Initial Intoxication Research Articles

Intoxication without anticipation: Disentangling pharmacological from expected effects of alcohol.

The pharmacological effects of alcohol on executive function, craving and subsequent alcohol-seeking have been well documented. Yet, insufficient methodological controls within existing alcohol administration paradigms have meant that the relative importance of alcohol's pharmacological and anticipatory effects remains in need of further elucidation. The objective of this study is to disentangle alcohol's pharmacological effects from its anticipatory effects on alcohol-related cognitions and subsequent consumption. Inhibitory control, attentional bias and craving were assessed pre- and post-consumption in 100 participants who were randomly allocated to one of four beverage conditions in a two by two design: (1) alcohol aware (alcohol with participant knowledge (pharmacological/anticipation effects)), (2) alcohol blind (alcohol without participant knowledge; in a novel grain alcohol masking condition (pharmacological/no anticipation effects)), (3) placebo (no alcohol but participants were deceived (anticipation/non-pharmacological effects)) and (4) pure control (no alcohol with participant knowledge (no anticipation/non-pharmacological effects)). Findings suggest that the pharmacological effects of alcohol result in greater inhibitory control impairments compared with anticipated effects. Anticipatory but not the pharmacological effects of alcohol were found to increase attentional bias. Both pharmacology and anticipation resulted in increased craving, though higher levels of craving were observed due to alcohol's pharmacology. Furthermore, alcohol pharmacology resulted in heightened ad libitum consumption; however, anticipation did not. Changes in craving partially mediated the relationship between initial intoxication and subsequent drinking, while inhibitory control impairments did not. Successive alcohol consumption appears driven primarily by the pharmacological effects of alcohol which are exerted via changes in craving.

The Effects of Placebo and Moderate Dose Alcohol on Attentional Bias, Inhibitory Control and Subjective Craving.

Previous research indicates that acute alcohol intoxication and placebo can inhibit people's control over consumption behaviour and heighten attentional bias (AB) towards alcohol-related stimuli and craving. We designed a study to disentangle anticipated from pharmacological effects of alcohol in order to gain a clearer view of their relative contributions to alcohol consumption. In a within-participants design (moderate alcohol dose, placebo and control), and over a minimum 2-week period, participants completed a battery of questionnaires and cognitive tasks, followed by a bogus taste task to measure ad libitum consumption. Both alcohol preload and placebo resulted in cognitive and psychological changes, including impaired inhibitory control, heightened AB and craving. However, ad libitum consumption only increased following alcohol and not placebo. Furthermore, inhibitory control impairments did not mediate the relationship between initial intoxication and ad libitum consumption, and findings indicate that increases in craving may mediate this association. Psychological processes such as craving may be more important in driving consummatory behaviour relative to transient changes in cognitive processes, such as inhibitory control.

Clozapine intoxication with severe adverse effects induced by an inflammatory and infectious process: a case report

BackgroundClozapine intoxication can be life-threatening. Outside of the common drug–drug interactions, tobacco smoking, and caffeine consumption, infectious and inflammatory processes are important contributors to clozapine intoxication. Although this relationship has been reported previously, the literature is scant of proper research articles describing the presentation and management of this unpredictable interaction. Therefore, clinicians need to rely heavily on case reports describing clozapine intoxication caused by inflammation and/or infection.Case presentationA 64-year-old Caucasian woman known for schizophrenia was brought to the emergency department (ED) with severe signs and symptoms of clozapine intoxication (general deterioration, drowsiness, neutropenia, and ileus). She was on clozapine 700 mg daily amongst other medications. The clozapine dose was stable for over 3 years, and there were no recent changes in her medications. The initial culprit was determined to be an infectious/inflammatory process of gastrointestinal origin with contribution from dehydration and constipation. Clozapine and norclozapine serum concentrations confirmed the intoxication: 1315 ng/mL and 653 ng/mL, respectively. She drastically improved with clozapine dose reduction and antibiotic therapy. She remained stable for years with clozapine 600 mg daily with stable clozapine serum levels.ConclusionThis case report illustrates the possibility of severe toxicity associated with an acute infectious and/or inflammatory process in patients on clozapine therapy. Clinicians must maintain a high level of suspicion in patients taking clozapine who develop and an infectious and/or inflammatory process. Constipation secondary to clozapine intoxication can exacerbate the initial intoxication process.

Continuous Theta Burst Transcranial Magnetic Stimulation of the Right Dorsolateral Prefrontal Cortex Impairs Inhibitory Control and Increases Alcohol Consumption

Previous research indicates that alcohol intoxication impairs inhibitory control and that the right dorsolateral prefrontal cortex (rDLPFC) is a functional brain region important for exercising control over thoughts and behaviour. At the same time, the extent to which changes in inhibitory control following initial intoxication mediate subsequent drinking behaviours has not been elucidated fully. Ascertaining the extent to which inhibitory control impairments drive alcohol consumption, we applied continuous theta burst transcranial magnetic stimulation (rDLPFC cTBS vs. control) to isolate how inhibitory control impairments (measured using the Stop-Signal task) shape ad libitum alcohol consumption in a pseudo taste test. Twenty participants (13 males) took part in a within-participants design; their age ranged between 18 and 27 years (M = 20.95, SD = 2.74). Results indicate that following rDLPFC cTBS participants’ inhibitory control was impaired, and ad libitum consumption increased. The relationship between stimulation and consumption did not appear to be mediated by inhibitory control in the present study. Overall, findings suggest that applying TMS to the rDLPFC may inhibit neural activity and increase alcohol consumption. Future research with greater power is recommended to determine the extent to which inhibitory control is the primary mechanism by which the rDLPFC exerts influence over alcohol consumption, and the degree to which other cognitive processes may play a role.

Resistance of microalgae to colloidal silver nanoparticles

Effect of colloidal silver nanoparticles on growth and structure of laboratory populations was investigated in chlorococcal algae Scenedesmus quadricauda (Turp.) Breb. and Monoraphidium arcuatum (Korsch.) Hind. in the range of concentrations from 0.0001 to 1 mg/L. The toxicity of colloidal silver was manifested at a concentration of 0.1 mg/L and higher and was associated with an algostatic effect, which duration directly depended on silver concentration in the medium. After a period of growth suppression at a concentration of 0.1 mg/L, in both species cell population in the culture was gradually recovered and the structure of population (ratio between the fractions of dividing, quiescent, and dead cells) became the same as in control material. The effect of adaptation of S. quadricauda to colloidal silver was detected upon successive passages to the media with toxic concentrations (0.1 and 0.5 mg/L), which depended on the concentration and duration of initial intoxication of the culture. The toxicity of cell-free filtrates from the culture of S. quadricauda, which was in contact with colloidal silver for different time periods, was estimated using intact culture of the same species, whose population on cell-free filtrates was close to control level. Transfer of the cells that were exposed to silver to a pure medium led to a long lag phase in all the cases. It is assumed that the main mechanism of algal population adaptation to higher concentrations (0.1 and 0.5 mg/L) of this toxicant depends on the selection of resistant cells present in the initial heterogeneous population in the course of primary exposure to colloidal silver. These resistant cells accidentally emerge in the population by means of rare spontaneous mutations occurring in the course of replication even before the contact with silver and have more perfect mechanisms of its detoxification.

Intravenous 0.9% sodium chloride therapy does not reduce length of stay of alcohol-intoxicated patients in the emergency department: A randomised controlled trial

BackgroundI.v. 0.9% sodium chloride (normal saline) is frequently used to treat ED patients with acute alcohol intoxication despite the lack of evidence for its efficacy.ObjectiveThe study aims to compare treatment with i.v. normal saline and observation with observation alone in ED patients with acute alcohol intoxication.MethodsA single-blind, randomised, controlled trial was conducted to compare a single bolus of 20 mL/kg i.v. normal saline plus observation with observation alone. One hundred and forty-four ED patients with uncomplicated acute alcohol intoxication were included. The study was conducted in one tertiary and one urban ED in Queensland, Australia. Primary outcome was ED length of stay (EDLOS). Secondary outcomes were treatment time, breath alcohol levels, intoxication symptom score, level of intoxication and associated healthcare costs.ResultsBoth groups were comparable at baseline: blood alcohol content (BAC) was similar between treatment and control groups (0.20 % BAC vs 0.19 % BAC, P = 0.44) as were initial intoxication symptom scores (22.0 vs 22.3, P = 0.90). Both groups had a similar EDLOS (287 min vs 274 min, P = 0.89; difference 13 min [95% CI −37–63]) and treatment time (244 min vs 232 min, P = 0.94; difference 12 min [95% CI −31–55]). Change of breath alcohol levels, intoxication score and level of intoxication were not significantly different between the two groups. Patients in the treatment group had an additional healthcare cost of A$31.92 compared with control.ConclusionsI.v. normal saline therapy added to observation alone does not decrease ED length of stay compared with observation alone. Intoxication symptom scores and general state of intoxication were similar in both groups. The present study suggests that either approach is reasonable, but observation alone might be preferred as it is less resource intensive.

Intravenous 0.9% sodium chloride therapy does not reduce length of stay of alcohol‐intoxicated patients in the emergency department: A randomised controlled trial

I.v. 0.9% sodium chloride (normal saline) is frequently used to treat ED patients with acute alcohol intoxication despite the lack of evidence for its efficacy. The study aims to compare treatment with i.v. normal saline and observation with observation alone in ED patients with acute alcohol intoxication. A single-blind, randomised, controlled trial was conducted to compare a single bolus of 20 mL/kg i.v. normal saline plus observation with observation alone. One hundred and forty-four ED patients with uncomplicated acute alcohol intoxication were included. The study was conducted in one tertiary and one urban ED in Queensland, Australia. Primary outcome was ED length of stay (EDLOS). Secondary outcomes were treatment time, breath alcohol levels, intoxication symptom score, level of intoxication and associated healthcare costs. Both groups were comparable at baseline: blood alcohol content (BAC) was similar between treatment and control groups (0.20 % BAC vs 0.19 % BAC, P = 0.44) as were initial intoxication symptom scores (22.0 vs 22.3, P = 0.90). Both groups had a similar EDLOS (287 min vs 274 min, P = 0.89; difference 13 min [95% CI -37-63]) and treatment time (244 min vs 232 min, P = 0.94; difference 12 min [95% CI -31-55]). Change of breath alcohol levels, intoxication score and level of intoxication were not significantly different between the two groups. Patients in the treatment group had an additional healthcare cost of A$31.92 compared with control. I.v. normal saline therapy added to observation alone does not decrease ED length of stay compared with observation alone. Intoxication symptom scores and general state of intoxication were similar in both groups. The present study suggests that either approach is reasonable, but observation alone might be preferred as it is less resource intensive.

Seletividade de cultivares de soja RR® submetidos a misturas em tanque de glyphosate + chlorimuron-ethyl associadas a óleo mineral e inseticidas

O uso de glyphosate para o controle de plantas daninhas em soja RR® apresenta características essenciais no conceito de praticabilidade. Entretanto, apesar de não permitido na legislação brasileira, tem-se aumentado a associação com outros herbicidas para manejo de espécies de difícil controle, assim como a sua mistura em tanque em combinação com inseticidas e adjuvantes. Com o objetivo de avaliar a seletividade de cultivares de soja RR® submetidos a misturas em tanque de formulações de glyphosate (Polaris®, Roundup Ready® e Roundup WG®) com chlorimuron-ethyl (Classic®), e suas associações com óleo mineral (Joint Oil®) e inseticidas novaluron (Gallaxy 100 EC®), permethrin (Piredan®) e methomyl (Lannate BR®), um experimento foi conduzido a campo na cidade de Maracaí-SP, na safra 2006/2007. O delineamento experimental utilizado foi o de blocos ao acaso, com quatro repetições, em esquema fatorial 16 x 4, sendo 16 as associações das misturas em tanque entre as formulações de glyphosate, óleo mineral e inseticidas e quatro cultivares: Monsoy 7210RR®, Monsoy 7979RR®, BRS 245RR® e CD 214RR®. Sintomas visuais de intoxicação inicial dos cultivares estudados foram caracterizados por clorose e encarquilhamento nas folhas para todas as misturas em tanque das formulações de glyphosate + chlorimuron-ethyl, associadas ou não ao óleo mineral e inseticidas novaluron, permethrin e methomyl. Todas as misturas em tanque não promoveram reduções significativas de produtividade para os cultivares Monsoy 7210RR®, Monsoy 7979RR® e BRS 245RR® e controlaram Ipomoea spp. com eficácia apenas satisfatória a partir dos 21 DAA (dias após aplicação).

A new model to study compensatory mechanisms in MPTP-treated monkeys exhibiting recovery

The cardinal symptoms in Parkinson's disease (PD), akinesia, rigidity and tremor, are only observed when the striatal level of dopamine is decreased by 60-80%. During the preclinical phase of PD, compensatory mechanisms are probably involved in delaying the appearance of motor symptoms. In a MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of PD, a spontaneous recovery has been reported after initial intoxication suggesting that compensatory mechanisms are activated in this model as well. Assuming that mechanisms are similar in these phenomena, the study of recovery in monkeys following MPTP intoxication may enable identification of compensatory mechanisms involved in the preclinical phase of PD. In order to maximize the temporal similarity between PD and the MPTP model, we assessed a new progressive monkey model in which spontaneous recovery is expressed systematically and to characterize it based on (1) its behavioural features, and (2) the presence of compensatory mechanisms revealed by an immunohistological approach comparing dopaminergic and serotoninergic innervation between monkeys either exhibiting behavioural recovery or stable motor symptoms. This immunohistological study focused on the substantia nigra, striatum and pallidum, and their anatomical and functional subdivisions: sensorimotor, associative and limbic. The behavioural analysis revealed that with progressive MPTP intoxication motor symptoms were initially expressed in all monkeys. Observable recovery from these symptoms occurred in all monkeys (7/7) within 3-5 weeks after the last MPTP injection, and most exhibited a full recovery. In contrast, acute intoxication induced stable motor symptoms. Despite this obvious behavioural difference, immunohistological methods revealed that the loss of dopaminergic cell bodies in substantia nigra was substantial and similar in both MPTP-treated groups. However, quantification of fibres revealed that recovered monkeys displayed more dopaminergic and serotoninergic fibres than those with stable motor symptoms in sensorimotor and associative territories of striatum and more dopaminergic fibres in internal pallidum. This study provides a new model of PD where all monkeys expressed functional recovery from motor symptoms despite a large dopaminergic neuronal loss. The immunohistological results suggest that both dopamine and serotonin could be implicated in the compensatory mechanisms.

Crescimento do eucalipto sob efeito da deriva de glyphosate

Um dos questionamentos no setor florestal é sobre os possíveis efeitos negativos da deriva de glyphosate sobre plantas de eucalipto ao longo de seu ciclo. Aos 30 dias após a aplicação (DAA) de 1.440 g ha-1 de glyphosate, para controle de plantas daninhas em talhão de Eucalyptus grandis x E. urophylla (híbrido urograndis) com 120 dias após o transplantio, selecionaram-se 120 plantas ao acaso, que apresentavam graus de intoxicação variáveis. Os tratamentos foram os seguintes intervalos: 0-5, 6-10, 11-20, 21-30, 31-40 e 41-50% de intoxicação das plantas, em que o intervalo de 0 - 5% foi considerado testemunha. Foram realizadas avaliações de altura e diâmetro, após a seleção das plantas, até os 360 DAA, sendo acompanhados durante esse período os sintomas de intoxicação. Aos 360 DAA, foi estimado o volume de madeira (m³) e calculado o ganho em altura e diâmetro durante o período de avaliação. Plantas com intoxicação inicial acima de 31% apresentaram menor altura e diâmetro aos 360 DAA. O ganho em altura foi menor em plantas com intoxicação inicial acima de 41%. Observou-se menor diâmetro a partir de 21% de intoxicação, com os menores valores de crescimento em diâmetro do caule observados em plantas com 41-50% de intoxicação. Os danos causados pela deriva do glyphosate afetaram a produção de madeira aos 360 DAA, em que plantas com 21-30, 31-40 e 41-50% de intoxicação apresentaram redução no volume de madeira de 18, 26 e 48%, respectivamente, em relação à testemunha. Os resultados confirmam os prejuízos ocasionados pela deriva do glyphosate em plantas de eucalipto. Novas avaliações devem ser realizadas para acompanhamento do crescimento e desenvolvimento das plantas até o final do ciclo do eucalipto, a fim de elucidar os efeitos da deriva do glyphosate sobre a produção final da cultura.

Like it is: Thoughts on the Career of Lewis Polsgrove

Special education as it relates to students with emotional or behavioral disorders (E/BD) is still relatively new. Even so, the complex nature of the problems manifested by students so identified has generated widespread dis-agreement and often contentious debate over both etiology and intervention. And, at times, a mix of social, political, and economic forces have converged to paint an uncertain future for the field. In the face of these challenges, a handful of individuals have afforded the profession unfaltering leadership and clear direction. Lewis Polsgrove is among them. Lew's career is punctuated by a commitment to removing barriers to achieving successful outcomes for students with E/BD. He has worked tirelessly to rid the field of flawed conceptual frameworks (e.g., Nelson & Polsgrove, 1984), bureaucratic constraints (Skiba, Polsgrove, & Nasstrom, 1996), and ineffective or harmful intervention strategies (Nelson, Scott, & Polsgrove, 1999). He has done so with compassion, humor, and humility.Lew's career has closely paralleled changes that have occurred in the field of special education. Early on, Lew worked as a counselor in a residential facility serving adjudicated delinquents. Fortunately for the field, he rebounded from any initial intoxication with that experience and any lingering psychodynamic hangover. Thereafter, his work has reflected an unwavering commitment to science over ideology and a positivistic perspective on special education.As I read Lew's thoughts about the field of special education, it seems clear that he sees too little consensus regarding what constitutes high-quality research; he also expresses consternation over the absence of a common perspective on research-based practices. Mir-roring his own actions, Lew urges us to be more vociferous about our position on issues that impact the lives of children and youths with E/BD. I concur. Given the current political scene, the stakes may never be higher or the consequences of inaction more harmful to students with E/BD. In addition, Lew voices dissatisfaction with our teacher preparation efforts. He expresses concern over the fact that beginning teachers often succumb to cultural norms of the workplace and embrace the ineffective practices of others. Most of us would concede that these issues pose enormous challenges to our teacher preparation efforts.Anyone familiar with Lew's work knows that he staunchly supports the process of scientific inquiry. We can infer that our ethical responsibility to ensure students with E/BD the most efficacious academic and behavioral supports demands that we squelch the growth of nonscientific paradigms and the promulgation of unsubstantiated practices. …

Persistence of botulinum neurotoxin action in cultured spinal cord cells 1,2

Primary dissociated fetal mouse spinal cord cultures were used to study the mechanisms underlying the differences in persistence of botulinum neurotoxin A (BoNT/A) and botulinum neurotoxin/E (BoNT/E) activities. Spinal cord cultures were exposed to BoNT/A (0.4 pM) for 2–3 days, which converted approximately half of the SNAP-25 to an altered form lacking the final nine C-terminal residues. The distribution of toxin-damaged to control SNAP-25 remained relatively unchanged for up to 80 days thereafter. Application of a high concentration of BoNT/E (250 pM) either 25 or 60 days following initial intoxication with BoNT/A converted both normal and BoNT/A-truncated SNAP-25 into a single population lacking the final 26 C-terminal residues. Excess BoNT/E was removed by washout, and recovery of intact SNAP-25 was monitored by Western blot analysis. The BoNT/E-truncated species gradually diminished during the ensuing 18 days, accompanied by the reappearance of both normal and BoNT/A-truncated SNAP-25. Return of BoNT/A-truncated SNAP-25 was observed in spite of the absence of BoNT/A in the culture medium during all but the first 3 days of exposure. These results indicate that proteolytic activity associated with the BoNT/A light chain persists inside cells for >11 weeks, while recovery from BoNT/E is complete in <3 weeks. This longer duration of enzymatic activity appears to account for the persistence of serotype A action.

Pulling the plug on futility

If the fashionableness of a new idea can be measured by the number of publications it generates these are piping times for the idea of “medical futility.” As it has been developed in the medical literature futility provides a basis for doctors to refuse demands for treatment from patients and families. According to the results of a Medline search, articles on futility have undergone a small scale population explosion: two articles in 1987, five in 1990, and 23 in 1993. As with any new intellectual tack, after the initial intoxication has begun to wear off we must ask soberly: “Are we any further ahead?” The idea of futility is admittedly seductive. Over the past few years the familiar “right to die” issue has been turned on its head. Rather than refusing life sustaining treatment in the face of intransigent doctors, patients (and their surrogates) have begun to demand treatment that doctors are reluctant to provide, either because its efficacy is questionable or, more problematically, because it serves goals that the doctors are reluctant to endorse. The most contentious of these cases have been those in which families have asked for aggressive life sustaining treatment for anencephalic children1 or patients in …

Alcohol challenge with sons of alcoholics: A critical review and analysis.

Studies are reviewed in which response to acute administration of alcohol was compared between individuals with and without family histories of alcoholism (FH+, FH-). This research represents a search for a psychobiological marker for alcoholism. A methodological critique of the procedures reported in this literature is then presented. Finally, a conceptual model is suggested in which differences in the response to alcohol between FH+ individuals and FH- individuals must be understood in relation to time after drinking alcohol. This Newtonian differentiator model proposes that sons of alcoholics exhibit acute sensitization as blood alcohol level rises and acute tolerance as blood alcohol level falls, compared with sons of nonalcoholics. Therefore, FH+ subjects find alcohol more rewarding because they accentuate the pleasurable, excitatory aspects of initial intoxication and attenuate the feelings of anxiety and depression that predominate as blood alcohol levels drop.

Effects of ethanol on plasma catecholamines and norepinephrine clearance.

Plasma catecholamines were measured in nine men after they had drunk either 0.5 or 1 ml/kg ethanol. Ethanol was found to induce a dose-dependent rise in plasma norepinephrine concentrations. Epinephrine concentrations were also raised in the initial intoxication phase. To determine whether ethanol raises plasma norepinephrine through increased release or decreased clearance (Cl), we infused norepinephrine into eight male subjects with and without prior ethanol, each subject acting as his own control. During infusions after ethanol, norepinephrine concentrations rose higher, and the mean circulatory Cl of norepinephrine was reduced from 76 to 47 ml/kg/min. This was associated with a prolongation of norepinephrine t 1/2 from 1.7 to 2.05 min. No significant difference in circulatory input of norepinephrine was found between infusions with and without ethanol. These results indicate that ethanol consumption increases plasma norepinephrine by reducing its circulatory Cl.

DELAYED PSYCHOSIS DUE TO L.S.D.

Two cases of delayed psychosis due to L.S.D. of such severity as to necessitate admission to mental hospital have been observed. Both patients, after initial intoxication with a single dose of L.S.D., reverted to complete normality and remained normal for between 2 weeks and 2 months before acute psychotic illnesses developed. The possibility of a delayed psychosis due to L.S.D. justifies discontinuation of the use of L.S.D. in psychiatry.

The Voice of the Redeemer in Paradise Lost

After the initial intoxication, the Fall of Man is delineated in Paradise Lost largely in terms of the charges and counter-charges, the fear and hatred, the self-aggrandizement and the isolation of Adam and Eve. Only after Adam's most bitter denunciation of Eve is the direction changed with Eve's famous “Forsake me not thus, Adam … ”(x.914–936). Eve's speech is the turning point, for it is here that one of the guilty pair first attempts to take upon herself the burden of guilt, shows love and asks for love. The direction once taken, Adam is moved to similar affection, and the resulting reconciliation between man and woman is the inevitable prologue and type of the ensuing reconciliation between man and God.