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The neurological manifestations of chronic inhalation of leaded gasoline.

Abnormal neurological signs were found in 46 of 50 children and adolescents chronically sniffing leaded gasoline. These abnormalities resolved within eight weeks in all but one case. Exaggerated deep reflexes, postural tremor and evidence of cerebellar dysfunction occurred in a highly significnat number of patients. Forty-nine had blood lead levels greater than or equal to 40ug/dl. The mean blood lead levels were significantly higher in those with (a) abnormally brisk deep reflexes and (b) with evidence of cerebellar dysfunction, than in those without these findings. Five optional treatment regimes were employed and a classification was used, based on clinical findings, initial blood lead levels and the response to the calcium disodium edatate mobilization test. 39 patients received chelation therapy. These data suggest that neurological manifestations occur frequently in those abusing leaded gasoline and that chelation therapy has an important place in their management.

Adolescent↗

Changing trends in heroin abuse in India: an assessment based on treatment records.

The study of drug addicts who were treated in the drug-abuse facilities of the All India Institute of Medical Sciences during the period from 1981 to May 1984 indicates a steady increase in the number of heroin addicts who sought treatment in those facilities. The majority of heroin addicts were under 30 years of age (87.6 per cent), unmarried (67.6 per cent), had reached either high school or college (80.0 per cent) and reported having taken up to one gram per day (56.6 per cent) of the drug for one year or less (63.8 per cent). Heroin was mainly smoked (74.3 per cent) and in some cases inhaled, sniffed or injected. Up to 1981 there were no heroin addicts recorded in the treatment facilities. Other studies in India support this evidence. On the basis of the recency of heroin addiction in India, and its trend and development in other countries of the region, the authors predict a rapid increase in heroin addiction and in the manufacture of heroin in the country.

Adolescent↗

Chronic and acute effects of "crack" cocaine on diffusing capacity, membrane diffusion, and pulmonary capillary blood volume in the lung.

STUDY OBJECTIVES: To evaluate possible alterations in the diffusing capacity of the lung for carbon monoxide (DLCO) or its components, membrane diffusing capacity of the lung for carbon monoxide (DMCO) and pulmonary capillary blood volume (Vc), in habitual smokers of "crack" cocaine (with or without tobacco) and following the short-term administration of inhaled cocaine base or IV cocaine HCl. DESIGN: Cross-sectional and longitudinal evaluation of DLCO and its components in smokers of cocaine alone, tobacco alone, and cocaine plus tobacco, and in nonsmokers and ex-smokers. Measurement of possible acute effects on DLCO and its components after experimental short-term administration of IV and smoked cocaine. SETTING: University and Veterans Affairs hospital research laboratories. PARTICIPANTS: Convenience sample of habitual smokers of crack cocaine with or without tobacco and matched control nonsmokers and ex-smokers, and smokers of tobacco only. MEASUREMENTS: DLCO, DMCO, and Vc. CONCLUSIONS: Neither habitual cocaine smoking in cross-sectional or longitudinal analysis nor the short-term administration of inhaled alkaloidal cocaine significantly affected DLCO or its component parts. In contrast, a clear cross-sectional effect of regular tobacco smoking was demonstrated.

Adult↗

Acute effects of some volatile nitrites on motor performance and lethality in mice.

Mice were examined for effects on lethality and motor performance on an inverted screen test following inhalation exposure to isoamyl, n-butyl and isobutyl nitrite. All three nitrites produced concentration-related effects on both measures, with EC50s for motor performance only about one-half of the LC50s for lethality. Isoamyl and isobutyl nitrite were equally potent on both lethality and motor performance measures, whereas n-butyl nitrite was significantly more potent than isoamyl and isobutyl for lethality. Slope estimates of the concentration-effect curves for lethality were significantly greater than those of the motor performance measure. The steepness of the concentration-effect curves and low LC50/EC50 ratios relative to abused organic solvents suggest that behaviorally active concentrations of volatile nitrites may put users at risk to other health consequences.

Aerosols↗

Nicotine delivery kinetics and abuse liability.

It is well established that nicotine meets all criteria of a highly addictive drug. However, as recognized by the U.S. surgeon general, the nicotine delivery system itself is an important determinant of the toxic and addictive effects engendered by nicotine use. Therefore, altering the form of nicotine dosing may allow for selective therapeutic action in efforts to develop safer and less addictive nicotine replacement therapies. While it is the case that initial tobacco use often escalates to compulsive use accompanied by tolerance and physical dependence, this is not usually observed with nicotine replacement therapies. These observations are consistent with laboratory data indicating that (a) nicotine polacrilex and transdermal systems deliver nicotine more slowly and at lower dose levels than tobacco-based forms, and (b) human data suggesting that the abuse liability of these systems is substantially lower than that of the tobacco-based nicotine delivery systems. Because the drug dosage form can be systematically manipulated and evaluated, further research in developing alternative nicotine delivery forms may hold substantial promise in the treatment of tobacco dependence. Psychological research methods can play an important part in their evaluation.

Administration, Cutaneous↗

Leaded gasoline abuse: the role of tetraethyl lead.

Volatile substance abuse is practised worldwide however reports of the abuse of leaded gasoline have been limited to northern Canada, southwestern USA and the Australian Outback. Chronic, heavy abuse of leaded gasoline results in an encephalopathy, cerebellar and corticospinal symptoms and signs, dementia, mental status alterations, and persistent organic psychosis. Much of this is due to the hydrocarbons of gasoline while the tetraethyl lead contributes to the altered mental status and is responsible for the persistent psychosis. Lead chelation therapy is not rational and has not been shown to benefit these patients.

Administration, Inhalation↗

Clinical, pathologic, and toxicologic findings in asthma deaths in Cook County, Illinois.

To identify factors contributing to asthma mortality and improve our understanding of airway pathology in fatal asthma, we studied 44 cases of fatal asthma using records of one pathologist in the Office of the Medical Examiner. Records included death certificates, autopsies, toxicology, accounts by family and friends of the terminal episode, medical history of the deceased, police and paramedic reports, and hospital charts. Additionally, we interviewed by telephone surviving family and friends. Six (17%) of 35 patients were using inhaled corticosteroids at time of death. Of the nine patients who had seen a physician within 2 weeks of death, two were using corticosteroids. Toxicology was positive in 16 (38%) of 42 cases. Of the 20 patients with sudden-onset asthma (prodrome of increasing symptoms < 1 hour before death), 9 (45%) had positive toxicology. Patients with both sudden-onset and slow-onset asthma (prodrome > 3 hours before death) had airway mucosal or submucosal eosinophilic or neutrophilic infiltrates or both, as well as airways with and without mucus plugging. These findings indicate that asthma deaths are confounded by substance abuse and lack of anti-inflammatory therapy, and there is a heterogeneity in histological findings in sudden-onset and slow-onset asthma.

Adolescent↗

[Drug use prevalence and school performance among adolescents].

OBJECTIVE: To assess the prevalence of drug use among teenagers. METHODS: A cross-sectional study was carried out in Pelotas, Southern Brazil, in 1998. An anonymous, self-administered questionnaire was answered by a sample of 2,410 students with ages ranging from 10 to 19 years old, registered in all public and private high schools of the area. The schools were visited up to three times to reach absent students. RESULTS: The attrition rate was 8%. The substances mostly used by the students were alcohol (86.8%), tobacco (41.0%), marijuana (13.9%), inhalants (11.6%), anxiolytic drugs (8.0%), amphetamines (4.3%), and cocaine (3.2%). Marijuana, inhalants and cocaine were used mainly by male students, while anxiolytics and amphetamines were used mainly by female students. Alcohol consumption in the last 30 days, frequent drug use, heavy drinking and alcohol intoxication were more prevalent among males. After controlling for confounding factors, there was still an association between drug use (except for alcohol and tobacco) and evening courses, higher degree of nonattendance in the previous month and higher rate of school failure. CONCLUSIONS: The prevalence of drug experimentation among high school teenagers is high, indicating the importance of early detection of risk groups and development of programs to prevent drug abuse and addiction.

Adolescent↗

Joint influence of alcohol, tobacco, and coffee on biological markers of heavy drinking in alcoholics.

BACKGROUND: Recent reports suggest that gamma-glutamyl transferase (GGT) decreases with coffee intake. The aim of this study was to examine the joint influence of alcohol, tobacco, cotinine, coffee, and caffeine on biological markers of heavy drinking in an alcoholic population. METHODS: Subjects were 160 alcohol-dependent inpatients. Biological assessments, performed at admission, were plasma levels of GGT, apolipoprotein AI, aspartate aminotransferase, and mean corpuscular volume (MCV), and urine cotinine and caffeine indexes. Years of alcohol abuse and of smoking, alcohol and coffee intake, and smoking rate were estimated in a semistructured interview, and Fagerström Tolerance Questionnaire was completed by inpatients. RESULTS: Coffee intake, but not caffeine, correlated negatively with biological markers of heavy drinking, after controlling for alcohol and tobacco intake. Years of smoking correlated positively to MCV, after controlling for alcohol and coffee intake. CONCLUSIONS: Concerning the effect of coffee, the most likely hypothesis is that noncaffeine coffee fractions have a protective effect on liver cells. Concerning the effect of smoking, one can propose that the increase of MCV with smoking could be a consequence of carbon monoxide inhalation, leading to hypoxemia, or of folate deficiency.

Adult↗

Dopamine D1 and D2 receptor mRNA up-regulation in the caudate-putamen and nucleus accumbens of rat brains by smoking.

Nicotine, the toxic substance that is exclusively absorbed from smoking, produces a wide array of behavior and collectively propels drug-seeking behaviors when abused. The neurotransmitter dopamine (DA) is important in the reward and reinforcing properties of many addictive drugs: however, the effect of nicotine by cigarette smoking itself on the expression of DA receptors in the caudate-putamen (CPu), nucleus accumbens (NAc) and olfactory tubercle (OTu) has not been elucidated completely. Hence, the effects of smoking and nicotine on DA receptors need to be defined. In this research, the effect of smoking and nicotine addiction on the DA D1 and D2 receptors in the rat CPu, NAc and OTu were studied. Adult male Spraque-Dawley (S.D., n=50) rats were administered with cigarette smoke (passive inhaled for 10 min and 1 h, 500 ml x 3 times/day, 4 weeks) and nicotine (oral, 3 mg/day). DA D1 and D2 receptor mRNA levels were determined by in situ hybridization and RNase protection assay (RPA). In the smoking groups (10 min and 1 h), DA D1 and D2 receptor mRNA greatly increased in the CPu and NAc, and most of all in the NAc. The nicotine treated group showed increased expression of DA D1 and D2 receptor mRNA too, but statistically less than in the smoking group. In the smoking group, DA D1 and D2 receptor mRNA levels were significantly higher in the CPu and NAc than in the nicotine group (P<.01). These results suggest that smoking and nicotine administration both influence DA receptor mRNAs in the CPu, NAc and OTu, in terms of up-regulation. The up-regulation was much more evident in the smoking group than in the nicotine group. In conclusion, we believe that smoking up-regulate the DA receptor mRNA expression significantly higher in rat CPu and NAc than nicotine but only a little bit higher in OTu.

Animals↗

In utero cocaine exposure: effect on neonatal breathing in guinea pigs.

Cocaine (COC) abuse during pregnancy may be a factor in the development of neonatal breathing abnormalities. To examine this possibility, pregnant Dunkin-Hartley guinea pigs were treated daily with s.c. injections of saline or 2, 6 or 12 mg/kg of COC during the second half of gestation. Treatments were assigned randomly to pregnant dams. Neonatal weight, breathing, ECG and EEG were recorded in unsedated animals using noninvasive techniques at intervals for 3 weeks after birth. Neonatal weight on Day 1 was decreased by exposure to the two highest doses of COC (P less than .05). The effects of drug treatment, day of study and response to inhalation of 5% CO2 were analyzed by repeated measures analysis of variance. A significant drug-, day- and CO2-effect on tidal volume (VT) and inspiratory minute volume (VI) was observed (P less than .01). COC exposure in utero increased the weight-normalized neonatal VT and VI on room air and 5% CO2 during the first 2 weeks of life in the absence of a measurable effect of drug exposure upon breathing frequency, heart rate or EEG power. The increase in VT and VI may be caused by an increase in metabolic rate (hyperpnea) or an alteration of ventilatory control (hyperventilation). Either mechanism could represent functional teratogenesis and either results in a greater ventilatory effort which increases the work of breathing and the consumption of oxygen. An increase in oxygen demand due to an increase in metabolism or an increase in ventilatory effort might compromise some neonates and contribute to an increased incidence of sudden-infant-death.

Animals↗

Deliberate hydrocarbon inhalation among low-socioeconomic adolescents not necessarily apprehended by the police.

Nearly 600 low socioeconomic adolescents were given a 17-item multiple choice questionnaire designed by the authors. Demographic data tended, in some respects, to be consistent with previous research. In other respects there were some differences, e.g., sniffing tends to also be a problem with females. The data suggested that there are differences between chronic and social sniffers and that these differences should be taken into account when designing treatment/prevention programs. Another suggestion is that sniffing tends to be a social activity that is engaged in because (1) it is readily available and (2) it relieves boredom. Prevention programs have tended to focus on making it more difficult to obtain access to solvents, but this has had only limited success. The development of alternatives to neighborhood boredom should also be seen as an integral and important part of drug-abuse prevention.

Administration, Intranasal↗

Correlates and changes over time in drug and alcohol use within a barrio population.

Extent and determinants of use of alcohol, marijuana, inhalants, and PCP were explored in a group of 339 Mexican American youths from the East Los Angeles Housing projects. Results from this study were compared to those from a similar survey carried out in the same area 2 years ago. Use of inhalants has declined markedly compared with prevalence reported in the previous report. However, use of alcohol and marijuana have increased across all age and sex cohorts. Prevalence of PCP use, explored for the first time in this report, was shown to be extremely high. Use of all drugs was generally predicted by age, sex, and number of peers reporting use. Self-concept factors, especially one's self-evaluation with respect to others, were also significant predictors to use of marijuana, inhalants, and PCP. However, alcohol use was not related to any self-concept factors. Language (Spanish-English) used both in the home and with peers was related to use of all substances studied. Limitations in the generalization of this study as a result of sampling problems are discussed.

Adolescent↗

Endogenous kappa opioid receptor systems modulate the responsiveness of mesoaccumbal dopamine neurons to ethanol.

BACKGROUND: Endogenous kappa-opioid receptor (KOPR) systems modulate the actions of several drugs of abuse. Their role in modulating the effects of ethanol is unknown. An increase in nucleus accumbens extracellular dopamine (DA) has been implicated in mediating the rewarding and locomotor-activating effects of ethanol and virtually all drugs of abuse. The present microdialysis studies were conducted to determine whether the lack of KOPR alters ethanol-evoked DA levels in the nucleus accumbens of naïve mice and whether a similar effect is observed in mice repeatedly exposed to ethanol. METHODS: Gene deletion techniques were used in conjunction with in vivo microdialysis to examine the influence of lack of KOPR on ethanol-evoked DA in the nucleus accumbens. To determine whether pharmacological inactivation of KOPR produces similar effects in naïve mice and those repeatedly exposed to ethanol, the KOPR antagonist norbinaltorphimine (n-BNI) was administered in wild-type mice before repeated air or ethanol vapor inhalation. Microdialysis was conducted 24 hours later. RESULTS: Acute ethanol administration increased DA levels in the nucleus accumbens of wild-type mice. In littermates lacking the KOPR gene, ethanol-evoked DA levels were enhanced. Prior ethanol exposure reduced ethanol-evoked DA levels in vehicle-treated and n-BNI-treated mice. Statistical analysis, however, revealed a significant main effect of n-BNI, indicating that KOPR blockade increased ethanol-evoked DA levels in naïve mice and repeated ethanol exposure attenuated, but did not abolish, this effect. CONCLUSIONS: These findings demonstrate that inhibition of KOPR leads to increased sensitivity to the DA-releasing effects of ethanol in the nucleus accumbens.

Animals↗

HCV infection in northeastern Brazil: unexpected high prevalence of genotype 3a and absence of African genotypes.

The genomic diversity of HCV embraces 6 genotypes and at least 52 subtypes with clinical and epidemiological correlations. There is a paucity of studies assessing HCV genotypes and biomolecular epidemiology in Brazil. We studied genotype distribution and epidemiological aspects in 232 HCV carriers, 133 (57.9%) males and 99 (42.1%) females, followed in the liver disease referral unit in Salvador, BA, northeastern Brazil. All of them were anti-HCV positive by 3rd generation ELISA assay, and HCV-RNA positive by RT-PCR. Genotyping was performed by INNOLIPA. Assessment of risk factors for HCV infection showed that 93 (40%) had past blood transfusion, 14 (6%) intravenous drug use, 19 (8%) inhalation of cocaine, 28 (12%) tattooing, 15 (7%) were health care workers, 5 (2%) had reused disposable syringes, 5 (2%) had multiple risk factors and in 53 (23%) no risk factor was determined. Genotype 1a was observed in 75 (32%), 1b in 72 (31%), 3a in 61 (26%), 2ab in 14 (6%); 5 (2.5%) had mixed genotypes and 5 (2.5%) were undetermined. Patients with genotype 1 had a higher mean age (P < 0.05) and no particular risk factors were associated with a specific genotype. Genotype 1 largely predominates in northeast Brazil followed by genotype 3 which, in this population, does not seem to be related to intravenous drug abuse, in contrast to some European studies. Although 80% of the Salvador population comprises African-Brazilians, no African genotype was identified, which may mean that HCV was introduced into this region via European immigration. This study demonstrated some peculiarities of HCV epidemiology in Brazil and strongly suggests that HCV introduction to this region was probably related to European immigration.

Adult↗

[Passive exposure in detection of low blood and urine cannabinoid concentrations].

Whenever small amounts of drugs are present in blood or urine samples, especially of substances that are preferentially smoked such as cannabinoids, the discrimination between active and passive inhalation may cause severe problems. The statement of a passive exposure by marijuana smoke has been scrutinized reviewing the literature. The pharmacokinetics of smoked marijuana as well as experimental data on cannabinoid concentrations in plasma and urine samples following passive exposure are summarized. As a conclusion it seems urgent to enlarge the existing data base.

Automobile Driving↗

[Functional repair of a major necrotic palatine defect caused by chronic cocaine inhalation].

INTRODUCTION: Chronic use of cocaine provokes vasoconstriction and irritation of the upper airway epithelium. These mechanisms can lead to tissue necrosis and perforations. CASE REPORT: A 37-year-old woman had major centrofacial necrosis subsequent to chronic inhalation of cocaine. The tissue loss involved the right wing of the right ala nasi, the bony and soft palate and nearly all of the lateronasal walls. A microanastomosed antebrachial fasciocutaneous flap was used for reconstruction of the nasal vault. A classical veloplasty was used to close the palate. Velar competency was improved with a second procedure with Ortricochea sphincter pharyngoplasty. Later loss of the antebrachial flap required salvage with a flap from the lateral border of the tongue which provided a satisfactory functional result. DISCUSSION: This case of extended necrosis is rare and treatment was complex. Such treatment can only be undertaken after total and definitive cessation of drug abuse, including tobacco smoking.

Adult↗

Acute respiratory failure from abused substances.

Acute respiratory failure is a common complication of drug abuse. It is more likely to develop in the setting of chronic lung disease or debility in those with limited respiratory reserve. Drugs may acutely precipitate respiratory failure by compromising respiratory pump function and/or by causing pulmonary pathology. Polysubstance overdoses are common, and clinicians should anticipate complications related to multiple drugs. Impairment of respiratory pump function may develop from central nervous system (CNS) depression (suppression of the medulla oblongata, stroke or seizures) or respiratory muscle fatigue (increased respiratory workload, metabolic acidosis). Drug-related respiratory pathology may result from parenchymal (aspiration-related events, pulmonary edema, hemorrhage, pneumothorax, infectious and non-infectious pneumonitides), airway (bronchospasm and hemorrhage), or pulmonary vascular insults (endovascular infections, hemorrhage, and vasoconstrictive events). Alcohol, cocaine, amphetamines, opiates, and benzodiazepines are the most commonly abused drugs that may induce events leading to acute respiratory failure. While decontamination and aggressive supportive measures are indicated, specific therapies to correct seizures, metabolic acidosis, pneumothorax, infections, bronchospasm, and agitation should be considered. Drug-related respiratory failure when due to CNS depression alone may portend well, but in patients with drug-related significant pulmonary pathology, a protracted course of illness may be anticipated.

Acute Disease↗