Home About us Contact
|
Home About us Contact | ||
|
|
||
Withdrawal Syndrome (withdrawal + syndrome)
Kinds of Withdrawal Syndrome Selected AbstractsAltered Motor Cortex Excitability to Magnetic Stimulation in Alcohol Withdrawal SyndromeALCOHOLISM, Issue 4 2010Raffaele Nardone Background:, Alcohol addiction is a complex brain disease caused by alterations in crucial neurotransmitter systems, including gamma-aminobutyric acid (GABA) and glutamate. These disturbances could be revealed by changes in cortical excitability parameters, as assessed by transcranial magnetic stimulation (TMS). This study was aimed to further investigate the complex pathophysiology of alcohol withdrawal syndrome (AWS). Methods:, Motor cortex excitability was examined in 13 subjects with AWS in a mild predelirial state, in 12 chronic alcoholics and in 15 age-matched control subjects, using a range of TMS protocols. Central motor conduction time, resting and active motor threshold, duration of the cortical silent period, short latency intracortical inhibition (SICI), and intracortical facilitation (ICF) to paired TMS were examined. Results:, Intracortical facilitation was significantly increased in the AWS patients when compared with the chronic alcoholics and the control subjects. The other TMS parameters did not differ significantly from the controls. Administration of a single oral dose of the glutamatergic antagonist riluzole in a subgroup of 8 patients significantly reduced ICF; motor threshold and SICI were not affected by riluzole. Conclusion:, Transcranial magnetic stimulation shows a selective increase in intracortical facilitation after ethanol withdrawal. Our findings support the theory that altered glutamatergic receptor function plays an important role in the pathogenesis of human alcohol withdrawal. This study provides further physiological evidence that antiglutamatergic approaches represent an efficacious alternative for treating alcohol withdrawal symptoms. [source] Heart Rate Variability and Sympathetic Skin Response in Male Patients Suffering From Acute Alcohol Withdrawal SyndromeALCOHOLISM, Issue 9 2006Karl-Jürgen Bär Background: Many symptoms of alcohol withdrawal (AW) such as tachycardia or elevated blood pressure might be explained by increased peripheral and central adrenergic activity. In contrast to many neurochemical studies of sympathetic activation during AW, only very few studies investigated autonomic balance using neurophysiological methods. Methods: We investigated heart rate variability (HRV) and sympathetic skin response (SSR) in male patients suffering from mild AW syndrome (n=20, no treatment required) and in patients with moderate to severe AW syndrome (n=20, clomethiazole treatment) in the acute stage. Sympathovagal influence was quantified using measures of time and frequency domain of HRV as well as modern nonlinear parameters (compression entropy). Furthermore, we obtained latencies and amplitudes of SSR to quantify isolated sympathetic influence. Measures were obtained during the climax of withdrawal symptomatology before treatment, 1 day after climax, and shortly before discharge from hospital. Alcohol withdrawal scores were obtained and correlated to autonomic measures. Results: Ambulatory blood pressure and AW scores revealed characteristic withdrawal symptoms in both patient groups. Apart from the nonlinear parameter compression entropy, Hc, measures of HRV revealed no sign of autonomic dysfunction in contrast to the significantly increased heart rates at the time of admission. Latencies and amplitudes of SSR did not indicate any increase of sympathetic activity. A negative correlation was found between Hc and mental withdrawal symptoms. Conclusions: We show here that classical measures for autonomic nervous system activity such as HRV and SSR are not suitable for describing the autonomic changes seen in acute AW, although a major role for the sympathetic nervous system has been proposed. This might be due to multiple dysregulation of metabolites in AWS or to subtle alcohol-induced damage to neuronal structures, issues that should be addressed in future studies. [source] Role of Parvalbumin in Estrogen Protection From Ethanol Withdrawal SyndromeALCOHOLISM, Issue 10 2005Mridula Rewal Abstract: Background: Parvalbumin (PA) is a calcium-binding protein that has been implicated in protecting neurons from hyperexcitability by sequestering intracellular calcium. This study examined whether ethanol exposure and/or ethanol withdrawal (EW) alter the levels of PA in a manner that is protected by 17,-estradiol (E2). Methods: Ovariectomized rats implanted with E2 (EW/E2) or oil pellets (EW/Oil) received chronic ethanol (7.5% w/v, 5 weeks) or control dextrin (Dex/Oil and Dex/E2) diets. At 0 hr, 24 hr, and 2 weeks of EW, three brain areas (the cerebellum, hippocampus, and cortex) were prepared for immunoblotting and immunohistological assessment of PA. Results: At 24 hr of EW, the EW/Oil group showed reduced levels of PA protein and PA-positive neurons in the cerebellum and hippocampus compared with the dextrin control and the EW/E2 groups. At 2 weeks of EW, the reduced levels of PA persisted in the cerebellum but recovered toward the control levels in the hippocampus. The cortex showed no change in PA levels in any of the treatment groups. When tested at 24 hr of EW, the magnitude of EW signs inversely correlated with the levels of PA in the cerebellum and hippocampus. Ethanol exposure itself did not affect PA levels. Conclusion: These data suggest that EW, rather than ethanol exposure, reduces PA levels in a manner that is brain region specific and that is protected by estrogen. Disturbed PA homeostasis is hypothesized to play a role in the hyperexcitability of EW signs. [source] Liver Disease in Heavy Drinkers With and Without Alcohol Withdrawal SyndromeALCOHOLISM, Issue 1 2004E. Barrio Abstract: Background: Withdrawal syndrome is a hallmark of alcohol dependence. The characteristics of alcohol consumption, closely related to dependence, could influence the development of alcoholic liver disease. The study aimed to investigate if patients with severe alcohol withdrawal syndrome have a peculiar profile of liver disease. Methods: The study included 256 heavy drinkers (aged 19,75 years, 70.3% males) admitted to an Internal Medicine Department. Patients admitted for complications of liver disease were not included. Severe alcohol withdrawal syndrome (seizures, disordered perceptions, or delirium) developed in 150 patients (58.6%). Alcohol consumption (daily quantity, duration, and pattern [regular or irregular]) was assessed by questionnaire. Liver biopsy was performed in all cases. Results: Patients with alcohol withdrawal syndrome showed a lower prevalence of liver cirrhosis and a higher prevalence of alcoholic hepatitis than patients without it. The negative association of alcohol withdrawal syndrome with liver cirrhosis persisted after we adjusted for sex, daily intake, duration, and pattern of alcohol consumption. Alcoholic hepatitis was independently associated with the irregular pattern of alcohol consumption, which was closely associated with severe alcohol withdrawal syndrome. Conclusions: The profile of liver injury is different in heavy drinkers who develop and who do not develop a severe alcohol withdrawal syndrome when admitted to the hospital. [source] Heroin-Administered Mice Involved in Oxidative Stress and Exogenous Antioxidant-Alleviated Withdrawal SyndromeBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2006Bo Xu It is well known that an increase in DA oxidative metabolism leads to increased reactive oxygen species (ROS) formation, and thus, ROS have been frequently associated with neuronal cell death due to damage to carbohydrates, amino acids, phospholipids, and nucleic acids. This study investigated whether there are oxidative stress and effects of exogenous antioxidants in heroin-administered mice. The heroin-dependent mice model was made via intraperitoneal injection. Oxidative damage of DNA, protein, and lipid was measured by analysis of single cell electrophoresis, the 2,4-dinitrophenylhydrazine method, and thiobarbituric acid method respectively. The activities of antioxidative enzymes and total antioxidant capacity were assayed by spectrophotometry. After administration with heroin, the mice not only showed decrease of total antioxidant capacity in serum and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione (GSH) peroxidase in brain, but also exhibited the oxidative damages of DNA, protein and lipid. On the other hand, exogenous antioxidants could restrain the oxidative stress, even alleviate withdrawal syndrome in heroin-administered mice. Our results also imply a possibility that ROS may participate in the whole process of dependence and withdrawal of heroin. Therefore, strategies of blocking oxidative stress may be useful in the development of therapy for opiate abuse. [source] Withdrawal syndrome following cessation of antihypertensive drug therapyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2005G. N. Karachalios Summary In this study, a review of the available information concerning abrupt withdrawal of antihypertensive drug therapy is presented. Abrupt withdrawal of these drugs can produce a syndrome of sympathetic overactivity that includes nervousness, tachycardia, headache, agitation and nausea 36,72 h after cessation of the drug. A withdrawal syndrome may occur after discontinuation of almost all types of antihypertensive drugs, but mostly occurs with clonidine, ,-blockers, methyldopa and guanabenz. Less commonly can produce a rapid increase of the blood pressure to pre-treatment levels or above, or both and/or myocardial ischaemia. Although the exact incidence of the syndrome is not known, it appears to be rare, at least in patients receiving standard doses of the above antihypertensive drugs. The best treatment is prevention. In this study regarding the withdrawal syndrome that follows cessation of antihypertensive drugs therapy, a reference to the abrupt discontinuation of the main categories of antihypertensive drugs is also attempted. [source] Liver Disease in Heavy Drinkers With and Without Alcohol Withdrawal SyndromeALCOHOLISM, Issue 1 2004E. Barrio Abstract: Background: Withdrawal syndrome is a hallmark of alcohol dependence. The characteristics of alcohol consumption, closely related to dependence, could influence the development of alcoholic liver disease. The study aimed to investigate if patients with severe alcohol withdrawal syndrome have a peculiar profile of liver disease. Methods: The study included 256 heavy drinkers (aged 19,75 years, 70.3% males) admitted to an Internal Medicine Department. Patients admitted for complications of liver disease were not included. Severe alcohol withdrawal syndrome (seizures, disordered perceptions, or delirium) developed in 150 patients (58.6%). Alcohol consumption (daily quantity, duration, and pattern [regular or irregular]) was assessed by questionnaire. Liver biopsy was performed in all cases. Results: Patients with alcohol withdrawal syndrome showed a lower prevalence of liver cirrhosis and a higher prevalence of alcoholic hepatitis than patients without it. The negative association of alcohol withdrawal syndrome with liver cirrhosis persisted after we adjusted for sex, daily intake, duration, and pattern of alcohol consumption. Alcoholic hepatitis was independently associated with the irregular pattern of alcohol consumption, which was closely associated with severe alcohol withdrawal syndrome. Conclusions: The profile of liver injury is different in heavy drinkers who develop and who do not develop a severe alcohol withdrawal syndrome when admitted to the hospital. [source] Pregabalin, tiapride and lorazepam in alcohol withdrawal syndrome: a multi-centre, randomized, single-blind comparison trialADDICTION, Issue 2 2010Giovanni Martinotti ABSTRACT Introduction The aim of this trial was to compare lorazepam with non-benzodiazepine medications such as pregabalin and tiapride in the treatment of alcohol withdrawal syndrome (AWS). These drugs were chosen for their inhibitorial effects on the hypersecretion of neurotransmitters usually observed in AWS. Craving reduction and improvement of psychiatric symptoms were the secondary end-points. Methods One hundred and ninety subjects affected by current alcohol dependence were considered consecutively: 111 were enrolled and divided into three groups of 37 subjects each. Within a treatment duration of 14 days, medication was given up to the following maximum doses (pregabalin 450 mg/day; tiapride 800 mg/day; lorazepam 10 mg/day). Withdrawal (CIWA-Ar), craving [visual analogue scale (VAS); Obsessive and Compulsive Drinking Scale (OCDS)], psychiatric symptoms [Symptom Check List 90 Revised (SCL-90-R)] and quality of life (QL-index) rating scales were applied. Results On the CIWA-Ar score, all the groups showed a significant reduction between times (P < 0.001) with a higher reduction for the pregabalin group (P < 0.01) on items regarding headache and orientation. Retention in treatment was lower in the tiapride group (P < 0.05), while the number of subjects remaining alcohol free was higher in the pregabalin group (P < 0.05). Significant reduction between baseline and the end of the treatment was found in all the groups at the OCDS and the VAS for craving, at the SCL-90-R and QL-index (P < 0.001). Discussion All the medications in the trial showed evidence of safety and efficacy in the treatment of uncomplicated forms of AWS, with some particular differences. The efficacy of pregabalin was superior to that of tiapride, used largely in research trials and, for some measures, to that of the ,gold standard', lorazepam. Accordingly, pregabalin may be considered as a potentially useful new drug for treatment of AWS, deserving further investigation. [source] Anabolic,androgenic steroid dependence: an emerging disorderADDICTION, Issue 12 2009Gen Kanayama ABSTRACT Aims Anabolic,androgenic steroids (AAS) are widely used illicitly to gain muscle and lose body fat. Here we review the accumulating human and animal evidence showing that AAS may cause a distinct dependence syndrome, often associated with adverse psychiatric and medical effects. Method We present an illustrative case of AAS dependence, followed by a summary of the human and animal literature on this topic, based on publications known to us or obtained by searching the PubMed database. Results About 30% of AAS users appear to develop a dependence syndrome, characterized by chronic AAS use despite adverse effects on physical, psychosocial or occupational functioning. AAS dependence shares many features with classical drug dependence. For example, hamsters will self-administer AAS, even to the point of death, and both humans and animals exhibit a well-documented AAS withdrawal syndrome, mediated by neuroendocrine and cortical neurotransmitter systems. AAS dependence may particularly involve opioidergic mechanisms. However, AAS differ from classical drugs in that they produce little immediate reward of acute intoxication, but instead a delayed effect of muscle gains. Thus standard diagnostic criteria for substance dependence, usually crafted for acutely intoxicating drugs, must be adapted slightly for cumulatively acting drugs such as AAS. Conclusions AAS dependence is a valid diagnostic entity, and probably a growing public health problem. AAS dependence may share brain mechanisms with other forms of substance dependence, especially opioid dependence. Future studies are needed to characterize AAS dependence more clearly, identify risk factors for this syndrome and develop treatment strategies. [source] Gamma-hydroxybutyric Acid Tolerance and Withdrawal in a Rat ModelACADEMIC EMERGENCY MEDICINE, Issue 7 2003Theodore C. Bania MD Long-term daily use of gamma-hydroxybutyrate (GHB) and related compounds has recently been associated with a withdrawal syndrome. To the best of the authors' knowledge, there are currently no animal models of GHB withdrawal. Objectives: The authors studied and described the effect of chronic dosing of GHB (3,6 days) on tolerance and withdrawal in a rat model. Methods: Rats were administered GHB every three hours via intraperitoneal catheter. Groups of rats (2 per group) were dosed with GHB for either 3 (24 doses), 4 (32 doses), 5 (40 doses), or 6 (48 doses) days. The GHB dose was 0.25 g/kg for doses 1,8, 0.75 g/kg for doses 9,12, 1 g/kg for doses 13,16, 1.25 g/kg for doses 17,24, 1.5 g/kg for doses 25,32, 1.75 g/kg for doses 33,40, and 2 g/kg for doses 41,48. Following the last dose of GHB, the rats were scored using a 16-point ethanol intoxication,withdrawal scale rating spontaneous behaviors, response to handling, grooming, and neurological signs. Lower scores indicate intoxication, while higher scores indicate withdrawal. Scores were recorded at hours 0, 1, 2, 3, 4, 5, 6, 9, 12, and 24. Results:Tolerance: Rats dosed with GHB for more days were less intoxicated one hour after their last GHB dose despite receiving higher doses. Withdrawal: The scores for all rats dosed with GHB increased at hours 4 (p = 0.028), 5 (p = 0.037), 6 (p = 0.007), and 9 (p = 0.024) after the last dose, indicating withdrawal. The scores demonstrated a linear increase dependent upon the number of days of GHB dosing at hours 3 (p < 0.000), 4 (p = 0.004), 5 (p = 0.002), and 12 (p = 0.039) as well as prior to the last dose at hour 0 (p = 0.000). No rats developed seizures. Conclusions: Tolerance and mild withdrawal in rats can be induced by administering intraperitoneal GHB every three hours for 3,6 days. More prolonged dosing and higher doses of GHB may be necessary to induce severe withdrawal. [source] Stopping smoking can cause constipationADDICTION, Issue 11 2003Peter Hajek ABSTRACT Setting Constipation is mentioned occasionally as a possible tobacco withdrawal symptom, but no systematic data have been published on this issue. Design Smokers' clinic patients provided ratings of their level of constipation on three occasions prior to their quit date, and then weekly after they stopped smoking. The total of 1067 participants maintained at least 1 week of continuous abstinence and provided usable data. Findings The three precessation ratings of constipation were stable. After cessation of smoking, the ratings increased significantly (P < 0.01). In 514 patients who maintained continuous abstinence for 4 weeks and provided complete data, constipation peaked at 2 weeks but remained elevated over the whole period. The net proportion of patients affected was 17%, including 9% who were symptom-free at baseline and became very or extremely constipated. In patients on nicotine replacement the increase in constipation, although significant, was less than in patients on bupropion. Conclusions Clinicians treating smokers need to be aware of a possibility that one in six quitters develop constipation, and that for about one in 11 the problem can be severe. Descriptions of tobacco withdrawal syndrome should include constipation. [source] PRECLINICAL STUDY: Is withdrawal hyperalgesia in morphine-dependent mice a direct effect of a low concentration of the residual drug?ADDICTION BIOLOGY, Issue 4 2009Vardit Rubovitch ABSTRACT Withdrawal of opioid drugs leads to a cluster of unpleasant symptoms in dependent subjects. These symptoms are stimulatory in nature and oppose the acute, inhibitory effects of opiates. The conventional theory that explains the opioid withdrawal syndrome assumes that chronic usage of opioid drugs activates compensatory mechanisms whose stimulatory effects are revealed upon elimination of the inhibitory opioid drug from the body. Based on previous studies that show a dose-dependent dual activity of opiates, including pain perception, we present here an alternative explanation to the phenomenon of withdrawal-induced hyperalgesia. According to this explanation, the residual low concentration of the drug that remains after cessation of its administration elicits the stimulatory withdrawal hyperalgesia. The goal of the present study was to test this hypothesis. In the present study we rendered mice dependent on morphine by a daily administration of the drug. Cessation of morphine application elicited withdrawal hyperalgesia that was completely blocked by a high dose of the opiate antagonist naloxone (100 mg/kg). Similarly, naloxone (2 mg/kg)-induced withdrawal hyperalgesia was also blocked by 100 mg/kg of naloxone. The blockage of withdrawal hyperalgesia by naloxone suggested the involvement of opioid receptors in the phenomenon and indicated that withdrawal hyperalgesia is a direct effect of a residual, low concentration of morphine. Acute experiments that show morphine- and naloxone-induced hyperalgesia further verified our hypothesis. Our findings offer a novel, alternative approach to opiate detoxifications that may prevent withdrawal symptoms by a complete blockage of the opioid receptors using a high dose of the opioid antagonist. [source] Neuroendocrine pathways of addictive behaviourADDICTION BIOLOGY, Issue 3-4 2004F Kiefer Alcohol intake is known to modulate plasma concentrations of neuroendocrine peptides. However, recent results suggest that the endocrine system may not only respond passively to alcohol intake but that, vice versa, it also actively modulates alcohol intake behaviour. The most coherent body of data concerns the hypothalamo,-,pituitary,-,adrenocortical (HPA) axis, with low corticotrophin-releasing hormone (CRH) being associated with more intense craving and increased probability of relapse after acute detoxification. Leptin, ,-endorphin and atrial natriuretic peptide (ANP), which indirectly regulate the HPA system, also may modulate the intensity of craving or the intensity of the alcohol withdrawal syndrome. Although most of the currently available data demonstrate association rather than causality between neuroendocrine changes and alcohol-related behaviours, they do provide testable hypotheses and open up perspectives of treating alcohol dependence via manipulation of the neuroendocrine axis. [source] Massage therapy improves the management of alcohol withdrawal syndromeFOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 1 2006Article first published online: 14 JUN 2010 [source] Effects of venlafaxine on ethanol withdrawal syndrome in ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2004Esra Sa Abstract The present study was designed to investigate the effects of venlafaxine, a serotonin and noradrenaline reuptake inhibitor (SNRI), on ethanol withdrawal syndrome in rats. Adult male Wistar rats (187,319 g) were used for the study. Ethanol (7.2%, v/v) was given to rats by a liquid diet for 21 days. Control rats were pair-fed an isocaloric liquid diet containing sucrose as a caloric substitute to ethanol. Venlafaxine (5, 10, 20 and 40 mg/kg) and saline were injected to rats intraperitoneally just before ethanol withdrawal. After the 2nd, 4th and 6th hour of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, agitation, stereotyped behaviour and wet dog shakes were recorded or rated. A second series of injections was given at the 6th hour after the first one, and rats were then tested for audiogenic seizures. Venlafaxine produced some inhibitory effects on locomotor hyperactivity, stereotypic behaviours and wet dog shakes. However, a two-way anova of the data did not indicate any significant effect. It reduced the incidence of the audiogenic seizures at the 6th hour of ethanol withdrawal. Venlafaxine (20 mg/kg) also prolonged the latency of the seizures significantly. Our results suggest that acute venlafaxine treatment has limited beneficial effects on ethanol withdrawal syndrome in rats. [source] Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine-addicted mother: Beneficial effect of dextromethorphanHIPPOCAMPUS, Issue 6 2006San Nan Yang Abstract Infants passively exposed to morphine or heroin through their addicted mothers usually develop characteristic withdrawal syndrome of morphine after birth. In such early life, the central nervous system exhibits significant plasticity and can be altered by various prenatal influences, including prenatal morphine exposure. Here we studied the effects of prenatal morphine exposure on postsynaptic density protein 95 (PSD-95), an important cytoskeletal specialization involved in the anchoring of the NMDAR and neuronal nitric oxide synthase (nNOS), of the hippocampal CA1 subregion from young offspring at postnatal day 14 (P14). We also evaluated the therapeutic efficacy of dextromethorphan, a widely used antitussive drug with noncompetitive antagonistic effects on NMDARs, for such offspring. The results revealed that prenatal morphine exposure caused a maximal decrease in PSD-95 expression at P14 followed by an age-dependent improvement. In addition, prenatal morphine exposure reduced not only the expression of nNOS and the phosphorylation of cAMP responsive element-binding protein at serine 133 (CREBSerine-133), but also the magnitude of long-term depression (LTD) at P14. Subsequently, the morphine-treated offspring exhibited impaired performance in long-term learning and memory at later ages (P28,29). Prenatal coadministration of dextromethorphan with morphine during pregnancy and throughout lactation could significantly attenuate the adverse effects as described above. Collectively, the study demonstrates that maternal exposure to morphine decreases the magnitude of PSD-95, nNOS, the phosphorylation of CREBSerine-133, and LTD expression in hippocampal CA1 subregion of young offspring (e.g., P14). Such alterations within the developing brain may play a role for subsequent neurological impairments (e.g., impaired performance of long-term learning and memory). The results raise a possibility that postsynaptic density proteins could serve an important role, at least in part, for the neurobiological pathogenesis in offspring from the morphine-addicted mother and provide tentative therapeutic strategy. © 2006 Wiley-Liss, Inc. [source] Withdrawal syndrome following cessation of antihypertensive drug therapyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2005G. N. Karachalios Summary In this study, a review of the available information concerning abrupt withdrawal of antihypertensive drug therapy is presented. Abrupt withdrawal of these drugs can produce a syndrome of sympathetic overactivity that includes nervousness, tachycardia, headache, agitation and nausea 36,72 h after cessation of the drug. A withdrawal syndrome may occur after discontinuation of almost all types of antihypertensive drugs, but mostly occurs with clonidine, ,-blockers, methyldopa and guanabenz. Less commonly can produce a rapid increase of the blood pressure to pre-treatment levels or above, or both and/or myocardial ischaemia. Although the exact incidence of the syndrome is not known, it appears to be rare, at least in patients receiving standard doses of the above antihypertensive drugs. The best treatment is prevention. In this study regarding the withdrawal syndrome that follows cessation of antihypertensive drugs therapy, a reference to the abrupt discontinuation of the main categories of antihypertensive drugs is also attempted. [source] Effects of flutamide as a second-line agent for maximum androgen blockade of hormone refractory prostate cancerINTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2007Kenji Nishimura Abstract: We analyzed clinical effects of flutamide as a second-line agent for maximum androgen blockade (MAB) in patients with relapsing prostate cancer who received bicalutamide as the first-line MAB agent. This study included 13 patients with progressive prostate cancer who had relapsed after first-line MAB, with bicalutamide at 80 mg/day. After checking for antiandrogen withdrawal syndrome, they were given flutamide at 375 mg/day as second-line MAB. The effectiveness of that therapy was evaluated by changes in prostatic specific antigen (PSA) levels, with response defined as a decrease of greater than 50% from the start of therapy. We also compared several factors between responders and non-responders. Nine (69.2%) of the 13 patients showed a decrease in PSA levels, of whom five (38.5%) had a greater than 50% decrease and were defined as responders. The median duration of PSA response was 11.0 months (range 5,20 months). Patients who had a longer duration of response to first-line MAB had a significantly greater response to second-line MAB. For advanced prostate cancer patients who progressed on first-line MAB with bicalutamide, flutamide administration as a second-line antiandrogen was found to be relatively effective, especially for those who showed a longer duration of response to the first-line MAB. Our results confirm previous findings that MAB using flutamide is an effective second-line hormonal therapy. [source] Molecular basis for the antiandrogen withdrawal syndromeJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2004Hiroshi Miyamoto Abstract In patients with prostate cancer who manifest disease progression during combined androgen blockade therapy, discontinuation of antiandrogen treatment might result in prostate-specific antigen decline, often associated with clinical improvement. The response called antiandrogen withdrawal syndrome is thus acknowledged as a general phenomenon. However, molecular mechanisms responsible for this syndrome are not completely understood. This article outlines the proposed mechanisms, including alterations of androgen receptor gene and its coregulatory proteins and activation of the signal transduction pathway, and the potential therapeutic approaches based on the specific mechanisms. © 2003 Wiley-Liss, Inc. [source] Behavioural and gene transcription alterations induced by spontaneous cannabinoid withdrawal in miceJOURNAL OF NEUROCHEMISTRY, Issue 1 2003José M. Oliva Abstract This study examined behavioural signs that occur during tolerance development to cannabinoid treatment and hormonal and gene expression alterations induced by spontaneous cannabinoid withdrawal in mice. Tolerance to CP-55,940 treatment developed for hypothermia, ambulatory and exploratory locomotor activity. Cessation of cannabinoid treatment resulted in a behavioural withdrawal syndrome characterized by a pronounced increase in ambulatory activity and rearings. Corticosterone plasma concentrations dramatically increased 24 and 72 h after cessation of cannabinoid treatment. Similarly, an increase (40%) in cannabinoid [35S]GTP,S binding autoradiography was detected on days 1 and 3 of abstinence. Spontaneous cannabinoid withdrawal produced time-related significant alterations in gene transcription: (i) decreased (20%) tyrosine hydroxylase (TH) mRNA levels in the ventral tegmental area and increased (50%) in substantia nigra; (ii) increased proenkephalin (PENK) gene expression more than 100% in caudate-putamen, nucleus accumbens, olfactory tubercle and piriform cortex; (iii) increased (20,40%) pro-opiomelanocortin (POMC) gene expression in the arcuate nucleus of the hypothalamus. These results suggest that spontaneous cannabinoid withdrawal occur after cessation of CP-55,940 treatment. This ,syndrome' includes behavioural, hormonal and gene transcription alterations that seems to be part of the regulation of neuronal plasticity induced by spontaneous cannabinoid withdrawal. [source] Altered Motor Cortex Excitability to Magnetic Stimulation in Alcohol Withdrawal SyndromeALCOHOLISM, Issue 4 2010Raffaele Nardone Background:, Alcohol addiction is a complex brain disease caused by alterations in crucial neurotransmitter systems, including gamma-aminobutyric acid (GABA) and glutamate. These disturbances could be revealed by changes in cortical excitability parameters, as assessed by transcranial magnetic stimulation (TMS). This study was aimed to further investigate the complex pathophysiology of alcohol withdrawal syndrome (AWS). Methods:, Motor cortex excitability was examined in 13 subjects with AWS in a mild predelirial state, in 12 chronic alcoholics and in 15 age-matched control subjects, using a range of TMS protocols. Central motor conduction time, resting and active motor threshold, duration of the cortical silent period, short latency intracortical inhibition (SICI), and intracortical facilitation (ICF) to paired TMS were examined. Results:, Intracortical facilitation was significantly increased in the AWS patients when compared with the chronic alcoholics and the control subjects. The other TMS parameters did not differ significantly from the controls. Administration of a single oral dose of the glutamatergic antagonist riluzole in a subgroup of 8 patients significantly reduced ICF; motor threshold and SICI were not affected by riluzole. Conclusion:, Transcranial magnetic stimulation shows a selective increase in intracortical facilitation after ethanol withdrawal. Our findings support the theory that altered glutamatergic receptor function plays an important role in the pathogenesis of human alcohol withdrawal. This study provides further physiological evidence that antiglutamatergic approaches represent an efficacious alternative for treating alcohol withdrawal symptoms. [source] Liver Disease in Heavy Drinkers With and Without Alcohol Withdrawal SyndromeALCOHOLISM, Issue 1 2004E. Barrio Abstract: Background: Withdrawal syndrome is a hallmark of alcohol dependence. The characteristics of alcohol consumption, closely related to dependence, could influence the development of alcoholic liver disease. The study aimed to investigate if patients with severe alcohol withdrawal syndrome have a peculiar profile of liver disease. Methods: The study included 256 heavy drinkers (aged 19,75 years, 70.3% males) admitted to an Internal Medicine Department. Patients admitted for complications of liver disease were not included. Severe alcohol withdrawal syndrome (seizures, disordered perceptions, or delirium) developed in 150 patients (58.6%). Alcohol consumption (daily quantity, duration, and pattern [regular or irregular]) was assessed by questionnaire. Liver biopsy was performed in all cases. Results: Patients with alcohol withdrawal syndrome showed a lower prevalence of liver cirrhosis and a higher prevalence of alcoholic hepatitis than patients without it. The negative association of alcohol withdrawal syndrome with liver cirrhosis persisted after we adjusted for sex, daily intake, duration, and pattern of alcohol consumption. Alcoholic hepatitis was independently associated with the irregular pattern of alcohol consumption, which was closely associated with severe alcohol withdrawal syndrome. Conclusions: The profile of liver injury is different in heavy drinkers who develop and who do not develop a severe alcohol withdrawal syndrome when admitted to the hospital. [source] A 5-Year Prospective Evaluation of DSM-IV Alcohol Dependence With and Without a Physiological ComponentALCOHOLISM, Issue 5 2003M. A. Schuckit Background: The DSM-III-R removed tolerance and withdrawal as required elements for a diagnosis of alcohol dependence. Although this practice was continued in DSM-IV, the more recent manual asked clinicians to note whether physiological aspects of withdrawal (tolerance and withdrawal) had ever been experienced. Few studies have determined the prognostic meaning of a history of a physiological component to DSM-IV alcohol dependence. Methods: Face-to-face structured interviews were used to evaluate the course of alcohol, drug, and psychiatric problems during the subsequent 5 years for 1094 alcohol-dependent men and women. These subjects had been classified into subgroups at the time of initial interview regarding evidence of tolerance or withdrawal, and all evaluations were based on DSM-IV criteria. At baseline, the application of DSM-IV diagnostic guidelines resulted in 649 (59.3%) individuals having a history of an alcohol withdrawal syndrome, with or without tolerance (group 1); 391 (35.7%) with histories of tolerance but not withdrawal (group 2); and 54 (4.9%) with no lifetime histories of tolerance or withdrawal (group 3). Results: During the 5-year follow-up, both the broad (group 1 plus 2 versus group 3) and narrow (group 1 versus group 2 plus group 3) definitions of physiological dependence were associated with more alcohol and drug problems. However, for most items, this differential primarily reflected differences between groups 1 and 3, with a less impressive effect by group 2. Although no group differences were noted for the rate of independent major depressive episodes, substance-induced depressions did differentiate among groups, a finding also most closely related to the distinction between groups 1 and 3. Conclusions: These data support the prognostic importance of noting the presence of a physiological component in alcohol dependence and indicate the potential relevance of limiting the definition of a physiological component to withdrawal. [source] Withdrawal of corticosteroids in inflammatory bowel disease patients after dependency periods ranging from 2 to 45 years: a proposed methodALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2009S. J. MURPHY Summary Background, Even in the biologic era, corticosteroid dependency in IBD patients is common and causes a lot of morbidity, but methods of withdrawal are not well described. Aim, To assess the effectiveness of a corticosteroid withdrawal method. Methods, Twelve patients (10 men, 2 women; 6 ulcerative colitis, 6 Crohn's disease), median age 53.5 years (range 29,75) were included. IBD patients with quiescent disease refractory to conventional weaning were transitioned to oral dexamethasone, educated about symptoms of the corticosteroid withdrawal syndrome (CWS) and weaned under the supervision of an endocrinologist. When patients failed to wean despite a slow weaning pace and their IBD remaining quiescent, low dose synthetic ACTH stimulation testing was performed to assess for adrenal insufficiency. Multivariate analysis was performed to assess predictors of a slow wean. Results, Median durations for disease and corticosteroid dependency were 21 (range 3,45) and 14 (range 2,45) years respectively. Ten patients (83%) were successfully weaned after a median follow-up from final wean of 38 months (range 5,73). Disease flares occurred in two patients, CWS in five and ACTH testing was performed in 10. Multivariate analysis showed that longer duration of corticosteroid use appeared to be associated with a slower wean (P = 0.056). Conclusions, Corticosteroid withdrawal using this protocol had a high success rate and durable effect and was effective in patients with long-standing (up to 45 years) dependency. As symptoms of CWS mimic symptoms of IBD disease flares, gastroenterologists may have difficulty distinguishing them, which may be a contributory factor to the frequency of corticosteroid dependency in IBD patients. [source] Severe withdrawal syndrome in three newborns subjected to continuous opioid infusion and seizure activity dependent on brain hypoxia , ischemia.PEDIATRIC ANESTHESIA, Issue 10 2006A possible link Summary Background :,The aim of this investigation was to verify whether brain hypoxia represented a risk factor for the occurrence and severity of opioid abstinence syndrome. Methods :,Three newborns who manifested seizure activity as a result of hypoxia, focal brain ischemia, and hypoxia and sepsis, respectively, were compared with 17 neonates who suffered from hypoxia without developing seizure activity. Results :,The first three neonates suffered a severe withdrawal syndrome (a rating on the neonatal abstinence score >17), the others did not. Conclusions :,It is hypothesized that brain hypoxia facilitated the occurrence and severity of the withdrawal syndrome because some key neurochemical processes (such as N -methyl- d -aspartate activation, protein kinase C activation and nitric oxide production) are common to both phenomena. [source] Reports of withdrawal syndrome with the use of SSRIs: a case/non-case study in the French Pharmacovigilance databasePHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2002T. Trenque Abstract The SSRIs can be associated with withdrawal reactions and the objective of this study is to test the existence of an association between reports of withdrawal syndromes with the selective serotonin re-uptake inhibitors in the French spontaneous reports database. All reactions are coded according to the WHO ART dictionary. Cases are reports of reactions of interest (withdrawal syndrome). Non-cases are all reports of reactions other than those being studied. We calculated the odds ratio (OR) as the ratio of the odds of the association of reports of withdrawal syndrome with SSRIs in cases and non-cases. SSRIs are clearly associated with a higher risk of withdrawal syndrome (OR: 5.05, 95% CI: 3.81,6.68) and in particular with venlafaxine and paroxetine (OR: 12.16, 95% CI: 6.17,23.35 and OR: 8.47, 95% CI: 5.63,12.65, respectively). The risk of withdrawal reactions appears to be greater with short half-life drugs such as paroxetine and venlafaxine. The precise mechanisms have not been identified. Copyright © 2002 John Wiley & Sons, Ltd. [source] Effect of crocus sativus L. (saffron) stigma and its constituents, crocin and safranal, on morphine withdrawal syndrome in micePHYTOTHERAPY RESEARCH, Issue 5 2010Hossein Hosseinzadeh Abstract Crocus sativus L. has been shown to interact with the opioid system. Thus, the effects of aqueous and ethanolic extracts of stigma and its constituents were evaluated on morphine-withdrawal syndrome in mice. Dependence was induced using subcutaneous (s.c.) injections of morphine for 3 days. On day 4, morphine was injected 0.5,h prior the interaperitoneal (i.p.) injections of the extracts, crocin, safranal, clonidine (0.3,mg/kg) or normal saline. Naloxone was injected (5,mg/kg i.p.) 2,h after the final dose of morphine and the number of episodes of jumping during 30,mm was considered as the intensity of the withdrawal syndrome. Clonidine, the aqueous and ethanolic extracts of saffron reduced the jumping activity. Safranal was injected (s.c.) 30,mm prior and 1 and 2,h after the injection of morphine. It potentiated some signs of withdrawal syndrome. The aqueous extract decreased the movement in all of the doses (80, 160, 320,mg/kg) and the ethanolic extract decreased it in the dose of 800,mg/kg in open field test. But crocin and the dose of 400,mg/kg ethanolic extract showed no effect on activity in this test. It is concluded that the extracts and crocin may have interaction with the opioid system to reduce withdrawal syndrome. Copyright © 2009 John Wiley & Sons, Ltd. [source] Effect of Rosmarinus of,cinalis L. aerial parts extract on morphine withdrawal syndrome in micePHYTOTHERAPY RESEARCH, Issue 8 2003Hossein Hosseinzadeh Abstract The effect the aqueous and ethanol extracts of Rosmarinus of,cinalis L. aerial parts on morphine withdrawal syndrome was investigated in mice. The aqueous and ethanol extracts induced a signi,cant antinociceptive activity in the writhing test. This activity was inhibited by naloxone pretreatment. Dependence was induced using subcutaneous injections of morphine daily for 3 days. On day 4, morphine was injected 2 h prior to the intraperitoneal injection of naloxone. The number of jumps during the 30 min period after naloxone injection was considered as a measure of the withdrawal syndrome. The results indicated that the aqueous (1.68 g/kg and 2.4 g/kg, i.p.) and ethanol (0.96 g/kg, i.p.) extracts reduced the number of jumps. Phytochemical study indicated that only the aqueous extract of R. of,cinalis has an alkaloid component. It is concluded that the aqueous and ethanol extracts of R. of,cinalis aerial parts could diminish morphine withdrawal syndrome. Copyright © 2003 John Wiley & Sons, Ltd. [source] Cannabis Withdrawal Among Non-Treatment-Seeking Adult Cannabis Users,THE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2006Marc L. Copersino PhD This study investigates the clinical significance of a cannabis withdrawal syndrome in 104 adult, non-treatment-seeking, primarily cannabis users who reported at least one serious attempt to stop using cannabis. Retrospective self-report data were obtained on eighteen potential cannabis withdrawal symptoms derived from the literature, including co-occurrence, time course, and any actions taken to relieve the symptom. Study findings provide evidence for the clinical significance of a cannabis withdrawal syndrome, based on the high prevalence and co-occurrence of multiple symptoms that follow a consistent time course and that prompt action by the subjects to obtain relief, including serving as negative reinforcement for cannabis use. [source] The Effectiveness of Combined Naloxone/Lofexidine in Opiate Detoxification: Results from a Double-blind Randomized and Placebo-controlled TrialTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 4 2003Tracy Beswick BSc. The efficacy of lofexidine/naloxone was compared with lofexidine/placebo in a double-blind, randomized, placebo-controlled trial in 89 opiate-dependent patients. There were no significant differences between the two groups in the proportion of patients completing detoxification or in the length of stay. Patients in the active naloxone group demonstrated gradual reductions in levels of withdrawal and craving over the detoxification period. At completion of detoxification, patients who received naloxone maintained a level of withdrawal consistently lower than that in the placebo group; however, naloxone did not substantially accelerate the resolution of the withdrawal syndrome. Implications for future research are discussed. [source] | ||||||||||||||||||||||||||||