Pupillary response to percutaneous auricular vagus nerve stimulation in alcohol withdrawal syndrome: A pilot trial.

BACKGROUND: Autonomic symptoms in alcohol withdrawal syndrome (AWS) are associated with a sympathetic-driven imbalance of the autonomic nervous system. To restore autonomic balance in AWS, novel neuromodulatory approaches could be beneficial. We conducted a pilot trial with percutaneous auricular vagus nerve stimulation (pVNS) in AWS and hypothesized that pVNS will enhance the parasympathetic tone represented by a reduction of pupillary dilation in a parasympatholytic pharmacological challenge. METHODS: Thirty patients suffering from alcohol use disorder, undergoing AWS, and stable on medication, were recruited in this open-label, single-arm pilot trial with repeated-measure design. Peripheral VNS (monophasic volt impulses of 1 msec, alternating polarity, frequency 1 Hz, amplitude 4 mV) was administered at the left cymba conchae for 72 h, followed by pupillometry under a tropicamide challenge. We assessed craving with a visual analog scale. We used pupillary mean as the dependent variable in a repeated-measures ANOVA (rmANOVA). RESULTS: A repeated-measures ANOVA resulted in a significant difference for pupillary diameter across time and condition (F(2,116) = 27.97, p < .001, ηp2 > .14). Tukey-adjusted post hoc analysis revealed a significant reduction of pupillary diameter after pVNS. Alcohol craving was significantly reduced after pVNS (p < .05, Cohen's d = 1.27). CONCLUSION: Our study suggests that pVNS activates the parasympathetic nervous system in patients with acute AWS, and that this activation is measurable by pupillometry. To this end, pVNS could be beneficial as a supportive therapy for AWS. Potential confounding effects of anti-craving treatment should be kept in mind.

[Addiction in DSM V and ICD-11 state of the art]. / Die Diagnose Abhängigkeit im DSM V und ICD-11 zum jetzigen Stand der Forschung.

Diagnoses are made for identifying rather homogeneous groups of patients being thereby relevant for research and for therapy. Therefore diagnostic manuals, like the DSM-IV and the ICD-10 are subjected to changing knowledge derived from research on one hand and to changes of clinical necessities. The diagnosis of substance related disorders, published for DSM-IV in 1994 and for the ICD-10 in 1992, has proven of value for epidemiological research and economic validation. In spite of these advantages the concept has prove to be too broad and rather unspecific for research, specific therapeutic strategies and for defining an illness course. During the last 20 years research has yielded many criteria of interest, which never entered DSM IV or ICD-10, remaining therefore on the level of single items, which are nowadays additionally assigned to all patients (like e. g. early versus late onset) or on the level of typologies (like e. g. Lesch's typology) demanding different treatments. To give an example: acamprosate has lasting relapse preventing effects in Lesch types I and II, while naltrexone is effective in types III and IV. For rendering an expertise in Germany, the referring literature recommends to utilize Lesch's typology additionally to the ICD-10 diagnosis, especially when prognosis or therapeutic strategies are demanded. Since 1999 different expert groups strive for including new criteria into DSM IV and ICD-10. The revised manuals should include easily assignable items for severity of different arrays (time illness onset, co-morbidity, withdrawal symptoms, bridge symptoms and neurological sequela). Different therapy stages (e. g. withdrawal or relapse prevention) need a different weighting of individual symptoms (e. g. degree of intoxication, severity of withdrawal is needed for acute treatment, while an assignment of co-morbidity and personality factors is necessary for relapse prevention). This quantifier is rendered by Lesch's typology, which is available in the form of a computer programme, based on a decision tree (see also www.ausam.at - Typology according to Lesch). Non substance related disorders should enter other diagnostic categories, like e. g. impulse control disorders. A revised diagnostic classification suggests presently offered therapeutic strategies to follow up with necessary modifications. A tailor made therapy according to subgroups can result in better long term performance of therapies offered to persons suffering form substance related disorders.

The connection of temperament with ADHD occurrence and persistence into adulthood - An investigation in 18 year old males.

BACKGROUND: This study intended to determine whether certain traits of temperament are associated with former and current ADHD symptomatology in a non-clinical sample of 18 year old males. METHODS: We performed a cross sectional descriptive study of 3280 men during the examination for military service. The investigation included a socio-demographic questionnaire, screening for substance abuse, temperament (TEMPS-M), past (WURS) and current (ADHD symptom checklist) ADHD symptomatology. RESULTS: We found a correlation of cyclothymic (p<.001), irritable (p<.001) and anxious (p<.05) temperament with occurrence and severity of past and present ADHD symptomatology. No significant correlation has been detected for hyperthymic and depressive temperament. Judged retrospectively, ADHD symptoms were strongly consistent over time. LIMITATIONS: The sample consists of men only. These had to be fit enough to be enlisted for military service; men with severe mental or physical disorders were thus excluded. Furthermore, the cross-sectional study design does not allow making conclusions about the temporal relationships between ADHD symptoms and substance misuse. CONCLUSIONS: These results indicate that a temperament based approach towards those affected by ADHD might be useful. Subtyping ADHD by integrating temperament profiles in diagnosis and treatment of the disorder could help explain some of the heterogeneity of the disease.

Carbohydrate deficient transferrin for detection of alcohol relapse after orthotopic liver transplantation for alcoholic cirrhosis.

Early diagnosis and monitoring of an alcohol relapse in patients after orthotopic liver transplantation for alcoholic cirrhosis is of importance for the long-term outcome. A prospective study of 97 patients who underwent orthotopic liver transplant for alcoholic cirrhosis has been performed. All of the recipients considered for analysis survived for at least 3 months and were under the care of one specialist psychologist. Mean follow-up amounted to 48.5+/-1.4 months. The rates of alcohol relapse at 1 and 3 years after orthotopic liver transplant were 6 and 9%, respectively. Carbohydrate-deficient transferrin is a biological marker for alcohol abuse independently of liver disease and has been used for the first time ever in liver graft recipients. A total of 830 values were included prospectively in the study population. Detection of alcohol relapse had a sensitivity of 92% and a specificity of 98%. Changes in carbohydrate-deficient transferrin levels indicated clandestine and sporadic drinking after transplantation. Furthermore, clinical events were not found to influence carbohydrate-deficient transferrin, either in patients with or without alcoholic relapse. In our opinion, carbohydrate-deficient transferrin is a useful screening marker for alcohol relapse in patients after orthotopic liver transplant for alcoholic cirrhosis, to select those patients who need special attention from the psychologist.

Hypnotic catalepsy-induced changes of regional cerebral glucose metabolism.

In an attempt to elucidate the physiological basis of hypnosis, we investigated the changes of whole-brain and regional cerebral glucose metabolism, from a state of resting wakefulness to a hypnotized state with whole-body catalepsy, using positron emission tomography and the 2[18F]fluorodeoxyglucose method in 15 highly hypnotizable adults. Neither the random order of study conditions nor any of the other experimental factors had a measurable effect, and there was no statistically significant global activation or metabolic depression. However, repeated measures analysis of variance revealed a statistically significant heterogeneity of symmetric regional responses: Mainly the occipital areas, including visual and paravisual cortex, became relatively deactivated, while some metabolic recruitment was found in structures involved in sensorimotor functions. The observed pattern of changes of regional cerebral activity corresponds with the shift of attention away from normal sensory input that hypnosis is known to produce.

Salsolinol and norsalsolinol in human urine samples.

The tetrahydroisoquinoline alkaloids salsolinol and norsalsolinol were found in human urine samples in concentrations ranging from 0.1 to 29.5 ng/ml. Great interindividual variation was found in urine levels of these alkaloids in a collection of chronic alcoholics and in a group of nonalcoholics. Thus, levels of the individual alkaloids are insufficient markers for distinguishing between alcoholics and nonalcoholics. However, by using the concentration ratio of norsalsolinol and salsolinol, the so-called dopamine-aldehyde adduct ratio (DAAR), significant differences between alcoholics (median 1.3) and nonalcoholics (median 0.6) were detected. This concentration ratio could serve as a marker for the processor state of the dopaminergic system.

Sensitivity and specificity of carbohydrate-deficient transferrin in drinking experiments and different patients.

Information provided by patients about the amounts of alcohol they drink may often be too subjective and therefore unreliable. Because of the possible serious consequences of interactions between alcohol and medication, reliable laboratory test markers for alcohol consumption are needed. Carbohydrate-deficient transferrin (CDT) is at present the best available objective measure of drinking behavior. During a withdrawal trial, 92 alcohol-dependent patients who had been admitted to a hospital in an ethanol-intoxicated state were monitored over the following 28 days by using the percent carbohydrate-deficient transferrin (%CDT of total transferrin) (%CDT) method. At the time of admission, 63% showed elevated %CDT levels. After a subsequent period of abstinence, a decrease in %CDT levels was apparent in four different groups of patients, whereas in two groups, comprising the greatest number of patients, normal %CDT levels were evident after 14 days of abstinence. In patients whose CDT levels were very high at study initiation, it took at least 21 to 28 days--and sometimes longer--for CDT to decrease to the radioimmunoassay (RIA) %CDT test cutoff point of 2.5. In a further study of 56 male alcohol-dependent patients, we measured liver enzyme concentrations, mean corpuscular volume (MCV), and four CDT variants on the first day of evidence of withdrawal syndrome. We found a significant correlation between results on the Munich Alcoholism Test (MALT) and MCV levels; among gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels; and among all four CDT variants. A cluster analysis yielded three clusters: (1) GGT, AST, and ALT levels; (2) MCV levels and MALT results; and (3) all CDT measurement variants. We conclude that these three clusters measure different detriments to the patient and that all available CDT variants are commensurate.

The course of alcoholism. Long-term prognosis in different types.

The disease concept of alcoholism was first introduced into the medical literature by Magnus Huss in 1984. Since that time many authors have attempted to define therapy-related sub-groups of chronic alcoholics but have been unsuccessful until now because alcoholism represents a complex development and becomes apparent in various clinical pictures. As the method of cross-sectional investigations does not seem to be able to produce reliable results, we performed a prospective long-term study of 444 alcoholics. The methodological claims in literature were taken into consideration like selection criteria, programmes and goals of therapy, follow-up rate and time, etc. Careful observation of the pertinent parts of the pathogenetic pathway leading to chronic alcoholism enabled the authors to establish 4 sub-groups of alcoholics relevant for treatment.

Distribution of GC-subtypes in a series of chronic alcoholics.

This article reports on the distribution of GC-(group specific component) subtypes in a series of chronic alcoholics (N = 100). The determination of the phenotypes was carried out by immunoblotting. The results are interpreted and discussed. We observed no association between alcoholism and GC-subtypes.

The reduction of alcohol consumption with novel pharmacological intervention.

The development of pharmacological agents in treating alcoholism represents one of many different ways to suppress alcohol intake. Regarding the hypothetical involvement of different neurochemical systems in "alcohol craving", specific substances have been examined in animals models (especially rats) and increasingly in man. Promising results in reducing "alcohol craving" were described in the use of different kinds of chemical substances. "Craving" therefore can hardly be explained on the basis of a deficit in only one neurochemical (neurotransmitter) system. This conclusion is supported by the data. The efficiacy of many anti-craving substances described in smaller studies must first be confirmed in clinical studies on a wider scale.

[Methanol--an up-to-now neglected constituent of all alcoholic beverages. A new biochemical approach to the problem of chronic alcoholism]. / Methanol--Ein bisher verkannter Bestandteil aller alkoholischen Getränke. Eine neue biochemische Annäherung an das Problem des chronischen Alkoholismus.

Alcoholism is usually understood as ethanolism. There is some evidence that its oxidation product acetaldehyde may condense with endogenous amines to form tetrahydroisoquinoline (TIQ) and - tetrahydro-beta-carboline (THBC) alkaloids which ultimately might be responsible for addiction. In most animal experiments pure ethanol solutions were fed, but chronic alcoholics prefer normal alcoholic beverages, and it is widely ignored that all these beverages without exception also contain methanol. Its metabolite formaldehyde is a much more potent reaction partner for TIQ and THBC formation than acetaldehyde. As our findings in chronic alcoholics proved that these persons in contrast to healthy subjects are able to oxidize methanol despite high ethanol levels, there must be a continuous leakage of formaldehyde. And it seems possible that methanol plays a more significant role in the pathophysiology and possibly the etiology of chronic alcoholism than ethanol.

[MAO-(monoamine oxidase-)inhibitor plus lithium. 1. Choice in psychopathologic rapidly changing bipolar manic-depressive patients (rapid cyclers)]. / MAO-(Monoaminoxidase)-Inhibitor plus Lithium. 1. Wahl bei psychopathologisch rasch wechselnden bipolaren manisch-depressiv Erkrankten ("Rapid cyclers").

Patients resistant to therapy with lithium or lithium plus tricyclic antidepressants were included in our study. They had shown no curtailment of depression, no lessening of the depth of depression nor any improvement in the manic symptoms. Therapeutic medication with lithium, lithium plus tricyclics, neuroleptics and/or tranquilizer had been tried out for at last three years and the episodes of the manic-depressive illness were documented over this period. The diagnosis in the case of these patients was manic-depressive illness, type bipolar I or II. We report one case covering three years of treatment showing the following trend: Psychopathology did not change after quitting anciliary medication and tricyclic antidepressants while lithium intake was continued. A low-dose MAO inhibitor (tranylcypromine 13.7 mg/die) in addition to lithium led to shortened and less pronounced depressive and manic episodes and more prolonged normorhythmic periods. This trend emerged with even greater clarity during the course of the study.

Prevalence of hepatitis G-virus infection in alcohol abusing patients with and without liver cirrhosis.

BACKGROUND: Hepatitis G (GBV-C/HGV) is an RNA-virus belonging to the flavivirus family and is capable of inducing hepatitis in rare cases. Its importance as a co-factor in the pathogenesis of liver disease needs to be clarified. AIMS: To determine the prevalence of HGV in chronic alcoholics with and without liver cirrhosis. PATIENTS: 86 alcoholics, 44 with liver cirrhosis and 42 without liver cirrhosis, were investigated; 93 healthy individuals served as controls. METHODS: Serum was tested for GBV-C/HGV-RNA by reverse-transcription polymerase chain reaction (RT-PCR) and for anti-E2, a marker of resolved GBV-C/HGV infection, by ELISA. GBV-C/HGV-RNA positive samples were sequenced and the GBV-C/HGV subtype determined. RESULTS: Eight out of 86 (9.3%) alcoholics were GBV-C/HGV-RNA positive, as compared to 2 out of 93 (2.2%) healthy controls (n. s.). Twenty-one (24.4%) alcoholics had anti-E2 in serum, whereas this antibody was found in 12 (12.9%) healthy persons only (n. s.). However, significantly more alcoholic patients (33.7%) than healthy controls (15.1%) had past or present contact with GBV-C/HGV (p = 0.006). 11.4% of alcoholic patients with liver cirrhosis and 7.1% of alcoholic patients without liver cirrhosis showed GBV-C/HGV-RNA. 34.1% of alcoholic patients with liver cirrhosis and 16.6% of alcoholic patients without liver cirrhosis had anti-E2. Among the 44 patients with liver cirrhosis, 8 out of 11 (72.7%) patients with variceal bleeding, but only 11 of 33 patients without bleeding had contact with GBV-C/HGV (p = 0.05). Seven out of 8 GBV-C/HGV-RNA positive alcoholics had genotype 2a, 1 had type 1a of GBV-C/HGV. CONCLUSION: Alcoholic patients have a significantly higher contact rate with GBV-C/HGV as compared to healthy controls. Alcoholics with liver cirrhosis tend to be more frequently infected than alcoholic patients without liver cirrhosis. A previous variceal bleeding episode is significantly associated with GBV-C/HGV infection.

[Possible interaction between ethanol and drugs and their significance for drug therapy in the elderly]. / Mögliche Interaktionen zwischen Ethanol und Pharmaka und deren Bedeutung für die medikamentöse Therapie im Alter.

Even though alcohol dependence is not often found in the elderly, alcohol consumption and alcohol abuse are both common. As the elderly also often take medication on a regular basis, this group is at particularly high risk for problems resulting from the concurrent use of these substances. Physical changes as a result of the aging process (e.g. reduction of body water, decrease of hepatic blood flow) and alcohol related diseases can influence the pharmacokinetics and pharmacodynamics of both ethanol as well as other drugs. Alcohol dehydrogenase (ADH), acetaldehydede hydrogenase (ALDH) and cytochrome P450 2E1 are the enzymes responsible for the metabolism of ethanol. These enzymes are also the sites of direct pharmacological interaction between ethanol and other drugs, however, altered effects of medication can also be caused by ethanol adding to or reducing the drug's effect. Although some of these effects result from heavy use of alcohol, others can also occur with moderate use. Interactions have most frequently been described for analgetics, psychopharmacologically active drugs, antihistamines, anticoagulants antihypertensive drugs and antibiotics.

[Does alcohol consumption promote the manifestation of strokes? Considerations on pathophysiology]. / Begünstigt Alkoholkonsum die Manifestation von Schlaganfällen? Uberlegungen zur Pathophysiologie.

Arterial hypertension is the most important risk factor in all types of stroke. The significance of alcohol in the pathogenesis of stroke is less well defined. Chronic alcoholism leads to an elevation of blood pressure. Thus, the association between alcohol and stroke might be the blood pressure effect of alcohol. However, some studies have shown a significant influence of alcohol on the incidence of stroke--especially of intracerebral haemorrhage and subarachnoid haemorrhage--even after adjustment for blood pressure. Many possible pathomechanisms are discussed. Alcohol inhibits aggregation of thrombocytes, and chronic alcohol abuse may induce thrombocytopenia, which could lead to a haemorrhagic stroke. Alcohol withdrawal leads to rebound thrombocytosis. Acute alcohol ingestion induces a decrease in fibrinolytic activity and an increase in factor VIII activity, which enhances the thrombotic potential. Additionally, alcohol increases plasma osmolarity, erythrocyte aggregability, haematocrit and blood viscosity, and decreases deformability of erythrocytes. The effects of alcohol on cerebral blood flow are still under debate; there is a deterioration in autoregulation of cerebral blood flow anyway. In animal studies alcohol induced dose-dependent vasospasm of the cerebral blood vessels, which could be a possible pathomechanism in ischaemic, as well as in haemorrhagic stroke. Chronic alcoholism is the most common cause of secondary non-ischaemic cardiomyopathy, which can lead to cerebral embolism via rhythm disorders or intracardiac thrombus formation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Craving for alcohol and prevention of relapse]. / Alkoholverlangen und Rückfallprophylaxe.

The long term course of alcohol dependence often includes one or several relapses, which can be divided into low (< 5 standard drinks = lapse, slip) and high intake of alcohol with loss of control (relapse). The biological etiology of relapse is derived from different phenomena such as alcohol craving, psychosocial reasons, development of withdrawal symptoms, different primary psychiatric diseases and "addiction memory". Moreover, the metabolism of alcohol itself substantially contributes to alcohol dependence. For about 100 years different definitions for subgroups of alcohol dependence have been described, of which the Lesch typology is internationally acknowledged, especially for medical treatment. This typology differentiates between four types of alcohol dependent patients in which prevention and treatment of relapse should be specific to the primary psychiatric disease of the patient and to alcohol related disabilities. The aim is a long term improvement of sobriety rates of alcohol dependent patients as well as quality of life and life expectancy.

[Cocaine abuse--with special reference to cerebrovascular complications]. / Cocain-Missbrauch--unter besonderer Berücksichtigung zerebrovaskulärer Komplikationen.

The role of drug abuse as a risk factor for cerebrovascular events has been underestimated, particularly in patients with juvenile stroke. The drug most often associated with acute cerebrovascular events is cocaine. After cocaine hydrochloride abuse intracerebral hemorrhages or subarachnoid hemorrhages--predominantly caused by ruptured aneurysms or arteriovenous malformations--are by far the most frequently observed cerebrovascular complications, whereas on abuse with the alkaloidal form ("crack") intracranial hemorrhages and ischemic strokes are encountered with equal frequency. In most cases, the time interval between drug abuse and the cerebrovascular event is less than 3 hours. Several pathophysiological mechanisms are discussed as serving as triggers for the cerebrovascular event, either alone or in combination. No specific antidote to cocaine is known. Nevertheless drug screening (urine analysis) should be performed immediately to allow optimal management of patients with drug-associated acute cerebrovascular events, especially in cases with juvenile stroke.

[Ethanol-independent methanol elimination in chronic alcoholics]. / Ethanolunabhängige Methanolelimination bei chronischen Alkoholikern.

72% of a collective of chronic alcoholics (DSM-III-R, ICD 9), who were admitted under the influence of alcohol in order to undergo alcohol withdrawal, showed a serum methanol concentration (SMC) above 10 mg/l. This level is usually considered to be the one for the detection of regular alcohol consumption. The SMC values were considerably higher in cases where alcoholic beverages with a higher methanol content were consumed rather than the ones lower in methanol. In the majority of patients a decrease of the methanol concentration could only be detected once an individually varying limit concentration of ethanol (0-0.62 g/kg) was reached. There were, however, a few exceptions where the elimination of methanol independent from the ethanol concentration could be seen. Contrasting the general collective, these 'ethanol independent' methanol eliminators showed a much higher serum level of ethanol and methanol at the time of admission. As a sign of addiction, all patients showed increased beta 60 values for ethanol and preferred high proof beverages, which at the same time have high methanol contents.

Lesch typology and temperament in opioid dependence: a cross-sectional study.

AIMS: The first aim of this study is to investigate the impact of different temperaments in opiate dependency patients. The second aim of this study is to define therapy relevant subgroups in opiate addiction for further basic clinical research and therapy. METHODS: In the time period from September to November 2010, 101 patients (72 males and 29 females) which fulfilled the diagnosis of opiate dependency according to DSM-IV-TR were recruited consecutively. All patients were in treatment at the Oum El Nour rehabilitation center/Lebanon (Inpatient and Outpatient groups). Lesch Alcoholism Typology modified for assessment of opiate addicts, and the briefTEMPS-M, Arabic version were used. RESULTS: The organic Type IV group was the most prevalent (48.5%) among the sample followed by the Affective Type III group (41.6%) and the minority represented the two other types (I & II). The organic Type IV group represented the major type in the cyclothymic and anxious temperament. In the contrary the other two groups (I & II) were the minority among the cyclothymics.

Suicidal ideation and temperament: an investigation among college students.

BACKGROUND: Suicide is a major health problem accounting for up to 1.5 percent of all deaths worldwide and represents one of the most common causes of death in adolescents and young adults. A number of studies has been performed to establish risk factors for suicide in patients with psychiatric disorders including temperamental features. This study set out to assess the relationship between suicidal ideation and temperament in young adults. METHODS: A cross-sectional sample of healthy college students (n=1381) was examined using a self-rating questionnaire. Suicidal ideation, social background, educational status, substance abuse, and affective temperament according to TEMPS-M were assessed. Predictors of lifetime suicidal ideation were examined in multivariate logistic regression analyses. RESULTS: Suicidal ideation was reported by 12.5% of all subjects at some point in their life and was higher in nicotine dependents, youth with alcohol related problems and users of illicit substances as well as in youth with lower educational status. Lifetime suicidal ideation was associated with the anxious, depressive and cyclothymic temperament in both sexes and the irritable temperament in males. These results remained significant after adjustment for smoking status, frequency of alcohol consumption, drug experience and educational status in a multivariate logistic regression analysis. LIMITATIONS: The use of self-rating instruments always reduces objectivity and introduces the possibility of misreporting. CONCLUSIONS: Considering the fact that many subjects completing suicide have never been diagnosed with mental disorders it might be reasonable to include an investigation of temperament in screenings for risk of suicide. This might be especially useful for health care professionals without mental health care background.