Biomedical subjects

O M Lesch

Publications and source records attributed to O M Lesch.

At least 19 recordsLinked to original sources

PubMed2003

Gender-related differences in pharmacological relapse prevention with flupenthixol decanoate in detoxified alcoholics.

A study recently finished by our research group elucidated the effectiveness of flupenthixol decanoate (FLX) in maintaining abstinence in detoxified alcoholics. Flupenthixol decanoate is an established antipsychotic drug, which is well known for its mild antidepressant and anxiolytic activity as well as for its minimal sedation at low doses. It blocks dopamine binding at a number of receptor subtypes, primarily at D-1, D-2, D-3 and with less affinity at D4-receptors. It also affects serotonin binding at 5-HT2A and 5-HT2C receptors. In a double-blind placebo-controlled multicenter trial, 77 women and 204 men suffering from moderate or severe DSM-II-R alcohol dependence were randomly assigned to either 10 mg FLX or placebo both injected every second week over a period of 24 weeks (treatment phase) succeeded by a medication-free 24-weeks follow-up period. In the overall analysis the number of patients relapsed after 24 weeks of treatment (=main criterion of efficacy) was significantly higher in the FLX treated group (85.2%) than under placebo (65.5%). However, when differentiating this result according to sex the analysis revealed a gender-related discrepancy: while male patients had an almost 4-fold higher risk to relapse under FLX than under placebo (OR=3.95) this risk was barely elevated for female patients (OR=1.51). A significantly negative outcome due to FLX treatment was restricted to male alcoholics solely. In conclusion, gender-related differences to pharmacological relapse prevention with FLX have probably contributed to a better treatment outcome in women than in men.

Adult↗

PubMed2003

Gender-specific differences in alcoholism: implications for treatment.

Alcohol abuse and alcoholism cut across gender, race and nationality. In general, more men than women are alcohol dependent or have alcohol problems, but women are at greater risk for adverse effects and alcohol-related diseases. Death rates among female alcoholics are 50 to 100 percent higher than those of men. Major physiological impairments, the diagnostic distribution, the psychosocial consequences and their implication on treatment will be outlined.

Alcohol-Related Disorders↗

PubMed2003

Flupenthixol versus risperidone: subjective quality of life as an important factor for compliance in chronic schizophrenic patients.

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.

Adolescent↗

PubMed2003

Gamma-hydroxybutyric acid in the treatment of alcohol withdrawal syndrome in patients admitted to hospital.

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.

Administration, Oral↗

PubMed2001

[Craving for alcohol and prevention of relapse].

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.

Adult↗

PubMed2001

[Possible interaction between ethanol and drugs and their significance for drug therapy in the elderly].

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.

Aged↗

PubMed2001

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.

Alcohol Drinking↗

PubMed2001

Alcohol biomarkers: clinical significance and biochemical basis.

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.

Alcoholism↗

PubMed2001

Pharmacological relapse prevention in alcohol dependence: from animal models to clinical trials.

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.

Acamprosate↗

PubMed1999

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.

Adult↗

PubMed1999

Postural control and lifetime alcohol consumption in alcohol-dependent patients.

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.

Adult↗

PubMed1998

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.

Adult↗

PubMed1998

Prevalence and course of psychiatric disorders among nursing home admissions.

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.

Aged↗

PubMed1997

[Stroke and intracranial hemorrhage after cocaine abuse].

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.

Adolescent↗

PubMed1997

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.

Alcoholism↗

PubMed1996

Formaldehyde-derived tetrahydroisoquinolines and tetrahydro-beta-carbolines in human urine.

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.

Alcoholism↗

PubMed1996

Comparison of acamprosate and placebo in long-term treatment of alcohol dependence.

BACKGROUND: About 50% of alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that acamprosate may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long-term acamprosate treatment in alcohol dependence. METHODS: In this multicentre, double-blind, placebo-controlled study, we recruited 455 patients, aged 18-65 years, with chronic or episodic alcohol dependence. Patients were randomly allocated treatment with acamprosate (1998 mg daily for bodyweight > 60 kg; 1332 mg daily for < or = kg) or placebo for 360 days. Patients were assessed on the day treatment started and on days 30, 90, 180, 270, and 360 by interview, self-report, questionnaire, and laboratory screening. Patients were classified as abstinent, relapsing, or non-attending. Time to first treatment failure (relapse or non-attendance) was the primary outcome measure. FINDINGS: Seven patients were excluded from the intention-to-treat analysis because they did not attend on the first treatment day and therefore received no medication. The acamprosate (n = 224) and placebo (n = 224) groups were well matched in terms of baseline demographic and alcohol-related variables. 94 acamprosate-treated and 85 placebo-treated patients completed the treatment phase: of those withdrawn, 104 (52 in each group) relapsed, 69 (33 vs 36, respectively) were lost to follow-up, 63 (31 vs 32) refused to continue treatment, 16 (15 vs 11) had concurrent illness, three (two vs one) died, ten (six vs four) had adverse side-effects, one (acamprosate treated) received the wrong medication, and three (placebo treated) were non-compliant. The proportion without treatment failure was higher in the acamprosate than in the placebo group throughout the treatment period (p < 0.001, Mantel-Cox). At the end of treatment, 41 (18.3%) acamprosate-treated and 16 (7.1%) placebo-treated patients had been continuously abstinent (p = 0.007). Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group (138.8 [SD 137.5] vs 103.8 [119.0] days; p = 0.012). 148 patients (79 acamprosate, 69 placebo) completed 27 months follow-up: 27 (11.9%) acamprosate-treated and 11 (4.9%) placebo-treated patients remained continuously abstinent, and the mean cumulative abstinence duration was 230.8 days (259.1) and 183.0 days (235.2), respectively. Apart from occasional diarrhoea, there was no difference in side-effects between groups. INTERPRETATION: Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for treatment of alcohol-dependent patients.

Acamprosate↗

PubMed1996

Psychiatric disorders in gynaecological, surgical and medical departments of general hospitals in an urban and a rural area of Austria.

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.

Adolescent↗