prompted the company to update the prescribing information for the drug. An analytical method using gas chromatography-mass spectrometry (GC-MS) without derivatization for the determination of tramadol and its metabolites is reported. An n-butyl chloride extraction is followed by GC-MS analysis using a 5% phenylmethylsilicone column (30 m x 0.32-micron i.d.). Analysis of 12 blood samples from tramadol-related deaths and four nonfatal intoxications involving tramadol revealed concentrations ranging from 0.03 to 22.59 mg/L for tramadol, from 0.02 to 1.84 mg/L for ODT, and from 0.01 to 2.08 mg/L for N-desmethyltramadol. Three deaths were clearly attributable to acute morphine toxicity, one was a doxepin overdose, and six were multiple drug overdoses. The role of tramadol in each death is explored.

Adolescent↗
PubMedDate not supplied

Ethanol content of various foods and soft drinks and their potential for interference with a breath-alcohol test.

A variety of breads and soft drinks were tested and found to contain low concentrations of alcohol. The potential for these products to generate false readings on an evidential breath-alcohol instrument was evaluated. Alcohol-free subjects ingested these products and then provided breath samples into a DataMaster. It was found that breath samples provided immediately after consumption of some of these products, or with them still present in the mouth, did produce low levels of apparent breath alcohol, which may or may not be rejected as invalid by the breath-test instrument. If the subject swallowed or expectorated the food or beverage and then observed a 15-min deprivation period during which nothing was introduced into the mouth, the apparent effect was eliminated. These findings emphasize the need for the mandatory pretest alcohol-deprivation period and the benefits of duplicate breath sampling.

Beverages↗
PubMedDate not supplied

Determination of gamma-hydroxybutyrate (GHB) in biological specimens by gas chromatography--mass spectrometry.

A simple liquid-liquid extraction procedure for the analysis of gamma-hydroxybutyrate (GHB) in biological fluids without conversion to its lactone, gamma-butyrolactone, is described. Following derivatization to its di-TMS derivative, GHB was detected using gas chromatography-electron impact mass spectrometry. Diethylene glycol was used as the internal standard. The limit of quantitation in 1 mL of blood was 1 mg/L, and a linear response was observed over the concentration range 1 to 100 mg/L. Coefficients of variation for both intra-assay precision and interassay reproducibility ranged between 3.9 and 12.0%. GHB was detected in the blood of a sexual assault victim (3.2 mg/L), in the blood of two driving (DUI) cases (33 and 34 mg/L), and in the blood and urine of two nonfatal GHB-overdose cases (blood 130 and 221 mg/L; urine 1.6 and 2.2 g/L). The observed clinical symptoms ranged from confusion, disorientation, vomiting, and nystagmus to ataxia, sinus bradycardia, unconsciousness, and apnea.

Accidents, Traffic↗
PubMedDate not supplied

Amphetamines: an update on forensic issues.

Methamphetamine is currently enjoying a resurgence of popularity as a recreational drug. It presents a number of challenges to the forensic toxicologist both analytically and interpretively, and these latter interpretive issues are considered here. This review also discusses the current popular syntheses which account for the widespread domestic synthesis of the drug; the demographics of methamphetamine use in the United States as assessed from the Drug Abuse Warning Network (DAWN) data; developments in research of the neurotransporter pharmacology of the drug and its implications for interpretive forensic toxicology; the psychomotor effects of the drug and its potential for cognitive and functional impairment; interpretive issues related to postmortem blood drug concentrations and how these are impacted by evidence for incomplete distribution and the potential for postmortem redistribution; and, finally, concerns caused by designer methamphetamine analogues. All data indicate that methamphetamine and its analogues will present significant interpretive challenges to forensic toxicologists as the popularity of the drug continues to grow.

Amphetamine-Related Disorders↗