PubMed HealthSearch

Biomedical subjects

C L Winek

Publications and source records attributed to C L Winek.

At least 19 recordsLinked to original sources

An outbreak of designer drug--related deaths in Pennsylvania.

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.

Designer Drugs

The stability of several compounds in formalin fixed tissues and formalin-blood solutions.

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.

Carbon Monoxide

Plasma versus bone marrow desipramine: a comparative study.

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.

Animals

Body distribution of ethchlorvynol.

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.

Adult

Determination of ethchlorvynol in body tissues and fluids after embalmment.

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.

Bile

The validity of urine alcohol analysis in drunk drivers.

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.

Accidents, Traffic

Blood versus bone marrow pentobarbital concentrations.

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.

Animals

Blood alcohol concentrations: factors affecting predictions.

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.

Accidents, Traffic

We want to train toxicologists for a need.

This country needs toxicologists in a variety of institutions, and needs toxicologists with different backgrounds. All programs in toxicology can't satisfy every specific need. Certification and accreditation will continue as solvable issues among the various organizations in toxicology.

Books

Toxicology of poinsettia.

1. The acute oral LD50 of poinsettia in Sprague Dawley rats were greater than 25 gm/kg for all plant parts tested. 2. Exaggerated oral dosing over a five-day period with as much as 125 gm/kg total dose did not produce any gross or microscopic pathology in Sprague Dawley rats. 3. A five-day total diet study of poinsettia produced no gross pathology in Sprague Dawley rats. 4. Poinsettia latex induced no local toxicity when instilled into the buccal cavity of Sprague Dawley rats. 5. Poinsettia latex induced no damage when instilled into the eyes of albino rabbits. 6. Upon repeated exposures poinsettia exhibited mild skin irritation in the albino rabbit. It is not considered to be a primary irritant. 7. Poinsettia induced skin photosensitivity in albino rabbits.

Animals

Acute and subacute toxicology and safety evaluation of triphenyl tin hydroxide (Vancide KS).

The acute oral LD50 in Sprague-Dawley rats was determined to be 171 mg/kg (100-295) for males and 268 mg/kg (205-344) for females. 2. A 1 ppm dietary supplement of Vancide KS for 90 days did not induce any abnormalities in weanling Sprague-Dawley rats. The parameters evaluated were serum glutamic-oxaloacetic transaminase (SGOT), hematocrit, differential white blood cell count, food consumption, and weight gain, along with histologic studies of the myocardium, spleen, liver, kidney, stomach, and small intestine. A 500 ppm diet was lethal. Weanling and older rats subjected to 1000 and 10,000 ppm diets died within 5 days. 3. Vancide KS induced no acute dermal toxicity, nor did it exhibit percutaneous absorption in New Zealand strain albino rabbits. 4. Vancide KS induced no chronic dermal toxicity in New Zealand strain albino rabbits. 5. Vancide KS was not shown to be teratogenic. It exhibited an antifertility action, especially in Sprague-Dawley rats dosed on day 1 through day 7 of timed-pregnancy. 6. Vancide KS was shown to be an eye irritant which induces corneal opacity. 7. Acute oral toxicity studies in Sprague-Dawley rats indicate that Vancide KS should be classified as a toxic substance as defined in the regulations under the Federal Hazardous Labeling Act. 8. The intravenous administration of 25 mg/kg of Vancide KS to New Zealand strain albino rabbits induced death preceded by topic convulsions. 9. Vancide KS did not induce skin sensitization in male adult guinea pigs.

Administration, Oral

Ethylene and diethylene glycol toxicity.

1. Blood concentrations of ethylene and diethylene glycol were evaluated in Sprague-Dawley rats at varying intervals following oral dosages of the glycols. 2. Ethylene and diethylene glycol in rat blood stored under refrigeration at 4 degrees +/- 10 degrees C for a period of 30 days exhibited minimal concentration losses, contrary to previous reports. 3. The amount of oxalate in the blood and kidneys of Sprague-Dawley rats doses with ethylene and diethylene glycol was quantitated. The animals dosed with ethylene glycol demonstrated significantly higher oxalate levels, particularly at 8 hr post-dosing, than similar animals dosed with diethylene glycol. 4. Ethylene glycol induced oxalate deposition within the kidney without significant histologic changes. Diethylene glycol induced histologic changes within the kidneys without kidney oxalate deposition. 5. Maximal kidney oxalate levels, following ethylene glycol dosage, occurred concurrently with peak blood oxalate concentrations. In the case of diethylene glycol, kidney oxalate levels did not peak until 4 hr after maximal blood oxalate levels. 6. Ethylene and diethylene glycol induced different modes of death in Sprague-Dawley rats.

Animals

Methapyrilene toxicity.

Seven cases of drug overdosage involving methapyrilene have been presented, five of which resulted in death. Methapyrilene blood levels ranged fron 1.2 to 3.0 mg% (Table 2). Five of the seven cases involved multiple drug dosage with ethanol, salicylamide, amobarbital, secobarbital, and/or scopolamine. Of the remaining cases, involving only methapyrilene, ome fatality occurred at a blood level of 2.7 mg%. The surviving case involved the reported ingestion of 100 tablets of Sleep-eze (2.5 gm methapyrilene), wherein serial lavage removed 1.1 gm of methapyrilene. Urinalysis revealed 2.52 mg% of methapyrilene in 1300 ml of urine. The methapyrilene blood level was too low to quantitate.

Adult

Factors affecting contamination of blood samples for ethanol determinations.

Contamination of blood samples collected for alcohol analysis from swabbing with an ethanolic antiseptic is minimal (less than 0.6 mg/100 ml or 0.0006 percent ethanol) when routine clinical technique is followed. When technicians were told to be deliberately sloppy, considerable contamination (89 mg/100 ml or 0.09 percent ethanol) occurred. The incidence and extent of contamination from banked blood intended for transfusions are minimal. Two percent of the 1,450 samples analyzed contained alcohol. The average blood alcohol concentration was 26 mg/100 ml or 0.03 percent ethanol. One microliter of rubbing alcohol per milliliter of whole blood, or one-tenth of a drop of rubbing alcohol per milliliter of whole blood, increases the BAC 56.5 mg/100 ml (0.06 percent ethanol) and 67.5 mg/100 ml (0.07 percent ethanol), respectively.

Blood Banks