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Biomedical subjects

A J Jenkins

Publications and source records attributed to A J Jenkins.

52 records · Page 3Linked to original sources
PubMed1995

Distribution of ethanol in postmortem liver.

The analysis of multiple specimens for ethanol has become a necessary and accepted practice in postmortem forensic toxicology. The correlation between blood and various body fluids has been well documented. However, there is little data on the distribution of ethanol in specimens such as the liver. In postmortem cases where blood is unavailable or contaminated, liver may be used for alcohol and drug analyses. This study reports the analysis, by head space gas chromatography, of heart blood and liver specimens for ethanol from 103 postmortem cases. The average liver/heart blood ratio in cases with a blood alcohol level (BAC) > or = 0.04 g/dL was 0.56, SD = 0.30, with a range of 0-1.40.

Alcoholic Intoxication↗
PubMed1994

Distribution of sertraline in postmortem cases.

Sertraline is a potent inhibitor of serotonin reuptake in the central nervous system and is used clinically to treat depression and obsessive-compulsive behavior. Over the course of one year, there were seven cases investigated by the Office of the Chief Medical Examiner, State of Maryland, in which sertraline was identified in postmortem specimens. Heart blood concentrations in the seven cases ranged from 0.23 to 0.46 mg/L; desmethylsertraline concentrations ranged from 0.08 to 0.99 mg/L. One similarity with tricyclic antidepressants is the high liver concentrations of drug and metabolite relative to the blood. One unusual finding is the small concentrations of drug and metabolite in the urine relative to other specimens. In none of these cases was the cause of death related to sertraline intoxication.

1-Naphthylamine↗
PubMed1994

Sweat testing for heroin, cocaine, and metabolites.

Although a variety of drugs have been detected in sweat, little information is available on the characteristics of drug excretion in sweat under controlled-dosing conditions. A series of clinical studies were designed to determine the identity, concentration, time course, dose dependency, and variability of drug and metabolite excretion in sweat following administration of single doses of cocaine and heroin to human subjects. Sweat was collected by means of a sweat patch that could be worn for a period of several days to several weeks at a time, resulting in accumulation of drug in the patch. Sweat patches were removed at specified times and frozen until analyzed by gas chromatography--mass spectrometry. Cocaine and heroin were the major analytes excreted in sweat following their administration. Smaller amounts of cocaine metabolites were also detected following cocaine administration. 6-Acetylmorphine appeared rapidly after heroin administration and continued to increase while heroin content decreased, suggesting that heroin was undergoing hydrolysis in the sweat patch. Cocaine appeared in sweat within 1-2 hours and peaked within 24 hours in an apparent dose-dependent manner. Analysis of duplicate adjacent patches from individual subjects who had been administered cocaine provided similar quantitative results, suggesting that intrasubject variability was relatively low, whereas intersubject variability was high. These observations regarding the excretion of cocaine and heroin analytes in sweat have important forensic implications to other fields such as hair analysis. Sweat excretion could be an important mechanism by which drugs enter hair. These data also suggest that the sweat patch could serve as a useful monitoring device in surveillance of individuals in treatment and probation programs.

Administration, Inhalation↗
PubMed1994

Pharmacokinetics and pharmacodynamics of smoked heroin.

Despite the current popularity of smoking as a route of drug self-administration, there have been few human studies characterizing the pharmacokinetics and pharmacodynamics of smoked drugs of abuse. A variety of technological difficulties are encountered in the design of smoking studies, such as delivering reproducible doses and limiting the amount of pyrolysis of parent drug. As part of a concerted research effort to deliver precise, smoked doses of drug, a computer-assisted smoking device was utilized that delivered single puffs of heroin vapor to human subjects under controlled clinical conditions. Recovery studies indicated that the smoking device delivered approximately 89% of parent heroin to subjects. Although only two qualified heroin smokers could be identified as eligible volunteers, their participation provided the unique opportunity to study the pharmacokinetics and pharmacodynamics of smoked heroin. The two subjects were administered four smoked heroin doses in ascending order. In addition, four intravenous doses of heroin were administered for comparison of effects and estimation of bioavailability. Concurrent physiological, behavioral, and performance measures were collected along with blood samples. Blood was analyzed for heroin, 6-acetylmorphine, and morphine by solid-phase extraction gas chromatography-mass spectrometry. Heroin appeared rapidly in blood after administration and peaked 1-5 minutes after smoking, which is similar to that observed following intravenous administration. Heroin concentrations declined rapidly to the limit of detection (1.0 ng/mL) by 30 minutes. 6-Acetylmorphine blood concentrations also peaked and declined rapidly after smoked heroin with peak concentrations occurring at 1-2 minutes after smoking. Morphine levels rose and decayed more slowly. Mean elimination half-lives for heroin, 6-acetylmorphine, and morphine were 3.3 min, 5.4 min, and 18.8 min, respectively, by the smoked route. The bioavailability of smoked heroin was highly variable. Physiological measures such as pupil diameter demonstrated a counterclockwise hysteresis compared with heroin blood levels. The rapid onset of pharmacological effects together with the early appearance of heroin and metabolites in blood following smoked heroin demonstrated the effectiveness of this route of drug administration. It is evident that the smoking route enables individuals to obtain similar pharmacological effects as are produced by intravenous administration of heroin.

Administration, Inhalation↗
PubMed1994

A fentanyl epidemic in Maryland 1992.

In early 1992, the Office of the Chief Medical Examiner, State of Maryland, encountered 30 cases where fentanyl was identified in the postmortem specimens. Twenty-five of the decedents were found in Baltimore City and five were found in the surrounding counties. Four of the decedents were female and eight of the victims were white. The blood fentanyl concentrations ranged from 2.2 to 100 micrograms/L. Ethanol and other abused drugs were detected in 28 of these cases. The cause of death in all cases was ethanol-, drug intoxication, or both.

Adult↗
PubMed1993

Validity testing of the EZ-SCREEN cannabinoid test.

Recently, a number of "quick tests" became available for use in on-site drug testing. These tests offer advantages in simplicity, ease of performance, and rapid access to test results. However, there is a paucity of data on the validity of these tests for the detection of drugs of abuse. This report describes a validity study of the EZ-SCREEN cannabinoid test for the detection of cannabinoids in urine. Three healthy, male volunteers with a history of marijuana use participated in the study. Each subject smoked 1, 2, or 4 marijuana cigarettes (2.6% THC) on each test day. Urine samples were collected and incorporated into a specimen set consisting of 178 clinical urine samples, 72 urine samples containing known amounts of drug, and 50 drug-free urine samples. The specimen set was randomized and analyzed under blind conditions by the EZ-SCREEN test and by GC/MS for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). Results were interpreted independently by three readers. Concordance analysis was performed by comparison of results of the EZ-SCREEN test with GC/MS. The EZ-SCREEN test was highly sensitive and produced positive results at a standard THCCOOH concentration of 5 ng/mL. While showing high sensitivity to THCCOOH, the assay demonstrated low cross-reactivity with delta 9-tetrahydrocannabinol (THC) and other cannabinoids. No false-positive results were recorded with 50 drug-free urine samples, but one reader recorded eight undecided results. Overall agreement between the three readers for the EZ-Screen results was approximately 80%. Delayed readings and photocopy readings tended to be less accurate than readings obtained at 3 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Plasma apolipoprotein (a) is increased in type 2 (non-insulin-dependent) diabetic patients with microalbuminuria.

Patients with Type 2 (non-insulin-dependent) diabetes mellitus complicated by microalbuminuria or albuminuria, have an increased risk of developing macrovascular disease and of early mortality. Because lipoprotein abnormalities have been associated with diabetic nephropathy, this study tested the hypothesis that levels of apolipoprotein (a) are elevated in patients with Type 2 diabetes and increased levels of urinary albumin loss. Levels of apolipoprotein (a) in diabetic patients with microalbuminuria (n = 26, geometric mean 195 U/l, 95% confidence interval 117-324) and albuminuria (n = 19, 281 U/l, 165-479) were higher than in non-diabetic control subjects (n = 140, 107 U/l, 85-134, p < 0.05), and in the albuminuric group than diabetic patients without urinary albumin loss (n = 58, 114 U/l, 76-169, p < 0.05). Patients with microalbuminuria and albuminuria had levels comparable with patients undergoing elective coronary artery graft surgery (n = 40, 193 U/l, 126-298). Apolipoprotein (a) levels were higher in diabetic patients with macrovascular disease than in those without (n = 49, 209 U/l, 143-306 vs n = 54, 116 U/l, 78-173, p < 0.05). These preliminary results suggest that raised apolipoprotein (a) levels of Type 2 diabetic patients with microalbuminuria and albuminuria may contribute to their propensity to macrovascular disease and early mortality.

Aged↗
PubMed1991

Increased plasma apolipoprotein(a) levels in IDDM patients with microalbuminuria.

Patients with insulin-dependent diabetes mellitus (IDDM) have a significantly increased risk of macrovascular disease, particularly if they have persistent proteinuria. To determine whether altered levels of apolipoprotein(a) [apo(a)], the plasminogenlike glycoprotein of the potentially atherogenic lipoprotein(a); contribute to the increased risk of atherosclerosis, apo(a) levels were measured in 107 patients with IDDM and compared with nondiabetic control subjects and male elective coronary artery graft patients. Apo(a) levels were increased in diabetic patients with microalbuminuria (geometric mean 245 U/L, 95% confidence interval [CI] 142-427, n = 30) and albuminuria (mean 196 U/L, 95% CI 97-397, n = 18) with levels comparable to patients with coronary artery disease (mean 193 U/L, 95% CI 126-298, n = 40), which were higher than in the control group (mean 107 U/L, 95% CI 85-134, n = 140; P = 0.016). Apo(a) levels in diabetic patients without microalbuminuria (mean 86 U/L, 95% CI 63-116, n = 59) were comparable with the control population and less than in those with microalbuminuria (P less than 0.001) and albuminuria (P = 0.014). The elevated apo(a) levels found in patients with IDDM and increased urinary albumin loss may contribute to their heightened risk of macrovascular disease.

Adult↗
PubMed1989

Arcuate area of the female rat maintained in vitro exhibits increased afternoon electrical activity.

The arcuate area of the rat hypothalamus has previously been shown to have increased neuronal activity in vivo corresponding to the estradiol-induced luteinizing hormone rise in the afternoon. The present experiments investigate the arcuate area to determine whether afternoon increases in activity occur in vitro and are dependent on estradiol pretreatment. Light-dark entrained pubertal rats were ovariectomized and implanted with estradiol- or cholesterol-filled silastic capsules. Two days later they were sacrificed at 10.00 h and coronal sections containing the arcuate area were maintained in oxygenated artificial cerebrospinal fluid at 34 degrees C. With estrogen pretreatment, units recorded from 11.00 to 15.00 h had a slow discharge with hourly mean rates ranging from 0.7 to 0.86 spikes/s. However, in the next hour the mean firing rate doubled (p less than 0.01) and an increase in units encountered per electrode penetration was observed. In tissue from animals sacrificed 3 h later, an increase in firing rate was also noted after 15.00 h, suggesting that a diurnal mechanism rather than a technical artifact was responsible for the timing of the activity increase. In control experiments with cholesterol capsules, electrical activity did not have a diurnal pattern. In summary, the arcuate area of the rat isolated in vitro was observed to display an increase in neuronal activity during the afternoon that was dependent on estrogen pretreatment and correlated to the time of day that luteinizing hormone rises are seen in intact animals. Although the arcuate area is involved in numerous functions, this electrical activity may represent interneurons controlling the release of luteinizing hormone-releasing hormone from axonal endings in the median eminence.

Animals↗
PubMed1988

Pressure support ventilation.

The management of patients with respiratory failure can be challenging. A relatively new technique may be useful in freeing these patients from mechanical ventilation. With a spontaneously taken breath, positive pressure is provided by a ventilator equipped to detect small changes in airway pressure. Pressure support ventilation may mean the difference between an independent life and ventilator dependency.

Humans↗
PubMed1986

A DNA fragment containing the groE genes can suppress mutations in the Escherichia coli dnaA gene.

An 8.2 kb fragment of E. coli chromosomal DNA, when cloned in increased copy number, suppresses the dnaA46 mutation, and an abundant protein of about 68 kd (60 kd when measured by us), encoded by the fragment, is essential for the suppression (Takeda and Hirota 1982). Mapping experiments show that the fragment originates from the 94 min region of the chromosome. It encodes several proteins but only one abundant polypeptide of the correct size, the product of the groEL gene. Suppression by the fragment is allele specific; those mutations which map to the centre of the gene are suppressed. Other initiation mutants including dnaA203, dnaA204, dnaA508, dnaAam, dnaC, dnaP and dnaB252 are not suppressed. Most suppressed strains are cold-sensitive suggesting an interaction between the mutant proteins (or their genes) and the suppressing protein or proteins.

Bacterial Proteins↗
PubMedDate not supplied

Validity testing of the accuPINCH THC test.

Self-contained drug-testing kits are currently being marketed for a variety of drugs of abuse. These tests are designed to provide rapid access to test results without the need for laboratory facilities. This report describes a validity study of the accuPINCH THC test, a self-contained test for cannabinoids in urine. Three healthy male volunteers with a history of marijuana use participated in the clinical study. Each subject smoked one, two, or four marijuana cigarettes (2.6% THC) on each test day. Urine samples were collected and incorporated into a specimen set consisting of 178 clinical samples, 72 urine samples containing known amounts of drug, and 50 drug-free urine samples. The specimen set was randomized and analyzed under blind conditions by the accuPINCH test and by gas chromatography-mass spectrometry (GC-MS) for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). AccuPINCH results were interpreted independently by three readers as positive at either two calibration points (positive A < 100 ng/mL THCCOOH; positive B > or = 100 ng/mL THCCOOH) or negative. Concordance analysis was performed by comparison of the accuPINCH results with GC-MS. In addition, the effects of changes in sample turbidity, temperature, and assay reading time on test outcome were assessed. For the clinical samples, positive B results were associated exclusively with THCCOOH concentrations greater than or equal to 15 ng/mL, whereas positive A and negative results were obtained at all concentrations. All drug-free urine samples were interpreted as either negative or positive A. The test demonstrated relatively low cross-reactivity with THC and other cannabinoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

A fatality due to alprazolam intoxication.

Alprazolam is one of the most widely prescribed benzodiazepines in the United States. It is generally considered a safe and effective drug for the treatment of anxiety disorders and panic attacks. Few overdoses that are due to the sole ingestion of alprazolam have been reported. This paper documents a fatality due to alprazolam intoxication and describes the distribution of alprazolam and an active metabolite, alpha-hydroxyalprazolam, in tissues obtained at autopsy. Qualitative identification of the drugs was achieved by full-scan gas chromatography-mass spectrometry, and quantitative analysis was performed by high-performance liquid chromatography. High concentrations of alprazolam were found in all specimens analyzed, but the metabolite was detected only in subclavian blood, urine, bile, and liver. A postmortem heart blood alprazolam concentration of 2.1 mg/L is the highest reported in the literature to date.

Adult↗
PubMedDate not supplied

Determination of olanzapine in a postmortem case.

Olanzapine, a new antipsychotic agent, was approved by the U.S. Food and Drug Administration in 1996 for use in the treatment of schizophrenia. It is structurally similar to clozapine, has a low incidence of extrapyramidal effects, and is effective in treating both the positive and negative symptoms of schizophrenia. This paper describes the determination of olanzapine in biological specimens obtained from the autopsy of a 35-year-old white male found dead in bed at a psychiatric facility. In the months prior to his death, the deceased was prescribed multiple medications, including olanzapine. Olanzapine was identified qualitatively by full scan gas chromatography-mass spectrometry, with quantitative analysis performed by liquid-liquid extraction followed by dual-column gas chromatography. The following concentrations were determined in the specimens analyzed: heart blood, 550 ng/mL; bile, 6346 ng/mL; and gastric contents, 157 ng/mL. Vitreous humor, cerebrospinal fluid, and urine specimens were negative. Although steady-state plasma concentrations of 10-25 ng/mL olanzapine have been reported, effective levels are known to be highly variable and a plasma concentration of 300 ng/mL has been tolerated without adverse effects. Based upon the autopsy, toxicological findings, and case investigation, the cause of death was determined to be intramyocardial arteriosclerosis with severe stenosis of the nodal artery due to hypertensive cardiovascular disease, and the manner was natural.

Adult↗
PubMedDate not supplied

Laser-Doppler velocimetry and photoplethysmography in the diagnosis of abnormal venous reflux.

Laser-Doppler Velocimetry (LDV) is useful in measurement of relative tissue blood flow. We have found a change in both the variability of the LDV waveform and its absolute level when measured in the supine and dependent limb, in patients with venous reflux. These changes correlated with simultaneous photo-plethysmographic (PPG) assessment of venous reflux and were more pronounced in patients with leg ulcers. These changes were also reduced by compression bandaging.

Humans↗