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The efficacy of flupentixol and risperidone were compared in a randomized double-blind study in 153 chronic schizophrenic patients. Flupentixol showed to be not inferior to risperidone concerning schizophrenic negative symptoms at week 8, 16 and 24. Positive symptoms and general psychopathology improved comparably, too. There was a trend in favor of flupentixol concerning the improvement of depressive symptoms and a trend in favor of risperidone concerning the improvement of preexisting parkinsonian symptoms. The study data justify to regard flupentixol as a "partial atypical" antipsychotic.

Objective: The primary aim of this paper was to compare the effects of flupenthixol and risperidone on subjective quality of life and attitude towards medication in chronic schizophrenic patients with mainly negative symptoms. In a spectrum ranging from its typical end "haloperidol" to its atypical end "clozapine", flupenthixol has typical and atypical characteristics., Methods: The effects of flupenthixol versus risperidone were investigated in a multicenter, double-blind trial, whereas subjective quality of life was assessed by means of the EuroQuol-Visual Analogue Scale and the patient satisfaction questionnaire. The attitude towards medication was assessed by means of the Drug Attitude Inventory-30 (DAI-30)., Results: Mean daily dose of study medication was 6.6 (SD 2.9) mg/day flupenthixol and 3.6 (SD 1.2) mg/day risperidone. Both groups showed a significant improvement regarding subjective quality of life and positive attitude towards medication. Especially the categories "control of their thoughts", concentration and "feeling better in general" ameliorated in both groups. In the flupenthixol group, the "ability to cope with stress", "feel more relaxed" and the "ability to achieve something" improved significantly more than in the risperidone group., Conclusions: (1) The spectrum of schizophrenia can be treated effectively with different neuroleptic treatments. (2) Flupenthixol especially improves the ability to cope with stress, the ability to achieve something and feeling more relaxed. (3) Subjective quality of life significantly increased with no difference between the groups., (Copyright 2003 S. Karger AG, Basel)

Gamma-hydroxybutyric acid is a gamma-aminobutyric acid analogue which can be found in the human brain and is believed to be a neurotransmitter in the central nervous system. In animal experiments as well as in humans gamma-hydroxybutyric acid has been shown to alleviate the symptoms of the alcohol withdrawal syndrome. 299 patients, who were admitted to hospital for reasons primarily unrelated to their alcohol dependence, were treated with gamma-hydroxybutyric acid when symptoms of the alcohol withdrawal syndrome occurred. Gamma-hydroxybutyric acid was usually given at a daily dose of 50 mg/kg in 3 divided doses, the clinical course of the patients was followed for 7 days or until discharge from hospital. Patients were 214 men and 82 women aged 18-87 years. The reasons for admission to hospital were frequently internal diseases, neurological/psychiatric problems, trauma or surgery. At the start of gamma-hydroxybutyric acid treatment, tremor was present in 81% of patients, sweating in 76% and unrest in 92%. Symptoms occurred 1-72 hours after admission. The efficacy of gamma-hydroxybutyric acid to ameliorate or suppress the symptoms of the alcohol withdrawal syndrome was judged to be excellent in 57%, good in 34%, fair in 18%, insufficient in 3% of patients. Drug tolerance was judged to be excellent in 79%, good in 17%, fair in 2% and poor only in 1% of patients. Adverse events were rare and mild. It is concluded that gamma-hydroxybutyric acid is an attractive alternative to tranquilizers in the management of the alcohol withdrawal syndrome in hospital.

The aim of this double-blind, comparative study was to assess the efficacy and safety of gamma-hydroxybutyrate (GHB) in ameliorating the symptoms of alcohol withdrawal. Newly admitted alcohol-dependent patients (n = 98) were randomized to receive either clomethiazole 1000 mg daily (CLO group) (n = 33), or 50 mg GHB/kg body wt (n = 33) or 100 mg GHB/kg body wt (n = 32). This dose was administered for 5 days, halved on day 6, and on days 7 and 8 only placebo was given. As CLO is available as capsules and GHB as syrup, a double-dummy method was used to try to ensure blindness. The groups were matched in terms of baseline demographic and alcohol-related variables. There was no difference between the three treatments in ratings of alcohol withdrawal symptoms nor requests for additional medication. After tapering off the active medication, there was no increase in withdrawal symptoms, indicating that physical tolerance did not develop to either GHB or CLO within the 5-day treatment period. The most frequently reported side-effect of GHB was transient vertigo, particularly after the evening double dose.

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 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.

Flupenthixol, with its broad receptor profile, interacts with a variety of dopamine and serotonin binding sites which are important in the neurobiology of alcohol dependence. Its pharmacology, together with encouraging results from both animal studies and clinical trials with cocaine users, led us to postulate that flupenthixol would significantly prevent relapse in detoxified alcohol-dependent individuals. We conducted a prospective, randomized, double-blind, placebo-controlled, multi-centre trial with two parallel groups and appropriate statistical evaluation. Subjects met criteria for moderate to severe alcohol dependence (DSM-III-R), without any concomitant psychiatric disorder. After complete detoxification, 281 women and men received either 10 mg of flupenthixol decanoate or placebo as i.m. injection every second week for 6 months on an out-patient basis, followed by 6 months of follow-up. Efficacy was based on absolute abstinence, with relapse being defined as consumption of any alcohol after inclusion in the study. In contrast to the hypothesis, flupenthixol did not reduce, but was associated with more, relapses. Though well tolerated, relapse rates after 6 months of treatment were 85.2% (flupenthixol) versus 65.5% (placebo), a highly significant difference from the medication. Flupenthixol was also inferior to placebo with regard to other secondary criteria of efficacy (cumulative abstinence duration, relapse rate after 12 months). These results indicate that a 10 mg dose of flupenthixol decanoate does not have a beneficial effect on abstinence maintenance in alcohol-dependent individuals.

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.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Jobst August-Ludwig Boening and Otto Michel Lesch. The presentations were (1) Pharmacological validation of a new animal model of alcoholism, by Rainer Spanagel; (2) Persisting loss of control as main criterion for alcohol addiction in rats and mice, by Jochen Wolffgramm; (3) Role of NMDA receptor subunits associated with protein kinase C in the prevention of alcohol dependence, by Minoru Narita; (4) Long-term follow up of continued naltrexone treatment, by David Sinclair; (5) Pharmacological treatment trials with dopaminergic and serotonergic substances: Myths or facts? by Gerhard A. Wiesbeck; and (6) Methodology and behavioral therapy of the U.S. acamprosate study, by Barbara J. Mason.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Raj Lakshman and Mikihiro Tsutsumi. The presentations were (1) Sialic acid index of apolipoprotein J: A new marker for chronic alcohol consumption, by P. Ghosh and M. R. Lakshman; (2) Microheterogeneity of serum glycoproteins in alcoholics, by M. Tsutsumi and S. Takase; (3) Probing protein-ethanol adducts with combinatorial peptide libraries displayed by filamentous phage, by H. Anni, O. Nikolaeva, and Y. Israel Y; (4) Carbohydrate-deficient transferrin as a marker for heavy alcohol use: What have we learned; Where do we go from here, by R. F. Anton; (5) Sensitivity and specificity of carbohydrate-deficient transferrin in drinking experiments and different patient groups, by O. M. Lesch; (6), Transferrin variants interfere with the measurement of carbohydrate-deficient transferrin, by A. Helender, G. Eriksson, and J-O. Jeppson; and (7) Chronic ethanol on protein trafficking in liver, by P. Marmillot, M. N. Rao, and M. R. Lakshman.

In an excellent methodological approach, the European acamprosate study project showed that acamprosate increases sobriety times. In one randomized prospective study (n = 260) comparing acamprosate and placebo, with a 1-year treatment phase and 1-year follow-up phase, the authors found that acamprosate is effective only in Lesch type I and type II patients. To investigate the possible influence of diagnostic subgrouping, we applied the Lesch typology in a co-work with the main researchers of the UK study. The UK results concerning acamprosate's effects in the types do not mirror the Vienna results, but the numbers of type I and type II patients, retrospectively found as included in the UK centers, were too small for any conclusions. The distribution of the types points to the fact that too many type III and IV patients had been included to give acamprosate the chance to be effective. Following our typology and also these studies, we developed special treatment approaches. For relapse prevention studies, the cumulative abstinence duration together with the Lesch typology seems to be promising., (Copyright 2001 National Science Council, ROC and S. Karger AG, Basel)

A considerable number of animal studies on the effects of dopaminergic agents on alcohol intake behavior have been performed. Acute alcohol administration in rats induces dopamine release in the caudate nucleus and in the nucleus accumbens, an effect related among others to reinforcement. It has been repeatedly suggested that D1 and D2 receptor activation mediates reward. As alcohol consumption and dopaminergic transmission seem to have a close relationship, all kinds of dopaminergic agents may be regarded as putative therapeutics for preventing relapse. In a prospective European double-blind multicenter clinical trial, comparing the D1, D2, D3 antagonist flupenthixol and placebo in 281 chronic alcohol-dependent patients (27.4% women), the application of the Lesch typology made an outcome differentiation possible. It could be shown in which patients flupenthixol administration was followed by a significantly higher relapse rate and in which patient groups no differences were found when compared to placebo., (Copyright 2001 National Science Council, ROC and S. Karger AG, Basel)

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.

Objectives: The aim of this study was to examine the relationship between alcohol consumption and postural control in alcohol-dependent patients., Material and Methods: Posturographic measurements were performed in 82 abstinent patients and in 54 healthy controls. The findings in the patients were compared with those in the controls as well as with the daily alcohol consumption, the consumption during 6 months before the admission for alcohol withdrawal therapy and the estimated lifetime alcohol consumption., Results: Postural control was impaired in alcohol-dependent patients compared to healthy controls. This impairment was related with the lifetime alcohol consumption, but not with the alcohol consumption per day and prior to admission, respectively. Comparing healthy controls, and alcohol-dependent patients with an estimated lifetime alcohol consumption of < 1000 kg and > or = 1000 kg revealed a significant increase in 6 of 8 sway parameters. Furthermore, the lifetime alcohol consumption increased significantly from patients with normal posturographic and clinical findings to those with abnormalities in both examinations., Conclusion: This study suggests that postural imbalance in abstinent alcohol-dependent patients is related to the lifetime alcohol consumption.

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.

Mnestic disturbances in alcoholics may be related to cholinergic deficiency as well as to central nervous system inactivation. After instillation of tropicamide, cholinergic receptors are blocked and pupillary dilatation occurs. It is assumed that the more severe the cognitive deterioration, the wider the pupillary dilatation. Pupillary oscillations reflect central activation. Changes of pupillary diameter after topical instillation of tropicamide and pupillary oscillations were measured in 44 alcohol-dependent patients aged 40-55 years, diagnosed according to the DSM-III-R as severe alcoholics (>7 symptoms), having been abstinent for at least 3 weeks (objectively tested with carbohydrate-deficient transferrin), compared with 18 healthy controls. The pupillary diameter of the left eye was measured eight times within 103 min, as were pupillary oscillations. Using Fourier analysis, the amplitudes of oscillations were measured in five frequency bands and the sum of the frequency bands was calculated. In addition, central activation was measured during a calculation test at 3 and 103 min. The pupillary dilatation of 22% in alcoholics compared to 14% of normal controls after tropicamide raises the question of a cholinergic deficit in alcohol dependence. With regard to basic activation, measured by Fourier analysis of pupillary oscillations, alcoholics demonstrated significantly lower power (sum of the frequency bands) than controls at baseline and at 3, 20, and 40 min (P < 0.01) as well as at 60, 80, 100, and 103 min (P < 0.05). After a cognitive task, a difference between alcoholics and healthy controls was found at 3 min. Alcoholics showed lower basic activation and decreased cognitive activation. By means of cross-validation, a differentiation between alcohol-dependent patients (n = 44 and n = 42 respectively) and normal controls (n = 18) was possible.

Several studies have shown that psychiatric disorders are common in nursing homes, but information on the course of psychiatric morbidity shortly after admission is still lacking. Therefore, we interviewed 262 residents of Austrian nursing homes within 2 weeks following admission, and a second time after 6 months. Using the Clinical Interview Schedule and its case criteria, prevalence was 76.3% at admission, and 69.9% 6 months later. In the intervening period, the mortality rate was markedly higher among psychiatric cases, and the incidence of new psychiatric cases (5.9%) was slightly lower than the rate of remission (8.6%). At both assessments, organic mental illness was the most frequent diagnosis. Nursing home residents suffering from psychiatric disorders were treated predominantly by general practitioners applying a psychotropic drug regimen.

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.

Cocaine abuse as a risk factor for acute cerebrovascular events has received too little attention, in particular in young patients. Cocaine hydrochloride causes mainly intracerebral and subarachnoidal bleeding, while crack (freebase) causes intracranial hemorrhage and ischemic infarctions with equal frequency. Although no specific antidote is known, an attempt should be made to detect the substance or its metabolites in the urine so as to provide optimal management, and encourage the patient to seek expert counselling.

Human urine samples were examined for the occurrence of formaldehyde-derived tetrahydroisoquinolines and tetrahydro-beta-carbolines generated by condensation of the methanol oxidation product with biogenic amines. Positive results were obtained for the tryptamine condensation product 1,2,3,4-tetrahydro-beta-carboline and the serotonine condensation product 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline as well as for the condensation products with tyramine, dopamine, adrenaline and noradrenaline 1,2,3,4-tetrahydroisoquinoline, 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, N-methyl-4,6,7-trihydroxy-1,2,3,4-tetrahydroisoquinoline, 4,6,7-trihydroxy-1,2,3,4-tetrahydroisoquinoline, and the metabolite 6-methoxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline. Negative results were obtained for N-methyl-1,2,3,4-tetrahydroisoquinoline and 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, N-methyl-1,2,3,4-tetrahydro-beta-carboline, 6-methyl-1,2,3,4-tetrahydro-beta-carboline, and 6-methoxy-1,2,3,4-tetrahydro-beta-carboline in samples of chronic alcoholics as well as in the urine of healthy volunteers. No correlation between alcohol ingestion or state of alcoholization could be demonstrated.

A total of 728 patients admitted to the medical, gynaecological and surgical departments of one urban and one rural general hospital in Austria were investigated for psychiatric morbidity. Using the Clinical Interview Schedule and its case criteria, the prevalence of psychiatric morbidity was found to be highest in medical departments (38.2%), followed by surgical departments (32.5%), and lowest in gynaecological departments (20.7%). Among medical and surgical patients, dementia and substance abuse disorders were the most frequent psychiatric categories, while in gynaecological departments neurotic disorders showed the highest frequency. For the sample as a whole, single status (i.e. unmarried, widowed or divorced), lower social class and rural catchment area of the general hospital predicted a high prevalence of psychiatric morbidity in a logistic regression analysis, while complications of childbirth, pregnancy or the puerperium, and diseases of the skin or the musculoskeletal system showed a negative association with psychiatric illness.

We investigated %CDT (carbohydrate-deficient transferrin) in 92 ethanol-intoxicated alcohol-dependent patients after consecutive admission to hospital and followed the for 28 days under controlled conditions. At admission, 63% (58 patients) showed elevated CDT (> 2.5%) and 34 patients (37%) had normal CDT levels (< 2.5%). No correlation of the %CDT values to alcohol-related disabilities, severity of the withdrawal syndrome, alcohol-drinking pattern before admission, or several other factors was found. The sensitivity of GGT (gamma-glutamyl transferase) was 58% for the same group of patients. Levels of %CDT decreased during the 28 days following abstinence, whereby we could separate four statistically different groups of "CDT decrease'. In two of these groups, comprising most of the cases studied, normal %CDT levels were reached after 14 days of abstinence. Those patients with %CDT levels exceeding the upper normal level after 14 days of sobriety, showed a decrease during the following 14 days to levels of 2.55-2.61%.

We investigated the usefulness of the laboratory marker of alcohol consumption carbohydrate-deficient transferrin (CDT) in 101 consecutively admitted patients in a surgical and internal medical ward of a hospital in a rural wine-growing area. Four major aspects were considered: the influence of liver disease, the method of expression of CDT values (relative % vs absolute units/1), level and pattern of alcohol consumption and comparison with y-glutamyl transferase (GGT). The results show that %CDT is a more valuable discriminating marker of high alcohol consumption than absolute CDT values and its usefulness in this respect is independent of changes in serum total transferrin levels, as in liver disease. Sensitivity and specificity of % CDT were 70 and 98% respectively, compared with 65 and 83% respectively for GGT.

This paper reports the results of a 3-week drinking experiment in 51 healthy male subjects, examining the value of %CDT (carbohydrate-deficient transferrin) in the context of different levels of alcohol intake. All healthy persons were urine-tested drug-free and underwent daily breath alcohol tests for the 7 days preceding, and during the whole 3 weeks of, the experiment. Subjects were divided into five groups, consuming different amounts of alcohol daily over a 3-h period in the presence of the investigators. The five groups consisted of 10, 9, 10, 16 and 6 subjects respectively and consumed a daily dose of ethanol of 20, 40, 60, 80 and 80 g respectively for 3 weeks. No significant changes in %CDT were detected in most subjects, even in the 80 g alcohol-consuming groups. The results suggest that CDT is not sensitive for the detection of short-term heavy drinking by healthy subjects.

Specific laboratory tests can be used to identify patients who are alcohol-dependent. The laboratory values of a number of biological 'markers', including carbohydrate-deficient transferrin, are often elevated in cases of chronic and acute alcohol abuse. Trait markers reflect a predisposition for alcoholism; state markers reflect actual alcohol consumption. It has been suggested that state markers can be subdivided into screening and relapse markers, and even further subdivided into pre-relapse markers, i.e. craving markers. We hypothesize that methanol metabolism and the presence of condensation products in the blood may serve as state and pre-relapse markers for alcoholism. Since the sensitivities and specificities of laboratory screening tests vary, and an absolute marker for alcoholism has yet to be identified, research in the area of biological markers for alcoholism should continue.

In recent years, the term 'chronic alcoholism' has had a meaning that is more descriptive than diagnostic. Several subtypes of alcoholism have been established and are now a necessary tool for studying therapy outcome. Alcohol-dependent patients can be subtyped based on clearly assigned dimensions (e.g. biological, sociological and psychological disturbances). Craving and the underlying disturbance must be treated. The number of pharmacological agents that may reduce alcohol intake has increased recently. We conducted a prospective long-term study based on four subtypes of alcohol-dependent patients to assess the efficacy of acamprosate. Our findings demonstrate that these patient subtypes are relevant to outcome in trials of pharmacological agents. We strongly recommend subtyping alcohol-dependent subjects in future trials, because the usefulness of effective drugs could be overlooked when they are tested in a heterogeneous population.

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.

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.

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.

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.

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 term alcoholism or alcohol dependence has acquired a broad range of meanings. The Plinius Maior Society herewith presents new classificatory considerations and suggests additional recording of special dimensions according to the individual hypothesis and design of a study.

Proceeding from the hypothesis that auditory hallucinations in psychotic patients have another biological basis than hallucinations provoked by hypnotic suggestion in healthy persons, we performed a symptom-comparative study by means of 99mTc-HMPAO single photon emission computed tomography. The results confirm the importance of pathogenesis in symptom-oriented psychiatric research.

Drug use in a given population, whether justified by a medical prescription or not, is a subject that is often emotionally rather than objectively discussed. In this study, objective data from the Austrian population are collected in order to provide a more comprehensible view of that complex phenomenon: drug use, abuse or addition seem to relate to various factors such as gender, age, profession and local differences. Physician's role in drug use in more or less important, depending on the nature of the substance. Indeed, tranquillizers and hypnotics are medically prescribed drugs although laxatives, geriatric and homeopathic medicines are rarely prescribed by a physician. However, these factors could account for only a part of this subject and other research should focus on the relations between physician, patient and the drug.

Since Magnus Huss introduced the diagnosis of 'chronic alcoholism' into medical literature in 1849, two unsolved problems concerning classification have remained: (1) Differentiation between problem drinkers and chronic alcoholics fluctuates, whereby the cut point of differentiation between abuse and addiction remains differently defined by different authors. Some authors view alcohol-induced damage as a building-stone of diagnosis of chronic alcoholism whereas other authors define these damages as illnesses developed as a consequence of chronic alcohol intake. This fact is also mirrored in the different definitions of chronic alcoholism by different classification systems, like ICD-9, DMS-III or DMS-III-R. Valid and reliable questionnaires, like the Munich Alcoholism Test or the Problem Drinking Scale did not succeed in solving this problem of definition, either. (2) The fact that chronic alcoholics are sick--in the sense of a biological-medical approach--is undoubted. Our research group was able to prove that chronic alcoholic patients metabolize methanol in a different way from that of healthy persons. The biological, sociological and psychopathological heterogeneity of this illness has been stressed for more than a century. A prospective long-term study carried out over 4-7 years has led to the development of a new typology in chronic alcoholism that is able to differentiate subgroups of chronic alcoholic patients cross-sectionally in a clinical, biochemical and neurophysiological way. Diagnosis according to this typology qualitatively differentiates patients in many spheres other than drinking behavior. These subgroups also require correspondingly modified therapeutic strategies.

Concrete cross-sectional studies of the organic brain syndrome, carried out periodically, attempt to establish for the parameters evaluation of substrate damage--and different noopsychopathological rating-scales for the measurement of brain capacity impairment. Beyond the level of the purely correlative-statistical point of view of the relationship between parameter and score changes, demanding for a quantitative model which could provide not only a description, but also an explanation for such a relationship. The fact that there can only be a question here of a "quantitative causality" embracing non-specificity of toxic substances and relative to acute and chronic diffuse organic brain syndromes. It results, that quantitative causality meets the requirements of an exponential function model and that one can validate such models through correlative-statistical methods. This has already been carried out by Ball and Taylor.

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.

In a symptom-oriented study 17 patients suffering from chronic auditory hallucinations were investigated by means of 99mTc-HMPAO-SPECT and compared with healthy controls. The results confirm the relative frontal hypoactivity in junction with a relative hyperactivity in the basal ganglia and mesial limbic structures in both hemispheres found in a previous pilot study in auditorily hallucinating patients. Our results should fortify the symptom-oriented approach in psychiatric research.

This paper presents a literature review as well as a study in 13 patients suffering from delusion of infestation. Symptoms found in MMPI are related to clinical experience. Our results suggest the distinction of three different groups of these patients: 1. Patients with predominantly hypochondric traits, with a distinct conviction to suffer from a severe, physical illness that is often looked at as incurable (hypochondriacal delusion of parasitosis). 2. Patients with paranoid symptoms and without hypochondric apprehensions. These patients usually hopelessly fight against their parasites, that impair their sphere of existence. Physical illness is denied. ("delusion of infestation"). 3. Patients with signs of both, hypochondrical as well as paranoid delusions ("hypochondriacal delusion of infestation").

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)

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.

The effects of biologically active light (BL) on subjective and objective quality of sleep and awakening, as well as circadian rhythms in cortisol, temperature and well-being were studied in 10 hospitalized normal female volunteers as compared with partial sleep deprivation (PSD). After 2 adaption days, three 24-hour periods were recorded before (baseline), during (intervention) and after (recovery) treatment with BL (exposure between 5.00-9.00 p.m. and 6.00-9.00 a.m.; light sensitivity: 2,800 lx at eye level) and PSD (1.30-6.00 a.m.). Somnopolygraphic investigations demonstrated a significant improvement in sleep maintenance both after BL and PSD, while sleep induction improved only after PSD. Subjectively experienced sleep quality increased after both treatments. However, subjective and objective awakening quality (objectivated by means of psychometric test battery) was improved by BL only, while PSD produced no changes or even a deterioration. Cortisol levels tended to be lowered by BL, while the troughs increased after PSD; there was also an earlier rise in cortisol levels after PSD than BL. No significant differences were found in regard to temperature. Subjectively experienced well-being tended to improve after both interventions. Our findings concerning the beneficial effect of BL on objective and subjective quality of sleep and awakening in normals encourages us to initiate a single-dose study with BL in depressed patients.

In 34 patients suffering from delusional parasitosis the relevance of an accurate differential diagnosis with respect to pharmacological treatment was investigated. Under a psychopharmacological therapy of the delusion's additional psychiatric symptomatology in 17 patients (50%) a full remission and in other 5 patients an improvement of the delusional symptoms was observed. The unexpected high recovery-rate is explained by the fact that all of the patients with additional depression showed a reduction also of the delusional symptomatology after a treatment with antidepressants. In contrast to that, patients with organic brain syndromes underlying the delusions had a significant worse outcome, which seems to be caused by the considerable lack of effective psychopharmacological treatment of such states. The results indicate that an accurate psychiatric differential diagnosis is of great importance for the psychopharmacological therapy of patients suffering from delusional parasitosis. In this context the Viennese decision-tree for delusional syndromes is discussed.

From the supposition that there exists a possible connection between certain psychopathological symptoms, and/or syndromes (e.g., hallucinations) and regional cerebral dysfunction, patients suffering from auditory and tactile hallucinations were investigated, in a symptom-oriented study, using the method of technetium-99m-Hexamethyl-propylenamine Oxime (99m-Tc-HMPAO)-Single Photon Emission Computed Tomography (SPECT) and compared with normal controls. The results support Jackson's hypothesis to the effect that hallucinatory phenomena will primarily occur when the normally inhibitive influence of the upper cortical centers over the lower brain structures diminishes, resulting in relative hyperactivity in the basal regions. In addition to the brain activity-changes generally observed in hallucinating patients, it was possible to identify regional cerebral blood flow (rCBF)-distribution patterns characteristic in certain forms of hallucinatory phenomena, i.e., a significant increase of activity in the hippocampal regions (including hippocampus, parahippocampus, and amygdala) only in patients with auditory hallucinations, and a significant reduction of rCBF in the inferior temporal regions in patients with tactile hallucinations.

We investigated 37 chronic schizophrenic patients with two objective rating scales (AMDP and Brief Psychiatric Rating Scale; BPRS) and compared the questioned symptoms with the Frankfurter Beschwerde Fragebogen (FBF), a questionnaire for subjective complaints which are close to the uncharacteristic 'basic' symptoms of schizophrenic patients. It was pointed out that the questions in the FBF relate mainly to uncharacteristic symptoms like disturbances of perception, concentration, attention, perceiving, and memory. These subjective symptoms of the FBF show a few correlations with the AMDP/BPRS rating. The total score of the FBF gave no further information about social functioning of patients with cognitive disturbances.