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Upper aerodigestive tract frostbite complicating volatile substance abuse.

Volatile substance abuse has become increasingly popular among today's youth. It has reportedly been used by up to 13% of teenage populations. Physicians need to be aware of the potential complications which may arise from this form of substance abuse. We describe the case of a young male who presented with massive edema affecting his lips, oral cavity, oropharynx and trachea. It was later discovered that his injury was secondary to thermal trauma related to the abuse of a fluorinated hydrocarbon propellant. This presentation may easily be confused with allergic or angioneurotic edema. Denial by the patient can lead to a further delay in diagnosis. This case is especially notable since frostbite injury involving the upper aerodigestive tract is extremely rare. We discuss the differential diagnosis and the management principals required in the care of this patient. We also present a pertinent review of the literature related to both volatile substance abuse and its complications involving the airway.

Administration, Inhalation↗

Reproductive and developmental toxicity of toluene: a review.

Toluene is a widely used industrial solvent, and humans may also have high exposures to toluene from the deliberate inhalation ("sniffing") of paint reducer, paint thinner, or paint for their narcotic effects. A number of case reports describe neonatal effects that have been attributed to toluene abuse during pregnancy. These effects may include intrauterine growth retardation, premature delivery, congenital malformations, and postnatal developmental retardation. The possibility of exposures to other fetotoxic agents, either as impurities or admixtures in toluene-containing products, or by deliberate or accidental exposures to other chemicals or drugs, cannot be excluded in these cases. The fetotoxic effects of toluene have been demonstrated in controlled studies in animals and are comparable to those observed in humans who have abused toluene-containing products before or during pregnancy. Intrauterine developmental retardation is the most clearly established effect in animals, as evidenced by decreased late fetal weight and retarded skeletal development. There is also limited evidence in rodents for skeletal and kidney abnormalities, as well as some evidence for effects on postnatal physical and possibly neurobehavioral development. Estimated daily exposures from experimental studies in animals are compared to estimated human daily intakes at the occupational permissible exposure level and at the level reported to produce euphoria in humans. Acceptable human intakes under California's Proposition 65 and under U.S. Environmental Protection Agency procedures are discussed.

Abnormalities, Drug-Induced↗

Subtypes of illicit drug users: a latent class analysis of data from an Australian twin sample.

This article applies methods of latent class analysis (LCA) to data on lifetime illicit drug use in order to determine whether qualitatively distinct classes of illicit drug users can be identified. Self-report data on lifetime illicit drug use (cannabis, stimulants, hallucinogens, sedatives, inhalants, cocaine, opioids and solvents) collected from a sample of 6265 Australian twins (average age 30 years) were analyzed using LCA. Rates of childhood sexual and physical abuse, lifetime alcohol and tobacco dependence, symptoms of illicit drug abuse/dependence and psychiatric comorbidity were compared across classes using multinomial logistic regression. LCA identified a 5-class model: Class 1 (68.5%) had low risks of the use of all drugs except cannabis; Class 2 (17.8%) had moderate risks of the use of all drugs; Class 3 (6.6%) had high rates of cocaine, other stimulant and hallucinogen use but lower risks for the use of sedatives or opioids. Conversely, Class 4 (3.0%) had relatively low risks of cocaine, other stimulant or hallucinogen use but high rates of sedative and opioid use. Finally, Class 5 (4.2%) had uniformly high probabilities for the use of all drugs. Rates of psychiatric comorbidity were highest in the polydrug class although the sedative/opioid class had elevated rates of depression/suicidal behaviors and exposure to childhood abuse. Aggregation of population-level data may obscure important subgroup differences in patterns of illicit drug use and psychiatric comorbidity. Further exploration of a 'self-medicating' subgroup is needed.

Australia↗

Diffuse alveolar hemorrhage temporally related to cocaine smoking.

Previous reports of respiratory complications from cocaine abuse have focused on pulmonary barotrauma or a reduction in carbon monoxide diffusing capacity. We report a patient who developed life-threatening alveolar hemorrhage following repeated inhalation of alkaloid cocaine.

Adult↗

Pattern-visual evoked potentials in thinner abusers.

Organic solvents cause injury to lipids of neuronal and glial membranes. A well known characteristic of workers exposed to thinner is optic neuropathy. We decided to look for neurophysiologic signs of visual damage in patients identified as thinner abusers. Pattern reversal visual evoked potentials was performed on 34 thinner abuser patients and 30 controls. P-100 wave latency was found to be longer on abuser than control subjects. Results show the possibility of central alterations on thinner abusers despite absence of clinical symptoms.

Administration, Inhalation↗

Prevalence of psychoactive drug use among medical students in Rio de Janeiro.

BACKGROUND: Drug use and abuse may hamper learning capabilities and the development of technical skills in medical students and, therefore, the quality of care offered to patients. The aim of this investigation was to estimate the prevalence of psychoactive drug use among medical students of public universities in Rio de Janeiro, Brazil, and to identify characteristics associated with substance use. METHOD: This was a cross-sectional investigation designed to include all medical students of four universities. The final sample included 1,054 students. Patterns of licit and illicit drug use (at least once in lifetime drug use, drug use in the last 30 days (LTD) and CAGE) before and during medical school were assessed by a multiple-choice, self-administered anonymous questionnaire. RESULTS: Alcohol abuse was more prevalent among male students from higher income families. Alcohol LTD use was more prevalent among male students with college-educated parents. Tobacco, cannabis and inhalant lifetime use was more prevalent among males and tranquillizer use among females. Tobacco, cannabis and tranquillizer lifetime use was more prevalent among students with divorced or dead parents. Inhalant lifetime use was more prevalent among students from higher income families. Students who had college-educated, divorced or dead parents or evidenced tobacco, cocaine or inhalant lifetime use were more prevalent among cannabis users. Male students from higher income families had higher prevalence of cocaine lifetime use. CONCLUSION: Substance use in this group of medical students is not widespread compared to rates reported for developed countries. Preventive efforts should focus on alcohol and cannabis use by medical students.

Adolescent↗

Simple colorimetric semiquantitation method of hippuric acid in urine for demonstration of toluene abuse.

A semiquantitative method for hippuric acid in toluene sniffers' urine was explored by modifying the method by Tomokuni and Ogata. The color of sample urine mixed with pyridine and benzenesulfonyl chloride was yellow, and became reddish by addition of distilled water. Using the color chart, the concentration of hippuric acid could be semiquantitated in a few minutes. The values determined by this method were compared with those obtained by high performance liquid chromatography, showing a coefficient of determination (r2) of 0.8594. This colorimetric method is thus useful for rapid screening for hippuric acid in urine, or toluene sniffing.

Administration, Inhalation↗

Determination of urinary hippuric acid in toluene abuse.

BACKGROUND: Volatile substance abuse is practiced mainly by adolescents and young adults. Its effects are central nervous system excitation followed by central nervous system depression, at times accompanied by seizures. It may cause sudden death as a result of ventricular arrhythmias, reflex vagal inhibition, respiratory depression, and anoxia. Chronic toxicity may involve the nervous system, heart, kidney, and liver. Toluene-based adhesives are among the most commonly inhaled substances. CASE REPORT: A 14-year-old female presented with confusion, hallucinations, and intermittent laughing and crying after having inhaled contact glue several times daily in the course of 5 days. Her condition improved within 3 h. Urinary hippuric acid was 93.9 g/g creatinine indicating heavy toluene exposure (biological exposure index, BEI, is 1.6 g/g creatinine). CONCLUSION: In this patient, urinary hippuric acid was a biomarker for her toluene abuse.

Adolescent↗

Dilated cardiomyopathy associated with toluene abuse.

The use of paint thinner and glue to achieve an euphoric state has been associated with serious social and health problems in children and young adults. We present the case of a 21-year-old man with dilated cardiomyopathy occurring following abuse of paint thinner and glue containing toluene as main compound. After cessation of toluene abuse, the patient recovered rapidly and completely. Because of the increasing prevalence of toluene abuse, harmful effects of this volatile agent on the heart are also discussed.

Adhesives↗

Self-administration of cannabinoids by experimental animals and human marijuana smokers.

Drug self-administration behavior has been one of the most direct and productive approaches for studying the reinforcing effects of psychoactive drugs, which are critical in determining their abuse potential. Cannabinoids, which are usually abused by humans in the form of marijuana, have become the most frequently abused illicit class of drugs in the United States. The early elucidation of the structure and stereochemistry of delta-9-tetrahydrocannabinol (THC) in 1964, which is now recognized as the principal psychoactive ingredient in marijuana, activated cannabinoid research worldwide. This review examines advances in research on cannabinoid self-administration behavior by humans and laboratory animals. There have been numerous laboratory demonstrations of the reinforcing effects of cannabinoids in human subjects, but reliable self-administration of cannabinoids by laboratory animals has only recently been demonstrated. It has now been shown that strong and persistent self-administration behavior can be maintained in experimentally and drug-naïve squirrel monkeys by doses of THC comparable to those in marijuana smoke inhaled by humans. Furthermore, reinforcing effects of some synthetic CB1 cannabinoid agonists have been recently reported using intravenous and intracerebroventricular self-administration procedures in rats and mice. These findings support previous conclusions that THC has a pronounced abuse liability comparable to other drugs of abuse under certain experimental conditions. Self-administration of THC by squirrel monkeys provides the most reliable animal model for human marijuana abuse available to date. This animal model now makes it possible to study the relative abuse liability of other natural and synthetic cannabinoids and to preclinically assess new therapeutic strategies for the treatment or prevention of marijuana abuse in humans.

Animals↗

Massive hemolysis following inhalation of volatile nitrites.

Volatile nitrites are drugs which have become widely used for their mood-altering and aphrodisiac effects. Their use has been associated with methemoglobinemia and mild hemolysis; more significant hemolysis has been noted in a patient with G6PD deficiency. We report here a case of massive hemolysis following inhalation of volatile nitrites in the absence of an apparent intrinsic red cell defect. It is important that health care workers are aware of side effects from these commonly abused substances.

Adult↗

Acute effects of inhaled dichloromethane on the EEG and sensory-evoked potentials of Fischer-344 rats.

Acute effects of inhaled dichloromethane on the spontaneous electroencephalogram (EEG) and sensory-evoked potentials (EPs) were characterized and compared to previously observed effects of toluene; both solvents are common components of abused solvent mixtures. Twelve adult male Fischer-344 rats with chronic epidural electrode implants served as subjects. Each rat was exposed for 60 min to 5,000, 10,000, and 15,000 ppm dichloromethane while held in a plastic restrainer that also served as a head-only exposure chamber. The sequence of exposures was counterbalanced across rats, and the exposures were separated by about one week. To characterize the time course of any changes, somatosensory and flash EPs were recorded every 5 min during the first 45 min of the exposures. As was the case with toluene, electrophysiologic waveforms recorded from different sensory systems, and components of these waveforms, reacted in different ways to dichloromethane. With respect to the FEP and SEP the two solvents produced quite different effects. Toluene increased the amplitudes of early FEP components, eliminated late components, induced oscillations in visual cortex, and had no discernible effects on component latencies. In contrast, dichloromethane eliminated the N1 component, at moderate exposure had little or no effects on amplitudes of the later components (N3 through N4), did not induce oscillations, and had significant effects on latencies. Whereas toluene dramatically increased SEP component amplitudes at moderate concentrations with diminishing effect at higher concentrations and exposure times, dichloromethane rather uniformly decreased SEP amplitude in a simple concentration-related way. Toluene and dichloromethane had similar effects on BAER component latencies. They both caused component (P1 through P5) latencies and the P1-P5 interwave time to increase. However, whereas toluene increased early and late (but not middle) component amplitudes, dichloromethane decreased the amplitudes of early and late components and increased the amplitudes of middle components. These results emphasize the acute pharmacologic specificity of different solvents and suggest that differences in chronic neurotoxicity might also be found; they also suggest that predictable interactions might be found with acute and chronic exposure to mixtures that contain such solvents.

Animals↗

[Repeated improper intravenous injection of fentanyl from a transdermal system].

We report on a 30 year-old male who misused transdermal fentanyl. He injected the contents of transdermal patches intravenously. Suffering from chronic pain following total hip replacement, he had received a prescription for this drug formulation from his general practitioner. During his stay in a pain clinic he was able to obtain a total of 13 fentanyl patches from other patients or local pharmacies. He became seriously ill with multiple organ dysfunction in the course of an infection of his thigh. After surgical and intensive care treatment he recovered soon, but the hip prosthesis had to be explanted. There are some reports in the literature of misuse of fentanyl patches. The contents may be ingested orally, or they can be inhaled. Aspirated with a syringe the content of fentanyl patches can also be injected intravenously, sometimes resulting in exit-us. Prescribers must be aware of the potential for abuse of fentanyl patches which can be stolen, sold or even removed from dead bodies.

Administration, Cutaneous↗

Drug "overdoses" among U.S. soldiers in Europe, 1978-1979. I. Demographics and toxicology.

The files of the Casualty Branch of the Military Personnel Center, Europe, Seventh Medical Command, and of the U.S. Army's Tenth Medical Lab were used to examine the epidemiology of "overdose" deaths of U.S. Army soldiers in Europe during the calendar years 1978 and 1979. A total of 91 cases were so identified; i.e., death was the direct result of injection, inhalation, or ingestion of an intoxicant, legal or illegal. Not included were deaths caused by trauma or drowning while intoxicated, deaths from disease secondary to chronic drug or alcohol abuse, and deaths due to chemicals not widely viewed as intoxicants. The monthly distribution of cases showed a spring peak similar to that reported by several studies of U.S. civilian drug deaths. No such similarity was apparent in terms of victim characteristics and circumstances, with soldier victims being nearly always male, equally often White as Black, 20-24 years old, very rarely suicides, and nearly always using heroin and/or alcohol. "Control" data from circumscribed subgroups of nonvictim European soldiers, however, show that victims did not differ markedly from the junior enlisted population from which they came, as least on the variables generally available in personnel and medical records.

Adult↗

[Neuroadaptive mechanisms form development of psychological dependence on volatile organic solvents].

Abuse of volatile organic solvents among youth remains a major social problem. Organic solvents are cheap and relatively easy to obtain, so they carry the risk of becoming a so-called "gateway drug" for users. Most research regarding organic solvents has until now focused on their neurotoxicity, specifically examining the mechanism of neuron death in terms of the involvement of substances such as nerve growth factor. However, systems to assess psychological dependence on volatile organic solvents that take into account the mechanism involved in the development of this dependence have not been established due to the difficulty of creating animal models. The conditioned place preference procedure, which can easily assess whether psychological dependence has been formed, has been phased in in recent years, and dependence assessment systems have been established for drug inhalation. There have also been new research developments regarding dependence on volatile organic solvents. The importance of mesolimbic dopamine neurons has been indicated in the expression of CNS stimulant action and the development of psychological dependence on drugs such as stimulants, cocaine, and heroin, which are typical abused drugs. It has recently become apparent that the increase in dopamine release in the nucleus accumbens accompanying activation of mesolimbic dopamine neurons, as has conventionally been proposed, is important to the expression of CNS stimulant action and the formation of psychological dependence in response to inhalation of toluene, a volatile organic solvent. Furthermore, research with regard to organic solvents' site of action is also proceeding based on studies using molecular biological techniques. Research regarding toluene is progressing, and the importance of receptors that gate ion channels such as N-methyl-D-aspartate (NMDA) and y-aminobutyric acid (GABA)A receptors as candidates for toluene's site of action has been indicated. Clarification of organic solvents' mechanism for the development of psychological dependence is expected to progress, thanks to analysis focusing on such new sites of action.

Animals↗

Consequences of paternal cocaine exposure in mice.

The present study examined the potential neuroteratological effects of paternal cocaine (COC) exposure using the novel mouse model of inhalational drug administration. In this model, mice were trained to self-administer COC in multi-hour daily inhalation sessions reminiscent of crack binges. The controls included males pair-fed with COC-inhaling animals as well as ad-lib-fed males. All males were bred with drug-naive females. The newborn pups sired by COC-inhaling males had a reduced biparietal head diameter, suggesting a decreased cerebral volume. When the pups reached adulthood, their sustained visuo-spatial attention and spatial working memory were tested using a 5-arm maze paradigm. During the attention tests, the percentage of correct trials at the shortest stimulus duration employed in the study (0.5 s) was significantly lower for the male offspring of COC-inhaling fathers as compared to the offspring of both pair-fed and ad-lib-fed controls. For the females sired by COC-inhaling fathers, the deficit was observed at light stimulus durations of 0.5 and 0.75 s. Also, during the working memory tests, the male offspring of COC-inhaling fathers required more sessions than the offspring of either pair-fed or ad-lib-fed fathers to reach the selected criterion at retention intervals of 16 min and longer. The impairment of working memory in female offspring of COC-inhaling fathers was even stronger, as the offspring needed more sessions to reach the criterion as compared to their control counterparts, even at retention intervals as short as 4 min. These findings suggest that paternal COC abuse prior to coitus may impact the development of the offspring, particularly if they are females. We further showed that chronic COC exposure in male mice does not result in substantial breakage of spermatozoal DNA, but significantly alters expression of DNA methyltransferases 1 and 3a in the germ cell-rich seminiferous tubules of the testis. Since these enzymes are essential for generating and maintaining parental gene imprinting in germ cells, our observations point to an intriguing possibility that COC may cause paternally induced neuroteratological effects by interfering with gene-imprinting patterns in male gametes.

Administration, Inhalation↗

Suicidal burns in Hong Kong Chinese.

There were 1063 acute burn patients admitted to the Burns Unit of Prince of Wales Hospital, Hong Kong, between March 1993 and February 1999. Eleven patients (1%) were burned due to attempted suicide. Seven were males and four were females, with a male:female ratio of 1.75:1. The median age was 38 years (range: 20-49 years) and the median extent of the burns was 55% total body surface area (range: 1-95%). Ten patients (90.9%) were self-incinerated and one patient attempted suicide by jumping into a hot bath. Seven patients (63.6%) suffered from severe smoke inhalation injury that required immediate intubation for ventilatory support. The average number of operations for the survivors was 3.7 (range: 0-8) and their median hospital stay was 42 days (range: 2-92 days). Four patients (36.4%) died from their injuries. Suicidal burns were more common among unemployed males with a history of psychiatric illness and substance abuse. Town gas (naphtha: a mixture of 49% hydrogen, 28.5% methane, 19.5% carbon dioxide and 3.0% carbon monoxide) was the most frequently used agent for self-immolation because it is probably the most convenient source of a fire accelerant in Hong Kong. Compared to the general burn population, this suicide group had a larger extent of burns, higher incidence of inhalation injury, required more operative treatment and longer hospital stay with a higher mortality rate.

Adult↗