Biomedical subjects
Publications and source records attributed to C L Winek.
A 13-year-old male was found dead in the woods subsequent to 1,1,1-trichloroethane (TCE) inhalation. Autopsy findings included tissue congestion of lung, liver and kidney. Certain precautions were taken in collecting and storing biological samples in order to prevent loss of TCE by evaporation. The availability of volatile solvents coupled with the increase of volatile substance abuse makes it easy for abusers to obtain.
Microwave irradiation is used as an alternative heating method for extraction over more conventional hot plate methods. We describe a fast, efficient method for the determination of selected drugs in human blood/serum using microwave extraction. The microwave extraction of organic substances requires special instrumentation and the results have been compared with the results from classical liquid/liquid extraction. The present microwave extractions were performed in an 'atmospheric pressure' system. Before irradiation with microwaves, an appropriate solvent mixture was added to the buffered specimen. Lidocaine, methadone, diazepam, nordiazepam, propoxyphene and norpropoxyphene were tested as model substances. The quantitation was performed by GC/NPD. The procedure has been applied successfully to a number of forensic cases. The use of microwaves decreases the time of extraction and the solvent consumption.
Zolpidem (Ambien) is an imidazopyridine hypnotic recently introduced in the USA. We report a case of a fatal overdose of Ambien. A 68-year-old female ingested at least 30 tablets of 10 mg Ambien (300 mg). She was found dead at home. Toxicological analyses revealed blood concentration of 4.1, 19.3 and 2.3 micrograms/ml of zolpidem, meprobamate and carisoprodol, respectively.
There is a paucity of data available on the effect of storage on blood alcohol concentration (BAC) at elevated temperatures. Changes in serum alcohol concentration (SAC) and BAC were studied. Serum samples spiked with alcohol in the presence or absence of preservative were stored at 26.7 degrees, 32.2 degrees or 37.8 degrees C respectively. Serum alcohol concentrations were determined daily on days 1 through 14, and on days 21 and 35. Under these controlled conditions, no significant change in SAC was observed at the aforementioned temperatures. Whole blood samples submitted from outside agencies were initially analyzed (day 1), then stored for 35 days at different elevated temperatures before a second analysis. The average loss in BAC was 19.20 +/- 15.6, 9.95 +/- 5.7, and 15.60 +/- 6.9% when the samples were stored at 26.7, 32.2 and 37.8 degrees C, respectively. The alcohol loss from whole blood samples may be attributed to chemical oxidation rather than to elevated temperatures. It is, therefore, concluded that a whole blood sample obtained from a living individual and stored in a locker, glove compartment or other environment where the temperature is elevated, may lose 10-19% of its alcohol content over 35 days of storage. On the other hand, when a serum or plasma sample is exposed to the same environment, no significant change in SAC was observed. The utility of this information is significant to the forensic toxicologist. The results of this study suggest that a whole blood sample analyzed after exposure to elevated temperature may have had, originally, a higher BAC.
This study was designed to determine the peak, plateau and absorption times of ethanol in a social drinking setting. For the purpose of this study, subjects who had drinking times of 30 min or greater were considered to fit the 'social drinking' category. Healthy subjects (31 male and two female) were tested immediately after they finished drinking. Blood alcohol concentrations (BACs) were measured using a breath testing instrument (Intoxilyzer 5000). Drinking time, type and volume of alcoholic beverage consumed, subject's weight, and a brief description of the breakfast meal were recorded for each subject. The peak, plateau and absorption times were determined for each subject. Peak time was the time interval between the end of drinking and the maximum blood alcohol measurement. Plateau time was the time interval between peak time and the end of absorption time, i.e. the interval between peak time and the beginning of dissipation. Absorption time was defined as the peak time plus plateau time. Among 31 subjects with drinking times of 30 min or greater, 23 (74.2%) had peak and absorption times of < 30 and < 60 min, respectively. Twenty four out of 31 (77.4%) social drinkers had an absorption time of < 60 min, regardless of their peak time. Overall, the average peak and absorption times were 17.4 +/- 17.3 (range 0-74) and 42.2 +/- 31.5 (range 1-130) min. Plateau times averaged 24.9 +/- 23.1 with a range of 0-74 min. It can be concluded from this study that in a social drinking setting, a shorter time to peak and faster rate of absorption may occur when ethanol is consumed over an extended period of time. This is in contrast to results reported in earlier studies involving bolus drinking, where longer absorption times occurred.
Nitrous oxide is a popular inhalation anesthetic-analgesic agent. Its euphoric action and its availability have led to its abuse. We report a case of fatal accidental asphyxia due to nitrous oxide abuse. The deceased was a hospital worker who had access to the hospital supply of nitrous oxide. His death was due to hypoxemia and asphyxiation, secondary to nitrous oxide inhalation.
This paper reports on the case of a 13-year-old white male who committed suicide by ingestion of heavy duty drain and sewer opener. He left behind a note indicating his suicide. This teenager was grieving over the suicide of one of his friends and was under counseling by a mental health therapist at school. Results of autopsy and toxicological analyses indicated the ingestion of a highly alkaline substance that is consistent with the ingredients of the drain opener mentioned.
In postmortem cases, a blood sample is frequently obtained by transthoracic (TT) puncture. The purpose of this study was to determine if, in traumatic death, blood samples collected by TT provided a valid sample for blood alcohol analysis. A retrospective study (1980-1986) was conducted to evaluate possible contamination of blood by GI alcohol in traumatic death cases. Out of 6000 cases reviewed, 19 cses with BACs > 500 mg/dl were found and 8 of these cases involved traumatic death with GI laceration and/or transection. The results of this study support the hypothesis that blood samples from the 8 cases had been contaminated, resulting in a falsely elevated BAC. A transthoracic study (1987-1989) was conducted under controlled conditions, where blood alcohol content of TT blood samples was compared with samples collected from the intact heart chamber. Seven out of 28 cases of traumatic injury revealed trauma to the GI tract. The results showed that when GI traumatic injury occurs and unabsorbed ethanol is present in the stomach, contamination of TT blood samples occurs and artificially elevated BACs are obtained. It is recommended that, in cases of traumatic injury, heart blood samples from the intact heart chamber, as well as samples of additional biological fluids, be collected to rule out the possibility of contamination and to ensure that the BAC used for forensic interpretation is accurate.
The stability of amitriptyline, nortriptyline, desipramine and imipramine in formalin-fixed human liver tissue and formalin solutions was investigated. The levels of the tricyclic and its primary demethylated metabolite in the frozen liver were determined and compared with levels obtained in the formalin-fixed liver and formalin solutions in which the liver was stored. It was obvious that some methylation of the secondary amine, nortriptyline, to the corresponding tertiary amine, amitriptyline, and of desipramine to imipramine took place in the formalin environment. Nortriptyline was not detected in most cases, suggesting that it may degrade more rapidly than desipramine. There was no consistent ratio between the concentration of the drug in the frozen liver tissue versus formalin-preserved tissue or versus formalin solution. The methylation rates of the secondary amines could not be quantitated. Storage of the liver tissue in formalin at room temperature resulted in leaching of the drugs into the formalin solution. The drugs tested may be detected for up to 22 months in the formalin-fixed liver and in the formalin medium.
3-Methylfentanyl ("China White") is a "designer" opiate that has caused more than 100 overdose deaths in California since 1979, but that has not been associated previously with deaths east of the Rocky Mountains. During 1988, 3-methylfentanyl was identified in 16 fatal overdose cases in Allegheny County, Pennsylvania, contributing to a fourfold rise in overdose mortality during October of that year. Morphine was detected in the blood of five persons (31%) and cocaine in the blood of three persons (19%) dying of 3-methylfentanyl overdoses; these were demographically similar to 99 other fatal overdose cases investigated by the county coroner from 1986 through 1988. This documents the contribution of 3-methylfentanyl to overdose mortality in an eastern city and the use of 3-methylfentanyl with other illegal drugs. Drug abusers in the northeastern United States should be considered at risk for more "designer drug" overdose outbreaks in the future.
Buffered formalin solutions were added to spiked blood samples containing diazepam, phenytoin, carbon monoxide and cyanide to give formalin-whole blood solutions of 5 and 8%. Sections of liver positive for desipramine, phenobarbital and phenytoin were placed in separate 5 and 8% formalin-water solutions. The formalin-blood solutions were monitored daily for 30 days, while the fixed liver and formalin-water samples were analyzed once a week for 4 weeks. In the formalin-blood solutions losses were found for diazepam and phenytoin over the 30-day period of at least 41% and 33%, respectively. Cyanide detection was not possible immediately after the addition of formalin and the presence of carboxyhemoglobin was difficult to detect after 1 week. In the liver, losses of phenobarbital and desipramine were greater than 60% while phenytoin showed little change. This study has revealed that the drugs examined at toxic concentrations can be detected, with variable recoveries, for up to 30 days after fixation with formalin. However, quantitative analysis for cyanide and carboxyhemoglobin may be significantly impaired in the presence of formaldehyde.
Correlation between plasma and bone marrow tricyclic antidepressants has not been studied before. Two groups of rabbits were given 10 and 20 mg of desipramine/kg body weight, respectively. Desipramine was administered to the animals once daily by mouth for 5 days. On the fifth day the animals were sacrificed and blood and bone marrow samples were collected and analyzed using a high performance liquid chromatographic (HPLC) method. Data showed that a correlation exists between bone marrow and blood desipramine. The bone marrow desipramine concentration increased as its blood levels increased. The average ratio of bone marrow to blood desipramine +/- S.D. (standard deviation) in both dosage groups was 37.2 +/- 4.46 with a range of 30.99-44.82. This investigation is promising and shows that bone marrow could be used as an alternative tissue in the absence of a suitable blood sample.
Ethchlorvynol (Placidyl) is a nonbarbiturate sedative hypnotic. Two fatal cases of ethchlorvynol overdose are reported. Toxicological analyses of body fluids and tissues were performed by gas chromatography using a flame-ionization detector. The quantitative method was sensitive and reproducible. Body distribution of ethchlorvynol in blood and other tissues is presented. Biological samples analyzed included blood, urine, bile, liver, kidney, eye fluid, and gastric contents. Results presented add to the pharmacokinetic data needed to study the disposition of drugs in different tissues. Findings in present two cases are compared with published toxicological data.
A 54 year-old female expired at her residence. Her husband, a physician, signed a certificate stating that her death was due to cerebrovascular accident (CVA) and released her body to a funeral home, where she was embalmed. Since the deceased had a long history of medical problems and drug abuse, an autopsy was performed and no evidence of CVA was found. Toxicological analyses of body fluids and tissues revealed the presence of ethchlorvynol in high concentration in the bile (112 mg/l). The bloody fluid collected from the heart contained a concentration of ethchlorvynol below the limit for quantitation. Other findings included phenobarbital (32.8 mg/l) in heart bloody fluid and methanol (an ingredient of embalming fluid). The significance of the findings is discussed in relation to embalmment prior to autopsy and toxicological analyses. Ethchlorvynol concentration in the bile is compared to other fatal cases due to ethchlorvynol overdose.
Blood and breath are the specimens of choice for determining alcohol levels. A random urine specimen may not reflect a blood level because of the influences due to the stage of absorption, the quantity of urine in the bladder, and the frequency of urination. A urine sample may accurately reflect a blood level only 30 minutes after the bladder is completely emptied. Individual states that permit urinalysis for alcohol must provide procedures for sample collection and statutory limit levels.
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Postmortem pentobarbital levels in rabbit heart blood and bone marrow were determined and compared. The average ratio of femur marrow/blood pentobarbital concentrations in 24 rabbits was 1.06 +/- 0.05. The average percent difference between actual plasma pentobarbital concentrations and calculated plasma pentobarbital concentrations was 5.82 +/- 1.96. Concentrations were determined by gas chromatography of extracted, derivatized pentobarbital.
As a result of extensive alcohol research conducted on both humans and animals, it is possible to predict a BAC, given pertinent data. In addition, it is possible to estimate from a given BAC the quantity of alcohol consumed. Caution must be used in these predictions, for certain factors will affect the final estimation. Absorption of alcohol is influenced by gastrointestinal contents and motility, and also the composition and quantity of the alcoholic beverage. The vascularity of tissues influences the distribution of alcohol, and their water content will determine the amount of alcohol present after equilibrium. Elimination of alcohol begins immediately after absorption. The elimination rate varies for individuals but falls between .015 percent to .020 percent per hour, with an average of .018 percent per hour. In addition to these factors, a BAC will depend on the subject's weight, percentage of alcohol in the beverage, and the rate of drinking. The principal effect of alcohol in the body is on the central nervous system. Its depressant effect consists of impairment to sensory, motor and learned functions. When combined with some other drugs, a more intoxicated state occurs. Although tolerance to alcohol at low blood concentrations is possible, the tolerance most noted is a learned tolerance among chronic drinkers. contamination of antemortem blood samples collected for alcohol analysis is minimal when swabbing with an ethanolic antiseptic is performed with routine clinical technique; sloppy swabbing has been shown to increase the BAC determination significantly. The alcoholic content of blood used for transfusion does not contribute significantly to the BAC of the recipient, since extensive dilution occurs; nor does the alcohol present in injectable medication contribute significantly. Although many factors may alter the concentration of alcohol present in autopsy specimens, postmortem synthesis of alcohol receives the most attention. The microorganisms that cause postmortem ethanol production can be inhibited by adding a preservative to the samples and storing them under refrigeration. Should putrefaction be present, it is recommended that, in addition to blood, several different specimens be collected and analyzed for the presence of alcohol. Antemortem blood samples containing ethanol, collected using sterile tubes and techniques, may be analyzed up to 14 days later with reasonable certainty that the ethanol level reflects that which was present at the time of collection.