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Barry Levine

Publications and source records attributed to Barry Levine.

At least 19 recordsLinked to original sources
PubMed2006

A comprehensive study on the variations in urinary concentrations of endogenous gamma-hydroxybutyrate (GHB).

This study was designed to supplement previous attempts to establish an accurate range of normal endogenous gamma-hydroxybutyrate (GHB) concentrations in random antemortem urine samples. Furthermore, its purpose was to ascertain the effect of gender, race, age, medications, and select medical conditions on endogenous concentrations of GHB in urine and the proposed endogenous urinary GHB cutoff of 10 microg/mL. Urine samples (n = 207) were provided by subjects who reported that they had never used GHB. As part of the collection process, subjects also completed a short survey to collect information about gender, race, age, orally ingested medications, and select medical conditions. All specimens were analyzed in duplicate for the presence of endogenous GHB using a previously reported headspace gas chromatography-mass spectrometry method. The data were analyzed for tendencies among different population groups. GHB concentrations ranged from 0.00 to 2.70 microg/mL in all specimens, with a median concentration of 0.24 microg/mL. Males (n = 130) had an average endogenous GHB concentration of 0.27 microg/mL (0.00-2.70 microg/mL), whereas females (n = 77) averaged 0.29 microg/mL (0.00-0.98 microg/mL). Select medical conditions and participants' race, age ranges, and medications that were used within 48 h prior to collection were also evaluated. We believe this to be the most comprehensive study on endogenous GHB concentrations in urine to date. The results of this study will aid the interpretation of low GHB concentrations measured in urine samples, particularly in investigations of drug-facilitated crimes.

Adult↗
PubMed2006

Tizanidine distribution in a postmortem case.

The case of a 57-year-old white female who was found deceased at home by her husband is presented. A suicide note was found at the scene. No remarkable findings were observed at autopsy. Comprehensive toxicological analysis of the heart blood identified ethanol (0.16 g/dL), diazepam (1.1 mg/L), and tizanidine (2.3 mg/L). Blood concentrations of tizanidine following therapeutic use do not exceed 0.025 mg/L. The medical examiner ruled that the cause of death was combined ethanol and multiple drug intoxication, and the manner of death was suicide.

Adrenergic alpha-Agonists↗
PubMed2006

Two cases of fatal amlodipine overdose.

Two fatal overdoses of the calcium channel blocker amlodipine are described. Postmortem samples were screened for volatiles and therapeutic and abused drugs. Amlodipine was measured by liquid chromatography-atmospheric pressure photoionization-mass spectrometry. The heart blood amlodipine concentrations for the two cases were 2.4 and 0.95 mg/L, and amlodipine was quantified in all other tissues. In the first case, venlafaxine and norvenlafaxine were also found, and the angiotensin receptor antagonist olmesartan was tentatively identified. The concentrations of amlodipine are compared with previously reported fatal and nonfatal overdoses. The medical examiners ruled in both cases that the manner of death was suicide and the causes of death were mixed drug intoxication and amlodipine intoxication.

Adult↗
PubMed2006

Distribution of ether in two postmortem cases.

Diethyl ether (ether) is a volatile liquid that was used in the 1800s as an anesthetic agent; however, it is no longer used for this purpose, partly because of its odor and flammability. Two postmortem cases in which ether was detected are presented. The first case was an 18-year-old male found hanging from a basement ceiling brace in a semi-sitting position with a gas mask covering his face. A container of Prestone starting fluid and a bong were found on the floor close to the body. The second case was a 20-year-old male found unresponsive in his dormitory room with two black plastic trash bags secured over his head. Two saturated rags and a resealable bag containing a clear liquid were contained within these trash bags. An almost empty can of Tradco starting fluid was also found at the scene. Ether concentrations were determined by headspace gas chromatography-mass spectrometry in the selective ion monitoring mode. In case #1, the medical examiner ruled that the cause of death was asphyxia due to hanging; the manner of death was undetermined. In case #2, the medical examiner ruled that the cause of death was asphyxia and the manner of death was suicide.

Adolescent↗
PubMed2005

A fatality involving metaxalone.

A case is presented of a 54-year-old white female found dead in a secured apartment. Postmortem toxicologic analysis of the heart blood identified acetaminophen (97 mg/L), citalopram (0.4 mg/L), gabapentin (24 mg/L) and metaxalone (21 mg/L). The metaxalone concentration is within the range of previously reported fatalities involving metaxalone. The medical examiner ruled that the cause of death was metaxalone and gabapentin intoxication and the manner of death was suicide.

Amines↗
PubMed2005

Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot study.

BACKGROUND: Endothelin receptor antagonism produces favorable short-term hemodynamic effects in heart failure, but the clinical effects of longer term therapy have not been evaluated. METHODS AND RESULTS: Three hundred and seventy patients with symptoms of heart failure at rest or on minimal exertion and a left ventricular ejection fraction <35% were randomly assigned (double-blind) to placebo (n = 126) or the endothelin receptor antagonist bosentan, titrated slowly (n = 121) or rapidly (n = 123) to a target dose of 500 mg twice daily. Treatment with the study drug was to be maintained for 26 weeks, whereas background medications for heart failure were kept constant. Safety concerns led to early termination of the trial when only 174 patients had had an opportunity to complete 26 weeks of therapy. Bosentan exerted no apparent benefit when all randomized patients were analyzed (P = .709). However, in the first 174 patients who were recruited at least 26 weeks before study termination and who could therefore be followed for the planned duration of the trial, patients in the bosentan groups were more likely to be improved (26% versus 19%) and were less likely to be worse (28% versus 43%), P = .045. When compared with placebo-treated patients, bosentan-treated patients had a increased risk of heart failure during the first month of treatment but a decreased risk of heart failure during the fourth, fifth, and sixth months of therapy. The major noncardiac adverse effects of bosentan included an increase in hepatic transaminases (in 15.6% of patients) and a decrease in hemoglobin (of about 1 g/L). CONCLUSION: Although bosentan exerted no favorable effects in the overall study, our findings suggest that the clinical responses to endothelin antagonism with bosentan in patients with severe chronic heart failure may be dependent on the duration of treatment.

Aged↗
PubMed2005

Tissue distribution of loperamide and N-desmethylloperamide following a fatal overdose.

We report a case involving a fatal intoxication with loperamide (Imodium). Loperamide is a synthetic opioid of the phenyl piperidine class used as an over-the-counter antidiarrheal. It exerts its effects through interaction with micro-opiate receptors in the intestine to reduce peristalsis. Loperamide lacks the typical euphoric opiate effects when administered at recommended doses. Both loperamide and its major metabolite, N-desmethylloperamide, were isolated by liquid-liquid extraction into n-butyl chloride from alkalinized samples. Extracts were analyzed by liquid chromatography-electrospray-mass spectrometry in selected-ion-monitoring mode. Rapid separation of the drug, metabolite, and internal standard (diphenoxylate) was achieved using a high-resolution C18 column with 1.8-microm particle diameter. The mobile phase consisted of 0.1% formic acid in deionized water (60%) and acetonitrile (40%) at a flow rate of 0.5 mL/min. Heart blood concentrations for loperamide and its metabolite were 1.2 mg/L and 3.3 mg/L, respectively. In contrast, reported peak plasma concentrations of loperamide after administration of recommended daily doses of 16 mg did not exceed 0.012 mg/L in controlled trials. Because the heart blood ethanol concentration was 0.08 g/dL, the medical examiner ruled that the cause of death was loperamide and ethanol intoxication, and the manner of death as undetermined.

Adult↗
PubMed2004

Urinary pharmacokinetics of 11-nor-9-carboxy-delta9-tetrahydrocannabinol after controlled oral delta9-tetrahydrocannabinol administration.

Understanding the pharmacokinetics of orally administered cannabinoids is vitally important for optimizing therapeutic usage and to determine the impact of positive tests on drug detection programs. In this study, gas chromatography-mass spectrometry (limit of quantitation = 2.5 ng/mL) was used to monitor the excretion of total 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THCCOOH) in 4381 urine voids collected from seven participants throughout a controlled clinical study of multiple oral doses of THC. The National Institute on Drug Abuse Institutional Review Board approved the study and each participant provided informed consent. Seven participants received 0, 0.39, 0.47, 7.5, and 14.8 mg THC/day for five days in this double blind, placebo-controlled, randomized protocol conducted on a closed research ward. No significant differences (P </= 0.05) were observed in mean time of maximum excretion rate, mean maximum excretion rate, and mean terminal elimination half-life (t(1/2)) between the four THC doses, with ranges of 67.4 to 94.9 h, 0.9 to 16.3 micro g/h, and 44.2 to 64.0 h, respectively. Mean apparent elimination t(1/2) of 24.1 +/- 7.8 and 21.1 +/- 4.3 h for the 7.5 and 14.8 mg/day doses, respectively, were calculated from the excretion rate curve prior to the last urine sample with a THCCOOH concentration >/= 15 ng/mL. An average of only 2.9 +/- 1.6%, 2.5 +/- 2.7%, 1.5 +/- 1.4%, and 0.6 +/- 0.5% of the THC in the 0.39, 0.47, 7.5, and 14.8 mg/day doses, respectively, was excreted as THCCOOH in the urine over each 14-day dosing session. This study demonstrated that the terminal urinary elimination t(1/2) of THCCOOH following oral administration was approximately two to three days for doses ranging from 0.39 to 14.8 mg/d. These data also demonstrate that the apparent urinary elimination t(1/2) of THCCOOH prior to reaching a 15 ng/mL concentration is significantly shorter than the terminal urinary elimination t(1/2). These controlled drug administration data should assist in the interpretation of urine cannabinoid results and provide clinicians with valuable information for future pharmacological studies.

Administration, Oral↗
PubMed2004

Hydroxycarbazepine distribution in three postmortem cases.

This paper presents three cases investigated by the Office of the Chief Medical Examiner where hydroxycarbazepine, the active metabolite of the anticonvulsant prodrug oxcarbazepine, was detected in the biological specimens submitted for toxicological analysis. Hydroxycarbazepine was quantitated using a single-step pH 5 extraction and detection on a DB-5 column by gas chromatography-nitrogen-phosphorus detection. In the three cases, the heart blood concentrations were 34.6, 40.5, and 3.7 mg/L, respectively. In cases 2 and 3, the peripheral blood concentrations were 36 and 4.1 mg/L, respectively. In each case, the medical examiner ruled that the hydroxycarbazepine was an incidental finding to the cause of death.

Anticonvulsants↗
PubMed2004

Use of prostate specific antigen in the identification of semen in postmortem cases.

Over the past 20 years, the use of prostate specific antigen (PSA) as evidence of the presence of semen in forensic cases has been well established. In this study, we compared a commercially available immunoradiometric assay (IRMA) for the identification of PSA with the identification of spermatozoa in swabs obtained from the vagina of deceased females. There was agreement between the 2 methods in 67 of the 80 cases (84%), including 18 cases where both the PSA was positive and sperm were observed microscopically. The remaining cases had 1 positive result and 1 negative result. We concluded that although there was substantial agreement between the presence of sperm and a positive PSA, there were enough discrepancies between the 2 methods (16%) to justify the use of both methodologies, if possible, to make the determination of sexual activity prior to death.

Autopsy↗
PubMed2004

Oxycodone intoxication in an infant: accidental or intentional exposure?

A case is presented of a 10 month old male who went into cardiac arrest at a local store. The infant subsequently expired and was autopsied at the Office of the Chief Medical Examiner, State of Maryland. The only remarkable finding was the detection of oxycodone in the postmortem specimens; the blood and liver oxycodone concentrations were 0.6 mg/L and 1.6 mg/kg, respectively. Oxycodone was identified and quantitated by gas chromatography-nitrogen-phosphorus detection and confirmed by full scan electron ionization gas chromatography-mass spectrometry. The medical examiner ruled that the cause of death was oxycodone intoxication, and the manner of death was homicide. The key toxicologic question in this case was whether or not it was reasonable for the infant to be exposed to oxycodone exclusively through breast milk or through an alternate source. It was concluded that, at best, there were serious concerns about the likelihood of drug exposure through consumption of breast milk.

Analgesics, Opioid↗
PubMed2003

Validated method for the simultaneous determination of Delta 9-tetrahydrocannabinol (THC), 11-hydroxy-THC and 11-nor-9-carboxy-THC in human plasma using solid phase extraction and gas chromatography-mass spectrometry with positive chemical ionization.

A fully validated, highly sensitive and specific method for the extraction and quantification of Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THCCOOH) in plasma is presented. This method incorporates Escherichia coli beta-glucuronidase hydrolysis to cleave glucuronic acid moieties to capture total analyte concentrations, and simultaneous solid phase extraction (SPE) of the three analytes in a single eluant with separation and quantification on a bench-top positive chemical ionization (PCI) gas chromatography-mass spectrometry (GC-MS) in the selected ion monitoring (SIM) mode. Quantitation was achieved by the addition of deuterated analogues for each analyte as internal standards (IS). Limits of quantitation (LOQ) were 0.5, 0.5 and 1.0 for THC, 11-OH-THC and THCCOOH, respectively, with linearity ranging up to 50 ng/ml for THC and 11-OH-THC, and 100 ng/ml for THCCOOH. Absolute recoveries ranged from 67.3 to 83.5% for all three analytes. Intra-assay accuracy and precision ranged from 1.2 to 12.2 and 1.4 to 4.7%, respectively. Inter-assay accuracy and precision ranged from 1.4 to 12.2 and 3.1 to 7.3%, respectively. This method was used to analyze plasma samples collected from individuals participating in a controlled oral THC administration study. Statistically significant (P< or =0.05) increases of 40% for 11-OH-THC and 42% for THCCOOH concentrations were found between hydrolyzed and non-hydrolyzed results. This method will be utilized in ongoing controlled cannabinoid administration studies and may be a useful analytical procedure for the fields of forensic toxicology and cannabinoid pharmacology.

Dronabinol↗
PubMed2003

Mixed drug intoxication involving zaleplon ("Sonata").

Zaleplon ("Sonata") is a pyrazolopyrimidine derivative approved for use in the United States for the treatment of insomnia. To date, there has been little data in the toxicological literature where zaleplon has been implicated as causing a fatal intoxication, either alone or in combination with other drugs. This report documents a case where zaleplon was identified in a suicide by multiple drug ingestion. The following zaleplon concentrations were found: heart blood 2.2mg/l; bile 8.6mg/l and urine 1.4mg/l. Zaleplon was also detected but not quantitated in the kidney and liver.

Acetamides↗
PubMed2003

Tissue distribution of xylazine in a suicide by hanging.

Xylazine (Rompun, Sedazine, AnaSed) is currently the most commonly used sedative-analgesic in veterinary medicine. There are nine published cases of xylazine's involvement in human drug-related deaths and impairment. However, blood concentrations were reported in only four of these cases. Three of these nine cases were fatalities involving xylazine, two of which involved xylazine alone but did not report blood concentrations because of extensive decomposition of the bodies. This report documents a case in which xylazine alone was identified in a suicide by hanging. The following xylazine concentrations were found: 2.3 mg/L in heart blood; 2.9 mg/L in peripheral (subclavian) blood; 6.3 mg/L in bile; 0.01 mg/L in urine; 6.1 mg/kg in liver; and 7.8 mg/kg in kidney.

Adult↗
PubMed2003

Tentative identification of novel oxycodone metabolites in human urine.

Oxycodone is a semisynthetic codeine derivative that has been used both as an analgesic and antitussive. In the mid 1990s, OxyContin was introduced as a slow-release formulation of oxycodone for use in patients with moderate to severe chronic pain from such ailments as arthritis, vertebral disc disease, and cancer. Doctors wrote 6.9 million prescriptions for OxyContin from May 2000 through May 2001. Thus, it is no surprise that hospitals and medical examiners' offices across the country have seen an increasing number of admissions and deaths resulting from oxycodone abuse and overdose. The laboratory identifies oxycodone as part of its routine abused and therapeutic drug-testing procedures. Routine gas chromatographic analysis of bile or urine in many of these cases revealed unidentified peaks in the region of oxycodone that appeared to be oxycodone metabolites. In humans, the only documented metabolites of oxycodone are oxymorphone and N-desmethyloxycodone (noroxycodone). This study attempts to characterize these compounds as "presumptive" metabolites based on circumstantial evidence from known metabolic pathways of oxycodone in other species, as well as of other opiates and narcotic analgesics.

Analgesics, Opioid↗
PubMed2003

Urinary cannabinoid detection times after controlled oral administration of delta9-tetrahydrocannabinol to humans.

BACKGROUND: Urinary cannabinoid excretion and immunoassay performance were evaluated by semiquantitative immunoassay and gas chromatography-mass spectrometry (GC/MS) analysis of metabolite concentrations in 4381 urine specimens collected before, during, and after controlled oral administration of tetrahydrocannabinol (THC). METHODS: Seven individuals received 0, 0.39, 0.47, 7.5, and 14.8 mg THC/day in this double-blind, placebo-controlled, randomized, clinical study conducted on a closed research ward. THC doses (hemp oils with various THC concentrations and the therapeutic drug Marinol) were administered three times daily for 5 days. All urine voids were collected over the 10-week study and later tested by Emit II, DRI, and CEDIA immunoassays and by GC/MS. Detection rates, detection times, and sensitivities, specificities, and efficiencies of the immunoassays were determined. RESULTS: At the federally mandated immunoassay cutoff (50 microg/L), mean detection rates were <0.2% during ingestion of the two low doses typical of current hemp oil THC concentrations. The two high doses produced mean detection rates of 23-46% with intermittent positive tests up to 118 h. Maximum metabolite concentrations were 5.4-38.2 microg/L for the low doses and 19.0-436 micro g/L for the high doses. Emit II, DRI, and CEDIA immunoassays had similar performance efficiencies of 92.8%, 95.2%, and 93.9%, respectively, but differed in sensitivity and specificity. CONCLUSIONS: The use of cannabinoid-containing foodstuffs and cannabinoid-based therapeutics, and continued abuse of oral cannabis require scientific data for accurate interpretation of cannabinoid tests and for making reliable administrative drug-testing policy. At the federally mandated cannabinoid cutoffs, it is possible but unlikely for a urine specimen to test positive after ingestion of manufacturer-recommended doses of low-THC hemp oils. Urine tests have a high likelihood of being positive after Marinol therapy. The Emit II and DRI assays had adequate sensitivity and specificity, but the CEDIA assay failed to detect many true-positive specimens.

Administration, Oral↗
PubMed2003

Fatal diphenhydramine intoxication in infants.

Diphenhydramine is an antihistamine available in numerous over-the-counter preparations. Often used for its sedative effects in adults, it can cause paradoxical central nervous system stimulation in children, with effects ranging from excitation to seizures and death. Reports of fatal intoxications in young children are rare. We present five cases of fatal intoxication in infants 6, 8, 9, 12, and 12 weeks old. Postmortem blood diphenhydramine levels in the cases were 1.6, 1.5, 1.6, 1.1 and 1.1 mg/L, respectively. Anatomic findings in each case were normal. In one case the child's father admitted giving the infant diphenhydramine in an attempt to induce the infant to sleep; in another case, a daycare provider admitted putting diphenhydramine in a baby bottle. Two cases remain unsolved; one case remains under investigation. The postmortem drug levels in these cases are lower than seen in adult fatalities. We review the literature on diphenhydramine toxicity, particularly as it pertains to small children, and discuss the rationale for treating these cases as fatal intoxications.

Diphenhydramine↗