Biomedical subjects

Otto M Lesch

Publications and source records attributed to Otto M Lesch.

9 recordsLinked to original sources

PubMed2006

Multiple substance use among young males.

Neurobiological studies hypothesize a common final pathway of addictive behavior in the mesolimbic dopaminergic system. Nicotine has been shown to sensitize the reward pathway, thereby causing increased drug-seeking behavior. Since there is evidence to suggest that nicotine, alcohol and other psychoactive substances act on the same final pathway and seem to augment their effects in animal subjects, drug intake behavior of humans would likely be reflected in increased substance use of nicotine-dependent persons. We used biological markers of substance use as well as questionnaires to assess the levels of psychoactive substance use among 18-year-old males in a naturalistic cross-sectional setting. We found that increasing levels of nicotine dependence were related to higher levels of alcohol abuse and dependence. Furthermore, higher levels of nicotine dependence were associated with elevated levels of recent cannabinoid use.

Adolescent↗

PubMed2006

Glutamic acid in withdrawal and weaning in patients classified according to Cloninger's and Lesch's typologies.

AIMS: Though glutamic acid is well known as a working excitatory in the CNS, its impact on the modulation of alcohol withdrawal symptoms and withdrawal fits are not yet clear. The study has been undertaken to examine the levels of glutamic acid in chronic alcohol-dependent patients at different stages of alcohol withdrawal and weaning and to examine any existence of any differences according to Cloninger's and Lesch's typologies. PATIENTS AND METHODS: One hundred and fifty-nine alcohol-dependent patients were assessed according to Cloninger's and Lesch's typologies and related to abstinence duration, age, and gender. Blood samples were taken for mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT) and glutamic acid, in order to find primarily any differences in glutamic acid according to the typologies, age, abstinence duration, and liver damage. RESULTS: There was no significant association between Cloninger's and Lesch's typologies. Cloninger's types 1 and 2 had an equal distribution of GGT and duration of abstinence, while Lesch's type I had more patients with high GGT, and more patients who were sober for a maximum of 2 days. Unlike in Lesch's types, glutamic acid levels did not differ according to Cloninger's types, as significantly higher glutamic acid values were found in Lesch's types I and IV. Glutamic acid values did not differ significantly in different age groups. CONCLUSIONS: Our study findings of varying glutamic acid levels seen in Lesch's typology, higher in types I and IV than in types II and III, are of significant clinical value and can be interpreted differently, as in type I high levels of glutamic acid is seen as a kindling phenomenon, while in type IV elevated levels might be related to either compulsivity of frequent repetition of drinking or withdrawal.

Adult↗

PubMed2006

Exclusion of trisialo-transferrin from carbohydrate-deficient transferrin measurement: advantage in patients with chronic liver disease?

BACKGROUND: Biological markers for chronic alcohol consumption like MCV or gammaGT or carbohydrate deficient transferrin (CDT) are useful, but far from being perfect. In patients with liver disease a reliable marker for chronic alcohol consumption as the underlying etiology is highly needed. Recently, a new ELISA based version of the carbohydrate-deficient-transferrin (CDT-TRISIALO (-)) assay has been developed, which measures asialo-, monosialo- and disialo transferrin, but excludes trisialo- transferrin; that modification suggests higher sensitivity and specificity in detecting recent alcohol consumption in patients. AIMS: The study goal was to evaluate the sensitivity, specificity, positive and negative predicitive value of this new carbohydrate-deficient-transferrin assay (CDT-TRISIALO (-)) in a group of patients with liver disease and to compare the results with that of the established CDT assay (CDT-TRISIALO (+)). PATIENTS AND METHODS: Our study population consisted of 110 consecutive patients (male: n = 80 [72.7 %], female: n = 30 [27.3 %]) with liver disease of the following etiologies: chronic alcohol consumption (n = 51 [46.4 %]; Out of them 30 alcohol abusing patients were assessed by cage = 1 and 21 alcohol dependent patients were assessed by cage = 2, chronic viral hepatitis (n = 33 [30.0 %]) including 25 [22.7 %] patients with chronic hepatitis C infection and 8 [7.3 %] patients with chronic hepatitis B infection), haemochromatosis (n = 4 [3.6 %]), mechanical cholestasis (n = 17 [15.5 %]) and other liver diseases (n = 5 [4.6 %] including autoimmune hepatitis (n = 2) and primary biliary cirrhosis (n = 3)). 27.3 % of our patients (n = 30) had no liver cirrhosis whereas the majority (72.7 %, n = 80) had liver cirrhosis. RESULTS: In our population of liver disease patients the CDT-TRISIALO (-) assay had a sensitivity of 72.7 % and specificity of 58.1 % for recent alcohol consumption at the published cutoff level of 2.6 %. The positive predictive value was 34.0 % and the negative predictive value was 87.8 %. Sensitivity and specificity of the CDT-TRISIALO (+) assay at the recommended cutoff level of 4.7 % were similar, 77.3 % and 49.3 %, respectively. The positive and negative predictive values were 30.9 % and 88.1 %. CDTTRISIALO (+) and CDT-TRISIALO (-) levels increased significantly with higher Child-Pugh stages. CONCLUSION: The newly developed carbohydrate deficient transferrin test (CDT-TRISIALO (-)) is of no advantage as compared to the established assay (CDT-TRISIALO (+)) when used in a patient population with liver disease. In that population, normal CDT-TRISIALO (-) helps to exclude recent alcohol consumption; this results from the high negative predictive value of a normal CDT-TRISIALO (-).

Adult↗

PubMed2005

Epidemiology of substance use in a representative sample of 18-year-old males.

AIMS: To assess recent drug use through urine testing as well as the prevalence of tobacco and alcohol dependence among young males and to analyse the associations between tobacco dependence and cannabis use (delta-9-tetrahydrocannabinol, THC), tobacco dependence, and alcohol dependence as well as between THC use and other illicit drug use. METHODS: Urine samples were collected, and nicotine and alcohol questionnaires were administered. Carbon monoxide was assessed in exhaled air. Data from young males from representative, selected districts of Lower Austria were recorded during the annual physical examination for mandatory military service. Out of all 18-year-old males in Austria 3.8% (n = 1902) were included in the study. Prevalence of recent illicit drug use, tobacco dependence (heavy smoking index, HSI), alcohol dependence (The 4-item cutting down, annoyance by criticism, guilty feeling, and eye-openers (CAGE) questionnaire), and associations between substance categories by means of logistic regression analyses were calculated. RESULTS: Alcohol abuse was found in 15.1% and alcohol dependence was found in 3.2%. According to the HSI 51.5% of males reported daily smoking, of whom 43.7% showed a mild level, and 7.8% a high level, of nicotine dependence. About 5.1% of the sample evidenced THC in urine. Opiates were identified in 2.7% of urine samples. Smokers showed a higher risk of THC use. THC users had a tendency to use cocaine and amphetamines more frequently than THC abstainers. CONCLUSION: Nicotine and alcohol dependence is common among young males. Biological assessment of illicit drug use seems to confirm previous questionnaire-based findings of associations between THC use and other illicit drugs. Urine testing seems to be an adequate method to analyse associations of THC use and other illicit drugs. In combination with questionnaires urine testing may be used for the assessment of associations of tobacco dependence and recent illicit drug use based on epidemiological surveys.

Adolescent↗

PubMed2005

Challenges and opportunities for medications development in alcoholism: an international perspective on collaborations between academia and industry.

This article represents the proceedings of a symposium presented at the 12th Congress of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, on September 30, 2004. The organizers and cochairs were Bankole A. Johnson, DSc, MD, PhD, and Karl Mann, MD. The presentations included the following: (1) A Perspective from Academia, by Bankole A. Johnson, DSc, MD, PhD; (2) A Perspective from NIAAA, by Mark L. Willenbring, MD; (3) A Perspective from US Clinical Practice, by Robert M. Swift, MD, PhD; (4) A European Perspective on Medications Development, by Otto M. Lesch, MD, PhD, and (5) A Scandinavian Perspective on Evidence-Based Addiction Treatment, by Mats Berglund, MD.

Academies and Institutes↗

PubMed2005

Comorbid alcohol and nicotine dependence: from the biomolecular basis to clinical consequences.

This article represents the proceedings of a symposium presented at the 12th Congress of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, on October 1, 2004. The organizers and cochairs were Nassima Ait-Daoud, MD, and Gerhard A. Wiesbeck, MD. The presentations included the following:L (1) The Role of Nicotinic Acetylcholine Receptors in Alcohol-Seeking Behavior, by Przemyslaw Bienkowski, MD, PhD; (2) Utilization of Linkage Analysis Combined with Microarray Technology to Identify Genes and Mechanisms Underlying Nicotine and Alcohol Use and Abuse in Humans and Rodents, by Ming D. Li, PhD; (3) Smoking and Alcoholic Chronic Pancreatitis: The Underestimated Risk?, by Roland H. Pfützer, MD; (4) Anticraving Medication in Alcohol and Nicotine Dependence, by Otto M. Lesch, MD, PhD; and (5) Pharmacotherapy for Promotion of Abstinence from Nicotine Among Alcohol-Dependent Individuals, by Bankole A. Johnson, DSc, MD, PhD.

Alcohol Deterrents↗

PubMed2003

[Comparative effectiveness of flupenthixol and risperidone on negative symptoms of schizophrenia].

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.

Antipsychotic Agents↗

PubMedDate not supplied

Double-blind controlled trial of gamma-hydroxybutyrate and clomethiazole in the treatment of alcohol withdrawal.

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.

Adult↗

PubMedDate not supplied

Differences in brain function between relapsing and abstaining alcohol-dependent patients, evaluated by EEG mapping.

AIMS: Early clinical electroencephalographers reported that low-voltage fast desynchronized patterns were frequently seen in chronic alcoholism, suggesting hyperarousal of the central nervous system (CNS). The aim of the present study was to investigate the brain function of drug-free, detoxified alcoholics, and compare this with that of normal controls, utilizing computerized quantitative EEG analysis and subsequent EEG mapping. Moreover, differences between patients relapsing or abstaining during 6 months of relapse prevention therapy, pharmacologically supported by either flupentixol decanoate 10 mg or placebo i.m. every 2 weeks, were determined. METHODS: 22 drug-free, detoxified patients (15 men, seven women) aged between 27 and 58 (mean 41.5 +/- 8.1) years, diagnosed as alcohol-dependent (ICD-10: F10.23) were included in the study. They were subdivided into abstainers (n = 11) and relapsers (n = 11), and matched with normal healthy controls according to age (mean 41.5 +/- 8.4 years) and sex. A 3-min vigilance-controlled EEG (V-EEG) was obtained and analysed off-line by multi-lead EEG power spectral analysis and subsequent mapping methods. RESULTS: The drug-free, detoxified, alcohol-dependent patients showed, as compared with controls, aberrant brain function characterized by a decrease in delta and slow alpha and an increase in beta activity as well as an acceleration of the total centroid. These findings were more pronounced in relapsing than in abstaining patients. After 6 months of treatment, abstaining patients showed an increase in slow activity, a decrease in fast alpha, an acceleration of the delta/theta centroid and a deceleration of the alpha centroid, reflecting a normalization of brain function. CONCLUSION: EEG maps of alcohol-dependent patients differ significantly from those of normal controls and patients suffering from other mental disorders and thus EEG mapping may be used for diagnostic purposes. Moreover, the quantitative EEG may also be of prognostic value as relapsing patients differ from abstaining ones, since they show a significantly more pronounced hyperarousal of the CNS.

Adult↗