PCR-Based Detection of Cephalosporium gramineum in Winter Wheat.

A polymerase chain reaction (PCR) assay was developed amplifying a 496-bp fragment of the internal transcribed spacer region of Cephalosporium gramineum genomic DNA at concentrations of 100 fg/µl. Winter wheat seed and seedlings were collected from field plots where C. gramineum was present. Seed was tested by PCR using 20-seed samples bulked for DNA extraction. Estimates of seed infection, based on isolation of the pathogen on semiselective medium and PCR, were comparable at 0.18 and 0.13% of winter wheat 'Stephens' (P = 0.6042), and 0.45 and 0.58% of experimental line WA7970 (P = 0.5636), respectively. PCR differentiated between plants with well-developed symptoms of Cephalosporium stripe and noninoculated plants. Positive PCR was obtained from 22% of asymptomatic leaf blades from inoculated plants. We found no false positives when PCR and C. gramineum isolation on a semiselective medium were performed using tissue from the same leaf. The PCR assay has potential to diagnose Cephalosporium stripe disease prior to the appearance of symptoms. Negative PCR for some samples from which C. gramineum was isolated suggests that C. gramineum may be present below the level of detection in some asymptomatic leaves. This PCR assay may be useful for investigations into C. gramineum infection of wheat.

[Combination treatment with SSRI and cognitive behavior therapy for relapse prevention of alcohol-dependent men. Results of a randomized, controlled multicenter therapeutic study]. / Rückfallverhinderung bei alkoholabhängigen Männern durch die Kombination von SSRI und kognitiver Verhaltenstherapie. Ergebnisse einer randomisierten kontrollierten, multizentrischen Therapiestudie.

BACKGROUND: This study evaluates the serotonergic antidepressant nefazodone (SSRI) vs placebo (PL) and specific cognitive-behavioral therapy (CBT) vs nondirective group counseling (GC) for relapse prevention in alcohol dependence in a large, prospective, randomized and placebo-controlled, double-blind study at three German university centers. METHODS: Male patients fulfilling at least five criteria for alcohol dependence according to DSM-IV and ICD-10 were eligible, after detoxification, for one of the following treatment combinations: SSRI+CBT, SSRI+GC, PL+CBT, and PL+GC. The SSRI or PL were administered throughout the evaluation period of 15 months. CBT or GC was applied during the first 12 weeks as group therapy according to operationalized manuals. The main outcome measures (assessed at 3 and 12 months of treatment) were the cumulative number of abstinent days, the amount of ethanol consumed during specified evaluation periods of 3 and 12 months, the number of relapses, and the duration of time until first relapse. RESULTS: After 12 weeks of treatment, no statistically significant differences in any outcome measure were observed between the four treatment combinations. After 52 weeks, the only significant difference was observed in the amount of ethanol consumed, with the SSRI+GC group showing higher intake. CONCLUSIONS: The results of this carefully designed clinical trial suggest that the four treatment combinations do not differ substantially in their efficacy in relapse prevention of nondepressed, severely alcohol-dependent patients. Nefazodone may even promote ethanol drinking in a subset of patients. Cognitive-behavioral therapy as performed in this study was associated with little additional benefit compared with structured GC.

Subchronic effects of olanzapine on sleep EEG in schizophrenic patients with predominantly negative symptoms.

BACKGROUND: It is well known that sleep disturbance is an integral symptom of schizophrenia. In recent studies, a deficit of delta sleep has been observed in schizophrenic patients. Antipsychotic drugs with serotonin (5-HT2) receptor-antagonistic properties are considered to have delta sleep promoting effects. We have investigated the effects of subchronic olanzapine treatment on sleep EEG in schizophrenic patients. METHODS: The effects of administration of olanzapine (15 to 20 mg) on sleep were studied for four weeks in 10 male, drug-free patients suffering from schizophrenia with predominantly negative symptoms. Conventional sleep EEG parameters were investigated at baseline and after treatment with olanzapine for four weeks. Additionally, spectral power analysis of the EEG signal in distinct frequency bands was computed for different sleep stages. Psychopathology (PANSS, HAMD-17, HAMA) and side effects were assessed weekly. RESULTS: All patients improved, as measured by PANSS global scores. Compared to baseline, there was a significant improvement of parameters of sleep efficiency and an increase of delta sleep as well as REM sleep. Regarding spectral power values, no significant differences between baseline and treatment conditions were found. CONCLUSIONS: Sleep improvement was due to parameters of sleep efficiency and delta sleep, which may be related to serotonin antagonistic properties of olanzapine.

Genetic Diversity and Aggressiveness of Ophiosphaerella korrae, a Cause of Spring Dead Spot of Bermudagrass.

The distribution of three Ophiosphaerella spp. that cause spring dead spot (SDS) of bermudagrass was studied by sampling at 24 locations in the southeastern United States. O. korrae was isolated from 73% of the 204 bermudagrass cores collected and was the only SDS pathogen recovered at most sites. O. herpotricha was isolated at three locations in Kentucky and one in North Carolina, and O. narmari was found at two locations in North Carolina. Most O. korrae isolates collected from Alabama, Kentucky, Mississippi, Tennessee, and Virginia clustered in an amplified fragment length polymorphism group (AFLP group II) that was distinct from Kentucky bluegrass isolates collected throughout North America and similar to bermudagrass isolates from Kansas and Oklahoma (AFLP group I). A third AFLP group (III) consisting of bermudagrass isolates from Mississippi and Virginia was identified. Isolates representing AFLP groups II and III grew more rapidly on potato dextrose agar at 25 and 30°C than those in group I. O. korrae isolates differed in their aggressiveness to two bermudagrass cultivars in greenhouse studies, but these differences were not associated with AFLP group, location, or host from which the isolate was collected.

Differential effects of high-dose amisulpride versus flupentixol on latent dimensions of depressive and negative symptomatology in acute schizophrenia: an evaluation using confirmatory factor analysis.

While many acutely ill schizophrenic patients suffer from depressive symptoms, most studies on the efficacy of antipsychotic drugs focus on positive and negative symptoms. Dimensional models of schizophrenic symptoms, based on confirmatory factor analysis (CFA) using structural equation modelling, offer a methodological alternative to compare antipsychotics on empirically justified latent factors. The present report is a refined analysis of a published double-blind study on the D2/D3-selective antagonist amisulpride (ASP) versus the mixed D1-5/5-HT2 antagonist flupentixol (FPX). CFA was applied to Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Bech-Rafaelsen Melancholia Scale and Simpson-Angus Scale subscores to examine differential effects of high doses of ASP and FPX on negative and depressive symptom dimensions in 126 acutely ill schizophrenic patients. A four-factor model comprising the full spectrum of acute symptomatology and a three-factor model ('negative', 'anhedonia-apathy', 'depressive') restricted to negative and depressive symptoms were yielded with an identical 'depressive' dimension in both models. Analyses of CFA-derived factor scores showed that ASP was significantly superior to FPX regarding the latent 'depressive' dimension, independent of baseline scores, dosage and changes in akinesia. Neither the negative' dimension nor 'anhedonia-apathy' showed significantly different treatment effects. CFA-based analyses appear to be suitable for psychotropic drug evaluation when more refined and data-related information on drug efficacy profiles are required.

No association between the dopamine d2 receptor taqi a1 allele and earlier age of onset of alcohol dependence according to different specified criteria.

BACKGROUND: The presence of the A1 allele of the dopamine D2 receptor TaqI restriction fragment length polymorphism has been reported to be associated with an earlier age of onset of alcohol dependence as a marker for severity. METHODS: We tested this hypothesis with special regard to the definition of the age of onset of alcoholism in 243 patients with alcohol dependence, according to DSM-IV criteria assessed by the standardized interview Münchner Composite International Diagnostic Interview (M-CIDI), consecutively admitted for detoxification. Additionally, the Addiction Severity Index (ASI) was performed. The TaqIA polymorphism was amplified by polymerase chain reaction (PCR), and the PCR product was digested by the restriction enzyme TaqI. Patients were subsequently divided into an A1 (presence of at least one A1 allele, n = 88) and an A2 group (absence of an A1 allele, n = 155). The following criteria for different definitions of age of onset were used: (1) age of onset of the first occurring symptom necessary for the diagnosis of alcohol dependence according to M-CIDI; (2) age of onset of the last symptom of alcohol dependence according to M-CIDI; (3) age of onset of more than 3 drinking days per week on a regular basis according to ASI; (4) age of onset of more than 3 drinking days-of more than five drinks per drinking day-or at least one binge drinking episode per week on a regular basis according to ASI. RESULTS: The frequency of the A1 allele in our patient sample was 0.208. No statistically significant association between the A1 allele and the age of onset of alcoholism was found. The mean age of onset according to criterion 1 was 30.4 +/- 10.8 years for the A1 group and 30.2 +/- 10.2 years for the A2 group (p = 0.89); for criterion 2, it was 33.3 +/- 10.0 years for the A1 group and 33.9 +/- 10.2 years for the A2 group (p = 0.77); for criterion 3, it was 18.0 +/- 7.5 years for the A1 group and 18.1 +/- 6.1 years for the A2 group (p = 0.92); and for criterion 4, it was 22.3 +/- 9.7 years for the A1 group and 21.8 +/- 8.5 years for the A2 group (p = 0.76). CONCLUSIONS: No association was found between the A1 polymorphism and age at onset of alcohol dependence according to different specified criteria.

Depressive factors and their relationships with other symptom domains in schizophrenia, schizoaffective disorder, and psychotic depression.

Relationships among different symptom domains were investigated in patients with acute exacerbation of schizophrenia with depressive symptoms, psychotic depression, or schizoaffective disorder, depressive subtype. Scores for depression and depressive factors were correlated with positive, negative, and extrapyramidal symptoms within diagnostic categories. No between-group differences in the relationship of different symptom domains could be found, and no substantial relationship between depression and positive symptoms could be revealed in any diagnostic subgroup. Only the retardation factor of depression showed a significant overlap with negative symptoms; depressive core symptoms did not. Core symptoms of depression were independent from other symptoms in all investigated diagnostic groups. Depression seems to represent a heterogeneous symptom domain with unique relationships of components to positive and negative symptoms across nosological borders. A more differentiated assessment, analysis, and treatment of depressive symptoms is therefore recommended for patients with combined depressive and psychotic symptoms.

Moderate and severe depression. Gradations for the Montgomery-Asberg Depression Rating Scale.

BACKGROUND: Despite its importance, no distinction between moderate and severe depression using the Montgomery-Asberg Depression Rating Scale (MADRS) based on a direct comparison with the Hamilton Depression Rating Scale (HAMD-17) is available. METHODS: HAMD-17 and MADRS ratings from N=40 at least moderately depressed inpatients with major depression (DSM-III-R) were analyzed. Linear and non-parametric correlations were computed and a MADRS cut-off score for severe depression using an HAMD-17 score of at least 28 points as reference was estimated. RESULTS: HAMD-17 and MADRS mean scores were 24.6+/-4.3 and 32.6+/-5.0 points, respectively. Linear correlation of both scores was r=0.70 (P<0.0005). A MADRS cut-off score of at least 35 points was estimated to separate 'moderate' from 'severe' depression corresponding to a HAMD-17 cut-off of 28 points with sufficient sensitivity and specificity. LIMITATIONS: The sample size was limited and no observer ratings directly assessing the severity of depression were used. CONCLUSIONS: The preliminary findings are in line with previous findings and suggest a cut-off score of 35 points to separate moderate from severe depression with the MADRS accepting an HAMD-17 score of >/=28 point as reference. Further studies on this issue are warranted.

Cue exposure in alcohol dependent patients: preliminary evidence for different types of cue reactivity.

Craving is considered to be an important phenomenon in addictive behaviours. However, there is still an unresolved debate on what craving for alcohol means, how it is best measured and which clinical and therapeutical consequences its presence or absence may imply. Cue reactivity paradigms have been developed to elicit craving under standardized experimental conditions. Here we present preliminary results characterizing alcohol-dependent patients with regard to subjective and psychophysiological aspects of exposure to alcohol-associated cues in a cue reactivity paradigm. Thirty-six patients fulfilling at least 5 criteria of alcohol dependence according to DSM-IV criteria were studied after detoxification. Cue reactivity was assessed as subjective (by visual analogue scales) and neurophysiological response (by ECG, EMG, electrodermal activity, respiratory frequency, salivation) to the presentation of the favourite alcoholic beverage or water. While 22% of the patients were both subjective and physiological responders, 42% of the subjects showed only a physiological reaction without subjective response, and 31% of the patients were neither a subjective nor a physiological reaction. Subjective responders to alcohol cues had significantly higher state anxiety levels than subjective non-responders. These results suggest that alcohol dependent patients may be divided into typological subgroups with respect to cue reactivity. Different types of cue reactivity might be important for treatment strategies involving repeated cue exposure or so-called anti-craving drugs.

Adenylyl cyclase activity is increased in younger, but decreased in older, alcoholic patients after detoxification.

Acute and chronic administration of ethanol leads to alterations of the adenylyl cyclase (AC) signal transduction pathway. This study examined whether the formation of cAMP by AC in lymphocytes correlates with age in alcoholic patients and in healthy controls. Blood was drawn for preparation of lymphocyte membranes and for determination of basal, GTPgammaS-stimulated, and forskolin-stimulated AC activity from 68 actively drinking alcoholic patients (age, mean +/- SD: 45 +/- 10; range: 26-69 years) after ethanol detoxification. The patients' AC activity correlated negatively with age. In contrast, no effect of age was observed in the healthy controls (age, mean +/- SD: 42 +/- 11; range: 24-65 years). The age-related decrease in AC activity of alcoholic patients could not be attributed to the duration of regular alcohol intake. It was partly due to the large variance of AC activity in younger and middle-aged alcoholics.

Carbohydrate-deficient transferrin (CDT) and HDL cholesterol (HDL) are highly correlated in male alcohol dependent patients.

BACKGROUND: Serum levels of total HDL cholesterol (HDL) are reportedly influenced by recent alcohol intake. We examined the correlation between HDL cholesterol and widely used markers of excessive alcohol intake, such as carbohydrate-deficient transferrin (CDT), gamma-glutamyl-transferase (GGT), or mean corpuscular volume of erythrocytes (MCV), of which CDT is thought to be the most specific. METHODS: Several serological markers [i.e., CDT, GGT, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), MCV, and HDL] were determined in 100 actively drinking male patients with alcohol dependence (DSM-IV) and in 27 non-alcohol-dependent controls, according to routine procedures. Spearman's rank correlation coefficients were calculated. RESULTS: We found a highly significant positive correlation between HDL and CDT (r(s) = 0.55; p < 0.0005) in patients, but not in controls (r(s) = 0.13;p = 0.51). HDL was also positively correlated with GGT, ALAT, ASAT, and MCV only in patients. CONCLUSIONS: HDL cholesterol, as a widely determined parameter, may represent a useful routine marker for recent excessive alcohol intake. High HDL cholesterol levels should alert clinicians to investigate a patient's recent pattern of alcohol consumption.

[Evaluation of standardized training for the "Positive and Negative Syndrome Scale" (PANSS)]. / Evaluation eines standardisierten Trainings für die "Positive and Negative Syndrome Scale" (PANSS).

The present analysis comprises 3 studies on the interrater reliability of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS; German version). To our knowledge this is the first empirical report on interrater reliability and on results of rater training of the German version of the PANSS despite the widespread use of the scale. In a total of 47 training participants with different clinical experience standardized PANSS rater training was carried out and subsequently evaluated. Therefore, concordance rates with an expert standard (C) and weighted coefficients kappa (kappa W) were calculated. As a main outcome of the studies, at least 3 training sessions were necessary but also sufficient to reach acceptable interrater reliability of the PANSS (C > 80%, kw > 0.60). In training participants with low psychiatric experience the level of interrater reliability of schizophrenic negative symptoms did not reach the results of positive symptoms after the training. Despite some conceptual limitations with respect to negative symptoms, the German version of the PANSS seems highly suitable to assess a broad spectrum of schizophrenic psychopathology in a reliable and economic manner. The present results also underline the practicability of our recommendations for conducting PANSS rater training in the clinical and scientific field as part of quality control and quality assurance in psychopathological assessment.

Effects of subchronic paroxetine administration on night-time endocrinological profiles in healthy male volunteers.

To evaluate the subchronic effects of paroxetine, a selective serotonin reuptake inhibitor, on nocturnal endocrinological profiles, eight healthy male volunteers with no personal or family history of a psychiatric or neurological disease were administered paroxetine (30 mg/day) or placebo in a double-blind cross-over design. Drugs were given as a single dose at 10:00 h for a period of 4 weeks each. Between days 21 and 28 of each treatment period, sleep EEG was registered for four consecutive nights from 23:00 to 07:00 h. During the last night, hormonal profiles for prolactin, growth hormone (GH), cortisol, corticotropin (ACTH), luteinizing hormone (LH), testosterone and melatonin were determined, and area-under-the-curve values were calculated. None of the endocrinological parameters revealed any statistically significant changes. A trend could be found for an increased cortisol production under paroxetine (P = 0.069). ACTH, LH, and melatonin showed slight and non-significant decreases. Prolactin release was only marginally elevated (+7%). The mean sleep onset GH release (as measured for a time period of 180 min after sleep onset) was decreased by about 30% under paroxetine. However, statistical significance could not be reached. For hGH, there was a delayed mean GH-peak under paroxetine. Nocturnal testosterone secretion remained almost unaltered. The lack of significant endocrinological alterations might be partially explained by both adaptational phenomena under subchronic treatment conditions and the extended time span between the single morning dose and the registration period, respectively.

Reliability and validity of the German version of the European Addiction Severity Index (EuropASI).

OBJECTIVE: This study provides data on the psychometric characteristics of the German version of the European Addiction Severity Index (EuropASI). The ASI is a frequently used clinical and research instrument that measures problem severity among people with substance dependence. METHOD: The German ASI was used in a sample of 112 consecutively admitted male psychiatric inpatients seeking treatment for severe alcohol problems. The conceptual structure of the German ASI subscales was investigated by analyzing the intercorrelations of the severity ratings and composite scores. Internal consistency, interrater reliability and concurrent validity in terms of correlations with other assessment instruments were evaluated. RESULTS: The German ASI subscales proved to be independent or moderately correlated (-0.17 < r < 0.34). Each correlation coefficient between corresponding severity ratings and composite scores was significant (p < .0005), ranging from r = 0.47 to r = 0.93. Reliability measures indicated moderate to good internal consistency (Cronbach's alpha: 0.69-0.92) and moderate to excellent interrater reliability (intraclass correlation coefficient: 0.62-0.99). Validity was supported by significantly higher ratings in the alcohol section in alcohol dependent patients compared to patients without dependence (t = 2.99, 108 df, p = .004). Significant correlations (p < .001) were found between the alcohol use section and the Michigan Alcoholism Screening Test (r = 0.34 composite score and r = 0.44 severity rating) and between psychiatric status and the Symptom Checklist-90-revised (r = 0.55/0.51), supporting concurrent validity. CONCLUSIONS: The German version presented evidence of acceptable psychometric properties and its applicability in German-speaking countries could be confirmed.

Three dimensions of depression in patients with acute psychotic disorders: a replication study.

Depressive symptoms in psychotic disorders are of high relevance but seem to be heterogeneous when assessed with a standard rating scale. The present analysis is a replication study on the dimensionality of the Bech-Rafaelsen Melancholia Scale (BRMES) in acutely psychotic patients with substantial depression defined according to a functional approach across the nosological borders of schizophrenia with major affective symptoms, schizoaffective disorder, depressed subtype, and major depression with psychotic features. The baseline data of 123 patients participating in a multicenter pharmacological trial were evaluated with structural equation models. A previously reported three-dimensional model of the BRMES comprising the facets retardation, depressive core symptoms, and accessory depressive symptoms was cross-validated by confirmatory factor analysis (CFA). The three-dimensional model proved to be superior to one-, two-, or four-factor models with respect to goodness-of-fit (goodness-of-fit index [GFI] = 0.91 and comparative fit index [CFI] = 0.89) and parsimony (adjusted GFI [AGFI] = 0.85). When comparing the present model with the previously reported model, a highly satisfactory correspondence emerged (CFI = 0.87). The results corroborate our previous findings that depression-like symptoms in acutely psychotic patients assessed by the BRMES can best be represented by a three-dimensional model and should not be treated as a homogeneous syndrome.

Addition of low-dose fluvoxamine to low-dose clozapine monotherapy in schizophrenia: drug monitoring and tolerability data from a prospective clinical trial.

Combining fluvoxamine and clozapine may be a strategy to improve therapeutic effects on negative symptoms in schizophrenic patients. Fluvoxamine, however, markedly inhibits the metabolism of clozapine, and hazardous side effects may result. This study prospectively investigated the safety and tolerability of an add-on therapy with fluvoxamine to a clozapine monotherapy in schizophrenic patients. Sixteen schizophrenic patients received 50 mg fluvoxamine as a comedication after having reached steady-state conditions under clozapine monotherapy. Patients were monitored for subjective adverse events, laboratory parameters, EEG and ECG recordings, orthostatic hypotension and their psychopathology. Concomitantly, serum concentrations of clozapine and metabolites were measured during monotherapy and after addition of fluvoxamine. In all patients, the serum concentrations of clozapine and metabolites were markedly increased (average: 2-3 fold, up to 5 fold for clozapine) after addition of fluvoxamine. Side effects remained almost unchanged in frequency and severity in spite of the pharmacokinetic interactions. ECG or laboratory parameters and orthostatic tests were similar under monotherapy and comedication. Minimal increases of EEG abnormalities were observed, but they were not associated with clinical impairment. Epileptic activities were always absent. The psychopathology improved which continued after start of the comedication. Though the addition of fluvoxamine to clozapine medication was well tolerated and critical side effects were absent, the combined treatment should be controlled by drug monitoring, as serum concentrations of clozapine increased to unpredictably high levels. Further studies have to find out if the combined treatment could be advantageous to clozapine monotherapy.

The Calgary Depression Rating Scale for Schizophrenia: development and interrater reliability of a German version (CDSS-G).

A German version of the Calgary Depression Rating Scale for Schizophrenia (CDSS-G) approved by the author of the original scale is presented comprising a semi-structured interview for 9 items to sensitively and specifically assess depression in schizophrenia and related disorders. The process of translation is outlined and the finally derived CDSS-G was investigated with respect to interrater reliability in three studies. To keep comparability with the CDSS source version a standard procedure was used. Two trained raters jointly assessed ten schizophrenic patients (study I). In a second study, videotapes with the CDSS-G were presented to clinically inexperienced raters (study II, N = 14/15) to test the agreement on the CDSS-G in this sample. Finally, in a third study clinically experienced researchers participated in a rater training (study III, N = 34). They carried out CDSS ratings on three patients with mild depressive symptoms. The dependence of interrater reliability on depression severity was investigated for all studied patients. Both intraclass correlation coefficients (ICC) and weighted kappa coefficients (kappa(w)) were calculated. The results revealed a high ICC = 0.97 in study I for the total CDSS-G score. Single item ICC values were all above 0.70. The results of study II revealed somewhat lower agreement on CDSS-G items and total scores in psychiatric novices with however acceptable values of kappa(w)>0.50 for the total scores. Study III yielded satisfactory results (0.66

Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic.

RATIONALE: EMD 57445 (panamesine) is a high affinity sigma ligand with the profile of an atypical antipsychotic in animal studies. It has been reported recently to have antipsychotic activity in schizophrenia. However, its metabolite, EMD 59983, binds also to D(2) and D(3) dopamine (DA) receptors. OBJECTIVES: The aim of this study was to test, using single photon emission computed tomography (SPECT) and [(123)I]iodobenzamide (IBZM) as the radiotracer, whether EMD 59983 would pass the blood-brain barrier and to what extent it would contribute to the effects of EMD 57445 in schizophrenia. METHODS: Two IBZM SPECT-scans were performed in five neuroleptic-free schizophrenic patients (DSM IV), one before and one after treatment with 60 mg panamesine daily for a treatment duration of 12-26 days. RESULTS: A high occupancy of striatal D(2)-like DA receptors similar to that induced by typical neuroleptics was observed in all patients treated with EMD 57445. CONCLUSIONS: Our results suggest that a possible antipsychotic activity of EMD 57445 in schizophrenia is not necessarily attributable to its affinity for sigma receptors, but could be simply due to the potent antidopaminergic effects of EMD 59983, its main metabolite.

Blood ethanol levels and adenylyl cyclase activity in lymphocytes of alcoholic patients.

BACKGROUND: The adenylyl cyclase (AC) signal transduction pathway is a target of acute and chronic ethanol actions. This study examined whether AC activity in lymphocyte membranes of male alcoholic patients correlated with blood concentrations of ethanol. METHODS: Patients (n = 13; mean age: 40 +/- 8 years) were studied on the day of admission (day 0) and 2 days later under detoxification. Moreover, 13 age-matched male healthy controls (mean age 40 +/- 9 years) were included. Lymphocyte membranes were prepared by differential centrifugation whereby blood ethanol was washed out. As a measure of AC activity the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate was determined without (basal activity) and with stimulation of the second messenger system by the guanosine triphosphate (GTP) analogue GTP gamma S (20 mumol/L) via the G-protein or by forskolin (100 mumol/L) acting directly on the AC enzyme. RESULTS: On day 0, when ethanol blood concentrations were 38-100 mmol/L, we found a significant negative correlation between ethanol blood levels and stimulated AC activities. On day 2, the negative correlation with blood ethanol levels of day 0 had disappeared. CONCLUSIONS: The consumption of ethanol affects the AC system in lymphocytes of alcohol-dependent patients by a persistent effect on the cAMP forming enzyme.