Biomedical subjects
Publications and source records attributed to W W Wahba.
Current blood-level data are presented for drugs and chemicals of toxicologic interest. The data represent an update of previously published compilations of therapeutic, toxic and lethal blood-levels.
The deceased was a 35 year old female who was found by her husband in the bathtub with her head and face submerged in the water. Autopsy findings were unremarkable. Toxicological analysis revealed the presence of ethanol (215 mg/dL) and cyclobenzaprine (1.786 mg/l) in the blood. This high concentration of cyclobenzaprine (Flexeril) in combination with alcohol proved to be fatal.
A 2-year-old male was found to have a third degree (full thickness) burn on his rear right thigh. The father discovered the burn at a physician's office where the child was being treated for an ear infection. The physician notified authorities of suspected physical child abuse.
Death due to heroin overdose and/or rapid injection of heroin is a frequent occurrence among opioid addicts. We present an unusual case of heroin fatality due to the injection of the drug in the penis. Blood, urine, bile, and vitreous humor concentrations of morphine were 0.68, 0.49, 0.32 and 0.062 microg/ml, respectively. Ethanol was detected at concentrations of 104, 124, 106, and 94 mg/dl in the blood, urine, bile, and vitreous humor, respectively. The cause of death was determined to be due to heroin and ethanol intoxication.
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.
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.
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.
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.
Amoxapine (Asendin), a recently introduced dibenzoxazepine, has been effective in clinical studies for the treatment of various types of depression. Three amoxapine-related deaths are reported. Quantitation of amoxapine was carried out by gas chromatography using 3% OV-17 column. Blood amoxapine concentrations were 11.5 mg/l, 2.8 mg/l, and 0.89 mg/l. The concentrations are many-fold higher than the reported therapeutic serum concentrations of 0.21 mg/l. These cases illustrate the potential toxicity and lethality of amoxapine overdose and the need for caution in prescribing a large amount of amoxapine to patients with suicidal tendencies.
Bone marrow may be utilized as an alternative biological sample in cases where uncontaminated blood samples are not available for analyses. Bone marrow/blood ratios of ethchlorvynol as a function of time and dosage level were determined in 40 rabbits. A modified quantitative analysis that produced accurate and reproducible results was employed for the determination of ethchlorvynol levels. Further, ten blood and bone marrow samples containing ethchlorvynol were chosen to study the effects of storage for a period of 24 hours. Studies of blood and bone marrow ethchlorvynol levels with time showed no linear relationship. Bone marrow/blood ratios as a function of dose resulted in close mean averages with a wide range of values. Significant losses in both blood and bone marrow ethchlorvynol levels were evidenced in most of the samples subjected to the 24-hour storage study.