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Biomedical subjects

B Levine

Publications and source records attributed to B Levine.

At least 127 records · Page 7Linked to original sources

An unusual morphine fatality.

A case is presented of a 90-year-old white female who apparently died of natural causes in a nursing home. Subsequent investigation indicated that the decedent had been administered an unauthorized bolus of morphine just prior to her death. The embalmed body was exhumed, an autopsy performed, and specimens were collected for toxicologic analysis. The liver contained 1.5 mg/kg of free morphine as measured by radioimmunoassay. The presence of morphine was confirmed by gas chromatography/mass spectrometry. A review of the literature as well as in-house data collected from narcotic deaths clearly suggest that the morphine measured in this case was consistent with a lethal concentration. The manner of death was homicide.

Aged↗

Persistence of alphaviruses in vertebrate hosts.

Alphaviruses are a group of arthropod-borne, positive-strand RNA viruses that cause acute encephalitis or arthritis. These viruses were previously thought to cause only acute infections in vertebrates, but recent evidence suggests that host immunological and tissue-specific factors may act together to promote the persistence of alphavirus genomes in vivo.

Alphavirus↗

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↗

A mexiletine intoxication.

A case is presented of a 26-year-old white male with a history of depression and previous suicide attempts. No anatomic cause of death was determined at the autopsy. Comprehensive toxicological analysis of the blood and urine specimens identified mexiletine, a class 1B antiarrhythmic drug. Mexiletine was detected by gas chromatography and confirmed by gas chromatography-mass spectrometry. Quantitations were as follows: heart blood, 38 mg/L; subclavian blood, 14 mg/L; urine, 370 mg/L; liver, 190 mg/kg; kidney, 170 mg/kg; vitreous humor, 17 mg/L; and bile, 440 mg/L. The medical examiner ruled that the cause of death was mexiletine intoxication and the manner of death was suicide.

Adult↗

Hemodynamic and neurohumoral effects of the angiotensin II antagonist losartan in patients with heart failure.

BACKGROUND: Losartan is a specific angiotensin II receptor antagonist with no agonist properties. This agent permits evaluation of the response to selective angiotensin II antagonism in patients with congestive heart failure. OBJECTIVE: A study was designed to assess the acute hemodynamic and neurohumoral response to losartan in a controlled, blinded fashion. DESIGN: Sixty-six patients in New York Heart Association functional class II, III or IV with a radionuclide ejection fraction of < 40% were randomly allocated to treatment with placebo and then sequentially to 5, 10, 25, 75 and 150 mg losartan. Hemodynamic and neurohumoral measurements were obtained at selected times for 24 h following ingestion of a single dose of losartan. RESULTS: Treatment with losartan led to dose-dependent vasodilation. Mean arterial pressure and systemic vascular resistance decreased progressively up to a dose of 25 mg. The higher doses of 75 and 150 mg did not produce additional vasodilation. Similarly, the decrease in pulmonary capillary wedge pressure was not greater with doses exceeding 25 mg. The increase in the cardiac index was modest and similar for all doses. No variation in the heart rate was observed at any dose. The hemodynamic changes were accompanied by marked neurohumoral changes. Large dose-related increases in plasma renin activity and angiotensin II levels were observed, especially following the 150-mg dose. Moderate reductions occurred in serum aldosterone and plasma noradrenaline. The peak effect for these parameters occurred 4-6 h after the dose, with persistent changes still evident 24 h after the dose. CONCLUSIONS: These data demonstrate that selective blockade of the angiotensin II receptor with losartan causes a favorable vasodilatory and neurohumoral response in patients with heart failure. Further studies are needed to determine the most effective dose in these patients. Nevertheless, losartan should be of substantial clinical use in the management of this large population.

Angiotensin Receptor Antagonists↗

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↗

Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene.

Little is known about virus-host cell interactions that regulate the lytic potential of viruses during productive replication. Sindbis virus (SV), a single-stranded positive-sense RNA virus in the alphavirus genus (family Togaviridae), results in lytic infection in most vertebrate cell lines, but persistent productive infection in post-mitotic neurons. The cellular oncogene bcl-2, which encodes an inner mitochondrial membrane protein of M(r) 26,000 (ref. 2), blocks programmed cell death (apoptosis) in neurons. We therefore investigated whether SV infection induces programmed cell death in non-neuronal cells, and if so, whether virus-induced programmed cell death can be blocked by transfection with bcl-2. We demonstrate that SV infection of baby hamster kidney (BHK-2), mouse neuroblastoma (N18), and rat prostatic adenocarcinoma (AT-3) cells results in programmed cell death, whereas SV infection of bcl-2-transfected AT-3 cells results in long-term persistent productive infection. Thus cellular bcl-2 oncogene expression plays a role in the establishment of persistent viral infection by blocking virus-induced programmed cell death.

Adenocarcinoma↗

Detection of amphetamine and methamphetamine in urine by gas chromatography/Fourier transform infrared (GC/FTIR) spectroscopy.

New methods for identification of amphetamines have been employed using gas chromatography/Fourier transform infrared spectroscopy (GC/FTIR). These methods have provided identification of the drug and its metabolites, with detection at the low picogram levels or less than 10 ng/mL. Developments in cryogenic sample deposition for GC/FTIR spectroscopy have increased the sensitivity of GC/FTIR to levels that match or surpass that of gas chromatography/mass spectrometry (GC/MS). This advancement in technology has allowed the highly selective ability of infrared spectroscopy to be used for identification and quantitation in studies where the analytes are in low concentrations. The limits of detection (LOD), quantitation (LOQ), and linearity (LOL), and precision have been determined in this study, and these instrumental parameters have been compared with those of established techniques.

Amphetamine↗

An intoxication involving BRON and verapamil.

A case is presented in which the body of a 19-year-old white male was found in his family's quarters by his mother. An autopsy failed to determine the cause of death, and specimens were sent out for toxicologic analysis. No ethanol or volatile substances were detected in the blood, urine, or vitreous fluid. Comprehensive drug testing of the urine identified chlorpheniramine, dihydrocodeine, methylephedrine, salicylate, and verapamil. The first three drugs listed appear together in an over-the-counter cold medication in Japan, under the trade name BRON. Blood quantitations (in mg/L) were as follows: chlorpheniramine, 2.6; dihydrocodeine, 4.7; methylephedrine, 5.6; salicylate, 150; and verapamil, 6.0. The cause of death was multiple drug intoxication, and the manner of death was suicide.

Adult↗

A multiple drug intoxication involving cyclobenzaprine and ibuprofen.

A 19-year-old black man presented to the emergency room with superficial cuts on the anterior wrists, lethargy, tachycardia, and metabolic acidosis. Multiple containers of medication were found at the scene. Dysrhythmias developed and the patient died 7 h after admission. No anatomic cause of death was identifiable at autopsy. Toxicologic analysis identified the following drugs in the blood (mg/L): cyclobenzaprine (0.3), phenylpropanolamine (2.5), chlorpheniramine (0.2), lidocaine (6.6), phenytoin (19), and ibuprofen (130). Lidocaine and phenytoin had been administered therapeutically. The major symptoms displayed by the patient were tachycardia and metabolic acidosis, symptoms consistent with cyclobenzaprine and ibuprofen intoxication, respectively. Therefore, the medical examiner ruled that the cause of death was multiple drug intoxication and that the manner of death was suicide.

Adult↗

Molecular analysis of neurovirulent strains of Sindbis virus that evolve during persistent infection of scid mice.

To understand the role of tissue-specific adaptation and antibody-induced selectional pressures in the evolution of neurovirulent viruses, we analyzed three strains of Sindbis virus isolated from the brains of persistently infected scid mice and four strains of Sindbis virus isolated from the brains of scid mice with viral reactivation following immune serum treatment. For each viral isolate, we tested neurovirulence in weanling BALB/c mice and sequenced regions of the E2 and E1 envelope glycoprotein genes that are known to contain important determinants of Sindbis virus neurovirulence. One strain isolated from a persistently infected scid mouse and two strains isolated from scid mice with viral reactivation were neurovirulent, resulting in mortality in 80 to 100% of weanling BALB/c mice. All three neurovirulent strains contained an A-->U change at nucleotide 8795, which predicts a Gln-->His substitution at E2 amino acid position 55. No nucleotide changes were detected in the other sequenced regions of the E2 and E1 envelope glycoprotein genes or in the avirulent isolates. Our findings indicate that tissue-specific adaptations, rather than antibody-induced selectional pressures, are a critical determinant of the evolution of neurovirulent strains of Sindbis virus and provide evidence that E2 His-55 is an important neuroadaptive mutation that confers neurovirulence properties on Sindbis virus.

Alphavirus Infections↗

Gender differences in AIDS-relevant condom attitudes and condom use.

Two studies, conducted approximately one year apart, examined gender differences in AIDS-relevant condom attitudes, condom use behaviors, and relationships among attitudes and condom use behaviors. Subjects (N = 248, N = 528) were undergraduates, primarily heterosexual. Females reported more favorable attitudes, with the exception of greater inhibition about buying and possessing condoms. Men engaged in preliminary condom use behaviors (carrying and keeping condoms at home) substantially more often than did women. Preliminary condom use behaviors predicted past and intended condom use more consistently for men than for women. Relationships between condom attitudes and condom use behaviors were generally similar for both sexes, with poorer self-control explaining the most variance in past and intended condom use. These results, interpreted from the perspective of Eagly's (1987) gender role theory, suggest that although females may indirectly influence condom use decisions, providing condoms is the expected role of males, infusing them with greater control over the interpersonal process.

Acquired Immunodeficiency Syndrome↗

Cholinesterase activity in postmortem blood as a screening test for organophosphate/chemical weapon exposure.

This study was undertaken to determine whether postmortem blood cholinesterase activity could be used as a screening test for exposure to nerve agents. Whole blood cholinesterase activity at 25 degrees C was analyzed for a one week period in order to simulate the battle field collection problems of: hemolyzed blood samples, delayed recovery of the specimen, and unrefrigerated transfer to the testing facility. A total of 53 nonpreserved post-mortem whole blood specimens were analyzed in triplicate for cholinesterase activity by the delta pH method of Michel. There was a negligible loss of cholinesterase activity by the seventh day of the study. The enzyme activities of the specimens had a mean value (range) of 0.48 (0.20 to 0.74) initially and 0.45 (0.07 to 0.70) pH units after one week. Whole blood from five healthy adults remained essentially unchanged during this period, with an initial value 0.59 (0.52 to 0.67) and a final value of 0.52 (0.46 to 0.62) pH units. To compare postmortem and simulated nerve agent values, aliquots from 18 of the original 53 postmortem specimens were frozen during day one of the study, thawed on day seven and a cholinesterase inhibitor added. These specimens were then analyzed with the other specimens. All values from inhibited specimens were essentially zero (0.0 to 0.01) pH units compared to a range of 0.07 to 0.61 pH units for matched, uninhibited, day seven postmortem specimens. Fifteen actual nonpreserved specimens from the battlefield were analyzed as verification of screen performance. Their results fell within the uninhibited postmortem range above.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Preservation↗

Two deaths involving isoflurane abuse.

Two deaths due to isoflurane abuse are reported. One case was a suicide and the other a multiple drug death including isoflurane. A simple headspace gas chromatographic method was used for isoflurane quantitation. A review of the literature did not reveal blood and tissue concentrations of isoflurane. Drug tissue distributions and a discussion of the toxicological findings are presented.

Adult↗

Interpretation of low postmortem concentrations of ethanol.

The interpretation of postmortem blood ethanol concentrations (BAC), especially those less than 0.05 g/dL can be complicated by postmortem ethanol formation. One method used by the toxicologist to respond to this possibility is to analyze multiple specimens for ethanol. Two useful specimens to analyze are vitreous humor and urine, because they are less susceptible to the putrefaction process. A negative vitreous humor and/or urine ethanol would suggest that the measured ethanol resulted from postmortem formation. Data were collected from the Office of the Chief Medical Examiner, State of Maryland and the Armed Forces Institute of Pathology on blood specimens with ethanol concentrations less than 0.05 g/dL to develop a reasonable threshold for interpretation in the absence of other specimens. A total of 381 cases with a BAC between 0.01 and 0.04 g/dL were studied over a 2 year period. Urine and vitreous humor specimens were tested where available. At a BAC of 0.01 g/dL, 54% of the cases were associated with a positive vitreous humor and/or urine ethanol concentration. This percentage increased to 63% when BAC equals 0.02 g/dL. Seventy-three percent and 92% of the cases had a positive alternate specimen if the BAC was 0.03 g/dL and 0.04 g/dL, respectively. In addition, 90% of the cases where both vitreous humor and urine were analyzed showed consistent results, that is both specimens were positive or negative. This suggests that in the absence of additional information, a BAC of 0.04 g/dL or higher probably resulted from ethanol consumption.

Alcohol Drinking↗