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Sample records for alcohol withdrawal severity

  1. Alcohol withdrawal

    MedlinePlus

    ... Seeing or feeling things that aren't there (hallucinations) Seizures Severe confusion ... alcohol withdrawal. You will be watched closely for hallucinations and other signs of delirium tremens. Treatment may ...

  2. Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine.

    PubMed

    Perez, Erika; Quijano-Cardé, Natalia; De Biasi, Mariella

    2015-09-01

    Alcohol and nicotine are among the top causes of preventable death in the United States. Unfortunately, people who are dependent on alcohol are more likely to smoke than individuals in the general population. Similarly, smokers are more likely to abuse alcohol. Alcohol and nicotine codependence affects health in many ways and leads to poorer treatment outcomes in subjects who want to quit. This study examined the interaction of alcohol and nicotine during withdrawal and compared abstinence symptoms during withdrawal from one of the two drugs only vs both. Our results indicate that simultaneous withdrawal from alcohol and nicotine produces physical symptoms that are more severe and last longer than those experienced during withdrawal from one of the two drugs alone. In animals experiencing withdrawal after chronic ethanol treatment, acute nicotine exposure was sufficient to prevent abstinence symptoms. Similarly, symptoms were prevented when alcohol was injected acutely in mice undergoing nicotine withdrawal. These experiments provide evidence for the involvement of the nicotinic cholinergic system in alcohol withdrawal. Furthermore, the outcomes of intracranial microinfusions of mecamylamine, a nonselective nicotinic receptor antagonist, highlight a major role for the nicotinic receptors expressed in medial habenula and interpeduncular nucleus during withdrawal. Overall, the data support the notion that modulating the nicotinic cholinergic system might help to maintain long-term abstinence from alcohol.

  3. FKBP5 Moderates Alcohol Withdrawal Severity: Human Genetic Association and Functional Validation in Knockout Mice

    PubMed Central

    Huang, Ming-Chyi; Schwandt, Melanie L; Chester, Julia A; Kirchhoff, Aaron M; Kao, Chung-Feng; Liang, Tiebing; Tapocik, Jenica D; Ramchandani, Vijay A; George, David T; Hodgkinson, Colin A; Goldman, David; Heilig, Markus

    2014-01-01

    Alcohol withdrawal is associated with hypothalamic–pituitary–adrenal (HPA) axis dysfunction. The FKBP5 gene codes for a co-chaperone, FK506-binding protein 5, that exerts negative feedback on HPA axis function. This study aimed to examine the effects of single-nucleotide polymorphisms (SNPs) of the FKBP5 gene in humans and the effect of Fkbp5 gene deletion in mice on alcohol withdrawal severity. We genotyped six FKBP5 SNPs (rs3800373, rs9296158, rs3777747, rs9380524, rs1360780, and rs9470080) in 399 alcohol-dependent inpatients with alcohol consumption 48 h before admission and recorded scores from the Clinical Institute Withdrawal Assessment-Alcohol revised (CIWA-Ar). Fkbp5 gene knockout (KO) and wild-type (WT) mice were assessed for alcohol withdrawal using handling-induced convulsions (HICs) following both acute and chronic alcohol exposure. We found the minor alleles of rs3800373 (G), rs9296158 (A), rs1360780 (T), and rs9470080 (T) were significantly associated with lower CIWA-Ar scores whereas the minor alleles of rs3777747 (G) and rs9380524 (A) were associated with higher scores. The haplotype-based analyses also showed an association with alcohol withdrawal severity. Fkbp5 KO mice showed significantly greater HICs during withdrawal from chronic alcohol exposure compared with WT controls. This study is the first to show a genetic effect of FKBP5 on the severity of alcohol withdrawal syndrome. In mice, the absence of the Fkbp5 gene enhances sensitivity to alcohol withdrawal. We suggest that FKBP5 variants may trigger different adaptive changes in HPA axis regulation during alcohol withdrawal with concomitant effects on withdrawal severity. PMID:24603855

  4. Similar withdrawal severity in adolescents and adults in a rat model of alcohol dependence.

    PubMed

    Morris, S A; Kelso, M L; Liput, D J; Marshall, S A; Nixon, K

    2010-02-01

    Alcohol use during adolescence leads to increased risk of developing an alcohol use disorder (AUD) during adulthood. Converging evidence suggests that this period of enhanced vulnerability for developing an AUD may be due to the adolescent's unique sensitivity and response to alcohol. Adolescent rats have been shown to be less sensitive to alcohol intoxication and withdrawal susceptibility; however, age differences in ethanol pharmacokinetics may underlie these effects. Therefore, this study investigated alcohol intoxication behavior and withdrawal severity using a modified Majchrowicz model of alcohol dependence that has been shown to result in similar blood ethanol concentrations (BECs) despite age differences. Adolescent (postnatal day, PND, 35) and adult rats (PND 70+) received ethanol according to this 4-day binge paradigm and were observed for withdrawal behavior for 17h. As expected, adolescents showed decreased sensitivity to alcohol-induced CNS depression as evidenced by significantly lower intoxication scores. Thus, adolescents received significantly more ethanol each day (12.3+/-0.1g/kg/day) than adults (9.2+/-0.2g/kg/day). Despite greater ethanol dosing in adolescent rats, both adolescent and adult groups had comparable peak BECs (344.5+/-10.2 and 338.5+/-7.8mg/dL, respectively). Strikingly, withdrawal severity was similar quantitatively and qualitatively between adolescent and adult rats. Further, this is the first time that withdrawal behavior has been reported for adolescent rats using this model of alcohol dependence. A second experiment confirmed the similarity in BECs at various time points across the binge. These results demonstrate that after consideration of ethanol pharmacokinetics between adults and adolescents by using a model that produces similar BECs, withdrawal severity is nearly identical. This study, in combination with previous reports on ethanol withdrawal in adolescents and adults, suggests only a BEC-dependent effect of ethanol on

  5. Inpatient alcohol withdrawal syndrome.

    PubMed

    Monte-Secades, R; Rabuñal-Rey, R; Guerrero-Sande, H

    2015-03-01

    A 55-year-old man was admitted for a femur fracture; an alcohol fetor was noted on admission. The following day, the patient began to experience tremors and nervousness. Intravenous haloperidol was administered. Shortly afterwards, the patient experienced two generalized seizures and then began to experience delirium and uncontrollable agitation. The patient was diagnosed with alcohol withdrawal syndrome; high doses of intravenous midazolam were prescribed and infused. A few hours later, the patient presented signs of respiratory depression, requiring a transfer to the intensive care unit. After a review of the medical history, it was determined that the patient had been admitted on 3 previous occasions due to alcohol withdrawal and had progressed to delirium tremens after experiencing seizures. Can the risk of alcohol withdrawal syndrome and the need for prophylactic treatment be assessed on admission? Were appropriate monitoring and treatment measures employed? Would it have been possible to change his outcome?

  6. Alcohol Withdrawal Syndrome: Benzodiazepines and Beyond

    PubMed Central

    Sachdeva, Ankur; Chandra, Mina

    2015-01-01

    Alcohol dependence is an increasing and pervasive problem. Alcohol withdrawal symptoms are a part of alcohol dependence syndrome and are commonly encountered in general hospital settings, in most of the departments. Alcohol withdrawal syndrome ranges from mild to severe. The severe complicated alcohol withdrawal may present with hallucinations, seizures or delirium tremens. Benzodiazepines have the largest and the best evidence base in the treatment of alcohol withdrawal, and are considered the gold standard. Others, such as anticonvulsants, barbiturates, adrenergic drugs, and GABA agonists have been tried and have evidence. Supportive care and use of vitamins is essential in the management. Symptom triggered regime is favoured over fixed tapering dose regime, although monitoring through scales is cumbersome. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on ‘Alcohol withdrawal syndrome’ in humans during the last 10 years. A total of 1182 articles came up. Articles not relevant to clinical utility and management were excluded based on the titles and abstract available. Full text articles, meta-analyses, systematic reviews and randomized controlled trials were obtained from this list and were considered for review. PMID:26500991

  7. A comparison of dexmedetomidine and placebo on the plasma concentrations of NGF, BDNF, GDNF, and epinephrine during severe alcohol withdrawal.

    PubMed

    Reynolds, Paul M; Mueller, Scott W; MacLaren, Robert

    2015-02-01

    Alcohol withdrawal and therapies may affect nerve growth factor (NGF), brain-derived neurotrophic growth factor (BDNF), glial-derived neurotrophic growth factor (GDNF), and epinephrine (EPI). This study evaluated dexmedetomidine (DEX) on NGF, BDNF, GDNF, and EPI in severe alcohol withdrawal and related their plasma concentrations to DEX concentrations. Twenty-four subjects were randomized to DEX 1.2 mcg/kg/hour (high dose [HD]), 0.4 mcg/kg/hour (low dose [LD]), or placebo. Blood was collected at 0 (T0), 48 (T48), and 96-120 (T96) hours after starting the study drug, and concentrations of these transmitters and DEX were determined. Similar NGF suppression occurred at T48 and T96 across all groups. BDNF and GDNF levels increased insignificantly at T48 in the placebo group but steadily declined in both DEX groups, with a trend toward significance in the HD group at T48. EPI concentrations declined significantly in the HD group at T48, only to increase at T96. Median DEX concentrations during the study were insignificantly higher in HD than LD. T0 values of BDNF (r = -0.47, p = 0.02) and GDNF (r = -0.37, p = 0.05) were inversely associated with the need for mechanical ventilation before study enrollment. No other clinical parameter was associated with the plasma concentrations of these transmitters. Daily lorazepam requirements were associated with the severity of withdrawal (r = 0.7, p < 0.0001) and DEX concentrations were inversely related to daily lorazepam requirements (r = -0.33, p = 0.008). DEX utilization suppressed EPI (r = -0.57, p = 0.004). EPI concentrations were associated with BDNF values at T0 (r = 0.55, p = 0.04) and throughout the study (r = 0.25, p = 0.04). In summary, the plasma concentrations of NGF, BDNF, GDNF, and EPI during alcohol withdrawal are variable and the effects of DEX were marginal. DEX administration and higher DEX concentrations attenuated lorazepam administration in the short-term and suppressed EPI.

  8. IDENTIFICATION AND MANAGEMENT OF ALCOHOL WITHDRAWAL SYNDROME

    PubMed Central

    Mirijello, Antonio; D’Angelo, Cristina; Ferrulli, Anna; Vassallo, Gabriele; Antonelli, Mariangela; Caputo, Fabio; Leggio, Lorenzo; Gasbarrini, Antonio; Addolorato, Giovanni

    2016-01-01

    Symptoms of alcohol withdrawal syndrome may develop within 6–24 hours after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for alcohol withdrawal syndrome is represented by benzodiazepines. Among them, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as alpha2-agonists (clonidine and dexmetedomidine) and beta-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptics can help control hallucinations. Finally, other medications for the treatment for alcohol withdrawal syndrome have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin, and topiramate. The usefulness of these agents will be discussed in the text. PMID:25666543

  9. Inpatient management of acute alcohol withdrawal syndrome.

    PubMed

    Perry, Elizabeth C

    2014-05-01

    Alcohol withdrawal is a common condition encountered in the hospital setting after abrupt discontinuation of alcohol in an alcohol-dependent individual. Patients may present with mild symptoms of tremulousness and agitation or more severe symptoms including withdrawal seizures and delirium tremens. Management revolves around early identification of at-risk individuals and symptom assessment using a validated tool such as the revised Clinical Institute Withdrawal Assessment for Alcohol score. Benzodiazepines remain the mainstay of treatment and can be administered using a front-loading, fixed-dose, or symptom-triggered approach. Long-acting benzodiazepines such as chlordiazepoxide or diazepam are commonly used and may provide a smoother withdrawal than shorter-acting benzodiazepines, but there are no data to support superiority of one benzodiazepine over another. Elderly patients or those with significant liver disease may have increased accumulation and decreased clearance of the long-acting benzodiazepines, and lorazepam or oxazepam may be preferred in these patients. Patients with symptoms refractory to high doses of benzodiazepines may require addition of a rescue medication such as phenobarbital, propofol or dexmedetomidine. Anticonvulsants (carbamazepine, valproate, gabapentin) may have a role in the management of mild to moderate withdrawal. Other medications such as β-antagonists or neuroleptics may offer additional benefit in select patients but should not be used a monotherapy.

  10. Outpatient management of alcohol withdrawal syndrome.

    PubMed

    Muncie, Herbert L; Yasinian, Yasmin; Oge', Linda

    2013-11-01

    Approximately 2% to 9% of patients seen in a family physician's office have alcohol dependence. These patients are at risk of developing alcohol withdrawal syndrome if they abruptly abstain from alcohol use. Alcohol withdrawal syndrome begins six to 24 hours after the last intake of alcohol, and the signs and symptoms include tremors, agitation, nausea, sweating, vomiting, hallucinations, insomnia, tachycardia, hypertension, delirium, and seizures. Treatment aims to minimize symptoms, prevent complications, and facilitate continued abstinence from alcohol. Patients with mild or moderate alcohol withdrawal syndrome can be treated as outpatients, which minimizes expense and allows for less interruption of work and family life. Patients with severe symptoms or who are at high risk of complications should receive inpatient treatment. In addition to supportive therapy, benzodiazepines, either in a fixed-dose or symptom-triggered schedule, are recommended. Medication should be given at the onset of symptoms and continued until symptoms subside. Other medications, including carbamazepine, oxcarbazepine, valproic acid, and gabapentin, have less abuse potential but do not prevent seizures. Typically, physicians should see these patients daily until symptoms subside. Although effective treatment is an initial step in recovery, long-term success depends on facilitating the patient's entry into ongoing treatment.

  11. Severe alcohol withdrawal syndrome: Evolution of care and impact of adjunctive therapy on course and complications of 171 intensive care unit patients.

    PubMed

    Puscas, Mircea; Hasoon, Mohammed; Eechevarria, Carlos; Cooper, Tracy; Tamura, Leslie; Chebbo, Ahmad; W Carlson, Richard

    2016-01-01

    This single site retrospective observational study assessed the evolution of sedation therapy for severe alcohol withdrawal syndrome in the intensive care unit. Patient records for 2 intervals were reviewed: Interval 1, which included 87 intensive care unit patients admitted January 2005 through September 2007, for whom benzodiazedpine monotherapy was utilized; and Interval 2, January 2010 through December 2010, for whom 54 of 84 (64.3%) intensive care unit patients, including all those intubated, received adjunctive agents, including dexmedetomidine or propofol. Clinical management was similar for both intervals, as well as prevalence of alcohol withdrawal syndrome versus total adult hospital admissions and comorbid conditions. Overall, respiratory failure (53 versus 39%), seizures (36 versus 18%), and pneumonia (51 versus 38%) were less frequent during Interval 2 (all p < .05), with lower benzodiazedpine basal dose requirements for those given adjunctive therapy. However, if instances of pneumonia or respiratory failure related to seizures prior to intensive care unit admission are excluded, the prevalence of these complications was similar (p = ns) for Interval 1 and Interval 2. Intensive care unit and hospital length of stay were not altered by adjunctive therapy, which was typically employed for more severely affected patients. High intensity sedation with adjunctive drugs led to few cardiovascular adverse events and may have facilitated management, but did not alter intensive care unit course of severe alcohol withdrawal syndrome.

  12. Alcohol Withdrawal and Cerebellar Mitochondria.

    PubMed

    Jung, Marianna E

    2015-08-01

    Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new

  13. Improving Nursing Knowledge of Alcohol Withdrawal

    PubMed Central

    Berl, Kimberly; Collins, Michelle L.; Melson, Jo; Mooney, Ruth; Muffley, Cheryl; Wright-Glover, Angela

    2015-01-01

    Christiana Care Health System implemented a Care Management Guideline for Alcohol Withdrawal Symptom Management, which provided direction for inpatient screening for alcohol withdrawal risk, assessment, and treatment. Nurses educated on its use expressed confusion with the use of the assessment tools, pharmacokinetics, and pathophysiology of alcohol withdrawal and delirium tremens. Reeducation was provided by nursing professional development specialists. Pre- and postsurveys revealed that nurses were more confident in caring for patients with alcohol withdrawal. (See CE Video, Supplemental Digital Content 1, http://links.lww.com/JNPD/A9) PMID:25816126

  14. Identification and management of alcohol withdrawal syndrome.

    PubMed

    Mirijello, Antonio; D'Angelo, Cristina; Ferrulli, Anna; Vassallo, Gabriele; Antonelli, Mariangela; Caputo, Fabio; Leggio, Lorenzo; Gasbarrini, Antonio; Addolorato, Giovanni

    2015-03-01

    Symptoms of alcohol withdrawal syndrome (AWS) may develop within 6-24 h after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for AWS is with benzodiazepines (BZDs). Among the BZDs, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed-dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as α2-agonists (clonidine and dexmetedomidine) and β-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptic agents can help control hallucinations. Finally, other medications for the treatment for AWS have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin and topiramate. The usefulness of these agents are discussed.

  15. Takotsubo cardiomyopathy triggered by alcohol withdrawal.

    PubMed

    Alexandre, Joakim; Benouda, Leila; Champ-Rigot, Laure; Labombarda, Fabien

    2011-07-01

    Takotsubo cardiomyopathy is a reversible cardiomyopathy frequently precipitated by a sudden emotional or physical stress. The exact physiopathology is still debated and may involve catecholamine-induced myocardial stunning. Alcohol withdrawal is associated with an hyperadrenergic state and may be a period at risk of cardiac events. We report a 56-year-old man with Takotsubo cardiomyopathy triggered by alcohol withdrawal.

  16. Treatment of alcohol withdrawal with gabapentin.

    PubMed

    Bozikas, Vasilis; Petrikis, Petros; Gamvrula, Katerina; Savvidou, Ioanna; Karavatos, Athanasios

    2002-01-01

    Gabapentin is an anticonvulsant agent, also effective in the treatment of mood disorders and anxiety disorders. Three cases of alcohol withdrawal treated with gabapentin are presented. All patients received gabapentin 400 mg tid for 3 days, 400 mg bid for 1 day, and finally 400 mg for 1 day. Withdrawal symptoms subsided and no adverse effects were observed. The possible effectiveness of gabapentin in the treatment of alcohol withdrawal warrants further investigation by systematic and well-designed studies.

  17. Treatment of alcohol withdrawal syndrome with gabapentin.

    PubMed

    Bonnet, U; Banger, M; Leweke, F M; Maschke, M; Kowalski, T; Gastpar, M

    1999-05-01

    Four in-patients with moderate alcohol-withdrawal syndromes benefited from treatment with gabapentin administered in an add-on fashion to clomethiazole. In comparison with the amount of clomethiazole required as estimated using a specially developed score during previous detoxifications of these patients at our hospital, gabapentin (400 mg q.i.d.) clearly reduced the amount of clomethiazole needed now Gabapentin, an anticonvulsant with favorable pharmacokinetic properties and tolerability, and with no known risk of dependence, may therefore be a useful new drug in the treatment of alcohol withdrawal. We believe that the potential value of gabapentin in alcohol withdrawal deserves further controlled studies.

  18. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Withdrawal of fuel alcohol. 19.729 Section 19.729 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU..., Withdrawal, and Transfer of Spirits § 19.729 Withdrawal of fuel alcohol. (a) For each shipment or...

  19. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Withdrawal of fuel alcohol. 19.729 Section 19.729 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU..., Withdrawal, and Transfer of Spirits § 19.729 Withdrawal of fuel alcohol. (a) For each shipment or...

  20. Divalproex in the treatment of alcohol withdrawal.

    PubMed

    Myrick, H; Brady, K T; Malcolm, R

    2000-02-01

    The present study represents an open-label clinical trial comparing treatment with a benzodiazepine (lorazepam) to divalproex in 11 inpatients with uncomplicated alcohol withdrawal syndrome. The trial used the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale. There were no significant differences in demographics or substance use parameters between the divalproex group (n = 6) or the lorazepam group (n = 5). A significant Group x CIWA-Ar score interaction [F(8,72) = 2.57, p < or = .01] was confirmed and further substantiated by a quadratic trend component for the interaction [F(1,9) = 24.9, p < or = .001]. This preliminary study supports further investigation of divalproex in the treatment of alcohol withdrawal.

  1. 27 CFR 19.997 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of fuel alcohol. 19.997 Section 19.997 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... and Transfers § 19.997 Withdrawal of fuel alcohol. For each shipment or other removal of fuel...

  2. Progressive alcohol-induced sperm alterations leading to spermatogenic arrest, which was reversed after alcohol withdrawal.

    PubMed

    Sermondade, Nathalie; Elloumi, Hanène; Berthaut, Isabelle; Mathieu, Emmanuelle; Delarouzière, Vanina; Ravel, Célia; Mandelbaum, Jacqueline

    2010-03-01

    This is a report of a 6-year follow-up of a male patient's semen parameters during heavy chronic alcohol intoxication and after withdrawal. A slowly progressive negative impact of alcohol could be observed: isolated moderate teratozoospermia was firstly noted followed by oligoasthenoteratospermia. Then a severe worsening resulted in cryptozoospermia and ultimately in azoospermia. At this moment, the histological analysis of a testicular biopsy revealed a maturation arrest of the germinal cells at the pachytene stage with no mature sperm cells. Alcohol withdrawal was then obtained, allowing a very fast and drastic improvement of semen characteristics; strictly normal semen parameters were observed after no more than 3 months. Taking into consideration these data, patients should be questioned about their alcohol intake before assisted reproductive technology and should be informed about this adverse effect. Moreover, this case report emphasizes how quickly benefits can be obtained after withdrawal, even in the case of heavy chronic alcohol intake.

  3. Severe Relapsing Clozapine-Withdrawal Catatonia

    PubMed Central

    Shahrour, Tarek; Siddiq, Muez; Ghalib, Saad

    2015-01-01

    Catatonia as a clozapine-withdrawal syndrome has only been documented in the medical literature as case reports. We are reporting a case in which a 32-year-old man develops a catatonic state upon withdrawal of clozapine. The state was quite severe and needed ICU admission. The course was chronic and intermittent which we think was caused by the poor adherence to antipsychotics. The importance of identifying such cases early is underlined. PMID:26788394

  4. Alcohol withdrawal syndrome--an auto-immune disease? A neuroimmunologic model for pathogenesis of alcohol withdrawal symptoms.

    PubMed

    Schubert, S

    1990-08-01

    A neuroimmunologic model of alcohol withdrawal symptoms is developed according to which these may be considered as an idiopathic auto-immune disease. During the alcohol abuse period of non-addicts, homeostasis may alter pathologically by gradual adaptation of the organism: auto-sensitisation develops and finally leads to the breakdown of auto-immune tolerance of the structural modifications set by alcohol withdrawal. The immunosystem regards the existing assimilation of alcohol as self, the withdrawal of alcohol as non-self. Alcohol withdrawal may be considered as an acknowledged physical stressor, and physical stressors as potential triggers of auto-immune diseases. Some so-called alcohol-induced diseases may originate in the pathogenic effects of preceding auto-immune responses to repeated alcohol withdrawals. Neuroimmunologic preconditions of potential auto-immune diseases exactly fit the alcohol withdrawal situation. Neuroimmunologic diseases themselves show close analogies respectively to alcohol withdrawal symptoms as well as to some alcohol-induced diseases. The myelin basis protein is assumed to be a potential auto-allergen. Finally withdrawal symptoms being the expression of physical dependence on alcohol, the model may highlight the very nature of physical dependence.

  5. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Withdrawal of fuel alcohol. 19.729 Section 19.729 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Distilled Spirits for Fuel Use Rules for...

  6. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Withdrawal of fuel alcohol. 19.729 Section 19.729 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Distilled Spirits for Fuel Use Rules for...

  7. Acute coronary ischemia during alcohol withdrawal: a case report

    PubMed Central

    2011-01-01

    Introduction The potential of alcohol withdrawal to cause acute coronary events is an area that needs the urgent attention of clinicians and researchers. Case presentation We report the case of a 52-year-old heavy-alcohol-using Sri Lankan man who developed electocardiogram changes suggestive of an acute coronary event during alcohol withdrawal. Despite the patient being asymptomatic, subsequent echocardiogram showed evidence of ischemic myocardial dysfunction. We review the literature on precipitation of myocardial ischemia during alcohol withdrawal and propose possible mechanisms. Conclusions Alcohol withdrawal is a commonly observed phenomenon in hospitals. However, the number of cases reported in the literature of acute coronary events occurring during withdrawal is few. Many cases of acute ischemia or sudden cardiac deaths may be attributed to other well known complications of delirium tremens. This is an area needing the urgent attention of clinicians and epidemiologists. PMID:21838872

  8. S100B and homocysteine in the acute alcohol withdrawal syndrome.

    PubMed

    Wedekind, Dirk; Neumann, Karolin; Falkai, Peter; Malchow, Berend; Engel, Kirsten Rita; Jamrozinski, Katja; Havemann-Reinecke, Ursula

    2011-03-01

    Elevations of serum homocysteine levels are a consistent finding in alcohol addiction. Serum S100B levels are altered in different neuropsychiatric disorders but not well investigated in alcohol withdrawal syndromes. Because of the close connection of S100B to ACTH and glutamate secretion that both are involved in neurodegeneration and symptoms of alcoholism the relationship of S100B and homocysteine to acute withdrawal variables has been examined. A total of 22 male and 9 female inpatients (mean age 46.9 ± 9.7 years) with an ICD-10 diagnosis of alcohol addiction without relevant affective comorbidity were examined on admission and after 24, 48, and 120 h during withdrawal. S100B and homocysteine levels in serum were collected, and severity of withdrawal symptoms (AWS-scale), applied withdrawal medication, initial serum ethanol levels and duration of addiction were recorded. Serum S100B and homocysteine levels declined significantly (P < .05) over time. Both levels declined with withdrawal syndrome severity. Females showed a trend to a more intense decline in serum S100B levels compared to males at day 5 (P = .06). Homocysteine levels displayed a negative relationship to applied amount of clomethiazole (P < .05) and correlated with age of onset of addiction. No withdrawal seizures were recorded during the trial. As it is known for homocysteine, S100B revealed to decline rapidly over withdrawal treatment in alcoholism. This effect is more pronounced in female patients. S100B could be of relevance in the neurobiology of alcohol withdrawal syndromes. It may be indirectly related to the level of stress level or glutamatergic activity during alcohol withdrawal.

  9. Anticonvulsants for the treatment of alcohol withdrawal syndrome and alcohol use disorders.

    PubMed

    Hammond, Christopher J; Niciu, Mark J; Drew, Shannon; Arias, Albert J

    2015-04-01

    Alcoholic patients suffer from harmful allostatic neuroplastic changes in the brain causing an acute withdrawal syndrome upon cessation of drinking followed by a protracted abstinence syndrome and an increased risk of relapse to heavy drinking. Benzodiazepines have long been the treatment of choice for detoxifying patients and managing alcohol withdrawal syndrome (AWS). Non-benzodiazepine anticonvulsants (NBACs) are increasingly being used both for alcohol withdrawal management and for ongoing outpatient treatment of alcohol dependence, with the goal of either abstinence or harm reduction. This expert narrative review summarizes the scientific basis and clinical evidence supporting the use of NBACs in treating AWS and for reducing harmful drinking patterns. There is less evidence in support of NBAC therapy for AWS, with few placebo-controlled trials. Carbamazepine and gabapentin appear to be the most promising adjunctive treatments for AWS, and they may be useful as monotherapy in select cases, especially in outpatient settings and for the treatment of mild-to-moderate low-risk patients with the AWS. The body of evidence supporting the use of the NBACs for reducing harmful drinking in the outpatient setting is stronger. Topiramate appears to have a robust effect on reducing harmful drinking in alcoholics. Gabapentin is a potentially efficacious treatment for reducing the risk of relapse to harmful drinking patterns in outpatient management of alcoholism. Gabapentin's ease of use, rapid titration, good tolerability, and efficacy in both the withdrawal and chronic phases of treatment make it particularly appealing. In summary, several NBACs appear to be beneficial in treating AWS and alcohol use disorders.

  10. MPDZ EXPRESSION IN THE CAUDOLATERAL SUBSTANTIA NIGRA PARS RETICULATA IS CRUCIALLY INVOLVED IN ALCOHOL WITHDRAWAL

    PubMed Central

    Kruse, L.C.; Walter, N.A.R.; Buck, K.J.

    2014-01-01

    Association studies implicate the multiple PDZ domain protein (MUPP1/MPDZ) gene in risk for alcoholism in humans and alcohol withdrawal in mice. Although manipulation of the Mpdz gene by homologous recombination and bacterial artificial chromosome transgenesis has suggested that its expression affects alcohol withdrawal risk, the potential confounding effects of linked genes and developmental compensation currently limit interpretation. Here, using RNA interference, we directly test the impact of Mpdz expression on alcohol withdrawal severity and provide brain regional mechanistic information. Lentiviral-mediated delivery of Mpdz short hairpin RNA (shRNA) to the caudolateral substantia nigra pars reticulata significantly reduces Mpdz expression and exacerbates alcohol withdrawal convulsions compared to control mice delivered a scrambled shRNA. Neither baseline nor pentylenetetrazol enhanced convulsions differed between Mpdz shRNA and control animals, indicating that Mpdz expression in the caudolateral substantia nigra pars reticulata does not generally affect seizure susceptibility. To our knowledge, these represent the first in vivo Mpdz RNA interference analyses, and provide the first direct evidence that Mpdz expression impacts behavior. Our results confirm that Mpdz is a quantitative trait gene for alcohol withdrawal and demonstrate that its expression in the caudolateral substantia nigra pars reticulata is crucially involved in risk for alcohol withdrawal. PMID:25109596

  11. A quantitative evaluation of alcohol withdrawal tremors.

    PubMed

    Aarabi, Parham; Norouzi, Narges; Dear, Taylor; Carver, Sally; Bromberg, Simon; Gray, Sara; Kahan, Mel; Borgundvaag, Bjug

    2015-01-01

    This paper evaluates the relation between Alcohol Withdrawal Syndrome tremors in the left and right hands of patients. By analyzing 122 recordings from 61 patients in emergency departments, we found a weak relationship between the left and right hand tremor frequencies (correlation coefficient of 0.63). We found a much stronger relationship between the expert physician tremor ratings (on CIWA-Ar 0-7 scale) of the two hands, with a correlation coefficient of 0.923. Next, using a smartphone to collect the tremor data and using a previously developed model for obtaining estimated tremor ratings, we also found a strong correlation (correlation coefficient of 0.852) between the estimates of each hand. Finally, we evaluated different methods of combining the data from the two hands for obtaining a single tremor rating estimate, and found that simply averaging the tremor ratings of the two hands results in the lowest tremor estimate error (an RMSE of 0.977). Looking at the frequency dependence of this error, we found that higher frequency tremors had a much lower estimation error (an RMSE of 1.102 for tremors with frequencies in the 3-6Hz range as compared to 0.625 for tremors with frequencies in the 7-10Hz range).

  12. K(Ca)2 channels: novel therapeutic targets for treating alcohol withdrawal and escalation of alcohol consumption.

    PubMed

    Mulholland, Patrick J

    2012-06-01

    Small-conductance, calcium-activated potassium (K(Ca)2) channels influence neuronal firing properties, intrinsic excitability, and NMDA receptor-dependent synaptic responses and plasticity. In this mini-review, we discuss new evidence that chronic alcohol-associated plasticity critically involves K(Ca)2 channels in hippocampus, ventral tegmental area, and nucleus accumbens. K(Ca)2 channel activity can modulate the magnitude of excitation of midbrain dopamine neurons induced by acute alcohol exposure. Emerging evidence indicates that K(Ca)2 channels regulate neuroadaptations to chronic alcohol that contribute to withdrawal hyperexcitability and escalation of voluntary alcohol consumption. Restoring K(Ca)2 channel activity can attenuate the severity of the alcohol withdrawal syndrome in vivo and withdrawal-associated neurotoxicity in vitro. Pharmacological modulation of K(Ca)2 channels can bi-directionally influence drinking behavior in rat and mouse models of voluntary alcohol consumption. Collectively, these studies using various rodent models have clearly indicated a central role for K(Ca)2 channels in the neuroplasticity of chronic alcohol exposure. In addition, accumulating evidence suggests that K(Ca)2 channels are a novel therapeutic target to alleviate the symptoms of alcohol withdrawal and reduce high amounts of alcohol drinking.

  13. Ethosuximide reduces electrographical and behavioral correlates of alcohol withdrawal seizure in DBA/2J mice

    PubMed Central

    Riegle, Melissa A.; Masicampo, Melissa M.; Caulder, Erin H.; Godwin, Dwayne W.

    2015-01-01

    Chronic alcohol abuse depresses the nervous system and, upon cessation, rebound hyperexcitability can result in withdrawal seizure. Withdrawal symptoms, including seizures, may drive individuals to relapse, thus representing a significant barrier to recovery. Our lab previously identified an upregulation of the thalamic T-type calcium (T channel) isoform CaV3.2 as a potential contributor to the generation and propagation of seizures in a model of withdrawal. In the present study, we examined whether ethosuximide (ETX), a T-channel antagonist, could decrease the severity of ethanol withdrawal seizures by evaluating electrographical and behavioral correlates of seizure activity. DBA/2J mice were exposed to an intermittent ethanol exposure paradigm. Mice were treated with saline or ETX in each withdrawal period, and cortical EEG activity was recorded to determine seizure severity. We observed a progression in seizure activity with each successive withdrawal period. Treatment with ETX reduced ethanol withdrawal-induced spike and wave discharges (SWDs), in terms of absolute number, duration of events, and contribution to EEG power reduction in the 6–10 Hz frequency range. We also evaluated the effects of ETX on handling-induced convulsions. Overall, we observed a decrease in handling-induced convulsion severity in mice treated with ETX. Our findings suggest that ETX may be a useful pharmacological agent for studies of alcohol withdrawal and treatment of resulting seizures. PMID:24933286

  14. Time-frequency visualization of alcohol withdrawal tremors.

    PubMed

    Carver, S; Norouzi, N; Bromberg, S; Gray, S; Kahan, M; Aarabi, P; Borgundvaag, B

    2014-01-01

    In this paper, we propose a signal processing method of assessing the severity tremors caused by alcohol withdrawal (AW) syndrome. We have developed an iOS application to calculate the Clinical Institute Withdrawal Assessment (CIWA) score which captures iPod movements using the built-in accelerometer in order to reliably estimate the tremor severity component of the score. We report on the characteristics of AW tremor, the accuracy of electronic assessment of tremor compared to expert clinician assessment, and the potential for using signal processing assessment to differentiate factitious from real tremor in patients seen in the emergency department, as well as in nurses mimicking a tremor. Our preliminary results are based on 84 recordings from 61 subjects (49 patients, 12 nurses). In general we found a linear relationship between energy measured by the accelerometer (in the 4.4-10 Hz range) and the expert rating of tremor severity. Additionally, we demonstrate that 75% of the recordings from patients with actual AW syndrome had a mean peak frequency higher than 7 Hz whereas only 17% of the nurses' factitious tremors were above 7 Hz, suggesting that tremor above 7 Hz could be a potential discriminator of real versus factitious tremors.

  15. Pharmacological evaluation of alcohol withdrawal-induced inhibition of exploratory behaviour and supersensitivity to harmine-induced tremor.

    PubMed

    Meert, T F

    1994-01-01

    Rats given a liquid diet containing 10% (v/v) alcohol consume high quantities of alcohol. Within 8 hr after cessation of the alcohol intake, the animals will show alcohol-withdrawal reactions including a supersensitivity to harmine-induced tremor and an inhibition of exploratory behaviour in a neutral environment. Several drugs can overcome one or more of these alcohol-withdrawal reactions. A reduction of the alcohol withdrawal-induced inhibition of exploration, in terms of both the number of transits into the open field and the time spent in the open field, was obtained with chlordiazepoxide, ritanserin, mianserin and propranolol. Of these four compounds, propranolol and mianserin were also active against the supersensitivity to both 5.00 and 10.00 mg/kg harmine-induced tremor. Chlordiazepoxide and ritanserin were only active against 5.00 mg/kg harmine. Other compounds that reversed the supersensitivity to harmine-induced tremor during alcohol withdrawal included buspirone, fluoxetine, haloperidol, clonidine, flunarizine and baclofen. Very limited effects on both alcohol-withdrawal reactions were observed with ondansetron, nimodipine and MK-801. Risperidone and SCH 23390 were inactive. These results demonstrate that some alcohol withdrawal reactions can be studied in a systematic way and that various pharmacological agents can differentially interact with these alcohol withdrawal reactions.

  16. Evolution of Metabolic Abnormalities in Alcoholic Patients during Withdrawal

    PubMed Central

    Vandemergel, X.; Simon, F.

    2015-01-01

    Chronic alcohol intoxication is accompanied by metabolic abnormalities. Evolution during the early withdrawal period has been poorly investigated. The aim of this study was to determine the evolution of metabolic parameters during alcohol withdrawal. Patients and Methods. Thirty-three patients admitted in our department for alcohol withdrawal were prospectively included. Results. Baseline hypophosphatemia was found in 24% of cases. FEPO4 was reduced from 14.2 ± 9% at baseline to 7.3 ± 4.2% at day 3 (P < 0.01). FEPO4 inversely correlated with albuminemia (rs = −0.41, P = 0.01). CPK level was 124 ± 104 IU/L in men and 145 ± 85 IU/L in women (nl < 308 and <192 IU/L, resp.), 7% and 28% of patients having a CPK level >nl, respectively. No correlation was found between the sodium and CPK levels (P = 0.75) nor between the CPK level and the amount of alcohol ingested (rs = 0.084, P = 0.097). Baseline urate level was elevated and returned to normal after three days. Baseline magnesium concentration was normal and stable over time. Conclusion. Chronic alcohol intoxication was accompanied by phosphaturia, rapidly reversible after alcohol withdrawal and inversely correlated with albuminemia, slight hyponatremia, low levels of 25 hydroxy vitamin D, elevated CPK level in about 30% of women, and hyperuricemia with rapid normalization. PMID:25810945

  17. [Alcohol withdrawal syndrome showing various progress: A case report].

    PubMed

    Nakata, Chihiro; Nara, Keinosuke; Kinoshita, Fumihiko; Kikuchi, Ken; Asai, Masahiro

    2015-06-01

    We experienced a case showing various psychotic symptoms following cessation of alcohol consumption. The symptoms included depressive state, delusion, confusion, psychomotor excitement and delirium, all of which disappeared in about two months. At first, we regarded all the symptoms as alcoholic hallucinosis, by a clinical standpoint, in spite of no auditory hallucination in this case. However, taking the overall clinical course into consideration, withdrawal syndrome could have been affected by some factors. One of the possibilities is that delusion might have been induced by aripiprazole. There still may be some other unknown influential factors on withdrawal, which are indicated by previous papers.

  18. A DOUBLE BLIND TRIAL OF GABAPENTIN VS. LORAZEPAM IN THE TREATMENT OF ALCOHOL WITHDRAWAL

    PubMed Central

    Myrick, Hugh; Malcolm, Robert; Randall, Patrick K.; Boyle, Elizabeth; Anton, Raymond F.; Becker, Howard C.; Randall, Carrie L.

    2009-01-01

    Introduction Some anticonvulsants ameliorate signs and symptoms of alcohol withdrawal, but have an unacceptable side effect burden. Among the advantages of using anticonvulsant agents in this capacity is their purported lack of interaction with alcohol that could increase psychomotor deficits, increase cognitive impairment, or increase intoxication. The aim of the current study was to evaluate alcohol use and symptom reduction of gabapentin as compared to lorazepam in the treatment of alcohol withdrawal in a double-blinded randomized clinical trial. Methods One hundred individuals seeking outpatient treatment of alcohol withdrawal with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) ratings ≥10 were randomized to double-blind treatment with two doses of gabapentin (900 mg tapering to 600 mg or 1200 tapering to 800 mg) or lorazepam (6 mg tapering to 4 mg) for four days. Severity of alcohol withdrawal was measured by the CIWA-Ar on days 1-4 of treatment and on days 5, 7 and 12 post-treatment and alcohol use monitored by verbal report and breath alcohol levels Results CIWA-Ar scores decreased over time in all groups; high-dose gabapentin was statistically superior but clinically similar to lorazepam (p=0.009). During treatment, lorazepam-treated participants had higher probabilities of drinking on the first day of dose decrease (day 2) and the second day off medication (day 6) as compared to gabapentin-treated participants (p=.0002). Post-treatment, gabapentin-treated participants had less probability of drinking during the follow-up post-treatment period (probability=.2 for 900 mg and probability=.3 for 1200mg) compared to the lorazepam-treated participants (probability=.55). The gabapentin groups also had less craving, anxiety, and sedation compared to lorazepam. Conclusions Gabapentin was well tolerated and effectively diminished the symptoms of alcohol withdrawal in our population especially at the higher target dose (1200mg) used in this

  19. Investigation of allyphenyline efficacy in the treatment of alcohol withdrawal symptoms.

    PubMed

    Ubaldi, Massimo; Del Bello, Fabio; Domi, Esi; Pigini, Maria; Nasuti, Cinzia

    2015-08-05

    We have recently demonstrated that allyphenyline, behaving as α2C-adrenoceptor/serotonin 5-HT1A receptor agonist and α2A-adrenoceptor antagonist, in mice enhanced morphine analgesia, attenuated morphine withdrawal symptoms, showed significant antidepressant-like activity and was devoid of sedative side effects. Opioid and alcohol withdrawal shares several common neurobiological and molecular mechanisms. Therefore, in this study we expanded our analysis of the pharmacological properties of allyphenyline by investigating its ability to prevent the expression of somatic withdrawal signs, anxiety-like behavior and hyperlocomotion associated with chronic ethanol intoxication. Rats were subjected to induction of ethanol dependence via repeated daily intragastric ethanol (20%) administration for 4 consecutive days. Twelve hours after the last alcohol administration, somatic alcohol withdrawal signs were scored. Results revealed a significant expression of physical withdrawal signs that were not affected by intraperitoneal (i.p.) administration of allyphenyline at the doses of 0.05, 0.275 and 0.5 mg/kg. In contrast, allyphenyline (0.05 and 0.275 mg/kg i.p.) significantly reduced hyperanxiety-like behavior observed 6 days after alcohol intoxication as measured using the defensive burying test. Allyphenyline also reduced open field hyperlocomotor activity associated with alcohol withdrawal. Notably, the anxiolytic effect of the compound, as well as the already reported antidepressant action, was observed at very low doses, suggesting the involvement of its α2C-adrenoceptor/serotonin 5-HT1A receptor agonism. Therefore, the present investigation suggests that allyphenyline might represent an interesting pharmacological tool to investigate the potential of compounds exhibiting α2C-adrenoceptor/serotonin 5-HT1A receptor agonism and α2A-adrenoceptor antagonism in the treatment of hyperanxiety and hyperlocomotion occurring during alcohol withdrawal in dependent subjects.

  20. Psychosocial withdrawal characteristics of nicotine compared with alcohol and caffeine.

    PubMed

    Miyata, Hisatsugu; Hironaka, Naoyuki; Takada, Kohji; Miyasato, Katsumasa; Nakamura, Koichi; Yanagita, Tomoji

    2008-10-01

    The purpose of the present study was to observe the psychosocial characteristics of withdrawal from cigarette smoking in comparison with those from caffeine (CAF) and alcoholic (ALC) beverage withdrawal. Twenty-seven healthy volunteers at a medial level of dependence on both cigarettes (nicotine, NCT) and either CAF or ALC, as judged by the DSM-IV-TR criteria for substance dependence, participated in this study. The participants were required to abstain from smoking and either CAF or ALC for 7 days, each one after another, with a 7-day interval. The order of abstinence was counterbalanced among the participants. Psychosocial parameters, including a desire for substances, social activity function, well-being, withdrawal symptoms, and vital signs, were assessed during the withdrawal periods. The study protocol was approved by the Jikei University Review Board. The results indicated that there were no differences in the maximum level of desire for a substance and the influence on social activity function between NCT and other substances during the withdrawal periods. As for withdrawal symptoms, NCT caused a more intensive degree of irritability than CAF or ALC, and a more intensive degree of difficulty concentrating and restlessness than did withdrawal from ALC. However, the subjective well-being questionnaire indicated no differences in these symptoms between NCT and other substances. The present results suggest that there are no significant differences in psychosocial manifestations regarding the difficulty in abstaining from NCT, CAF, and ALC.

  1. Central Pontine Myelinolysis Induced by Alcohol Withdrawal: A Case Report

    PubMed Central

    2017-01-01

    Central pontine myelinolysis (CPM) is a demyelinating disorder characterized by the loss of myelin in the center of the basis pons, and is mainly caused by the rapid correction of hyponatremia. We report the case of a young woman who presented with gait disturbance and alcohol withdrawal, and who was eventually diagnosed with CPM. Generally, the cause and pathogenesis of CPM in chronic alcoholics remain unclear. In this cases, the CPM may be unrelated to hyponatremia or its correction. However, it is possible that the osmotic pressure changes due to refeeding syndrome after alcohol withdrawal was the likely cause in this case. This case illustrates the need for avoiding hasty, and possibly incomplete diagnoses, and performing more intensive test procedures to ensure a correct diagnosis. PMID:28289647

  2. Environmental enrichment may protect against neural and behavioural damage caused by withdrawal from chronic alcohol intake.

    PubMed

    Nobre, Manoel Jorge

    2016-12-01

    Exposure to stress and prolonged exposure to alcohol leads to neuronal damages in several brain regions, being the medial prefrontal cortex (mPFC) one of the most affected. These changes presumably reduce the ability of the organism to cope with these stimuli and may underlie a series of maladaptive behaviours among which include drug addiction and withdrawal. Drug-addicted individuals show a pattern of behavior similar to patients with lesions of the mPFC. This impairment in the decision-making could be one of the mechanisms responsible for the transition from the casual to compulsive drug use. The environmental enrichment (EE) has a protective effect on the neural and cognitive impairments induced by psychoactive drugs, including ethyl alcohol. The present study aims to determine the influence of withdrawal from intermittent long-term alcohol exposure on alcohol preference, emotional reactivity and neural aspects of early isolated or grouped reared rats kept under standard or complex environments and the influence of social isolation on these measures, as well. Our results point out new insights on this matter showing that the EE can attenuate the adverse effects of withdrawal and social isolation on rat's behavior. This effect is probably due to its protective action on the mPFC integrity, including the cingulate area 1 (Cg1), and the prelimbic (PrL) and infralimbic cortex (IL), what could account for the absence of changes in the emotional reactivity in EE alcohol withdrawal rats. We argue that morphological changes at these cortical levels can afford the emotional, cognitive and behavioural dysregulations verified following withdrawal from chronic alcohol intake.

  3. Childhood neglect and increased withdrawal and depressive severity in crack cocaine users during early abstinence.

    PubMed

    Francke, Ingrid D'avila; Viola, Thiago Wendt; Tractenberg, Saulo Gantes; Grassi-Oliveira, Rodrigo

    2013-10-01

    Studies have shown that environmental factors, such as exposure to childhood maltreatment, might shift the course of addiction. Little is known, however, about whether childhood physical neglect (PN) influences the severity of withdrawal and depressive symptoms during the detoxification period. This is a 3 weeks follow-up study. The participants were divided into 2 groups: those with a history of PN (PN+) (n=32) and those without a history of PN (PN-) (n=48). Clinical variables were assessed with the SCID-I, BDI-II, Childhood Trauma Questionnaire, Addiction Severity Index and Cocaine Selective Severity Assessment. Depressive symptom assessments were repeated at three time points. Withdrawal symptom assessments were repeated at five different points following detoxification. A repeated measures analysis of covariance indicated that the PN+ group exhibited a significantly lower reduction in the severity of withdrawal symptoms compared to the PN- group (p<0.05). Post hoc analyses showed that after 12 days of treatment, the severity of withdrawal symptoms in the PN+ group did not decrease in the same level as was observed in the PN- group. Moreover, a strong correlation was found between the severity of depression and the intensity of the abstinence symptoms during treatment. Patients who reported more depressive symptoms also exhibited more severe withdrawal symptoms. The ASI-6 indicated higher severity problems related to alcohol and psychiatric disorders in the PN+ groups. Our data support the role of childhood PN in the contingencies of the detoxification process of crack cocaine-dependent women.

  4. Adrenergic Inhibition with Dexmedetomidine to Treat Stress Cardiomyopathy during Alcohol Withdrawal: A Case Report and Literature Review

    PubMed Central

    Harris, Zachary M.; Alonso, Alvaro; Kennedy, Thomas P.

    2016-01-01

    Stress (Takotsubo) cardiomyopathy is a form of reversible left ventricular dysfunction with a heightened risk of ventricular arrhythmia thought to be caused by high circulating catecholamines. We report a case of stress cardiomyopathy that developed during severe alcohol withdrawal successfully treated with dexmedetomidine. The case involves a 53-year-old man with a significant history of alcohol abuse who presented to a teaching hospital with new-onset seizures. His symptoms of acute alcohol withdrawal were initially treated with benzodiazepines, but the patient later developed hypotension, and stress cardiomyopathy was suspected based on ECG and echocardiographic findings. Adjunctive treatment with the alpha-2-adrenergic agonist, dexmedetomidine, was initiated to curtail excessive sympathetic outflow of the withdrawal syndrome, thereby targeting the presumed pathophysiology of the cardiomyopathy. Significant clinical improvement was observed within one day of initiation of dexmedetomidine. These findings are consistent with other reports suggesting that sympathetic dysregulation during alcohol withdrawal produces ideal pathobiology for stress cardiomyopathy and leads to ventricular arrhythmogenicity. Stress cardiomyopathy should be recognized as a complication of alcohol withdrawal that significantly increases cardiac-related mortality. By helping to correct autonomic dysregulation of the withdrawal syndrome, dexmedetomidine may be useful in the treatment of stress-induced cardiomyopathy. PMID:27006838

  5. Adrenergic Inhibition with Dexmedetomidine to Treat Stress Cardiomyopathy during Alcohol Withdrawal: A Case Report and Literature Review.

    PubMed

    Harris, Zachary M; Alonso, Alvaro; Kennedy, Thomas P

    2016-01-01

    Stress (Takotsubo) cardiomyopathy is a form of reversible left ventricular dysfunction with a heightened risk of ventricular arrhythmia thought to be caused by high circulating catecholamines. We report a case of stress cardiomyopathy that developed during severe alcohol withdrawal successfully treated with dexmedetomidine. The case involves a 53-year-old man with a significant history of alcohol abuse who presented to a teaching hospital with new-onset seizures. His symptoms of acute alcohol withdrawal were initially treated with benzodiazepines, but the patient later developed hypotension, and stress cardiomyopathy was suspected based on ECG and echocardiographic findings. Adjunctive treatment with the alpha-2-adrenergic agonist, dexmedetomidine, was initiated to curtail excessive sympathetic outflow of the withdrawal syndrome, thereby targeting the presumed pathophysiology of the cardiomyopathy. Significant clinical improvement was observed within one day of initiation of dexmedetomidine. These findings are consistent with other reports suggesting that sympathetic dysregulation during alcohol withdrawal produces ideal pathobiology for stress cardiomyopathy and leads to ventricular arrhythmogenicity. Stress cardiomyopathy should be recognized as a complication of alcohol withdrawal that significantly increases cardiac-related mortality. By helping to correct autonomic dysregulation of the withdrawal syndrome, dexmedetomidine may be useful in the treatment of stress-induced cardiomyopathy.

  6. Altered voltage-gated calcium channels in rat inferior colliculus neurons contribute to alcohol withdrawal seizures.

    PubMed

    N'Gouemo, Prosper

    2015-08-01

    We have previously reported that enhanced susceptibility to alcohol withdrawal seizures (AWS) parallels the enhancement of the current density of high-threshold voltage-gated Ca(2+) (CaV) channels in rat inferior colliculus (IC) neurons. However, whether this increased current density is a cause or consequence of AWS is unclear. Here, I report changes in the current density of CaV channels in IC neurons during the course of alcohol withdrawal and the potential anticonvulsant effect of intra-IC infusions of L- and P-type CaV channel antagonists. Whole-cell currents were activated by depolarizing pulses using barium as the charge carrier. Currents and seizure susceptibility were evaluated in control animals 3h after alcohol intoxication, as well as 3h (before AWS), 24h (when AWS susceptibility is maximal), and 48h (when AWS susceptibility is no longer present) after alcohol withdrawal. Nifedipine, nimodipine (L-type antagonists) or ω-agatoxin TK (P-type antagonist) were infused intra-IC to probe the role of CaV channels in the pathogenesis of AWS. CaV current density and conductance in IC neurons were significantly increased 3 and 24h after alcohol withdrawal compared with the control group or the group tested 3h following ethanol intoxication. Blockade of L-type CaV channels within the IC completely suppressed AWS, and inhibition of P-type channels reduced AWS severity. These findings suggest that the enhancement of CaV currents in IC neurons occurs prior to AWS onset and that alterations in L- and P-type CaV channels in these neurons may underlie the pathogenesis of AWS.

  7. Infections in severe alcoholic hepatitis

    PubMed Central

    Karakike, Eleni; Moreno, Christophe; Gustot, Thierry

    2017-01-01

    Severe alcoholic hepatitis (sAH), defined by a modified discriminant function ≥32, is the most severe form of alcohol-induced liver disease and is associated with a 1-month mortality rate of around 30%. Corticosteroid treatment remains the only therapeutic option that improves short-term survival. Infectious complications, occurring in approximately 50% of patients, are the main causes of death, even in patients who benefit from corticosteroids. Liver failure, recent alcohol consumption and immunosuppressive drugs contribute to this infectious risk. Although infection is a well-described feature of cirrhosis, little is known about the characteristics of infections in sAH. Infection is mainly of bacterial origin and frequently affects the respiratory tract. Pathogens classically observed in cirrhosis, such as gram-negative bacilli, are frequently involved, but opportunistic pathogens, such as fungi (Aspergillus fumigatus, Pneumocystis jirovecii) or viruses (Cytomegalovirus, Herpes simplex) may appear, mainly related to corticosteroid treatment. A high level of suspicion with systematic screening and prompt, adequate treatment are warranted to improve outcomes in these patients. Prophylactic strategies in this high-risk population should be assessed in well-designed trials. PMID:28243035

  8. Withdrawal severity after chronic intermittent ethanol in inbred mouse strains

    PubMed Central

    Metten, Pamela; Sorensen, Michelle L.; Cameron, Andy Jade; Yu, Chia-Hua; Crabbe, John C.

    2010-01-01

    Background To study withdrawal, ethanol is usually administered chronically without interruption. However, interest has recurred in models of episodic exposure. Increasing evidence suggests that chronic intermittent exposure to ethanol leads to a sensitization effect in both withdrawal severity and in ethanol consumption. The goal of the present study was to examine mouse inbred strain differences in withdrawal severity following chronic intermittent exposure using the handling induced convulsion as the behavioral endpoint. We also sought to compare the withdrawal responses of inbred strains across acute, chronic continuous, and chronic intermittent exposure regimens. Methods Male mice from 15 standard inbred strains were exposed to ethanol vapor for 16 hours each day for 3 days and removed to an air chamber during the intervening 8 hours. Mice in the control groups were handled the same, except that they were exposed only to air. Daily blood ethanol concentrations were averaged for each mouse to estimate total dose of ethanol experienced. Results Across strains, mice had an average daily blood ethanol concentration (BEC) of 1.45 ± 0.02 mg/ml and we restricted the range of this value to 1.00 to 2.00 mg/ml. To evaluate strain differences, we divided data into two dose groups based on BEC, Low Dose (1.29 ± 0.1 mg/ml) and High Dose (1.71 ± 0.02 mg/ml). After the third inhalation exposure, ethanol- and air-exposed groups were tested hourly for handling-induced convulsions for 10 hr and at hr 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of air control values) in both dose groups. Conclusion The chronic intermittent exposure paradigm is sufficient to elicit differential withdrawal responses across nearly all strains. Data from the High Dose groups correlated well with withdrawal data derived from prior acute (single high dose) and chronic continuous (for 72 hrs) ethanol withdrawal studies, supporting the influence of common

  9. Dissociating Motivational From Physiological Withdrawal in Alcohol Dependence: Role of Central Amygdala κ-Opioid Receptors

    PubMed Central

    Kissler, Jessica L; Walker, Brendan M

    2016-01-01

    Chronic intermittent alcohol vapor exposure leads to increased dynorphin (DYN) A-like peptide expression and heightened kappa-opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA) and these neuroadaptive responses differentiate alcohol-dependent from non-dependent phenotypes. Important for therapeutic development efforts is understanding the nature of the stimulus that drives dependence-like phenotypes such as escalated alcohol self-administration. Accordingly, the present study examined the impact of intra-CeA KOR antagonism on escalated operant alcohol self-administration and physiological withdrawal symptoms during acute withdrawal and protracted abstinence in rats previously exposed to chronic intermittent alcohol vapor. Following operant training, rats were implanted with intra-CeA guide cannula and exposed to long-term intermittent alcohol vapor exposure that resulted in escalated alcohol self-administration and elevated physiological withdrawal signs during acute withdrawal. Animals received intra-CeA infusions of the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 2, 4, or 6 μg) prior to operant alcohol self-administration sessions and physiological withdrawal assessment during acute withdrawal and protracted abstinence. The results indicated that site-specific KOR antagonism in the CeA ameliorated escalated alcohol self-administration during both acute withdrawal and protracted abstinence test sessions, whereas KOR antagonism had no effect on physiological withdrawal scores at either time point. These results dissociate escalated alcohol self-administration from physiological withdrawal symptoms in relation to KOR signaling in the CeA and help clarify the nature of the stimulus that drives escalated alcohol self-administration during acute withdrawal and protracted abstinence. PMID:26105136

  10. Treatment of acute alcohol withdrawal with gabapentin: results from a controlled two-center trial.

    PubMed

    Bonnet, Udo; Banger, Markus; Leweke, F Markus; Specka, Michael; Müller, Bernhard W; Hashemi, Thilo; Nyhuis, Peter W; Kutscher, Sven; Burtscheidt, Wilhelm; Gastpar, Markus

    2003-10-01

    A few case reports and data from animal experiments point to a possible efficacy of gabapentin (GP) in the treatment of alcohol withdrawal syndrome (AWS). Because of ethical considerations, the efficacy of GP in acute AWS was tested in an add-on fashion to clomethiazole (CLO). Given that the symptom-triggered amount of CLO required to limit AWS within the first 24 hours is related to the severity of AWS, we tested this amount of CLO during placebo (P) or GP (400 mg qid) under double blind, randomized conditions. Sixty-one patients (P = 29/GP = 32) suffering from alcohol dependence (ICD-10) and without any other psychiatric condition or psychotropic medication were included. The groups were not significantly different in baseline characteristics (eg, demographic data, severity of AWS). Both ITT and completer analyses revealed no significant differences between the groups considering the primary effectiveness measure: amount of CLO required in the first 24 hours (P = 6.1 +/- 5.4/GP = 6.2 +/- 4.7 capsules). In addition, premature discontinuations (P = 3/GP = 2) and decreases in Mainz Alcohol Withdrawal Scores were not significantly different in the first 48 hours of AWS (secondary effectiveness measures). Tolerability of combined CLO/GP was studied throughout the whole treatment comprising a 5-day lasting reduction part subsequent to the first 48 hours. Throughout the whole 7-day treatment a total of 5 and 2 patients dropped out and 6 and 5 patients reported adverse clinical events in the P and GP groups, respectively. All together, GP (400 mg qid) was no better than P in saving initial consumption of CLO or decreasing initial Mainz Alcohol Withdrawal Scores suggesting that GP was ineffective in the management of acute AWS in this model. The combination of GP and CLO was safe.

  11. Comparison of enteral ethanol and benzodiazepines for alcohol withdrawal in neurocritical care patients.

    PubMed

    Gipson, Gregory; Tran, Kim; Hoang, Cuong; Treggiari, Miriam

    2016-09-01

    We designed a study to evaluate the use of benzodiazepines and ethanol in patients being assessed for alcohol withdrawal and compare outcomes between the two agents. This is a retrospective chart review of patients admitted to neurocritical care or neurosurgical services who were at risk for ethanol withdrawal between June 2011 and September 2015. Patients were divided into two groups based on the first medication administered for alcohol withdrawal management, either benzodiazepine (n=50) or enteral ethanol (n=50). The primary endpoint was the maximum change in Clinical Institute Withdrawal Assessment of Alcohol scale (CIWA) score within the first 24hours. Secondary endpoints included maximum and minimum CIWA score in 5days, length of stay, and change in Glasgow Coma Scale. Study groups differed by mortality risk, level of coma at admission, and other clinical characteristics, with the ethanol group appearing less severely ill. There was no significant difference between the two groups in the maximum change in CIWA score at 24hours (-0.97, 95%CI: -3.21 to 1.27, p=0.39). Hospital and intensive care unit length of stay was 6.5 days and 1 day shorter for the ethanol group (p=0.03 and p=0.02, respectively). In summary, enteral ethanol was preferentially used in patients who are more likely to be capable of tolerating oral intake. We found that the change from baseline in CIWA score or other physiologic variables was not substantially different between the two agents. The overall utility of benzodiazepines and enteral ethanol remains unclear for this population and further study is needed to determine superiority.

  12. Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal

    PubMed Central

    Cosgrove, Kelly P.; McKay, Reese; Esterlis, Irina; Kloczynski, Tracy; Perkins, Evgenia; Bois, Frederic; Pittman, Brian; Lancaster, Jack; Glahn, David C.; O’Malley, Stephanie; Carson, Richard E.; Krystal, John H.

    2014-01-01

    Understanding the effects of tobacco smoking on neuroadaptations in GABAA receptor levels over alcohol withdrawal will provide critical insights for the treatment of comorbid alcohol and nicotine dependence. We conducted parallel studies in human subjects and nonhuman primates to investigate the differential effects of tobacco smoking and nicotine on changes in GABAA receptor availability during acute and prolonged alcohol withdrawal. We report that alcohol withdrawal with or without concurrent tobacco smoking/nicotine consumption resulted in significant and robust elevations in GABAA receptor levels over the first week of withdrawal. Over prolonged withdrawal, GABAA receptors returned to control levels in alcohol-dependent nonsmokers, but alcohol-dependent smokers had significant and sustained elevations in GABAA receptors that were associated with craving for alcohol and cigarettes. In nonhuman primates, GABAA receptor levels normalized by 1 mo of abstinence in both groups—that is, those that consumed alcohol alone or the combination of alcohol and nicotine. These data suggest that constituents in tobacco smoke other than nicotine block the recovery of GABAA receptor systems during sustained alcohol abstinence, contributing to alcohol relapse and the perpetuation of smoking. PMID:25453062

  13. Central pontine and extrapontine myelinolysis that developed during alcohol withdrawal, without hyponatremia, in a chronic alcoholic.

    PubMed

    An, Jae Young; Park, Sung Kyung; Han, Si Ryung; Song, In Uk

    2010-01-01

    Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are osmotic demyelination syndrome. A 45-year-old man with a history of alcoholism visited the ER with dysarthria and dysphagia for 2 days. These symptoms occurred 3 days after he had stopped drinking alcohol. The neurological symptoms progressed to anarthria, pseudobulbar palsy and gait disturbance. During admission, the electrolyte studies were within the normal range. Diffusion-weighted images revealed high signal intensities in the pons, thalamus and basal ganglia. Apparent diffusion coefficient image showed low signal intensities in the pontine lesion, but isosignal intensities in the extrapontine lesion. The symptoms gradually improved after 1 month with only conservative treatment. The 1 month-follow-up MRI showed significant reduction of the previous extrapontine lesions. These findings suggest that cytotoxic edema is central to the pathogenesis of CPM, but vasogenic edema plays an important role in the pathogenesis of EPM occurring during alcohol withdrawal.

  14. Sodium oxybate: a review of its use in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence.

    PubMed

    Keating, Gillian M

    2014-01-01

    A liquid formulation of sodium oxybate (Alcover(®)), the sodium salt of γ-hydroxybutyric acid (GHB), is approved in Italy and Austria for use in alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence. This article reviews the efficacy and tolerability of sodium oxybate in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence, as well as summarizing its pharmacological properties. Results of randomized controlled trials indicate that sodium oxybate was at least as effective as diazepam and clomethiazole in patients with alcohol withdrawal syndrome, rapidly alleviating symptoms, and was at least as effective as naltrexone or disulfiram in the maintenance of abstinence in alcohol-dependent patients. Sodium oxybate was generally well tolerated. The risk of sodium oxybate abuse is generally low when it is administered to alcohol-dependent patients at its approved dosage, under the supervision of a designated family member and with continuous strict medical surveillance. However, certain patient groups, such as patients with alcohol dependence and borderline personality disorder or who are in remission from heroin or cocaine addiction, may not be suitable candidates for sodium oxybate therapy because of an increased risk of abuse. In conclusion, sodium oxybate is a useful option for the treatment of alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence.

  15. Recruitment of medial prefrontal cortex neurons during alcohol withdrawal predicts cognitive impairment and excessive alcohol drinking

    PubMed Central

    George, Olivier; Sanders, Chelsea; Freiling, John; Grigoryan, Edward; Vu, Shayla; Allen, Camryn D.; Crawford, Elena; Mandyam, Chitra D.; Koob, George F.

    2012-01-01

    Chronic intermittent access to alcohol leads to the escalation of alcohol intake, similar to binge drinking in humans. Converging lines of evidence suggest that impairment of medial prefrontal cortex (mPFC) cognitive function and overactivation of the central nucleus of the amygdala (CeA) are key factors that lead to excessive drinking in dependence. However, the role of the mPFC and CeA in the escalation of alcohol intake in rats with a history of binge drinking without dependence is currently unknown. To address this issue, we examined FBJ murine osteosarcoma viral oncogene homolog (Fos) expression in the mPFC, CeA, hippocampus, and nucleus accumbens and evaluated working memory and anxiety-like behavior in rats given continuous (24 h/d for 7 d/wk) or intermittent (3 d/wk) access to alcohol (20% vol/vol) using a two-bottle choice paradigm. The results showed that abstinence from alcohol in rats with a history of escalation of alcohol intake specifically recruited GABA and corticotropin-releasing factor (CRF) neurons in the mPFC and produced working memory impairments associated with excessive alcohol drinking during acute (24–72 h) but not protracted (16 –68 d) abstinence. Moreover, abstinence from alcohol was associated with a functional disconnection of the mPFC and CeA but not mPFC and nucleus accumbens. These results show that recruitment of a subset of GABA and CRF neurons in the mPFC during withdrawal and disconnection of the PFC–CeA pathway may be critical for impaired executive control over motivated behavior, suggesting that dysregulation of mPFC interneurons may be an early index of neuroadaptation in alcohol dependence. PMID:23071333

  16. How Imaging Glutamate, GABA, and Dopamine Can Inform the Clinical Treatment of Alcohol Dependence and Withdrawal

    PubMed Central

    Hillmer, Ansel T.; Mason, Graeme F.; Fucito, Lisa M.; O’Malley, Stephanie S.; Cosgrove, Kelly P.

    2015-01-01

    Neuroimaging studies have dramatically advanced our understanding of the neurochemical basis of alcohol dependence, a major public health issue. In this paper we review the research generated from neurochemical-specific imaging modalities including magnetic resonance spectrometry (MRS), positron emission tomography (PET), and single photon emission computed tomography (SPECT) in studies of alcohol dependence and withdrawal. We focus on studies interrogating γ-aminobutryic acid (GABA), glutamate, and dopamine, as these are prominent neurotransmitter systems implicated in alcohol dependence. Highlighted findings include diminished dopaminergic functioning and modulation of the GABA system by tobacco smoking during alcohol withdrawal. Then, we consider how these findings impact the clinical treatment of alcohol dependence and discuss directions for future experiments to address existing gaps in the literature, e.g., sex differences and smoking comorbidity. These and other considerations provide opportunities to build upon the current neurochemistry imaging literature of alcohol dependence and withdrawal, which may usher in improved therapeutic and relapse prevention strategies. PMID:26510169

  17. A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal.

    PubMed

    Mariani, John J; Rosenthal, Richard N; Tross, Susan; Singh, Prameet; Anand, Om P

    2006-01-01

    Gabapentin was compared with phenobarbital for the treatment of alcohol withdrawal in a randomized, open-label, controlled trial in 27 inpatients. There were no significant differences in the proportion of treatment completers between treatment groups or the proportion of patients in each group requiring rescue medication for breakthrough signs and symptoms of alcohol withdrawal. There were no significant treatment differences in withdrawal symptoms or psychological distress, nor were there serious adverse events. These findings suggest that gabapentin may be as effective as phenobarbital in the treatment of alcohol withdrawal. Given gabapentin's favorable pharmacokinetic profile, further study of its effectiveness in treating alcohol withdrawal is warranted.

  18. Sex differences in acute ethanol withdrawal severity after adrenalectomy and gonadectomy in Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant mice.

    PubMed

    Strong, Moriah N; Kaufman, Katherine R; Crabbe, John C; Finn, Deborah A

    2009-08-01

    Recent findings suggest that the ability of ethanol (EtOH) to increase the levels of neurosteroids with potent gamma-aminobutyric acid (GABA)ergic properties can influence measures of EtOH sensitivity. Earlier studies determined that removal of the adrenals and gonads diminished the steroidogenic effect of EtOH and significantly increased acute EtOH withdrawal severity in two inbred mouse strains that differed in withdrawal severity, suggesting the contribution of anticonvulsant GABAergic steroids to acute withdrawal in intact animals. Thus, the goal of the present study was to investigate the consequence of steroid removal on acute EtOH withdrawal through excision of the adrenals and gonads, in another genetic animal model of EtOH withdrawal differences, the Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) selected lines. Male and female WSP and WSR mice underwent surgical removal of the adrenals and gonads or no organ removal (SHAM). One to 2 weeks later, baseline handling-induced convulsions (HICs) were assessed, mice were given a 4 g/kg dose of EtOH, and HICs were measured hourly for 12 h and then at 24 h. The combination surgery significantly increased EtOH withdrawal in WSP and WSR female mice, as measured by area under the curve (AUC) and peak HIC scores. The AUC was significantly positively correlated with plasma corticosterone levels and significantly negatively correlated with progesterone levels. In contrast, surgical status did not alter withdrawal severity in male WSP and WSR mice. Overall, the increase in acute EtOH withdrawal severity in female WSP and WSR mice after adrenalectomy and gonadectomy corroborate our recent evidence that withdrawal from a high dose of EtOH can be modulated by anticonvulsant steroids produced in the periphery.

  19. Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice.

    PubMed

    Farook, Justin M; Krazem, Ali; Lewis, Ben; Morrell, Dennis J; Littleton, John M; Barron, Susan

    2008-09-03

    In the present study, we examined the effects of acamprosate for its ability to reduce handling induced convulsions (HICs) during alcohol withdrawal. Diazepam was used as a positive control. Swiss Webster male mice received three daily IP injections of alcohol (2.5 g/kg) or alcohol (2.5 g/kg)+methylpyrazole (4-MP) (9 mg/kg). (4-MP, being an alcohol dehydrogenase inhibitor slows down the breakdown of alcohol. 4-MP in combination with alcohol exhibits a dramatic increase in blood alcohol level compared to alcohol alone). Ten hours following the last alcohol injection, the mice were picked up by the tail and examined for their seizure susceptibility (HICs). Diazepam, a benzodiazepine known to reduce seizures during alcohol withdrawal, significantly reduced these HICs at doses of 0.25, 0.5 and 1 mg/kg (p's<0.001). Acamprosate, an anti-relapse compound used clinically in newly abstinent alcoholics, also reduced these HICs at doses of 100, 200 and 300 mg/kg (p's<0.05). This study supports the use of acamprosate during periods of alcohol withdrawal as well as during abstinence.

  20. A Systems Approach Implicates a Brain Mitochondrial Oxidative Homeostasis Co-expression Network in Genetic Vulnerability to Alcohol Withdrawal

    PubMed Central

    Walter, Nicole A. R.; Denmark, DeAunne L.; Kozell, Laura B.; Buck, Kari J.

    2017-01-01

    Genetic factors significantly affect vulnerability to alcohol dependence (alcoholism). We previously identified quantitative trait loci on distal mouse chromosome 1 with large effects on predisposition to alcohol physiological dependence and associated withdrawal following both chronic and acute alcohol exposure in mice (Alcdp1 and Alcw1, respectively). We fine-mapped these loci to a 1.1–1.7 Mb interval syntenic with human 1q23.2-23.3. Alcw1/Alcdp1 interval genes show remarkable genetic variation among mice derived from the C57BL/6J and DBA/2J strains, the two most widely studied genetic animal models for alcohol-related traits. Here, we report the creation of a novel recombinant Alcw1/Alcdp1 congenic model (R2) in which the Alcw1/Alcdp1 interval from a donor C57BL/6J strain is introgressed onto a uniform, inbred DBA/2J genetic background. As expected, R2 mice demonstrate significantly less severe alcohol withdrawal compared to wild-type littermates. Additionally, comparing R2 and background strain animals, as well as reciprocal congenic (R8) and appropriate background strain animals, we assessed Alcw1/Alcdp1 dependent brain gene expression using microarray and quantitative PCR analyses. To our knowledge this includes the first Weighted Gene Co-expression Network Analysis using reciprocal congenic models. Importantly, this allows detection of co-expression patterns limited to one or common to both genetic backgrounds with high or low predisposition to alcohol withdrawal severity. The gene expression patterns (modules) in common contain genes related to oxidative phosphorylation, building upon human and animal model studies that implicate involvement of oxidative phosphorylation in alcohol use disorders (AUDs). Finally, we demonstrate that administration of N-acetylcysteine, an FDA-approved antioxidant, significantly reduces symptoms of alcohol withdrawal (convulsions) in mice, thus validating a phenotypic role for this network. Taken together, these studies

  1. Alteration of prolactin serum levels during alcohol withdrawal correlates with craving in female patients.

    PubMed

    Hillemacher, Thomas; Bayerlein, Kristina; Wilhelm, Julia; Reulbach, Udo; Frieling, Helge; Bönsch, Dominikus; Kornhuber, Johannes; Bleich, Stefan

    2005-12-01

    Dopaminergic transmission has been suggested to be a main mechanism mediating reinforcement, withdrawal and craving in alcohol dependency. Dopamine is associated with prolactin secretion, acting as a prolactin inhibitor. The aim of the present study was to investigate whether there is an association between altered prolactin levels and craving during early and late alcohol withdrawal. Therefore, we examined 145 patients suffering from alcohol dependency after admission to the detoxification unit, assessing craving with the Obsessive Compulsive Drinking Scale (OCDS) and measuring prolactin serum levels during early withdrawal (-EW: day 0 or day 1) and late withdrawal (-LW: day 7-day 10). We observed a significant influence of the alteration of prolactin during withdrawal on craving in female patients (Spearman's rho, OCDS-EW: r=-0.607, p=0.001; OCDS-LW: r=-0.730, p<0.001; n=26). The association between prolactin alteration in percentage and craving in females was confirmed with general linear models (OCDS-EW: F=15.819, p=0.001, r(2)=0.530; OCDS-LW: F=17.091, p<0.001, r(2)=0.535). In male patients we did not find any significant results. Our findings support the previously described role of the hypothalamic-pituitary-adrenal (HPA) axis in the neurobiology of alcohol craving and show evidence of an association between increased prolactin serum levels and lower craving during alcohol withdrawal in female patients.

  2. Comparative Evaluation of Medical vs. Social Treatment of Alcohol Withdrawal Syndrome.

    ERIC Educational Resources Information Center

    McGovern, Mark P.

    1983-01-01

    Compared medical and social setting detoxification treatments of alcohol withdrawal syndrome regarding the degree to which each involved alcoholics (N=200) in ongoing rehabilitative efforts. Results showed highly significant differences between treatment models, with the social setting model showing significantly greater rates of commitment to…

  3. Acute withdrawal, protracted abstinence and negative affect in alcoholism: Are they linked?

    PubMed Central

    Heilig, M.; Egli, M.; Crabbe, J.C.; Becker, H.C.

    2012-01-01

    The role of withdrawal-related phenomena in development and maintenance of alcohol addiction remains under debate. A “self-medication” framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that, in most patients, these symptoms abate over 3 – 6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: 1) Are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence? 2) Is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal? 3) To what extent is susceptibility to negative affect that persists into protracted abstinence heritable? PMID:20148778

  4. Attenuation of alcohol withdrawal syndrome and blood cortisol level with forced exercise in comparison with diazepam.

    PubMed

    Motaghinejad, Majid; Bangash, Mohammad Yasan; Motaghinejad, Ozra

    2015-01-01

    Relieving withdrawal and post-abstinence syndrome of alcoholism is one of the major strategies in the treatment of alcohol addicted patients. Diazepam, chlordiazepoxide, and topiramate are the approved medications that were used for this object. To assess the role of non-pharmacologic therapy in the management of alcohol withdrawal syndrome, we analyzed effects of forced exercise by treadmill on alcohol dependent mice as an animal model. A total of 60 adult male mice were divided into 5 groups, from which 4 groups became dependent to alcohol (2 g/kg/day) for 15 days. From day 16, treatment groups were treated by diazepam (0.5mg/kg), forced exercise, and diazepam (0.5 mg/kg) concurrent with forced exercise for two weeks; And the positive control group received same dose of alcohol (2 g/kg/day) for two weeks. The negative control group received normal saline for four weeks. Finally, on day 31, all animals were observed for withdrawal signs, and Alcohol Total Withdrawal Score (ATWS) was determined. Blood cortisol levels were measured in non-fasting situations as well. Present findings showed that ATWS significantly decrease in all treatment groups in comparison with positive control group (P<0.05 for groups received diazepam and treated by forced exercise and P<0.001 for group under treatment diazepam + forced exercise). Moreover, blood cortisol level significantly decreased in all treatment groups (P<0.001). This study suggested that forced exercise and physical activity can be useful as adjunct therapy in alcoholism and can ameliorate side effects and stress situation of withdrawal syndrome periods.

  5. Hypothalamic-pituitary-adrenal axis activity, dehydroepiandrosterone sulphate and their relationships with aggression in early and late alcohol withdrawal.

    PubMed

    Ozsoy, Saliha; Esel, Ertugrul

    2008-02-15

    The study aims at investigating the relationship between hypothalamic-pituitary-adrenal (HPA) axis alterations and aggression level in alcoholic patients during early and late alcohol withdrawal. Serum levels of basal cortisol and dehydroepiandrosterone sulphate (DHEAS) were measured three times, and cortisol and DHEAS response to dexamethasone twice during the early and late withdrawal periods in alcohol dependent males (n=30) and once in healthy control males (n=20). Abnormal cortisol non-suppression response to dexamethasone in dexamethasone suppression test (DST) was observed in some proportion of the patients in early withdrawal, which normalized in late withdrawal. The study revealed reduced basal DHEAS levels and reduced DHEAS response to dexamethasone in late withdrawal. When the patients were assessed in two separate groups as high- and low-aggressives, in the high-aggression group abnormality in DST was observed during both early and late withdrawal periods, in the low-aggression group it was observed only in early withdrawal. While basal DHEAS levels were low in the high-aggression group only in early withdrawal, it was reduced in the low-aggression group during late withdrawal period. Some alterations of the HPA axis during alcohol withdrawal might be associated not only with alcohol use per se but also with aggressivity tendency of alcoholic patients.

  6. A study of gabapentin in the treatment of tonic-clonic seizures of alcohol withdrawal syndrome.

    PubMed

    Rustembegovic, Avdo; Sofic, Emin; Tahirović, Ismet; Kundurović, Zlata

    2004-01-01

    In this study for thirty (30) patients with alcohol withdrawal syndrome, the response to anticolvusant gabapentin was assessed. Thirty (30) patients with median age of 57.0 years and median body weight of 79.1 kg were treated with gabapentin 3 x 300 mg daily for up 30 days. The preliminary findings of this study suggest that gabapentin is very effective against tonic-clonic seizures in alcohol withdrawal syndrome. Gabapentin was safe and well tolerated. For twenty (20) patients no side effect were observed.

  7. EFFECT OF FLUOXETINE AND BROMOCRIPTINE ON CRAVING OCCURRING DURING WITHDRAWAL FROM ALCOHOL

    PubMed Central

    Chatterjee, Sudipto; Isaac, Mohan K.

    1996-01-01

    Craving is an integral element in the understanding of alcohol dependence. Recent human and animal research implicates the serotonergic and dopaminergic systems in the mediation of excessive alcohol consumption. In this study, a cue-based approach was used to qualify and quantify craving occurring during acute withdrawal from alcohol. Fifty alcoholics were given either placebo, bromocriptine or fluoxetine in a randomised double-blind fashion and craving was sequentially measured over the next 15 days. Both fluoxetine and bromocriptine significantly attenuated total craving scores without similarly affecting withdrawal symptoms. The results suggest the importance of neurotransmitters in mediating craving. The significance of these data in the light of various behavioural and neurochemical models have been discussed. PMID:21584128

  8. A case of mistaken identity: alcohol withdrawal, schizophrenia, or central pontine myelinolysis?

    PubMed Central

    Schneider, Paul; Nejtek, Vicki A; Hurd, Cheryl L

    2012-01-01

    Demyelination is a hallmark of central pontine myelinolysis (CPM). Neuropsychiatric manifestations of this condition include weakness, quadriplegia, pseudobulbar palsy, mood changes, psychosis, and cognitive disturbances. These psychiatric symptoms are also associated with schizophrenia and alcohol withdrawal. Thus, it is clinically relevant to differentiate between CPM, schizophrenia, and alcohol withdrawal as the treatment and prognostic outcomes for each diagnosis are distinct. We present a series of events that led to a misdiagnosis of a patient admitted to the medical emergency center presenting with confusion, psychomotor agitation, and delirium who was first diagnosed with schizophrenia and alcohol withdrawal by emergency medical physicians and later discovered by the psychiatric consult team to have CPM. With a thorough psychiatric evaluation, a review of the laboratory results first showing mild hyponatremia (127 mmol/L), subsequent hypernatremia (154 mmol/L), and magnetic resonance brain imaging, psychiatrists concluded that CPM was the primary diagnosis underlying the observed neuropsychopathology. This patient has mild impairments in mood, cognition, and motor skills that remain 12 months after her emergency-center admission. This case report reminds emergency clinicians that abnormal sodium metabolism can have long-term and devastating psychopathological and neurological consequences. Differentiating between CPM, schizophrenia, and alcohol withdrawal using neuroimaging techniques and preventing the risks for CPM using slow sodium correction are paramount. PMID:22347796

  9. Functional Role of the Polymorphic 647 T/C Variant of ENT1 (SLC29A1) and Its Association with Alcohol Withdrawal Seizures

    PubMed Central

    Nam, Hyung Wook; Lee, Moonnoh R.; Preuss, Ulrich W.; Zill, Peter; Yoon, Gihyun; Colby, Colin; Mrazek, David A.; Choi, Doo-Sup

    2011-01-01

    Background Adenosine is involved in several neurological and behavioral disorders including alcoholism. In cultured cell and animal studies, type 1 equilibrative nucleoside transporter (ENT1, slc29a1), which regulates adenosine levels, is known to regulate ethanol sensitivity and preference. Interestingly, in humans, the ENT1 (SLC29A1) gene contains a non-synonymous single nucleotide polymorphism (647 T/C; rs45573936) that might be involved in the functional change of ENT1. Principal Findings Our functional analysis showed that prolonged ethanol exposure increased adenosine uptake activity of mutant cells (ENT1-216Thr) compared to wild-type (ENT1-216Ile) transfected cells, which might result in reduced extracellular adenosine levels. We found that mice lacking ENT1 displayed increased propensity to ethanol withdrawal seizures compared to wild-type littermates. We further investigated a possible association of the 647C variant with alcoholism and the history of alcohol withdrawal seizures in subjects of European ancestry recruited from two independent sites. Analyses of the combined data set showed an association of the 647C variant and alcohol dependence with withdrawal seizures at the nominally significant level. Conclusions Together with the functional data, our findings suggest a potential contribution of a genetic variant of ENT1 to the development of alcoholism with increased risk of alcohol withdrawal-induced seizures in humans. PMID:21283641

  10. Affective cue-induced escalation of alcohol self-administration and increased 22-kHz ultrasonic vocalizations during alcohol withdrawal: role of kappa-opioid receptors.

    PubMed

    Berger, Anthony L; Williams, Angela M; McGinnis, Molly M; Walker, Brendan M

    2013-03-01

    Negative affect promotes dysregulated alcohol consumption in non-dependent and alcohol-dependent animals, and cues associated with negative affective states induce withdrawal-like symptoms in rats. This study was designed to test the hypotheses that: (1) the kappa-opioid receptor (KOR) system mediates phenotypes related to alcohol withdrawal and withdrawal-like negative affective states and (2) cues associated with negative affective states would result in dysregulated alcohol consumption when subsequently presented alone. To accomplish these goals, intracerebroventricular infusion of the KOR antagonist nor-binaltorphimine (nor-BNI) was assessed for the ability to attenuate the increase in 22-kHz ultrasonic vocalizations (USVs) associated with alcohol withdrawal and KOR activation in adult male wistar rats. Furthermore, cues associated with a KOR agonist-induced negative affective state were assessed for the ability to dysregulate alcohol consumption and the efficacy of intracerebroventricular KOR antagonism to reduce such dysregulation was evaluated. KOR antagonism blocked the increased number of 22-kHz USVs observed during acute alcohol withdrawal and a KOR agonist (U50,488) resulted in a nor-BNI reversible increase in 22-kHz USVs (mimicking an alcohol-dependent state). Additionally, cues associated with negative affective states resulted in escalated alcohol self-administration, an effect that was nor-BNI sensitive. Taken together, this study implicates negative affective states induced by both alcohol withdrawal and conditioned stimuli as being produced, in part, by activity of the DYN/KOR system.

  11. Pregabalin for the Treatment of Drug and Alcohol Withdrawal Symptoms: A Comprehensive Review.

    PubMed

    Freynhagen, Rainer; Backonja, Miroslav; Schug, Stephan; Lyndon, Gavin; Parsons, Bruce; Watt, Stephen; Behar, Regina

    2016-12-01

    Treatments for physical dependence and associated withdrawal symptoms following the abrupt discontinuation of prescription drugs (such as opioids and benzodiazepines), nicotine, alcohol, and cannabinoids are available, but there is still a need for new and more effective therapies. This review examines evidence supporting the potential use of pregabalin, an α2δ voltage-gated calcium channel subunit ligand, for the treatment of physical dependence and associated withdrawal symptoms. A literature search of the MEDLINE and Cochrane Library databases up to and including 11 December 2015 was conducted. The search term used was '(dependence OR withdrawal) AND pregabalin'. No other date limits were set and no language restrictions were applied. Works cited in identified articles were cross-referenced and personal archives of references also searched. Articles were included based on the expert opinions of the authors. There is limited evidence supporting the role of pregabalin for the treatment of physical dependence and accompanying withdrawal symptoms associated with opioids, benzodiazepines, nicotine, cannabinoids, and alcohol, although data from randomized controlled studies are sparse. However, the current evidence is promising and provides a platform for future studies, including appropriate randomized, placebo- and/or comparator-controlled studies, to further explore the efficacy and safety of pregabalin for the treatment of withdrawal symptoms. Given the potential for pregabalin misuse or abuse, particularly in individuals with a previous history of substance abuse, clinicians should exercise caution when using pregabalin in this patient population.

  12. [Severe metabolic acidosis in an alcoholic].

    PubMed

    Sonne, Morten Egede; Rudolph, Søren Finnemann; Pott, Frank Christian

    2008-09-29

    Severe metabolic acidosis is associated with poor prognosis. We present a patient with profound alcohol and starvation-related combined lactic and keto acidosis (lactate = 29 mM; pH = 6.83) who made a good recovery following 18 hours of intensive care therapy. A brief summary of the proposed mechanism by which these metabolic derangements develop is presented.

  13. The search for insight: Clients' psychological experiences of alcohol withdrawal in a voluntary, residential, health care setting.

    PubMed

    Smith, Morgan

    2004-04-01

    This study utilized a life history approach to describe clients' psychological experiences of the alcohol withdrawal process while voluntarily residing in a specialist alcohol withdrawal facility. Reflection on the past and anticipation of the future frequently occupied the thoughts of participants as they sought insight in to their lives. These insights were associated with a range of emotions that included embarrassment, shame, optimism, feelings of support and a sense of loss of control. The findings provide additional information on the human experience of alcohol withdrawal and, thus, increase empathy, understanding and knowledge. This increased understanding can be utilized to improve the quality of nursing care provided to this complex client group.

  14. Intra-cerebral and intra-nasal melanocortin-4 receptor antagonist blocks withdrawal hyperalgesia in alcohol-dependent rats.

    PubMed

    Roltsch Hellard, Emily A; Impastato, Renata A; Gilpin, Nicholas W

    2016-01-24

    Humans diagnosed with alcohol use disorder are more sensitive to painful stimuli during withdrawal, which suggests that excessive alcohol drinking worsens pain outcomes. Alcohol-dependent rats exhibit increases in nociceptive sensitivity during withdrawal. Data from animal models suggest that brain melanocortin-4 receptors (MC4Rs) mediate alcohol drinking and nociception. Here we tested: (1) the effect of alcohol dependence on thermal nociception in rats, and (2) the ability of acute alcohol and (3) MC4R antagonists to reverse hyperalgesia during withdrawal in alcohol-dependent rats. Rats were trained to self-administer operant alcohol and were tested for baseline thermal nociception. Half of the rats were made dependent on alcohol, then all rats were cannulated in the lateral ventricle. We tested the effects of acute alcohol drinking, acute fixed-dose alcohol, intra-ventricular agouti-related protein (endogenous MC4R antagonist), intra-ventricular HS014 (synthetic MC4R antagonist) and intra-nasal HS014 on hyperalgesia during withdrawal in alcohol-dependent rats, relative to non-dependent drinkers and alcohol-naïve controls. Alcohol-dependent rats exhibit thermal hyperalgesia that is abolished by alcohol drinking, bolus alcohol and intra-ventricular and intra-nasal MC4R antagonists. These manipulations did not affect thermal nociception in non-dependent drinkers and alcohol-naïve controls, suggesting that alcohol dependence produces neuroadaptations in brain MC4R systems. These results suggest that brain MC4R systems may be an effective therapeutic target for reducing nociception in the alcohol-dependent organism.

  15. Comparative Evaluation of Partial α2 -Adrenoceptor Agonist and Pure α2 -Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice.

    PubMed

    Arora, Shivani; Vohora, Divya

    2016-08-01

    As an addictive drug, alcohol produces withdrawal symptoms if discontinued abruptly after chronic use. Clonidine (CLN), a partial α2 -adrenergic agonist, and mirtazapine (MRT), an antagonist of α2 -adrenoceptor, both clinically aid alcohol withdrawal. Considering different mechanisms of action of the two drugs, this study was designed to see how far these two mechanistically different drugs differ in their ability to decrease the severity of ethanol withdrawal syndrome. The effect of CLN and MRT on ethanol withdrawal-induced anxiety, depression and memory impairment was analysed using EPM, FST and PAR tests, respectively. Animals received distilled water, ethanol and/or either of the drugs (CLN and MRT) in different doses. Relapse to alcohol use was analysed by CPP test. Animals received ethanol as a conditioning drug and distilled water, CLN or MRT as test drug. CLN and MRT both alleviated anxiety in a dose-dependent manner. MRT (4 mg/kg) was more effective than CLN (0.1 mg/kg) in ameliorating the anxiogenic effect of alcohol withdrawal. However, CLN treatment increased depression. It significantly decreased swimming time and increased immobility time, whereas MRT treatment decreased immobility time and increased climbing and swimming time during abstinence. The effect was dose dependent for both drugs. The results of PAR test show that CLN treatment worsens working memory. Significant increase in SDE and TSZ and decrease in SDL were observed in CLN-treated animals. MRT treatment, on the other hand, improved working memory at both doses. Further, both CLN and MRT alleviated craving. A significant decrease in time spent in the ethanol-paired chamber was seen. MRT treatment at both doses showed better effect than CLN in preventing the development of preference in CPP test. These findings indicate a potential therapeutic use and better profile of mirtazapine over clonidine in improving memory, as well as in alleviating depression, anxiety and craving associated

  16. Excitability of jcBNST neurons is reduced in alcohol-dependent animals during protracted alcohol withdrawal.

    PubMed

    Szücs, Attila; Berton, Fulvia; Sanna, Pietro Paolo; Francesconi, Walter

    2012-01-01

    Alcohol dependence and withdrawal has been shown to cause neuroadaptive changes at multiple levels of the nervous system. At the neuron level, adaptations of synaptic connections have been extensively studied in a number of brain areas and accumulating evidence also shows the importance of alcohol dependence-related changes in the intrinsic cellular properties of neurons. At the same time, it is still largely unknown how such neural adaptations impact the firing and integrative properties of neurons. To address these problems, here, we analyze physiological properties of neurons in the bed nucleus of stria terminalis (jcBNST) in animals with a history of alcohol dependence. As a comprehensive approach, first we measure passive and active membrane properties of neurons using conventional current clamp protocols and then analyze their firing responses under the action of simulated synaptic bombardment via dynamic clamp. We find that most physiological properties as measured by DC current injection are barely affected during protracted withdrawal. However, neuronal excitability as measured from firing responses under simulated synaptic inputs with the dynamic clamp is markedly reduced in all 3 types of jcBNST neurons. These results support the importance of studying the effects of alcohol and drugs of abuse on the firing properties of neurons with dynamic clamp protocols designed to bring the neurons into a high conductance state. Since the jcBNST integrates excitatory inputs from the basolateral amygdala (BLA) and cortical inputs from the infralimbic and the insular cortices and in turn is believed to contribute to the inhibitory input to the central nucleus of the amygdala (CeA) the reduced excitability of the jcBNST during protracted withdrawal in alcohol-dependent animals will likely affect ability of the jcBNST to shape the activity and output of the CeA.

  17. Clinical Evolution of Central Pontine Myelinolysis in a Patient with Alcohol Withdrawal: A Blurred Clinical Horizon

    PubMed Central

    Yazdani, Dina F.

    2016-01-01

    Central pontine myelinolysis (CPM), a potentially fatal and debilitating neurological condition, was first described in 1959 in a study on alcoholic and malnourished patients. It is a condition most frequently related to rapid correction of hyponatremia. Chronic alcoholism associated CPM tends to be benign with a favorable prognosis compared to CPM secondary to rapid correction of hyponatremia. We describe a normonatremic, alcoholic patient who presented with CPM after a rapid rise in his sodium levels. Our case illustrates the fact that CPM can manifest even in patients who are normonatremic at baseline. Rapid rises in sodium levels should be promptly reversed before clinical symptoms manifest in patient with risk factors for CPM irrespective of their baseline sodium levels. Furthermore, clinical evolution of CPM can be difficult to discern from the natural course of alcohol withdrawal delirium, requiring astuteness and maintenance of a high degree of clinical suspicion on the part of the physician. PMID:27610136

  18. Excretion of beta-carbolines harman and norharman in 24-hour urine of chronic alcoholics during withdrawal and controlled abstinence.

    PubMed

    Wodarz, N; Wiesbeck, G A; Rommelspacher, H; Riederer, P; Böning, J

    1996-06-01

    Animal experiments suggest that endogenous substances that could result from the interaction between neurotransmitters (dopamine and indoleamines) and ethanol and its metabolite acetaldehyde might be involved in the pathogenesis and maintenance of alcohol dependence. Therefore, aromatic beta-carbolines (norharman and harman) were investigated repeatedly in 24-hr urine of 13 male severe alcoholics without any psychiatric comorbidity during a controlled inpatient abstention program of up to 8 weeks. Harman excretion was approximately 2-fold above levels in control subjects, with a steady decline after 3 weeks of abstinence and lower levels in patients with a longer duration of alcohol dependence. Severity of withdrawal symptoms and actual feelings of anxiety/depression were negatively associated with urinary harman excretion. Positive associations could be established with daily ethanol consumption the month before admission and the score on the scale "reward dependence" according to Cloninger's Tridimensional Personality Questionnaire. Moreover, patients without alcohol-dependent first-degree relatives and higher "reward dependence" exhibited an increased excretion of harman. Therefore, harman levels might characterize a distinct subgroup of alcoholic patients, who in part resemble the so-called type l alcoholics of Cloninger. However, this awaits further study in a larger number of individuals. In contrast, norharman excretion was elevated up to 6-fold, compared with nonalcoholics over 6 to 8 weeks of controlled abstention. No correlations to demographic or clinical variables could be observed. Therefore, increased norharman levels might be proposed as a "residual marker" or a trait variable. Whether the observed changes are specific markers of at least certain aspects of alcoholism or dependence remain to be elucidated.

  19. Cost-effectiveness analysis of baclofen and chlordiazepoxide in uncomplicated alcohol-withdrawal syndrome

    PubMed Central

    Reddy, Vikram K.; Girish, K.; Lakshmi, Pandit; Vijendra, R.; Kumar, Ajay; Harsha, R.

    2014-01-01

    Objectives: Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acidB (GABAB) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS. Materials and Methods: This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (CEA) of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS. Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol (CIWA-Ar) scores. Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone. Both direct and indirect medical costs were considered and the CEA was analyzed in both patient's perspective and third-party perspective. Results: The average cost-effectiveness ratio (ACER) in patient's perspective of baclofen and chlordiazepoxide was Rs. 5,308.61 and Rs. 2,951.95 per symptom-free day, respectively. The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs. 895.01 and Rs. 476.29 per symptom-free day, respectively. Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test (U = 253.50, P = 0.03). Conclusion: Both study drugs provided relief of withdrawal symptoms. Chlordiazepoxide was more cost-effective than baclofen. Baclofen was relatively less effective and more expensive than chlordiazepoxide. PMID:25097273

  20. Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms.

    PubMed

    Anton, Raymond F; Myrick, Hugh; Baros, Alicia M; Latham, Patricia K; Randall, Patrick K; Wright, Tara M; Stewart, Scott H; Waid, Randy; Malcolm, Robert

    2009-08-01

    Improved treatment of alcohol dependence is a high priority, including defining subtypes that might respond differently. We evaluated a medication combination of intravenous flumazenil (FMZ) and oral gabapentin (GBP) in alcoholics who did and did not exhibit pretreatment alcohol withdrawal (AW) symptoms. Sixty alcohol-dependent individuals (44 with low AW and 16 with high AW) were randomized to receive FMZ (2 mg of incremental bolus for 20 minutes for 2 consecutive days) and GBP (up to 1200 mg nightly for 39 days) or their inactive placebos. Alcohol withdrawal was measured for the first 2 days, and drinking, sleep parameters, and adverse events were monitored during weekly evaluations, along with behavioral counseling sessions. Percent days abstinent (PDA) during treatment and time to first heavy drinking (TFHD) day were primary outcome variables. There was an interaction between the pretreatment AW status and the medication group on PDA (P = 0.0006) and TFHD (P = 0.06). Those in the high AW group had more PDA and more TFHD if treated with active medications, whereas those in the low AW group had more PDA and more TFHD if treated with placebo. This interaction remained for those totally abstinent (P = 0.03) and was confirmed by percent carbohydrate-deficient transferrin values. In addition, the pattern of response remained up to 8 weeks after treatment. In addition, in those with high AW, greater improvement in AW symptoms was observed in the active medication group compared with the placebo group. These results suggest a differential response to FMZ/GBP treatment, depending on pretreatment AW status that should be taken into account during future treatment trials.

  1. Comparison of cannabis and tobacco withdrawal: severity and contribution to relapse.

    PubMed

    Budney, Alan J; Vandrey, Ryan G; Hughes, John R; Thostenson, Jeff D; Bursac, Zoran

    2008-12-01

    This naturalistic telephone survey study compared perceptions of withdrawal severity in 67 daily cannabis users and 54 daily tobacco cigarette smokers who made quit attempts during the prior 30 days. A Withdrawal Symptom Checklist assessed the severity of abstinence symptoms and a Likert scale assessed perceived relations between abstinence symptoms and relapse. A composite Withdrawal Discomfort Score did not differ significantly between groups (M = 13.0 for cannabis, vs. M = 13.2 for tobacco). Individual symptom severity ratings were also of similar magnitude, except craving and sweating were slightly higher for tobacco. Both groups reported that withdrawal contributed substantially to relapse, and the strength of these ratings was similar across groups. The diverse convenience sample examined in this study adds external validity and generalizability to prior studies that included only users not planning to quit or excluded many common types of cannabis users. The comparable withdrawal experience from these heterogeneous cannabis and tobacco users supports previous findings from controlled laboratory studies and indicates that real-world, frequent cannabis users perceive that withdrawal symptoms negatively affect their desire and ability to quit.

  2. Nicotine Withdrawal in U.S. Smokers with Current Mood, Anxiety, Alcohol Use, and Substance Use Disorders

    PubMed Central

    Weinberger, Andrea H.; Desai, Rani A.; McKee, Sherry A.

    2009-01-01

    Background The current study examined tobacco withdrawal symptoms and withdrawal-related discomfort and relapse in smokers with and without current mood disorders, anxiety disorders, alcohol use disorders (AUD), and substance use disorders (SUD). Methods The subsample of current daily smokers (n=8,213) from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, Wave 1, 2001–2002, full sample n=43,093) were included in these analyses. Cross-sectional data compared smokers with and without current psychiatric disorders on withdrawal symptoms using logistic regression models. The effects of having a co-morbid psychiatric disorder and AUD/SUD compared to a psychiatric disorder alone on nicotine withdrawal were also examined. Results Participants with a current mood disorder, anxiety disorder, AUD, or SUD were more likely to report withdrawal symptoms and reported more withdrawal symptoms than those without current disorders. Having a current mood disorder, anxiety disorder, and SUD was also associated with increased likelihood of withdrawal-related discomfort and relapse. There were no significant interactions between psychiatric disorders and AUDs/SUDs on withdrawal symptoms or behavior. Conclusions Participants with a current Axis I disorder were more likely to experience tobacco withdrawal symptoms and withdrawal-related discomfort and relapse. Having a co-morbid psychiatric disorder and AUD/SUD did not synergistically increase the experience of withdrawal-related symptoms or relapse. It is important to identify Axis I disorders in smokers and provide these smokers with more intensive and/or longer treatments to help them cope with withdrawal symptoms and prevent relapse. PMID:20006451

  3. A proposed model for community-assisted alcohol withdrawal in primary care in the UK Armed Forces.

    PubMed

    Faerestrand, Nicholas H; Coetzee, R H

    2015-12-01

    Alcohol misuse and related morbidity continues to represent a challenge to the both the National Health Service (NHS) and the Defence Medical Services (DMS). A significant part of the management of patients who misuse alcohol involves planned assisted withdrawal for dependent drinkers. Traditionally, assisted alcohol withdrawal has been conducted in an in-patient setting owing to the perceived risks of carrying out this treatment. Current evidence shows that community-based approaches offer a safe and effective alternative to the traditional in-patient model with significant cost savings. This article proposes a model for community-assisted alcohol withdrawal (CAAW) for use within the DMS. It considers current guidelines and models already in operation within the NHS, offering evaluation and adjustments to fit the requirements that are applicable to the UK Armed Forces medical environment.

  4. Alterations in alcohol consumption, withdrawal seizures, and monoamine transmission in rats treated with phentermine and 5-hydroxy-L-tryptophan.

    PubMed

    Halladay, A K; Wagner, G C; Sekowski, A; Rothman, R B; Baumann, M H; Fisher, H

    2006-04-01

    We have previously shown that coadministration of the dopamine (DA) agonist phentermine plus the serotonergic agonist fenfluramine suppresses alcohol intake and withdrawal seizures in rats. In the present study, phentermine and the serotonin (5-HT) precursor, 5-hydroxy-L-tryptophan (5-HTP), were administered alone, or in combination, to rats fed on a 6% alcohol-containing diet or an isocaloric control diet. Following a 9-h withdrawal period from the alcohol-containing diet, phentermine enhanced the effects of 5-HTP on both reduction of alcohol withdrawal seizures as well as changes in striatal serotonin. Food intake was monitored for 24 h after drug treatment, and neurochemical measures were examined at various time points. Phentermine alone reduced food intake in all diet conditions, but this anorectic effect was followed by hyperphagia in control rats. Phentermine plus 5-HTP reduced the consumption of the alcohol-containing diet, while its effects on consumption of control diets were mixed. In vivo microdialysis in rat nucleus accumbens revealed that phentermine increased extracellular DA, whereas 5-HTP caused marked elevations in extracellular 5-HT. Coadministration of phentermine and 5-HTP evoked simultaneous elevations in extracellular DA and 5-HT that mirrored the effects of each drug alone. Collectively, these findings show that coadministered phentermine plus 5-HTP is effective in reducing alcohol intake and suppressing alcohol withdrawal seizures. These therapeutic actions may be related to elevations in synaptic DA and 5-HT in critical brain regions.

  5. Glutamatergic hyperfunctioning during alcohol withdrawal syndrome: therapeutic perspective with zinc and magnesium.

    PubMed

    Prior, Pedro Luis; Galduróz, José Carlos Fernandes

    2011-09-01

    It is known that the glutamatergic pathways are hyperfunctioning during alcohol withdrawal syndrome. It has been demonstrated that hyperfunctioning of this system causes a great damage to the superior cortical activity, the ability to concentrate and the control of impulses. Recent studies show that the cations zinc and magnesium modulate the glutamatergic function, reducing it to non-toxic levels, yet not reducing it to the point of depriving this neurotransmitter of its normal activity. New perspectives of treatment focus on the modulation of this system, having, as a result, reestablishment of impulse control abilities, damage prevention to the hippocampus and the amygdala and prevention of future relapses.

  6. The polymorphism GABABR1 T1974C[rs29230] of the GABAB receptor gene is not associated with the diagnosis of alcoholism or alcohol withdrawal seizures.

    PubMed

    Köhnke, Michael; Schick, Sandra; Lutz, Ulrich; Köhnke, Annette; Vonthein, Reinhard; Kolb, Werner; Batra, Anil

    2006-06-01

    As the inhibitory neurotransmitter gamma aminobutyric acid (GABA) modulates ethanol consumption, alcohol withdrawal symptoms and seizure generation by interacting with the GABAB receptor, the genes encoding for the GABAB receptor can be considered as candidate genes for alcoholism and alcohol withdrawal seizures (AWS). As the polymorphism GABABR1 T1974C[rs29230] of the GABAB receptor gene had been associated with alcoholism and EEG abnormalities in prior studies, the present examination investigated if the polymorphism is associated with the diagnosis of alcoholism or AWS. After genotyping the allele and genotype frequencies of a group of alcoholics with a history of AWS (n = 69) were compared with the results of a group of alcoholics with only mild withdrawal symptoms (n = 97). Additionally a group of healthy controls (n = 101) was compared with individuals with the diagnosis of alcoholism (n = 220). As no significant differences were found between the compared groups, this study gave no further evidence for GABABR1 T1974C[rs29230] as a candidate for alcoholism or AWS.

  7. Critical thoughts on current rodent models for evaluating potential treatments of alcohol addiction and withdrawal

    PubMed Central

    Ripley, Tamzin L; Stephens, David N

    2011-01-01

    Despite years of neurobiological research that have helped to identify potential therapeutic targets, we do not have a reliable pharmacological treatment for alcoholism. There are a range of possible explanations for this failure, including arguments that alcoholism is a spectrum disorder and that different population subtypes may respond to different treatments. This view is supported by categorisations such as early- and late-onset alcoholism, whilst multifactorial genetic factors may also alter responsivity to pharmacological agents. Furthermore, experience of alcohol withdrawal may play a role in future drinking in a way that may distinguish alcoholism from other forms of addiction. Additionally, our neurobiological models, based largely upon results from rodent studies, may not mimic specific aspects of the human condition and may reflect different underlying phenomena and biological processes from the clinical pattern. As a result, potential treatments may be targeting inappropriate aspects of alcohol-related behaviours. Instead, we suggest a more profitable approach is (a) to identify well-defined intermediate behavioural phenotypes in human experimental models that reflect defined aspects of the human clinical disorder and (b) to develop animal models that are homologous with those phenotypes in terms of psychological processes and underlying neurobiological mechanisms. This review describes an array of animal models currently used in the addiction field and what they tell us about alcoholism. We will then examine how established pharmacological agents have been developed using only a limited number of these models, before describing some alternative novel approaches to achieving homology between animal and human experimental measures. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21470204

  8. Influence of increased adrenergic activity and magnesium depletion on cardiac rhythm in alcohol withdrawal.

    PubMed Central

    Denison, H; Jern, S; Jagenburg, R; Wendestam, C; Wallerstedt, S

    1994-01-01

    OBJECTIVE--To investigate the prevalence of arrhythmias in alcoholic men during detoxification and its relation to neuroendocrine activation and electrolyte disturbances. DESIGN--Consecutive case-control study. SETTING--Primary and secondary care, detoxification ward. PATIENTS AND CONTROLS--19 otherwise healthy alcoholic men (DSM-III-R) with withdrawal symptoms necessitating detoxification in hospital. 19 age matched, healthy non-alcoholic men as controls for Holter recordings. INTERVENTIONS--Treatment with chlomethiazole; additional treatment with carbamazepine in patients with previous seizures. MAIN OUTCOME MEASURES--Computer based analyses of mean heart rate and arrhythmias from 24 hour Holter recordings, 24 hour urinary excretion of adrenaline and noradrenaline, magnesium retention measured by means of intravenous loading test, and serum concentrations of electrolytes. RESULTS--The 24 hour mean heart rate was higher in the alcoholic men (97.4 beats/minute, 95% confidence interval (CI) 91.2 to 103.6) than in the controls (69.6 beats/minute, 95% CI 65.4 to 73.8, P < 0.001). However, there was no difference in diurnal heart rate variation. The prevalence of premature supraventricular depolarisations was lower in the alcoholic men (P < 0.05). Neither atrial fibrillation nor malignant ventricular arrhythmias occurred. The sinus tachycardia in the alcoholic men correlated with the concomitant urinary excretion of catecholamines (P < 0.05). The mean serum magnesium concentration was 0.78 mmol/l (95% CI 0.73 to 0.83) in the alcoholic men and 0.83 mmol/l (95% CI 0.81 to 0.85) in a reference population of 55 men aged 40. Magnesium depletion (defined as magnesium retention > 30%) was detected in 10 alcoholic men (53%). Three alcoholic men had serum potassium concentrations < or = 3.3 mmol/l on admission. CONCLUSION--Increased adrenergic activity, magnesium depletion, and hypokalaemia are often seen after heavy drinking, but in alcoholic men without clinical heart disease

  9. Aggression and increased glutamate in the mPFC during withdrawal from intermittent alcohol in outbred mice

    PubMed Central

    Hwa, Lara S.; Nathanson, Anna J.; Shimamoto, Akiko; Tayeh, Jillian K.; Wilens, Allison R.; Holly, Elizabeth N.; Newman, Emily L.; DeBold, Joseph F.; Miczek, Klaus A.

    2015-01-01

    Rationale Disrupted social behavior, including occasional aggressive outbursts, is characteristic of withdrawal from long-term alcohol (EtOH) use. Heavy EtOH use and exaggerated responses during withdrawal may be treated using glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonists. Objectives The current experiments explore aggression and medial prefrontal cortex (mPFC) glutamate as consequences of withdrawal from intermittent access to EtOH, and changes in aggression and mPFC glutamate caused by NMDAR antagonists memantine and ketamine. Methods Swiss male mice underwent withdrawal following 1-8 weeks of intermittent access to 20% EtOH. Aggressive and non-aggressive behaviors with a conspecific were measured 6-8 h into EtOH withdrawal after memantine or ketamine (0-30 mg/kg, i.p.) administration. In separate mice, extracellular mPFC glutamate after memantine was measured during withdrawal using in vivo microdialysis. Results At 6-8 h withdrawal from EtOH, mice exhibited more convulsions and aggression, and decreased social contact compared to age-matched water controls. Memantine, but not ketamine, increased withdrawal aggression at the 5 mg/kg dose in mice with a history of 8 weeks EtOH but not 1 or 4 weeks of EtOH or in water drinkers. Tonic mPFC glutamate was higher during withdrawal after 8 weeks EtOH compared to 1 week EtOH or 8 weeks water. Five mg/kg memantine increased glutamate in 8 week EtOH mice, but also in 1 week EtOH and water drinkers. Conclusions These studies reveal aggressive behavior as a novel symptom of EtOH withdrawal in outbred mice and confirm a role of NMDARs during withdrawal aggression and for disrupted social behavior. PMID:25899790

  10. Clinical applications of sodium oxybate (GHB): from narcolepsy to alcohol withdrawal syndrome.

    PubMed

    Busardò, F P; Kyriakou, C; Napoletano, S; Marinelli, E; Zaami, S

    2015-12-01

    Gamma-hydroxybutyrate (GHB) is a short chain fatty acid endogenously produced within the central nervous system (CNS) and acts as a precursor and metabolite of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Although, it is an illegal recreational drug of abuse, its sodium salt (sodium oxybate) has been utilized as a medication for a number of medical conditions. The first aim of this review was to focus on current applications of sodium oxybate for the treatment of narcolepsy, with a particular emphasis on the key symptoms of this disorder: cataplexy and excessive daytime sleepiness (EDS). Secondly, the effectiveness of sodium oxybate therapy for the treatment of alcohol withdrawal syndrome (AWS) and the maintenance of alcohol abstinence has been assessed. Nowadays, sodium oxybate is the first-line treatment for narcolepsy and it is highly effective in meliorating sleep architecture, decreasing EDS and the frequency of cataplexy attacks in narcoleptic patients. Sodium oxybate currently finds also application in the treatment of AWS and the maintenance of alcohol abstinence in alcoholics. Most of the studies evaluating the efficacy of GHB in the treatment of AWS use a dosage of 50 mg/kg divided in three or four administrations per day. Human studies showed that GHB (dose of 50 mg/kg, divided in three administrations per day) is capable to increase the number of abstinent days, reduce alcohol craving and decrease the number of drinks per day. However, there is limited randomized evidence and, thus, GHB cannot be reliably compared to clomethiazole or benzodiazepines. Some randomized data suggest that GHB is better than naltrexone and disulfiram regarding abstinence maintenance and prevention of craving in the medium term i.e. 3-12 months. It is recommended that GHB should be used only under strict medical supervision, since concerns about the abuse/misuse of the drug and the addiction potential have been arisen.

  11. Heart failure due to ‘stress cardiomyopathy’: a severe manifestation of the opioid withdrawal syndrome

    PubMed Central

    Spadotto, Veronica; Zorzi, Alessandro; ElMaghawry, Mohamed; Pittoni, Giovanni Maria

    2013-01-01

    Takotsubo cardiomyopathy (TTC) is a transient left ventricular (LV) dysfunction due to akinesia of the LV mid-apical segments (‘apical ballooning’) in the absence of critical coronary stenoses which can be complicated in the acute phase by heart failure, mitral regurgitation, life-threatening ventricular arrhythmias, or apical LV thrombosis. The syndrome is typically precipitated by intense emotional or physical stress; however, other causes of sympathetic overstimulation including administration of exogenous sympathomimetics or withdrawal of sympathetic antagonists can trigger TTC. We report the case of a patient who unexpectedly developed an ‘apical ballooning’ with severe reduction in the LV systolic function and heart failure after the withdrawal of methadone. The case supports the concept that increased sympathetic activity secondary to opioids withdrawal can trigger a stress-induced severe LV dysfunction. Physicians should be aware that the abrupt discontinuation of a long-term therapy with opioids may lead to serious cardiac complications. The administration of clonidine may be considered to prevent early clinical manifestations of addictive withdrawal, including TTC. PMID:24062938

  12. Effects of Alcoholism Severity and Smoking on Executive Neurocognitive Function

    PubMed Central

    Glass, J.M.; Buu, A.; Adams, K.M.; Nigg, J.T.; Puttler, L.I.; Jester, J.M.; Zucker, R.A.

    2009-01-01

    Aims Neurocognitive deficits in chronic alcoholic men are well documented and include impairments in memory, visual-spatial processing, problem solving and executive function. The cause of these deficits is unclear, but could include direct effects of alcohol toxicity, pre-existing cognitive deficits that may predispose towards substance abuse, comorbid psychiatric disorders (e.g., depression) and comorbid abuse of substances other than alcohol. For example, cigarette smoking occurs at a much higher rate among persons with alcoholism and has been linked to poor cognitive performance. Until recently, the negative effects of smoking on cognitive function in alcoholism have been ignored. Methods The effects of alcoholism and smoking are examined in a community recruited sample of alcoholic and non-alcoholic men (N=240) using standard neuropsychological measures and reaction-time measures of executive function. Alcoholism severity was measured as an average of alcoholism diagnoses across the study duration (12 yrs). Smoking was measured in pack-years. Results Both alcoholism and smoking were negatively correlated with a composite executive function score. For component measures, alcoholism was negatively correlated with a broad range of measures, whereas smoking was negatively correlated with measures that emphasize response speed. In regression analyses, both smoking and alcoholism are significant predictors of executive function composite. However; when IQ is included in the regression analyses, alcoholism severity is no longer a significant predictor. Conclusions Both smoking and alcoholism were related to executive function. However, the effect of alcoholism on EF was not independent of IQ, suggesting that the alcoholism effect was generalized, perhaps affecting a wide range of cognitive abilities of which executive function is a component. On the other hand, the effect of smoking on measures relying on response speed were independent of IQ, suggesting a more

  13. Pharmacological activation/inhibition of the cannabinoid system affects alcohol withdrawal-induced neuronal hypersensitivity to excitotoxic insults.

    PubMed

    Rubio, Marina; Villain, Hélène; Docagne, Fabian; Roussel, Benoit D; Ramos, José Antonio; Vivien, Denis; Fernandez-Ruiz, Javier; Ali, Carine

    2011-01-01

    Cessation of chronic ethanol consumption can increase the sensitivity of the brain to excitotoxic damages. Cannabinoids have been proposed as neuroprotectants in different models of neuronal injury, but their effect have never been investigated in a context of excitotoxicity after alcohol cessation. Here we examined the effects of the pharmacological activation/inhibition of the endocannabinoid system in an in vitro model of chronic ethanol exposure and withdrawal followed by an excitotoxic challenge. Ethanol withdrawal increased N-methyl-D-aspartate (NMDA)-evoked neuronal death, probably by altering the ratio between GluN2A and GluN2B NMDA receptor subunits. The stimulation of the endocannabinoid system with the cannabinoid agonist HU-210 decreased NMDA-induced neuronal death exclusively in ethanol-withdrawn neurons. This neuroprotection could be explained by a decrease in NMDA-stimulated calcium influx after the administration of HU-210, found exclusively in ethanol-withdrawn neurons. By contrast, the inhibition of the cannabinoid system with the CB1 receptor antagonist rimonabant (SR141716) during ethanol withdrawal increased death of ethanol-withdrawn neurons without any modification of NMDA-stimulated calcium influx. Moreover, chronic administration of rimonabant increased NMDA-stimulated toxicity not only in withdrawn neurons, but also in control neurons. In summary, we show for the first time that the stimulation of the endocannabinoid system is protective against the hyperexcitability developed during alcohol withdrawal. By contrast, the blockade of the endocannabinoid system is highly counterproductive during alcohol withdrawal.

  14. Chronic alcohol consumption leads to neurochemical changes in the nucleus accumbens that are not fully reversed by withdrawal.

    PubMed

    Pereira, Pedro A; Neves, João; Vilela, Manuel; Sousa, Sérgio; Cruz, Catarina; Madeira, M Dulce

    2014-01-01

    Neuropeptide Y (NPY)- and acetylcholine-containing interneurons of the nucleus accumbens (NAc) seem to play a major role in the rewarding effects of alcohol. This study investigated the relationship between chronic alcohol consumption and subsequent withdrawal and the expression of NPY and acetylcholine in the NAc, and the possible involvement of nerve growth factor (NGF) in mediating the effects of ethanol. Rats ingesting an aqueous ethanol solution over 6months and rats subsequently deprived from ethanol during 2months were used to estimate the total number and the somatic volume of NPY and cholinergic interneurons, and the numerical density of cholinergic varicosities in the NAc. The tissue content of choline acetyltransferase (ChAT) and catecholamines were also determined. The number of NPY interneurons increased during alcohol ingestion and returned to control values after withdrawal. Conversely, the number and the size of cholinergic interneurons, and the amount of ChAT were unchanged in ethanol-treated and withdrawn rats, but the density of cholinergic varicosities was reduced by 50% during alcohol consumption and by 64% after withdrawal. The concentrations of dopamine and norepinephrine were unchanged both during alcohol consumption and after withdrawal. The administration of NGF to withdrawn rats significantly increased the number of NPY-immunoreactive neurons, the size of cholinergic neurons and the density of cholinergic varicosities. Present data show that chronic alcohol consumption leads to long-lasting neuroadaptive changes of the cholinergic innervation of the NAc and suggest that the cholinergic system is a potential target for the development of therapeutic strategies in alcoholism and abstinence.

  15. Withdrawal from chronic intermittent alcohol exposure increases dendritic spine density in the lateral orbitofrontal cortex of mice.

    PubMed

    McGuier, Natalie S; Padula, Audrey E; Lopez, Marcelo F; Woodward, John J; Mulholland, Patrick J

    2015-02-01

    Alcohol use disorders (AUDs) are associated with functional and morphological changes in subfields of the prefrontal cortex. Clinical and preclinical evidence indicates that the orbitofrontal cortex (OFC) is critical for controlling impulsive behaviors, representing the value of a predicted outcome, and reversing learned associations. Individuals with AUDs often demonstrate deficits in OFC-dependent tasks, and rodent models of alcohol exposure show that OFC-dependent behaviors are impaired by chronic alcohol exposure. To explore the mechanisms that underlie these impairments, we examined dendritic spine density and morphology, and NMDA-type glutamate receptor expression in the lateral OFC of C57BL/6J mice following chronic intermittent ethanol (CIE) exposure. Western blot analysis demonstrated that NMDA receptors were not altered immediately following CIE exposure or after 7 days of withdrawal. Morphological analysis of basal dendrites of layer II/III pyramidal neurons revealed that dendritic spine density was also not affected immediately after CIE exposure. However, the total density of dendritic spines was significantly increased after a 7-day withdrawal from CIE exposure. The effect of withdrawal on spine density was mediated by an increase in the density of long, thin spines with no change in either stubby or mushroom spines. These data suggest that morphological neuroadaptations in lateral OFC neurons develop during alcohol withdrawal and occur in the absence of changes in the expression of NMDA-type glutamate receptors. The enhanced spine density that follows alcohol withdrawal may contribute to the impairments in OFC-dependent behaviors observed in CIE-treated mice.

  16. The Effect of Intermittent Alcohol Vapor or Pulsatile Heroin on Somatic and Negative Affective Indices during Spontaneous Withdrawal in Wistar Rats

    PubMed Central

    Williams, Angela M.; Reis, Daniel J.; Powell, Alexa S.; Neira, Louis J.; Nealey, Kathryn A.; Ziegler, Cole E.; Kloss, Nina; Bilimoria, Jessica L.; Smith, Chelsea E.; Walker, Brendan M.

    2012-01-01

    Rationale Once dependent on alcohol or opioids, negative affect may accompany withdrawal. Dependent individuals are hypothesized to “self-medicate” in order to cope with withdrawal, which promotes escalated drug or alcohol use. Objectives The current study aimed to develop a reliable animal model to assess symptoms that occur during spontaneous alcohol and opioid withdrawal. Methods Dependence was induced using intermittent alcohol exposure or pulsatile heroin delivery and assessed for the presence of withdrawal symptoms during acute withdrawal by measuring somatic signs, behavior in the forced swim test (FST) and air-puff induced 22-kHz ultrasonic vocalizations (USVs). Additional animals subjected to eight weeks of alcohol vapor exposure were evaluated for altered somatic signs, operant alcohol self-administration and 22-kHz USV production, as well as performance in the elevated plus-maze (EPM). Results During spontaneous withdrawal from pulsatile heroin or intermittent alcohol vapor, animals displayed increased somatic withdrawal signs, FST immobility and 22-kHz USV production, but did not show any behavioral change in the EPM unless the duration of exposure was extended to four weeks. Following eight weeks of alcohol vapor exposure, animals displayed somatic withdrawal signs, escalated alcohol self-administration and increased 22-kHz USVs. Conclusions These paradigms provide consistent methods to evaluate the behavioral ramifications, and neurobiological substrates, of alcohol and opioid dependence during spontaneous withdrawal. As immobility in the FST and percent open-arm time in the EPM were dissociable, with 22-kHz USVs paralleling immobility in the FST, assessment of air-puff induced 22-kHz USVs could provide an ethologically-valid alternative to the FST. PMID:22461104

  17. [Withdrawal of artificial nutrition and hydration in severe stroke: medical, legal and ethical considerations].

    PubMed

    Tannier, C; Crozier, S; Zuber, M; Constantinides, Y; Delezie, E; Gisquet, E; Grignoli, N; Lamy, C; Louvet, F; Pinel, J-F

    2015-02-01

    In the majority of cases, severe stroke is accompanied by difficulty in swallowing and an altered state of consciousness requiring artificial nutrition and hydration. Because of their artificial nature, nutrition and hydration are considered by law as treatment rather basic care. Withdrawal of these treatments is dictated by the refusal of unreasonable obstinacy enshrined in law and is justified by the risk of severe disability and very poor quality of life. It is usually the last among other withholding and withdrawal decisions which have already been made during the long course of the disease. Reaching a collegial consensus on a controversial decision such as artificial nutrition and hydration withdrawal is a difficult and complex process. The reluctance for such decisions is mainly due to the symbolic value of food and hydration, to the fear of "dying badly" while suffering from hunger and thirst, and to the difficult distinction between this medical act and euthanasia. The only way to overcome such reluctance is to ensure flawless accompaniment, associating sedation and appropriate comfort care with a clear explanation (with relatives but also caregivers) of the rationale and implications of this type of decision. All teams dealing with this type of situation must have thoroughly thought through the medical, legal and ethical considerations involved in making this difficult decision.

  18. Identification of a QTL in Mus musculus for Alcohol Preference, Withdrawal, and Ap3m2 Expression Using Integrative Functional Genomics and Precision Genetics

    PubMed Central

    Bubier, Jason A.; Jay, Jeremy J.; Baker, Christopher L.; Bergeson, Susan E.; Ohno, Hiroshi; Metten, Pamela; Crabbe, John C.; Chesler, Elissa J.

    2014-01-01

    Extensive genetic and genomic studies of the relationship between alcohol drinking preference and withdrawal severity have been performed using animal models. Data from multiple such publications and public data resources have been incorporated in the GeneWeaver database with >60,000 gene sets including 285 alcohol withdrawal and preference-related gene sets. Among these are evidence for positional candidates regulating these behaviors in overlapping quantitative trait loci (QTL) mapped in distinct mouse populations. Combinatorial integration of functional genomics experimental results revealed a single QTL positional candidate gene in one of the loci common to both preference and withdrawal. Functional validation studies in Ap3m2 knockout mice confirmed these relationships. Genetic validation involves confirming the existence of segregating polymorphisms that could account for the phenotypic effect. By exploiting recent advances in mouse genotyping, sequence, epigenetics, and phylogeny resources, we confirmed that Ap3m2 resides in an appropriately segregating genomic region. We have demonstrated genetic and alcohol-induced regulation of Ap3m2 expression. Although sequence analysis revealed no polymorphisms in the Ap3m2-coding region that could account for all phenotypic differences, there are several upstream SNPs that could. We have identified one of these to be an H3K4me3 site that exhibits strain differences in methylation. Thus, by making cross-species functional genomics readily computable we identified a common QTL candidate for two related bio-behavioral processes via functional evidence and demonstrate sufficiency of the genetic locus as a source of variation underlying two traits. PMID:24923803

  19. Identification of a QTL in Mus musculus for alcohol preference, withdrawal, and Ap3m2 expression using integrative functional genomics and precision genetics.

    PubMed

    Bubier, Jason A; Jay, Jeremy J; Baker, Christopher L; Bergeson, Susan E; Ohno, Hiroshi; Metten, Pamela; Crabbe, John C; Chesler, Elissa J

    2014-08-01

    Extensive genetic and genomic studies of the relationship between alcohol drinking preference and withdrawal severity have been performed using animal models. Data from multiple such publications and public data resources have been incorporated in the GeneWeaver database with >60,000 gene sets including 285 alcohol withdrawal and preference-related gene sets. Among these are evidence for positional candidates regulating these behaviors in overlapping quantitative trait loci (QTL) mapped in distinct mouse populations. Combinatorial integration of functional genomics experimental results revealed a single QTL positional candidate gene in one of the loci common to both preference and withdrawal. Functional validation studies in Ap3m2 knockout mice confirmed these relationships. Genetic validation involves confirming the existence of segregating polymorphisms that could account for the phenotypic effect. By exploiting recent advances in mouse genotyping, sequence, epigenetics, and phylogeny resources, we confirmed that Ap3m2 resides in an appropriately segregating genomic region. We have demonstrated genetic and alcohol-induced regulation of Ap3m2 expression. Although sequence analysis revealed no polymorphisms in the Ap3m2-coding region that could account for all phenotypic differences, there are several upstream SNPs that could. We have identified one of these to be an H3K4me3 site that exhibits strain differences in methylation. Thus, by making cross-species functional genomics readily computable we identified a common QTL candidate for two related bio-behavioral processes via functional evidence and demonstrate sufficiency of the genetic locus as a source of variation underlying two traits.

  20. Ethnic Differences in Presentation and Severity of Alcoholic Liver Disease

    PubMed Central

    Durbin-Johnson, Blythe; Halsted, Charles H.; Medici, Valentina

    2015-01-01

    Background The frequency of alcoholic liver disease (ALD), including alcoholic steatosis, hepatitis and cirrhosis, varies significantly by ethnicity. Methods With the goal to assess the role of ethnicity in determining the age of onset and severity of ALD and to compare the risk factors for its progression among ethnic groups, we conducted a retrospective chart review of all patients with ALD who were admitted or were followed as outpatients at University of California Davis Medical Center between 2002 and 2010. After excluding HBsAg and HIV positive subjects, we reviewed the charts of 791 ALD patients including 130 with alcoholic fatty liver, 154 with alcoholic hepatitis, and 507 with alcoholic cirrhosis. Results When controlling for all variables in the model, Hispanic patients presented at significantly 4-10 years younger ages than White/Caucasian patients, in each of the three disease severity categories and the results were confirmed after excluding HCV Ab/RNA positive subjects. There were more obese Hispanic patients than White/Caucasian patients, whereas the proportion of patients with hepatitis C was significantly greater in African/American subjects with alcoholic hepatitis and the proportion of patients with diabetes mellitus was significantly lower in White/Caucasian subjects than in Hispanic subjects with cirrhosis. The proportion of subjects with severe alcoholic hepatitis was similar in Hispanic and White/Caucasian patients, but lower in African/American subjects. Conclusion Ethnicity is a major factor affecting the age and severity of presentation of different subtypes of ALD. PMID:25702770

  1. Dexmedetomidine for the treatment of alcohol withdrawal syndrome: rationale and current status of research.

    PubMed

    Muzyk, Andrew J; Kerns, Suzanne; Brudney, Scott; Gagliardi, Jane P

    2013-11-01

    Dexmedetomidine is currently used in the US in the treatment of alcohol withdrawal syndrome (AWS) in the intensive care unit (ICU) setting, although data to support this practice are limited. Dexmedetomidine targets the noradrenergic system, an important but frequently overlooked secondary mechanism in the development of AWS, and, in doing so, may reduce the need for excessive benzodiazepine use which can increase the risk of γ-aminobutyric acid (GABA)-mediated deliriogenesis and respiratory depression. The purpose of this narrative review is to evaluate available literature reporting on the safety and efficacy of dexmedetomidine for AWS in the ICU setting. An English-language MEDLINE search (1966 to July 2013) was performed to identify articles evaluating the efficacy and safety of dexmedetomidine for AWS. Case series, case reports and controlled trials were evaluated for topic relevance and clinical applicability. Reference lists of articles retrieved through this search were reviewed to identify any relevant publications. Studies focusing on the safety and efficacy of dexmedetomidine for AWS in humans were selected. Studies were included if they were published as full articles; abstracts alone were not included in this review. Eight published case studies and case series were identified. Based on a limited body of evidence, dexmedetomidine shows promise as a potentially safe and possibly effective adjuvant treatment for AWS in the ICU. Prospective, well-controlled studies are needed to confirm the safety and efficacy of the use of dexmedetomidine in AWS.

  2. Conceptualizing withdrawal-induced escalation of alcohol self-administration as a learned, plasticity-dependent process.

    PubMed

    Walker, Brendan M

    2012-06-01

    This article represents one of five contributions focusing on the topic "Plasticity and neuroadaptive responses within the extended amygdala in response to chronic or excessive alcohol exposure" that were developed by awardees participating in the Young Investigator Award Symposium at the "Alcoholism and Stress: A Framework for Future Treatment Strategies" conference in Volterra, Italy on May 3-6, 2011 that was organized/chaired by Drs. Antonio Noronha and Fulton Crews and sponsored by the National Institute on Alcohol Abuse and Alcoholism. This review discusses the dependence-induced neuroadaptations in affective systems that provide a basis for negative reinforcement learning and presents evidence demonstrating that escalated alcohol consumption during withdrawal is a learned, plasticity-dependent process. The review concludes by identifying changes within extended amygdala dynorphin/kappa-opioid receptor systems that could serve as the foundation for the occurrence of negative reinforcement processes. While some evidence contained herein may be specific to alcohol dependence-related learning and plasticity, much of the information will be of relevance to any addictive disorder involving negative reinforcement mechanisms. Collectively, the information presented within this review provides a framework to assess the negative reinforcing effects of alcohol in a manner that distinguishes neuroadaptations produced by chronic alcohol exposure from the actual plasticity that is associated with negative reinforcement learning in dependent organisms.

  3. Transcription factor AP2 beta involved in severe female alcoholism.

    PubMed

    Nordquist, Niklas; Göktürk, Camilla; Comasco, Erika; Nilsson, Kent W; Oreland, Lars; Hallman, Jarmila

    2009-12-11

    Susceptibility to alcoholism and antisocial behavior exhibits an evident link to monoaminergic neurotransmission. The serotonin system in particular, which is associated with regulation of mood and behavior, has an influence on personality characters that are firmly connected to risk of developing alcoholism and antisocial behavior, such as impulsiveness, and aggression. The transcription factor TFAP2b has repeatedly been shown to be involved in monoaminergic transmission, likely due to a regulatory effect on genes that are fundamental to this system, e.g. monoamine oxidase type A, and the serotonin transporter. Recent research has identified a functional polymorphism in the gene encoding TFAP2B that regulates its level of expression. In the present study we have compared a sample of female alcoholics (n=107), sentenced to institutional care for their severe addiction, contrasted against a control sample of adolescent females (n=875). The results showed that parental alcohol misuse was significantly more common among the alcoholic females, and also that parental alcohol misuse was associated with a reduction in age of alcohol debut. We also addressed the question of whether a functional TFAP2b polymorphism was associated with alcoholism. Results showed that the high-functioning allele was significantly more common among the female alcoholics, compared to the non-alcoholic controls. Furthermore, the results also indicated that psychosocial factors, in terms of parental alcohol misuse, depression or psychiatric disorder, had an influence on the association. It was observed that the genetic association was restricted to the subset of cases that had not experienced these negative psychosocial factors.

  4. Lorazepam and MK-801 effects on behavioral and electrographic indices of alcohol withdrawal sensitization.

    PubMed

    Veatch, Lynn M; Becker, Howard C

    2005-12-14

    Repeated cycles of chronic ethanol exposure and withdrawal result in sensitization of withdrawal-related CNS hyperexcitability that generally reflects an imbalance in activity of GABA and glutamate systems. Many pharmacological treatments for ethanol withdrawal target neuroadaptive changes in GABA and glutamate neurotransmission. The present study utilized a mouse model of repeated withdrawals to evaluate the ability of lorazepam and MK-801 treatments to antagonize behavioral and electroencephalographic (EEG) measures of sensitized withdrawal seizure activity. Adult male C3H/He mice received chronic intermittent ethanol vapor exposure in inhalation chambers (16 h/day) and during each withdrawal cycle, separate groups of mice were evaluated for handling-induced convulsions (HIC) or abnormal EEG (high-voltage "brief spindle episodes" (BSE)) activity. Lorazepam (0.5-1.0 mg/kg) or MK-801 (0.1-0.3 mg/kg) treatment at 1 h into each of three withdrawal cycles reduced behavioral (HIC) and electrographic (BSE) signs of seizure activity in a dose-related fashion compared to vehicle-treated mice. During a subsequent untreated withdrawal, mice previously treated with lorazepam or MK-801 for earlier withdrawals exhibited reduced HIC activity during the acute phase but exacerbated HIC activity during the protracted phase of this final (fourth) withdrawal cycle. Both lorazepam and MK-801 treatment conditions resulted in enhanced BSE activity during the entire fourth (untreated) withdrawal episode. Collectively, these results suggest that while treatment of repeated ethanol withdrawals with a benzodiazepine (lorazepam) or an NMDA receptor antagonist (MK-801) may have some initial benefits in ameliorating the development of sensitized withdrawal excitability, such treatment may also render subjects more vulnerable to seizure activity at later time points.

  5. Withdrawal Symptoms and Nicotine Dependence Severity Predict Virtual Reality Craving in Cigarette-Deprived Smokers

    PubMed Central

    Cooper, Kim N.; Mahoney, James J.; Bordnick, Patrick S.; Salas, Ramiro; Kosten, Thomas R.; Dani, John A.; De La Garza, Richard

    2015-01-01

    Introduction: Virtual reality (VR) has been shown to be effective in eliciting responses to nicotine cues in cigarette smokers. The primary aim of this study was to investigate whether cigarette-deprived smokers would exhibit increased craving and changes in heart rate when viewing cigarette related cues as compared to non-smoking cues in a VR environment, and the secondary aim was to assess the extent to which self-assessed measures of withdrawal and dependence correlated with VR craving. Methods: Nicotine-dependent cigarette smokers were recruited for a 2 day study. On Day 1, participants smoked as usual and on Day 2 were deprived from smoking overnight. On both days, participants completed self-assessment questionnaires on withdrawal, craving, and nicotine-dependence. Participants completed a VR session during the cigarette deprivation condition only (Day 2). During this session, they were exposed to active smoking and placebo (non-smoking) cues. Results: The data show that self-reported levels of “craving” (p < .01) and “thinking about cigarettes” (p < .0001) were significantly greater after exposure to the active cues versus non-smoking cues. Significant increases in heart rate were found for 3 of 4 active cues when compared to non-smoking cues (p < .05). Finally, significant positive correlations were found between self-reported craving prior to the VR session and craving induced by active VR cues (p < .01). Conclusions: In this report, active VR cues elicited craving during cigarette deprivation. This is the first study to demonstrate that self-reported craving, withdrawal symptoms, and nicotine dependence severity predict cue-induced craving in the VR setting. PMID:25475087

  6. Drug withdrawal convulsions and susceptibility to convulsants after short-term selective breeding for acute ethanol withdrawal.

    PubMed

    Metten, P; Belknap, J K; Crabbe, J C

    1998-09-01

    High Alcohol Withdrawal (HAW) and Low Alcohol Withdrawal (LAW) mice were selectively bred from a foundation population of C57BL6/J (B6) x DBA/2J (D2) F2 intercross progeny for display of intense or mild handling-induced withdrawal convulsions, respectively, following a single injection of a hypnotic dose of ethanol (alcohol; 4 g/kg). The HAW line had significantly greater alcohol withdrawal severity scores compared to the LAW line after only a single generation of selection; the magnitude of the line difference was 8-fold by the fourth selected generation. We tested these lines for severity of withdrawal convulsions following the benzodiazepine, diazepam; the gaseous anesthetic, nitrous oxide; the imidazopyridine, zolpidem and the barbiturate, pentobarbital. In all cases, HAW mice had significantly greater withdrawal severity than mice of the LAW line. These results indicate that some genes influencing withdrawal convulsion severity following ethanol also affect withdrawal from other CNS depressants. D2 mice are more sensitive to a variety of convulsants than B6 mice (and have more severe withdrawal convulsions). We, therefore, tested separate groups of mice of both selectively bred lines for threshold sensitivity to pentylenetetrazol (PTZ), N-methyl-D-aspartate (NMDA) and kainic acid (KA). No line differences were detected. These results indicate that genes influencing severity of withdrawal from several depressant drugs are largely different from those affecting susceptibility to GABAergic or glutamatergic convulsants.

  7. Susceptibility to ethanol withdrawal seizures is produced by BK channel gene expression.

    PubMed

    Ghezzi, Alfredo; Krishnan, Harish R; Atkinson, Nigel S

    2014-05-01

    Alcohol withdrawal seizures are part of the symptomatology of severe alcohol dependence and are believed to originate from long-term neural adaptations that counter the central nervous system depressant effects of alcohol. Upon alcohol withdrawal, however, the increased neural excitability that was adaptive in the presence of alcohol becomes counter-adaptive and produces an imbalanced hyperactive nervous system. For some individuals, the uncovering of this imbalance by alcohol abstention can be sufficient to generate a seizure. Using the Drosophila model organism, we demonstrate a central role for the BK-type Ca(2+) -activated K(+) channel gene slo in the production of alcohol withdrawal seizures.

  8. Daily home-based spirometry during withdrawal of inhaled corticosteroid in severe to very severe chronic obstructive pulmonary disease

    PubMed Central

    Rodriguez-Roisin, Roberto; Tetzlaff, Kay; Watz, Henrik; Wouters, Emiel FM; Disse, Bernd; Finnigan, Helen; Magnussen, Helgo; Calverley, Peter MA

    2016-01-01

    The WISDOM study (NCT00975195) reported a change in lung function following withdrawal of fluticasone propionate in patients with severe to very severe COPD treated with tiotropium and salmeterol. However, little is known about the validity of home-based spirometry measurements of lung function in COPD. Therefore, as part of this study, following suitable training, patients recorded daily home-based spirometry measurements in addition to undergoing periodic in-clinic spirometric testing throughout the study duration. We subsequently determined the validity of home-based spirometry for detecting changes in lung function by comparing in-clinic and home-based forced expiratory volume in 1 second in patients who underwent stepwise fluticasone propionate withdrawal over 12 weeks versus patients remaining on fluticasone propionate for 52 weeks. Bland–Altman analysis of these data confirmed good agreement between in-clinic and home-based measurements, both across all visits and at the individual visits at study weeks 6, 12, 18, and 52. There was a measurable difference between the forced expiratory volume in 1 second values recorded at home and in the clinic (mean difference of −0.05 L), which may be due to suboptimal patient effort in performing unsupervised recordings. However, this difference remained consistent over time. Overall, these data demonstrate that home-based and in-clinic spirometric measurements were equally valid and reliable for assessing lung function in patients with COPD, and suggest that home-based spirometry may be a useful tool to facilitate analysis of changes in lung function on a day-to-day basis. PMID:27578972

  9. Correlates of nicotine withdrawal severity in smokers during a smoke-free psychiatric hospitalization.

    PubMed

    Soyster, Peter; Anzai, Nicole E; Fromont, Sebastien C; Prochaska, Judith J

    2016-11-01

    Psychiatric hospitals are increasingly adopting smoke-free policies. Tobacco use is common among persons with mental illness, and nicotine withdrawal (NW), which includes symptoms of depression, anxiety, anger/irritability, and sleep disturbance, may confound psychiatric assessment and treatment in the inpatient setting. This study aimed to characterize NW and correlates of NW severity in a sample of smokers hospitalized for treatment of mental illness in California. Participants (N=754) were enrolled between 2009 and 2013, and averaged 17 (SD=10) cigarettes/day prior to hospitalization. Though most (70%) received nicotine replacement therapy (NRT) during hospitalization, a majority (65%) reported experiencing moderate to severe NW. In a general linear regression model, NW symptoms were more severe for women, African American patients, and polysubstance abusers. Though invariant by psychiatric diagnostic category, greater NW was associated with more severe overall psychopathology and greater cigarette dependence. The full model explained 46% of the total variation in NW symptom severity (F [19, 470]=23.03 p<0.001). A minority of participants (13%) refused NRT during hospitalization. Those who refused NRT reported milder cigarette dependence and stated no prior use of NRT. Among smokers hospitalized for mental illness, NW severity appears multidetermined, related to cigarette dependence, demographic variables, psychiatric symptom severity, and other substance use. Assessment and treatment of NW in the psychiatric hospital is clinically warranted and with extra attention to groups that may be more vulnerable or naïve to cessation pharmacotherapy.

  10. Correlates of nicotine withdrawal severity in smokers during a smoke-free psychiatric hospitalization☆

    PubMed Central

    Soyster, Peter; Anzai, Nicole E.; Fromont, Sebastien C.; Prochaska, Judith J.

    2016-01-01

    Psychiatric hospitals are increasingly adopting smoke-free policies. Tobacco use is common among persons with mental illness, and nicotine withdrawal (NW), which includes symptoms of depression, anxiety, anger/irritability, and sleep disturbance, may confound psychiatric assessment and treatment in the inpatient setting. This study aimed to characterize NW and correlates of NW severity in a sample of smokers hospitalized for treatment of mental illness in California. Participants (N = 754) were enrolled between 2009 and 2013, and averaged 17 (SD = 10) cigarettes/day prior to hospitalization. Though most (70%) received nicotine replacement therapy (NRT) during hospitalization, a majority (65%) reported experiencing moderate to severe NW. In a general linear regression model, NW symptoms were more severe for women, African American patients, and polysubstance abusers. Though invariant by psychiatric diagnostic category, greater NW was associated with more severe overall psychopathology and greater cigarette dependence. The full model explained 46% of the total variation in NW symptom severity (F [19, 470] = 23.03 p < 0.001). A minority of participants (13%) refused NRT during hospitalization. Those who refused NRT reported milder cigarette dependence and stated no prior use of NRT. Among smokers hospitalized for mental illness, NW severity appears multidetermined, related to cigarette dependence, demographic variables, psychiatric symptom severity, and other substance use. Assessment and treatment of NW in the psychiatric hospital is clinically warranted and with extra attention to groups that may be more vulnerable or naïve to cessation pharmacotherapy. PMID:26892910

  11. Withdrawal from free-choice ethanol consumption results in increased packing density of glutamine synthetase-immunoreactive astrocytes in the prelimbic cortex of alcohol-preferring rats.

    PubMed

    Miguel-Hidalgo, José Javier

    2006-01-01

    Excess activation of glutamatergic neurotransmission in the cerebral cortex following ethanol withdrawal is considered to contribute to significant behavioural disturbances, and to alcohol craving. Astrocytes may play a role in these manifestations because astrocytes are essential in the regulation of released glutamate and its conversion to glutamine through the enzyme glutamine synthetase (GS). However, it is unclear if withdrawal from free-choice ethanol drinking causes changes in the numbers of astrocytes expressing GS or the cytoskeletal protein of astrocytes glial fibrillary acidic protein (GFAP). Alcohol-preferring (P) rats exposed to free-choice ethanol drinking were either maintained without forced interruption of ethanol drinking, subjected to a 3-day withdrawal period at the end of 2 months, or subjected to three 3-day withdrawal periods along 6 months. At 2 months, P rats were also compared with alcohol-naïve alcohol non-preferring rats (NP) rats. Packing density of GS and GFAP-immunoreactive (IR) astrocytes was measured in sections from the prelimbic cortex (PLC) using the optical disector probe. An alcohol deprivation effect was observed in P rats with withdrawals during a 6-month ethanol drinking period. Ethanol withdrawal significantly increased the packing density of GS- and GFAP-IR astrocytes in the PLC of P rats as compared with P rats with continuous access to ethanol. In addition, there was a positive correlation between the pre-withdrawal ethanol consumption and the packing density of GS-IR astrocytes. The present results suggest the involvement of astrocytes in the regulation of the glutamatergic activation associated with withdrawal from free-choice ethanol consumption and point to differential adaptations of GS and GFAP to prolonged alcohol drinking in the PLC of P rats.

  12. Efficacy of transcranial magnetotherapy in the complex treatment of alcohol withdrawal syndrome.

    PubMed

    Staroverov, A T; Zhukov, O B; Raigorodskii, Yu M

    2009-11-01

    A total of 54 patients with alcoholism were studied during abstinence. Of these, 29 patients in the experimental group received basal therapy supplemented with physical treatment consisting of transcranial dynamic magnetotherapy (TcDMT), while the control group of 25 patients received only basal therapy. Comparison of the status of patients in the experimental and control groups during treatment demonstrated advantages of TcDMT in relation to improving the functional state of the CNS, memory, and attention, the autonomic nervous system, and the psychoemotional status of the patients (with decreases in the severity of anxiety and depression).

  13. Voluntary co-consumption of alcohol and nicotine: Effects of abstinence, intermittency, and withdrawal in mice.

    PubMed

    O'Rourke, Kyu Y; Touchette, Jillienne C; Hartell, Elizabeth C; Bade, Elizabeth J; Lee, Anna M

    2016-10-01

    Alcohol and nicotine are often used together, and there is a high rate of co-occurrence between alcohol and nicotine addiction. Most animal models studying alcohol and nicotine interactions have utilized passive drug administration, which may not be relevant to human co-addiction. In addition, the interactions between alcohol and nicotine in female animals have been understudied, as most studies have used male animals. To address these issues, we developed models of alcohol and nicotine co-consumption in male and female mice that utilized voluntary, oral consumption of unsweetened alcohol, nicotine and water. We first examined drug consumption and preference in single-drug, sequential alcohol and nicotine consumption tests in male and female C57BL/6 and DBA/2J mice. We then tested chronic continuous and intermittent access alcohol and nicotine co-consumption procedures. We found that male and female C57BL/6 mice readily co-consumed unsweetened alcohol and nicotine. In our continuous co-consumption procedures, we found that varying the available nicotine concentration during an alcohol abstinence period affected compensatory nicotine consumption during alcohol abstinence, and affected rebound alcohol consumption when alcohol was re-introduced. Consumption of alcohol and nicotine in an intermittent co-consumption procedure produced higher alcohol consumption levels, but not nicotine consumption levels, compared with the continuous co-consumption procedures. Finally, we found that intermittent alcohol and nicotine co-consumption resulted in physical dependence. Our data show that these voluntary co-consumption procedures can be easily performed in mice and can be used to study behavioral interactions between alcohol and nicotine consumption, which may better model human alcohol and nicotine co-addiction.

  14. Does Reducing Withdrawal Severity Mediate Nicotine Patch Efficacy? A Randomized Clinical Trial

    ERIC Educational Resources Information Center

    Ferguson, Stuart G.; Shiffman, Saul; Gwaltney, Chad J.

    2006-01-01

    Nicotine replacement therapy (NRT) repeatedly has been shown to improve smoking treatment outcome. The major mechanism posited for this improvement in outcome is that NRT reduces nicotine craving and withdrawal. The authors tested this hypothesized mechanism of action using real-time data on craving and withdrawal, collected by ecological…

  15. Alcohol Use Problem Severity and Problem Behavior Engagement among School-Based Youths in Minnesota

    ERIC Educational Resources Information Center

    Mancha, Brent E.; Rojas-Neese, Vanessa C.; Latimer, William W.

    2010-01-01

    This study created an alcohol use problem severity taxonomy and examined its association to engagement in other problem behaviors. Minnesota youths were categorized based on their frequency of alcohol use and DSM-IV alcohol abuse and dependence criteria. Greater alcohol use problem severity was generally associated with higher prevalence of…

  16. The influence of a chronic adolescent nicotine exposure on ethanol withdrawal severity during adulthood in C3H mice.

    PubMed

    Riley, Hugh H; Zalud, André W; Diaz-Granados, Jaime L

    2010-02-01

    Animal and human studies have shown tolerance, consumption, relapse, and behavioral interactions between ethanol and nicotine, but little is understood about their interaction, especially as it relates to ethanol withdrawal in adulthood for subjects who have an adolescent history of using these drugs. This study investigated nicotine's influence on ethanol withdrawal seizures in two different age groups of male C3H mice. Adolescent and adult male C3H mice, beginning at postnatal day 28 or 70, respectively, were subjected to a 7-day chronic exposure to ethanol only, ethanol plus nicotine, nicotine only, or vehicle treatment. Six weeks later, all the groups were subjected to chronic exposure to ethanol vapors and the severity of their ethanol withdrawal seizures was assessed by handling-induced convulsions. An adolescent exposure to chronic nicotine resulted in an exacerbation of ethanol withdrawal seizures in adulthood. Given this, adolescence may contain a neurophysiological critical period that is sensitive to nicotine and which may result in an altered response to ethanol dependency in adulthood. These findings have serious implications for the long-term consequences following co-abuse of these drugs during adolescence.

  17. Predicting Post-Treatment-Initiation Alcohol Use among Patients with Severe Mental Illness and Alcohol Use Disorders

    ERIC Educational Resources Information Center

    Bradizza, Clara M.; Maisto, Stephen A.; Vincent, Paula C.; Stasiewicz, Paul R.; Connors, Gerard J.; Mercer, Nicole D.

    2009-01-01

    Few investigators studying alcohol abuse among individuals with a severe mental illness (SMI) have examined predictors of posttreatment alcohol outcomes. In the present study, a multivariate approach based on a theoretical model was used to study the relationship between psychosocial factors and post-treatment-initiation alcohol use. Predictors of…

  18. Case of severe alcoholic hepatitis treated with granulocytapheresis

    PubMed Central

    Watanabe, Yukari; Kamimura, Kenya; Iwasaki, Tomohiro; Abe, Hiroyuki; Takahashi, Shunsaku; Mizuno, Ken-ichi; Takeuchi, Manabu; Eino, Atsushi; Narita, Ichiei; Terai, Shuji

    2016-01-01

    Severe alcoholic hepatitis (AH) has a high mortality, and it is associated with encephalopathy, acute renal failure, sepsis, gastrointestinal bleeding, and endotoxemia. The 28-d mortality remains poor (34%-40%), because no effective treatment has been established. Recently, corticosteroids (CS) have been considered effective for significantly improving the prognosis of those with AH, as it prevents the production of pro-inflammatory cytokines. However, CS are not always appropriate as an initial therapeutic option, such as in cases with an infection or resistance to CS. We describe a patient with severe AH complicated by a severe infection caused by the multidrug resistance bacteria (Pseudomonas aeruginosa), and was successfully treated with granulocytapheresis monotherapy without using CS. The experience of this case will provide understanding of the disease and information treating cases without using CS. PMID:27900326

  19. A rapid increase in lipoprotein (a) levels after ethanol withdrawal in alcoholic men

    SciTech Connect

    Kervinen, K.; Savolainen, J.J.; Kesaeniemi, Y.A. )

    1991-01-01

    Plasma concentrations of lipoprotein (a) (Lp(a)) were studied in 11 male alcoholics at the end of a drinking period and monitored during subsequent abstinence. Lp(a) levels showed a daily increase for four consecutive days after the beginning of abstinence, the values for the third and the fourth day being significantly higher than those of the first day. The changes in Lp(a) showed no association with the changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels. In one alcoholic subject with a heterozygous form of familial hypercholesterolemia who was monitored for 11 days, the Lp(a) levels rose up to the fourth day and remained at a high level thereafter. These results suggest that ethanol ingestion may be associated with a lower of Lp(a) levels, which may contribute to the delayed progression of atherosclerosis observed in alcohol drinkers.

  20. Effect of variations in treatment regimen and liver cirrhosis on exposure to benzodiazepines during treatment of alcohol withdrawal syndrome

    PubMed Central

    Gershkovich, Pavel; Wasan, Kishor M; Ribeyre, Charles; Ibrahim, Fady; McNeill, John H

    2015-01-01

    Purpose: Benzodiazepines (BDZs) are the drugs of choice to prevent the symptoms of alcohol withdrawal syndrome (AWS). Various treatment protocols are published and have been shown to be effective in both office-managed and facility-managed treatment of AWS. The aim of this scientific commentary is to demonstrate the differences in the expected exposure to BDZs during AWS treatment using different treatment regimens available in the literature, in patients with or without alcoholic liver cirrhosis. Methods: Diazepam and lorazepam AWS protocols were examined and reviewed in the literature, and blood plasma levels were examined and compared, respectively. Results: Considerable variation in the blood levels with the different dosing schedules was found. Because the drugs are metabolized differently, we have also shown that liver disease affects the blood levels of diazepam, but not of lorazepam. Conclusions: Differences in treatment regimens, the choice of BDZ, as well as the presence of liver cirrhosis can substantially alter the exposure of patients to drugs used for AWS treatment. Outpatient treatment of AWS has been shown to be relatively safe and effective for the treatment of AWS but patients should be carefully monitored. PMID:26322116

  1. Effects of lorazepam tolerance and withdrawal on GABA[sub A] receptor operated chloride channels in mice selected for differences in ethanol withdrawal severity

    SciTech Connect

    Allan, A.M.; Baier, L.D.; Zhang, Xiaoying )

    1992-01-01

    Withdrawal seizure prone (WSP) and withdrawal seizure resistant (WSR) mice were treated with 5 mg/kg lorazepam for 7 days via implanted osmotic mini pumps. Following chronic drug treatment, brains were assayed for GABA-mediated chloride flux (GABA-Cl[sup [minus

  2. Predicting Post Treatment-Initiation Alcohol Use Among Patients With Severe Mental Illness and Alcohol Use Disorders

    PubMed Central

    Bradizza, Clara M.; Maisto, Stephen A.; Vincent, Paula C.; Stasiewicz, Paul R.; Connors, Gerard J.; Mercer, Nicole D.

    2010-01-01

    Few studies examining alcohol abuse among individuals with a severe mental illness (SMI) have examined predictors of post-treatment alcohol outcomes. The present study uses a multivariate approach based on a theoretical model to study the relationship between psychosocial factors and post treatment-initiation alcohol use. Predictors of alcohol use outcomes were examined in 278 individuals diagnosed with a current DSM-IV schizophrenia-spectrum or bipolar disorder and an alcohol use disorder (AUD). At 6-months follow-up after initiating treatment, 144 of 228 available participants (63%) had good clinical outcomes. The results of structural equation modeling indicated that type of pretreatment residential setting was directly related to treatment with participants living in supervised settings (41%) reporting significantly more days of treatment (β = .34, p < .001). In addition, participants with more psychiatric symptoms, assessed by the Brief Symptom Inventory and Structured Clinical Interview for the Positive and Negative Syndrome Scale, reported significantly fewer treatment days (β = −.20, p < .001). Number of days participants attended treatment was indirectly associated with alcohol use outcomes and was mediated by use of alcohol coping skills, such that more frequent use of alcohol-specific coping skills was associated with less post treatment-initiation alcohol use (β = −.34, p < .001). This study emphasizes the favorable prognosis for alcohol outcomes among treated individuals with a SMI and AUD and the importance of psychosocial interventions, particularly those that result in better alcohol-specific coping skills. PMID:19968390

  3. Relationship of attention-deficit/hyperactivity disorder symptom severity with severity of alcohol-related problems in a sample of inpatients with alcohol use disorder

    PubMed Central

    Bozkurt, Muge; Evren, Cuneyt; Umut, Gokhan; Evren, Bilge

    2016-01-01

    Purpose Attention-deficit/hyperactivity disorder (ADHD) has been shown to be related to a higher risk of developing psychiatric problems such as depressive disorders, substance use disorder, and impulsivity. Adults who have comorbid ADHD and alcohol use disorder (AUD) are at greater risk of negative outcomes. Thus, it is important to evaluate the relationship of ADHD symptoms and the severity of alcohol-related problems among patients with AUD. The aim of the present study was to evaluate the effect of ADHD symptoms on severity of alcohol-related problems, while controlling the effects of depression and impulsivity in a sample of inpatients with AUD. Patients and methods Participants (n=190) were evaluated with the Beck Depression Inventory, the Short Form Barratt Impulsiveness Scale, the Michigan Alcohol Screening Test, and the Adult ADHD Self-Report Scale. Results Severity of the scale scores was positively correlated with each other. Although severity of depression and impulsivity (particularly non-planning impulsivity) predicted the severity of alcohol-related problems in a linear regression model, when severity of ADHD symptoms was included in the analysis, the inattentive subscale score, in particular, predicted the severity of alcohol-related problems together with non-planning impulsivity, whereas depression was no longer a predictor. Conclusion These findings suggest that, together with non-planning impulsivity, symptoms of ADHD (particularly inattentive factor) are an important factor that predict alcohol-related problems, while controlling the severity of depressive symptoms among inpatients with AUD. PMID:27462159

  4. Alcohol Use Disorders

    MedlinePlus

    ... Search Alcohol & Your Health Overview of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol ... less effect than before? Found that when the effects of alcohol were wearing off, you had withdrawal symptoms, such ...

  5. Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic- pituitary-adrenal axis activation

    PubMed Central

    Reynolds, Anna R.; Saunders, Meredith A.; Brewton, Honoree’ W.; Winchester, Sydney R.; Elgumati, Ibrahim S.; Prendergast, Mark A.

    2015-01-01

    Background The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. Methods Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 1100 hrs on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60 mg/kg/i.g.) or a placebo and withdrawal was monitored. Results Peak BELs of 225.52 mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g. aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. Conclusions The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence. PMID:26143299

  6. Influence of Volatile Anesthesia on the Release of Glutamate and other Amino Acids in the Nucleus Accumbens in a Rat Model of Alcohol Withdrawal: A Pilot Study

    PubMed Central

    Seidemann, Thomas; Spies, Claudia; Morgenstern, Rudolf; Wernecke, Klaus-Dieter; Netzhammer, Nicolai

    2017-01-01

    Background Alcohol withdrawal syndrome is a potentially life-threatening condition, which can occur when patients with alcohol use disorders undergo general anesthesia. Excitatory amino acids, such as glutamate, act as neurotransmitters and are known to play a key role in alcohol withdrawal syndrome. To understand this process better, we investigated the influence of isoflurane, sevoflurane, and desflurane anesthesia on the profile of excitatory and inhibitory amino acids in the nucleus accumbens (NAcc) of alcohol-withdrawn rats (AWR). Methods Eighty Wistar rats were randomized into two groups of 40, pair-fed with alcoholic or non-alcoholic nutrition. Nutrition was withdrawn and microdialysis was performed to measure the activity of amino acids in the NAcc. The onset time of the withdrawal syndrome was first determined in an experiment with 20 rats. Sixty rats then received isoflurane, sevoflurane, or desflurane anesthesia for three hours during the withdrawal period, followed by one hour of elimination. Amino acid concentrations were measured using chromatography and results were compared to baseline levels measured prior to induction of anesthesia. Results Glutamate release increased in the alcohol group at five hours after the last alcohol intake (p = 0.002). After 140 min, desflurane anesthesia led to a lower release of glutamate (p < 0.001) and aspartate (p = 0.0007) in AWR compared to controls. GABA release under and after desflurane anesthesia was also significantly lower in AWR than controls (p = 0.023). Over the course of isoflurane anesthesia, arginine release decreased in AWR compared to controls (p < 0.001), and aspartate release increased after induction relative to controls (p20min = 0.015 and p40min = 0.006). However, amino acid levels did not differ between the groups as a result of sevoflurane anesthesia. Conclusions Each of three volatile anesthetics we studied showed different effects on excitatory and inhibitory amino acid concentrations. Under

  7. Alcohol-based hand sanitizers: severe intoxication in children.

    PubMed

    2012-07-01

    Alcohol-based hand sanitizers are an alternative to hand washing with soap and water when water is unavailable. Their use has increased over the last decade. Cases of acute intoxication have been reported in children after accidental ingestion of alcohol-based hand sanitizers, sometimes leading to inebriation, agitation, drowsiness, impaired consciousness, and blood alcohol levels sometimes exceeding 2 g/I. In practice, alcohol-based hand sanitizers should be kept out of reach of children and should only be used when hand washing with soap and water is not possible. The possibility of alcohol intoxication should be borne in mind when a child suddenly presents with behaviour problems or altered consciousness.

  8. DIFFERENTIAL EFFECTS OF SINGLE VERSUS REPEATED ALCOHOL WITHDRAWAL ON THE EXPRESSION OF ENDOCANNABINOID SYSTEM-RELATED GENES IN THE RAT AMYGDALA

    PubMed Central

    Serrano, Antonia; Rivera, Patricia; Pavon, Francisco J.; Decara, Juan; Suárez, Juan; de Fonseca, Fernando Rodriguez; Parsons, Loren H.

    2011-01-01

    Background Endogenous cannabinoids such as anandamide and 2-arachidonoylglycerol (2-AG) exert important regulatory influences on neuronal signaling, participate in short- and long-term forms of neuroplasticity, and modulate stress responses and affective behavior in part through the modulation of neurotransmission in the amygdala. Alcohol consumption alters brain endocannabinoid levels, and alcohol dependence is associated with dysregulated amygdalar function, stress responsivity and affective control. Methods The consequence of long-term alcohol consumption on the expression of genes related to endocannabinoid signaling was investigated using quantitative RT-PCR analyses of amygdala tissue. Two groups of ethanol-exposed rats were generated by maintenance on an ethanol liquid diet (10%): one group received continuous access to ethanol for 15 days, while the second group was given intermittent access to the ethanol diet (5 days/week for 3 weeks). Control subjects were maintained on an isocaloric ethanol-free liquid diet. To provide an initial profile of acute withdrawal amygdala tissue was harvested following either 6 or 24 hours of ethanol withdrawal. Results Acute ethanol withdrawal was associated with significant changes in mRNA expression for various components of the endogenous cannabinoid system in the amygdala. Specifically, reductions in mRNA expression for the primary clearance routes for anandamide and 2-AG (FAAH and MAGL, respectively) were evident, as were reductions in mRNA expression for CB1, CB2 and GPR55 receptors. Although similar alterations in FAAH mRNA were evident following either continuous or intermittent ethanol exposure, alterations in MAGL and cannabinoid receptor-related mRNA (e.g. CB1, CB2, GPR55) were more pronounced following intermittent exposure. In general, greater withdrawal-associated deficits in mRNA expression were evident following 24 versus 6 hours of withdrawal. No significant changes in mRNA expression for enzymes involved in

  9. College Students' Perceptions of Severity and Willingness to Seek Psychological Help For Drug and Alcohol Problems

    ERIC Educational Resources Information Center

    Lowinger, Robert Jay

    2012-01-01

    A sample of 201 college students were surveyed with respect to their perceptions of severity and willingness to seek psychological help for drug and alcohol problems. Results indicated that students perceive alcohol problems as significantly less serious than drug problems and are significantly less willing to seek help for alcohol problems. Males…

  10. Withdrawal-associated increases and decreases in functional neural connectivity associated with altered emotional regulation in alcoholism.

    PubMed

    O'Daly, Owen G; Trick, Leanne; Scaife, Jess; Marshall, Jane; Ball, David; Phillips, Mary L; Williams, Stephen S C; Stephens, David N; Duka, Theodora

    2012-09-01

    Alcoholic patients who have undergone multiple detoxifications/relapses show altered processing of emotional signals. We performed functional magnetic resonance imaging during performance of implicit and explicit versions of a task in which subjects were presented with morphs of fearful facial emotional expressions. Participants were abstaining, multiply detoxified (MDTx; n=12) or singly detoxified patients (SDTx; n=17), and social drinker controls (n=31). Alcoholic patients were less able than controls to recognize fearful expressions, and showed lower activation in prefrontal areas, including orbitofrontal cortex and insula, which mediate emotional processing. The decrease in activation was greater in MDTx patients who also showed decreased connectivity between insula and prefrontal areas, and between amygdala and globus pallidus. In the explicit condition, the strength of connectivity between insula and areas involved in regulation of emotion (inferior frontal cortex and frontal pole) was negatively correlated with both the number of detoxifications and dependency (measured by the severity of alcohol dependency (SADQ) and control over drinking score (Impaired Control questionnaire, ICQ)). In contrast, increased connectivity was found between insula and the colliculus neuronal cluster, and between amygdala and stria terminalis bed nucleus. In the implicit condition, number of detoxifications and ICQ score correlated positively with connectivity between amygdala and prefrontal cortical areas involved in attentional and executive processes. Repeated episodes of detoxification from alcohol are associated with altered function both in fear perception pathways and in cortical modulation of emotions. Such changes may confer increased sensitivity to emotional stress and impaired social competence, contributing to relapse.

  11. Adolescent Mice Are Resilient to Alcohol Withdrawal-Induced Anxiety and Changes in Indices of Glutamate Function within the Nucleus Accumbens

    PubMed Central

    Lee, Kaziya M.; Coelho, Michal A.; McGregor, Hadley A.; Solton, Noah R.; Cohen, Matan; Szumlinski, Karen K.

    2016-01-01

    Binge-drinking is the most prevalent form of alcohol abuse and while an early life history of binge-drinking is a significant risk factor for subsequent alcoholism and co-morbid affective disorders, relatively little is known regarding the biobehavioral impact of binge-drinking during the sensitive neurodevelopmental period of adolescence. In adult mice, a month-long history of binge-drinking elicits a hyper-glutamatergic state within the nucleus accumbens (Acb), coinciding with hyper-anxiety. Herein, we employed a murine model of binge-drinking to determine whether or not: (1) withdrawal-induced changes in brain and behavior differ between adult and adolescent bingers; and (2) increased behavioral signs of negative affect and changes in Acb expression of glutamate-related proteins would be apparent in adult mice with less chronic binge-drinking experience (14 days, approximating the duration of mouse adolescence). Adult and adolescent male C57BL/6J mice were subjected to a 14-day binge-drinking protocol (5, 10, 20 and 40% alcohol (v/v) for 2 h/day), while age-matched controls received water. At 24 h withdrawal, half of the animals from each group were assayed for negative affect, while tissue was sampled from the shell (AcbSh) and core (AcbC) subregions of the remaining mice for immunoblotting analyses. Adult bingers exhibited hyper-anxiety when tested for defensive marble burying. Additionally, adult bingers showed increased mGlu1, mGlu5, and GluN2b expression in the AcbSh and PKCε and CAMKII in the AcbC. Compared to adults, adolescent mice exhibited higher alcohol intake and blood alcohol concentrations (BACs); however, adolescent bingers did not show increased anxiety in the marble-burying test. Furthermore, adolescent bingers also failed to exhibit the same alcohol-induced changes in mGlu and kinase protein expression seen in the adult bingers. Irrespective of age, bingers exhibited behavioral hyperactivity in the forced swim test (FST) compared to water

  12. Change in Psychiatric Symptomatology after Benfotiamine Treatment in Males is a Function of Lifetime Alcoholism Severity

    PubMed Central

    Manzardo, Ann M.; Pendleton, Tiffany; Poje, Albert; Penick, Elizabeth C.; Butler, Merlin G.

    2015-01-01

    Background Severe alcoholism can be associated with significant nutritional and vitamin deficiency, especially vitamin B1 (thiamine) which is associated with serious illness and neurological deficits that influence mood and cognition. We previously reported reduced alcohol consumption among female but not male alcoholics after supplementation with the high potency thiamine analog benfotiamine (BF). As a follow-up, we have examined the relationship between lifetime alcoholism severity and psychiatric symptoms among the alcohol dependent men from this cohort and their response to BF treatment. Methods Eighty-five adult men (mean age = 48 ± 8 yrs) meeting DSM-IV-TR criteria for current alcohol dependence participated in a randomized, double-blind, placebo-controlled trial of 600 mg BF vs placebo (PL) for 6 months. Psychometric testing included a derived Lifetime Alcoholism Severity Score (AS), Symptom Checklist 90R (SCL-90R), and the Barratt Impulsivity Scale (BIS) at baseline and at 6 months with data analyzed using ANOVA and MANOVA modeling. Results Baseline SCL-90-R scale scores for men with high alcoholism severity (AS ≥ 24; N=46 HAS) were significantly greater than for men with low alcoholism severity (AS < 24; N=39 LAS), but BIS scores did not differ. MANOVA modeling identified a significant treatment effect (F=2.5, df=10, p<0.03) and treatment x alcoholism severity level interaction (F=2.5, dfnum=10, dfden=30, p<0.03) with SCL-90-R scores showing a reduction in symptoms among BF treated, high severity males. Conclustion BF appears to reduce psychiatric distress and may facilitate recovery in severely affected males with lifetime alcohol dependence and should be considered for adjuvant therapy in alcohol rehabilitation. PMID:25908323

  13. Parent's alcoholism severity and family topic avoidance about alcohol as predictors of perceived stigma among adult children of alcoholics: Implications for emotional and psychological resilience.

    PubMed

    Haverfield, Marie C; Theiss, Jennifer A

    2016-01-01

    Alcoholism is a highly stigmatized condition, with both alcohol-dependent individuals and family members of the afflicted experiencing stigmatization. This study examined the severity of a parent's alcoholism and family topic avoidance about alcohol as two factors that are associated with family members' perceptions of stigma. Three dimensions of stigma were considered: discrimination stigma, disclosure stigma, and positive aspect stigma. In addition, this study assessed associations between perceived stigmatization and individuals' experiences of depressive symptoms, self-esteem, and resilience. Adult children of alcoholics (N = 622) were surveyed about family conditions, perceived stigma, and their emotional and psychological well-being. Regression analyses revealed that the severity of a parent's alcoholism predicted all three types of stigma for females, but not for males. In addition, family topic avoidance about alcohol predicted all types of stigma for males and discrimination stigma and positive aspect stigma for females. With few exceptions, the three types of stigma predicted depressive symptoms, self-esteem, and resilience for both male and female adult children of alcoholics. The results are discussed in terms of their implications for promoting a family environment that mitigates stigma and encourages emotional and psychological well-being. In 2012, approximately 3.3 million deaths worldwide were due to the harmful use of alcohol (World Health Organization [WHO], 2014). Individuals who abuse alcohol are susceptible to a variety of negative health outcomes (Rehm et al., 2009) and display inappropriate social behaviors (Klingemann, 2001; Schomerus et al., 2011a). General societal perceptions tend to characterize alcohol-dependent individuals as irresponsible and lacking in self-control (Schomerus et al., 2011b). Research in the United Kingdom found that 54% of the population believes alcohol-dependent individuals are personally to blame for their own

  14. Cue Reactivity Is Associated with Duration and Severity of Alcohol Dependence: An fMRI Study

    PubMed Central

    Sjoerds, Zsuzsika; van den Brink, Wim; Beekman, Aartjan T. F.; Penninx, Brenda W. J. H.; Veltman, Dick J.

    2014-01-01

    Introduction With the progression of substance dependence, drug cue-related brain activation is thought to shift from motivational towards habit pathways. However, a direct association between cue-induced brain activation and dependence duration has not yet been shown. We therefore examined the relationship between alcohol cue-reactivity in the brain, cue-induced subjective craving and alcohol dependence duration and severity. Since alcohol dependence is highly comorbid with depression/anxiety, which may modulate brain responses to alcohol cues, we also examined the relation between comorbid depression/anxiety and cue-reactivity. Methods We compared 30 alcohol dependent patients with 15 healthy controls and 15 depression/anxiety patients during a visual alcohol cue-reactivity task using functional magnetic resonance imaging blood oxygenated level-dependent responses and subjective craving as outcomes. Within the alcohol dependent group we correlated cue-reactivity with alcohol dependence severity and duration, with cue-induced craving and with depression/anxiety levels. Results Alcohol dependent patients showed greater cue-reactivity in motivational brain pathways and stronger subjective craving than depression/anxiety patients and healthy controls. Depression/anxiety was not associated with cue-reactivity, but depression severity in alcohol dependent patients was positively associated with craving. Within alcohol dependence, longer duration of alcohol dependence was associated with stronger cue-related activation of the posterior putamen, a structure involved in habits, whereas higher alcohol dependence severity was associated with lower cue-reactivity in the anterior putamen, an area implicated in goal-directed behavior preceding habit formation. Conclusion Cue-reactivity in alcohol dependence is not modulated by comorbid depression or anxiety. More importantly, the current data confirm the hypothesis of a ventral to dorsal striatal shift of learning processes

  15. Anxiety sensitivity and panic reactivity to bodily sensations: relation to quit-day (acute) nicotine withdrawal symptom severity among daily smokers making a self-guided quit attempt.

    PubMed

    Marshall, Erin C; Johnson, Kirsten; Bergman, Jenna; Gibson, Laura E; Zvolensky, Michael J

    2009-10-01

    The current investigation explored the main and interactive effects of panic attacks in response to laboratory-induced bodily sensations and anxiety sensitivity in predicting acute nicotine withdrawal symptoms among daily smokers making a self-guided quit attempt. Participants were 99 daily smokers (58% women; M(age) = 28.4 years, SD = 11.7) who completed a battery of questionnaires, a voluntary hyperventilation challenge, and a measure of nicotine withdrawal symptoms 12 hr after making a self-guided quit attempt. Results indicated that the interaction of anxiety sensitivity and panic responsivity to the challenge predicted quit-day nicotine withdrawal symptom severity above and beyond the main effects (p < .05). The form of the interaction indicated that the relationship between postchallenge panic attack status and acute nicotine withdrawal was more robust among individuals who were low in anxiety sensitivity. Individuals who did not experience a panic attack posthyperventilation who were also low in anxiety sensitivity reported the lowest levels of nicotine withdrawal. Results suggest that anxiety sensitivity may be less relevant with regard to acute nicotine withdrawal severity among individuals with panic-related problems.

  16. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  17. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  18. Peroxisome proliferator-activated receptors α and γ are linked with alcohol consumption in mice and withdrawal and dependence in humans

    PubMed Central

    Blednov, Yuri A.; Benavidez, Jillian M.; Black, Mendy; Ferguson, Laura B.; Schoenhard, Grant L.; Goate, Alison M.; Edenberg, Howard J.; Wetherill, Leah; Hesselbrock, Victor; Foroud, Tatiana; Harris, R. Adron

    2014-01-01

    Background Peroxisome proliferator-activated receptor (PPAR) agonists reduce voluntary ethanol consumption in rat models and are promising therapeutics in the treatment of drug addictions. We studied the effects of different classes of PPAR agonists on chronic ethanol intake and preference in mice with a genetic predisposition for high alcohol consumption and then examined human genome wide association data for polymorphisms in PPAR genes in alcohol-dependent subjects. Methods Two different behavioral tests were used to measure intake of 15% ethanol in C57BL/6J male mice: 24-hour two-bottle choice and limited access (3-hour) two-bottle choice, drinking in the dark. We measured the effects of pioglitazone (10 and 30 mg/kg), fenofibrate (50 and 150 mg/kg), GW0742 (10 mg/kg), tesaglitazar (1.5 mg/kg) and bezafibrate (25 and 75 mg/kg) on ethanol intake and preference. Fenofibric acid, the active metabolite of fenofibrate, was quantified in mouse plasma, liver, and brain by LC-MS/MS. Data from a human genome wide association study (GWAS) completed in the Collaborative Study on the Genetics of Alcoholism (COGA) was then used to analyze the association of single nucleotide polymorphisms (SNPs) in different PPAR genes (PPARA, PPARD, PPARG, and PPARGC1A) with two phenotypes: DSM-IV alcohol dependence (AD) and the DSM-IV criterion of withdrawal. Results Activation of two isoforms of PPARs, α and γ, reduced ethanol intake and preference in the two different consumption tests in mice. However, a selective PPARδ agonist or a pan agonist for all three PPAR isoforms did not decrease ethanol consumption. Fenofibric acid, the active metabolite of the PPARα agonist fenofibrate, was detected in liver, plasma, and brain after 1 or 8 days of oral treatment. The GWAS from COGA supported an association of SNPs in PPARA and PPARG with alcohol withdrawal and PPARGC1A with AD but found no association for PPARD with either phenotype. Conclusions We provide convergent evidence using both

  19. Safety and efficacy of flumazenil for reversal of iatrogenic benzodiazepine-associated delirium toxicity during treatment of alcohol withdrawal, a retrospective review at one center.

    PubMed

    Moore, Philip W; Donovan, J Ward; Burkhart, Keith K; Waskin, Jeffrey A; Hieger, Michelle A; Adkins, Audrey R; Wert, Yijin; Haggerty, David A; Rasimas, J J

    2014-06-01

    Both alcohol withdrawal syndrome (AWS) and benzodiazepines can cause delirium. Benzodiazepine-associated delirium can complicate AWS and prolong hospitalization. Benzodiazepine delirium can be diagnosed with flumazenil, a GABA-A receptor antagonist. By reversing the effects of benzodiazepines, flumazenil is theorized to exacerbate symptoms of AWS and precludes its use. For patients being treated for alcohol withdrawal, flumazenil can diagnose and treat benzodiazepine delirium without precipitating serious or life-threatening adverse events. Hospital admission records were retrospectively reviewed for patients with the diagnosis of AWS who received both benzodiazepines and flumazenil from December 2006 to June 2012 at a university-affiliated inpatient toxicology center. The day of last alcohol consumption was estimated from available blood alcohol content or subjective history. Corresponding benzodiazepine, flumazenil, and adjunctive sedative pharmacy records were reviewed, as were demographic, clinical course, and outcome data. Eighty-five patients were identified (average age 50.3 years). Alcohol concentrations were detectable for 42 patients with average 261 mg/dL (10-530 mg/dL). Eighty patients were treated with adjunctive agents for alcohol withdrawal including antipsychotics (n = 57), opioids (n = 27), clonidine (n = 35), and phenobarbital (n = 23). Average time of flumazenil administration was 4.7 days (1-11 days) after abstinence, and average dose was 0.5 mg (0.2-1 mg). At the time of flumazenil administration, delirium was described as hypoactive (n = 21), hyperactive (n = 15), mixed (n = 41), or not specified (n = 8). Response was not documented in 11 cases. Sixty-two (72.9 %) patients had significant objective improvement after receiving flumazenil. Fifty-six patients required more than one dose (average 5.6 doses). There were no major adverse events and minor adverse effects included transiently increased anxiety

  20. Fear of driving license withdrawal in patients with insulin-treated diabetes mellitus negatively influences their decision to report severe hypoglycemic events to physicians

    PubMed Central

    Brož, Jan; Brabec, Marek; Janíčková Žďárská, Denisa; Fedáková, Zuzana; Hoskovcová, Lucie; You, Jee Young; Doničová, Viera; Hlaďo, Petr; Rahelić, Dario; Kvapil, Milan; Polák, Jan

    2015-01-01

    Background Under current European Union legislation, two severe hypoglycemic events within 12 months is grounds for driving license withdrawal. The aim of the study reported here was to determine whether fear of such a withdrawal could lead to patients concealing severe hypoglycemia from physicians, which could negatively impact further treatment decisions. Methods A total of 663 patients with insulin-treated diabetes were anonymously surveyed about whether they would conceal severe hypoglycemic events from their physicians, if revealing them could result in driving license withdrawal. This investigation utilized an adapted and expanded questionnaire by Graveling et al. Results Of all diabetic patients surveyed, 26.17% would most likely not report hypoglycemia, and 25.86% were undecided. In a group of patients with type 1 diabetes, 31.83% would likely not report hypoglycemic events, and 25.06% were undecided. The patients least likely to report severe hypoglycemic events were those who indicated that vehicles were partly essential for work, and who also had more than two hypoglycemic events monthly. Conclusion A considerable percentage of diabetic patients would likely conceal severe hypoglycemic events from their physicians due to fear of driving license withdrawal. Patient failure to report severe hypoglycemic events can potentially lead to physicians being misinformed regarding the patient’s condition, which could lead to inadequate monitoring and treatment. PMID:26491264

  1. Problematic alcohol use among individuals with HIV: relations with everyday memory functioning and HIV symptom severity.

    PubMed

    Heinz, Adrienne J; Fogler, Kethera A; Newcomb, Michael E; Trafton, Jodie A; Bonn-Miller, Marcel O

    2014-07-01

    Problematic alcohol use has been shown to negatively impact cognitive functions germane to achieving optimal HIV health outcomes. The present study, a secondary data analysis, examined the impact of problematic alcohol use on aspects of everyday memory functioning in a sample of 172 HIV-infected individuals (22 % female; Mage = 48.37 years, SD = 8.64; 39 % Black/non-Hispanic). Additionally, we tested whether self-reported memory functioning explained the relation between problematic alcohol use and HIV symptom severity. Results indicated that problematic patterns of alcohol use were associated with lower total memory functioning, retrieval (e.g., recall-difficulty) and memory for activity (e.g., what you did yesterday) and greater HIV symptom severity. Memory functioning mediated the relation between problematic alcohol use and HIV symptom severity. However, the direction of this relation was unclear as HIV symptom severity also mediated the relation between problematic alcohol use and memory functioning. Findings highlight the importance of integrated care for HIV and alcohol use disorders and suggest that routine alcohol and cognitive screenings may bolster health outcomes among this vulnerable population.

  2. Examining the Associations among Severity of Injunctive Drinking Norms, Alcohol Consumption, and Alcohol-Related Negative Consequences: The Moderating Roles of Alcohol Consumption and Identity

    PubMed Central

    Lewis, Melissa A.; Neighbors, Clayton; Geisner, Irene Markman; Lee, Christine M.; Kilmer, Jason R.; Atkins, David C.

    2009-01-01

    The present study examined a range of injunctive norms for alcohol use and related consequences from less severe behaviors (e.g., drinking with friends) to more severe behaviors (e.g., drinking enough alcohol to pass out), and their relationship with alcohol consumption and alcohol-related negative consequences among college students. In addition, this research aimed to determine if these relationships between injunctive norms and consequences were moderated by alcohol consumption and level of identification with the typical same-sex college student. A random sample (N = 1,002) of undergraduates (56.9% female) completed a Web–based survey that was comprised of measures of drinking behavior, perceived approval of drinking behaviors that ranged in severity (i.e., injunctive norms), and level of identification with the typical same-sex college student. Results suggest that the association between negative consequences and injunctive drinking norms depend on one's own drinking behavior, identification with other students, and the severity of the alcohol use and related consequences for which injunctive norms are assessed. Findings are discussed in terms of false consensus and false uniqueness effects, and deviance regulation perspectives. Implications for preventative interventions are discussed. PMID:20565144

  3. Severity of alcohol use and problem behaviors among school-based youths in Puerto Rico

    PubMed Central

    Latimer, William W.; Rojas, Vanessa Cecilia; Mancha, Brent Edward

    2009-01-01

    Objectives The present study sought to: (a) categorize youths into groups based on their level of alcohol use and number of symptoms of alcohol abuse and dependence defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), and (b) examine whether these categories were associated with other problem behaviors in which youths engage (marijuana use, sexual intercourse, and having been arrested or having trouble with the law). Methods The study is based on a cross-sectional survey administered to 972 school-based youths from one middle school and one high school in San Juan, Puerto Rico. Youths were categorized based on their alcohol use and alcohol problems. These categories were then examined for associations with lifetime marijuana use, lifetime sexual intercourse, and having been arrested or having had trouble with the law in the past year. The original eight categories of alcohol use were collapsed into six categories based on the results. Results For virtually every group characterized by higher severity of alcohol use and alcohol problems, researchers found an increasing prevalence of marijuana use in their lifetimes, increasing odds of sexual intercourse in their lifetimes, and having had trouble with the law in the past year. Conclusions Knowing about variations in alcohol use and alcohol problems may be instrumental in measuring the degree to which youths may also be engaging in a range of other elevated risk behaviors and a progression to more serious forms of alcohol and drug use. PMID:18510792

  4. Behavioral economic measures of alcohol reward value as problem severity indicators in college students.

    PubMed

    Skidmore, Jessica R; Murphy, James G; Martens, Matthew P

    2014-06-01

    The aims of the current study were to examine the associations among behavioral economic measures of alcohol value derived from 3 distinct measurement approaches, and to evaluate their respective relations with traditional indicators of alcohol problem severity in college drinkers. Five behavioral economic metrics were derived from hypothetical demand curves that quantify reward value by plotting consumption and expenditures as a function of price, another metric measured proportional behavioral allocation and enjoyment related to alcohol versus other activities, and a final metric measured relative discretionary expenditures on alcohol (RDEA). The sample included 207 heavy-drinking college students (53% female) who were recruited through an on-campus health center or university courses. Factor analysis revealed that the alcohol valuation construct comprises 2 factors: 1 factor that reflects participants' levels of alcohol price sensitivity (demand persistence), and a second factor that reflects participants' maximum consumption and monetary and behavioral allocation toward alcohol (amplitude of demand). The demand persistence and behavioral allocation metrics demonstrated the strongest and most consistent multivariate relations with alcohol-related problems, even when controlling for other well-established predictors. The results suggest that behavioral economic indices of reward value show meaningful relations with alcohol problem severity in young adults. Despite the presence of some gender differences, these measures appear to be useful problem indicators for men and women.

  5. DOUBLE-BLIND, RANDOMIZED PLACEBO-CONTROLLED CLINICAL TRIAL OF BENFOTIAMINE FOR SEVERE ALCOHOL DEPENDENCE

    PubMed Central

    Manzardo, Ann M.; He, Jianghua; Poje, Albert; Penick, Elizabeth C.; Campbell, Jan; Butler, Merlin G.

    2013-01-01

    Background Alcohol dependence is associated with severe nutritional and vitamin deficiency. Vitamin B1 (thiamine) deficiency erodes neurological pathways that may influence the ability to drink in moderation. The present study examines tolerability of supplementation using the high-potency thiamine analogue, benfotiamine (BF), and BF’s effects on alcohol consumption in severely affected, self-identified, alcohol dependent subjects. Methods A randomized, double-blind, placebo-controlled trial was conducted on 120 non-treatment seeking, actively drinking, alcohol dependent men and women volunteers (mean age=47 years) from the Kansas City area who met DSM-IV-TR criteria current alcohol dependence. Subjects were randomized to receive 600 mg benfotiamine or placebo (PL) once daily by mouth for 24 weeks with 6 follow-up assessments scheduled at 4 week intervals. Side effects and daily alcohol consumption were recorded. Results Seventy (58%) subjects completed 24 weeks of study (N=21 women; N=49 men) with overall completion rates of 55% (N=33) for PL and 63% (N=37) for BF groups. No significant adverse events were noted and alcohol consumption decreased significantly for both treatment groups. Alcohol consumption decreased from baseline levels for 9 of 10 BF treated women after 1 month of treatment compared with 2 of 11 on PL. Reductions in total alcohol consumption over 6 months were significantly greater for BF treated women (BF: N=10, −611±380 Std Dev; PL: N=11, −159±562 Std Dev, p-value=0.02). Conclusions BF supplementation of actively drinking alcohol dependent men and women was well-tolerated and may discourage alcohol consumption among women. The results do support expanded studies of BF treatment in alcoholism. PMID:23992649

  6. The association of genetic polymorphisms in the κ-opioid receptor 1 gene with body weight, alcohol use, and withdrawal symptoms in patients with methadone maintenance.

    PubMed

    Wang, Sheng-Chang; Tsou, Hsiao-Hui; Chung, Ren-Hua; Chang, Yao-Sheng; Fang, Chiu-Ping; Chen, Chia-Hui; Ho, Ing-Kang; Kuo, Hsiang-Wei; Liu, Shu Chih; Shih, Yu-Huei; Wu, Hsiao-Yu; Huang, Bo-Hau; Lin, Keh-Ming; Chen, Andrew C H; Hsiao, Chin-Fu; Liu, Yu-Li

    2014-04-01

    Methadone is a synthetic opioid that binds to the κ-opioid receptor with a low affinity. This study tested the hypotheses that the genetic polymorphisms in the κ-opioid receptor 1 (OPRK1) gene region are associated with methadone treatment responses in a Taiwan methadone maintenance treatment (MMT) cohort. Seventeen single nucleotide polymorphisms (SNPs) in OPRK1 were selected and genotyped on DNA of 366 MMT patients. Six SNPs from rs7843965 to rs1051660 (intron 2 to exon 2) were significantly associated with body weight (P < 0.007). A haplotype of 4 SNPs rs7832417-rs16918853-rs702764-rs7817710 (exon 4 to intron 3) was associated with bone or joint aches (P ≤ 0.004) and with the amount of alcohol use (standard drinks per day; global P < 0.0001). The haplotype rs10958350-rs7016778-rs12675595 was associated with gooseflesh skin (global P < 0.0001), yawning (global P = 0.0001), and restlessness (global P < 0.0001) withdrawal symptoms. The findings suggest that genetic polymorphisms in OPRK1 were associated with the body weight, alcohol use, and opioid withdrawal symptoms in MMT patients.

  7. Alcohol consumption increases locomotion in an open field and induces Fos-immunoreactivity in reward and approach/withdrawal-related neurocircuitries.

    PubMed

    Wscieklica, Tatiana; de Barros Viana, Milena; Le Sueur Maluf, Luciana; Pouza, Kathlein Cristiny Peres; Spadari, Regina Célia; Céspedes, Isabel Cristina

    2016-02-01

    Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take the drug, loss of control in limiting intake and, eventually, the emergence of a negative emotional state when access to the drug is prevented. Both dopamine and corticotropin-releasing factor (CRF)-mediated systems seem to play important roles in the modulation of alcohol abuse and dependence. The present study investigated the effects of alcohol consumption on anxiety and locomotor parameters and on the activation of dopamine and CRF-innervated brain regions. Male Wistar rats were given a choice of two bottles for 31 days, one containing water and the other a solution of saccharin + alcohol. Control animals only received water and a solution of 0.2% saccharin. On the 31st day, animals were tested in the elevated plus-maze and open field, and euthanized immediately after the behavioral tests. An independent group of animals was treated with ethanol and used to measure blood ethanol concentration. Results showed that alcohol intake did not alter behavioral measurements in the plus-maze, but increased the number of crossings in the open field, an index of locomotor activity. Additionally, alcohol intake increased Fos-immunoreactivity (Fos-ir) in the prefrontal cortex, in the shell region of the nucleus accumbens, in the medial and central amygdala, in the bed nucleus of the stria terminalis, in the septal region, and in the paraventricular and dorsomedial hypothalamus, structures that have been linked to reward and to approach/withdrawal behavior. These observations might be relevant to a better understanding of the behavioral and physiological alterations that follow alcohol consumption.

  8. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  9. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  10. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  11. ROSTROVENTRAL CAUDATE PUTAMEN INVOLVEMENT IN ETHANOL WITHDRAWAL IS INFLUENCED BY A CHROMOSOME 4 LOCUS

    PubMed Central

    Chen, G.; Buck, K.J.

    2010-01-01

    Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force that sustains alcohol use and abuse and may contribute to relapse in dependent individuals. Although no animal model duplicates alcoholism, models for specific factors, like withdrawal, are useful for identifying potential genetic and neural determinants of liability in humans. Previously, we identified a quantitative trait locus (QTL) and gene (Mpdz, which encodes the multi-PDZ domain protein) on chromosome 4 with a large effect on alcohol withdrawal in mice. Using congenic mice that confirm this QTL and c-Fos expression as a high-resolution marker of neuronal activation, we report that congenic mice demonstrate significantly less neuronal activity associated with alcohol withdrawal in the rostroventral caudate putamen (rvCP), but not other parts of the striatum, compared with background strain mice. Moreover, bilateral rvCP lesions significantly increase alcohol withdrawal severity. Using retrograde (fluorogold) and anterograde (Texas Red conjugated dextran amine) tract tracing, we found that ~25% of c-Fos immunoreactive rvCP neurons project to caudolateral substantia nigra pars reticulata (clSNr), which we previously found is crucially involved in withdrawal following acute and repeated alcohol exposure. Our results expand upon work suggesting that this QTL impacts alcohol withdrawal via basal ganglia circuitry associated with limbic function, and indicate that an rvCP-clSNr projection plays a critical role. Given the growing body of evidence that the syntenic region of human chromosome 9p and MPDZ are associated with alcohol abuse, our results may facilitate research on alcohol dependence and associated withdrawal in clinical populations. PMID:20608999

  12. Insomnia in Alcohol Dependent Subjects is Associated with Greater Psychosocial Problem Severity

    PubMed Central

    Chaudhary, Ninad S.; Kampman, Kyle M.; Kranzler, Henry R.; Grandner, Michael A.; Debbarma, Swarnalata; Chakravorty, Subhajit

    2015-01-01

    Introduction Although psychosocial problems are commonly associated with both alcohol misuse and insomnia, very little is known about the combined effects of insomnia and current alcohol dependence on the severity of psychosocial problems. The present study evaluates whether the co-occurrence of insomnia and alcohol dependence is associated with greater psychosocial problem severity. Methods Alcohol dependent individuals (N=123) were evaluated prior to participation in a placebo-controlled medication trial. The Short Index of Problems (SIP), Addiction Severity Index (ASI), Insomnia Severity Index (ISI), and Time Line Follow Back (TLFB), were used to assess psychosocial, employment, and legal problems; insomnia symptoms; and alcohol consumption, respectively. Bivariate and multivariate analyses were used to evaluate the relations between insomnia and psychosocial problems. Results Subjects’ mean age was 44 years (SD=10.3), 83% were male, and their SIP sub-scale scores approximated the median for normative data. A quarter of subjects reported no insomnia; 29% reported mild insomnia; and 45% reported moderate-severe insomnia. The insomnia groups did not differ on alcohol consumption measures. The ISI total score was associated with the SIP total scale score (β=0.23, p=0.008). Subjects with moderate-severe insomnia had significantly higher scores on the SIP total score, and on the social and impulse control sub-scales, and more ASI employment problems and conflicts with their spouses than others on the ASI. Conclusion In treatment-seeking alcohol dependent subjects, insomnia may increase alcohol-related adverse psychosocial consequences. Longitudinal studies are needed to clarify the relations between insomnia and psychosocial problems in these subjects. PMID:26151580

  13. The effects of alcohol and benzodiazepines on the severity of ski accidents.

    PubMed

    Barnas, C; Miller, C H; Sperner, G; Sperner-Unterweger, B; Beck, E; Hinterhuber, H; Fleischhacker, W W

    1992-10-01

    Urine samples from 402 victims of ski accidents were analyzed for the presence of benzodiazepines (BZD) and alcohol. Eighty-one (20%) samples were positive for alcohol; BZD were detected in 34 (8.5%) cases. Ten of the samples (2.5%) were found to be positive for both alcohol and BZD. Subjects who were positive for either alcohol or BZD or both were older than the other persons examined. The prevalence of alcohol was significantly higher among male accident victims. BZD intake could be demonstrated to have a significant influence on the severity of injuries. Besides an increased awareness of the need for skier education regarding drug use, heightened attention of medical caregivers is warranted to inform their patients about potential accident hazards in sport activities when BZD are prescribed.

  14. Linkage of an alcoholism-related severity phenotype to chromosome 16.

    PubMed

    Foroud, T; Bucholz, K K; Edenberg, H J; Goate, A; Neuman, R J; Porjesz, B; Koller, D L; Rice, J; Reich, T; Bierut, L J; Cloninger, C R; Nurnberger, J I; Li, T K; Conneally, P M; Tischfield, J A; Crowe, R; Hesselbrock, V; Schuckit, M; Begleiter, H

    1998-12-01

    There is substantial evidence for a significant genetic component to the risk for alcoholism. In searching for genes that contribute to this risk, the diagnostic criteria for alcohol dependence may not be the optimal phenotype; rather, creation of a more homogeneous phenotype will lead to a more homogeneous genetic etiology. Items from the Semi-Structured Assessment for the Genetics of Alcoholism collected from 830 individuals in 105 alcoholic families were used in a latent class analysis to identify a more homogeneous alcoholism-related phenotype. A four-class solution was chosen: class 1, unaffected group; class 2, mildly problematic group; class 3, moderately affected group; and class 4, severely affected group. Classes 3 and 4 had higher symptom endorsement probabilities than classes 1 and 2 for items reflecting severe alcohol dependence, and were combined to provide enough sibling pairs for genetic linkage analysis. A total of 291 markers distributed throughout the genome, with an average intermarker distance of 14 cM, were genotyped. Linkage analysis was performed to detect loci underlying classes 3 and 4, the moderately and severely affected alcoholics, of whom 88% met the Collaborative Study of the Genetics of Alcoholism, and >99% met ICD-10 criteria for alcohol dependence. Evidence for a locus on chromosome 16, near the marker D16S675, was found with a maximum multipoint lod score of 4.0. Analysis of additional markers on chromosome 16 yielded a lod score of 3.2, narrowed the critical region, and placed the gene between D16S475 and D16S675 in a 15 cM interval.

  15. Zolpidem withdrawal delirium

    PubMed Central

    Mattoo, Surendra K.; Gaur, Navendu; Das, Partha P.

    2011-01-01

    The Z-category hypnotics are promoted for their relative safety. However, this view is challenged by the emerging clinical evidence in the form of zolpidem related intoxication delirium and seizures, and dependence and complicated withdrawal. We report the case of a zolpidem-naive alcohol-dependent inpatient that, while undergoing alcohol de-addiction, was prescribed zolpidem for insomnia and developed delirium during taper-off. He was successfully detoxified for alcohol, treated for delirium and put on disulfiram prophylaxis. The case highlights the need for being cautious while using zolpidem for insomnia in alcohol dependent subjects. PMID:22144786

  16. Distal and proximal factors related to aggression severity among patients in substance abuse treatment: family history, alcohol use and expectancies.

    PubMed

    Chermack, Stephen T; Wryobeck, John M; Walton, Maureen A; Blow, Frederic C

    2006-05-01

    This study examined the relationships among distal (paternal and maternal family history of alcohol problems and violence) and proximal (general alcohol use, acute use associated with conflict incidents, alcohol-aggression expectancies) factors and physical aggression severity among 125 men and 125 women recruited from substance abuse treatment. Paternal alcohol problem history (PA) was related to alcohol-aggression expectancies, but no family history factors were related to general or acute alcohol use. Separate analyses examining predictors of aggression were conducted, one with general alcohol use and one with acute alcohol use. In both analyses, alcohol use and the maternal violence (MV) by PA interaction were significant. Specifically, MV was associated with aggression severity for those with a history of PA. The general alcohol use model also revealed significant alcohol by expectancy and MV by gender interactions. The findings suggest that expectancies are not the primary mediator of the alcohol-aggression relationship, alcohol use measurement issues may impact whether expectancies are observed to moderate the alcohol-aggression relationship, and that both maternal and paternal family history factors appear to impact aggression severity.

  17. Direct and indirect symptom severity indicators of alcohol dependence and the personality concept of the biosocial model.

    PubMed

    Andó, Bálint; Rózsa, Sándor; Kurgyis, Eszter; Szkaliczki, Andrea; Demeter, Ildikó; Szikszay, Petronella; Demetrovics, Zsolt; Janka, Zoltán; Álmos, Péter Z

    2014-03-01

    Temperament and character factors are strongly related to the developmental, clinical, and treatment aspects of alcohol dependence. This study had the aim of revealing the underlying personality structure and individual differences in the symptoms of alcohol dependence measured by multiple severity indicators. Patients with alcohol dependence exhibited higher levels of novelty seeking and harm avoidance, and lower levels of persistence, self-directedness, and cooperativeness. Especially novelty seeking was connected with more severe alcohol dependence. These characteristics could be useful targets of interventions and Temperament and Character Inventory is therefore a useful measurement to identify patients with more severe alcohol-related problems.

  18. Reliability and Validity of the Turkish Version of the Addiction Severity Index in Male Alcohol Dependents

    PubMed Central

    DEMİRBAŞ, Hatice; ÖZGÜR İLHAN, İnci; DOĞAN, Yıldırım Beyatlı; CANATAN, Ayşe

    2014-01-01

    Introduction We aimed to evaluate the psychometric characteristics of the Turkish translation of the Addiction Severity Index (ASI) in 115 male alcohol-dependent patients. Method The reliability of the instrument was assessed by measuring test-retest, interrater and internal reliabilities. In the validity analysis, the correlation coefficients between corresponding severity ratings and composite scores of each subscale and concurrent validity were assessed. Moreover, the discriminant validity and concurrent validity scores were calculated. Results The test-retest reliability of the ASI scores ranged from .79 to .91. The interrater reliability assigned by three raters was high (.74 to .99). Cronbach’s alpha coefficient for internal consistency was .85 for all scales, and it varied between .64 and .77 for the subscales. The Beck Depression Inventory moderately correlated with the Psychatric status, and the MacAndrew Alcoholism Scale correlated with the Alcohol and Drug Use subscales of the Addiction Severity Index (ASI). The correlation coefficient was .91 for the alcohol use subscale. Conclusion The results obtained in this study suggest that the Turkish version of the ASI could be used as a reliable and valid instrument in alcohol-dependent patients.

  19. Sex Differences in Ethanol's Anxiolytic Effect and Chronic Ethanol Withdrawal Severity in Mice with a Null Mutation of the 5α-Reductase Type 1 Gene.

    PubMed

    Tanchuck-Nipper, Michelle A; Ford, Matthew M; Hertzberg, Anna; Beadles-Bohling, Amy; Cozzoli, Debra K; Finn, Deborah A

    2015-05-01

    Manipulation of endogenous levels of the GABAergic neurosteroid allopregnanolone alters sensitivity to some effects of ethanol. Chronic ethanol withdrawal decreases activity and expression of 5α-reductase-1, an important enzyme in allopregnanolone biosynthesis encoded by the 5α-reductase-1 gene (Srd5a1). The present studies examined the impact of Srd5a1 deletion in male and female mice on several acute effects of ethanol and on chronic ethanol withdrawal severity. Genotype and sex did not differentially alter ethanol-induced hypothermia, ataxia, hypnosis, or metabolism, but ethanol withdrawal was significantly lower in female versus male mice. On the elevated plus maze, deletion of the Srd5a1 gene significantly decreased ethanol's effect on total entries versus wildtype (WT) mice and significantly decreased ethanol's anxiolytic effect in female knockout (KO) versus WT mice. The limited sex differences in the ability of Srd5a1 genotype to modulate select ethanol effects may reflect an interaction between developmental compensations to deletion of the Srd5a1 gene with sex hormones and levels of endogenous neurosteroids.

  20. Cocaine withdrawal

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000947.htm Cocaine withdrawal To use the sharing features on this page, please enable JavaScript. Cocaine withdrawal occurs when someone who has used a ...

  1. The Incidence and Severity of Hangover the Morning after Moderate Alcohol Intoxication

    PubMed Central

    Howland, Jonathan; Rohsenow, Damaris J; Greece, Jacey; Almeida, Alissa; Minsky, Sara J; Allensworth-Davies, Donald; Arnedt, J Todd; Hermos, John

    2013-01-01

    Background Differential propensity for hangover may play a role in determining individuals’ drinking practices so predictors of incidence and severity are needed. Methods Data were combined from three randomized crossover trials investigating the residual effects of heavy drinking on next-day performance. All 172 participants received either an alcoholic beverage (M=.115 g% breath alcohol concentration [BrAC]) or placebo matched on type and amount one night and a week later received the other beverage. Alcoholic beverages were vodka, bourbon or high alcohol beer. After each drinking session, following a 9-hour period for sleep and breakfast, participants completed questionnaire a hangover measure. Results No hangover was reported by 24% of participants, mild hangover by 44% and moderate hangover by 32%. Neither alcoholic beverage type nor participant characteristics (sex, age, drinking practices, tobacco use, or family history of alcohol problems) were associated with incidence of hangover. Conclusion The majority of people experienced mild to moderate hangover the morning after this level of intoxication. Further studies are required to investigate other hypothesized causes of variation in the propensity for hangover. PMID:18412754

  2. Acute Abdominal Aorta Thrombosis and Ischemic Rhabdomyolysis Secondary to Severe Alcohol Intoxication

    PubMed Central

    Abbas, Syed Farhat; Farooq, Madeeha; Rasheed, Amna; Ali, Furqan

    2016-01-01

    Acute alcohol intoxication is a common cause of emergency visits worldwide. Although moderate alcohol consumption is protective against coronary artery disease, binge drinking is associated with adverse cardiovascular and neurological outcomes and may even cause sudden death. Although, few past accounts of venous thrombosis with alcohol binge drinking are available, arterial thrombosis with the condition has never been reported in the literature. We present the unusual case of a young Afghan male, who presented to us with painful, tender and swollen legs three days after a heavy alcohol binge on a Saturday night. He was diagnosed as a case of acute limb ischemia secondary to massive abdominal aorta and bilateral femoral artery thrombosis. He also had acute renal failure secondary to rhabdomyolysis. Cardiac workup revealed new onset paroxysmal atrial fibrillation and a large thrombus in the left ventricular cavity. His blood ethanol level was high. He was treated by a multidisciplinary team; urgent surgical thrombectomy for thrombotic complications, intravenous fluid hydration and later renal replacement therapy for acute renal failure. To the best of our knowledge, such a constellation of clinical features in association with severe acute alcohol intoxication has not been reported in the literature. We believe, the procoagulant nature of high blood ethanol levels and the onset of atrial fibrillation after the heavy alcohol binge, known as the holiday heart syndrome, precipitated the thrombotic events leading to rhabdomyolysis and acute renal failure. Through this case, we conclude that a very heavy alcohol binge may cause thrombotic occlusion of the abdominal aorta and femoral arteries resulting in ischemic rhabdomyolysis and acute renal failure. A high index of suspicion must be kept, especially for a patient presenting with tender, swollen lower limbs and acute renal failure after an alcohol binge. PMID:28083449

  3. Antidepressant Withdrawal

    MedlinePlus

    Diseases and Conditions Depression (major depressive disorder) If you stop taking antidepressants, could you experience antidepressant withdrawal? Do withdrawal symptoms mean you were addicted to the drug? Answers from Daniel K. Hall-Flavin, M.D. Antidepressant withdrawal is possible if you ...

  4. Alcoholic delirium tremens with hollow viscus perforation scheduled for emergency laparotomy

    PubMed Central

    Talikoti, Anand T; Sindhu, BS; Kavyashree, SP; Kumar, KS Kishore

    2012-01-01

    Alcohol is a drug consumed at some time in life by up to 80% of the population according to western statistics. Wide differences in socioeconomic status in India contribute to various degrees and severity of alcoholism and its associated complications. The symptoms of alcohol withdrawal range from such minor ones as insomnia and tremulousness to severe complications such as withdrawal seizures and delirium tremens. Although alcohol withdrawal syndrome has been reported in the literature in post-operative periods and in Intensive Care Unit, there is paucity of information on treatment and preparation of a patient with alcohol withdrawal syndrome coming for emergency surgical procedures. The surgical stress and deranged liver function in such cases poses an additional challenge to the anaesthesiologist. Here, we report the successful management of a case of acute alcoholic delirium tremens who presented with hollow viscous perforation for emergency exploratory laparotomy. PMID:22701216

  5. Serotonin transporter (5-HTTLPR) and monoamine oxidase (MAOA) promoter polymorphisms in women with severe alcoholism.

    PubMed

    Gokturk, Camilla; Schultze, Stefan; Nilsson, Kent W; von Knorring, Lars; Oreland, Lars; Hallman, Jarmila

    2008-12-01

    The serotonin system is known to play a pivotal role for mood, behaviour and psychic illness as e.g. alcoholism. Alcoholism in both males and females has been associated with polymorphisms in genes encoding for proteins of importance for central serotonergic function. Genotyping of two functional polymorphisms in the promoter region of the serotonin transporter and monoamine oxidase-A, respectively, (5-HTT-LPR and MAOA-VNTR), was performed in a group of women with severe alcohol addiction. A large sample of adolescent females from a normal population was used as controls. A significantly higher frequency of the LL 5-HTT genotype (high activity) was found in female addicts without a known co-morbid psychiatric disorder than in the controls. Genotype of the MAOA-VNTR polymorphism did not differ significantly between addicts and controls. However, within the group of alcoholics, when the patients with known co-morbid psychiatric disorders were excluded, aggressive anti-social behaviour was significantly linked to the presence of the high activity MAOA allele. The pattern of associations between genotypes of 5-HTT-LPR and MAOA-VNTR in women with severe alcoholism differs from most corresponding studies on males.

  6. Growth hormone response to the GABA-B agonist baclofen in 3-week abstinent alcoholics.

    PubMed

    Ozsoy, Saliha; Esel, Ertugrul; Turan, Tayfun; Kula, Mustafa

    2007-12-01

    Gamma-aminobutyric acid (GABA) dysfunction is a known feature of alcoholism. We investigated GABA-B receptor activity in 3-week abstinent alcoholics using the growth hormone (GH) response to baclofen, a GABA-B receptor agonist. The study aimed to investigate the relationship between GABA-B receptor activity and alcohol withdrawal. GH response to baclofen was measured in alcohol-dependent males without depression (n = 22) who were on day 21 of alcohol abstinence and in healthy control male subjects (n = 23). After 20mg baclofen was given orally to the subjects, blood samples for GH assay were obtained every 30 min for the subsequent 150 min. The patients were divided into two subgroups (continuing withdrawal and recovered withdrawal subgroups) according to their withdrawal symptom severity scores on day 21 of alcohol cessation. Baclofen administration significantly altered GH secretion in the controls, but not in the patients. When GH response to baclofen was assessed as DeltaGH, it was lower in the patients with continuing withdrawal symptoms than in the controls and in the recovered withdrawal group. Impaired GH response to baclofen in all patients mainly pertained to the patients whose withdrawal symptoms partly continued. Our results suggest that reduced GABA-B receptor activity might be associated with longer-term alcohol withdrawal symptoms in alcoholic patients.

  7. Neuropsychological Impairment and Relapse Following Inpatient Detoxification in Severe Alcohol Dependence

    ERIC Educational Resources Information Center

    Morrison, Fraser

    2011-01-01

    The aim of the study was to examine the relationship between neuropsychological impairment in severe alcohol dependence and relapse. This was assessed following inpatient detoxification over a period of three months. Participants were tested on measures of neuropsychological functioning at the end of a seven to ten day stay in an inpatient alcohol…

  8. 27 CFR 13.22 - Withdrawal of applications.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Withdrawal of applications. 13.22 Section 13.22 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING PROCEEDINGS Applications § 13.22 Withdrawal of applications....

  9. Decompensation of chronic stable alcoholic liver disease by severe exfoliative dermatitis.

    PubMed

    Shawcross, Debbie L; Mookerjee, Rajeshwar P; Jalan, Rajiv

    2003-04-01

    Of the numerous precipitants of hepatic decompensation in chronic liver disease, there are no reports in the literature documenting an acute decompensation following an acute episode of severe dermatitis. This case highlights the haemodynamic consequences of a severe flare up of exfoliative dermatitis in a patient with stable chronic alcoholic liver disease, speculates on the mechanism by which this may provoke clinical decompensation and the impact this may have upon liver failure.

  10. Operant alcohol self-administration in dependent rats: focus on the vapor model

    PubMed Central

    Vendruscolo, Leandro F.; Roberts, Amanda J.

    2013-01-01

    Alcoholism (alcohol dependence) is characterized by a compulsion to seek and ingest alcohol (ethanol), loss of control over intake, and the emergence of a negative emotional state during withdrawal. Animal models are critical in promoting our knowledge of the neurobiological mechanisms underlying alcohol dependence. Here, we review the studies involving operant alcohol self-administration in rat models of alcohol dependence and withdrawal with the focus on the alcohol vapor model. In 1996, the first articles were published reporting that rats made dependent on alcohol by exposure to alcohol vapors displayed increased operant alcohol self-administration during acute withdrawal compared with nondependent rats (i.e., not exposed to alcohol vapors). Since then, it has been repeatedly demonstrated that this model reliably produces physical and motivational symptoms of alcohol dependence. The functional roles of various systems implicated in stress and reward, including opioids, dopamine, corticotropin-releasing factor (CRF), glucocorticoids, neuropeptide Y (NPY), γ-aminobutyric acid (GABA), norepinephrine, and cannabinoids, have been investigated in the context of alcohol dependence. The combination of models of alcohol withdrawal and dependence with operant self-administration constitutes an excellent tool to investigate the neurobiology of alcoholism. In fact, this work has helped lay the groundwork for several ongoing clinical trials for alcohol dependence. Advantages and limitations of this model are discussed, with an emphasis on what future directions of great importance could be. PMID:24290310

  11. Operant alcohol self-administration in dependent rats: focus on the vapor model.

    PubMed

    Vendruscolo, Leandro F; Roberts, Amanda J

    2014-05-01

    Alcoholism (alcohol dependence) is characterized by a compulsion to seek and ingest alcohol (ethanol), loss of control over intake, and the emergence of a negative emotional state during withdrawal. Animal models are critical in promoting our knowledge of the neurobiological mechanisms underlying alcohol dependence. Here, we review the studies involving operant alcohol self-administration in rat models of alcohol dependence and withdrawal with the focus on the alcohol vapor model. In 1996, the first articles were published reporting that rats made dependent on alcohol by exposure to alcohol vapors displayed increased operant alcohol self-administration during acute withdrawal compared with nondependent rats (i.e., not exposed to alcohol vapors). Since then, it has been repeatedly demonstrated that this model reliably produces physical and motivational symptoms of alcohol dependence. The functional roles of various systems implicated in stress and reward, including opioids, dopamine, corticotropin-releasing factor (CRF), glucocorticoids, neuropeptide Y (NPY), γ-aminobutyric acid (GABA), norepinephrine, and cannabinoids, have been investigated in the context of alcohol dependence. The combination of models of alcohol withdrawal and dependence with operant self-administration constitutes an excellent tool to investigate the neurobiology of alcoholism. In fact, this work has helped lay the groundwork for several ongoing clinical trials for alcohol dependence. Advantages and limitations of this model are discussed, with an emphasis on what future directions of great importance could be.

  12. Add-on gabapentin in the treatment of opiate withdrawal.

    PubMed

    Martínez-Raga, José; Sabater, Ana; Perez-Galvez, Bartolome; Castellano, Miguel; Cervera, Gaspar

    2004-05-01

    Gabapentin is an antiepileptic drug shown to be effective in the treatment of pain disorders and appears to be useful as well for several psychiatric disorders, including bipolar disorder, anxiety disorders, alcohol withdrawal and cocaine dependence. Gabapentin, at a dose of 600 mg three times a day, was evaluated as an add-on medication to a standard detoxification regime in seven heroin dependent individuals undergoing outpatient opiate withdrawal treatment. All seven patients successfully completed opiate detoxification and commenced opiate antagonist treatment with naltrexone on day five of withdrawal treatment, as scheduled. No adverse event was noted. Gabapentin appeared to lead a reduction in symptomatic medication and an overall beneficial effect on symptoms of heroin withdrawal.

  13. 27 CFR 19.424 - Authorized withdrawals free of tax.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... free of tax. 19.424 Section 19.424 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Withdrawals Spirits Withdrawn Free of Tax § 19.424 Authorized withdrawals free of tax. A proprietor may withdraw spirits from bonded premises free of tax as provided in this chapter: (a) Upon receipt of a...

  14. 27 CFR 19.424 - Authorized withdrawals free of tax.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... free of tax. 19.424 Section 19.424 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Withdrawals Spirits Withdrawn Free of Tax § 19.424 Authorized withdrawals free of tax. A proprietor may withdraw spirits from bonded premises free of tax as provided in this chapter: (a) Upon receipt of a...

  15. 27 CFR 19.424 - Authorized withdrawals free of tax.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... free of tax. 19.424 Section 19.424 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Withdrawals Spirits Withdrawn Free of Tax § 19.424 Authorized withdrawals free of tax. A proprietor may withdraw spirits from bonded premises free of tax as provided in this chapter: (a) Upon receipt of a...

  16. Alcohol

    MedlinePlus

    ... that's how many accidents occur. continue What Is Alcoholism? What can be confusing about alcohol is that ... develop a problem with it. Sometimes, that's called alcoholism (say: al-kuh-HOL - ism) or being an ...

  17. Alcohol

    MedlinePlus

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  18. The impact of alcohol use severity on anxiety treatment outcomes in a large effectiveness trial in primary care

    PubMed Central

    Wolitzky-Taylor, Kate; Brown, Lily A.; Roy-Byrne, Peter; Sherbourne, Cathy; Stein, Murray B.; Sullivan, Greer; Bystritsky, Alexander; Craske, Michelle G.

    2014-01-01

    Objective The presence of anxiety disorders is associated with poorer alcohol use disorder treatment outcomes, but little is known about the impact of alcohol use problems on anxiety disorder treatment outcomes despite their high comorbidity. The current study examined the impact of alcohol use symptom severity on anxiety disorder treatment outcomes in a multi-site primary care effectiveness study of anxiety disorder treatment. Method Data came from the Coordinated Anxiety Learning and Management (CALM) effectiveness trial. Participants (N = 1004) were randomized to an evidence-based anxiety intervention (including cognitive behavioral therapy and medications) or usual care in primary care. Participants completed measures of alcohol use, anxiety, and depression a baseline, 6-mo, 12-mo, and 18-mo follow-up periods. Patients with alcohol dependence were excluded. Results There were no significant moderating (Treatment Group x Alcohol Use Severity) interactions. The majority of analyses revealed no predictive effects of alcohol use severity on outcome; however, alcohol problems at baseline were associated with somewhat higher anxiety and depression symptoms at the 18-mo follow-up. Conclusions These data indicate that patients with alcohol problems in primary care can be effectively treated for anxiety disorders. Baseline alcohol problems were associated with some poorer long-term outcomes, but this was evident across CALM and usual care. These findings provide preliminary evidence that there may be no need to postpone treatment of anxiety disorders until alcohol problems are addressed, at least among those who have mild to moderate alcohol problems. Replication with more severe alcohol use disorders is needed. PMID:25615523

  19. Alcohol

    MedlinePlus

    ... de los dientes Video: Getting an X-ray Alcohol KidsHealth > For Kids > Alcohol Print A A A What's in this article? ... What Is Alcoholism? Say No en español El alcohol Getting the Right Message "Hey, who wants a ...

  20. Psychometric properties of the Spanish version of the Cocaine Selective Severity Assessment to evaluate cocaine withdrawal in treatment-seeking individuals.

    PubMed

    Pérez de los Cobos, José; Trujols, Joan; Siñol, Núria; Vasconcelos e Rego, Lisiane; Iraurgi, Ioseba; Batlle, Francesca

    2014-09-01

    Reliable and valid assessment of cocaine withdrawal is relevant for treating cocaine-dependent patients. This study examined the psychometric properties of the Spanish version of the Cocaine Selective Severity Assessment (CSSA), an instrument that measures cocaine withdrawal. Participants were 170 cocaine-dependent inpatients receiving detoxification treatment. Principal component analysis revealed a 4-factor structure for CSSA that included the following components: 'Cocaine Craving and Psychological Distress', 'Lethargy', 'Carbohydrate Craving and Irritability', and 'Somatic Depressive Symptoms'. These 4 components accounted for 56.0% of total variance. Internal reliability for these components ranged from unacceptable to good (Chronbach's alpha: 0.87, 0.65, 0.55, and 0.22, respectively). All components except Somatic Depressive Symptoms presented concurrent validity with cocaine use. In summary, while some properties of the Spanish version of the CSSA are satisfactory, such as interpretability of factor structure and test-retest reliability, other properties, such as internal reliability and concurrent validity of some factors, are inadequate.

  1. Family dysfunction differentially affects alcohol and methamphetamine dependence: a view from the Addiction Severity Index in Japan.

    PubMed

    Sugaya, Nagisa; Haraguchi, Ayako; Ogai, Yasukazu; Senoo, Eiichi; Higuchi, Susumu; Umeno, Mitsuru; Aikawa, Yuzo; Ikeda, Kazutaka

    2011-10-01

    We investigated the differential influence of family dysfunction on alcohol and methamphetamine dependence in Japan using the Addiction Severity Index (ASI), a useful instrument that multilaterally measures the severity of substance dependence. The participants in this study were 321 male patients with alcohol dependence and 68 male patients with methamphetamine dependence. We conducted semi-structured interviews with each patient using the ASI, which is designed to assess problem severity in seven functional domains: Medical, Employment/Support, Alcohol use, Drug use, Legal, Family/Social relationships, and Psychiatric. In patients with alcohol dependence, bad relationships with parents, brothers and sisters, and friends in their lives were related to current severe psychiatric problems. Bad relationships with brothers and sisters and partners in their lives were related to current severe employment/support problems, and bad relationships with partners in their lives were related to current severe family/social problems. The current severity of psychiatric problems was related to the current severity of drug use and family/social problems in patients with alcohol dependence. Patients with methamphetamine dependence had difficulty developing good relationships with their father. Furthermore, the current severity of psychiatric problems was related to the current severity of medical, employment/support, and family/social problems in patients with methamphetamine dependence. The results of this study suggest that family dysfunction differentially affects alcohol and methamphetamine dependence. Additionally, family relationships may be particularly related to psychiatric problems in these patients, although the ASI was developed to independently evaluate each of seven problem areas.

  2. 27 CFR 13.22 - Withdrawal of applications.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Withdrawal of applications. 13.22 Section 13.22 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... label approval, or distinctive liquor bottle approval, may withdraw such application at any time...

  3. 27 CFR 13.22 - Withdrawal of applications.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Withdrawal of applications. 13.22 Section 13.22 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... label approval, or distinctive liquor bottle approval, may withdraw such application at any time...

  4. Alcohol criteria endorsement and psychiatric and drug use disorders among DUI offenders: Greater severity among women and multiple offenders

    PubMed Central

    McCutcheon, Vivia V.; Heath, Andrew C.; Edenberg, Howard J.; Grucza, Richard A.; Hesselbrock, Victor M.; Kramer, John R.; Bierut, Laura Jean; Bucholz, Kathleen K.

    2010-01-01

    Purpose Data from the Collaborative Study on the Genetics of Alcoholism (COGA), a high-risk family study of alcohol dependence, were used to examine differences in alcohol diagnostic criteria endorsement and psychiatric and drug use disorders by gender and by number of DUI offenses. Results Individuals with two or more DUIs exhibited greater severity of alcohol dependence than those with none or one DUI. This severity was characterized in three ways: (1) higher endorsement of alcohol diagnostic criterion items, with evidence of greater severity among women, (2) higher prevalence of co-occurring lifetime psychiatric disorders, and (3) higher rates of drug use and of dependence on cocaine, stimulants, and, for women only, marijuana and opiates. Conclusions By examining gradations of disorder within a combination of two high-risk indicators, DUI and family vulnerability, this study provides useful information for clinical research about individuals with chronic and severe alcohol problems. In addition, the observed gender differences in this high-risk sample will contribute to the literature on alcohol dependence among women at the more severe end of the dependence spectrum. PMID:19167170

  5. Alcohol

    MedlinePlus

    ... parents and other adults use alcohol socially — having beer or wine with dinner, for example — alcohol seems ... besides just hanging out in someone's basement drinking beer all night. Plan a trip to the movies, ...

  6. Alcoholism.

    ERIC Educational Resources Information Center

    Caliguri, Joseph P., Ed.

    This extensive annotated bibliography provides a compilation of documents retreived from a computerized search of the ERIC, Social Science Citation Index, and Med-Line databases on the topic of alcoholism. The materials address the following areas of concern: (1) attitudes toward alcohol users and abusers; (2) characteristics of alcoholics and…

  7. Alcohol May Not Cause Partner Violence but It Seems to Make It Worse: A Cross National Comparison of the Relationship between Alcohol and Severity of Partner Violence

    ERIC Educational Resources Information Center

    Graham, Kathryn; Bernards, Sharon; Wilsnack, Sharon C.; Gmel, Gerhard

    2011-01-01

    This study assesses whether severity of physical partner aggression is associated with alcohol consumption at the time of the incident, and whether the relationship between drinking and aggression severity is the same for men and women and across different countries. National or large regional general population surveys were conducted in 13…

  8. The Relationship Between the Quantity of Alcohol Consumed and the Severity of Sexual Assaults Committed by College Men

    PubMed Central

    ABBEY, ANTONIA; CLINTON-SHERROD, A. MONIQUE; McAUSLAN, PAM; ZAWACKI, TINA; BUCK, PHILIP O.

    2015-01-01

    Researchers have suggested that intoxicated perpetrators may act more violently than other perpetrators, although empirical findings have been mixed. Past research has focused on whether or not alcohol was consumed, rather than the quantity consumed, and this may explain these inconsistent findings. The authors hypothesized that the quantity of alcohol consumed would have a curvilinear relationship to the severity of the assault. Data were collected from 113 college men who reported that they had committed a sexual assault since the age of 14. The quantity of alcohol that perpetrators consumed during the assault was linearly related to how much aggression they used and was curvilinearly related to the type of sexual assault committed. The quantity of alcohol that victims consumed during the assault was linearly related to the type of sexual assault committed. Strategies for improving assessment of alcohol consumption in sexual assault research are discussed. PMID:14675511

  9. Twenty-one year mortality in a dialysis unit: changing effect of withdrawal from dialysis.

    PubMed

    Bordenave, K; Tzamaloukas, A H; Conneen, S; Adler, K; Keller, L K; Murata, G H

    1998-01-01

    To characterize the factors affecting the decision to withdraw from dialysis, the authors compared patients withdrawing from dialysis (n=62) with patients dying from all other causes (n=242) over 21 years (1976-1996) in a single dialysis unit. Compared with those who died from other causes, patients who withdrew were older (67+/-11 vs 61+/-11 years); were more likely to have severe physical impairment (87% vs 62%) and severe restriction of activities of daily living (77% vs 46%); and had higher frequencies of congestive heart failure (81 % vs 62%), myocardial infarction (60% vs 42%), peripheral vascular disease (71 % vs 40%), and diabetes mellitus (66% vs 36%) (p < or = 0.014). Dialysis modality; duration of dialysis; the degree of family support; index of disease severity; the use of tobacco, alcohol, or illicit drugs; and the frequency of ischemic heart disease, dysrhythmia, pericarditis, cardiac arrest, cerebrovascular accident, hypertension, obstructive lung disease, cancer, and human immunodeficiency virus did not differ between the two groups. Stepwise logistic regression showed that dialysis during 1990-1996, severe limitation of activities of daily living, and diabetes mellitus were independent risk factors for withdrawal. During 1990-1996, 44% of the deaths were caused by withdrawal from treatment. In addition to other factors, dialysis in the 1990s is a strong predictor of withdrawal from dialysis. The reasons for the increased rate of withdrawal from dialysis in recent years, and the effect of this increased rate of withdrawal on mortality, need further evaluation.

  10. Motor vehicle crashes: the association of alcohol consumption with the type and severity of injuries and outcomes.

    PubMed

    Plurad, David; Demetriades, Demetrios; Gruzinski, Ginger; Preston, Christy; Chan, Linda; Gaspard, Donald; Margulies, Daniel; Cryer, Gill

    2010-01-01

    The effect of alcohol ingestion on short-term outcomes for trauma patients is indeterminate. Experimental and clinical reports often conflict. The objective of this study was to investigate the prevalence of positive alcohol screens, the effect of alcohol ingestion on injury patterns, severity, and outcomes in patients who were involved in motor vehicle crashes (MVC). MVC patients aged > 10 years treated in any of the 13 trauma centers in Los Angeles County during the calendar year 2003 were studied. All patients underwent routine alcohol screening on admission. The alcohol negative group ("no ETOH") had a blood alcohol level (BAL) of < or = 0.005 g/dL. Low and high alcohol groups ("low ETOH" and "high ETOH") had a BAL of > 0.005 g/dL to < 0.08 g/dL and > or = 0.08 g/dL, respectively. Logistic regression was performed to compare injury severity, complications, survival, and length of hospital stay among the three groups. Of the 3025 patients studied, 2013 (67%) were in the no ETOH group, 216 (7%) were in the low ETOH group, and 796 (26%) were in the high ETOH group. Levels were not associated with injury severity, Emergency Department hypotension, or Intensive Care Unit length of stay. Patients with an injury severity score > 15 and a high BAL had a higher incidence of severe head trauma (head abbreviated injury score > 3) and increased incidence of sepsis. However, in this group of severely injured, the high ETOH group had a significantly better survival rate than patients in the no ETOH group (adjusted odds ratio 0.41, 95% confidence interval 0.16-0.94, p = 0.05). Severely injured MVC victims with a high BAL have a higher incidence of severe head trauma and septic complications than no ETOH patients. However, the high ETOH group had superior adjusted survival rates.

  11. ALCOHOL USE BY URBAN BICYCLISTS IS ASSOCIATED WITH MORE SEVERE INJURY, GREATER HOSPITAL RESOURCE USE, AND HIGHER MORTALITY

    PubMed Central

    Sethi, Monica; Heyer, Jessica; Wall, Stephen; DiMaggio, Charles; Shinseki, Matthew; Slaughter, Dekeya; Frangos, Spiros G

    2017-01-01

    Alcohol use is a risk factor for severe injury in pedestrians struck by motor vehicles. Our objective was to investigate alcohol use by bicyclists and its effects on riding behaviors, medical management, injury severity, and mortality within a congested urban setting. A hospital-based, observational study of injured bicyclists presenting to a Level I regional trauma center in New York City was conducted. Data were collected prospectively from 2012 to 2014 by interviewing all bicyclists presenting within 24 h of injury and supplemented with medical record review. Variables included demographic characteristics, scene-related data, Glasgow Coma Scale (GCS), computed tomography (CT) scans, and clinical outcomes. Alcohol use at the time of injury was determined by history or blood alcohol level (BAL) >0.01 g/dL. Of 689 bicyclists, 585 (84.9%) were male with a mean age of 35.2. One hundred four (15.1%) bicyclists had consumed alcohol prior to injury. Alcohol use was inversely associated with helmet use (16.5% [9.9–25.1] vs. 43.2% [39.1–47.3]). Alcohol-consuming bicyclists were more likely to fall from their bicycles (42.0% [32.2–52.3] vs. 24.2% [20.8–27.9]) and less likely to be injured by collision with a motor vehicle (52.0% [41.7–62.1] vs. 67.5% [63.5–71.3]). 80% of alcohol-consuming bicyclists underwent CT imaging at presentation compared with 51.5% of non-users. Mortality was higher among injured bicyclists who had used alcohol (2.9% [0.6–8.2] vs. 0.0% [0.0–0.6]). Adjusted multivariable analysis revealed that alcohol use was independently associated with more severe injury (Adjusted Odds Ratio 2.27, p = 0.001, 95% Confidence Interval 1.40–3.68). Within a dense urban environment, alcohol use by bicyclists was associated with more severe injury, greater hospital resource use, and higher mortality. As bicycling continues to increase in popularity internationally, it is important to heighten awareness about the risks and consequences of bicycling while

  12. Alcohol may not cause partner violence but it seems to make it worse: a cross national comparison of the relationship between alcohol and severity of partner violence.

    PubMed

    Graham, Kathryn; Bernards, Sharon; Wilsnack, Sharon C; Gmel, Gerhard

    2011-05-01

    This study assesses whether severity of physical partner aggression is associated with alcohol consumption at the time of the incident, and whether the relationship between drinking and aggression severity is the same for men and women and across different countries. National or large regional general population surveys were conducted in 13 countries as part of the GENACIS collaboration. Respondents described the most physically aggressive act done to them by a partner in the past 2 years, rated the severity of aggression on a scale of 1 to 10, and reported whether either partner had been drinking when the incident occurred. Severity ratings were significantly higher for incidents in which one or both partners had been drinking compared to incidents in which neither partner had been drinking. The relationship did not differ significantly for men and women or by country. We conclude that alcohol consumption may serve to potentiate violence when it occurs, and this pattern holds across a diverse set of cultures. Further research is needed that focuses explicitly on the nature of alcohol's contribution to intimate partner aggression. Prevention needs to address the possibility of enhanced dangers of intimate partner violence when the partners have been drinking and eliminate any systemic factors that permit alcohol to be used as an excuse. Clinical services for perpetrators and victims of partner violence need to address the role of drinking practices, including the dynamics and process of aggressive incidents that occur when one or both partners have been drinking.

  13. Pharmacotherapeutic Treatment of Alcohol Dependence: An Overview

    ERIC Educational Resources Information Center

    Graves, Erin; Goodwin, Lloyd R., Jr.

    2008-01-01

    Pharmacotherapy medications can reduce the likelihood of relapse, decrease craving intensity and severity of withdrawal symptoms, and bolster the likelihood of achieving and maintaining recovery goals for many individuals seeking recovery from alcohol dependence. An overview of the benefits and concerns of integrating pharmacotherapeutic…

  14. Intracultural accusations of assimilation and alcohol use severity among Hispanic emerging adults: Moderating effects of acculturation, enculturation, and gender.

    PubMed

    Cano, Miguel Ángel

    2016-12-01

    Individuals, including Hispanics, tend to drink most heavily during emerging adulthood (ages 18-25 years old). Research has suggested that intercultural stressors (e.g., ethnic discrimination) may increase levels of alcohol use among Hispanics. However, the relationship between intracultural stressors (e.g., accusations of assimilation-when Hispanics accuse a member of their heritage group of acculturating to U.S. culture) and alcohol use has been examined to a lesser extent. Accordingly, the present study aimed to (a) examine the association between family accusations of assimilation and alcohol use severity; and (b) examine if acculturation domains, enculturation domains, and gender moderated that association. A hierarchical multiple regression and moderation analyses were conducted on a cross-sectional sample of 181 Hispanic emerging adults. Results indicated that higher family accusations of assimilation were associated with higher levels of alcohol use severity (β = .18, p < .05), and all variables entered in the model accounted for ΔR2 = 15.1% of the variance of alcohol use severity. A moderation analysis indicated that higher family accusations of assimilation were associated with higher alcohol use severity among men, but not women. Of the four acculturation/enculturation domains, none had a moderation effect. However, there was a statistically significant three-way interaction among family accusations of assimilation, gender, and affective enculturation. This three-way interaction suggests that among men, higher family accusations of assimilation were associated with higher alcohol use severity at lower levels of affective enculturation. This study addresses a literature gap on intracultural stressors and substance use among Hispanics, and discusses recommendations for future research. (PsycINFO Database Record

  15. Family-based association analysis of alcohol dependence criteria and severity

    PubMed Central

    Wetherill, Leah; Kapoor, Manav; Agrawal, Arpana; Bucholz, Kathleen; Koller, Daniel; Bertelsen, Sarah E.; Le, Nhung; Wang, Jen-Chyong; Almasy, Laura; Hesselbrock, Victor; Kramer, John; Nurnberger, John I.; Schuckit, Marc; Tischfield, Jay A.; Xuei, Xiaoling; Porjesz, Bernice; Edenberg, Howard J.; Goate, Alison M.; Foroud, Tatiana

    2013-01-01

    Background Despite the high heritability of alcohol dependence (AD), the genes found to be associated with it account for only a small proportion of its total variability. The goal of this study was to identify and analyze phenotypes based on homogeneous classes of individuals to increase the power to detect genetic risk factors contributing to the risk of AD. Methods The 7 individual DSM-IV criteria for AD were analyzed using latent class analysis (LCA) to identify classes defined by the pattern of endorsement of the criteria. A genome-wide association study was performed in 118 extended European American families (n = 2,322 individuals) densely affected with AD to identify genes associated with AD, with each of the seven DSM-IV criteria, and with the probability of belonging to two of three latent classes. Results Heritability for DSM-IV AD was 61%, and ranged from 17-60% for the other phenotypes. A SNP in the olfactory receptor OR51L1 was significantly associated (7.3 × 10−8) with the DSM-IV criterion of persistent desire to, or inability to, cut down on drinking. LCA revealed a three-class model: the “low risk” class (50%) rarely endorsed any criteria, and none met criteria for AD; the “moderate risk” class (33) endorsed primarily 4 DSM-IV criteria, and 48% met criteria for AD; the “high risk” class (17%) manifested high endorsement probabilities for most criteria and nearly all (99%) met criteria for AD One single nucleotide polymorphism (SNP) in a sodium leak channel NALCN demonstrated genome-wide significance with the high risk class (p=4.1 × 10−8). Analyses in an independent sample did not replicate these associations. Conclusion We explored the genetic contribution to several phenotypes derived from the DSM-IV alcohol dependence criteria. The strongest evidence of association was with SNPs in NALCN and OR51L1. PMID:24015780

  16. Alcohol

    MedlinePlus

    ... created when grains, fruits, or vegetables are fermented . Fermentation is a process that uses yeast or bacteria ... change the sugars in the food into alcohol. Fermentation is used to produce many necessary items — everything ...

  17. Alcohol.

    ERIC Educational Resources Information Center

    Schibeci, Renato

    1996-01-01

    Describes the manufacturing of ethanol, the effects of ethanol on the body, the composition of alcoholic drinks, and some properties of ethanol. Presents some classroom experiments using ethanol. (JRH)

  18. Liver asialoglycoprotein receptor levels correlate with severity of alcoholic liver damage in rats.

    PubMed

    Casey, Carol A; McVicker, Benita L; Donohue, Terrence M; McFarland, Melinda A; Wiegert, Robert L; Nanji, Amin A

    2004-01-01

    It has been demonstrated that the oral administration of ethanol (Lieber-DeCarli liquid diet) to rats results in a decreased expression and content of the asialoglycoprotein receptor (ASGP-R) in the resultant fatty liver. In the present study, we wanted to determine whether the extent of impaired receptor content was correlated with the severity of liver pathology by using the intragastric feeding model. When ASGP-R protein and mRNA levels were measured in animals infused with ethanol or dextrose in the presence of fish oil (FO) or medium-chain triglyceride as the source of fat, more significant impairments to the ASGP-R were observed in the FO-ethanol group compared with the medium-chain triglyceride-ethanol group. Furthermore, only the FO-ethanol group showed pathological liver changes. These results demonstrate that a correlation exists between the progression of alcohol-associated liver injury, as defined by the severity of liver pathology, and an ethanol-induced decline in ASGP-R content.

  19. 5' UTR polymorphism of dopamine receptor D1 (DRD1) associated with severity and temperament of alcoholism.

    PubMed

    Kim, Dai-Jin; Park, Byung Lae; Yoon, Sujung; Lee, Hae-Kook; Joe, Keun-Ho; Cheon, Young-Hoon; Gwon, Do-Hoon; Cho, Sung-Nam; Lee, Hye Won; NamGung, Suk; Shin, Hyoung Doo

    2007-06-15

    Multiple dopamine receptors in the dopaminergic system may be prime candidates for genetic influence on alcohol abuse and dependence due to their involvement in reward and reinforcing mechanisms. Genetic polymorphisms in dopamine receptor genes are believed to influence the development and/or severity of alcoholism. To examine the genetic effects of the Dopamine Receptor D1 (DRD) gene family (DRD1-DRD5) in the Korean population, 11 polymorphisms in the DRD gene family were genotyped and analyzed in 535 alcohol-dependent subjects and 273 population controls. Although none of the polymorphisms of DRD1-5 genes were found to be associated with the risk of alcoholism, one 5' UTR polymorphism in the DRD1 (DRD1-48A>G) gene was significantly associated with severity of alcohol-related problem, as measured by the Alcohol Use Disorders Identification Test (AUDIT) in a gene dose-dependent manner, i.e., 24.37 (+/-8.19) among patients with -48A/A genotype, 22.37 (+/-9.49) among those with -48A/G genotype, and 17.38 (+/-8.28) among those with -48G/G genotype (P=0.002). The genetic effects of DRD1-48A>G were further analyzed with other phenotypes among alcohol-dependent subjects. Interestingly, the DRD1-48A>A genotype was also found to be associated with novelty seeking (NC), harm avoidance (HA), and persistence (P) (P =0.01, 0.02, and 0.003, respectively). The information derived from this study could be valuable for understanding the genetic factors involved in alcoholic phenotypes and genetic distribution of the DRD gene family, and could facilitate further investigation in other ethnic groups.

  20. 27 CFR 19.536 - Authorized withdrawals free of tax.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... free of tax. 19.536 Section 19.536 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... Withdrawal of Spirits Free of Tax § 19.536 Authorized withdrawals free of tax. Pursuant to the regulations in this chapter, spirits may be withdrawn from bonded premises free of tax— (a) On receipt of a...

  1. Parent Alcoholism Impacts the Severity and Timing of Children's Externalizing Symptoms

    ERIC Educational Resources Information Center

    Hussong, Andrea M.; Huang, Wenjing; Curran, Patrick J.; Chassin, Laurie; Zucker, Robert A.

    2010-01-01

    Although previous studies show that children of alcoholic parents have higher rates of externalizing symptoms compared to their peers, it remains unclear whether the timing of children's externalizing symptoms is linked to that of their parent's alcohol-related symptoms. Using a multilevel modeling approach, we tested whether children aged 2…

  2. Student-Generated Protective Behaviors to Avert Severe Harm Due to High-Risk Alcohol Consumption

    ERIC Educational Resources Information Center

    Smith, Sandi W.; LaPlante, Carolyn; Wibert, Wilma Novales; Mayer, Alex; Atkin, Charles K.; Klein, Katherine; Glazer, Edward; Martell, Dennis

    2011-01-01

    High-risk alcohol consumption is a significant problem on college campuses that many students see as a rite of passage in their development into adulthood. Developing effective prevention campaigns designed to lessen or avert the risks associated with alcohol consumption entails understanding how students perceive harmful consequences as well as…

  3. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity.

    PubMed

    Leclercq, Sophie; Matamoros, Sébastien; Cani, Patrice D; Neyrinck, Audrey M; Jamar, François; Stärkel, Peter; Windey, Karen; Tremaroli, Valentina; Bäckhed, Fredrik; Verbeke, Kristin; de Timary, Philippe; Delzenne, Nathalie M

    2014-10-21

    Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut-brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence.

  4. Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity

    PubMed Central

    Leclercq, Sophie; Matamoros, Sébastien; Cani, Patrice D.; Neyrinck, Audrey M.; Jamar, François; Stärkel, Peter; Windey, Karen; Tremaroli, Valentina; Bäckhed, Fredrik; Verbeke, Kristin; de Timary, Philippe; Delzenne, Nathalie M.

    2014-01-01

    Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut–brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence. PMID:25288760

  5. Parent alcoholism impacts the severity and timing of children's externalizing symptoms.

    PubMed

    Hussong, Andrea M; Huang, Wenjing; Curran, Patrick J; Chassin, Laurie; Zucker, Robert A

    2010-04-01

    Although previous studies show that children of alcoholic parents have higher rates of externalizing symptoms compared to their peers, it remains unclear whether the timing of children's externalizing symptoms is linked to that of their parent's alcohol-related symptoms. Using a multilevel modeling approach, we tested whether children aged 2 through 17 showed elevated mother-, father- and child-reported externalizing symptoms (a) at the same time that parents showed alcohol-related consequences (time-varying effects), (b) if parents showed greater alcohol-related consequences during the study period (proximal effects), and (c) if parents had a lifetime diagnosis of alcoholism that predated the study period (distal effects). We used integrative data analysis to combine samples from two prospective studies to test these hypotheses. Distal effects of parent alcoholism on increased child externalizing symptoms were large and consistent. In addition, proximal and time-varying effects of parent alcohol symptoms were also found. Implications for preventing escalations in externalizing symptoms among this high-risk population are discussed.

  6. 27 CFR 19.532 - Withdrawals of spirits for use in wine production.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... use in wine production. 19.532 Section 19.532 Alcohol, Tobacco Products and Firearms ALCOHOL AND... Withdrawals Withdrawal of Spirits Without Payment of Tax § 19.532 Withdrawals of spirits for use in wine production. Wine spirits may be withdrawn to a bonded wine cellar without payment of tax for use in...

  7. [The effect of alcohol consumption on the severity of injuries, prognosis and mortality--a review of literature].

    PubMed

    Borowska-Solonynko, Aleksandra; Dabkowska, Agnieszka; Raczkowska, Zuzanna; Kwietniewski, Wojciech

    2012-01-01

    The paper is a review of the most current academic literature published in the English language and addressing the effect of alcohol consumption on the severity of injuries, prognosis and mortality with special emphasis placed on the consultative usefulness of such publications. The report was inspired by repeated questions asked in association with expert opinions on the effects of injuries and addressing a possible effect of alcohol consumption by the victims on the severity of injuries and prognosis. In case of such questions, a valuable supplement to an opinion based on on the expert's professional experience may be found in an analysis of publications focusing on the subject. The present review was based on two databases "Web of science" and "Medline" (2000-2011). Initially, 372 abstracts were taken into account. Subsequently, 42 articles were thoroughly studied. The analyzed material represented both experimental and research approaches to the problem. The experimental approach was based on tests carried out on animals in laboratories, whereas the research approach was based on the observations of patients admitted to hospitals with injuries. The literature overview indicates a neuroprotective feature of alcohol and an improved prognosis in intoxicated people suffering from isolated head injuries, even though the severity of their injuries is much higher than in the cases of sober people. In cases of polytrauma injuries, the influence of alcohol is explicitly negative, but does not increase mortality.

  8. [Causes of the people death from drunkenness and alcoholism].

    PubMed

    Erokhin, Iu A; Paukov, V S; Kirillov, Iu A

    2012-01-01

    We analyzed causes of 1008 people death, who abused by alcohol. Among them 2 groups were separated out: people died due to drunkenness and due to alcoholism. The structure of the death was similar in the both groups, however depended on alcoholism stages. The major cause of the death in group of drunkenness people was acute heart insufficiency, less commonly--lung pathology, and very rarely--brain vessels pathology and liver cirrhosis. In group of people, who died due to alcoholism, lung pathology was the major cause of these deaths, acute heart insufficiency was occurred less commonly, and very rare brain pathology because of delirium tremens or alcohol withdrawal syndrome, as so liver cirrhosis with complications. Hemorrhagic pancreonecrosis after alcoholic excess was found out in both groups, but it was more often in people, who died due to drunkenness. Obtained results show importance of chronic alcoholism identification as a disease with several stages including drunkenness and alcoholism.

  9. A STUDY OF SERUM PROLACTIN AND PLASMA HUMAN GROWTH HORMONE IN MALE ALCOHOLICS

    PubMed Central

    Sengupta, Somnath; Ray, Rajat; Desai, Nimesh; Shetty, K. Taranath

    1997-01-01

    Serum levels of prolactin (PRL) and Human Growth Hormone (HGH) were assayed in 38 male alcoholics and 24 male control subjects using radioimmunoassay (RIA) technique. Biochemical parameters of hepatic function and severity of withdrawal state were also assessed. Significantly elevated values of plasma HGH were found in alcoholics as a group. Nineteen percent and eight percent of the patient had elevated serum PRL and HGH levels respectively. Evidence of advanced liver disease was scant and withdrawal symptoms were by and large mild. The findings indicate a dysfunction in hypothalamic adenohypophyseal axis in a subgroup of alcoholics. PMID:21584040

  10. The relationship between self-reported cocaine withdrawal symptoms and history of depression.

    PubMed

    Helmus, T C; Downey, K K; Wang, L M; Rhodes, G L; Schuster, C R

    2001-01-01

    This study examined the relationship between cocaine withdrawal and lifetime history of depression (major depression, dysthymia). Participants with a history of regular cocaine use (n = 146) were administered the Structured Clinical Interview for the DSM-IV (SCID) and were asked to recall whether they experienced any of the six DSM-IV cocaine withdrawal symptoms. Results of bivariate analyses demonstrated that those meeting criteria for the cocaine withdrawal syndrome (dysphoria plus two or more other symptoms), in comparison to those who did not, were significantly (P<.001) more likely to have a lifetime history of depression. Lifetime history of depression was also more common in those individuals reporting the withdrawal symptoms of "dysphoria" (P<.001), "insomnia/hypersomnia" (P<.05), "vivid unpleasant dreams" (P<.01), and "psychomotor agitation/retardation" (P<.01). These relationships remained significant after controlling for demographics, severity of addiction, and the presence of opiate, alcohol and cannabis dependence or abuse. The withdrawal symptoms of "fatigue" and "increased appetite" were not associated with mood history. Results suggest that lifetime history of depression is strongly related to whether or not a cocaine abuser self-reports withdrawal symptoms. Several competing hypotheses regarding the nature of this relationship are discussed.

  11. Limits of Current Approaches to Diagnosis Severity Based on Criterion Counts: An Example with DSM-5 Alcohol Use Disorder

    PubMed Central

    Lane, Sean P.; Sher, Kenneth J.

    2014-01-01

    Within DSM-5, some diagnoses are now associated with a severity gradient based on the number of diagnostic criteria satisfied. Reasons for questioning the validity of this approach include the implicit assumptions of equal criterion severity and strict additivity of criteria combinations. To assess the implications of heterogeneity of criterion configurations on severity grading, we examined the association between all observed combinations of DSM-5 alcohol use disorder criteria endorsement, at each level of number of criteria endorsed, and multiple validity measures among 22,177 past-year drinkers from Wave 2 of the NESARC. Substantial variability of implied severity across criteria combinations was observed at each level of endorsement, with nontrivial overlap in implied severity across criterion counts. Findings suggest severity indices are at best imprecise and, potentially, misleading. These problems are likely inherent in traditional polythetic approaches to diagnosis and almost certainly applicable to other disorders. Approaches for improving severity grading are proposed. PMID:26783505

  12. Severe dysphagia as the presenting symptom of Wernicke-Korsakoff syndrome in a non-alcoholic man.

    PubMed

    Karaiskos, Ilias; Katsarolis, Ioannis; Stefanis, Leonidas

    2008-02-01

    We present the case of a non-alcoholic man, who, following severe malnutrition, presented with dysphagia that necessitated gastrostomy tube placement. The patient subsequently developed encephalopathy, at which point thiamine deficiency was suspected and thiamine supplementation initiated. The encephalopathy and the dysphagia resolved, but the patient was left with a dense amnestic deficit consistent with Korsakoff syndrome. MRI at the time of the encephalopathy revealed lesions consistent with Wernicke-Korsakoff syndrome. This case represents a remarkable example of Wernicke-Korsakoff syndrome that for a prolonged time period had as its sole manifestation severe dysphagia. To our knowledge, there is only one similar case reported in the literature. This case serves to alert neurologists that isolated dysphagia may be the presenting symptom of this classic neurological syndrome even in the absence of alcoholism.

  13. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  14. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  15. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  16. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  17. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  18. Alcohol use disorders and current pharmacological therapies: the role of GABA(A) receptors.

    PubMed

    Liang, Jing; Olsen, Richard W

    2014-08-01

    Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create large problems both for society and for the drinkers themselves. To date, no therapeutic can effectively solve these problems. Understanding the underlying mechanisms leading to AUD is critically important for developing effective and safe pharmacological therapies. Benzodiazepines (BZs) are used to reduce the symptoms of alcohol withdrawal syndrome. However, frequent use of BZs causes cross-tolerance, dependence, and cross-addiction to alcohol. The FDA-approved naltrexone and acamprosate have shown mixed results in clinical trials. Naltrexone is effective to treat alcohol dependence (decreased length and frequency of drinking bouts), but its severe side effects, including withdrawal symptoms, are difficult to overcome. Acamprosate showed efficacy for treating alcohol dependence in European trials, but two large US trials have failed to confirm the efficacy. Another FDA-approved medication, disulfiram, does not diminish craving, and it causes a peripheral neuropathy. Kudzu is the only natural medication mentioned by the National Institute on Alcohol Abuse and Alcoholism, but its mechanisms of action are not yet established. It has been recently shown that dihydromyricetin, a flavonoid purified from Hovenia, has unique effects on GABAA receptors and blocks ethanol intoxication and withdrawal in alcoholic animal models. In this article, we review the role of GABAA receptors in the treatment of AUD and currently available and potentially novel pharmacological agents.

  19. Alcohol use disorders and current pharmacological therapies: the role of GABAA receptors

    PubMed Central

    Liang, Jing; Olsen, Richard W

    2014-01-01

    Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create large problems both for society and for the drinkers themselves. To date, no therapeutic can effectively solve these problems. Understanding the underlying mechanisms leading to AUD is critically important for developing effective and safe pharmacological therapies. Benzodiazepines (BZs) are used to reduce the symptoms of alcohol withdrawal syndrome. However, frequent use of BZs causes cross-tolerance, dependence, and cross-addiction to alcohol. The FDA-approved naltrexone and acamprosate have shown mixed results in clinical trials. Naltrexone is effective to treat alcohol dependence (decreased length and frequency of drinking bouts), but its severe side effects, including withdrawal symptoms, are difficult to overcome. Acamprosate showed efficacy for treating alcohol dependence in European trials, but two large US trials have failed to confirm the efficacy. Another FDA-approved medication, disulfiram, does not diminish craving, and it causes a peripheral neuropathy. Kudzu is the only natural medication mentioned by the National Institute on Alcohol Abuse and Alcoholism, but its mechanisms of action are not yet established. It has been recently shown that dihydromyricetin, a flavonoid purified from Hovenia, has unique effects on GABAA receptors and blocks ethanol intoxication and withdrawal in alcoholic animal models. In this article, we review the role of GABAA receptors in the treatment of AUD and currently available and potentially novel pharmacological agents. PMID:25066321

  20. Reversed Scototaxis during Withdrawal after Daily-Moderate, but Not Weekly-Binge, Administration of Ethanol in Zebrafish

    PubMed Central

    Holcombe, Adam; Howorko, Adam; Powell, Russell A.; Schalomon, Melike; Hamilton, Trevor J.

    2013-01-01

    Alcohol abuse can lead to severe psychological and physiological damage. Little is known, however, about the relative impact of a small, daily dose of alcohol (daily-moderate schedule) versus a large, once per week dose (weekly-binge schedule). In this study, we examined the effect of each of these schedules on behavioural measures of anxiety in zebrafish (Danio rerio). Adult wild-type zebrafish were administered either 0.2% ethanol on a daily-moderate schedule or 1.4% ethanol on a weekly-binge schedule for a period of 21 days, and then tested for scototaxis (preference for darkness) during withdrawal. Compared to a control group with no alcohol exposure, the daily-moderate group spent significantly more time on the light side of the arena (indicative of decreased anxiety) on day two of withdrawal, but not day 9 of withdrawal. The weekly-binge group was not significantly different from the control group on either day of withdrawal and showed no preference for either the light or dark zones. Our results indicate that even a small dose of alcohol on a daily basis can cause significant, though reversible, changes in behaviour. PMID:23675478

  1. Severity of alcohol dependence is associated with the fatty acid amide hydrolase Pro129Thr missense variant.

    PubMed

    Sloan, Matthew E; Gowin, Joshua L; Yan, Jia; Schwandt, Melanie L; Spagnolo, Primavera A; Sun, Hui; Hodgkinson, Colin A; Goldman, David; Ramchandani, Vijay A

    2017-02-01

    The endocannabinoid system plays an important role in reward and addiction. One of the two main endocannabinoid neurotransmitters, anandamide, is metabolized by fatty acid amide hydrolase, an enzyme with a functional genetic polymorphism (FAAH Pro129Thr, rs324420). The Thr129 allele has been linked to problem drug and alcohol use, but the association has not been widely replicated and may be stronger for clinical measures of severity rather than categorical diagnosis. In the present study, we sought to determine whether the Thr129 allele was associated with both alcohol dependence (AD) diagnosis and severity in a sample of 1434 European American and African American individuals, 952 of whom were diagnosed with lifetime AD. Participants were genotyped for FAAH rs324420, and ancestry was determined via a genome-wide panel of ancestry informative markers. Subjects participated in Structured Clinical Interviews for psychiatric disorders and 90-day Timeline Followback interviews to assess recent alcohol use. European American participants with current AD had a higher Thr129 allele frequency than non-dependent controls. In European Americans with lifetime AD, there were significantly different distributions of drinking days and binge drinking days between the two genotype groups, with Thr129 carriers reporting a median of 10 fewer abstinent days and 13 more binge drinking days than Pro129/Pro129 homozygotes. In African American participants, there were no significant differences between Thr129 allele frequency in cases and controls and no significant differences in measures of AD severity by genotype. These findings provide evidence that the Pro129Thr missense variant is associated with AD severity in European Americans.

  2. Loss of flexibility in alcohol-taking rats: promoting factors.

    PubMed

    Turyabahika-Thyen, Katja; Wolffgramm, Jochen

    2006-01-01

    Alcohol consumption in humans can move from a flexible pattern of intake to an inflexible (addictive) one. Several endogenous and exogenous factors are discussed to be involved in this transition. The purpose of this study was to examine factors that might promote the development of inflexibility. Over a period of 52 weeks (long-term) rats had continuously free choice between differently concentrated alcohol solutions and tap water (four-bottle paradigm). After 4 months of alcohol deprivation, a retest with free choice of alcohol was performed. Bitter-taste conditions were used to test the flexibility of alcohol taking. In the retest alcohol-experienced rats revealed a much higher alcohol intake than previously alcohol-naive ones. Part of the alcohol-experienced animals showed impairment of flexibility in alcohol taking. During long-term choice, some groups were submitted to experimental interventions that might affect addiction development (stress, withdrawal, limited access, adverse consequences). Rats with limited access to alcohol at the end of the long-term choice period took more alcohol and were less flexible in the retest than any other group. It is suggested that an unsatisfied urge for alcohol leads to impairment of control over alcohol drinking.

  3. Negative Symptoms are Associated with Less Alcohol Use, Craving, and “High” in Alcohol Dependent Patients with Schizophrenia

    PubMed Central

    Batki, Steven L.; Leontieva, Luba; Dimmock, Jacqueline A.; Ploutz-Snyder, Robert

    2008-01-01

    Background Alcohol use disorders (AUDs) frequently co-occur with and exacerbate schizophrenia, yet the specific relationships between schizophrenia symptoms and alcohol use remain unclear. Methods PANSS scores were correlated with measures of alcohol and other substance use in patients with schizophrenia-spectrum disorders and AUDs entering a trial of monitored naltrexone treatment. Data were analyzed from the first 80 participants; 55% had schizophrenia and 45% had schizoaffective disorder. All had AUDs; 95% had alcohol dependence and 5% alcohol abuse; 34% also had cannabis abuse/dependence and 31% cocaine abuse/dependence. Results PANSS Negative scores were inversely correlated with Addiction Severity Index alcohol composite score, alcohol craving, quality of alcohol “high” (euphoria), and with frequency of cannabis use. An exploratory analysis indicated that the negative symptoms that may most strongly correlate with less alcohol use, craving or euphoria were passive/apathetic social withdrawal, blunted affect, difficulty in abstract thinking, and stereotyped thinking. Higher PANSS Composite scores, indicating the predominance of positive over negative PANSS symptoms, correlated with more alcohol craving and cannabis use. Higher PANSS General scores were associated with more alcohol craving. Conclusions These findings extend previous reports of the association of negative schizophrenia symptoms with less alcohol and substance use to patients with AUDs and indicate that this relationship also includes less alcohol craving and less alcohol euphoria. The findings may also provide some initial evidence that specific negative symptoms may be key to these relationships. PMID:18701256

  4. Neurophysiological Measures and Alcohol Use Disorder (AUD): Hypothesizing Links between Clinical Severity Index and Molecular Neurobiological Patterns

    PubMed Central

    Vitali, Mario; Napolitano, Carmen; Berman, Marlene Oscar; Minuto, Simona Flamminii; Battagliese, Gemma; Attilia, Maria Luisa; Braverman, Eric R; Romeo, Marina; Blum, Kenneth; Ceccanti, Mauro

    2016-01-01

    Background In 1987, Cloninger proposed a clinical description and classification of different personality traits genetically defined and independent from each other. Moreover, he elaborated a specific test the TCI to investigate these traits/states. The study of craving in Alcohol Use Disorder (AUD) assumed a greater significance, since ever more data seems to suggest a direct correlation between high levels of craving and a higher risk of relapse in alcoholics. Thus, our study aim is to explore the possible correlations among TCI linked molecular neurobiological pattern (s), craving and alcohol addiction severity measures in a sample of Italian alcoholics. Materials and Methods 191 alcoholics were recruited in a Day Hospital (DH) setting at the Alcohol Addiction Program Latium Region Referral Center, Sapienza University of Rome. After 7 days detoxification treatment a psychodiagnostic protocol was administered, including TCI, VAS-C, ASI and SADQ. All patients signed an Institutional Review Board (IRB) approved informed consent. Results Principally, we detected a significant positive correlation between HA-scale scores and the VAS scale: increasing in HA-scale corresponds to an increase in craving perception for both intensity (r=0.310; p ≤ 0.001) and frequency (r=0.246; p ≤ 0.001). Moreover, perception of dependence severity, measured with SADQ was also found to be significantly associated positively to both HA-scale (r=0.246; p ≤ 0.001) and NS-scale (r=0.224; p ≤ 0.01). While, for character scales, Persistence (r=−0.195; p=.008) and Self-directedness (r=−0.294; p ≤ 0.001) was negatively associated with ASI linked to alcohol problems. Self-directedness was also negatively correlated with ASI linked to family and social problems (r=−0.349; p ≤ 0.001), employment and support problems (r=−0.220; p=0.003) and psychiatric problems (r=−0.358; p ≤ 0.001). Cooperativeness was a negative correlate with Legal Problems (r=−0.173; p=0.019). and Self

  5. [Treatment processes of pre-alcoholism and alcohol dependence targeted towards drinking reduction].

    PubMed

    Yoshimura, Atsushi; Maesato, Hitoshi; Hisatomi, Nobuko; Higuchi, Susumu

    2013-02-01

    Since the 1990s, we have suggested the concept of pre-alcoholism which encompasses patients who have drunk a great deal of alcohol leading to alcohol related problems such as health issues, domestic violence, drunken driving and black-outs. Pre-alcoholism excludes alcohol-dependent patients who have experienced continuous drinking or withdrawal symptoms. We have treated many outpatients with pre-alcoholism for several years. Our regimen demands that the patients must be abstinent for half a year at the beginning of their treatment. After half a year they can choose whether they will continue to be abstinent or they will resume drinking with the aim of reducing their total alcohol consumption. The study clarified the character of pre-alcoholism by investigation of the patients' background and re-diagnosis of the patients based on the International Classification of Diseases, 10th Revision (ICD-10). A remarkable ratio of pre-alcoholic patients was diagnosed with alcohol dependence under ICD-10. We classified pre-alcoholic patients into two groups, one diagnosed as having ICD-10-classed alcohol dependence and the other which did not fulfill the ICD-10 diagnostic criteria of alcohol dependence, and examined the therapeutic processes of the two groups. It was shown that most pre-alcoholic patients could finally take required courses of treatment by themselves without regard to diagnosis under ICD-10, even if they chose any treatment and made alcohol related mistakes on the way. Our findings suggested that pre-alcoholic patients, a portion of whom may have exhibited mild alcohol dependence, could select drinking reduction as a primary goal of treatment after a certain period of abstinence.

  6. Gabapentin for the treatment of ethanol withdrawal.

    PubMed

    Voris, John; Smith, Nancy L; Rao, Subba M; Thorne, Diana L; Flowers, Queen J

    2003-06-01

    Benzodiazepines (BZDs) are the drug of choice for the suppression of alcohol withdrawal symptoms. Gabapentin, a drug approved for use as adjunctive therapy in the treatment of partial seizures, has none of the BZD-type difficulties (drug interactions, abuse potential). We retrospectively report on the use of gabapentin for ethanol withdrawal in 49 patients. Thirty-one patients were treated in the outpatient program and 18 in the general inpatient psychiatric unit. Positive outcomes as evidenced by completion of gabapentin therapy were achieved in 25 out of 31 outpatients and 17 out of 18 inpatients. Statistical significance was reached regarding the positive relationship between prior ethanol use and inpatient "as needed" benzodiazepine use. Both sets of data suggest that gabapentin works well for the mild to moderate alcohol withdrawal patient.

  7. The Differential Impact of Alcohol and Interpersonal Violence on the Severity of Violent Traumatic Brain Injuries among American Indians.

    PubMed

    Linton, Kristen F; Perrin, Paul B

    2017-04-03

    Research shows connections between substance use and traumatic brain injury (TBI), high rates of substance use and interpersonal violence (IPV) in American Indians with TBI, and connections between IPV and TBI. This study assessed the effects of substance use at the time of a violent TBI and possible mediators such as American Indian race on injury severity (injury severity score [ISS]). A secondary data analysis of 3,351 individuals who experienced a TBI due to violence was conducted. American Indians with TBI were more likely to experience IPV (χ(2) = 4.19; p = .04) and had significantly higher blood alcohol content level (BAC) scores (t = - 16.78; p = .000) than other racial groups. A regression model explained 27% of the variance in ISS. Significant interaction terms uncovered positive relationships between: (a) American Indian race and ISS when the injury aetiology was not IPV and BAC scores were lower than the legal limit, and (b) IPV and ISS when patients were not American Indian. Alcohol was negatively associated with ISS among American Indians, suggesting that BAC may impact individuals with TBI differentially as a function of race.

  8. Advances in alcoholic liver disease: An update on alcoholic hepatitis

    PubMed Central

    Liang, Randy; Liu, Andy; Perumpail, Ryan B; Wong, Robert J; Ahmed, Aijaz

    2015-01-01

    Alcoholic hepatitis is a pro-inflammatory chronic liver disease that is associated with high short-term morbidity and mortality (25%-35% in one month) in the setting of chronic alcohol use. Histopathology is notable for micro- and macrovesicular steatosis, acute inflammation with neutrophil infiltration, hepatocellular necrosis, perivenular and perisinusoidal fibrosis, and Mallory hyaline bodies found in ballooned hepatocytes. Other findings include the characteristic eosinophilic fibrillar material (Mallory’s hyaline bodies) found in ballooned hepatocytes. The presence of focal intense lobular infiltration of neutrophils is what typically distinguishes alcoholic hepatitis from other forms of hepatitis, in which the inflammatory infiltrate is primarily composed of mononuclear cells. Management consists of a multidisciplinary approach including alcohol cessation, fluid and electrolyte correction, treatment of alcohol withdrawal, and pharmacological therapy based on the severity of the disease. Pharmacological treatment for severe alcoholic hepatitis, as defined by Maddrey’s discriminant factor ≥ 32, consists of either prednisolone or pentoxifylline for a period of four weeks. The body of evidence for corticosteroids has been greater than pentoxifylline, although there are higher risks of complications. Recently head-to-head trials between corticosteroids and pentoxifylline have been performed, which again suggests that corticosteroids should strongly be considered over pentoxifylline. PMID:26576078

  9. Advances in alcoholic liver disease: An update on alcoholic hepatitis.

    PubMed

    Liang, Randy; Liu, Andy; Perumpail, Ryan B; Wong, Robert J; Ahmed, Aijaz

    2015-11-14

    Alcoholic hepatitis is a pro-inflammatory chronic liver disease that is associated with high short-term morbidity and mortality (25%-35% in one month) in the setting of chronic alcohol use. Histopathology is notable for micro- and macrovesicular steatosis, acute inflammation with neutrophil infiltration, hepatocellular necrosis, perivenular and perisinusoidal fibrosis, and Mallory hyaline bodies found in ballooned hepatocytes. Other findings include the characteristic eosinophilic fibrillar material (Mallory's hyaline bodies) found in ballooned hepatocytes. The presence of focal intense lobular infiltration of neutrophils is what typically distinguishes alcoholic hepatitis from other forms of hepatitis, in which the inflammatory infiltrate is primarily composed of mononuclear cells. Management consists of a multidisciplinary approach including alcohol cessation, fluid and electrolyte correction, treatment of alcohol withdrawal, and pharmacological therapy based on the severity of the disease. Pharmacological treatment for severe alcoholic hepatitis, as defined by Maddrey's discriminant factor ≥ 32, consists of either prednisolone or pentoxifylline for a period of four weeks. The body of evidence for corticosteroids has been greater than pentoxifylline, although there are higher risks of complications. Recently head-to-head trials between corticosteroids and pentoxifylline have been performed, which again suggests that corticosteroids should strongly be considered over pentoxifylline.

  10. Adolescent intermittent ethanol exposure diminishes anhedonia during ethanol withdrawal in adulthood.

    PubMed

    Boutros, Nathalie; Semenova, Svetlana; Markou, Athina

    2014-06-01

    Adolescent alcohol use may interfere with neurodevelopment, increasing the likelihood of adult alcohol use disorders (AUDs). We investigated whether adolescent intermittent ethanol (AIE) exposure alters the adult reward response to ethanol. Adolescent rats were administered ethanol once (moderate exposure; Cohort 1) or three times per day (severe exposure; Cohort 2) in a 2 days on/2 days off pattern. In adulthood, subjects responded for electrical stimulation directed at the posterior lateral hypothalamus in a discrete-trial intracranial self-stimulation (ICSS) procedure that provides current-intensity thresholds as a measure of brain reward function. The effects of ethanol administration and withdrawal were assessed. Control rats showed dose-dependent threshold elevations after acute ethanol, indicating reward deficits. A majority of moderately AIE-exposed rats (Cohort 1) showed threshold lowering after ethanol, suggesting ethanol-induced reward enhancement in this sub-set of rats. Rats exposed to severe AIE (Cohort 2) showed no threshold elevation or lowering, suggesting a blunted affective ethanol response. Daily ethanol induced threshold elevations 24h after administration in control rats but not in either group of AIE-exposed rats, suggesting decreased sensitivity to the negative affective state of ethanol withdrawal. Withdrawal from a 4-day ethanol binge produced robust and enduring threshold elevations in all rats, although threshold elevations were diminished in rats exposed to severe AIE. These results indicate that AIE exposure diminished reward deficits associated with ethanol intoxication and withdrawal and may have increased ethanol-induced reward enhancement in a sub-set of rats. In humans, enhanced ethanol reward accompanied by reduced withdrawal severity may contribute to the development of AUDs.

  11. Meta-analysis of DSM alcohol use disorder criteria severities: structural consistency is only ‘skin deep’

    PubMed Central

    Lane, S. P.; Steinley, D.; Sher, K. J.

    2016-01-01

    Background Item response theory (IRT) analyses of alcohol use disorder (AUD) and other psychological disorders are a predominant method for assessing overall and individual criterion severity for psychiatric diagnosis. However, no investigation has established the consistency of the relative criteria severities across different samples. Method PubMed/Medline, PsycINFO, Web of Science and ProQuest databases were queried for entries relating to alcohol use and IRT. Study data were extracted using a standardized data entry sheet. Consistency of reported criteria severities across studies was analysed using generalizability theory to estimate generalized intraclass correlations (ICCs). Results A total of 451 citations were screened and 34 papers (30 unique samples) included in the research synthesis. The AUD criteria set exhibited low consistency in the ordering of criteria using both traditional [ICC = 0.16, 95% confidence interval (CI) 0.06–0.56] and generalized (ICC = 0.18, 95% CI 0.15–0.21) approaches. These results were partially accounted for by previously studied factors such as age and type of sample (e.g. clinical v. community), but the largest source of unreliability was the diagnostic instrument employed. Conclusions Despite the robust finding of unidimensional structure of AUDs, inconsistency in the relative severities across studies suggests low replicability, challenging the generalizability of findings from any given study. Explicit modeling of well-studied factors like age and sample type is essential and increases the generalizability of findings. Moreover, while the development of structured diagnostic interviews is considered a landmark contribution toward improving psychiatric research, variability across instruments has not been fully appreciated and is substantial. PMID:27019218

  12. Membrane Tolerance to Ethanol is Rapidly Lost after Withdrawal: A Model for Studies of Membrane Adaptation

    NASA Astrophysics Data System (ADS)

    Taraschi, Theodore F.; Ellingson, John S.; Wu, Alice; Zimmerman, Robert; Rubin, Emanuel

    1986-06-01

    The structural properties of liver microsomes and erythrocytes obtained from rats that had been chronically administered ethanol were examined by electron spin resonance (ESR) following ethanol withdrawal for 1-10 days. Membranes obtained from control animals exhibited considerable molecular disordering upon the addition of ethanol in vitro (50-100 mM). Conversely, microsomal and erythrocyte membranes from alcoholic animals were resistant to this disordering by ethanol (membrane tolerance). These membrane properties were also apparent in lipid bilayers comprised of either total lipids or phospholipids isolated from the control and alcoholic animals. While several weeks of ethanol administration were required for both erythrocytes and microsomes to develop membrane tolerance, erythrocytes from alcoholic animals were disordered by ethanol in vitro after the animals had been withdrawn from ethanol for only 1 day. The same rapid loss of tolerance was observed in microsomes after 2 days of withdrawal. The same time course for the loss of tolerance was observed in lipid bilayers prepared from the total lipid and phospholipid extracts. No significant differences in the cholesterol/phospholipid ratio were observed between the microsomal or erythrocyte membranes isolated before and after withdrawal. Thus, alterations in the microsomal and erythrocyte phospholipids, and not cholesterol content, were responsible for conveying membrane tolerance. Membrane structural properties can be rapidly adjusted in a mammalian system in response to the withdrawal of the external membrane perturbant ethanol. The withdrawal model, which begins with established membrane tolerance and leads to rapid and complete loss of tolerance, provides a model to analyze the compositional changes responsible for this tolerance to disordering by ethanol.

  13. Clonidine withdrawal induced sympathetic surge.

    PubMed

    Shaw, Michael; Matsa, Ramprasad

    2015-06-02

    A 30-year-old man with a history of epilepsy and substance misuse presented to the hospital with status epilepticus. Difficult seizure control necessitated anaesthetising the patient followed by intubation and ventilation. A clonidine infusion was started as the patient developed withdrawal syndrome and was difficult to wean off mechanical ventilation. Once the withdrawal syndrome was controlled, the clonidine was abruptly stopped. Two hours after stopping the infusion, the patient developed high-grade fever, severe hypertension, tachycardia, profound sweating and lacrimation. The patient then developed respiratory distress syndrome secondary to acute pulmonary oedema. Clonidine withdrawal as a cause of such response was proposed. Reversal of symptoms and successful reweaning was achieved by restarting a low-dose clonidine infusion followed by slow downward titration and use of oral clonidine as a step-down measure. The patient was subsequently discharged from the intensive care unit.

  14. Neurologic effects of alcoholism.

    PubMed Central

    Diamond, I; Messing, R O

    1994-01-01

    Alcoholism, a worldwide disorder, is the cause of a variety of neurologic disorders. In this article we discuss the cellular pathophysiology of ethanol addition and abuse as well as evidence supporting and refuting the role of inheritance in alcoholism. A genetic marker for alcoholism has not been identified, but neurophysiologic studies may be promising. Some neurologic disorders related to longterm alcoholism are due predominantly to inadequate nutrition (the thiamine deficiency that causes Wernicke's encephalopathy), but others appear to involve the neurotoxicity of ethanol on brain (alcohol withdrawal syndrome and dementia) and peripheral nerves (alcoholic neuropathy and myopathy). Images PMID:7975567

  15. Confined Selective Withdrawal

    NASA Astrophysics Data System (ADS)

    Evangelio, Alvaro; Campo-Cortes, Francisco; Gordillo, Jose Manuel

    2014-11-01

    It is well known that the controlled production of monodisperse simple and composite emulsions possesses uncountable applications in medicine, pharmacy, materials science and industry. Here we present both experiments and slender-body theory regarding the generation of simple emulsions using a configuration that we have called Confined Selective Withdrawal, since it is an improved configuration of the classical Selective Withdrawal. We consider two different situations, namely, the cases when the outer flow Reynolds number is high and low, respectively. Several geometrical configurations and a wide range of viscosity ratios are analyzed so that the physics behind the phenomenon can be fully understood. In addition, we present both experiments and theory regarding the generation of composite emulsions. This phenomenon is only feasible when the outer flow Reynolds number is low enough. In this case, we propose a more complex theory which requires the simultaneous resolution of two interfaces in order to predict the shape of the jet and the sizes of the drops formed. The excellent agreement between our slender-body approximation and the experimental evidence fully validates our theories.

  16. Prevalence of biopsy-proven non-alcoholic fatty liver disease in severely obese subjects without metabolic syndrome.

    PubMed

    Qureshi, K; Abrams, G A

    2016-04-01

    Obesity is a major risk factor for non-alcoholic fatty liver disease (NAFLD). NAFLD encompasses simple fatty liver (FL) and non-alcoholic steatohepatitis (NASH) in its spectrum. NASH can progress to liver cirrhosis and is associated with liver cancer. Not all obese subjects have insulin resistance (IR) or develop metabolic syndrome (MS). This study evaluates the prevalence of NAFLD in severely obese subjects without MS. We retrospectively reviewed 445 charts from our database of severely obese subjects with clinical suspicion of NAFLD and who were selected for laparoscopic Roux-en-Y gastric bypass surgery. One hundred five subjects who did not have MS, as defined by the International Diabetes Foundation, based on comprehensive pre-operative metabolic evaluation were included. Liver biopsy specimens were evaluated for NAFLD. 24% of morbidly obese (mean body mass index [BMI] 48 kg m(-2) ) adult subjects (mean age 38 years) who underwent bariatric surgery did not have MS. NAFLD was identified in 77 (73%) on liver biopsy, out of which 59 (56%) were labelled as FL and 18 (17%) had histological diagnosis of NASH. Age, gender, race and BMI were the same among all groups. Among NAFLD subjects, 22% did not have any additional metabolic component of MS, while 36% had low high-density lipoprotein, 27% had hypertension, 8% had high triglycerides and 6% had hyperglycaemia. IR calculated by HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) and diagnosis of hyperglycaemia was statistically higher in NASH group compared to those who did not have NASH. NAFLD is highly prevalent in morbidly obese individuals who undergo bariatric surgery despite the absence of MS. Diagnosis of hyperglycaemia in such subjects suggests the presence of IR and may have underlying NASH, which is a progressive form of NAFLD.

  17. Validation of differential GDAP1 DNA methylation in alcohol dependence and its potential function as a biomarker for disease severity and therapy outcome.

    PubMed

    Brückmann, Christof; Di Santo, Adriana; Karle, Kathrin Nora; Batra, Anil; Nieratschker, Vanessa

    2016-06-02

    Alcohol dependence is a severe disorder contributing substantially to the global burden of disease. Despite the detrimental consequences of chronic alcohol abuse and dependence, effective prevention strategies as well as treatment options are largely missing to date. Accumulating evidence suggests that gene-environment interactions, including epigenetic mechanisms, play a role in the etiology of alcohol dependence. A recent epigenome-wide study reported widespread alterations of DNA methylation patterns in alcohol dependent patients compared to control individuals. In the present study, we validate and replicate one of the top findings from this previous investigation in an independent cohort: the hypomethylation of GDAP1 in patients. To our knowledge, this is the first independent replication of an epigenome-wide finding in alcohol dependence. Furthermore, the AUDIT as well as the GSI score were negatively associated with GDAP1 methylation and we found a trend toward a negative association between GDAP1 methylation and the years of alcohol dependency, pointing toward a potential role of GDAP1 hypomethylation as biomarker for disease severity. In addition, we show that the hypomethylation of GDAP1 in patients reverses during a short-term alcohol treatment program, suggesting that GDAP1 DNA methylation could also serve as a potential biomarker for treatment outcome. Our data add to the growing body of knowledge on epigenetic effects in alcohol dependence and support GDAP1 as a novel candidate gene implicated in this disorder. As the role of GDAP1 in alcohol dependence is unknown, this novel candidate gene should be followed up in future studies.

  18. Neuroimaging Insights into the Role of Cortical GABA Systems and the Influence of Nicotine on the Recovery from Alcohol Dependence

    PubMed Central

    Cosgrove, Kelly P.; Esterlis, Irina; Mason, Graeme F.; Bois, Frederic; O'Malley, Stephanie S.; Krystal, John H.

    2011-01-01

    This paper reviews evidence suggesting that nicotine and tobacco smoke profoundly modulate the effects of alcohol on γ-aminobutyric acid (GABA) neuronal function, specifically at the GABAA-benzodiazepine receptor (GABAA-BZR). The focus of this paper is on recent neuroimaging evidence in preclinical models as well as clinical experiments. First, we review findings implicating the role of alcohol at the GABAA-BZR and discuss the changes in GABAA-BZR availability during acute and prolonged alcohol withdrawal. Second, we discuss preclinical evidence that suggests nicotine affects GABA neuronal function indirectly by a primary action at neuronal nicotinic acetylcholine receptors. Third, we show how this evidence converges in studies that examine GABA levels and GABAA-BZRs in alcohol-dependent smokers and nonsmokers, suggesting that tobacco smoking attenuates the chemical changes that occur during alcohol withdrawal. Based on a comprehensive review of literature, we hypothesize that tobacco smoking minimizes the changes in GABA levels that typically occur during the acute cycles of drinking in alcohol-dependent individuals. Thus, during alcohol withdrawal, the continued tobacco smoking decreases the severity of the withdrawal-related changes in GABA chemistry. PMID:21276806

  19. Structural and Affinity Determinants in the Interaction between Alcohol Acyltransferase from F. x ananassa and Several Alcohol Substrates: A Computational Study

    PubMed Central

    Herrera, Raúl; Caballero, Julio; Alzate-Morales, Jans H.

    2016-01-01

    Aroma and flavor are important factors of fruit quality and consumer preference. The specific pattern of aroma is generated during ripening by the accumulation of volatiles compounds, which are mainly esters. Alcohol acyltransferase (AAT) (EC 2.3.1.84) catalyzes the esterification reaction of aliphatic and aromatic alcohols and acyl-CoA into esters in fruits and flowers. In Fragaria x ananassa, there are different volatiles compounds that are obtained from different alcohol precursors, where octanol and hexanol are the most abundant during fruit ripening. At present, there is not structural evidence about the mechanism used by the AAT to synthesize esters. Experimental data attribute the kinetic role of this enzyme to 2 amino acidic residues in a highly conserved motif (HXXXD) that is located in the middle of the protein. With the aim to understand the molecular and energetic aspects of volatiles compound production from F. x ananassa, we first studied the binding modes of a series of alcohols, and also different acyl-CoA substrates, in a molecular model of alcohol acyltransferase from Fragaria x ananassa (SAAT) using molecular docking. Afterwards, the dynamical behavior of both substrates, docked within the SAAT binding site, was studied using routine molecular dynamics (MD) simulations. In addition, in order to correlate the experimental and theoretical data obtained in our laboratories, binding free energy calculations were performed; which previous results suggested that octanol, followed by hexanol, presented the best affinity for SAAT. Finally, and concerning the SAAT molecular reaction mechanism, it is suggested from molecular dynamics simulations that the reaction mechanism may proceed through the formation of a ternary complex, in where the Histidine residue at the HXXXD motif deprotonates the alcohol substrates. Then, a nucleophilic attack occurs from alcohol charged oxygen atom to the carbon atom at carbonyl group of the acyl CoA. This mechanism is in

  20. Structural and Affinity Determinants in the Interaction between Alcohol Acyltransferase from F. x ananassa and Several Alcohol Substrates: A Computational Study.

    PubMed

    Navarro-Retamal, Carlos; Gaete-Eastman, Carlos; Herrera, Raúl; Caballero, Julio; Alzate-Morales, Jans H

    2016-01-01

    Aroma and flavor are important factors of fruit quality and consumer preference. The specific pattern of aroma is generated during ripening by the accumulation of volatiles compounds, which are mainly esters. Alcohol acyltransferase (AAT) (EC 2.3.1.84) catalyzes the esterification reaction of aliphatic and aromatic alcohols and acyl-CoA into esters in fruits and flowers. In Fragaria x ananassa, there are different volatiles compounds that are obtained from different alcohol precursors, where octanol and hexanol are the most abundant during fruit ripening. At present, there is not structural evidence about the mechanism used by the AAT to synthesize esters. Experimental data attribute the kinetic role of this enzyme to 2 amino acidic residues in a highly conserved motif (HXXXD) that is located in the middle of the protein. With the aim to understand the molecular and energetic aspects of volatiles compound production from F. x ananassa, we first studied the binding modes of a series of alcohols, and also different acyl-CoA substrates, in a molecular model of alcohol acyltransferase from Fragaria x ananassa (SAAT) using molecular docking. Afterwards, the dynamical behavior of both substrates, docked within the SAAT binding site, was studied using routine molecular dynamics (MD) simulations. In addition, in order to correlate the experimental and theoretical data obtained in our laboratories, binding free energy calculations were performed; which previous results suggested that octanol, followed by hexanol, presented the best affinity for SAAT. Finally, and concerning the SAAT molecular reaction mechanism, it is suggested from molecular dynamics simulations that the reaction mechanism may proceed through the formation of a ternary complex, in where the Histidine residue at the HXXXD motif deprotonates the alcohol substrates. Then, a nucleophilic attack occurs from alcohol charged oxygen atom to the carbon atom at carbonyl group of the acyl CoA. This mechanism is in

  1. Associations between Expectancies of Alcohol and Drug Use, Severity of Partner Violence, and Posttraumatic Stress among Women

    ERIC Educational Resources Information Center

    Peters, Erica N.; Khondkaryan, Enna; Sullivan, Tami P.

    2012-01-01

    Women who experience recurrent intimate partner violence (IPV) may use alcohol or drugs because they expect that these substances will help them cope with the negative physical and psychological sequelae of IPV. However, expectancies for alcohol and drug use have not been explored among this population of women. We used the Relaxation and…

  2. The Process of Withdrawal

    ERIC Educational Resources Information Center

    Chickering, Arthur W.; Hannah, William

    1969-01-01

    Study of college dropouts and students who plan to withdraw from 13 small institutions. Discusses how motivation, personal and financial problems, life styles, goal orientation, parents, friends, college staff and environment contribute to or prevent student withdrawals. Proposes ways of dealing with problem. (AD)

  3. Quantifying the Clinical Significance of Cannabis Withdrawal

    PubMed Central

    Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

    2012-01-01

    Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

  4. Alcoholism and Alcohol Abuse

    MedlinePlus

    ... their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that causes ... groups. NIH: National Institute on Alcohol Abuse and Alcoholism

  5. Homocysteine and alcoholism.

    PubMed

    Bleich, S; Degner, D; Javaheripour, K; Kurth, C; Kornhuber, J

    2000-01-01

    Chronic alcohol consumption can induce alterations in the function and morphology of most if not all brain systems and structures. However, the exact mechanism of brain damage in alcoholics remains unknown. Partial recovery of brain function with abstinence suggests that a proportion of the deficits must be functional in origin (i.e. plastic changes of nerve cells) while neuronal loss from selected brain regions indicates permanent and irreversible damage. There is growing evidence that chronic alcoholism is associated with a derangement in the sulfur amino acid metabolism. Recently, it has been shown that excitatory amino acid (EAA) neurotransmitters and homocysteine levels are elevated in patients who underwent withdrawal from alcohol. Furthermore, it has been found that homocysteine induces neuronal cell damage by stimulating NMDA receptors as well as by producing free radicals. Homocysteine neurotoxicity via overstimulation of N-methyl-D-aspartate receptors may contribute to the pathogenesis of both brain shrinkage and withdrawal seizures linked to alcoholism.

  6. Patient satisfaction with treatment for alcohol use disorders: comparing patients with and without severe mental health symptoms

    PubMed Central

    McCallum, Stacey L; Andrews, Jane M; Gaughwin, Matthew D; Turnbull, Deborah A; Mikocka-Walus, Antonina A

    2016-01-01

    Background Previous studies suggest patients with co-occurring alcohol use disorders (AUDs) and severe mental health symptoms (SMHS) are less satisfied with standard AUD treatment when compared to patients with an AUD alone. This study compared patient satisfaction with standard AUD treatment among patients with and without SMHS and explored how standard treatment might be improved to better address the needs of these patients. Methods Eighty-nine patients receiving treatment for an AUD either at an inpatient hospital, outpatient clinic, inpatient detoxification, or residential/therapeutic community services were surveyed. Patient satisfaction with treatment was assessed using the Treatment Perception Questionnaire (range: 0–40). Patients were stratified according to their score on the Depression Anxiety Stress Scale. Forty patients scored in the extremely severe range of depression (score >14) and/or anxiety (score >10) (indicating SMHS) and 49 patients did not. An inductive content analysis was also conducted on qualitative data relating to areas of service improvement. Results Patients with SMHS were found to be equally satisfied with treatment (mean =25.10, standard deviation =8.12) as patients with an AUD alone (mean =25.43, standard deviation =6.91). Analysis revealed that being an inpatient in hospital was associated with reduced treatment satisfaction. Patients with SMHS were found to be significantly less satisfied with staffs’ understanding of the type of help they wanted in treatment, when compared to patients with AUDs alone. Five areas for service improvement were identified, including staff qualities, informed care, treatment access and continuity, issues relating to inpatient stay, and addressing patients’ mental health needs. Conclusion While findings suggest that AUD treatment services adequately meet the needs of patients with SMHS in treatment, patients with SMHS do feel that staff lack understanding of their treatment needs. Findings have

  7. Alcohol use severity and depressive symptoms among late adolescent Hispanics: Testing associations of acculturation and enculturation in a bicultural transaction model.

    PubMed

    Cano, Miguel Ángel; de Dios, Marcel A; Castro, Yessenia; Vaughan, Ellen L; Castillo, Linda G; Lorenzo-Blanco, Elma I; Piña-Watson, Brandy; Berger Cardoso, Jodi; Ojeda, Lizette; Cruz, Rick A; Correa-Fernandez, Virmarie; Ibañez, Gladys; Auf, Rehab; Molleda, Lourdes M

    2015-10-01

    Research has indicated that Hispanics have high rates of heavy drinking and depressive symptoms during late adolescence. The purpose of this study was to test a bicultural transaction model composed of two enthnocultural orientations (acculturation and enculturation); and stressful cultural transactions with both the U.S. culture (perceived ethnic discrimination) and Hispanic culture (perceived intragroup marginalization) to predict alcohol use severity and depressive symptoms among a sample of 129 (men=39, women=90) late adolescent Hispanics (ages 18-21) enrolled in college. Results from a path analysis indicated that the model accounted for 18.2% of the variance in alcohol use severity and 24.3% of the variance in depressive symptoms. None of the acculturation or enculturation domains had statistically significant direct effects with alcohol use severity or depressive symptoms. However, higher reports of ethnic discrimination were associated with higher reports of alcohol use severity and depressive symptoms. Similarly, higher reports of intragroup marginalization were associated with higher depressive symptoms. Further, both ethnic discrimination and intragroup marginalization functioned as mediators of multiple domains of acculturation and enculturation. These findings highlight the need to consider the indirect effects of enthnocultural orientations in relation to health-related outcomes.

  8. Gene-alcohol interactions identify several novel blood pressure loci including a promising locus near SLC16A9

    PubMed Central

    Simino, Jeannette; Sung, Yun Ju; Kume, Rezart; Schwander, Karen; Rao, D. C.

    2013-01-01

    Alcohol consumption is a known risk factor for hypertension, with recent candidate studies implicating gene-alcohol interactions in blood pressure (BP) regulation. We used 6882 (predominantly) Caucasian participants aged 20–80 years from the Framingham SNP Health Association Resource (SHARe) to perform a genome-wide analysis of SNP-alcohol interactions on BP traits. We used a two-step approach in the ABEL suite to examine genetic interactions with three alcohol measures (ounces of alcohol consumed per week, drinks consumed per week, and the number of days drinking alcohol per week) on four BP traits [systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure]. In the first step, we fit a linear mixed model of each BP trait onto age, sex, BMI, and antihypertensive medication while accounting for the phenotypic correlation among relatives. In the second step, we conducted 1 degree-of-freedom (df) score tests of the SNP main effect, alcohol main effect, and SNP-alcohol interaction using the maximum likelihood estimates (MLE) of the parameters from the first step. We then calculated the joint 2 df score test of the SNP main effect and SNP-alcohol interaction using MixABEL. The effect of SNP rs10826334 (near SLC16A9) on SBP was significantly modulated by both the number of alcoholic drinks and the ounces of alcohol consumed per week (p-values of 1.27E-08 and 3.92E-08, respectively). Each copy of the G-allele decreased SBP by 3.79 mmHg in those consuming 14 drinks per week vs. a 0.461 mmHg decrease in non-drinkers. Index SNPs in 20 other loci exhibited suggestive (p-value ≤ 1E-06) associations with BP traits by the 1 df interaction test or joint 2 df test, including 3 rare variants, one low-frequency variant, and SNPs near/in genes ESRRG, FAM179A, CRIPT-SOCS5, KAT2B, ADCY2, GLI3, ZNF716, SLIT1, PDE3A, KERA-LUM, RNF219-AS1, CLEC3A, FBXO15, and IGSF5. SNP-alcohol interactions may enhance discovery of novel variants with large effects that can be

  9. Schizophrenia patients with polydipsia and water intoxication are characterized by greater severity of psychotic illness and a more frequent history of alcohol abuse.

    PubMed

    Poirier, Simon; Legris, Geneviève; Tremblay, Philippe; Michea, Rodrigo; Viau-Guay, Laurence; Mérette, Chantal; Bouchard, Roch-Hugo; Maziade, Michel; Roy, Marc-André

    2010-05-01

    Polydipsia and water intoxication (PWI) are relatively frequent among schizophrenic subjects, particularly in institutional settings and may lead to severe complications. However, little is known on their association with other characteristics of psychosis. Hence, we took advantage of a cohort of 114 subjects extensively assessed on natural history and clinical variables to examine the correlates of PWI in chronic schizophrenia. We randomly sampled DSM-IV schizophrenic subjects from: i) a lower functioning subgroup, i.e., long-term psychiatric wards or highly structured group housing facilities; and ii) a higher functioning subgroup, i.e., patients living in the community without supervision. Subjects were assessed from multiple sources for lifetime severity of positive, disorganisation, negative and depressive symptoms, premorbid adjustment, age of onset, level of functioning, comorbid diagnoses of substance abuse and lifetime history of PWI. Twelve subjects (10.5%) met our PWI criteria. We observed more severe psychotic symptoms, earlier onset, poorer current adjustment and more frequent prior alcohol use disorder in PWI subjects. When restricting comparisons to patients living in institutional setting, differences on clinical and natural history variables vanished but the association between PWI and prior alcohol abuse persisted (72.7% in PWI vs. 21.4% in non-PWI subjects, p<0.01). Onset of alcohol abuse predated the onset of PWI by a mean of 12.8 years. PWI schizophrenic subjects are characterized by a non-specific greater severity on a broad array of clinical and natural history variables and by a specific association with prior alcohol abuse. Thus, our data suggest that a greater severity of illness and a prior history of alcohol use disorders interact in increasing the risk of developing PWI in chronic schizophrenic patients.

  10. A differential role for neuropeptides in acute and chronic adaptive responses to alcohol: behavioural and genetic analysis in Caenorhabditis elegans.

    PubMed

    Mitchell, Philippa; Mould, Richard; Dillon, James; Glautier, Steven; Andrianakis, Ioannis; James, Christopher; Pugh, Amanda; Holden-Dye, Lindy; O'Connor, Vincent

    2010-05-03

    Prolonged alcohol consumption in humans followed by abstinence precipitates a withdrawal syndrome consisting of anxiety, agitation and in severe cases, seizures. Withdrawal is relieved by a low dose of alcohol, a negative reinforcement that contributes to alcohol dependency. This phenomenon of 'withdrawal relief' provides evidence of an ethanol-induced adaptation which resets the balance of signalling in neural circuits. We have used this as a criterion to distinguish between direct and indirect ethanol-induced adaptive behavioural responses in C. elegans with the goal of investigating the genetic basis of ethanol-induced neural plasticity. The paradigm employs a 'food race assay' which tests sensorimotor performance of animals acutely and chronically treated with ethanol. We describe a multifaceted C. elegans 'withdrawal syndrome'. One feature, decrease reversal frequency is not relieved by a low dose of ethanol and most likely results from an indirect adaptation to ethanol caused by inhibition of feeding and a food-deprived behavioural state. However another aspect, an aberrant behaviour consisting of spontaneous deep body bends, did show withdrawal relief and therefore we suggest this is the expression of ethanol-induced plasticity. The potassium channel, slo-1, which is a candidate ethanol effector in C. elegans, is not required for the responses described here. However a mutant deficient in neuropeptides, egl-3, is resistant to withdrawal (although it still exhibits acute responses to ethanol). This dependence on neuropeptides does not involve the NPY-like receptor npr-1, previously implicated in C. elegans ethanol withdrawal. Therefore other neuropeptide pathways mediate this effect. These data resonate with mammalian studies which report involvement of a number of neuropeptides in chronic responses to alcohol including corticotrophin-releasing-factor (CRF), opioids, tachykinins as well as NPY. This suggests an evolutionarily conserved role for neuropeptides

  11. Neonatal drug withdrawal.

    PubMed

    Hudak, Mark L; Tan, Rosemarie C

    2012-02-01

    Maternal use of certain drugs during pregnancy can result in transient neonatal signs consistent with withdrawal or acute toxicity or cause sustained signs consistent with a lasting drug effect. In addition, hospitalized infants who are treated with opioids or benzodiazepines to provide analgesia or sedation may be at risk for manifesting signs of withdrawal. This statement updates information about the clinical presentation of infants exposed to intrauterine drugs and the therapeutic options for treatment of withdrawal and is expanded to include evidence-based approaches to the management of the hospitalized infant who requires weaning from analgesics or sedatives.

  12. Epigenetics-beyond the genome in alcoholism.

    PubMed

    Starkman, Bela G; Sakharkar, Amul J; Pandey, Subhash C

    2012-01-01

    Genetic and environmental factors play a role in the development of alcoholism. Whole-genome expression profiling has highlighted the importance of several genes that may contribute to alcohol abuse disorders. In addition, more recent findings have added yet another layer of complexity to the overall molecular mechanisms involved in a predisposition to alcoholism and addiction by demonstrating that processes related to genetic factors that do not manifest as DNA sequence changes (i.e., epigenetic processes) play a role. Both acute and chronic ethanol exposure can alter gene expression levels in specific neuronal circuits that govern the behavioral consequences related to tolerance and dependence. The unremitting cycle of alcohol consumption often includes satiation and self-medication with alcohol, followed by excruciating withdrawal symptoms and the resultant relapse, which reflects both the positive and negative affective states of alcohol addiction. Recent studies have indicated that behavioral changes induced by acute and chronic ethanol exposure may involve chromatin remodeling resulting from covalent histone modifications and DNA methylation in the neuronal circuits involving a brain region called the amygdala. These findings have helped identify enzymes involved in epigenetic mechanisms, such as the histone deacetylase, histone acetyltransferase, and DNA methyltransferase enzymes, as novel therapeutic targets for the development of future pharmacotherapies for the treatment of alcoholism.

  13. Infection does not increase long-term mortality in patients with acute severe alcoholic hepatitis treated with corticosteroids

    PubMed Central

    Dhanda, Ashwin D; Sinha, Ashish; Hunt, Vicky; Saleem, Sarah; Cramp, Matthew E; Collins, Peter L

    2017-01-01

    AIM To determine whether infection in patients with acute severe alcoholic hepatitis (AAH) treated with corticosteroids is associated with increased mortality. METHODS Consecutive patients with AAH were treated with steroids and recruited to the study. Clinically relevant infections (body temperature > 38 °C or < 36 °C for more than 4 h, ascitic neutrophil count > 0.25 ×109/L, consolidation on chest radiograph or clinically relevant positive microbiological culture of bodily fluid) were recorded prospectively. Clinical and laboratory parameters were recorded and survival at 90 d and 6 mo was determined. Univariate analysis of factors associated with 90-d mortality was performed and significant variables included in a multivariate analysis. RESULTS Seventy-two patients were included in the final analysis (mean age 47.9 years, 26% female, mean discriminant function 53.0). Overall mortality in the group occurred in 15 (21%), 23 (32%) and 31 (43%) at day 28, day 90 and 1 year respectively. 36 (50%) had a clinically relevant infection during their hospitalisation (23 after initiation of steroids). The median time to development of incident infection after commencement of steroids was 10 d. The commonest site of infection was ascites (31%) and bacteraemia (31%) followed by urinary tract (19%) and respiratory tract (8%). Forty-one separate organisms were isolated in 33 patients; the most frequent genus was Escherichia (22%) and Enterococcus (20%). Infection was not associated with 90-d or 1 year mortality but was associated with higher creatinine, model for end-stage liver disease and Lille score. Baseline urea was the only independent predictor of 90-d mortality. CONCLUSION Clinically relevant infections are common in patients with AAH but are not associated with increased 90-d or 1 year mortality. PMID:28373772

  14. Neural Correlates of the Severity of Cocaine, Heroin, Alcohol, MDMA and Cannabis Use in Polysubstance Abusers: A Resting-PET Brain Metabolism Study

    PubMed Central

    Moreno-López, Laura; Stamatakis, Emmanuel A.; Fernández-Serrano, Maria José; Gómez-Río, Manuel; Rodríguez-Fernández, Antonio; Pérez-García, Miguel; Verdejo-García, Antonio

    2012-01-01

    Introduction Functional imaging studies of addiction following protracted abstinence have not been systematically conducted to look at the associations between severity of use of different drugs and brain dysfunction. Findings from such studies may be relevant to implement specific interventions for treatment. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and the severity of use of cocaine, heroin, alcohol, MDMA and cannabis in a sample of polysubstance users with prolonged abstinence from all drugs used. Methods Our sample consisted of 49 polysubstance users enrolled in residential treatment. We conducted correlation analyses between estimates of use of cocaine, heroin, alcohol, MDMA and cannabis and brain metabolism (BM) (using Statistical Parametric Mapping voxel-based (VB) whole-brain analyses). In all correlation analyses conducted for each of the drugs we controlled for the co-abuse of the other drugs used. Results The analysis showed significant negative correlations between severity of heroin, alcohol, MDMA and cannabis use and BM in the dorsolateral prefrontal cortex (DLPFC) and temporal cortex. Alcohol use was further associated with lower metabolism in frontal premotor cortex and putamen, and stimulants use with parietal cortex. Conclusions Duration of use of different drugs negatively correlated with overlapping regions in the DLPFC, whereas severity of cocaine, heroin and alcohol use selectively impact parietal, temporal, and frontal-premotor/basal ganglia regions respectively. The knowledge of these associations could be useful in the clinical practice since different brain alterations have been associated with different patterns of execution that may affect the rehabilitation of these patients. PMID:22768136

  15. The development of a sexual abuse severity score: characteristics of childhood sexual abuse associated with trauma symptomatology, somatization, and alcohol abuse.

    PubMed

    Zink, Therese; Klesges, Lisa; Stevens, Susanna; Decker, Paul

    2009-03-01

    Childhood sexual abuse (CSA) is common and is associated with both mental and physical health problems in adulthood. Using data from an age- and sex-stratified population survey of 600 Olmsted County, Minnesota, residents, a Sexual Abuse Severity Score was developed. The abuse characteristics of 156 CSA respondents were associated with self-reported trauma, somatization, and alcohol use. Characteristics included age of first sexual abuse, more than one perpetrator, degree of coercion, severity of abuse (i.e., attempted intercourse is more severe than fondling), and the number of occurrences. This is one of the few reports to develop a risk summary that quantifies the severity of CSA.

  16. Naloxone-induced withdrawal in patients with buprenorphine dependence.

    PubMed

    Nigam, A K; Srivastava, R P; Saxena, S; Chavan, B S; Sundaram, K R

    1994-03-01

    Naloxone-induced withdrawal was studied in seven patients currently dependent only on injecting buprenorphine, within 3 to 6 hours of their last dose. Withdrawal severity began to rise from 5 minutes and reached a peak at 60 minutes after 1.2 mg naloxone given intravenously. The mean withdrawal severity score was significantly higher at 30, 60 and 90 minutes compared to the baseline. The most frequent withdrawal signs and symptoms were mydriasis, systolic hypertension, tachypnoea, muscle pains, yawning, anxiety, restlessness and craving.

  17. Epigenetic basis of the dark side of alcohol addiction.

    PubMed

    Pandey, Subhash C; Kyzar, Evan; Zhang, Huaibo

    2017-02-04

    Alcoholism is a complex brain disease characterized by three distinct stages of the addiction cycle that manifest as neuroadaptive changes in the brain. One such stage of the addiction cycle is alcohol withdrawal and the negative affective states that promote drinking and maintain addiction. Repeated alcohol use, genetic predisposition to alcoholism and anxiety, and alcohol exposure during crucial developmental periods all contribute to the development of alcohol-induced withdrawal and negative affective symptoms. Epigenetic modifications within the amygdala have provided a molecular basis of these negative affective symptoms, also known as the dark side of addiction. Here, we propose that allostatic change within the epigenome in the amygdala is a prime mechanism of the biological basis of negative affective states resulting from, and contributing to, alcoholism. Acute alcohol exposure produces an anxiolytic response which is associated with the opening of chromatin due to increased histone acetylation, increased CREB binding protein (CBP) levels, and histone deacetylase (HDAC) inhibition. After chronic ethanol exposure, these changes return to baseline along with anxiety-like behaviors. However, during withdrawal, histone acetylation decreases due to increased HDAC activity and decreased CBP levels in the amygdala circuitry leading to the development of anxiety-like behaviors. Additionally, innately higher expression of the HDAC2 isoform leads to a deficit in global and gene-specific histone acetylation in the amygdala that is associated with a decrease in the expression of several synaptic plasticity-associated genes and maintaining heightened anxiety-like behavior and excessive alcohol intake. Adolescent alcohol exposure also leads to higher expression of HDAC2 and a deficit in histone acetylation leading to decreased expression of synaptic plasticity-associated genes and high anxiety and drinking behavior in adulthood. All these studies indicate that the

  18. Cocaine withdrawal symptoms identify "Type B" cocaine-dependent patients.

    PubMed

    Ahmadi, Jamshid; Kampman, Kyle; Dackis, Charles; Sparkman, Thorne; Pettinati, Helen

    2008-01-01

    Recent studies of substance dependence typologies briefly show that multivariate systems originally developed for identifying subtypes of alcoholics, such as Babor's Type A and B system, may also be valid in abusers of other substances, such as cocaine. Type B patients are characterized by an earlier onset of addiction and more severe symptoms of their addiction, psychopathology, and impulsivity. The Type B classification has also been associated with deficits in serotonergic function. We have found that patients who exhibit more severe cocaine withdrawal symptoms, as measured by scores on the Cocaine Selective Severity Assessment (CSSA), have poor treatment outcome and share many characteristics with "Type B" patients. In this paper, we review baseline characteristics of cocaine-dependent patients from several recently completed outpatient cocaine dependence treatment trials to assess the association of cocaine withdrawal symptom severity and the Type B profile. Identifying subtypes of cocaine-dependent patients may improve our ability to treat cocaine dependence by targeting treatments for specific subtypes of patients. We examined the ability of the CSSA scores to capture Type B characteristics in cocaine dependence by analyzing a series of cocaine medication trials that included 255 cocaine-dependent subjects. High CSSA scores at baseline were associated with a history of violent behavior, a family history of substance abuse, antisocial personality disorder, higher addiction severity, and co-morbid psychiatric diseases. Patients with high CSSA scores are also more likely to meet criteria for Type B (Type II) cocaine dependence. Identifying Type B cocaine-dependent patients may help to develop targeted psychosocial or pharmacological treatments for these difficult-to-treat patients.

  19. NOX2-generated oxidative stress is associated with severity of ultrasound liver steatosis in patients with non-alcoholic fatty liver disease

    PubMed Central

    2014-01-01

    Background Chronic oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. However, so far, few studies reported increased circulating levels of oxidative stress markers in patients with non-alcoholic fatty liver and no study has been performed with newer markers of systemic oxidative stress. The aim was to assess the relationship between urinary 8-iso-prostaglandin F2α and serum soluble NOX2-derived peptide and the severity of liver steatosis in subjects with non-alcoholic fatty liver. Methods The study was performed in 264 consecutive patients referred for suspected metabolic disease. Steatosis was defined according to Hamaguchi ultrasonographic criteria. Oxidative stress was assessed by urinary 8-iso- prostaglandin F2α and serum soluble NOX2-derived peptide levels. Results Patients with non-alcoholic fatty liver had higher (p < 0.001) mean values of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide, alanine aminotransferase, Cytokeratin-18 and homeostasis model of insulin resistance and lower values of serum adiponectin as compared to those without. Prevalence of metabolic syndrome and of its clinical features was significantly higher in patients with non-alcoholic fatty liver. Same findings were also observed after the exclusion of obese subjects, or subjects with diabetes or with metabolic syndrome and in those not taking statin medication. In addition, the levels of urinary 8-iso-PGF2α were independent predictors of non-alcoholic fatty liver and a strong association of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide with the severity of steatosis at ultrasound was also observed. Conclusions We demonstrated increased markers of oxidative stress in subjects with non-alcoholic fatty liver. Urinary 8-iso-PGF2α and serum soluble NOX2-derived peptide levels were independent from obesity, diabetes and metabolic syndrome and increased with the severity of liver

  20. Impact of sex: determination of alcohol neuroadaptation and reinforcement.

    PubMed

    Wiren, Kristine M; Hashimoto, Joel G; Alele, Paul E; Devaud, Leslie L; Price, Kimber L; Middaugh, Lawrence D; Grant, Kathleen A; Finn, Deborah A

    2006-02-01

    This article represents the proceedings of a symposium at the Research Society on Alcoholism meeting in Santa Barbara, California. The organizers/chairs were Kristine M. Wiren and Deborah A. Finn. Following a brief introduction by Deborah Finn, the presentations were (1) The Importance of Gender in Determining Expression Differences in Mouse Lines Selected for Chronic Ethanol Withdrawal Severity, by Kristine M. Wiren and Joel G. Hashimoto; (2) Sex Differences in Ethanol Withdrawal Involve GABAergic and Stress Systems, by Paul E. Alele and Leslie L. Devaud; (3) The Influence of Sex on Ethanol Consumption and Reward in C57BL/6 Mice, by Kimber L. Price and Lawrence D. Middaugh; and (4) Sex Differences in Alcohol Self-administration in Cynomolgus Monkeys, by Kathleen A. Grant.

  1. ['Nothing' or 'just a bit'? 'Much' or 'too much'? Impulsivity traits as markers of severity transitions within non-problematic and problematic ranges of alcohol and Internet use].

    PubMed

    J F, Navas; A, Torres; A, Cándido; J C, Perales

    2014-01-01

    This study aims to explore the relationship between impulsivity traits and perceived negative consequences of alcohol consumption and Internet use. More specifically, impulsivity traits - positive and negative urgency, sensation seeking, lack of premeditation, and lack of perseverance - in (1) the occurrence of initial negative consequences linked to use, and (2) the transition from consequences possibly indicating a problematic behavior to consequences very likely indicating a clinical problem. For this, 709 first-year college students were assessed using the UPPS-P impulsive behavior scale, and the Multicage CAD-4 scale for addictive behaviors. Logistic regressions were used to discriminate (a) between individuals with a 0-score and individuals with a 1-score in the Multicage scales (low severity range), and (b) between individuals with a 2-score and individuals with 3/4-score (high severity range), separately for alcohol and Internet use. For alcohol use, positive urgency and lack of premeditation marked the transition from 0 to 1 scores, whereas negative urgency marked the transition from 2 to 3/4 scores. For Internet use, however, none of the UPPS-P dimensions significantly marked the transition from 0 to 1 (occurrence of initial negative consequences), and positive urgency marked the transition from 2 to 3/4 (from possible to very likely problematic behavior). Negative urgency arises as a pathologization marker for alcohol abuse, whereas changes in non-clinical levels are linked to impulsivity elicited by appetitive emotions. Impulsivity does not seem to play any role in low severity levels of Internet use, and positive urgency marks the transition between high severity scores. These differential patterns are indicative of different etiological paths for excessive Internet use and substance abuse.

  2. 77 FR 15378 - Agency Information Collection Activities: Application for Withdrawal of Bonded Stores for Fishing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-15

    ... permission of the CBP port director for the withdrawal and lading of bonded merchandise (especially alcoholic beverages) for use on board fishing vessels involved in international trade. The applicant must certify...

  3. 27 CFR 28.28 - Withdrawal of wine and distilled spirits from customs bonded warehouses.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Withdrawal of wine and... Miscellaneous Provisions Customs Bonded Warehouses § 28.28 Withdrawal of wine and distilled spirits from customs bonded warehouses. Wine and bottled distilled spirits entered into customs bonded warehouses as...

  4. 27 CFR 28.28 - Withdrawal of wine and distilled spirits from customs bonded warehouses.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Withdrawal of wine and... Miscellaneous Provisions Customs Bonded Warehouses § 28.28 Withdrawal of wine and distilled spirits from customs bonded warehouses. Wine and bottled distilled spirits entered into customs bonded warehouses as...

  5. 27 CFR 28.28 - Withdrawal of wine and distilled spirits from customs bonded warehouses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Withdrawal of wine and... Miscellaneous Provisions Customs Bonded Warehouses § 28.28 Withdrawal of wine and distilled spirits from customs bonded warehouses. Wine and bottled distilled spirits entered into customs bonded warehouses as...

  6. 27 CFR 28.28 - Withdrawal of wine and distilled spirits from customs bonded warehouses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of wine and... Miscellaneous Provisions Customs Bonded Warehouses § 28.28 Withdrawal of wine and distilled spirits from customs bonded warehouses. Wine and bottled distilled spirits entered into customs bonded warehouses as...

  7. 27 CFR 28.28 - Withdrawal of wine and distilled spirits from customs bonded warehouses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Withdrawal of wine and... Miscellaneous Provisions Customs Bonded Warehouses § 28.28 Withdrawal of wine and distilled spirits from customs bonded warehouses. Wine and bottled distilled spirits entered into customs bonded warehouses as...

  8. Alcohol Usage and Abrupt Cessation Modulate Diurnal Activity

    PubMed Central

    Norrell, Stacy; Reyes-Vasquez, Cruz; Burau, Keith; Dafny, Nachum

    2010-01-01

    Alcohol has many effects throughout the body. The effect on circadian rhythms and the correlation of these effects to withdrawal effects of alcohol present interesting findings. By measuring 3 planes of activity of female Sprague-Dawley rats during alcohol usage and continuing study through the first two days following withdrawal of alcohol allow for the observation of a drastic modulation of the circadian pattern of activity. PMID:20615456

  9. Efficacy and tolerability of buccal buprenorphine in opioid-experienced patients with moderate to severe chronic low back pain: results of a phase 3, enriched enrollment, randomized withdrawal study

    PubMed Central

    Gimbel, Joseph; Spierings, Egilius L.H.; Katz, Nathaniel; Xiang, Qinfang; Tzanis, Evan; Finn, Andrew

    2016-01-01

    Abstract A buccal film of buprenorphine (BBUP) was evaluated for safety and efficacy in a multicenter, double-blind, placebo-controlled, enriched-enrollment, randomized-withdrawal study in opioid-experienced patients (30 to ≤160 mg/d morphine sulfate equivalent) with moderate to severe chronic low back pain taking around-the-clock opioid analgesics. Patients' opioid doses were tapered to ≤30 mg morphine sulfate equivalent before open-label titration with BBUP (range, 150-900 μg every 12 hours). Patients who responded (received adequate analgesia that was generally well tolerated for 14 days) were randomized to receive buprenorphine (n = 254) or placebo (n = 257) buccal film. The primary efficacy variable was the change from baseline to week 12 of double-blind treatment in mean average daily pain-intensity scores using a rating scale of 0 (no pain) to 10 (worst pain imaginable). In the intent-to-treat population, mean pain scores were 6.7 after opioid taper and declined to 2.8 after the BBUP titration period. After randomization, mean pain scores were lower in the BBUP group than in the placebo group; the difference between groups in the mean change from baseline to week 12 was −0.98 (95% CI, −1.32 to −0.64; P < 0.001). A significantly larger percentage of patients receiving BBUP than placebo had pain reductions ≥30% and ≥50% (P < 0.001 for both). In the double-blind portion of the study, the only adverse event reported more frequently with BBUP than placebo and in ≥5% of patients was vomiting (5.5% vs 2.3%). These findings demonstrate the efficacy and tolerability of BBUP in opioid-experienced patients taking around-the-clock opioid treatment for chronic low back pain. PMID:27434505

  10. 27 CFR 22.113 - Receipt of tax-free alcohol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Receipt of tax-free alcohol. 22.113 Section 22.113 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Withdrawal...

  11. 27 CFR 22.113 - Receipt of tax-free alcohol.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Receipt of tax-free alcohol. 22.113 Section 22.113 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Withdrawal...

  12. Molecular mechanisms of synaptic remodeling in alcoholism.

    PubMed

    Kyzar, Evan J; Pandey, Subhash C

    2015-08-05

    Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the "dark side" of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism.

  13. 19 CFR 144.36 - Withdrawal for transportation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... transportation to another port of entry if withdrawal for consumption or exportation can be accomplished at the... immediately for consumption or exportation, or designate a warehouse to which it may be sent and, upon his... paragraph (d) of this section. With the exception of alcohol and tobacco products, this procedure shall...

  14. 27 CFR 44.61 - Removals, withdrawals, and shipments authorized.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... this part. Effective Date Note: At 78 FR 38573, June 27, 2013, § 44.61 was revised, effective Aug. 26, 2013 through Aug. 26, 2016. ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Removals, withdrawals,...

  15. Student Withdrawal Study.

    ERIC Educational Resources Information Center

    Hayward, Craig

    This document addresses the problem of students withdrawing from courses before completion and in the process attempts to devise ways that Mendocino College can aid students complete their courses. The report uses findings from two research reports. The first report was completed at the Florida Community College (FCC), which discovered that 75% of…

  16. Hypertension after clonidine withdrawal.

    PubMed

    Husserl, F E; deCarvalho, J G; Batson, H M; Frohlich, E D

    1978-05-01

    Rebound hypertension occurred in two patients upon clonidine withdrawal. Treatment of the hypertensive crisis consists of both alpha- and beta-adrenergic receptor blockade, reserpine, or the reintroduction of clonidine. With effective control of pressure during the crisis, long-term antihypertensive therapy must be resumed.

  17. Withdrawal Method (Coitus Interruptus)

    MedlinePlus

    ... RA, et al. Coitus interruptus (withdrawal). In: Contraceptive Technology. 20th ed. New York, N.Y.: Ardent Media; 2011. Zieman M. Overview of contraception. http://www.uptodate.com/home. Accessed Jan. 29, 2015. Lentz GM, et al. Family planning. In: Comprehensive ...

  18. Mediating role of childhood emotional abuse on the relationship between severity of ADHD and PTSD symptoms in a sample of male inpatients with alcohol use disorder.

    PubMed

    Evren, Cuneyt; Umut, Gokhan; Bozkurt, Muge; Evren, Bilge; Agachanli, Ruken

    2016-05-30

    The aim of the present study was to evaluate relationship of PTSD symptom severity with severity of ADHD symptoms while controlling the effect of childhood trauma in a sample of male inpatients with alcohol use disorder (AUD). Participants included 190 male inpatients with AUD. Participants were evaluated with the Childhood Trauma Questionnaire (CTQ-28), the Adult ADHD Self-Report Scale (ASRS) and PTSD Checklist Civilian version (PCL-C). PTSD and ADHD scores were mildly correlated with severity of childhood trauma and types of traumas, the only exception was emotional neglect, which was not correlated with PTSD and ADHD. Severity of ADHD symptoms was associated with the severity of PTSD symptoms, together with the severity of childhood trauma in a linear regression model. In another linear regression model where dimensions of ADHD and childhood trauma were considered as independent variables, emotional abuse and both inattentive and hyperactive/impulsive dimensions of ADHD were associated with the severity of PTSD. These findings suggest that the severity of adult ADHD symptoms is related with the severity of PTSD symptoms, while severity of childhood trauma, particularly emotional abuse may have an mediating role on this relationship among male inpatients with AUD.

  19. First case of stress cardiomyopathy as a result of methadone withdrawal secondary to drug-drug interaction.

    PubMed

    Lemesle, Frédéric; Lemesle, Florence; Nicola, Walid; Pierre Jonville-Béra, Annie

    2010-03-01

    We describe the first case of stress cardiomyopathy secondary to a drug-drug interaction. A 44-year-old man was admitted for acute agitation, hallucinations, tachycardia, and fever within 2 hours of ingestion of naltrexone prescribed to stop alcohol consumption. He had been receiving methadone (120 mg/d) for several months for a history of heroin use; thus, acute opiate withdrawal syndrome secondary to naltrexone treatment was diagnosed. Because electrocardiography showed diffuse ST-segment elevation, a transthoracic echocardiography was performed. It revealed apical akinesia of the left ventricle with a reduction in systolic function. The echocardiogram showed an ejection fraction of 35%, apical and midventricular wall motion abnormalities of the left ventricle, and a cardiac output of 4 L/min without coronary stenosis. The patient was transferred to the cardiologic intensive care unit with a diagnosis of transient left ventricular apical ballooning syndrome secondary to acute opiate withdrawal syndrome. It is likely that opioid withdrawal, inducing a marked increase in catecholamine plasma concentrations, contributed to the development of stress cardiomyopathy. To our knowledge, this is the first case of stress cardiomyopathy described after abrupt opiate withdrawal secondary to a drug-drug interaction.

  20. [Electrophysiological features (EEG) of ethanol withdrawal syndromes on isolated perfused rat brain].

    PubMed

    Tezikov, E B; Litvicki, P F

    2015-01-01

    On isolated rat brains we studied native EEC and its derivates (mean EEC amplitude and power spectrums - Fourier transformation) during perfusion with ethanol (65 Mm/ L) and after its withdrawal. Previously rats were undergone ethanol burden for 6 days according to Majchrowicz procedures to get alcohol withdrawal syndrome. Duration perfusion without ethanol was 5, 10 and 20 min depending on the experimental schedule. Ethanol infusion between periods of withdrawal comprised 20 min. 55% of isolated brains shown epileptiform activity after 1-2 min of ethanol withdrawal but others manifested only increased mean amplitude and the power spectrums of EEC as well as an appearance of single or batch spikes. Differences between in vivo and in vitro conditions can be explained by the accelerated rate of ethanol elimination. The high positive correlation was obtained between EEC findings at the 5-th min of the first ethanol withdrawal and the same findings at the 5-th min of ethanol withdrawal in the second and the third episodes of ethanol withdrawal. Prolongation of withdrawal period more than 5th min caused brain death showing epileptiform activity. Isolated rat brain is the convenient subject to study pathogenesis of excitability of neurons and examination of drugs to treat alcohol withdrawal syndrome.

  1. Social Withdrawal in Childhood

    PubMed Central

    Rubin, Kenneth H.; Coplan, Robert J.; Bowker, Julie C.

    2013-01-01

    Socially withdrawn children frequently refrain from social activities in the presence of peers. The lack of social interaction in childhood may result from a variety of causes, including social fear and anxiety or a preference for solitude. From early childhood through to adolescence, socially withdrawn children are concurrently and predictively at risk for a wide range of negative adjustment outcomes, including socio-emotional difficulties (e.g., anxiety, low self-esteem, depressive symptoms, and internalizing problems), peer difficulties (e.g., rejection, victimization, poor friendship quality), and school difficulties (e.g., poor-quality teacher-child relationships, academic difficulties, school avoidance). The goals of the current review are to (a) provide some definitional, theoretical, and methodological clarity to the complex array of terms and constructs previously employed in the study of social withdrawal; (b) examine the predictors, correlates, and consequences of child and early-adolescent social withdrawal; and (c) present a developmental framework describing pathways to and from social withdrawal in childhood. PMID:18851686

  2. Prolonged cannabis withdrawal in young adults with lifetime psychiatric illness.

    PubMed

    Schuster, Randi Melissa; Fontaine, Madeleine; Nip, Emily; Zhang, Haiyue; Hanly, Ailish; Eden Evins, A

    2017-02-27

    Young adults with psychiatric illnesses are more likely to use cannabis and experience problems from use. It is not known whether those with a lifetime psychiatric illness experience a prolonged cannabis withdrawal syndrome with abstinence. Participants were fifty young adults, aged 18-25, recruited from the Boston-area in 2015-2016, who used cannabis at least weekly, completed the Structured Clinical Interview for DSM-IV to identify Axis I psychiatric diagnoses (PD+ vs PD-), and attained cannabis abstinence with a four-week contingency management protocol. Withdrawal symptom severity was assessed at baseline and at four weekly abstinent visits using the Cannabis Withdrawal Scale. Cannabis dependence, age of initiation, and rate of abstinence were similar in PD+ and PD- groups. There was a diagnostic group by abstinent week interaction, suggesting a difference in time course for resolution of withdrawal symptoms by group, F(4,46)=3.8, p=0.009, controlling for sex, baseline depressive and anxiety symptoms, and frequency of cannabis use in the prior 90days. In post hoc analyses, there was a difference in time-course of cannabis withdrawal. PD- had significantly reduced withdrawal symptom severity in abstinent week one [t(46)=-2.2, p=0.03], while PD+ did not report improved withdrawal symptoms until the second abstinent week [t(46)=-4.1, p=0.0002]. Cannabis withdrawal symptoms improved over four weeks in young people with and without a lifetime psychiatric diagnosis. However, those with a psychiatric illness reported one week delayed improvement in withdrawal symptom severity. Longer duration of cannabis withdrawal may be a risk factor for cannabis dependence and difficulty quitting.

  3. 27 CFR 19.419 - Withdrawals of spirits for use in wine production.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... use in wine production. 19.419 Section 19.419 Alcohol, Tobacco Products and Firearms ALCOHOL AND... in wine production. A proprietor may withdraw wine spirits without payment of tax for transfer in bond to a bonded wine cellar for use in wine production. The proprietor, as consignor, must prepare...

  4. 27 CFR 19.419 - Withdrawals of spirits for use in wine production.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... use in wine production. 19.419 Section 19.419 Alcohol, Tobacco Products and Firearms ALCOHOL AND... in wine production. A proprietor may withdraw wine spirits without payment of tax for transfer in bond to a bonded wine cellar for use in wine production. The proprietor, as consignor, must prepare...

  5. 27 CFR 19.419 - Withdrawals of spirits for use in wine production.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... use in wine production. 19.419 Section 19.419 Alcohol, Tobacco Products and Firearms ALCOHOL AND... in wine production. A proprietor may withdraw wine spirits without payment of tax for transfer in bond to a bonded wine cellar for use in wine production. The proprietor, as consignor, must prepare...

  6. 27 CFR 19.419 - Withdrawals of spirits for use in wine production.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... use in wine production. 19.419 Section 19.419 Alcohol, Tobacco Products and Firearms ALCOHOL AND... in wine production. A proprietor may withdraw wine spirits without payment of tax for transfer in bond to a bonded wine cellar for use in wine production. The proprietor, as consignor, must prepare...

  7. Rodent Models of Genetic Contributions to Motivation to Abuse Alcohol

    PubMed Central

    Crabbe, John C.

    2016-01-01

    The distinction between alcohol use (normative) and abuse (unfortunately common) implies dysregulation of motivation directed toward the drug. Genetic contributions to abuse risk are mediated through personality differences, other predispositions to drink excessively, and differences in sensitivity to the acute and chronic consequences of the drug. How to assess motivation in laboratory animals is not straightforward but risk factors for and consequences of alcohol abuse can be modeled with reasonable fidelity in laboratory rodents. Remarkably few rodent studies focus on the genetic contributions to alcohol’s reinforcing value: almost all examine preferential drinking of unflavored alcohol over water. Such studies will likely never avoid the confounding role of taste preferences and most often yield intake levels insufficient to yield a pharmacologically significant blood alcohol level. Genotypes that avoid alcohol probably do so based on pre-ingestive sensory cues; however, post-ingestive consequences are also important. Thus, the quest for improved measures of reinforcing value continues. We have genetic differences aplenty, but still lack evidence that any genotype will readily self-administer alcohol to the devastating extent that many alcoholics will. Encouraging results that are emerging include improved behavioral methods for elevating alcohol intake and inferring alcohol reinforcement, as well as new genetic animal models. Several ingenious assays to index alcohol’s motivational effects have been used extensively. Alcoholic drinking that attempts to prevent or to alleviate withdrawal symptoms has been modeled. Another characteristic of alcoholic drinking is its persistence despite abundant evidence to the drinker of the damaging effects of the excessive drinking on work, relationships, and/or health. Modeling such persistence in rodents has been uncommon to date. New genetic animal models include lines of mice selectively bred for chronic high drinking

  8. Inhibitory effects of several saturated fatty acids and their related fatty alcohols on the growth of Candida albicans.

    PubMed

    Hayama, Kazumi; Takahashi, Miki; Yui, Satoru; Abe, Shigeru

    2015-12-01

    We examined the effect of 5 saturated fatty acids and their related alcohols on the growth of Candida albicans. The inhibitory effects of these compounds against the yeast and hyphal growth forms of C. albicans were examined using the modified NCCLS method and crystal violet staining, respectively. Among these compounds, capric acid inhibited both types of growth at the lowest concentration. The IC(80), i.e., the concentration at which the compounds reduced the growth of C. albicans by 80% in comparison with the growth of control cells, of capric acid for the hyphal growth of this fungus, which is indispensable for its mucosal invasion, was 16.7 μM. These fatty acids, including capric acid, have an unpleasant smell, which may limit their therapeutic use. To test them at reduced concentrations, the combined effect of these fatty acids and oligonol, a depolymerized polyphenol, was evaluated in vitro. These combinations showed potent synergistic inhibition of hyphal growth [fractional inhibitory concentration (FIC) index = 0.319]. Our results demonstrated that capric acid combined with oligonol could be used as an effective anti-Candida compound. It may be a candidate prophylactic or therapeutic tool against mucosal Candida infection.

  9. Alcohol disrupts sleep homeostasis.

    PubMed

    Thakkar, Mahesh M; Sharma, Rishi; Sahota, Pradeep

    2015-06-01

    Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired

  10. 27 CFR 22.113 - Receipt of tax-free alcohol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Receipt of tax-free alcohol. 22.113 Section 22.113 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Withdrawal...

  11. 27 CFR 22.113 - Receipt of tax-free alcohol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Receipt of tax-free alcohol. 22.113 Section 22.113 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Withdrawal...

  12. 27 CFR 22.113 - Receipt of tax-free alcohol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Receipt of tax-free alcohol. 22.113 Section 22.113 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Withdrawal...

  13. Anhedonia as a component of the tobacco withdrawal syndrome.

    PubMed

    Cook, Jessica W; Piper, Megan E; Leventhal, Adam M; Schlam, Tanya R; Fiore, Michael C; Baker, Timothy B

    2015-02-01

    Animal research suggests that anhedonia is a tobacco withdrawal symptom, but this topic has not been addressed definitively in research with humans. This research sought to determine whether anhedonia is (a) an element of the tobacco withdrawal syndrome in humans and (b) an impediment to successful tobacco cessation. Data were from 1,175 smokers (58.3% women; 85.5% White) participating in a randomized double-blind, placebo-controlled trial of smoking cessation pharmacotherapies. Ecological momentary assessments for 5 days before and 10 days after the target quit day were used to assess anhedonia and other established withdrawal symptoms. Consistent with drug withdrawal, anhedonia showed an inverted-U pattern of change in response to tobacco cessation and was associated with the severity of other withdrawal symptoms and tobacco dependence. Postquit anhedonia was associated with decreased latency to relapse (hazard ratio = 1.09, 95% confidence interval [CI] [1.02, 1.17]) and with lower 8-week point-prevalence abstinence (odds ratio = .91, 95% CI [.86, .97])-relations that remained significant when other withdrawal symptoms were included as predictors. Finally, nicotine replacement therapy nearly fully suppressed the increase in abstinence-related anhedonia (β = -.66, p < .001), suggesting agonist suppression of withdrawal. Results suggest that anhedonia is a unique and motivationally significant element of the tobacco withdrawal syndrome in humans. These results have implications for defining and assessing tobacco use disorder and for understanding and treating tobacco addiction.

  14. Clinical and Biological Risk Factors for Neuropsychological Impairment in Alcohol Use Disorder

    PubMed Central

    Ritz, Ludivine; Coulbault, Laurent; Lannuzel, Coralie; Boudehent, Céline; Segobin, Shailendra; Eustache, Francis; Vabret, François; Pitel, Anne Lise; Beaunieux, Hélène

    2016-01-01

    The effects of alcoholism on cognitive and motor functioning are heterogeneous. While the role of some factors (patterns of alcohol consumption, eating habits or associated liver disease) has been hypothesized, the origins of this heterogeneity remain difficult to establish. The goals of the present study were thus to identify the clinical and biological risk factors for alcohol-related neuropsychological impairments and to determine the threshold beyond which these risk factors can be considered significant. Thirty alcoholic patients and 15 healthy controls had a blood test and underwent a neuropsychological examination. Alcohol severity measures, and liver, thiamine and malnutrition variables, were included in logistic regression models to determine the risk factors for cognitive and motor impairments (executive functions, visuospatial abilities, verbal episodic memory, ataxia), as well as those related to the severity of patients’ overall neuropsychological profile (moderate or severe impairments). Liver fibrosis was found to be a risk factor for executive impairments and also for ataxia, when it was associated with long-term alcohol misuse and symptoms of withdrawal. Altered thiamine metabolism was solely predictive of verbal episodic memory impairments. This combination of biological abnormalities was associated with a profile of moderate neuropsychological impairments. Malnutrition was associated with a profile of more severe impairments. Malnutrition, altered liver function and thiamine metabolism explain, at least partially, the heterogeneity of alcohol-related neuropsychological impairments. Our findings could allow clinicians to identify patients at particular risk of severe neuropsychological impairments before the onset of irreversible and debilitating neurological complications. PMID:27617840

  15. Withdrawal from intermittent ethanol exposure increases probability of burst firing in VTA neurons in vitro.

    PubMed

    Hopf, F Woodward; Martin, Miquel; Chen, Billy T; Bowers, M Scott; Mohamedi, Maysha M; Bonci, Antonello

    2007-10-01

    Changing the activity of ventral tegmental area (VTA) dopamine neurons from pacemaker to burst firing is hypothesized to increase the salience of stimuli, such as an unexpected reward, and likely contributes to withdrawal-associated drug-seeking behavior. Accordingly, pharmacological, behavioral, and electrophysiological data suggest an important role of the VTA in mediating alcohol-dependent behaviors. However, the effects of repeated ethanol exposure on VTA dopamine neuron ion channel function are poorly understood. Here, we repeatedly exposed rats to ethanol (2 g/kg ethanol, ip, twice per day for 5 days), then examined the firing patterns of VTA dopamine neurons in vitro after 7 days withdrawal. Compared with saline-treated animals, the function of the small conductance calcium-dependent potassium channel (SK) was reduced in ethanol-treated animals. Consistent with a role for SK in regulation of burst firing, NMDA applied during firing facilitated the transition to bursting in ethanol-treated but not saline-treated animals; NMDA consistently induced bursting only in saline-treated animals when SK was inhibited. Also, enhanced bursting in ethanol-treated animals was not a result of differences in NMDA-induced depolarization. Further, I(h) was also reduced in ethanol-treated animals, which delayed recovery from hyperpolarization, but did not account for the increased NMDA-induced bursting in ethanol-treated animals. Finally, repeated ethanol exposure and withdrawal also enhanced the acute locomotor-activating effect of cocaine (15 mg/kg, ip). Thus withdrawal after repeated ethanol exposure produced several alterations in the physiological properties of VTA dopamine neurons, which could ultimately increase the ability of VTA neurons to produce burst firing and thus might contribute to addiction-related behaviors.

  16. Cocaine withdrawal in Planaria.

    PubMed

    Raffa, R B; Valdez, J M

    2001-10-26

    Cocaine-exposed planarians displayed abstinence-induced withdrawal behavior when placed into cocaine-free, but not cocaine-containing, water. The effect, manifested and quantified using a new spontaneous locomotor velocity metric, was dose-dependently related to cocaine exposure (8x10(-9) to 8x10(-5) M). Ultraviolet light (254 nm=7.83x10(-19) J), which was previously shown to interfere with drug-receptor interactions in Planaria, enhanced the abstinence-induced decreased locomotor velocity.

  17. Circadian wheel-running activity during withdrawal from chronic intermittent ethanol exposure in mice

    PubMed Central

    Logan, Ryan W.; Seggio, Joseph A.; Robinson, Stacy L.; Richard, Gregory R.; Rosenwasser, Alan M.

    2010-01-01

    Alcohol withdrawal is associated with affective-behavioral disturbances in both human alcoholics and in animal models. In general, these phenomena are potentiated by increased alcohol exposure duration and by prior withdrawal episodes. Previous studies have also reported locomotor hypoactivity during ethanol withdrawal in rats and mice, but only in novel test environments, not in the home-cage. In the present study, we examined the effects of withdrawal from chronic intermittent ethanol (CIE) vapor exposure on the level and circadian periodicity of wheel-running activity in C57BL/6J mice. CIE treatment resulted in reductions in wheel-running activity relative to plain-air controls that persisted for about one week after withdrawal. Analysis of circadian waveforms indicated that reduced activity occurred throughout the night phase, but that daily activity patterns were otherwise unaltered. CIE failed to alter free-running circadian period or phase in animals maintained under constant darkness. These results show that ethanol withdrawal can result in locomotor hypoactivity even in the habitual, home-cage environment, and suggest that withdrawal-related reductions in wheel-running activity may reflect the specific motivational significance of this behavior. PMID:20682191

  18. Response to anticoagulant drug withdrawal.

    PubMed

    Mulligan, R

    1987-09-01

    This study evaluated 44 separate medication withdrawal periods in 17 subjects who were attending a hospital anticoagulation clinic for management of anticoagulation medication. The data suggest that when anticoagulant withdrawal is needed for particular dental procedures, a 2-day hold is an effective period of medication withdrawal. No thromboembolic events were observed after any of the withdrawal periods. Further, no posttreatment hemorrhagic episodes were observed when the anticoagulant medication was reinstituted after dental treatment. Prothrombin time blood levels should be determined in the immediate pretreatment period, however, because the prothrombin time can fluctuate even in the best maintained patients.

  19. Tobacco, Alcohol, Drugs, and Pregnancy

    MedlinePlus

    ... What are fetal alcohol spectrum disorders? • What is fetal alcohol syndrome? • What amounts of alcohol can cause FAS? • Is ... disabilities that can last a lifetime. What is fetal alcohol syndrome? Fetal alcohol syndrome (FAS) is the most severe ...

  20. Validation of AshTest as a Non-Invasive Alternative to Transjugular Liver Biopsy in Patients with Suspected Severe Acute Alcoholic Hepatitis

    PubMed Central

    Rudler, Marika; Mouri, Sarah; Charlotte, Frederic; Cluzel, Philippe; Ngo, Yen; Munteanu, Mona; Lebray, Pascal; Ratziu, Vlad; Thabut, Dominique; Poynard, Thierry

    2015-01-01

    Background/Aims According to guidelines, the histological diagnosis of severe alcoholic steatohepatitis (ASH) can require liver biopsy if a specific treatment is needed. The blood test AshTest (BioPredictive, Paris, France) has been initially validated for the non-invasive diagnosis of ASH in a large population of heavy drinkers. The aim was to validate the AshTest accuracy in the specific context of use of patients with suspected severe ASH, in order to reduce the need for transjugular biopsy before deciding treatment. Methods The reference was liver biopsy, performed using the transjugular route, classified according to its histological severity as none, minimal, moderate or severe. Biopsies were assessed by the same experienced pathologist, blinded to simultaneous AshTest results. Results A total of 123 patients with severe clinical ASH (recent jaundice and Maddrey function greater or equal to 32) were included, all had cirrhosis and 80% had EASL histological definition of ASH. 95% of patients received prednisolone; and the 2-year mortality was 63%. The high AshTest performance was confirmed both for the binary outcome [AUROC = 0.803 (95%CI 0.684–0.881)] significantly higher than the AST/ALT AUROC [0.603 (0.462–0.714); P<0.001], and for the severity of ASH-score system by the Obuchowski measures for [mean (SE) 0.902 (0.017) vs. AST/ALT 0.833 (0.023); P = 0.01], as well as for the diagnosis and severity of ballooning, PMN and Mallory bodies. According to attributability of discordances, AshTest had a 2–7% risk of 2 grades misclassification. Conclusion These results confirmed the diagnostic performance of AshTest in cirrhotic patients with severe clinical ASH, in the specific context of use of corticosteroid treatment. AshTest is an appropriate non-invasive alternative to transjugular liver biopsy. PMID:26252713

  1. 27 CFR 19.420 - Withdrawals of spirits without payment of tax for experimental or research use.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... without payment of tax for experimental or research use. 19.420 Section 19.420 Alcohol, Tobacco Products... SPIRITS PLANTS Transfers, Receipts, and Withdrawals Spirits Withdrawn Without Payment of Tax § 19.420 Withdrawals of spirits without payment of tax for experimental or research use. A scientific...

  2. 27 CFR 19.420 - Withdrawals of spirits without payment of tax for experimental or research use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... without payment of tax for experimental or research use. 19.420 Section 19.420 Alcohol, Tobacco Products... SPIRITS PLANTS Transfers, Receipts, and Withdrawals Spirits Withdrawn Without Payment of Tax § 19.420 Withdrawals of spirits without payment of tax for experimental or research use. A scientific...

  3. 27 CFR 19.421 - Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... use in production of nonbeverage wine and nonbeverage wine products. 19.421 Section 19.421 Alcohol....421 Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products. A proprietor may withdraw spirits without payment of tax for transfer to a bonded wine cellar for use in...

  4. 27 CFR 19.421 - Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... use in production of nonbeverage wine and nonbeverage wine products. 19.421 Section 19.421 Alcohol....421 Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products. A proprietor may withdraw spirits without payment of tax for transfer to a bonded wine cellar for use in...

  5. 27 CFR 19.421 - Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... use in production of nonbeverage wine and nonbeverage wine products. 19.421 Section 19.421 Alcohol....421 Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products. A proprietor may withdraw spirits without payment of tax for transfer to a bonded wine cellar for use in...

  6. 27 CFR 19.421 - Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... use in production of nonbeverage wine and nonbeverage wine products. 19.421 Section 19.421 Alcohol....421 Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products. A proprietor may withdraw spirits without payment of tax for transfer to a bonded wine cellar for use in...

  7. Emergent intrathecal baclofen withdrawal after pseudomeningocele aspiration.

    PubMed

    Smith, Timothy R; Mithal, Divakar S; Park, Anne; Bohnen, Angela; Adel, Joseph; Rosenow, Joshua M

    2013-01-01

    Intrathecal baclofen (ITB) infusion has become a common treatment for severe spasticity. Many complications of these drug delivery systems have been reported such as those related to improper dosing, mechanical failure of the implanted pump or catheter, or post-operative wound issues. We report a case of ITB withdrawal after pseudomeningocele aspiration. A 21 year-old male with spastic quadriparesis due to traumatic brian injury (TBI) presented with a pseudomeningocele surrounding an ITB pump (215 mcg/day, continuous) implanted in the abdomen. The pseudomeningocele was percutaneously aspirated and approximately 15 hours later the patient developed signs and symptoms of acute baclofen withdrawal. As a result, the patient underwent an exploration of the ITB infusion system with an intraoperative epidural blood patch. The symptoms of ITB withdrawal improved over the next 18 hours. The subcutaneous cerebrospinal fluid (CSF) collection partially recurred 48 hours later, but this resolved after a second epidural blood patch. The case illustrates a unique presentation of a serious complication of ITB infusion. This underscores that timely diagnosis and treatment of acute baclofen withdrawal is key to optimal outcomes.

  8. Student Withdrawal Survey: College Withdrawal, Spring 1986. Research Report 1.

    ERIC Educational Resources Information Center

    Montemayor, J. Joaquin; And Others

    A sample of students who withdrew from Mesa (Arizona) Community College (MCC) during spring 1986 was surveyed to determine reasons for withdrawal and dropout characteristics. Study findings included the following: (1) the primary reason for withdrawing was conflicting job hours, with 52% of the students who were employed working over 40 hours per…

  9. 19 CFR 24.4 - Optional method for payment of estimated import taxes on alcoholic beverages upon entry, or...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. 24.4 Section 24... estimated import taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. (a) Application to defer. An importer, including a transferee of alcoholic beverages in a Customs bonded...

  10. 19 CFR 24.4 - Optional method for payment of estimated import taxes on alcoholic beverages upon entry, or...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. 24.4 Section 24... estimated import taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. (a) Application to defer. An importer, including a transferee of alcoholic beverages in a Customs bonded...

  11. 19 CFR 24.4 - Optional method for payment of estimated import taxes on alcoholic beverages upon entry, or...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. 24.4 Section 24... estimated import taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. (a) Application to defer. An importer, including a transferee of alcoholic beverages in a Customs bonded...

  12. 19 CFR 24.4 - Optional method for payment of estimated import taxes on alcoholic beverages upon entry, or...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. 24.4 Section 24... estimated import taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. (a) Application to defer. An importer, including a transferee of alcoholic beverages in a Customs bonded...

  13. 19 CFR 24.4 - Optional method for payment of estimated import taxes on alcoholic beverages upon entry, or...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. 24.4 Section 24... estimated import taxes on alcoholic beverages upon entry, or withdrawal from warehouse, for consumption. (a) Application to defer. An importer, including a transferee of alcoholic beverages in a Customs bonded...

  14. A DNA Element Regulates Drug Tolerance and Withdrawal in Drosophila

    PubMed Central

    Li, Xiaolei; Ghezzi, Alfredo; Pohl, Jascha B.; Bohm, Arun Y.; Atkinson, Nigel S.

    2013-01-01

    Drug tolerance and withdrawal are insidious responses to drugs of abuse; the first increases drug consumption while the second punishes abstention. Drosophila generate functional tolerance to benzyl alcohol sedation by increasing neural expression of the slo BK-type Ca2+ activated K+ channel gene. After drug clearance this change produces a withdrawal phenotype—increased seizure susceptibility. The drug-induced histone modification profile identified the 6b element (60 nt) as a drug responsive element. Genomic deletion of 6b produces the allele, sloΔ6b, that reacts more strongly to the drug with increased induction, a massive increase in the duration of tolerance, and an increase in the withdrawal phenotype yet does not alter other slo-dependent behaviors. The 6b element is a homeostatic regulator of BK channel gene expression and is the first cis-acting DNA element shown to specifically affect the duration of a drug action. PMID:24086565

  15. A Comparative Study of the Clinical Efficacy and Safety of Lorazepam and Chlordiazepoxide in Alcohol Dependence Syndrome

    PubMed Central

    Padma, Lakshminarayana; Swaminath, Gopalrao; Thimmaiah, Rohini S.

    2015-01-01

    Background: Currently, benzodiazepines are the preferred drugs in the management of alcohol withdrawal symptoms. Chlordiazepoxide and diazepam, the most frequently used drugs have a long duration of action and are converted to active metabolites in the liver, while lorazepam is shorter acting, with no active metabolites. Objective: To compare and evaluate the safety and efficacy of lorazepam and chlordiazepoxide in patients with alcohol dependence syndrome with symptoms of alcohol withdrawal. Materials and Methods: This was a prospective, randomized, double-blind, study carried out at a teaching hospital in Bangalore. Sixty patients aged ≥18 y with alcohol dependence syndrome with mild-to-moderate withdrawal symptoms were allocated at a ratio of 1:1 to either lorazepam or chlordiazepoxide, by means of a computer-generated randomization chart. Thirty patients each were started with lorazepam tablets 8 mg/day and chlordiazepoxide 80 mg/day. For both treatment groups, the dose was tapered and at the end of 8 days, the patients were drug-free. The severity of alcohol dependence was assessed using the Severity of Alcohol Dependence Questionnaire (SADQ). The CIWA-Ar was used for quantification of withdrawal symptoms. Liver function tests were performed at baseline and at the end of the study. Results: Of the 60 patients included in the study, 15 patients each had mild and moderate withdrawal symptoms in the chlordiazepoxide group and 17 and 13 patients respectively in the lorazepam group, based on the SADQ score. At baseline, the mean CIWA-Ar scores were similar in both the treatment groups: 24.77±5.98 in the chlordiazepoxide group and 24.90±6.12 in the lorazepam group. There was a significant intragroup decrease in the CIWA-Ar scores measured from baseline to the end of 8 days (p<0.0001) and 12 days (p<0.0001) in both treatment groups; however, there was no significant difference between the two groups. There was no significant difference observed in the liver

  16. Clinical experience of baclofen in alcohol dependence: A chart review

    PubMed Central

    Rozatkar, Abhijit R.; Kapoor, Abhishek; Sidana, Ajeet; Chavan, Bir Singh

    2016-01-01

    Introduction: Craving is recognized as a formidable barrier in the management of patients with alcohol dependence. Among pharmacological agents that have been used in experimental studies for reduction in craving, baclofen appears to have a significant advantage over other agents. Methodology: The study is retrospective chart review of patients (n = 113) who have been treated with baclofen for alcohol dependence in a tertiary hospital of North India. Baseline assessments included sociodemography, motivation, quantity-frequency of alcohol use, and other alcohol-related clinical parameters. Weekly assessments, for a period of 4 weeks, were extracted from records which included dose of baclofen, craving intensity, and alcohol consumption. Results: The study sample was predominantly male, mean age of 41.49 (±9.75) years, most having a family history of substance use (70.97%), and many reporting binge use pattern in last year (49.46%). Baseline assessment revealed 48.7% of the sample was in precontemplation phase for alcohol use and 70% reported severe and persistent craving. This persistent craving was reported by only 15% of the sample by the end of 4 weeks treatment with baclofen (20–40 mg/day). Thirty-four percent of patients reported continued problematic use of alcohol by the end of 4 weeks. Conclusion: Our clinical experience suggests that baclofen reduces craving and alcohol consumption including in those with poor motivation. The drug causes few side effects and does not add to the intoxication effect of alcohol. Considering that baclofen is safe in those with liver cirrhosis and reduces withdrawal symptoms due to alcohol, a controlled trial comparing it with standard treatment is required. PMID:28163402

  17. Severe Central Sleep Apnea Associated With Chronic Baclofen Therapy: A Case Series.

    PubMed

    Olivier, Pierre-Yves; Joyeux-Faure, Marie; Gentina, Thibaut; Launois, Sandrine H; d'Ortho, Marie Pia; Pépin, Jean-Louis; Gagnadoux, Frédéric

    2016-05-01

    Baclofen, a gamma-aminobutyric acid-B agonist with muscle-relaxant properties, is widely used in patients with severe spasticity. In animals, baclofen has been shown to decrease respiratory drive. In humans, however, use of baclofen at the standard dose did not significantly impair sleep-disordered breathing in a susceptible population of snorers. Recently, there has been increasing interest in the role of baclofen for the treatment of alcohol dependence. We describe severe central sleep apnea (CSA) in four patients with none of the conditions commonly associated with CSA who were receiving chronic baclofen therapy for alcohol withdrawal. In one patient, baclofen withdrawal was associated with a complete resolution of CSA. Three patients were treated by adaptive servo-ventilation while continuing their treatment with baclofen. Given the increasing number of patients receiving baclofen for alcohol withdrawal treatment, physicians should be aware that these patients might be affected by severe CSA. Future studies are required to determine the mechanisms, prevalence, and treatment modalities of sleep-disordered breathing associated with baclofen usage.

  18. The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans.

    PubMed

    Qiu, Bin; Luczak, Susan E; Wall, Tamara L; Kirchhoff, Aaron M; Xu, Yuxue; Eng, Mimy Y; Stewart, Robert B; Shou, Weinian; Boehm, Stephen L; Chester, Julia A; Yong, Weidong; Liang, Tiebing

    2016-08-05

    FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2.0 g/kg EtOH; (3) Blood alcohol concentration (BAC) was measured after 3 h limited access of alcohol; (4) Brain region expression of Fkbp5 was identified using LacZ staining; (5) Baseline corticosterone (CORT) was assessed. Additionally, two SNPs, rs1360780 (C/T) and rs3800373 (T/G), were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162) from 21-26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT). Finally, single nucleotide polymorphisms (SNPs) in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans.

  19. The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans

    PubMed Central

    Qiu, Bin; Luczak, Susan E.; Wall, Tamara L.; Kirchhoff, Aaron M.; Xu, Yuxue; Eng, Mimy Y.; Stewart, Robert B.; Shou, Weinian; Boehm, Stephen L.; Chester, Julia A.; Yong, Weidong; Liang, Tiebing

    2016-01-01

    FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2.0 g/kg EtOH; (3) Blood alcohol concentration (BAC) was measured after 3 h limited access of alcohol; (4) Brain region expression of Fkbp5 was identified using LacZ staining; (5) Baseline corticosterone (CORT) was assessed. Additionally, two SNPs, rs1360780 (C/T) and rs3800373 (T/G), were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162) from 21–26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT). Finally, single nucleotide polymorphisms (SNPs) in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans. PMID:27527158

  20. Cuesta College Student Withdrawal Survey.

    ERIC Educational Resources Information Center

    Hagen, Peter F.; Cartnal, Ryan

    The spring 1999 student withdrawal survey was made available for approximately two weeks before the final withdrawal deadline to all students who formally dropped a class through the admissions office at either the North County or San Luis Obsipo campus of Cuesta College in California. A total of 438 useable surveys were collected. The identical…

  1. Val158Met COMT polymorphism and risk of aggression in alcohol dependence.

    PubMed

    Soyka, Michael; Zill, Peter; Koller, Gabi; Samochowiec, Agnieszka; Grzywacz, Anna; Preuss, Ulrich W

    2015-01-01

    Aggression, violence and antisocial behavior are common in alcoholism, but their biological basis is poorly understood. Several studies and recent meta-analyses indicate that in schizophrenia the catecholamine-O-methyltransferase (COMT) Val158Met genotype may be associated with aggression, most often in methionine allele carriers. We tested this hypothesis in a sample of treatment-seeking alcohol-dependent in-patients (293 German patients and 499 controls, and additional 190 Polish patients as replication sample). As expected, patients with a history of violent or non-violent crime were more often male, had an earlier onset of alcoholism and more withdrawal seizures and delirium tremens, and were more likely to have a history of suicide attempts. COMT genotype was not associated with a history of violent or non-violent crime. More studies are needed on the neurobiological basis of aggression and violence in alcoholism.

  2. Molecular basis of alcoholism.

    PubMed

    Most, Dana; Ferguson, Laura; Harris, R Adron

    2014-01-01

    Acute alcohol intoxication causes cellular changes in the brain that last for hours, while chronic alcohol use induces widespread neuroadaptations in the nervous system that can last a lifetime. Chronic alcohol use and the progression into dependence involve the remodeling of synapses caused by changes in gene expression produced by alcohol. The progression of alcohol use, abuse, and dependence can be divided into stages, which include intoxication, withdrawal, and craving. Each stage is associated with specific changes in gene expression, cellular function, brain circuits, and ultimately behavior. What are the molecular mechanisms underlying the transition from recreational use (acute) to dependence (chronic)? What cellular adaptations result in drug memory retention, leading to the persistence of addictive behaviors, even after prolonged drug abstinence? Research into the neurobiology of alcoholism aims to answer these questions. This chapter will describe the molecular adaptations caused by alcohol use and dependence, and will outline key neurochemical participants in alcoholism at the molecular level, which are also potential targets for therapy.

  3. Alcohol and violence: neuropeptidergic modulation of monoamine systems

    PubMed Central

    Miczek, Klaus A.; DeBold, Joseph F.; Hwa, Lara S.; Newman, Emily L.; de Almeida, Rosa M. M.

    2015-01-01

    Neurobiological processes underlying the epidemiologically-established link between alcohol and several types of social, aggressive, and violent behavior remain poorly understood. Acute low doses of alcohol, as well as withdrawal from long-term alcohol use, may lead to escalated aggressive behavior in a subset of individuals. An urgent task will be to disentangle the host of interacting genetic and environmental risk factors in individuals that are predisposed to engage in escalated aggressive behavior. The modulation of 5-hydroxytryptamine impulse flow by gamma-aminobutyric acid (GABA) and glutamate, acting via distinct ionotropic and metabotropic receptor subtypes in the dorsal raphe nucleus during alcohol consumption, is of critical significance in the suppression and escalation of aggressive behavior. In anticipation and reaction to aggressive behavior, neuropeptides such as corticotropin-releasing factor, neuropeptide Y, opioid peptides, and vasopressin interact with monoamines, GABA, and glutamate to attenuate and amplify aggressive behavior in alcohol-consuming individuals. These neuromodulators represent novel molecular targets for intervention that await clinical validation. Intermittent episodes of brief social defeat during aggressive confrontations are sufficient to cause long-lasting neuroadaptations that can lead to the escalation of alcohol consumption. PMID:26285061

  4. Alcohol and violence: neuropeptidergic modulation of monoamine systems.

    PubMed

    Miczek, Klaus A; DeBold, Joseph F; Hwa, Lara S; Newman, Emily L; de Almeida, Rosa M M

    2015-09-01

    Neurobiological processes underlying the epidemiologically established link between alcohol and several types of social, aggressive, and violent behavior remain poorly understood. Acute low doses of alcohol, as well as withdrawal from long-term alcohol use, may lead to escalated aggressive behavior in a subset of individuals. An urgent task will be to disentangle the host of interacting genetic and environmental risk factors in individuals who are predisposed to engage in escalated aggressive behavior. The modulation of 5-hydroxytryptamine impulse flow by gamma-aminobutyric acid (GABA) and glutamate, acting via distinct ionotropic and metabotropic receptor subtypes in the dorsal raphe nucleus during alcohol consumption, is of critical significance in the suppression and escalation of aggressive behavior. In anticipation and reaction to aggressive behavior, neuropeptides such as corticotropin-releasing factor, neuropeptide Y, opioid peptides, and vasopressin interact with monoamines, GABA, and glutamate to attenuate and amplify aggressive behavior in alcohol-consuming individuals. These neuromodulators represent novel molecular targets for intervention that await clinical validation. Intermittent episodes of brief social defeat during aggressive confrontations are sufficient to cause long-lasting neuroadaptations that can lead to the escalation of alcohol consumption.

  5. Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish.

    PubMed

    Khor, Beng-Siang; Jamil, Mohd Fadzly Amar; Adenan, Mohamad Ilham; Shu-Chien, Alexander Chong

    2011-01-01

    A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway.

  6. Acute inflammatory bowel disease complicating chronic alcoholism and mimicking carcinoid syndrome.

    PubMed

    Ballo, Piercarlo; Dattolo, Pietro; Mangialavori, Giuseppe; Ferro, Giuseppe; Fusco, Francesca; Consalvo, Matteo; Chiodi, Leandro; Pizzarelli, Francesco; Zuppiroli, Alfredo

    2012-05-01

    We report the case of a woman with a history of chronic alcohol abuse who was hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion, nausea, vomiting, abdominal pain, alternations of high blood pressure with phases of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and cortisol. Although carcinoid syndrome was hypothesized, abdominal computed tomography and colonoscopy showed non-specific inflammatory bowel disease with severe colic wall thickening, and multiple colic biopsies confirmed non-specific inflammation with no evidence of carcinoid cells. During the following days diarrhea slowly decreased and the patient's condition progressively improved. One year after stopping alcohol consumption, the patient was asymptomatic and serum potassium was normal. Chronic alcohol exposure is known to have several deleterious effects on the intestinal mucosa and can favor and sustain local inflammation. Chronic alcohol intake may also be associated with high blood pressure, behavior disorders, abnormalities in blood pressure regulation with episodes of hypotension during hospitalization due to impaired baroreflex sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5-hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased urinary cortisol as a result of hypothalamic-pituitary-adrenal axis dysregulation. These considerations, together with the regression of symptoms and normalization of potassium levels after stopping alcohol consumption, suggest the intriguing possibility of a alcohol-related acute inflammatory bowel disease mimicking carcinoid syndrome.

  7. Acute Inflammatory Bowel Disease Complicating Chronic Alcoholism and Mimicking Carcinoid Syndrome

    PubMed Central

    Ballo, Piercarlo; Dattolo, Pietro; Mangialavori, Giuseppe; Ferro, Giuseppe; Fusco, Francesca; Consalvo, Matteo; Chiodi, Leandro; Pizzarelli, Francesco; Zuppiroli, Alfredo

    2012-01-01

    We report the case of a woman with a history of chronic alcohol abuse who was hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion, nausea, vomiting, abdominal pain, alternations of high blood pressure with phases of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and cortisol. Although carcinoid syndrome was hypothesized, abdominal computed tomography and colonoscopy showed non-specific inflammatory bowel disease with severe colic wall thickening, and multiple colic biopsies confirmed non-specific inflammation with no evidence of carcinoid cells. During the following days diarrhea slowly decreased and the patient's condition progressively improved. One year after stopping alcohol consumption, the patient was asymptomatic and serum potassium was normal. Chronic alcohol exposure is known to have several deleterious effects on the intestinal mucosa and can favor and sustain local inflammation. Chronic alcohol intake may also be associated with high blood pressure, behavior disorders, abnormalities in blood pressure regulation with episodes of hypotension during hospitalization due to impaired baroreflex sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5-hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased urinary cortisol as a result of hypothalamic-pituitary-adrenal axis dysregulation. These considerations, together with the regression of symptoms and normalization of potassium levels after stopping alcohol consumption, suggest the intriguing possibility of a alcohol-related acute inflammatory bowel disease mimicking carcinoid syndrome. PMID:22949895

  8. Herbal mixtures consisting of puerarin and either polyenylphosphatidylcholine or curcumin provide comprehensive protection against alcohol-related disorders in P rats receiving free choice water and 15% ethanol in pure water.

    PubMed

    Singh, Ashok K; Jiang, Yin; Benlhabib, Elhabib; Gupta, Shveta

    2007-09-01

    Chronic alcohol drinking has been associated with the development of a number of abnormalities, including neuron-behavioral disorders, liver, pancreas, and heart-related diseases and inflammation and immune disorders. Because diverse mechanisms are involved in the development of these disorders, the commonly used receptor- or enzyme-specific drugs do not provide comprehensive protection against the adverse effects of alcoholism. This study describes possible therapeutic potency of puerarin (PU) from kudzu root, polyenylphosphatidylcholine from soy (SPCh), and curcumin (CU) from turmeric against alcohol's addiction-related and inflammatory-related abnormalities in alcohol-preferring P rats receiving free choice water and 15% ethanol in water. P-rats were fed once daily either the vehicle (for control) or different doses of PU, SPCh, CU, PU + SPCh, or PU + CU. The rats were divided in two groups: one received water alone, and the other free choice water and ethanol. Four rats from each group were fitted with electroencephalogram (EEG) electrodes for EEG recording. After 70 days of alcohol drinking, alcohol was withdrawn for 2 weeks, and the withdrawal symptoms were assessed. This study showed that alcohol drinking for 70 days (1) caused liver inflammation characterized by elevated tumor necrosis factor-alpha, interleukin-1beta, and matrix metalloproteinase-9 expression and (2) dysregulated lipopolysaccharide (LPS)-induced pleurisy. Alcohol withdrawal after 70 days of drinking generated severe withdrawal symptoms including seizure-type EEG activity. PU suppressed the addiction-mediated abnormalities but did not affect the inflammation-related abnormalities, while SPCh or CU suppressed only the inflammation-related abnormalities in alcohol-drinking rats subjected to LPS-induced pleurisy. A combination of PU with SPCh or CU suppressed both the addiction-related and inflammation-related abnormalities of alcohol drinking. Therefore, a mixture consisting of PU and either

  9. Molecular composition and size distribution of sugars, sugar-alcohols and carboxylic acids in airborne particles during a severe urban haze event caused by wheat straw burning

    NASA Astrophysics Data System (ADS)

    Wang, Gehui; Chen, Chunlei; Li, Jianjun; Zhou, Bianhong; Xie, Mingjie; Hu, Shuyuan; Kawamura, Kimitaka; Chen, Yan

    2011-05-01

    Molecular compositions and size distributions of water-soluble organic compounds (WSOC, i.e., sugars, sugar-alcohols and carboxylic acids) in particles from urban air of Nanjing, China during a severe haze event caused by field burning of wheat straw were characterized and compared with those in the summer and autumn non-haze periods. During the haze event levoglucosan (4030 ng m -3) was the most abundant compound among the measured WSOC, followed by succinic acid, malic acid, glycerol, arabitol and glucose, being different from those in the non-haze samples, in which sucrose or azelaic acid showed a second highest concentration, although levoglucosan was the highest. The measured WSOC in the haze event were 2-20 times more than those in the non-hazy days. Size distribution results showed that there was no significant change in the compound peaks in coarse mode (>2.1 μm) with respect to the haze and non-haze samples, but a large difference in the fine fraction (<2.1 μm) was found with a sharp increase during the hazy days mostly due to the increased emissions of wheat straw burning. Molecular compositions of organic compounds in the fresh smoke particles from wheat straw burning demonstrate that sharply increased concentrations of glycerol and succinic and malic acids in the fine particles during the haze event were mainly derived from the field burning of wheat straw, although the sources of glucose and related sugar-alcohols whose concentrations significantly increased in the fine haze samples are unclear. Compared to that in the fresh smoke particles of wheat straw burning an increase in relative abundance of succinic acid to levoglucosan during the haze event suggests a significant production of secondary organic aerosols during transport of the smoke plumes.

  10. Copy number variation in exportin-4 (XPO4) gene and its association with histological severity of non-alcoholic fatty liver disease

    PubMed Central

    Zain, Shamsul Mohd; Mohamed, Zahurin; Pirmohamed, Munir; Tan, Hwa Li; Alshawsh, Mohammed Abdullah; Mahadeva, Sanjiv; Chan, Wah-Kheong; Mustapha, Nik Raihan Nik; Mohamed, Rosmawati

    2015-01-01

    A recent genome-wide copy number (CNV) scan identified a 13q12.11 duplication in the exportin-4 (XPO4) gene to be associated with non-alcoholic steatohepatitis (NASH). We sought to confirm the finding in a larger cohort and to assess the serum XPO4 pattern in a broad spectrum of non-alcoholic fatty liver disease (NAFLD) cases. We analysed 249 NAFLD patients and 232 matched controls using TaqMan assay and serum XPO4 was measured. Copy number distribution was as follows: copy number neutral (NAFLD: 53.8%, controls: 68.6%), copy number losses (NAFLD: 13.3%, controls: 12.9%), copy number gains (NAFLD: 32.9%, controls: 18.5%). CNV gain was significantly associated with a greater risk of NAFLD (adjusted OR 2.22, 95% CI 1.42–3.46, P = 0.0004) and NASH (adjusted OR 2.33, 95% CI 1.47–3.68, P = 0.0003). Interestingly, subjects carrying extra copy number showed significantly higher serum ALT and triglyceride (P < 0.05). Serum XPO4 levels progressively declined (P = 0.043) from controls (24.6 ng/mL) to simple steatosis (20.8 ng/mL) to NASH (13.8 ng/mL). In conclusion, XPO4 CNV duplication was associated with histological severity of NAFLD, and accompanied by changes in serum XPO4 levels providing insights into NAFLD pathogenesis, and has the potential for biomarker development. PMID:26293807

  11. MAOA Alters the Effects of Heavy Drinking and Childhood Physical Abuse on Risk for Severe Impulsive Acts of Violence Among Alcoholic Violent Offenders

    PubMed Central

    Tikkanen, Roope; Ducci, Francesca; Goldman, David; Holi, Matti; Lindberg, Nina; Tiihonen, Jari; Virkkunen, Matti

    2011-01-01

    Background A polymorphism in the promoter region of the monoamine oxidase A gene (MAOA) has been shown to alter the effect of persistent drinking and childhood maltreatment on the risk for violent and antisocial behaviors. These findings indicate that MAOA could contribute to inter-individual differences in stress resiliency. Methods Recidivism in severe violent crimes was assessed after 8 years of nonincarcerated follow-up in a male sample of 174 impulsive Finnish alcoholic violent offenders, the majority of whom exhibited antisocial (ASPD) or borderline personality disorder (BPD) or both. We examined whether MAOA genotype alters the effects of heavy drinking and childhood physical abuse (CPA) on the risk for committing impulsive recidivistic violent crimes. Results Logistic regression analyses showed that both heavy drinking and CPA were significant independent predictors of recidivism in violent behavior (OR 5.2, p = 0.004 and OR 5.3, p = 0.003) among offenders having the high MAOA activity genotype (MAOA-H), but these predictors showed no effect among offenders carrying the low MAOA activity genotype (MAOA-L). Conclusion Carriers of the MAOA-H allele have a high risk to commit severe recidivistic impulsive violent crimes after exposure to heavy drinking and CPA. PMID:20201935

  12. Effects of oxytocin on nicotine withdrawal in rats.

    PubMed

    Manbeck, Katherine E; Shelley, David; Schmidt, Clare E; Harris, Andrew C

    2014-01-01

    Development of medications that attenuate symptoms of nicotine withdrawal may be useful for facilitating smoking cessation. The neuropeptide oxytocin (OXY) decreases withdrawal signs and other addiction-related effects of several drugs of abuse in animals, but has not been examined in a preclinical model of nicotine addiction. The goal of this study was to examine the effects of OXY on nicotine withdrawal in rats, measured as increases in somatic signs and elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior) during antagonist-precipitated withdrawal from a chronic nicotine infusion. Effects of OXY on baseline ICSS thresholds in non-dependent rats were also evaluated. OXY (0.06 - 1.0mg/kg, i.p.) blocked withdrawal-induced elevations in somatic signs in nicotine-dependent rats without affecting somatic signs in non-dependent rats. In contrast, OXY did not affect nicotine withdrawal-induced elevations in ICSS thresholds. Relatively high doses of OXY (0.75 or 2.0mg/kg) elevated baseline ICSS thresholds in non-dependent rats. These findings demonstrate that OXY blocks somatic signs but not elevations in ICSS thresholds during antagonist-precipitated nicotine withdrawal. The ability of higher OXY doses to elevate baseline ICSS thresholds in non-dependent rats may reflect an aversive and/or motoric effect. These data suggest that OXY-based medications may be useful for treating the somatic component of the nicotine withdrawal syndrome, but may not be effective in attenuating withdrawal-induced anhedonia.

  13. Intrathecal Clonidine Pump Failure Causing Acute Withdrawal Syndrome With 'Stress-Induced' Cardiomyopathy.

    PubMed

    Lee, Hwee Min D; Ruggoo, Varuna; Graudins, Andis

    2016-03-01

    Clonidine is a central alpha(2)-agonist antihypertensive used widely for opioid/alcohol withdrawal, attention deficit hyperactivity disorder and chronic pain management. We describe a case of clonidine withdrawal causing life-threatening hypertensive crisis and stress-induced cardiomyopathy. A 47-year-old man with chronic back pain, treated with clonidine for many years via intrathecal pump (550 mcg/24 h), presented following a collapse and complaining of sudden worsening of back pain, severe headache, diaphoresis, nausea and vomiting. A few hours prior to presentation, his subcutaneous pump malfunctioned. On presentation, vital signs included pulse 100 bpm, BP 176/103 mmHg, temperature 37.8 °C and O2 saturation 100 % (room air). Acute clonidine withdrawal with hypertensive crisis was suspected. Intravenous clonidine loading dose and a 50 mcg/h infusion were commenced. Five hours later, severe chest pain, dyspnoea, tachycardia, hypoxia, with BP 180/120 mmHg and pulmonary edema ensued. ECG showed sinus tachycardia with no ST elevation. Repeated intravenous clonidine doses were given (25 mcg every 5-10 min), with ongoing clonidine infusion to control blood pressure. Glyceryl trinitrate infusion, positive pressure ventilation and intravenous benzodiazepines were added. Bedside echocardiogram showed stress-induced cardiomyopathy pattern. Serum troponin-I was markedly elevated. His coronary angiography showed minor irregularities in the major vessels. Over the next 3 days in the ICU, drug infusions were weaned. Discharge was 12 days later on oral clonidine, metoprolol, perindopril, aspirin and oxycodone-SR. Two months later, his echocardiogram was normal. The intrathecal pump was removed. We report a case of stress-induced cardiomyopathy resulting from the sudden cessation of long-term intrathecal clonidine. This was managed by re-institution of clonidine and targeted organ-specific therapies.

  14. Alcoholism's Hidden Curriculum.

    ERIC Educational Resources Information Center

    Gress, James R.

    1988-01-01

    Discusses children of alcoholics as victims of fetal alcohol syndrome, family violence, retarded social development, and severe emotional scars. These children bring family roles to school that allow survival in the alcoholic home but are dysfunctional outside it. Educators can take certain steps to address these students' problems. Includes six…

  15. Alcoholism, Alcohol, and Drugs

    ERIC Educational Resources Information Center

    Rubin, Emanuel; Lieber, Charles S.

    1971-01-01

    Describes research on synergistic effects of alcohol and other drugs, particularly barbiturates. Proposes biochemical mechanisms to explain alcoholics' tolerance of other drugs when sober, and increased sensitivity when drunk. (AL)

  16. Alcoholism: genes and mechanisms.

    PubMed

    Oroszi, Gabor; Goldman, David

    2004-12-01

    Alcoholism is a chronic relapsing/remitting disease that is frequently unrecognized and untreated, in part because of the partial efficacy of treatment. Only approximately one-third of patients remain abstinent and one-third have fully relapsed 1 year after withdrawal from alcohol, with treated patients doing substantially better than untreated [1]. The partial effectiveness of strategies for prevention and treatment, and variation in clinical course and side effects, represent a challenge and an opportunity to better understand the neurobiology of addiction. The strong heritability of alcoholism suggests the existence of inherited functional variants of genes that alter the metabolism of alcohol and variants of other genes that alter the neurobiologies of reward, executive cognitive function, anxiety/dysphoria, and neuronal plasticity. Each of these neurobiologies has been identified as a critical domain in the addictions. Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.

  17. Low effective organizational strategies in visual memory performance of unmedicated alcoholics during early abstinence

    PubMed Central

    Daig, Isolde; Mahlberg, Richard; Schroeder, Franziska; Gudlowski, Yehonala; Wrase, Jana; Wertenauer, Florian; Bschor, Tom; Esser, Guenter; Heinz, Andreas; Kienast, Thorsten

    2010-01-01

    Objective: Alcohol-dependent patients in early abstinence show an impairment of cognitive functions which can be seen in poor implementation of newly learned skills for avoiding relapse. Executive dysfunction may persist during abstinence in alcohol-dependent persons, thus mitigating long-term abstinence. This study assessed visual memory function and choice of organizational strategies in alcoholics, as these are major factors necessary to implement ongoing behavior changes which are required for maintaining abstinence. Methods: We investigated 25 severely alcohol-dependent male patients between days 7 to 10 of abstinence, immediately after clinical withdrawal symptoms have ceased, compared to 15 healthy age, sex, and education matched controls. Pharmacological therapy had been terminated at least four half-lifes before inclusion into the study. Visual perceptual learning and organizational strategies were assessed with the Rey-Osterrieth Complex Figure Test (R-OCF). Results: There were no group differences in copying or recalling the figure, but time differences occurred. Alcoholics and healthy controls performed worse in recalling than in copying. But, alcoholics used less effective organizational strategies. Conclusions: There was a deficit in choice of organizational strategy in newly abstinent and unmedicated alcohol-dependent patients. Due to the imperfect organizational strategies, alcoholics might need auxiliary therapeutic care to strengthen their cognitive ability. PMID:21160546

  18. Linkage Scan of Alcohol Dependence in the UCSF Family Alcoholism Study

    PubMed Central

    Gizer, Ian R.; Ehlers, Cindy L.; Vietan, Cassandra; Seaton-Smith, Kimberly L.; Feiler, Heidi S.; Lee, James V.; Segall, Samantha K.; Gilder, David A.; Wilhelmsen, Kirk C.

    2010-01-01

    Ample data suggest alcohol dependence represents a heritable condition, and several research groups have performed linkage analysis to identify genomic regions influencing this disorder. In the present study, a genome-wide linkage scan for alcohol dependence was conducted in a community sample of 565 probands and 1080 first-degree relatives recruited through the UCSF Family Alcoholism Study. The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was used to derive DSM-IV alcohol dependence diagnoses. Although no loci achieved genome-wide significance (i.e., LOD score > 3.0), several linkage peaks of interest (i.e., LOD score > 1.0) were identified. When the strict DSM-IV alcohol dependence diagnosis requiring the temporal clustering of symptoms served as the phenotype, linkage peaks were identified on chromosomes 1p36.31–p36.22, 2q37.3, 8q24.3, and 18p11.21–p11.2. When the temporal clustering of symptoms was not required, linkage peaks were again identified on chromosomes 1p36.31–p36.22 and 8q24.3 as well as novel loci on chromosomes 1p22.3, 2p24.3–p24.1, 9p24.1–p23, and 22q12.3–q13.1. Follow-up analyses were conducted by performing linkage analysis for the 12 alcohol dependence symptoms assessed by the SSAGA across the support intervals for the observed linkage peaks. These analyses demonstrated that different collections of symptoms often assessing distinct aspects of alcohol dependence (e.g., uncontrollable drinking and withdrawal vs. tolerance and drinking despite health problems) contributed to each linkage peak and often yielded LOD scores exceeding that reported for the alcohol dependence diagnosis. Such findings provide insight into how specific genomic regions may influence distinct aspects of alcohol dependence. PMID:20817416

  19. Water withdrawals in Florida, 2012

    USGS Publications Warehouse

    Marella, Richard L.

    2015-09-01

    The largest percentage of freshwater withdrawals was from the South Florida Water Management District (46 percent), followed by the St. Johns River Water Management District (20 percent), Southwest Florida Water Management District (19 percent), Northwest Florida Water Management District (9 percent), and Suwannee River Water Management District (6 percent). The South Florida Water Management District accounted for the largest percentage of freshwater withdrawals for public-supply use (46 percent), commercial-industrial-mining self-supplied use (24 percent), agricultural self-supplied use (59 percent), and recreational-landscape irrigation use (63 percent). The Northwest Florida Water Management District accounted for the largest percentage of freshwater withdrawals for power-generation use (44 percent), and the Southwest Florida Water Management District accounted for the largest percentage of saline-water withdrawals for power-generation use (58 percent).

  20. Carisoprodol Tolerance and Precipitated Withdrawal

    PubMed Central

    Gatch, Michael B.; Nguyen, Jacques D.; Carbonaro, Theresa; Forster, Michael J.

    2011-01-01

    Aims Carisoprodol is a muscle relaxant that acts at the GABAA receptor. Concerns about the abuse liability of carisoprodol are increasing, but evidence that carisoprodol produces tolerance and a significant withdrawal syndrome has yet to be established. The purpose of the current study was to determine if repeated administration of carisoprodol produces tolerance and withdrawal signs in a mouse model. Methods Carisoprodol (0, 100, 200, 300, or 500 mg/kg bid, i.p.) was administered to Swiss-Webster mice for 4 days and loss-of-righting reflex was measured 20 to 30 minutes following each administration. On the fourth day, bemegride (20 mg/kg), flumazenil (20 mg/kg), or vehicle was administered following carisoprodol and withdrawal signs were measured. Separate groups of mice receiving the same treatment regimen and dose range were tested for spontaneous withdrawal at 6, 12 and 24 hr after the last dose of carisoprodol. Results The righting reflex was dose-dependently impaired following the first administration of carisoprodol. A 75 to 100% decrease in the magnitude of the impairment occurred over the four days of exposure, indicating the development of tolerance to the carisoprodol-elicited loss-of-righting reflex. Withdrawal signs were not observed within 24 hours following spontaneous withdrawal; however, bemegride and flumazenil each precipitated withdrawal within 15 to 30 min of administration. Conclusions Carisoprodol treatment resulted in tolerance and antagonist-precipitated withdrawal, suggesting it may have an addiction potential similar to that of other long-acting benzodiazepine or barbiturate compounds. PMID:22055010

  1. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  2. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  3. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  4. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  5. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  6. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  7. ALCOHOL USE DISORDERS IN THE ELDERLY: A BRIEF OVERVIEW FROM EPIDEMIOLOGY TO TREATMENT OPTIONS

    PubMed Central

    Caputo, Fabio; Vignoli, Teo; Leggio, Lorenzo; Addolorato, Giovanni; Zoli, Giorgio; Bernardi, Mauro

    2016-01-01

    Alcohol-use-disorders (AUDs) afflict 1–3% of elderly subjects. The CAGE, SMAST-G, and AUDIT are the most common and validated questionnaires used to identify AUDs in the elderly, and some laboratory markers of alcohol abuse (AST, GGT, MCV, and CDT) may also be helpful. In particular, the sensitivity of MCV or GGT in detecting alcohol misuse is higher in older than in younger populations. The incidence of medical and neurological complications during alcohol withdrawal syndrome in elderly alcoholics is higher than in younger alcoholics. Chronic alcohol abuse is associated with tissue damage to several organs. Namely, an increased level of blood pressure is more frequent in the elderly than in younger adults, and a greater vulnerability to the onset of alcoholic liver disease, and an increasing risk of breast cancer in menopausal women have been described. In addition, the prevalence of dementia in elderly alcoholics is almost 5 times higher than in non-alcoholic elderly individuals, approximately 25% of elderly patients with dementia also present AUDs, and almost 20% of individuals aged 65 and over with a diagnosis of depression have a co-occurring AUD. Moreover, prevention of drinking relapse in older alcoholics is, in some cases, better than in younger patients; indeed, more than 20% of treated elderly alcohol-dependent patients remain abstinent after four years. Considering that the incidence of AUDs in the elderly is fairly high, and AUDs in the elderly are still underestimated, more studies in the fields of epidemiology, prevention and pharmacological and psychotherapeutic treatment of AUDs in the elderly are warranted. PMID:22575256

  8. Cannabis Withdrawal, Posttreatment Abstinence, and Days to First Cannabis Use Among Emerging Adults in Substance Use Treatment: A Prospective Study

    PubMed Central

    Davis, Jordan P.; Smith, Douglas C.; Morphew, Jason W.; Lei, Xinrong; Zhang, Saijun

    2015-01-01

    Very little prospective research investigates how cannabis withdrawal is associated with treatment outcomes, and this work has not used the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) thresholds for cannabis withdrawal. The sample included 110 emerging adults entering outpatient substance use treatment who were heavy cannabis users with no other drug use and limited alcohol use. We used survival analyses to predict days to first use of cannabis and logistic regression to predict whether participants were abstinent and living in the community at 3 months. Those meeting criteria for cannabis withdrawal were more likely to return to use sooner than those not meeting criteria for cannabis withdrawal. However, the presence of cannabis withdrawal was not a significant predictor of 3-month abstinence. Emerging adults with DSM-5 cannabis withdrawal may have difficulty initiating abstinence in the days following their intake assessment, implying the need for strategies to mitigate their more rapid return to cannabis use. PMID:26877548

  9. Sex differences in cannabis withdrawal symptoms among treatment-seeking cannabis users.

    PubMed

    Herrmann, Evan S; Weerts, Elise M; Vandrey, Ryan

    2015-12-01

    Over 300,000 individuals enter treatment for cannabis-use disorders (CUDs) in the United States annually. Cannabis withdrawal is associated with poor CUD-treatment outcomes, but no prior studies have examined sex differences in withdrawal among treatment-seeking cannabis users. Treatment-seeking cannabis users (45 women and 91 men) completed a Marijuana Withdrawal Checklist (Budney, Novy, & Hughes, 1999, Budney, Moore, Vandrey, & Hughes, 2003) at treatment intake to retrospectively characterize withdrawal symptoms experienced during their most recent quit attempt. Scores from the 14-item Composite Withdrawal Discomfort Scale (WDS), a subset of the Marijuana Withdrawal Checklist that corresponds to valid cannabis withdrawal symptoms described in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; APA, 2013) were calculated. Demographic and substance-use characteristics, overall WDS scores, and scores on individual WDS symptoms were compared between women and men. Women had higher overall WDS scores than men, and women had higher scores than men on 6 individual symptoms in 2 domains, mood symptoms (i.e., irritability, restlessness, increased anger, violent outbursts), and gastrointestinal symptoms (i.e., nausea, stomach pain). Follow-up analyses isolating the incidence and severity of WDS symptoms demonstrated that women generally reported a higher number of individual withdrawal symptoms than men, and that they reported experiencing some symptoms as more severe. This is the first report to demonstrate that women seeking treatment for CUDs may experience more withdrawal then men during quit attempts. Prospective studies of sex differences in cannabis withdrawal are warranted.

  10. [Assessment of changes in physiological status of alcohol-dependent patients in the course of 10-day detoxication treatment].

    PubMed

    Slósarska, M; Wójcik, M; Habrat, B

    1994-01-01

    Heart rate, respiratory rate, postural muscle tone and tapping in 14 alcohol dependent patients (type II ac. Cloninger) during 10 days of detoxification were investigated. Despite subjective mood increased, no longer observed were tachycardia and clinical symptoms of alcohol withdrawal; increased muscle tonus and faster respiration rhythm were observed. The observed physiological changes in alcohol dependent patients after 10 days of abstinence suggest that continuation of pharmacotherapy and psychotherapy after detoxification in acute alcohol withdrawal is recommended.

  11. Who withdraws? Psychological individual differences and employee withdrawal behaviors.

    PubMed

    Zimmerman, Ryan D; Swider, Brian W; Woo, Sang Eun; Allen, David G

    2016-04-01

    Psychological individual differences, such as personality, affectivity, and general mental ability, have been shown to predict numerous work-related behaviors. Although there is substantial research demonstrating relationships between psychological individual differences and withdrawal behaviors (i.e., lateness, absenteeism, and turnover), there is no integrative framework providing scholars and practitioners a guide for conceptualizing how, why, and under what circumstances we observe such relationships. In this integrative conceptual review we: (a) utilize the Cognitive-Affective Processing System framework (Mischel & Shoda, 1995) to provide an overarching theoretical basis for how psychological individual differences affect withdrawal behaviors; (b) create a theoretical model of the situated person that summarizes the existing empirical literature examining the effect of psychological differences on withdrawal behavior; and (c) identify future research opportunities based on our review and integrative framework.

  12. Alcohol Alert

    MedlinePlus

    ... Us You are here Home » Alcohol Alert Alcohol Alert The NIAAA Alcohol Alert is a quarterly bulletin that disseminates important research ... text. To order single copies of select Alcohol Alerts, see ordering Information . To view publications in PDF ...

  13. Alcoholic neuropathy

    MedlinePlus

    Neuropathy - alcoholic; Alcoholic polyneuropathy ... The exact cause of alcoholic neuropathy is unknown. It likely includes both a direct poisoning of the nerve by the alcohol and the effect of poor nutrition ...

  14. Alcoholism - resources

    MedlinePlus

    Resources - alcoholism ... The following organizations are good resources for information on alcoholism : Alcoholics Anonymous -- www.aa.org Al-Anon Family Groups www.al-anon.org National Institute on Alcohol ...

  15. Aripiprazole in the treatment of patients with alcohol dependence: a double-blind, comparison trial vs. naltrexone.

    PubMed

    Martinotti, G; Di Nicola, M; Di Giannantonio, M; Janiri, L

    2009-03-01

    Substantial evidence suggests that both partial dopamine agents and mixed 5-HT1A/2A receptor drugs independently show significant efficacy in reducing alcohol use in both animals and humans. Aripiprazole, which acts as a dopamine/5-HT system stabilizer, approaches the optimal characteristics sought in medication to be considered for testing in the treatment of alcohol dependence. In this randomised, double-blind, confrontation trial with naltrexone, we aimed to investigate the efficacy of aripiprazole on alcohol-drinking indices. Craving and psychiatric symptom improvements were the secondary end points. Seventy-five alcohol dependent subjects were detoxified and were subsequently randomised into two groups, receiving 50 mg of naltrexone and 5-15 mg of aripiprazole, respectively. Craving (Visual Analogue Scale; Obsessive and Compulsive Drinking Scale) and withdrawal (Clinical Institute Withdrawal Assessment) rating scales were applied; psychiatric symptoms were evaluated through the Symptom Check List 90-Revised. The number of subjects remained alcohol free for the entire study period (16 weeks) and the number of subjects relapsed were not significantly different in the two groups. The survival function showed that patients treated with aripiprazole remained abstinent from any alcohol amount for a longer time with respect to those treated with naltrexone. As for craving scores, patients treated with naltrexone showed a better outcome. Results from this study globally place aripiprazole at the same range of efficacy of naltrexone, one of the approved drugs used in alcohol relapse prevention. If it could be demonstrated in placebo-controlled trials that aripiprazole is efficacious in decreasing alcohol use, lessening craving, and attenuating psychopathological symptom severity, we will have gained a powerful agent for the treatment of alcohol-dependent subjects.

  16. Resilient But Addicted: The Impact of Resilience on the Relationship between Smoking Withdrawal and PTSD

    PubMed Central

    Asnaani, Anu; Alpert, Elizabeth; McLean, Carmen P.; Foa, Edna B.

    2015-01-01

    Nicotine use is common among people with posttraumatic stress disorder (PTSD). Resilience, which is reflected in one's ability to cope with stress, has been shown to be associated with lower cigarette smoking and posttraumatic stress symptoms, but relationships among these three variables have not been examined. This study investigates the relationships of resilience and nicotine withdrawal with each other and in relation to PTSD symptoms. Participants were 118 cigarette smokers with PTSD seeking treatment for PTSD and nicotine use. Data were randomly cross-sectionally sampled from three time points: week 0, week 12, and week 27 of the study. Hierarchical multiple regression analyses revealed main effects of both resilience and nicotine withdrawal symptoms on PTSD severity, controlling for the sampled time point, negative affect, and expired carbon monoxide concentration. Consistent with prior research, PTSD severity was higher among individuals who were less resilient and for those who had greater nicotine withdrawal. There was an interaction between resilience and nicotine withdrawal on self-reported PTSD severity, such that greater resilience was associated with lower PTSD severity only among participants with low nicotine withdrawal symptoms. Among individuals with high nicotine withdrawal, PTSD severity was high, regardless of resilience level. These results suggest that resilience is a protective factor for PTSD severity for those with low levels of nicotine withdrawal, but at high levels of nicotine withdrawal, the protective function of resilience is mitigated. PMID:25881517

  17. Resilient but addicted: The impact of resilience on the relationship between smoking withdrawal and PTSD.

    PubMed

    Asnaani, Anu; Alpert, Elizabeth; McLean, Carmen P; Foa, Edna B

    2015-06-01

    Nicotine use is common among people with posttraumatic stress disorder (PTSD). Resilience, which is reflected in one's ability to cope with stress, has been shown to be associated with lower cigarette smoking and posttraumatic stress symptoms, but relationships among these three variables have not been examined. This study investigates the relationships of resilience and nicotine withdrawal with each other and in relation to PTSD symptoms. Participants were 118 cigarette smokers with PTSD seeking treatment for PTSD and nicotine use. Data were randomly cross-sectionally sampled from three time points: week 0, week 12, and week 27 of the study. Hierarchical multiple regression analyses revealed main effects of both resilience and nicotine withdrawal symptoms on PTSD severity, controlling for the sampled time point, negative affect, and expired carbon monoxide concentration. Consistent with prior research, PTSD severity was higher among individuals who were less resilient and for those who had greater nicotine withdrawal. There was an interaction between resilience and nicotine withdrawal on self-reported PTSD severity, such that greater resilience was associated with lower PTSD severity only among participants with low nicotine withdrawal symptoms. Among individuals with high nicotine withdrawal, PTSD severity was high, regardless of resilience level. These results suggest that resilience is a protective factor for PTSD severity for those with low levels of nicotine withdrawal, but at high levels of nicotine withdrawal, the protective function of resilience is mitigated.

  18. Association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population.

    PubMed

    Park, Chul-Soo; Park, So-Young; Lee, Chul-Soon; Sohn, Jin-Wook; Hahn, Gyu-Hee; Kim, Bong-Jo

    2006-06-01

    Family, twin, and adoption studies have demonstrated that genes play an important role in the development of alcoholism. We investigated the association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population. The genotype of the GABAA receptor gene polymorphisms were determined by performing polymerase chain reaction genotyping for 172 normal controls and 162 male alcoholics who are hospitalized in alcoholism treatment institute. We found a significant association between the genetic polymorphisms of the GABAA alpha1 and GABAA alpha6 receptor gene and alcoholism. The GG genotype of the GABAA alpha1 receptor gene was associated with the onset age of alcoholism and alcohol withdrawal symptoms, and a high score on the Korean version of the ADS. However, there was no association between the genetic polymorphisms of the GABAA beta2 and gamma2 receptor gene and alcoholisms. Our finding suggest that genetic polymorphisms of the GABAA alpha1 and GABAA alpha6 receptor gene may be associated with the development of alcoholism and that the GG genotype of the GABAA alpha1 receptor gene play an important role in the development of the early onset and the severe type of alcoholism.

  19. Severity of non-alcoholic fatty liver disease is associated with high systemic levels of tumor necrosis factor alpha and low serum interleukin 10 in morbidly obese patients.

    PubMed

    Paredes-Turrubiarte, Gabriela; González-Chávez, Antonio; Pérez-Tamayo, Ruy; Salazar-Vázquez, Beatriz Y; Hernández, Vito S; Garibay-Nieto, Nayeli; Fragoso, José Manuel; Escobedo, Galileo

    2016-05-01

    Morbid obesity has been shown to increase the risk to develop hepatic steatosis, also referred to as non-alcoholic fatty liver disease (NAFLD). Emerging evidence suggests that the severity of NAFLD may associate with increased serum levels of inflammatory markers as well as decreased concentration of mediators with anti-inflammatory actions, such as tumor necrosis factor alpha (TNF-α) and interleukin (IL) 10, respectively. We thus examined the serum levels of TNF-α and IL-10 in 102 morbidly obese women and men (body mass index > 40 kg/m(2)), exhibiting different grades of NAFLD. Blood glucose, glycated hemoglobin, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides, high- and low-density lipoproteins, parameters of liver function, TNF-α, and IL-10 were measured in each subject. The stage of NAFLD was estimated by abdominal ultrasound imaging. In comparison with morbidly obese subjects without steatosis, morbidly obese patients with NAFLD showed increased age (39.23 ± 9.80 years), HOMA-IR (6.74 ± 1.62), total cholesterol (219.7 ± 9.58 mg/dl), aspartate aminotransferase (36.25 ± 3.24 UI/l), gamma-glutamyl transpeptidase (37.12 ± 3.41 UI/l), and TNF-α (37.41 ± 1.72 pg/ml) as well as decreased serum levels of IL-10 (61.05 ± 2.43 pg/ml). Interestingly, the systemic levels of TNF-α increased, while IL-10 decreased in accordance with the severity of NAFLD, which supports a role for systemic inflammatory mediators in promoting steatosis progression. Further clinical prospective studies need to be addressed to elucidate the role of TNF-α and IL-10 in the development of NAFLD while also establishing their clinical utility in the assessment of morbidly obese patients at higher risk to develop severe steatosis.

  20. Alcohol Alert: Genetics of Alcoholism

    MedlinePlus

    ... 84 Alcohol Alert Number 84 Print Version The Genetics of Alcoholism Why can some people have a ... to an increased risk of alcoholism. Cutting-Edge Genetic Research in Alcoholism Although researchers already have made ...

  1. GABAB receptor ligands for the treatment of alcohol use disorder: preclinical and clinical evidence

    PubMed Central

    Agabio, Roberta; Colombo, Giancarlo

    2014-01-01

    The present paper summarizes the preclinical and clinical studies conducted to define the “anti-alcohol” pharmacological profile of the prototypic GABAB receptor agonist, baclofen, and its therapeutic potential for treatment of alcohol use disorder (AUD). Numerous studies have reported baclofen-induced suppression of alcohol drinking (including relapse- and binge-like drinking) and alcohol reinforcing, motivational, stimulating, and rewarding properties in rodents and monkeys. The majority of clinical surveys conducted to date—including case reports, retrospective chart reviews, and randomized placebo-controlled studies—suggest the ability of baclofen to suppress alcohol consumption, craving for alcohol, and alcohol withdrawal symptomatology in alcohol-dependent patients. The recent identification of a positive allosteric modulatory binding site, together with the synthesis of in vivo effective ligands, represents a novel, and likely more favorable, option for pharmacological manipulations of the GABAB receptor. Accordingly, data collected to date suggest that positive allosteric modulators of the GABAB receptor reproduce several “anti-alcohol” effects of baclofen and display a higher therapeutic index (with larger separation—in terms of doses—between “anti-alcohol” effects and sedation). PMID:24936171

  2. Alcohol and the law.

    PubMed

    Karasov, Ariela O; Ostacher, Michael J

    2014-01-01

    Society has had an interest in controlling the production, distribution, and use of alcohol for millennia. The use of alcohol has always had consequences, be they positive or negative, and the role of government in the regulation of alcohol is now universal. This is accomplished at several levels, first through controls on production, importation, distribution, and use of alcoholic beverages, and second, through criminal laws, the aim of which is to address the behavior of users themselves. A number of interventions and policies reduce alcohol-related consequences to society by regulating alcohol pricing, targeting alcohol-impaired driving, and limiting alcohol availability. The legal system defines criminal responsibility in the context of alcohol use, as an enormous percentage of violent crime and motor death is associated with alcohol intoxication. In recent years, recovery-oriented policies have aimed to expand social supports for recovery and to improve access to treatment for substance use disorders within the criminal justice system. The Affordable Care Act, also know as "ObamaCare," made substantial changes to access to substance abuse treatment by mandating that health insurance include services for substance use disorders comparable to coverage for medical and surgical treatments. Rather than a simplified "war on drugs" approach, there appears to be an increasing emphasis on evidence-based policy development that approaches alcohol use disorders with hope for treatment and prevention. This chapter focuses on alcohol and the law in the United States.

  3. An Evaluation of the Usefulness of Extracorporeal Liver Support Techniques in Patients Hospitalized in the ICU for Severe Liver Dysfunction Secondary to Alcoholic Liver Disease

    PubMed Central

    Piechota, Mariusz; Piechota, Anna

    2016-01-01

    Background The mortality rate in patients with severe liver dysfunction secondary to alcoholic liver disease (ALD) who do not respond to the standard treatment is exceptionally high. Objectives The main aim of this study was to evaluate the usefulness of applying extracorporeal liver support techniques to treat this group of patients. Patients and Methods The data from 23 hospital admissions of 21 patients with ALD who were admitted to the department of anesthesiology and intensive therapy (A&IT) at the Dr Wł. Biegański Regional Specialist Hospital in Łódź between March 2013 and July 2015 were retrospectively analyzed. Results A total of 111 liver dialysis procedures were performed during the 23 hospitalizations, including 13 dialyses using fractionated plasma separation and adsorption (FPSA) with the Prometheus® system, and 98 procedures using the single pass albumin dialysis (SPAD) system. Upon admission to the intensive care unit (ICU), the median (interquartile range [IQR]) Glasgow coma scale (GCS), sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation (APACHE) II, and simplified acute physiology score (SAPS) II scores were 15 (14 - 15), 9 (7 - 13), 17 (14 - 24), and 32 (22 - 50), respectively. The ICU, 30-day, and three-month mortality rates were 43.48%, 39.13%, and 73.91%, respectively. As determined by the receiver operative characteristic (ROC) analysis for single-factor models, the significant predictors of death in the ICU included the patients’ SOFA, APACHE II, SAPS II, and model of end-stage liver disease modified by the united network for organ sharing (MELD UNOS Modification) scores; the duration of stay (in days) in the A&IT Department; and bile acid, creatinine and albumin levels upon ICU admission. The ROC analysis indicated the significant discriminating power of the SOFA, APACHE II, SAPS II, and MELD UNOS modification scores on the three-month mortality rate. Conclusions The application of

  4. Alcoholic hepatitis: current management.

    PubMed

    Spengler, Erin K J; Dunkelberg, Jeffrey; Schey, Ron

    2014-10-01

    Alcoholic hepatitis is an acute manifestation of alcoholic liver disease with mortality as high as 40-50% in severe cases. Patients usually have a history of prolonged alcohol abuse with or without a known history of liver disease. Although there is significant range in severity at presentation, patients with severe alcoholic hepatitis typically present with anorexia, fatigue, fever, jaundice, and ascites. The use of either pentoxifylline or corticosteroids in those with severe disease (Maddrey's discriminate function >32) has significant mortality benefit. The addition of N-acetylcysteine to corticosteroids decreases the incidences of hepatorenal syndrome, infection, and short-term mortality, but does not appear to significantly affect 6-month mortality. Nutritional support with high-calorie, high-protein diet is recommended in all patients screening positive for malnutrition. Liver transplantation for a highly selected group of patients with severe alcoholic hepatitis may be an option in the future, but is not currently recommended or available at most transplant institutions.

  5. CHRONIC ALCOHOL NEUROADAPTATION AND STRESS CONTRIBUTE TO SUSCEPTIBILITY FOR ALCOHOL CRAVING AND RELAPSE

    PubMed Central

    BREESE, GEORGE R.; SINHA, RAJITA; HEILIG, MARKUS

    2010-01-01

    Alcoholism is a chronic relapsing disorder. Major characteristics observed in alcoholics during an initial period of alcohol abstinence are altered physiological functions and a negative emotional state. Evidence suggests that a persistent, cumulative adaptation involving a kindling/allostasis-like process occurs during the course of repeated chronic alcohol exposures that is critical for the negative symptoms observed during alcohol withdrawal. Basic studies have provided evidence for specific neurotransmitters within identified brain sites being responsible for the negative emotion induced by the persistent cumulative adaptation following intermittent-alcohol exposures. After an extended period of abstinence, the cumulative alcohol adaptation increases susceptibility to stress- and alcohol cue-induced negative symptoms and alcohol seeking, both of which can facilitate excessive ingestion of alcohol. In the alcoholic, stressful imagery and alcohol cues alter physiological responses, enhance negative emotion, and induce craving. Brain fMRI imaging following stress and alcohol cues has documented neural changes in specific brain regions of alcoholics not observed in social drinkers. Such altered activity in brain of abstinent alcoholics to stress and alcohol cues is consistent with a continuing ethanol adaptation being responsible. Therapies in alcoholics found to block responses to stress and alcohol cues would presumably be potential treatments by which susceptibility for continued alcohol abuse can be reduced. By continuing to define the neurobiological basis of the sustained alcohol adaptation critical for the increased susceptibility of alcoholics to stress and alcohol cues that facilitate craving, a new era is expected to evolve in which the high rate of relapse in alcoholism is minimized. 250 PMID:20951730

  6. Topographic quantitative EEG amplitude in recovered alcoholics.

    PubMed

    Pollock, V E; Schneider, L S; Zemansky, M F; Gleason, R P; Pawluczyk, S

    1992-05-01

    Topographic measures of electroencephalographic (EEG) amplitude were used to compare recovered alcoholics (n = 14) with sex- and age-matched control subjects. Delta, alpha, and beta activity did not distinguish the groups, but regional differences in theta distribution did. Recovered alcoholics showed more uniform distributions of theta amplitudes in bilateral anterior and posterior regions compared with controls. Because a minimum of 5 years had elapsed since the recovered alcoholic subjects fulfilled DSM-III-R criteria for alcohol abuse or dependence, it is unlikely these EEG theta differences reflect the effects of withdrawal.

  7. Binge ethanol withdrawal: Effects on post-withdrawal ethanol intake, glutamate-glutamine cycle and monoamine tissue content in P rat model.

    PubMed

    Das, Sujan C; Althobaiti, Yusuf S; Alshehri, Fahad S; Sari, Youssef

    2016-04-15

    Alcohol withdrawal syndrome (AWS) is a medical emergency situation which appears after abrupt cessation of ethanol intake. Decreased GABA-A function and increased glutamate function are known to exist in the AWS. However, the involvement of glutamate transporters in the context of AWS requires further investigation. In this study, we used a model of ethanol withdrawal involving abrupt cessation of binge ethanol administration (4 g/kg/gavage three times a day for three days) using male alcohol-preferring (P) rats. After 48 h of withdrawal, P rats were re-exposed to voluntary ethanol intake. The amount of ethanol consumed was measured during post-withdrawal phase. In addition, the expression of GLT-1, GLAST and xCT were determined in both medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). We also measured glutamine synthetase (GS) activity, and the tissue content of glutamate, glutamine, dopamine and serotonin in both mPFC and NAc. We found that binge ethanol withdrawal escalated post-withdrawal ethanol intake, which was associated with downregulation of GLT-1 expression in both mPFC and NAc. The expression of GLAST and xCT were unchanged in the ethanol-withdrawal (EW) group compared to control group. Tissue content of glutamate was significantly lower in both mPFC and NAc, whereas tissue content of glutamine was higher in mPFC but unchanged in NAc in the EW group compared to control group. The GS activity was unchanged in both mPFC and NAc. The tissue content of DA was significantly lower in both mPFC and NAc, whereas tissue content of serotonin was unchanged in both mPFC and NAc. These findings provide important information of the critical role of GLT-1 in context of AWS.

  8. [Treatment of alcohol dependence: rational and arguable approaches].

    PubMed

    Sivolap, Iu P

    2014-01-01

    Treatment of alcohol dependence consist of alcohol detoxification with withdrawal alleviation and relapse prevention or maintenance therapy. Drugs of choice for alcohol withdrawal cure are benzodiazepines and anticonvulsants are an alternative for them. Relapse prevention and alcohol abuse alleviation are carried out using disulfiram, acamprosate, naltrexone and nalmefene. Moreover, therapeutic possibilities of memantine, gabapentine, pregabalin, baclofen, modafinil, ondansetron D-cycloserine and aripiprazole are studying nowadays. Use of selective serotonin reuptake inhibitors including fluvoxamine for alcohol patients is of great importance due to frequent comorbidity of alcoholism, depression and anxiety. There are some doubtful methods of alcoholism treatment accepted in Russian addictive medicine such as clearance detoxification and use of antipsychotics for craving elimination.

  9. Sexual dysfunctions in alcohol-dependent men: A study from north India

    PubMed Central

    Pendharkar, Shreyas; Mattoo, Surendra K.; Grover, Sandeep

    2016-01-01

    Background & objectives: Sexual dysfunctions have been reported in alcohol-dependent men. Most of the studies conducted had limitation of using non-validated measures of sexual dysfunction and sampling design. This study was, therefore, conducted to determine the typology, demographic and clinical correlates of sexual dysfunction in alcohol-dependent men. Methods: One hundred and one patients with alcohol dependence (AD) attending the Drug De-addiction and Treatment Centre and 50 healthy controls were evaluated in this cross-sectional study. Participants in both the groups were assessed on Arizona Sexual experience scale (ASEX), Dyadic Adjustment Scale (DAS), Hamilton Depression Rating Scale (HDRS) and State-Trait Anxiety Inventory (STAI). In addition, patients with AD were assessed on Severity of Alcohol Dependence Questionnaire (SADQ) for severity of AD and revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar) to ensure that no participant was in active alcohol withdrawal state. Results: Overall, 58.4 per cent of patients in the AD group had sexual dysfunction. Among the domains, the highest frequency was seen for dysfunction for arousal (57.4%), followed by problems in desire (54.4%), erection (36.6%), satisfaction with orgasm (34.6%) and ability to reach orgasm was least affected (12.87%). The patient and control groups differed significantly in overall dyadic adjustment, in the domains of dyadic satisfaction and affective expression. Interpretation & conclusions: The finding of this study showed that a significant proportion of patients with AD has sexual dysfunction. Longitudinal studies using validated assessment tools should be done to confirm these findings. PMID:28139538

  10. Lorazepam withdrawal catatonia: a case report.

    PubMed

    Sivakumar, Thanapal; Yadav, Anil; Sood, Mamta; Khandelwal, Sudhir K

    2013-12-01

    Catatonia is a rare manifestation of benzodiazepine withdrawal in elderly patients who have used it for a long time. We present a case of lorazepam withdrawal catatonia and highlight issues in diagnosis and management.

  11. 21 CFR 314.620 - Withdrawal procedures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Efficacy Studies Are Not Ethical or Feasible § 314.620 Withdrawal procedures. (a) Reasons to withdraw... diligence; (3) Use after marketing demonstrates that postmarketing restrictions are inadequate to...

  12. 21 CFR 314.620 - Withdrawal procedures.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Efficacy Studies Are Not Ethical or Feasible § 314.620 Withdrawal procedures. (a) Reasons to withdraw... Evaluation and Research (CDER) will give the applicant notice of an opportunity for a hearing on...

  13. 21 CFR 314.620 - Withdrawal procedures.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Efficacy Studies Are Not Ethical or Feasible § 314.620 Withdrawal procedures. (a) Reasons to withdraw... Evaluation and Research (CDER) will give the applicant notice of an opportunity for a hearing on...

  14. 21 CFR 314.620 - Withdrawal procedures.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Efficacy Studies Are Not Ethical or Feasible § 314.620 Withdrawal procedures. (a) Reasons to withdraw... Evaluation and Research (CDER) will give the applicant notice of an opportunity for a hearing on...

  15. Quantification of Ten Neuroactive Steroids in Plasma in Withdrawal Seizure–Prone and –Resistant Mice During Chronic Ethanol Withdrawal

    PubMed Central

    Snelling, Christopher; Tanchuck-Nipper, Michelle A.; Ford, Matthew M.; Jensen, Jeremiah P.; Cozzoli, Debra K.; Ramaker, Marcia J.; Helms, Melinda; Crabbe, John C.; Rossi, David J.; Finn, Deborah A.

    2014-01-01

    Rationale The rapid membrane actions of neuroactive steroids, particularly via an enhancement of γ-aminobutyric acidA receptors (GABAARs), participate in the regulation of central nervous system excitability. Prior evidence suggests an inverse relationship between endogenous GABAergic neuroactive steroid levels and behavioral changes in excitability during ethanol withdrawal. Objectives Previously, we found that ethanol withdrawal significantly decreased plasma allopregnanolone (ALLO) levels, a potent GABAergic neuroactive steroid, and decreased GABAAR sensitivity to ALLO in Withdrawal Seizure–Prone (WSP) but not in Withdrawal Seizure–Resistant (WSR) mice. However, the effect of ethanol withdrawal on levels of other endogenous GABAAR-active steroids is not known. Methods After validation of a gas chromatography-mass spectrometry method for the simultaneous quantification of 10 neuroactive steroids, we analyzed plasma from control male WSP-1 and WSR-1 mice and during ethanol withdrawal. Results We quantified levels of 9 neuroactive steroids in WSP-1 and WSR-1 plasma; levels of pregnanolone were not detectable. Basal levels of 5 neuroactive steroids were higher in WSR-1 versus WSP-1 mice. Ethanol withdrawal significantly suppressed 5 neuroactive steroids in WSP-1 and WSR-1 mice, including ALLO. Conclusions Due to lower basal levels of some GABAAR-active steroids in WSP-1 mice, a withdrawal-induced decrease in WSP-1 mice may have a greater physiological consequence than a similar decrease in WSR-1 mice. Because WSP-1 mice also exhibit a reduction in GABAAR sensitivity to neuroactive steroids during withdrawal, it is possible that the combined decrease in neuroactive steroids and GABAAR sensitivity during ethanol withdrawal in WSP-1 mice represents a neurochemical substrate for severe ethanol withdrawal. PMID:24871700

  16. Ectopic hippocampal neurogenesis in adolescent male rats following alcohol dependence.

    PubMed

    McClain, Justin A; Morris, Stephanie A; Marshall, S Alexander; Nixon, Kimberly

    2014-07-01

    The adolescent hippocampus is highly vulnerable to alcohol-induced damage, which could contribute to their increased susceptibility to alcohol use disorder. Altered adult hippocampal neurogenesis represents one potential mechanism by which alcohol (ethanol) affects hippocampal function. Based on the vulnerability of the adolescent hippocampus to alcohol-induced damage, and prior reports of long-term alcohol-induced effects on adult neurogenesis, we predicted adverse effects on adult neurogenesis in the adolescent brain following abstinence from alcohol dependence. Thus, we examined neurogenesis in adolescent male rats during abstinence following a 4-day binge model of alcohol dependence. Bromodeoxyuridine and Ki67 immunohistochemistry revealed a 2.2-fold increase in subgranular zone cell proliferation after 7 days of abstinence. Increased proliferation was followed by a 75% increase in doublecortin expression and a 56% increase in surviving bromodeoxyuridine-labeled cells 14 and 35 days post-ethanol exposure, respectively. The majority of newborn cells in ethanol and control groups co-localized with NeuN, indicating a neuronal phenotype and therefore a 1.6-fold increase in hippocampal neurogenesis during abstinence. Although these results mirror the magnitude of reactive neurogenesis described in adult rat studies, ectopic bromodeoxyuridine and doublecortin positive cells were detected in the molecular layer and hilus of adolescent rats displaying severe withdrawal symptoms, an effect that has not been described in adults. The presence of ectopic neuroblasts suggests that a potential defect exists in the functional incorporation of new neurons into the existing hippocampal circuitry for a subset of rats. Age-related differences in functional incorporation could contribute to the increased vulnerability of the adolescent hippocampus to ethanol.

  17. Vasopressin Regulation and Renal Fluid and Electrolyte Handling in Rat Models of Acute and Chronic alcohol Exposure

    DTIC Science & Technology

    2004-10-01

    evaluating fluid and electrolyte regulating ability in models of acute and chronic alcohol exposure and alcohol withdrawal, and 2) uncovering mechanisms ...be used to define mechanisms behind alcohol effects better than study of humans because conditions of alcohol dosing, hydration status, and fluid...vasopressin receptor regulation, and have determined that altered renal responsiveness to vasopressin is the main mechanism behind fluid balance perturbations

  18. Estimated freshwater withdrawals in Texas, 1990

    USGS Publications Warehouse

    Lurry, Dee L.

    1994-01-01

    This report presents 1990 freshwater withdrawal estimates for Texas by source and category. Withdrawal source is either ground water or surface water. Withdrawal categories include: self-supplied irrigation, thermoelectric-power generation, water supply, industrial and mining, and other (domestic, commercial, livestock). Withdrawal data are aggregated by county, major aquifer, and principal river basin. Only the four major categories of irrigation, thermoelectric-power generation, water supply, and industrial and mining are illustrated in this report, although all data are tabulated.

  19. Update on Alcoholic Hepatitis.

    PubMed

    Torok, Natalie J

    2015-11-02

    Alcoholic liver disease is one of the most prevalent liver diseases worldwide, and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%-50% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies.

  20. 29 CFR 4208.7 - Adjustment of withdrawal liability for subsequent withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CORPORATION WITHDRAWAL LIABILITY FOR MULTIEMPLOYER PLANS REDUCTION OR WAIVER OF PARTIAL WITHDRAWAL LIABILITY... a partial or complete withdrawal from a plan subsequent to a partial withdrawal from that plan in a prior plan year shall be reduced in accordance with part 4206 of this chapter....

  1. 29 CFR 4219.18 - Withdrawal in a plan year in which substantially all employers withdraw.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Withdrawal in a plan year in which substantially all employers withdraw. 4219.18 Section 4219.18 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION WITHDRAWAL LIABILITY FOR MULTIEMPLOYER PLANS NOTICE, COLLECTION, AND REDETERMINATION OF WITHDRAWAL LIABILITY Redetermination...

  2. 46 CFR 391.5 - Qualified withdrawals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false Qualified withdrawals. 391.5 Section 391.5 Shipping... TAX ASPECTS OF THE CAPITAL CONSTRUCTION FUND § 391.5 Qualified withdrawals. (a) In general. (1) A qualified withdrawal is one made from the fund during the taxable year which is in accordance with...

  3. 46 CFR 391.5 - Qualified withdrawals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 8 2013-10-01 2013-10-01 false Qualified withdrawals. 391.5 Section 391.5 Shipping... TAX ASPECTS OF THE CAPITAL CONSTRUCTION FUND § 391.5 Qualified withdrawals. (a) In general. (1) A qualified withdrawal is one made from the fund during the taxable year which is in accordance with...

  4. 46 CFR 391.5 - Qualified withdrawals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false Qualified withdrawals. 391.5 Section 391.5 Shipping... TAX ASPECTS OF THE CAPITAL CONSTRUCTION FUND § 391.5 Qualified withdrawals. (a) In general. (1) A qualified withdrawal is one made from the fund during the taxable year which is in accordance with...

  5. A Detection Model of College Withdrawal

    ERIC Educational Resources Information Center

    Pleskac, Timothy J.; Keeney, Jessica; Merritt, Stephanie M.; Schmitt, Neal; Oswald, Frederick L.

    2011-01-01

    Many students during their college careers consider withdrawing from their respective college or university. Understanding why some students decide to withdraw yet others persist has implications for both the well being of students as well as for institutes of higher education. The present study develops a model of the decision to withdraw drawing…

  6. Student Withdrawal Survey. Research Report 2.

    ERIC Educational Resources Information Center

    Montemayor, J. Joaquin; And Others

    In spring 1984, a three-part withdrawal study was conducted at Glendale (Arizona) Community College (GCC) to investigate reasons for course withdrawal, and official and unofficial college withdrawal. Study findings, based on responses from 138 students who withdrew from courses, 282 students who officially withdrew from GCC, and 9 students who…

  7. 46 CFR 390.10 - Nonqualified withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Nonqualified withdrawals. 390.10 Section 390.10 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS UNDER PUBLIC LAW 91-469 CAPITAL CONSTRUCTION FUND § 390.10 Nonqualified withdrawals. (a) In general—(1) Defined. Any withdrawal from a...

  8. Dextromethorphan psychosis, dependence and physical withdrawal.

    PubMed

    Miller, Shannon C

    2005-12-01

    As part of a synthesis of evidence regarding the abuse and addiction liability of dextromethorphan (DM), an over-the-counter cough medicine available in over 140 preparations, an uncommonly published case of dextromethorphan dependence (addiction) is described, with specific, rarely published complications. The individual was interviewed and several medical databases were also reviewed (Medline, 1966-present; PubMed) for all content relating to the Keywords: dextromethorphan, abuse, dependence, cough medicine, addiction, withdrawal, psychosis. The patient evidenced history suggesting substance dependence, substance-induced psychosis and substance withdrawal in relation to DM. A literature review revealed that DM has specific serotonergic and sigma-1 opioidergic properties. Dextrorphan (DOR), the active metabolite of DM, has similar properties; however, DOR is a weaker sigma opioid receptor agonist, and a stronger NMDA receptor antagonist. DM and DOR display specific biological features of addiction, and are capable of inducing specific psychiatric sequelae. A specific, reproducible toxidrome with significant psychiatric effects occurred, when DM was abused at greater than indicated doses, with more profound and potentially life-threatening effects at even higher doses. DM withdrawal appears evident. DM's active metabolite, DOR, has pharmacodynamic properties and intoxication effects similar to dissociatives, and may be more responsible for the dissociative effect that this DM abuser sought. However, it is this same metabolite that may be fraught with the potentially life-threatening psychoses and dissociative-induced accidents, as well as addiction. While DM has been hypothesized as the most commonly abused dissociative, health-care providers seem largely unaware of its toxidrome and addiction liability.

  9. Glutamatergic targets for new alcohol medications

    PubMed Central

    Spanagel, Rainer; Krystal, John H.

    2013-01-01

    Rationale An increasingly compelling literature points to a major role for the glutamate system in mediating the effects of alcohol on behavior and the pathophysiology of alcoholism. Preclinical studies indicate that glutamate signaling mediates certain aspects of ethanol’s intoxicating and rewarding effects, and undergoes adaptations following chronic alcohol exposure that may contribute to the withdrawal, craving and compulsive drug-seeking that drive alcohol abuse and alcoholism. Objectives We discuss the potential for targeting the glutamate system as a novel pharmacotherapeutic approach to treating alcohol use disorders, focusing on five major components of the glutamate system: the N-methyl-D-aspartate (NMDA) receptor and specific NMDA subunits, the glycineB site on the NMDA receptors (NMDAR), L-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid ionotropic (AMPA) and kainate (KAR) receptors, metabotropic receptors (mGluR), and glutamate transporters. Results Chronic alcohol abuse produces a hyperglutamatergic state, characterized by elevated extracellular glutamate and altered glutamate receptors and transporters. Pharmacologically manipulating glutamatergic neurotransmission alters alcohol-related behaviors including intoxication, withdrawal, and alcohol-seeking, in rodents and human subjects. Blocking NMDA and AMPA receptors reduces alcohol consumption in rodents, but side-effects may limit this as a therapeutic approach. Selectively targeting NMDA and AMPA receptor subunits (e.g., GluN2B, GluA3), or the NMDAR glycineB site offers an alternative approach. Blocking mGluR5 potently affects various alcohol-related behaviors in rodents, and mGluR2/3 agonism also suppresses alcohol consumption. Finally, glutamate transporter upregulation may mitigate behavioral and neurotoxic sequelae of excess glutamate caused by alcohol. Conclusions Despite the many challenges that remain, targeting the glutamate system offers genuine promise for developing new

  10. Nontraditional Student Withdrawal from Undergraduate Accounting Programmes: A Holistic Perspective

    ERIC Educational Resources Information Center

    Fortin, Anne; Sauvé, Louise; Viger, Chantal; Landry, France

    2016-01-01

    A collaborative project of several Quebec universities, this study investigates nontraditional student withdrawal from undergraduate accounting programmes. A nontraditional student is older than 24, or is a commuter or a part-time student, or combines some of these characteristics. Univariate and multivariate analyses of student dropout factors…

  11. Interstellar Alcohols

    NASA Technical Reports Server (NTRS)

    Charnley, S. B.; Kress, M. E.; Tielens, A. G. G. M.; Millar, T. J.

    1995-01-01

    We have investigated the gas-phase chemistry in dense cores where ice mantles containing ethanol and other alcohols have been evaporated. Model calculations show that methanol, ethanol, propanol, and butanol drive a chemistry leading to the formation of several large ethers and esters. Of these molecules, methyl ethyl ether (CH3OC2H5) and diethyl ether (C2H5)2O attain the highest abundances and should be present in detectable quantities within cores rich in ethanol and methanol. Gas-phase reactions act to destroy evaporated ethanol and a low observed abundance of gas-phase C,H,OH does not rule out a high solid-phase abundance. Grain surface formation mechanisms and other possible gas-phase reactions driven by alcohols are discussed, as are observing strategies for the detection of these large interstellar molecules.

  12. Nicotine withdrawal among adolescents with acute psychopathology: an item response analysis.

    PubMed

    Strong, David R; Kahler, Christopher W; Ramsey, Susan E; Abrantes, Ana; Brown, Richard A

    2004-06-01

    The present study explored the relationship between psychopathology and the experience of nicotine withdrawal among 191 adolescent smokers deprived of nicotine during a psychiatric hospitalization. Using methods based in item response theory, we demonstrated the ability of symptoms of nicotine withdrawal to cohere in measuring the withdrawal syndrome. After controlling for nicotine dependence, we found that several disorders showed significant but modest univariate relationships with individual withdrawal symptoms. After controlling for comorbidity with other disorders, we found that depressive and conduct disorders maintained significant but modest relationships with increased withdrawal severity. Item analyses across groups suggested that girls, individuals with a depressive disorder, and individuals with a conduct disorder tended to report higher levels of nicotine withdrawal but did not appear to inflate their scores because of disorder- or gender-specific reporting bias. Although levels of acute distress were related to withdrawal severity, the six-item withdrawal index showed good discriminant validity in this sample by demonstrating stronger correlations with craving and level of dependence than could be accounted for by levels of distress alone.

  13. Alcohol hangover: mechanisms and mediators.

    PubMed

    Swift, R; Davidson, D

    1998-01-01

    Hangovers are a frequent, though unpleasant, experience among people who drink to intoxication. Despite the prevalence of hangovers, however, this condition is not well understood scientifically. Multiple possible contributors to the hangover state have been investigated, and researchers have produced evidence that alcohol can directly promote hangover symptoms through its effects on urine production, the gastrointestinal tract, blood sugar concentrations, sleep patterns, and biological rhythms. In addition, researchers postulate that effects related to alcohol's absence after a drinking bout (i.e., withdrawal), alcohol metabolism, and other factors (e.g., biologically active, nonalcohol compounds in beverages; the use of other drugs; certain personality traits; and a family history of alcoholism) also may contribute to the hangover condition. Few of the treatments commonly described for hangover have undergone scientific evaluation.

  14. Perspectives on the neuroscience of alcohol from the National Institute on Alcohol Abuse and Alcoholism.

    PubMed

    Reilly, Matthew T; Noronha, Antonio; Warren, Kenneth

    2014-01-01

    Mounting evidence over the last 40 years clearly indicates that alcoholism (alcohol dependence) is a disorder of the brain. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has taken significant steps to advance research into the neuroscience of alcohol. The Division of Neuroscience and Behavior (DNB) was formed within NIAAA in 2002 to oversee, fund, and direct all research areas that examine the effects of alcohol on the brain, the genetic underpinnings of alcohol dependence, the neuroadaptations resulting from excessive alcohol consumption, advanced behavioral models of the various stages of the addiction cycle, and preclinical medications development. This research portfolio has produced important discoveries in the etiology, treatment, and prevention of alcohol abuse and dependence. Several of these salient discoveries are highlighted and future areas of neuroscience research on alcohol are presented.

  15. Withdrawal from dialysis: ethical issues.

    PubMed

    Conneen, S; Tzamaloukas, A H; Adler, K; Keller, L K; Bordenave, K; Murata, G H

    1998-04-01

    Since 1991, death following withdrawal from dialysis has increased greatly in our dialysis unit. This report is based on our observations of those patients who followed that course. Four types of patients who withdrew from dialysis were identified: those with a terminal illness, demented patients, those with a progressive disability, and those who had no serious medical problem other than end-stage renal failure. We analyzed the risk factors for withdrawal and attempted to define the ethical principles involved in each patient category. The authors conclude that although the decision of a competent patient to stop dialysis must be honored, some of those deaths might be preventable if patients on chronic dialysis are prospectively followed and treated by those who are expert in the behavior of patients with chronic illness.

  16. The Fetal Alcohol Syndrome.

    ERIC Educational Resources Information Center

    Umbreit, John; Ostrow, Lisa S.

    1980-01-01

    Fetal alcohol syndrome is a pattern of altered growth and morphogenesis found in about half the offspring of severely and chronically alcoholic women who continue drinking throughout their pregnancy. Of children studied, mild to moderate mental retardation was the most common disorder, occurring in 44 percent of the cases. (PHR)

  17. Do Alcohol Misuse, Service Utilisation, and Demographic Characteristics Differ between UK Veterans and Members of the General Public Attending an NHS General Hospital?

    PubMed Central

    Murphy, Dominic; Palmer, Emily; Westwood, Greta; Busuttil, Walter; Greenberg, Neil

    2016-01-01

    The aim of this paper was to provide insights into alcohol misuse within UK veterans to inform as to whether their presentations differ from the general public. This was done by exploring differences in the severity of alcohol misuse between UK veterans and the general public admitted to a general NHS hospital over an 18 month period using retrospective data. All patients admitted to the hospital were screened for alcohol misuse. Those deemed as experiencing problems were referred for specialist nurse-led support. A total of 2331 individuals were referred for this supported and administered with a standardised assessment that included measures of the severity of alcohol difficulties (AUDIT), dependency levels (LDQ), and assessed for the presence of withdrawal symptoms (CIWA-Ar). In addition, information was collected on service utilisation, referral category (medical or mental health), other substance misuse, and demographic characteristics. No differences were found between the severity of reported alcohol difficulties between veterans and non-veterans. Evidence was found to suggest that veterans were more likely to be referred for support with alcohol difficulties at an older age and to be admitted to hospital for longer periods of time. This could have considerable cost implications for the NHS. It was more common for veterans to present at hospital with physical health difficulties prior to being referred for support for alcohol. PMID:27827830

  18. Chronic alcohol exposure alters transcription broadly in a key integrative brain nucleus for homeostasis: the nucleus tractus solitarius.

    PubMed

    Covarrubias, Maria Yolanda; Khan, Rishi L; Vadigepalli, Rajanikanth; Hoek, Jan B; Schwaber, James S

    2005-12-14

    Chronic exposure to alcohol modifies physiological processes in the brain, and the severe symptoms resulting from sudden removal of alcohol from the diet indicate that these modifications are functionally important. We investigated the gene expression patterns in response to chronic alcohol exposure (21-28 wk) in the rat nucleus tractus solitarius (NTS), a brain nucleus with a key integrative role in homeostasis and cardiorespiratory function. Using methods and an experimental design optimized for detecting transcriptional changes less than twofold, we found 575 differentially expressed genes. We tested these genes for significant associations with physiological functions and signaling pathways using Gene Ontology terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, respectively. Chronic alcohol exposure resulted in significant NTS gene regulation related to the general processes of synaptic transmission, intracellular signaling, and cation transport as well as specific neuronal functions including plasticity and seizure behavior that could be related to alcohol withdrawal symptoms. The differentially expressed genes were also significantly enriched for enzymes of lipid metabolism, glucose metabolism, oxidative phosphorylation, MAP kinase signaling, and calcium signaling pathways from KEGG. Intriguingly, many of the genes we found to be differentially expressed in the NTS are known to be involved in alcohol-induced oxidative stress and/or cell death. The study provides evidence of very extensive alterations of physiological gene expression in the NTS in the adapted state to chronic alcohol exposure.

  19. The Clarence Herbert case: was withdrawal of treatment justified?

    PubMed

    Connery, J R

    1984-02-01

    Clarence Herbert, 55, stopped breathing following routine surgery in August 1981. Though a respirator restored his breathing, the lack of oxygen had caused severe brain damage, and Mr. Herbert was in a coma. Whether he could recover beyond a vegetative state was not known. Two days after her husband was placed on the respirator, Mrs. Herbert authorized the withdrawal of all life-support means. Mr. Herbert died six days later. Charges of murder by deprivation of treatment against the two attending physicians were dismissed in a lower court, a decision that was upheld in the state appeals court. Because court accounts are unclear, it is impossible to judge whether withdrawal of treatment was moral in this case. This case, however, raises a question about life-sustaining treatment in general. What is the moral criterion for withdrawal: quality of life or quality of treatment? The quality-of-life principle removes the obligation to take life-sustaining measures when a person's life does not or will not meet certain standards. Quality of treatment permits the withdrawal of even minimally burdensome treatment if it is considered useless. Though the California case appears to rest on these principles, withdrawing treatment from a person in a permanent coma, such as Mr. Herbert, implies that the quality of life is so low that life is not worth preserving, if the patient has no potential for conscious life, others have no duty to preserve it. This judgment may be acceptable in a terminal case when treatment truly is useless; however, withdrawing treatment that is useful in prolonging life cannot be justified.

  20. Substance abuse and withdrawal in the intensive care unit. Contemporary issues.

    PubMed

    Jenkins, D H

    2000-06-01

    Because 36% of intentional injury victims are drug dependent, the association between drug abuse and violence, especially in urban settings, is high. Withdrawal syndromes in ICU patients confuse their clinical management, may be extremely difficult to diagnose, are often lethal, need to be suspected, and should be prophylaxed against; therefore, all ICU patients should be considered to be at high risk for drug or alcohol dependence, should be tested for evidence of such drugs, and should be interviewed (together with their family members) for the presence of drug dependence traits. Appropriate patients should be referred for formal evaluation and treatment. Withdrawal syndromes must be promptly recognized, differentiated from traumatic or metabolic deterioration, and immediately treated. As patients are unique, so is their drug dependence. Individualized withdrawal therapy, not a "one method fits all" approach, works best. The mainstay of most withdrawal therapy is supportive care and benzodiazepine therapy. Also, considering the high rate of multiple intoxicants present in trauma patients, withdrawal can occur from multiple agents in a single patient, further compounding these difficulties. Withdrawal from unusual substances, such as GHB, or from therapeutic interventions (e.g., prolonged opioid or benzodiazepine administration) also must be considered.

  1. Effects of ethanol exposure and withdrawal on dendritic morphology and spine density in the nucleus accumbens core and shell.

    PubMed

    Peterson, Veronica L; McCool, Brian A; Hamilton, Derek A

    2015-01-12

    Exposure to drugs of abuse can result in profound structural modifications on neurons in circuits involved in addiction that may contribute to drug dependence, withdrawal and related processes. Structural alterations on medium spiny neurons (MSNs) of the nucleus accumbens (NAc) have been observed following exposure to and withdrawal from a variety of drugs; however, relatively little is known about the effects of alcohol exposure and withdrawal on structural alterations of NAc MSNs. In the present study male rats were chronically exposed to vaporized ethanol for 10 days and underwent 1 or 7 days of withdrawal after which the brains were processed for Golgi-Cox staining and analysis of dendritic length, branching and spine density. MSNs of the NAc shell and core underwent different patterns of changes following ethanol exposure and withdrawal. At 1 day of withdrawal there were modest reductions in the dendritic length and branching of MSNs in both the core and the shell compared to control animals exposed only to air. At 7 days of withdrawal the length and branching of shell MSNs was reduced, whereas the length and branching of core MSNs were increased relative to the shell. The density of mature spines was increased in the core at 1 day of withdrawal, whereas the density of less mature spines was increased in both regions at 7 days of withdrawal. Collectively, these observations indicate that MSNs of the NAc core and shell undergo distinct patterns of structural modifications following ethanol exposure and withdrawal suggesting that modifications in dendritic structure in these regions may contribute differentially to ethanol withdrawal.

  2. Three-dimensional mapping of local cerebral perfusion in alcoholic encephalopathy with and without Wernicke-Korsakoff syndrome

    SciTech Connect

    Hata, T.; Meyer, J.S.; Tanahashi, N.; Ishikawa, Y.; Imai, A.; Shinohara, T.; Velez, M.; Fann, W.E.; Kandula, P.; Sakai, F.

    1987-02-01

    Seventeen severe chronic alcoholic patients with and without Wernicke-Korsakoff syndrome (WKS) were examined prospectively after being treated by withdrawal from alcohol. The WKS patients also received thiamine supplements. Three-dimensional measurements of local cerebral blood flow (LCBF) and local partition coefficients (L lambda) were made utilizing xenon contrast computed tomography (Xe CT-CBF). Results were displayed as color-coded brain maps before and after treatment and these were correlated with neurological and cognitive examinations. Before treatment chronic alcoholics without WKS (n = 10) showed diffuse reductions of LCBF values throughout all gray matter including hypothalamus, vicinity of nucleus basalis of Meynert, thalamus, and basal ganglia. Similar, but more severe, reductions were seen in patients with WKS (n = 7), however, white matter perfusion was also reduced. In WKS, most prominent reductions of LCBF were also seen in hypothalamus and basal forebrain nuclei but thalamus, basal ganglia, and limbic systems were severely reduced. After treatment, both groups with alcoholic encephalopathy showed marked clinical improvement and cerebral perfusion was restored toward normal. Chronic alcohol abuse, in the absence of thiamine deficiency, reduces CBF by direct neurotoxic effects. If thiamine deficiency is also present, more severe and localized hemodynamic reductions are superimposed.

  3. Three-dimensional mapping of local cerebral perfusion in alcoholic encephalopathy with and without Wernicke-Korsakoff syndrome.

    PubMed

    Hata, T; Meyer, J S; Tanahashi, N; Ishikawa, Y; Imai, A; Shinohara, T; Velez, M; Fann, W E; Kandula, P; Sakai, F

    1987-02-01

    Seventeen severe chronic alcoholic patients with and without Wernicke-Korsakoff syndrome (WKS) were examined prospectively after being treated by withdrawal from alcohol. The WKS patients also received thiamine supplements. Three-dimensional measurements of local cerebral blood flow (LCBF) and local partition coefficients (L lambda) were made utilizing xenon contrast computed tomography (Xe CT-CBF). Results were displayed as color-coded brain maps before and after treatment and these were correlated with neurological and cognitive examinations. Before treatment chronic alcoholics without WKS (n = 10) showed diffuse reductions of LCBF values throughout all gray matter including hypothalamus, vicinity of nucleus basalis of Meynert, thalamus, and basal ganglia. Similar, but more severe, reductions were seen in patients with WKS (n = 7), however, white matter perfusion was also reduced. In WKS, most prominent reductions of LCBF were also seen in hypothalamus and basal forebrain nuclei but thalamus, basal ganglia, and limbic systems were severely reduced. After treatment, both groups with alcoholic encephalopathy showed marked clinical improvement and cerebral perfusion was restored toward normal. Chronic alcohol abuse, in the absence of thiamine deficiency, reduces CBF by direct neurotoxic effects. If thiamine deficiency is also present, more severe and localized hemodynamic reductions are superimposed.

  4. The role of GABA(A) receptors in the development of alcoholism.

    PubMed

    Enoch, Mary-Anne

    2008-07-01

    Alcoholism is a common, heritable, chronic relapsing disorder. GABA(A) receptors undergo allosteric modulation by ethanol, anesthetics, benzodiazepines and neurosteroids and have been implicated in the acute as well as the chronic effects of ethanol including tolerance, dependence and withdrawal. Medications targeting GABA(A) receptors ameliorate the symptoms of acute withdrawal. Ethanol induces plasticity in GABA(A) receptors: tolerance is associated with generally decreased GABA(A) receptor activation and differentially altered subunit expression. The dopamine (DA) mesolimbic reward pathway originating in the ventral tegmental area (VTA), and interacting stress circuitry play an important role in the development of addiction. VTA GABAergic interneurons are the primary inhibitory regulators of DA neurons and a subset of VTA GABA(A) receptors may be implicated in the switch from heavy drinking to dependence. GABA(A) receptors modulate anxiety and response to stress; important elements of sustained drinking and relapse. The GABA(A) receptor subunit genes clustered on chromosome 4 are highly expressed in the reward pathway. Several recent studies have provided strong evidence that one of these genes, GABRA2, is implicated in alcoholism in humans. The influence of the interaction between ethanol and GABA(A) receptors in the reward pathway on the development of alcoholism together with genetic and epigenetic vulnerabilities will be explored in this review.

  5. Suicidal Behavior and Alcohol Abuse

    PubMed Central

    Pompili, Maurizio; Serafini, Gianluca; Innamorati, Marco; Dominici, Giovanni; Ferracuti, Stefano; Kotzalidis, Giorgio D.; Serra, Giulia; Girardi, Paolo; Janiri, Luigi; Tatarelli, Roberto; Sher, Leo; Lester, David

    2010-01-01

    Suicide is an escalating public health problem, and alcohol use has consistently been implicated in the precipitation of suicidal behavior. Alcohol abuse may lead to suicidality through disinhibition, impulsiveness and impaired judgment, but it may also be used as a means to ease the distress associated with committing an act of suicide. We reviewed evidence of the relationship between alcohol use and suicide through a search of MedLine and PsychInfo electronic databases. Multiple genetically-related intermediate phenotypes might influence the relationship between alcohol and suicide. Psychiatric disorders, including psychosis, mood disorders and anxiety disorders, as well as susceptibility to stress, might increase the risk of suicidal behavior, but may also have reciprocal influences with alcohol drinking patterns. Increased suicide risk may be heralded by social withdrawal, breakdown of social bonds, and social marginalization, which are common outcomes of untreated alcohol abuse and dependence. People with alcohol dependence or depression should be screened for other psychiatric symptoms and for suicidality. Programs for suicide prevention must take into account drinking habits and should reinforce healthy behavioral patterns. PMID:20617037

  6. Association of Serum Adiponectin, Leptin, and Resistin Concentrations with the Severity of Liver Dysfunction and the Disease Complications in Alcoholic Liver Disease

    PubMed Central

    Surdacka, Agata; Smolen, Agata

    2013-01-01

    Background and aims. There is growing evidence that white adipose tissue is an important contributor in the pathogenesis of alcoholic liver disease (ALD). We investigated serum concentrations of total adiponectin (Acrp30), leptin, and resistin in patients with chronic alcohol abuse and different grades of liver dysfunction, as well as ALD complications. Materials and Methods. One hundred forty-seven consecutive inpatients with ALD were prospectively recruited. The evaluation of plasma adipokine levels was performed using immunoenzymatic ELISA tests. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications. Results. Acrp30 and resistin levels were significantly higher in patients with ALD than in controls. Lower leptin levels in females with ALD compared to controls, but no significant differences in leptin concentrations in males, were found. High serum Acrp30 level revealed an independent association with advanced liver dysfunction, as well as the development of ALD complications, that is, ascites and hepatic encephalopathy. Conclusion. Gender-related differences in serum leptin concentrations may influence the ALD course, different in females compared with males. Serum Acrp30 level may serve as a potential prognostic indicator for patients with ALD. PMID:24259947

  7. Estimated freshwater withdrawals in Washington, 2010

    USGS Publications Warehouse

    Lane, Ron C.; Welch, Wendy B.

    2015-03-18

    The amount of public- and self-supplied water used for domestic, irrigation, livestock, aquaculture, industrial, mining, and thermoelectric power was estimated for state, county, and eastern and western regions of Washington during calendar year 2010. Withdrawals of freshwater for offstream uses were estimated to be about 4,885 million gallons per day. The total estimated freshwater withdrawals for 2010 was approximately 15 percent less than the 2005 estimate because of decreases in irrigation and thermoelectric power withdrawals.

  8. The gene transcription factor cyclic AMP-responsive element binding protein: role in positive and negative affective states of alcohol addiction.

    PubMed

    Pandey, Subhash C

    2004-10-01

    The gene transcription factor cyclic adenosine monophosphate (cAMP)-responsive element binding (CREB) protein is a nuclear protein that regulates synaptic plasticity via modulating the expression of several (cAMP)-inducible genes. Alcohol addiction is a complex psychiatric disorder and is characterized by a compulsive and uncontrolled pattern of alcohol drinking by an individual in spite of the adverse consequences of its abuse. Ethanol produces both euphoric (reward and reinforcing) and dysphoric (negative withdrawal reactions) effects and these are most likely involved in the initiation and maintenance of alcohol use and abuse. Several neurotransmitter systems in the brain might be involved in the effects of alcohol but the exact molecular mechanisms of both the positive and negative affective states of alcohol abuse are still unclear. Recent research in molecular neurosciences using animal models have identified the role of extended amygdaloid (shell structures of nucleus accumbens [NAc] and central and medial amygdaloid nuclei) CREB signaling in positive and negative affective states of alcohol drinking behaviors. This review article highlights the current findings on the role of nucleus accumbal and amygdaloid CREB signaling in behavioral consequences of alcohol use and abuse.

  9. Dystonia in Methylphenidate Withdrawal: A Case Report.

    PubMed

    Grau-López, Lara; Daigre, Constanza; Mercado, Nestor; Casas, Miquel; Roncero, Carlos

    Few studies have described movement disorders as withdrawal symptoms during psychostimulant detoxification. Although dystonia has been reported as an uncommon adverse effect of methylphenidate treatment, it has not been described in the context of methylphenidate withdrawal. We report a case of dystonia as the main withdrawal symptom in a methylphenidate-dependent adult participating in an inpatient methylphenidate detoxification program. Although movement disorders such as dystonia are very rare adverse effects of methylphenidate withdrawal, practitioners need to be alert to this risk in order to initiate appropriate treatment.

  10. 5 CFR 1604.7 - Withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... the spouse of a civilian participant covered under the Federal Employees' Retirement System; those... account contains combat zone contributions, the withdrawal will be distributed pro rata from all...

  11. Alcoholic and non-alcoholic steatohepatitis

    PubMed Central

    Neuman, Manuela G.; French, Samuel W.; French, Barbara A.; Seitz, Helmut K.; Cohen, Lawrence B.; Mueller, Sebastian; Osna, Natalia A.; Kharbanda, Kusum K.; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J.; McKillop, Iain H.; Kirpich, Irina A.; McClain, Craig J.; Bataller, Ramon; Nanau, Radu M.; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomas, Paul G.; Ganesan, Murali; Malnick, Steve

    2015-01-01

    This paper is based upon the “Charles Lieber Satellite Symposia” organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its comorbidities with chronic viral hepatitis in the presence or absence of human deficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible

  12. Alcoholic and non-alcoholic steatohepatitis.

    PubMed

    Neuman, Manuela G; French, Samuel W; French, Barbara A; Seitz, Helmut K; Cohen, Lawrence B; Mueller, Sebastian; Osna, Natalia A; Kharbanda, Kusum K; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J; McKillop, Iain H; Kirpich, Irina A; McClain, Craig J; Bataller, Ramon; Nanau, Radu M; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomes, Paul G; Ganesan, Murali; Malnick, Steve

    2014-12-01

    This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible

  13. Performance of several Saccharomyces strains for the alcoholic fermentation of sugar-sweetened high-strength wastewaters: Comparative analysis and kinetic modelling.

    PubMed

    Comelli, Raúl N; Seluy, Lisandro G; Isla, Miguel A

    2016-12-25

    This work focuses on the performance of ten commercial Saccharomyces yeast strains in the batch alcoholic fermentation of sugars contained in selected industrial wastewaters from the soft drink industry. Fermentation has been applied successfully to treat these effluents prior to their disposal. Although many strains were investigated, similar behaviour was observed between all of the Saccharomyces strains tested. When media were inoculated with 2gL(-1) of yeast, all strains were able to completely consume the available sugars in less than 14h. Thus, any of the strains studied in this work could be used in non-conventional wastewater treatment processes based on alcoholic fermentation. However, ethanol production varied between strains, and these differences could be significant from a production point of view. Saccharomyces bayanus produced the most ethanol, with a mean yield of 0.44gethanolgsugarconsumed(-1) and an ethanol specific production rate of 5.96gethanol (Lh)(-1). As the assayed soft drinks wastewaters contain about 105gsugar/L of fermentable sugars, the concentration of ethanol achieved after the fermentations process was 46.2gethanol/L. A rigorous kinetic modelling methodology was used to model the Saccharomyces bayanus fermentation process. The kinetic model included coupled mass balances and a minimal number of parameters. A simple unstructured model based on the Andrews equation (substrate inhibition) was developed. This model satisfactorily described biomass growth, sugar consumption and bioethanol production. In addition to providing insights into the fermentative performance of potentially relevant strains, this work can facilitate the design of large-scale ethanol production processes that use wastewaters from the sugar-sweetened beverage industry as feedstock.

  14. Prevalence of Children with Severe Fetal Alcohol Spectrum Disorders in Communities Near Rome, Italy: New Estimated Rates Are Higher than Previous Estimates

    PubMed Central

    May, Philip A.; Fiorentino, Daniela; Coriale, Giovanna; Kalberg, Wendy O.; Hoyme, H. Eugene; Aragón, Alfredo S.; Buckley, David; Stellavato, Chandra; Gossage, J. Phillip; Robinson, Luther K.; Jones, Kenneth Lyons; Manning, Melanie; Ceccanti, Mauro

    2011-01-01

    Objective: To determine the population-based epidemiology of fetal alcohol syndrome (FAS) and other fetal alcohol spectrum disorders (FASD) in towns representative of the general population of central Italy. Methods: Slightly revised U.S. Institute of Medicine diagnostic methods were used among children in randomly-selected schools near Rome. Consented first grade children (n = 976) were screened in Tier I for height, weight, or head circumference and all children ≤10th centile on one of these measurements were included in the study. Also, teachers referred children for learning or behavioral problems. Children meeting either of these two criteria, along with randomly-selected controls, advanced to Tier II which began with a dysmorphology examination. Children with a possible FASD, and controls, advanced to Tier III for neurobehavioral testing, and their mothers were interviewed for maternal risks. Final diagnoses using indicators of dysmorphology, neurobehavior, and maternal risk were made in formally-structured, interdisciplinary case conferences. Results: Case control comparisons of physical, neurobehavioral, and maternal risk variables are presented for 46 children with an FASD and 116 randomly-selected controls without a diagnosis on the FASD continuum. Rates of diagnoses within the FASD continuum are then estimated from these in-school data via three different methods. The range of rates of FAS produced by these methods is between 4.0 to 12.0 per 1,000; Partial FAS ranges from 18.1 to 46.3 per 1,000; and an FASD was found in 2.3% to 6.3% of the children. Conclusions: These rates are substantially higher than previous estimates of FAS and overall FASD for the general populations of Western Europe and the U. S., and raise questions as to the total impact of FASD on mental deficit in mainstream populations of Western Europe and the United States where the majority are middle class and are not believed to be characterized by heavy episodic drinking. PMID

  15. [Treatment of iatrogenic Cushing syndrome: questions of glucocorticoid withdrawal].

    PubMed

    Igaz, Péter; Rácz, Károly; Tóth, Miklós; Gláz, Edit; Tulassay, Zsolt

    2007-02-04

    Iatrogenic Cushing's syndrome is the most common form of hypercortisolism. Glucocorticoids are widely used for the treatment of various diseases, often in high doses that may lead to the development of severe hypercortisolism. Iatrogenic hypercortisolism is unique, as the application of exogenous glucocorticoids leads to the simultaneous presence of symptoms specific for hypercortisolism and the suppression of the endogenous hypothalamic-pituitary-adrenal axis. The principal question of its therapy is related to the problem of glucocorticoid withdrawal. There is considerable interindividual variability in the suppression and recovery of the hypothalamic-pituitary-adrenal axis, therefore, glucocorticoid withdrawal and substitution can only be conducted in a stepwise manner with careful clinical follow-up and regular laboratory examinations regarding endogenous hypothalamic-pituitary-adrenal axis activity. Three major complications which can be associated with glucocorticoid withdrawal are: i. reactivation of the underlying disease, ii. secondary adrenal insufficiency, iii. steroid withdrawal syndrome. Here, the authors summarize the most important aspects of this area based on their clinical experience and the available literature data.

  16. Label-Free Proteomic Analysis of Protein Changes in the Striatum during Chronic Ethanol Use and Early Withdrawal

    PubMed Central

    Ayers-Ringler, Jennifer R.; Oliveros, Alfredo; Qiu, Yanyan; Lindberg, Daniel M.; Hinton, David J.; Moore, Raymond M.; Dasari, Surendra; Choi, Doo-Sup

    2016-01-01

    The molecular mechanisms underlying the neuronal signaling changes in alcohol addiction and withdrawal are complex and multifaceted. The cortico-striatal circuit is highly implicated in these processes, and the striatum plays a significant role not only in the early stages of addiction, but in the developed-addictive state as well, including withdrawal symptoms. Transcriptional analysis is a useful method for determining changes in gene expression, however, the results do not always accurately correlate with protein levels. In this study, we employ label-free proteomic analysis to determine changes in protein expression within the striatum during chronic ethanol use and early withdrawal. The striatum, composed primarily of medium spiny GABAergic neurons, glutamatergic and dopaminergic nerve terminals and astrocytes, is relatively homogeneous for proteomic analysis. We were able to analyze more than 5000 proteins from both the dorsal (caudate and putamen) and ventral (nucleus accumbens) striatum and identified significant changes following chronic intermittent ethanol exposure and acute (8 h) withdrawal compared to ethanol naïve and ethanol exposure groups respectively. Our results showed significant changes in proteins involved in glutamate and opioid peptide signaling, and also uncovered novel pathways including mitochondrial function and lipid/cholesterol metabolism, as revealed by changes in electron transport chain proteins and RXR activation pathways. These results will be useful in the development of novel treatments for alcohol withdrawal and thereby aid in recovery from alcohol use disorder. PMID:27014007

  17. Alcohol Calorie Calculator

    MedlinePlus

    ... Alcohol Calorie Calculator Weekly Total 0 Calories Alcohol Calorie Calculator Find out the number of beer and ... Calories College Alcohol Policies Interactive Body Calculators Alcohol Calorie Calculator Alcohol Cost Calculator Alcohol BAC Calculator Alcohol ...

  18. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  19. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  20. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  1. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  2. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  3. [Gabapentin treatment in a female patient with panic disorder and adverse effects under carbamazepine during benzodiazepine withdrawal].

    PubMed

    Himmerich, Hubertus; Nickel, Thomas; Dalal, Mira A; Müller, Marianne B

    2007-03-01

    Despite their addictive potential, benzodiazepines belong to the most often prescribed drugs. We report on a patient with alprazolam dependence, who initially was treated with carbamazepine because of severe withdrawal symptoms. Due to liver enzyme elevation related to carbamazepine, we had to stop this treatment and instead of that started gabapentin treatment. Under this new therapy, the patient showed a dramatic relief of withdrawal symptoms and of the panic attacks recurring during withdrawal. Hence, due to their effectiveness and tolerability, newer anticonvulsants could be considered as medication for benzodiazepine withdrawal and as an alternative for benzodiazepine treatment in panic disorders.

  4. Therapy for alcoholic liver disease

    PubMed Central

    Jaurigue, Maryconi M; Cappell, Mitchell S

    2014-01-01

    Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and

  5. κ opioid regulation of anxiety-like behavior during acute ethanol withdrawal.

    PubMed

    Valdez, Glenn R; Harshberger, Erin

    2012-07-01

    Withdrawal is one of the defining characteristics of alcohol dependence, and is often characterized by impaired physiological function and enhanced negative affect. Recent evidence suggests that the dynorphin (DYN)/kappa opioid receptor (KOR) system may be a key mediator in the negative affect often associated with drugs of abuse. The objective of the present experiments was to determine the role of the DYN/KOR system in the regulation of anxiety-related behavior during acute withdrawal from ethanol. Rats were fed an ethanol liquid diet and following removal, the ability of the KOR antagonist nor-BNI to attenuate the increased anxiogenic-like response characteristic of ethanol withdrawal was investigated using the elevated plus maze. A comparison study was also conducted examining anxiety-related behavior following direct activation of KORs via injections of the KOR agonist U50,488. Rats experiencing ethanol withdrawal showed a significant decrease in open arm exploration compared to controls, an effect that was blocked by nor-BNI. Similar decreases in open arm exploration were observed following injections with the KOR agonist, U50,488, an effect also reversed by pretreatment with nor-BNI. These results suggest that similar mechanisms are involved in the regulation of ethanol withdrawal- and KOR agonist-induced changes in behavior. Given the potential role of enhanced negative affect in persistent ethanol drinking, understanding the role of the DYN/KOR system in regulating anxiety associated with withdrawal may be critical in understanding the factors associated with the nature of alcohol dependence.

  6. Hyponatremia in an Elderly Patient due to Isolated Hypoaldosteronism Occurring after Licorice Withdrawal

    PubMed Central

    Hataya, Yuji; Oba, Akifumi; Yamashita, Takafumi; Komatsu, Yasato

    2017-01-01

    Hyponatremia is one of the most common electrolyte disorders encountered in the elderly. We present the case of an 81-year-old man who developed hyponatremia due to isolated hypoaldosteronism occurring after licorice withdrawal. He had severe hypokalemia with hypertension and was diagnosed with pseudoaldosteronism. He had been taking a very small dose of licorice as a mouth refresher since his early adulthood. Five months after licorice withdrawal, he developed hypovolemic hyponatremia, which was resolved with administration of fludrocortisone acetate. Our experience with this case suggests that isolated hypoaldosteronism occurring after licorice withdrawal should be considered as a potential cause of hyponatremia in elderly patients. PMID:28090048

  7. Assessment of affective and somatic signs of ethanol withdrawal in C57BL/6J mice using a short term ethanol treatment

    PubMed Central

    Perez, EE; De Biasi, M

    2015-01-01

    Alcohol is one of the most prevalent addictive substances in the world. Withdrawal symptoms result from abrupt cessation of alcohol consumption in habitual drinkers. The emergence of both affective and physical symptoms produces a state that promotes relapse. Mice provide a preclinical model that could be used to study alcohol dependence and withdrawal while controlling for both genetic and environmental variables. The use of a liquid ethanol diet offers a reliable method for the induction of alcohol dependence in mice, but this approach is impractical when conducting high throughput pharmacological screens or when comparing multiple strains of genetically engineered mice. The goal of this study was to compare withdrawal associated behaviors in mice chronically treated with a liquid ethanol diet vs. mice treated with a short-term ethanol treatment that consisted of daily ethanol injections containing the alcohol dehydrogenase inhibitor, 4-methylpyrazole. Twenty-four hours after ethanol treatment, mice were tested in the open field arena, the elevated plus maze, the marble burying test or for changes in somatic signs during spontaneous ethanol withdrawal. Anxiety-like and compulsive-like behavior, as well as physical signs, were all significantly elevated in mice undergoing withdrawal, regardless of the route of ethanol administration. Therefore, a short-term ethanol treatment can be utilized as a screening tool for testing genetic and pharmacological agents before investing in a more time consuming ethanol treatment. PMID:25817777

  8. Assessment of affective and somatic signs of ethanol withdrawal in C57BL/6J mice using a short-term ethanol treatment.

    PubMed

    Perez, E E; De Biasi, M

    2015-05-01

    Alcohol is one of the most prevalent addictive substances in the world. Withdrawal symptoms result from abrupt cessation of alcohol consumption in habitual drinkers. The emergence of both affective and physical symptoms produces a state that promotes relapse. Mice provide a preclinical model that could be used to study alcohol dependence and withdrawal while controlling for both genetic and environmental variables. The use of a liquid ethanol diet offers a reliable method for the induction of alcohol dependence in mice, but this approach is impractical when conducting high-throughput pharmacological screens or when comparing multiple strains of genetically engineered mice. The goal of this study was to compare withdrawal-associated behaviors in mice chronically treated with a liquid ethanol diet vs. mice treated with a short-term ethanol treatment that consisted of daily ethanol injections containing the alcohol dehydrogenase inhibitor, 4-methylpyrazole. Twenty-four hours after ethanol treatment, mice were tested in the open field arena, the elevated plus maze, the marble burying test, or for changes in somatic signs during spontaneous ethanol withdrawal. Anxiety-like and compulsive-like behaviors, as well as physical signs, were all significantly elevated in mice undergoing withdrawal, regardless of the route of ethanol administration. Therefore, a short-term ethanol treatment can be utilized as a screening tool for testing genetic and pharmacological agents before investing in a more time-consuming ethanol treatment.

  9. Alcohol use, alcohol problems, and problem behavior engagement among students at two schools in northern Mexico

    PubMed Central

    Mancha, Brent E.; Rojas, Vanessa C.; Latimer, William W.

    2012-01-01

    This study examined the association between alcohol use problem severity, defined by number of DSM-IV alcohol Abuse and Dependence symptoms and frequency of alcohol use, and problem behavior engagement among Mexican students. A confidential survey was administered to 1229 students in grades 7–12 at two schools in a northern border city in Mexico. Youths were categorized into five groups based on their alcohol use frequency and symptoms of DSM-IV alcohol Abuse and Dependence, specifically: no lifetime alcohol use, lifetime alcohol use but none in the past year, past year alcohol use, one or two alcohol Abuse or Dependence symptoms, and three or more alcohol Abuse or Dependence symptoms. The association between five levels of alcohol use problem severity and three problem behaviors, lifetime marijuana use, lifetime sexual intercourse, and past year arrest/law trouble, was examined using chi-square or Fisher’s exact tests. Several alcohol use problem severity categories were significantly different with respect to rates of lifetime marijuana use, lifetime sexual intercourse, and past year arrest/law trouble. Higher alcohol use problem severity was associated with greater endorsement of problem behaviors. Knowing about variations in adolescent alcohol use and alcohol problems may be instrumental in determining if youths are also engaging in a range of other risk behaviors. Considering varying levels of alcohol use and alcohol problems is important for effective targeted prevention and treatment interventions. PMID:22840814

  10. Alcohol Use Disorders in Pregnancy

    PubMed Central

    DeVido, Jeffrey; Bogunovic, Olivera; Weiss, Roger D.

    2015-01-01

    Alcohol use disorders (AUD) during pregnancy are less prevalent than in non-pregnant women, but they can create a host of clinical challenges when encountered. Unfortunately, there is little research information available to guide clinical decision-making in this population. Drinking alcohol during pregnancy can have negative consequences on both fetus and mother, but there is controversy regarding the volume of alcohol consumption that correlates with these consequences. There is little evidence to support the use of pharmacologic interventions for AUD during pregnancy. Similarly, there are few data to guide management of alcohol detoxification in pregnant women, and the use of benzodiazepines (the mainstay of most alcohol detoxification protocols) in pregnant women is controversial. Despite a lack of robust data to guide management of AUDs in pregnancy, clinicians must nonetheless make management decisions when confronted with these challenging situations. Therefore, this paper reviews the epidemiology of AUDs in pregnancy, and the pharmacologic management of both AUDs and alcohol withdrawal in pregnant women, to better inform clinicians about what is known about managing these co-occurring conditions. PMID:25747924

  11. 27 CFR 19.534 - Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... use in production of nonbeverage wine and nonbeverage wine products. 19.534 Section 19.534 Alcohol... Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products. Spirits... bonded wine cellar for use in the production of nonbeverage wine and nonbeverage wine products. (Sec....

  12. 5 CFR 1604.7 - Withdrawals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... spousal rights in the context of a withdrawal (and the process by which a service member may obtain an... any) can be transferred only if the IRA or plan accepts such funds. (d) Separation. The definition of separation from service at § 1604.2 applies when determining a service member's eligibility for a withdrawal....

  13. 42 CFR 457.170 - Withdrawal process.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Withdrawal process. 457.170 Section 457.170 Public... Plans for Child Health Insurance Programs and Outreach Strategies § 457.170 Withdrawal process. (a... amendment, or any portion of a proposed State plan or plan amendment, at any time during the review...

  14. Spinal Surgery and Abrupt Intrathecal Baclofen Withdrawal.

    PubMed

    Zheng, Karl; Brodsky, Jay B

    2015-11-01

    Abrupt cessation of intrathecal baclofen can lead to a serious withdrawal syndrome. The anesthesiologist must be prepared to avoid intraoperative interruption of baclofen delivery before starting spinal surgery and to recognize and treat the symptoms of baclofen withdrawal in the immediate postoperative period.

  15. Behavioral measures of anxiety during opiate withdrawal.

    PubMed

    Grasing, K; Wang, A; Schlussman, S

    1996-10-01

    Heightened anxiety is a major component of the withdrawal syndromes associated with ethanol and sedative hypnotic medications. Because of similarities between the opiate and sedative-hypnotic withdrawal syndromes as well as data implicating heightened noradrenergic tone with opiate withdrawal, we investigated changes in anxiety measures identified by plus-maze and social interaction testing during opiate withdrawal. Because Sprague Dawley rats had very low levels of entry into plus-maze open arms, further studies were conducted using the Long-Evans strain. Long-Evans rats received continuous infusions of morphine sulfate at 44 mg/kg per day delivered by osmotic pump over 7 days while control animals received inert implants. During the first 3 days of withdrawal, the number and time of entries into open and closed arms of a plus-maze was recorded. Both social and aggressive behaviors were scored durings pairings of groups of two socially naive animals. Body weight was significantly reduced in morphine-treated animals prior to and during withdrawal. Both the number of entries into open plus-maze arms and the time spent in open areas increased over the 3 days of testing. However, no difference in plus-maze activity was detected between morphine-treated and control subjects. On the third day of withdrawal, social interaction time was greater in pairs of withdrawn and control subjects compared to pairs of two control subjects. In conclusion, behavioral measures of anxiety are not increased during opiate withdrawal.

  16. 14 CFR 93.223 - Slot withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES Allocation of Commuter and Air Carrier IFR... essential air service operations or eliminating slots. Before withdrawing any slots under this section to.... (d) The following withdrawal priority rule shall be used to permit application of the...

  17. New mechanisms and perspectives in nicotine withdrawal

    PubMed Central

    Jackson, K.J.; Muldoon, P.P.; De Biasi, M.; Damaj, M.I.

    2014-01-01

    Diseases associated with tobacco use constitute a major health problem worldwide. Upon cessation of tobacco use, an unpleasant withdrawal syndrome occurs in dependent individuals. Avoidance of the negative state produced by nicotine withdrawal represents a motivational component that promotes continued tobacco use and relapse after smoking cessation. With the modest success rate of currently available smoking cessation therapies, understanding mechanisms involved in the nicotine withdrawal syndrome are crucial for developing successful treatments. Animal models provide a useful tool for examining neuroadaptative mechanisms and factors influencing nicotine withdrawal, including sex, age, and genetic factors. Such research has also identified an important role for nicotinic receptor subtypes in different aspects of the nicotine withdrawal syndrome (e.g., physical vs. affective signs). In addition to nicotinic receptors, the opioid and endocannabinoid systems, various signal transduction pathways, neurotransmitters, and neuropeptides have been implicated in the nicotine withdrawal syndrome. Animal studies have informed human studies of genetic variants and potential targets for smoking cessation therapies. Overall, the available literature indicates that the nicotine withdrawal syndrome is complex, and involves a range of neurobiological mechanisms. As research in nicotine withdrawal progresses, new pharmacological options for smokers attempting to quit can be identified, and treatments with fewer side effects that are better tailored to the unique characteristics of patients may become available. PMID:25433149

  18. 46 CFR 390.9 - Qualified withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Qualified withdrawals. 390.9 Section 390.9 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS UNDER PUBLIC LAW 91-469 CAPITAL CONSTRUCTION FUND § 390.9 Qualified withdrawals. (a) In general—(1) Defined. In accordance with 46 U.S.C....

  19. 46 CFR 391.5 - Qualified withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Qualified withdrawals. 391.5 Section 391.5 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS UNDER PUBLIC LAW 91-469 FEDERAL INCOME TAX ASPECTS OF THE CAPITAL CONSTRUCTION FUND § 391.5 Qualified withdrawals. (a) In general. (1)...

  20. Different alcohol exposures induce selective alterations on the expression of dynorphin and nociceptin systems related genes in rat brain.

    PubMed

    D'Addario, Claudio; Caputi, Francesca F; Rimondini, Roberto; Gandolfi, Ottavio; Del Borrello, Elia; Candeletti, Sanzio; Romualdi, Patrizia

    2013-05-01

    Molecular mechanisms of adaptive transformations caused by alcohol exposure on opioid dynorphin and nociceptin systems have been investigated in the rat brain. Alcohol was intragastrically administered to rats to resemble human drinking with several hours of exposure: water or alcohol (20% in water) at a dose of 1.5 g/kg three times daily for 1 or 5 days. The development of tolerance and dependence were recorded daily. Brains were dissected 30 minutes (1- and 5-day groups) or 1, 3 or 7 days after the last administration for the three other 5-day groups (groups under withdrawal). Specific alterations in opioid genes expression were ascertained. In the amygdala, an up-regulation of prodynorphin and pronociceptin was observed in the 1-day group; moreover, pronociceptin and the kappa opioid receptor mRNAs in the 5-day group and both peptide precursors in the 1-day withdrawal group were also up-regulated. In the prefrontal cortex, an increase in prodynorhin expression in the 1-day group was detected. These data indicate a relevant role of the dynorphinergic system in the negative hedonic states associated with multiple alcohol exposure. The pattern of alterations observed for the nociceptin system appears to be consistent with its role of functional antagonism towards the actions of ethanol associated with other opioid peptides. Our findings could help to the understanding of how alcohol differentially affects the opioid systems in the brain and also suggest the dynorphin and nociceptin systems as possible targets for the treatment and/or prevention of alcohol dependence.

  1. Alcoholism and critical illness: A review

    PubMed Central

    Mehta, Ashish Jitendra

    2016-01-01

    Alcohol is the most commonly used and abused drug in the world, and alcohol use disorders pose a tremendous burden to healthcare systems around the world. The lifetime prevalence of alcohol abuse in the United States is estimated to be around 18%, and the economic consequences of these disorders are staggering. Studies on hospitalized patients demonstrate that about one in four patients admitted to critical care units will have alcohol-related issues, and unhealthy alcohol consumption is responsible for numerous clinical problems encountered in intensive care unit (ICU) settings. Patients with alcohol use disorders are not only predisposed to developing withdrawal syndromes and other conditions that often require intensive care, they also experience a considerably higher rate of complications, longer ICU and hospital length of stay, greater resource utilization, and significantly increased mortality compared to similar critically ill patients who do not abuse alcohol. Specific disorders seen in the critical care setting that are impacted by alcohol abuse include delirium, pneumonia, acute respiratory distress syndrome, sepsis, gastrointestinal hemorrhage, trauma, and burn injuries. Despite the substantial burden of alcohol-induced disease in these settings, critical care providers often fail to identify individuals with alcohol use disorders, which can have significant implications for this vulnerable population and delay important clinical interventions. PMID:26855891

  2. Genome-wide examination of myoblast cell cycle withdrawal duringdifferentiation

    SciTech Connect

    Shen, Xun; Collier, John Michael; Hlaing, Myint; Zhang, Leanne; Delshad, Elizabeth H.; Bristow, James; Bernstein, Harold S.

    2002-12-02

    Skeletal and cardiac myocytes cease division within weeks of birth. Although skeletal muscle retains limited capacity for regeneration through recruitment of satellite cells, resident populations of adult myocardial stem cells have not been identified. Because cell cycle withdrawal accompanies myocyte differentiation, we hypothesized that C2C12 cells, a mouse myoblast cell line previously used to characterize myocyte differentiation, also would provide a model for studying cell cycle withdrawal during differentiation. C2C12 cells were differentiated in culture medium containing horse serum and harvested at various time points to characterize the expression profiles of known cell cycle and myogenic regulatory factors by immunoblot analysis. BrdU incorporation decreased dramatically in confluent cultures 48 hr after addition of horse serum, as cells started to form myotubes. This finding was preceded by up-regulation of MyoD, followed by myogenin, and activation of Bcl-2. Cyclin D1 was expressed in proliferating cultures and became undetectable in cultures containing 40 percent fused myotubes, as levels of p21(WAF1/Cip1) increased and alpha-actin became detectable. Because C2C12 myoblasts withdraw from the cell cycle during myocyte differentiation following a course that recapitulates this process in vivo, we performed a genome-wide screen to identify other gene products involved in this process. Using microarrays containing approximately 10,000 minimally redundant mouse sequences that map to the UniGene database of the National Center for Biotechnology Information, we compared gene expression profiles between proliferating, differentiating, and differentiated C2C12 cells and verified candidate genes demonstrating differential expression by RT-PCR. Cluster analysis of differentially expressed genes revealed groups of gene products involved in cell cycle withdrawal, muscle differentiation, and apoptosis. In addition, we identified several genes, including DDAH2 and Ly

  3. Amphetamine withdrawal and sleep disturbance.

    PubMed

    Gossop, M R; Bradley, B P; Brewis, R K

    1982-01-01

    Sleep duration and indices of disturbed sleep, such as night-time waking and day-time sleep, were investigated in amphetamine users following hospital admission and withdrawal from the drug. Compared to controls, the amphetamine group showed an initial period of oversleeping and, towards the end of the first week, they showed a considerable degree of reduced sleep which persisted for the 20 days of this study. There was greater variability in sleep duration within the amphetamine group on almost all nights, and the variability in sleep duration from one night to the next was also greater. More night-time sleep disturbance was evident among the amphetamine ex-users. These results are discussed with respect to previous work and the pattern is seen to be more complex than had been imagined. A tentative neurochemical model is suggested and clinical implications are considered.

  4. An integrative analysis of ethanol tolerance and withdrawal in zebrafish (Danio rerio).

    PubMed

    Tran, Steven; Chatterjee, Diptendu; Gerlai, Robert

    2015-01-01

    The zebrafish is emerging as a popular animal model for alcohol (ethanol or EtOH) addiction due to its simplicity and practical advantages. Two phenomena associated with ethanol addiction are the development of tolerance and withdrawal. Using a multi-level approach in the current study, we characterise ethanol tolerance and withdrawal in zebrafish. We first investigate the temporal trajectory of ethanol concentration in the zebrafish brain in response to an acute exposure and during withdrawal. We report that ethanol concentrations approach a steady state within 60 min of exposure to 0.50% and 1.00% v/v ethanol and rapidly decline and return to zero within 60 min following withdrawal from chronic ethanol exposure (0.50% v/v). We characterise the changes associated with ethanol tolerance and withdrawal in zebrafish by focusing on three domains relevant to ethanol addiction: motor patterns, physiological responses (i.e. cortisol levels), and neurochemical alterations. The use of multiple domains of investigation allowed an in-depth analysis of ethanol induced changes in zebrafish.

  5. National Institute on Alcohol Abuse and Alcoholism

    MedlinePlus

    ... Alcohol Awareness Month April is Alcohol Awareness Month Biosensor Challenge Learn more College Drinking Learn More Alcohol Dependence Get the facts Alcohol Awareness Month Biosensor Challenge College Drinking Alcohol Dependence Latest News New & ...

  6. Prattville intake, Lake Almanor, California, hydraulic model study on selective withdrawal modifications. Final report

    SciTech Connect

    Vermeyen, T.

    1995-07-01

    Bureau of Reclamation conducted this hydraulic model study to provide Pacific Gas and Electric Company with an evaluation of several selective withdrawal structures that are being considered to reduce intake flow temperatures through the Prattville Intake at Lake Almanor, California. Release temperature control using selective withdrawal structures is being considered in an effort to improve the cold-water fishery in the North Fork of the Feather River.

  7. Spleen-Derived Interleukin-10 Downregulates the Severity of High-Fat Diet-Induced Non-Alcoholic Fatty Pancreas Disease

    PubMed Central

    Gotoh, Koro; Inoue, Megumi; Shiraishi, Kentaro; Masaki, Takayuki; Chiba, Seiichi; Mitsutomi, Kimihiko; Shimasaki, Takanobu; Ando, Hisae; Fujiwara, Kansuke; Katsuragi, Isao; Kakuma, Tetsuya; Seike, Masataka; Sakata, Toshiie; Yoshimatsu, Hironobu

    2012-01-01

    Obesity is associated with systemic low-grade inflammation and is a risk factor for non-alcoholic fatty pancreas disease (NAFPD), but the molecular mechanisms of these associations are not clear. Interleukin (IL)-10, a potent anti-inflammatory cytokine, is released during acute pancreatitis and is known to limit inflammatory responses by downregulating the release of proinflammatory mediators. The origin of IL-10 that suppresses pancreatitis has not been investigated. Since obesity is known to reduce expression of proinflammatory cytokines in the spleen, we examined whether spleen-derived IL-10 regulates NAFPD caused by high-fat (HF) diet-induced obesity. The following investigations were performed: 1) IL-10 induction from spleen was examined in male mice fed a HF diet; 2) triglyceride content, expression of pro- and anti-inflammatory cytokines and infiltration of M1 and M2 macrophages were determined to evaluate ectopic fat accumulation and inflammatory responses in the pancreas of splenectomy (SPX)-treated mice fed HF diet; 3) exogenous IL-10 was systemically administered to SPX-treated obese mice and the resulting pathogenesis caused by SPX was assessed; and 4) IL-10 knockout (IL-10KO) mice were treated with SPX and ectopic fat deposition and inflammatory conditions in the pancreas were investigated. Obesity impaired the ability of the spleen to synthesize cytokines, including IL-10. SPX aggravated fat accumulation and inflammatory responses in the pancreas of HF diet-induced obese mice and these effects were inhibited by systemic administration of IL-10. Moreover, SPX had little effect on fat deposition and inflammatory responses in the pancreas of IL-10KO mice. Our findings indicate that obesity reduces IL-10 production by the spleen and that spleen-derived IL-10 may protect against the development of NAFPD. PMID:23285260

  8. Alcohols toxicology

    SciTech Connect

    Wimer, W.W.; Russell, J.A.; Kaplan, H.L.

    1984-01-01

    A comprehensive reference volume which summarizes literature reports of the known consequences of human and animal contact with alcohols and alcohol-derived substances is presented. Following a discussion of alcohol nomenclature and a brief history of alcohols, the authors have provided detailed chapters on the toxicology of methanol, ethanol, normal and isopropanol, and the butanols. Properties of these alcohols are compared; industrial hygiene and exposure limits are discussed. Additional sections are included covering processing and production technology and exhaust emissions studies. Of particular interest are the section containing abstracts and synopses of principal works and the extensive bibliography of studies dating from the 1800s. 331 references, 26 figures, 56 tables

  9. Alcoholism: Current Marker Research

    DTIC Science & Technology

    1984-03-01

    genetically determined characteristics such as color blindness and blood type . GENETIC MARKER STUDIES In 1966 Dr. Cruz-Coke and Dr. Varela reported that...and recovery from severe alcoholism symptoms. ■󈧒:584-587) Blood - typing marker studies have produced similar mixed results. One study published in...1959 showed a high correlation among 939 alcoholics and blood type A. (20:4 60-4 61) A similar study in 1973 reported no blood type distribution

  10. The current situation of treatment systems for alcoholism in Korea.

    PubMed

    Kim, Jee Wook; Lee, Boung Chul; Kang, Tae-Cheon; Choi, Ihn-Geun

    2013-02-01

    Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care.

  11. Targeting glutamate uptake to treat alcohol use disorders

    PubMed Central

    Rao, P.S.S.; Bell, Richard L.; Engleman, Eric A.; Sari, Youssef

    2015-01-01

    Alcoholism is a serious public health concern that is characterized by the development of tolerance to alcohol's effects, increased consumption, loss of control over drinking and the development of physical dependence. This cycle is often times punctuated by periods of abstinence, craving and relapse. The development of tolerance and the expression of withdrawal effects, which manifest as dependence, have been to a great extent attributed to neuroadaptations within the mesocorticolimbic and extended amygdala systems. Alcohol affects various neurotransmitter systems in the brain including the adrenergic, cholinergic, dopaminergic, GABAergic, glutamatergic, peptidergic, and serotonergic systems. Due to the myriad of neurotransmitter and neuromodulator systems affected by alcohol, the efficacies of current pharmacotherapies targeting alcohol dependence are limited. Importantly, research findings of changes in glutamatergic neurotransmission induced by alcohol self- or experimenter-administration have resulted in a focus on therapies targeting glutamatergic receptors and normalization of glutamatergic neurotransmission. Glutamatergic receptors implicated in the effects of ethanol include the ionotropic glutamate receptors (AMPA, Kainate, and NMDA) and some metabotropic glutamate receptors. Regarding glutamatergic homeostasis, ceftriaxone, MS-153, and GPI-1046, which upregulate glutamate transporter 1 (GLT1) expression in mesocorticolimbic brain regions, reduce alcohol intake in genetic animal models of alcoholism. Given the hyperglutamatergic/hyperexcitable state of the central nervous system induced by chronic alcohol abuse and withdrawal, the evidence thus far indicates that a restoration of glutamatergic concentrations and activity within the mesocorticolimbic system and extended amygdala as well as multiple memory systems holds great promise for the treatment of alcohol dependence. PMID:25954150

  12. What is the latent structure of alcohol use disorders? A taxometric analysis of the Personality Assessment Inventory Alcohol Problems Scale in male and female prison inmates.

    PubMed

    Walters, Glenn D; Diamond, Pamela M; Magaletta, Philip R

    2010-03-01

    Three indicators derived from the Personality Assessment Inventory (PAI) Alcohol Problems scale (ALC)-tolerance/high consumption, loss of control, and negative social and psychological consequences-were subjected to taxometric analysis-mean above minus below a cut (MAMBAC), maximum covariance (MAXCOV), and latent mode factor analysis (L-Mode)-in 1,374 federal prison inmates (905 males, 469 females). Whereas the total sample yielded ambiguous results, the male subsample produced dimensional results, and the female subsample produced taxonic results. Interpreting these findings in light of previous taxometric research on alcohol abuse and dependence it is speculated that while alcohol use disorders may be taxonic in female offenders, they are probably both taxonic and dimensional in male offenders. Two models of male alcohol use disorder in males are considered, one in which the diagnostic features are categorical and the severity of symptomatology is dimensional, and one in which some diagnostic features (e.g., withdrawal) are taxonic and other features (e.g., social problems) are dimensional.

  13. The Development of a Sexual Abuse Severity Score: Characteristics of Childhood Sexual Abuse Associated with Trauma Symptomatology, Somatization, and Alcohol Abuse

    ERIC Educational Resources Information Center

    Zink, Therese; Klesges, Lisa; Stevens, Susanna; Decker, Paul

    2009-01-01

    Childhood sexual abuse (CSA) is common and is associated with both mental and physical health problems in adulthood. Using data from an age- and sex-stratified population survey of 600 Olmsted County, Minnesota, residents, a Sexual Abuse Severity Score was developed. The abuse characteristics of 156 CSA respondents were associated with…

  14. Behavioral expression of opiate withdrawal is altered after prefrontocortical dopamine depletion in rats: monoaminergic correlates.

    PubMed

    Espejo, E F; Serrano, M I; Caillé, S; Stinus, L

    2001-08-01

    The objective of this study was to establish the effects of prefrontocortical dopamine depletion on opiate withdrawal and prefrontocortical neurochemical changes elicited by morphine dependence and withdrawal. The dopaminergic content was also measured in the nucleus accumbens during withdrawal, in order to detect reactive changes induced by prefrontocortical lesion. Withdrawal was induced by naloxone in morphine-dependent rats. Monoamine levels were analyzed post-mortem by high performance liquid cromatography. The results showed that chronic morphine dependence did not modify basal levels of monoamines in sham rats, revealing neuroadaptation of prefrontocortical dopamine, noradrenaline and serotonin systems to chronic morphine. The neuroadaptive phenomenon remained after prefrontocortical lesion (> 79% dopamine depletion). On the other hand, a strong increase of dopamine, noradrenaline, and serotonin contents in the medial prefrontal cortex of sham rats was detected during opiate withdrawal. However, in lesioned rats, the increase of prefrontocortical dopamine and serotonin content, but not that of noradrenaline, was much lower. In the nucleus accumbens, prefrontocortical lesion reactively enhanced the dopaminergic tone and, although opiate withdrawal reduced dopaminergic activity in both sham and lesioned rats, this reduction was less intense in the latter group. At a behavioral level, some symptoms of physical opiate withdrawal were exacerbated in lesioned rats (writhing, mastication, teeth-chattering, global score) and exploration was reduced. The findings hence indicate that: (i) prefrontocortical monoaminergic changes play a role in the behavioral expression of opiate withdrawal; (ii) the severity of some withdrawal signs are related to the dopaminergic and serotonergic tone of the medial prefrontal cortex rather than to the noradrenergic one, and (iii) an inverse relationship between mesocortical and mesolimbic dopaminergic systems exists.

  15. Demand and withdraw communication among couples experiencing husband violence.

    PubMed

    Holtzworth-Munroe, A; Smutzler, N; Stuart, G L

    1998-10-01

    Two studies compared marital communication behaviors of violent and nonviolent couples. In Study 1, violent distressed (VD) men reported more husband demand-wife withdraw than did nonviolent men. Distressed men reported less mutual constructive communication and more mutual blame and avoidance than did nondistressed men. Interactions of VD, violent nondistressed (VND), nonviolent distressed (NVD), and nonviolent nondistressed couples were coded in Study 2. VD spouses tended to engage in the most demand and withdraw and the least positive behavior; violent couples had the highest levels of contempt. On some codes, VND couples resembled NVD couples, suggesting that violence without distress may correlate differently with marital communication than violence in combination with distress and that severity of violence is important to consider.

  16. Hallucinations after abrupt withdrawal of oral and intrathecal baclofen.

    PubMed

    D'Aleo, Giangaetano; Cammaroto, Simona; Rifici, Carmela; Marra, Giuseppe; Sessa, Edoardo; Bramanti, Placido; Di Bella, Paolo

    2007-01-01

    Since 1977 several cases of hallucinations after abrupt withdrawal of oral baclofen have been described. There are no reports of hallucinations after gradual withdrawal of oral baclofen. No one has ever described visual hallucinations after abrupt interruption of intrathecal baclofen therapy. We describe five personally observed cases of visual hallucinations occurring after sudden interruption of baclofen (in two of these cases, intrathecal baclofen) therapy. The patients were immediately submitted to routine EEG, visual evoked potentials and standard brain magnetic resonance imaging (MRI). A few days later they also underwent polysomnography, fundus oculi examination and brain MRI of the temporal lobe. All these examinations were normal. We hypothesise that these symptoms could be due to biochemical and molecular changes, chiefly in glutamatergic n-methyl-d-aspartate, GABA-A, and GABA-B receptor response, leading to increased excitability and spontaneous activity as a result of chronic use of baclofen.

  17. The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded pilot experiment.

    PubMed

    Dews, P B; Curtis, G L; Hanford, K J; O'Brien, C P

    1999-12-01

    Reports of symptoms when regular caffeine consumption is stopped have appeared in the medical literature, but the frequency and significance of this phenomenon have remained controversial. The objective of this study was to collect information on the prevalence and severity of caffeine withdrawal in the general population and determine the incidence and type of symptoms reported on blind abrupt and gradual caffeine cessation among coffee drinkers reporting past episodes of caffeine-withdrawal symptoms. A community-based telephone survey was followed by a stratified, randomized, double-blind controlled study. Participants included 11,112 persons spontaneously calling to inquire about studies not related to caffeine and 57 regular caffeine users selected from among the callers because of self-reported caffeine-withdrawal symptoms. Gradual or abrupt withdrawal from caffeine was compared to continuation of the same caffeine level. In a survey of 11,112 persons, 61% reported daily caffeine consumption, and 11% of the caffeine consumers reported symptoms upon stopping caffeine. Among the regular caffeine users, only 0.9% of males and 5.5% of females reported symptoms significant enough to interfere with normal activities when they abruptly stopped caffeine. A group of those reporting withdrawal symptoms were randomly assigned to three subsamples. In the group subjected to abrupt withdrawal (N = 18), 6 (33.3%) reported symptoms (e.g., headaches and tiredness). Including decreases in functional ratings, a total of 7 of the 18 (38.8%) could be considered to have experienced caffeine withdrawal. The gradual withdrawal group (N = 20) reported minimal if any caffeine withdrawal symptoms. A third group (N = 18) was kept on a level dose of caffeine for comparison. When participants are unaware of the caffeine-withdrawal focus of the study, these results suggest that both the frequency and severity of caffeine-withdrawal symptoms are much lower than found in some previous reports

  18. Perception of sweet taste is important for voluntary alcohol consumption in mice.

    PubMed

    Blednov, Y A; Walker, D; Martinez, M; Levine, M; Damak, S; Margolskee, R F

    2008-02-01

    To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: alpha-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild-type mice, whereas Tas1r3 null mice were not different from wild type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion (CTA) to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in CTA to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol.

  19. Novel MPDZ/MUPP1 transgenic and knockdown models confirm Mpdz's role in ethanol withdrawal and support its role in voluntary ethanol consumption.

    PubMed

    Milner, Lauren C; Shirley, Renee L; Kozell, Laura B; Walter, Nicole A; Kruse, Lauren C; Komiyama, Noboru H; Grant, Seth G N; Buck, Kari J

    2015-01-01

    Association studies implicate multiple PDZ domain protein (MPDZ/MUPP1) sequence and/or expression in risk for alcoholism in humans and ethanol withdrawal (EW) in mice, but confirmation has been hindered by the dearth of targeted genetic models. We report the creation of transgenic (MPDZ-TG) and knockout heterozygote (Mpdz(+/-) ) mice, with increased (2.9-fold) and decreased (53%) target expression, respectively. Both models differ in EW compared with wild-type littermates (P ≤ 0.03), providing compelling evidence for an inverse relationship between Mpdz expression and EW severity. Additionally, ethanol consumption is reduced up to 18% (P = 0.006) in Mpdz(+/-) , providing the first evidence implicating Mpdz in ethanol self-administration.

  20. Brief report: Perceptions of social withdrawal during emerging adulthood in Lagos, Nigeria.

    PubMed

    Bowker, Julie C; Ojo, Adesola Adebusola; Bowker, Matthew H

    2016-02-01

    The study of social withdrawal subtypes is no longer limited to Western societies but has extended to non-Western countries, such as China. This study considers, for the first time, social withdrawal subtypes in an African country (Nigeria) by examining emerging adults' (N = 151; 54% female; Mage = 19.92 years, SD = 2.54) perceptions, attitudes, and responses to shy, unsociable, and socially competent behaviors. Results revealed that Nigerian emerging adults perceived significant differences between shy, unsociable, and socially competent behavior in several ways incommensurate with participants of previous studies conducted in North America, Europe, and China. Findings highlight the diversity of social meanings attached to social withdrawal in non-Western societies, and point to the need for additional research on social withdrawal and its perception in Africa.

  1. Limiting and Withdrawing Life Support in the PICU: For Whom Are These Options Discussed?

    PubMed Central

    Keele, Linda; Meert, Kathleen L.; Berg, Robert A.; Dalton, Heidi; Newth, Christopher J. L.; Harrison, Rick; Wessel, David L.; Shanley, Thomas; Carcillo, Joseph; Morrison, Wynne; Funai, Tomohiko; Holubkov, Richard; Dean, J. Michael; Pollack, Murray

    2016-01-01

    . Of those who survived, 40 children (53.4%) were discharged with severe or very severe functional abnormalities, and 15 (20%) with coma/vegetative state. Conclusions Clinical factors reflecting type and severity of illness, sociodemographics, and institutional practices may influence whether limitation or withdrawal of life support is discussed with families of PICU patients. Most children whose families discuss limitation or withdrawal of life support die during their PICU stay; survivors often have substantial disabilities. PMID:26669647

  2. Preventing Fetal Alcohol Syndrome and Other Alcohol-Related Birth Defects: Teacher's Manual and Student Text. High School Edition.

    ERIC Educational Resources Information Center

    Howard, Elizabeth; And Others

    This teacher's manual presents lesson plans for a high-school instructional unit on Fetal Alcohol Syndrome and its less severe manifestations, Alcohol-Related Birth Defects. The lessons cover alcohol's effects during pregnancy, the history of concern about alcohol's effects, consequences of alcohol use in pregnancy, lifestyle risk reduction, and…

  3. No association between the TaqI A1 RFLP of the D2 receptor gene and alcoholism in a Mexican population

    SciTech Connect

    Cruz-Fuentes, C.; Carmarena, B.; Eroza, V.

    1994-09-01

    The suggested association of the A1 allele of the D2 dopamine receptor (DRD2) human gene with alcoholism was studied by comparing the DRD2/TaqI genotypes of 36 healthy controls and 38 individuals who met the DSM-III-R diagnostic criteria for alcohol dependence. All subjects were unrelated, with parents and grandparents of Mexican origin. The alcoholics in our sample suffered one of the following conditions: delirium tremens (16.6%), alcohol hallucinosis (56.6%) or uncomplicated alcohol withdrawal (26.4%). Eight-eight percent of the controls carried the A1 allele. The frequency of the DRD2 A1 allele in the Mexican urban sample (pA1 = 0.61) was 2 to 3-fold higher than reported in Caucasian populations from the USA and Europe, but similar to the allele frequencies found in defined Amerindian populations. There were not significant differences in the prevalence or allele frequency between alcoholics (pA1 = 0.64) and controls, regardless if the alcoholics were subtyped accordingly to severity, age of onset or positive family history. Alcoholics had higher scores than controls in the neuroticism (N) and psychoticism (P) subscales on the Eysenck personality test: alcoholics P = 6.2 {+-} 2.9, N = 16.0 {+-} 4.2 vs. controls P = 2.5 {+-} 2.3, N = 5.7 {+-} 5.1; p<0.001 and p<0.001, respectively. However, no relationship between personality traits and genotypes was found. Our results do not support a consistent association between the TaqI A1 RFLP for the DRD2 gene and alcoholism.

  4. Estimated Freshwater Withdrawals in Oklahoma, 1990

    USGS Publications Warehouse

    Lurry, Dee L.; Tortorelli, Robert L.

    1996-01-01

    This report presents 1990 freshwater withdrawal estimates for Oklahoma by source and category. Withdrawal source is either ground water or surface water. Withdrawal categories include: irrigation, water supply, livestock, thermoelectric-power generation, domestic and commercial, and industrial and mining. Withdrawal data are aggregated by county, major aquifer, and principal river basin. Only the four major categories of irrigation, water supply, livestock, and thermoelectric-power generation are illustrated in this report, although data for all categories are tabulated. The U.S. Geological Survey (USGS) established the National Water-Use Information Program in 1977 to collect uniform, current, and reliable information on water use. The Oklahoma District of the USGS and the Oklahoma Water Resources Board participate in a cooperative program to collect and publish water-use information for Oklahoma. Data contained in this report were made available through the cooperative program.

  5. Living with an alcoholic partner: Problems faced and coping strategies used by wives of alcoholic clients

    PubMed Central

    Sharma, Nitasha; Sharma, Sunita; Ghai, Sandhya; Basu, Debashish; Kumari, Deepika; Singh, Dharamveer; Kaur, Gagandeep

    2016-01-01

    Background: Alcoholism is considered as a major health as well as a social problem. Often the family members of alcoholics suffer intense psychological, physical and social trauma due to the core drinking problem of the family member. Most deeply affected are the wives of alcoholics. Aim: The present descriptive study aimed to investigate the problems faced and coping strategies used by the wives of alcoholics. Methodology: A total of 30 wives of alcoholic clients seeking treatment in De-addiction Centre were interviewed for the same. The problems were identified using a non standardized 17 item structured questionnaire while coping in wives of alcoholics was assessed using standardized tool. Results: The findings revealed the problems faced by alcoholics wives were in multiple domains viz. physical, psychological and social. While most highly reported were the emotional problems and least reported were the problems of physical violence. Coping strategies used by wives of alcoholics were reported in three major styles: engaged, tolerant and withdrawal. Conclusion and Recommendations: The problems faced by alcoholics have often wedged the attention in society yet finding and applying effective interventions to reduce the pain and suffering of being a partner of alcoholic is still a challenge. PMID:28163410

  6. Unique Scopolamine Withdrawal Syndrome After Standard Transdermal Use.

    PubMed

    Manno, Maurizio; Di Renzo, Gianfranco; Bianco, Pasquale; Sbordone, Carmine; De Matteis, Francesco

    2015-01-01

    We report the case of a 62-year-old woman who developed a withdrawal syndrome after using a standard 1.5-mg transdermal scopolamine (TDS) patch behind the ear to prevent motion sickness during sailing. The patient, who had used TDS occasionally for years without significant adverse effects, more recently, having worn a patch continuously for 7 days, approximately 24 to 36 hours after removing the patch developed dizziness, nausea, sweating, fatigue, and drowsiness. All symptoms disappeared without therapy in about 2 days. Approximately 1 year after the first episode, though, a very similar, more severe disabling reaction developed on 2 occasions. Drowsiness and malaise were accompanied by severe asthenia, orthostatic sweating, inability to stand, and hypotension. All clinical tests (electrocardiogram; spirometry; blood cell count; plasma levels of cortisol, sodium, and potassium; and liver and kidney function tests) were negative, and symptoms disappeared slowly, after several days. Although we are certain that scopolamine was responsible for the symptoms, we are less clear as to the nature of the disorder. The effects being more severe after a more prolonged use of the TDS patch, the increase in severity each successive time, and the time lag between removing the patch and appearance of symptoms all indicated a withdrawal syndrome for which several mechanisms may be suggested.

  7. Alcoholic cardiomyopathy: Pathophysiologic insights

    PubMed Central

    Piano, Mariann R.; Phillips, Shane A.

    2014-01-01

    Alcoholic cardiomyopathy is a specific heart muscle disease found in individuals with a history of long-term heavy alcohol consumption. Alcoholic cardiomyopathy is associated with a number of adverse histological, cellular, and structural changes within the myocardium. Several mechanisms are implicated in mediating the adverse effects of ethanol, including the generation of oxidative stress, apoptotic cell death, impaired mitochondrial bioenergetics/stress, derangements in fatty acid metabolism and transport, and accelerated protein catabolism. In this review, we discuss the evidence for such mechanisms and present the potential importance of drinking patterns, genetic susceptibility, nutritional factors, race, and sex. The purpose of this review is to provide a mechanistic paradigm for future research in the area of alcoholic cardiomyopathy. PMID:24671642

  8. Total water withdrawals in Mississippi, 1990

    USGS Publications Warehouse

    Johnson, P.M.

    1994-01-01

    During 1990, the amount of water withdrawn from ground- and surface-water sources in Mississippi was about 3,600 Mgal/d (million gallons per day). Of this amount, 91 percent, or 3,300 Mgal/d, was withdrawn from freshwater sources. Of the total freshwater withdrawals, about 82 percent, or 2,700 Mgal/d, was withdrawn from ground-water sources. Total water withdrawals in Mississippi in 1990 for eight categories of use were as follows: irrigation, 1,900 Mgal/d; thermoelectric power, 700 Mgal/d; aquaculture, 400 Mgal/d; public supply, 320 Mgal/d; industrial and mining, 270 Mgal/d; domestic, 33 Mgal/d; commercial, 16 Mgal/d; and livestock, 16 Mgal/d. Overall, total withdrawals increased by 20 percent from 1985 to 1990, although the total population decreased about 2 percent. During the same period, total freshwater withdrawals increased by about 17 percent. Total saline with- drawals increased by about 60 percent from 1985 due to an increase in salin withdrawals for thermo- electric power generation. Total fresh and saline surface-water withdrawals decreased by about 6 percent from 1985, due to decrease in surface-water withdrawals for irrigation. Fresh ground-water withdrawals in Mississippi increased by about 33 percent, primarily due to an increase in irrigation. Since 1960, total ground- and surface-water with- drawals increased 70 percent for the same period. Irrigation had the greatest increase in with- drawals since 1960, with a 269 percent increase. Public supply had the second greatest, with a 178 percent increase.

  9. 5 CFR 1620.22 - Withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... subpart can make a post-employment withdrawal election described at 5 U.S.C. 8433(b): (1) Upon separation... section, a post-employment withdrawal election can be made by: (i) A justice or judge of the United States (as defined in 28 U.S.C. 451) who retires under 28 U.S.C. 317(a) or (b) or 372(a); (ii) A...

  10. 5 CFR 1620.22 - Withdrawals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... subpart can make a post-employment withdrawal election described at 5 U.S.C. 8433(b): (1) Upon separation... section, a post-employment withdrawal election can be made by: (i) A justice or judge of the United States (as defined in 28 U.S.C. 451) who retires under 28 U.S.C. 317(a) or (b) or 372(a); (ii) A...

  11. 5 CFR 1620.22 - Withdrawals.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... subpart can make a post-employment withdrawal election described at 5 U.S.C. 8433(b): (1) Upon separation... section, a post-employment withdrawal election can be made by: (i) A justice or judge of the United States (as defined in 28 U.S.C. 451) who retires under 28 U.S.C. 317(a) or (b) or 372(a); (ii) A...

  12. 48 CFR 752.7024 - Withdrawal of students.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Withdrawal of students... Withdrawal of students. For use in contracts for participant training with an educational institution. Withdrawal of Students (APR 1984) (a) The Government may, at its option and at any time, withdraw any...

  13. 48 CFR 752.7024 - Withdrawal of students.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Withdrawal of students... Withdrawal of students. For use in contracts for participant training with an educational institution. Withdrawal of Students (APR 1984) (a) The Government may, at its option and at any time, withdraw any...

  14. 48 CFR 752.7024 - Withdrawal of students.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Withdrawal of students... Withdrawal of students. For use in contracts for participant training with an educational institution. Withdrawal of Students (APR 1984) (a) The Government may, at its option and at any time, withdraw any...

  15. 48 CFR 752.7024 - Withdrawal of students.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Withdrawal of students... Withdrawal of students. For use in contracts for participant training with an educational institution. Withdrawal of Students (APR 1984) (a) The Government may, at its option and at any time, withdraw any...

  16. 48 CFR 752.7024 - Withdrawal of students.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Withdrawal of students... Withdrawal of students. For use in contracts for participant training with an educational institution. Withdrawal of Students (APR 1984) (a) The Government may, at its option and at any time, withdraw any...

  17. 21 CFR 514.7 - Withdrawal of applications without prejudice.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Withdrawal of applications without prejudice. 514... Withdrawal of applications without prejudice. The sponsor may withdraw his pending application from.... Such withdrawal may be made without prejudice to a future filing. Upon resubmission, the...

  18. 21 CFR 514.7 - Withdrawal of applications without prejudice.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Withdrawal of applications without prejudice. 514... Withdrawal of applications without prejudice. The sponsor may withdraw his pending application from.... Such withdrawal may be made without prejudice to a future filing. Upon resubmission, the...

  19. 21 CFR 514.7 - Withdrawal of applications without prejudice.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Withdrawal of applications without prejudice. 514... Withdrawal of applications without prejudice. The sponsor may withdraw his pending application from.... Such withdrawal may be made without prejudice to a future filing. Upon resubmission, the...

  20. 21 CFR 514.7 - Withdrawal of applications without prejudice.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Withdrawal of applications without prejudice. 514... Withdrawal of applications without prejudice. The sponsor may withdraw his pending application from.... Such withdrawal may be made without prejudice to a future filing. Upon resubmission, the...

  1. 21 CFR 514.7 - Withdrawal of applications without prejudice.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Withdrawal of applications without prejudice. 514... Withdrawal of applications without prejudice. The sponsor may withdraw his pending application from.... Such withdrawal may be made without prejudice to a future filing. Upon resubmission, the...

  2. Patterns of Withdrawal Behaviors. Working Paper 83-10.

    ERIC Educational Resources Information Center

    Rosse, Joseph G.

    Studies of employee tardiness, absence, and turnover generally adhere to one of five models: generalized withdrawal, which proposes positive intercorrelations among withdrawal behaviors; independent forms, which hypothesizes non-significant correlations among withdrawal behaviors; progression of withdrawal, which suggests that individuals engage…

  3. 19 CFR 144.27 - Withdrawal from warehouse by transferee.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal from warehouse by transferee. 144.27...; DEPARTMENT OF THE TREASURY (CONTINUED) WAREHOUSE AND REWAREHOUSE ENTRIES AND WITHDRAWALS Transfer of Right To Withdraw Merchandise from Warehouse § 144.27 Withdrawal from warehouse by transferee. At any time...

  4. 19 CFR 144.38 - Withdrawal for consumption.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TREASURY (CONTINUED) WAREHOUSE AND REWAREHOUSE ENTRIES AND WITHDRAWALS Withdrawals from Warehouse § 144.38 Withdrawal for consumption. (a) Form. Withdrawals for consumption of merchandise in bonded warehouses shall... any correction thereof reported after the filing of the warehouse entry. Additionally, on...

  5. 19 CFR 144.31 - Right to withdraw.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) WAREHOUSE AND REWAREHOUSE ENTRIES AND WITHDRAWALS Withdrawals from Warehouse § 144.31 Right to withdraw. Withdrawals from bonded warehouse may be made only by the person primarily liable for the payment of duties on the merchandise being withdrawn, i.e., the importer of record on the warehouse...

  6. 29 CFR 4207.8 - Liability for subsequent partial withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... immediately preceding the plan year in which the partial withdrawal occurs include a plan year during the... 29 Labor 9 2010-07-01 2010-07-01 false Liability for subsequent partial withdrawals. 4207.8... WITHDRAWAL LIABILITY FOR MULTIEMPLOYER PLANS REDUCTION OR WAIVER OF COMPLETE WITHDRAWAL LIABILITY §...

  7. 43 CFR 2310.4 - Review and extensions of withdrawals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Review and extensions of withdrawals. 2310... Withdrawals, General: Procedure § 2310.4 Review and extensions of withdrawals. (a) Discretionary withdrawals... provisions of section 204(c) of the Act (43 U.S.C. 1714(c)), or section 204(d) of the Act (43 U.S.C....

  8. 43 CFR 2310.4 - Review and extensions of withdrawals.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Review and extensions of withdrawals. 2310... Withdrawals, General: Procedure § 2310.4 Review and extensions of withdrawals. (a) Discretionary withdrawals... provisions of section 204(c) of the Act (43 U.S.C. 1714(c)), or section 204(d) of the Act (43 U.S.C....

  9. 43 CFR 2310.4 - Review and extensions of withdrawals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Review and extensions of withdrawals. 2310... Withdrawals, General: Procedure § 2310.4 Review and extensions of withdrawals. (a) Discretionary withdrawals... provisions of section 204(c) of the Act (43 U.S.C. 1714(c)), or section 204(d) of the Act (43 U.S.C....

  10. 12 CFR 1263.26 - Voluntary withdrawal from membership.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Voluntary withdrawal from membership. 1263.26... BANKS Withdrawal and Removal From Membership § 1263.26 Voluntary withdrawal from membership. (a) In general. (1) Any institution may withdraw from membership by providing to the Bank written notice of...

  11. 12 CFR 1263.26 - Voluntary withdrawal from membership.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 9 2013-01-01 2013-01-01 false Voluntary withdrawal from membership. 1263.26... BANKS Withdrawal and Removal From Membership § 1263.26 Voluntary withdrawal from membership. (a) In general. (1) Any institution may withdraw from membership by providing to the Bank written notice of...

  12. 12 CFR 1263.26 - Voluntary withdrawal from membership.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 10 2014-01-01 2014-01-01 false Voluntary withdrawal from membership. 1263.26... BANKS Withdrawal and Removal From Membership § 1263.26 Voluntary withdrawal from membership. (a) In general. (1) Any institution may withdraw from membership by providing to the Bank written notice of...

  13. 12 CFR 925.26 - Voluntary withdrawal from membership.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Voluntary withdrawal from membership. 925.26... ASSOCIATES MEMBERS OF THE BANKS Withdrawal and Removal From Membership § 925.26 Voluntary withdrawal from membership. (a) In general. (1) Any institution may withdraw from membership by providing to the Bank...

  14. Antiepileptic Drug Withdrawal in Dogs with Epilepsy.

    PubMed

    Gesell, Felix Kaspar; Hoppe, Sonja; Löscher, Wolfgang; Tipold, Andrea

    2015-01-01

    Epilepsy is one of the most common neurological disorders in dogs and is treated by chronic administration of antiepileptic drugs (AEDs). In human beings with epilepsy, it is common clinical practice to consider drug withdrawal after a patient has been in remission (seizure free) for three or more years, but withdrawal is associated with the risk of relapse. In the present study, the consequences of AED withdrawal were studied in dogs with epilepsy. Therefore, 200 owners of dogs with idiopathic or presumed idiopathic epilepsy were contacted by telephone interview, 138 cases could be enrolled. In 11 cases, the therapy had been stopped after the dogs had become seizure free for a median time of 1 year. Reasons for AED withdrawal were appearance or fear of adverse side effects, financial aspects, and the idea that the medication could be unnecessary. Following AED withdrawal, four of these dogs remained seizure free, seven dogs suffered from seizure recurrence, of which only three dogs could regain seizure freedom after resuming AED therapy. Due to the restricted case number, an exact percentage of dogs with seizure recurrence after AED withdrawal cannot be given. However, the present study gives a hint that similar numbers as in human patients are found, and the data can help owners of epileptic dogs and the responsible clinician to decide when and why to stop antiepileptic medication.

  15. Antiepileptic Drug Withdrawal in Dogs with Epilepsy

    PubMed Central

    Gesell, Felix Kaspar; Hoppe, Sonja; Löscher, Wolfgang; Tipold, Andrea

    2015-01-01

    Epilepsy is one of the most common neurological disorders in dogs and is treated by chronic administration of antiepileptic drugs (AEDs). In human beings with epilepsy, it is common clinical practice to consider drug withdrawal after a patient has been in remission (seizure free) for three or more years, but withdrawal is associated with the risk of relapse. In the present study, the consequences of AED withdrawal were studied in dogs with epilepsy. Therefore, 200 owners of dogs with idiopathic or presumed idiopathic epilepsy were contacted by telephone interview, 138 cases could be enrolled. In 11 cases, the therapy had been stopped after the dogs had become seizure free for a median time of 1 year. Reasons for AED withdrawal were appearance or fear of adverse side effects, financial aspects, and the idea that the medication could be unnecessary. Following AED withdrawal, four of these dogs remained seizure free, seven dogs suffered from seizure recurrence, of which only three dogs could regain seizure freedom after resuming AED therapy. Due to the restricted case number, an exact percentage of dogs with seizure recurrence after AED withdrawal cannot be given. However, the present study gives a hint that similar numbers as in human patients are found, and the data can help owners of epileptic dogs and the responsible clinician to decide when and why to stop antiepileptic medication. PMID:26664952

  16. Withdrawing Benzodiazepines in Patients With Anxiety Disorders.

    PubMed

    Lader, Malcolm; Kyriacou, Andri

    2016-01-01

    The large class of CNS-depressant medications-the benzodiazepines-have been extensively used for over 50 years, anxiety disorders being one of the main indications. A substantial proportion (perhaps up to 20-30 %) of long-term users becomes physically dependent on them. Problems with their use became manifest, and dependence, withdrawal difficulties and abuse were documented by the 1980s. Many such users experience physical and psychological withdrawal symptoms on attempted cessation and may develop clinically troublesome syndromes even during slow tapering. Few studies have been conducted to establish the optimal withdrawal schedules. The usual management comprises slow withdrawal over weeks or months together with psychotherapy of various modalities. Pharmacological aids include antidepressants such as the SSRIs especially if depressive symptoms supervene. Other pharmacological agents such as the benzodiazepine antagonist, flumazenil, and the hormonal agent, melatonin, remain largely experimental. The purpose of this review is to analyse the evidence for the efficacy of the usual withdrawal regimes and the newer agents. It is concluded that little evidence exists outside the usual principles of drug withdrawal but there are some promising leads.

  17. Effects of alcohol on the membrane excitability and synaptic transmission of medium spiny neurons in the nucleus accumbens

    PubMed Central

    Marty, Vincent N.; Spigelman, Igor

    2013-01-01

    Chronic and excessive alcohol drinking lead to alcohol dependence and loss of control over alcohol consumption, with serious detrimental health consequences. Chronic alcohol exposure followed by protracted withdrawal causes profound alterations in the brain reward system that leads to marked changes in reinforcement mechanisms and motivational state. These long-lasting neuroadaptations are thought to contribute to the development of cravings and relapse. The nucleus accumbens (NAcc), a central component of the brain reward system, plays a critical role in alcohol-induced neuroadaptive changes underlying alcohol-seeking behaviors. Here we review the findings that chronic alcohol exposure produces long-lasting neuroadaptive changes in various ion channels that govern intrinsic membrane properties and neuronal excitability, as well as excitatory and inhibitory synaptic transmission in the NAcc that underlie alcohol-seeking behavior during protracted withdrawal. PMID:22445807

  18. Withdrawal from methylphenidate increases neural reactivity of dorsal midbrain.

    PubMed

    Ferreira, R; Bassi, G S; Cabral, A; Nobre, M J

    2010-12-01

    Ritalin (methylphenidate hydrochloride, MP) is a non-amphetamine psychostimulant and is the drug of choice to treat children and adults diagnosed with the attention deficit hyperactivity disorder (ADHD). Several studies have demonstrated that rats treated with MP during early developmental stage exhibit alterations in anxiety-related processes such as an increased response to stressful stimuli and elevated plasma levels of corticosterone. Accordingly, the present study was designed to further characterize the neural and behavioral consequences of withdrawal from MP in adult rats and its influence on the neural reactivity of the dorsal midbrain. After initial exposure to an elevated plus-maze (EPM), brainstem neural activation, elicited by exposure to EPM aversive cues, was analyzed using a Fos-protein immunolabeling technique. Additional independent groups of animals were submitted to electrical stimulation of the dorsal column (DPAG) or the startle response procedure, in order to verify the influence of withdrawal from MP on the expression of unconditioned fear induced by DPAG activation and the effects of or withdrawal from MP on motor response, respectively. Our results provide new findings about the influence of MP treatment in adult rats, showing that, after a sudden MP treatment-break, increased anxiety, associated with the neural sensitization of anxiety-related regions, ensues.

  19. Phytotherapy of opioid dependence and withdrawal syndrome: a review.

    PubMed

    Tabatabai, Seyed Meghdad; Dashti, Saeedeh; Doosti, Fatemeh; Hosseinzadeh, Hossein

    2014-06-01

    Development of tolerance and dependence is a major problem associated with opioid treatment. Withdrawal syndrome is common between medical and illicit users of these agents. Phytomedicine has shown promise in the treatment of this complicated psychosomatic condition. In this study, the effects of plant extracts and active components on morphine dependence and withdrawal syndrome are discussed. Proper keywords were used to search through PubMed, Google Scholar, and SciVerse, as well as two local scientific databases, www.iranmedex.com and www.SID.com. All relevant results (original articles, meeting abstracts, patents, etc.) published from 2000 to 2013 were chosen for final review. A total of 35 plant species were studied on this subject. Plants from Lamiaceae, Ranunculaceae, and Apiaceae families were especially effective. A few studies were carried out on human subjects and the rest in animal models. Opioid dependence and withdrawal syndrome remain an intimidating challenge. Nonetheless, plants and their derivatives are suitable sources for their treatment. Although there are several plants shown to be effective in animal models, few clinical studies are available.

  20. Cholinergic modulation of food and drug satiety and withdrawal.

    PubMed

    Avena, Nicole M; Rada, Pedro V

    2012-06-06

    Although they comprise only a small portion of the neurons in the region, cholinergic interneurons in the dorsal striatum appear to play an important role in the regulation of various appetitive behaviors, in part, through their interactions with mesolimbic dopamine (DA) systems. In this review, we describe studies that suggest that the activity of cholinergic interneurons in the nucleus accumbens (NAc) and cholinergic projections to the ventral tegmental area (VTA) affect feeding behavior. In vivo microdialysis studies in rats have revealed that the cessation of a meal is associated with a rise in acetylcholine (ACh) levels in the NAc. ACh activation will suppress feeding, and this is also associated with an increase in synaptic accumulation of ACh. Further, we discuss how, in addition to their role in the ending of a meal, cholinergic interneurons in the NAc play an integral role in the cessation of drug use. Another cholinergic system involved in different aspects of appetitive behavior is the projection from the pedunculpontine nuclei directly to the VTA. Activation of this system enhances behaviors through activation of the mesolimbic DA system, and antagonism of ACh receptors in the VTA can reduce drug self-administration. Finally, we discuss the role of accumbens ACh in both drug and palatable food withdrawal. Studies reveal that accumbens ACh is increased during withdrawal from several different drugs of abuse (including cocaine, nicotine and morphine). This rise in extracellular levels of ACh, coupled with a decrease in extracellular levels of DA, is believed to contribute to an aversive state, which can manifest as behaviors associated with drug withdrawal. This theory has also been applied to studies of overeating and/or "food addiction," and the findings suggest a similar imbalance in DA/ACh levels, which is associated with behavioral indications of drug-like withdrawal. In summary, cholinergic neurons play an important role in the modulation of both