Monoamine oxidase activity in blood platelets in alcoholism.

A newly developed assay form monoamine oxidase (MAO) activity in blood platelets was applied in 50 alcoholic patients. The assay is the direct measurement of serotonin oxidation by MAO employing a double microcolumn technique on Sephadex G-10 and Amberlite CG-50 for separating 5-HIAA formed, which is measured flourimetrically. Rebound of MAO activity levels after withdrawal of alcohol was observed to be more pronounced in the patients with delirium tremens than those who exhibited no outstanding abstinent symptomatolgy. MAO ACTIVITY LEVELS MEASURED IN THE 1ST WEEK OF ALCOHOL WITHDRAWAL WERE 3.49+/-1.15 (Mean+/-S.D.) nmol/mg protein/hour in the alcoholic patients with delirium tremens, a value significantly lower than that in the subjects without (p less than 0.001) and that in the male normal subjects (p less than 0.001). Four weeks after withdrawal of alcohol, the reduced MAO activity levels in the alcoholic population were restored to normal levels. These data demonstrate that physical dependency for alchol occurred evidently in the alcoholic patients examined. Delirium tremens and other psychotic symptoms in alcoholism may be manifested as impaired serotonin metabolism in the brain, which may be due to MAO inhibition caused by excessive alcohol intake.     

Circadian rhythms of hormone concentrations in alcohol withdrawal

Abstract We investigated the circadian rhythm of hormones (Cortisol, melatonin) in alcoholic patients during and 1 month after alcohol withdrawal. Patients with delirium tremens had irregular serum hormone concentration rhythms during withdrawal, which normalized after the withdrawal period. Patients without delirium tremens had normal circadian rhythms even during the withdrawal period. We speculated that the disturbance of the biological oscillator, in terms of the decline of synchronizing function or the decrease in synchronizing factors, caused abnormal circadian rhythms of hormone release during delirium tremens.     

Monoamine Oxidase Activity in Blood Platelets From Manic and Depressed Patients

To evaluate the possible abnormality in MAO activity in affective disorders, blood platelet samples were obtained from 80 patients with mania and depression. Blood-platelet MAO activity was measured by a newly developed assay procedures using serotonin as substrate. MAO activities in 121 normal adult subjects were in a range of 2.49-12.05 nM/mg protein/hour, with the mean values of 4.91 ±1.72 (±S.D.) for men and 6.88±1.99 for women. (p<0.001) MAO activities in the manic and depressed patients were in a range of 0.65–13.40 nM/mg protein/hour, and both manic and depressed patients showed the mean value very similar to that in the normal subjects. Bipolar depressed patients did not exhibited lower MAO activity in the blood platelets than other clinical subtypes of depressive illness, including unipolar, involutional, neurotic and chronic characterological, and first-episode depressions. No significant differences were established between these five subcategories of depression, while significant higher values were evident in female than male patients (p<0.001). No correlation was found between the MAO activity and serotonin levels in the blood platelets either in the normal subjects or in the depressed patients.     

酒精戒断所致震颤谵妄与非震颤谵妄患者DNA 氧化损伤的比较

目的 DNA氧化损伤标记物8-羟基脱氧鸟苷(8-OHd G)与酒精戒断有密切联系,本研究通过对酒精戒断所致震颤谵妄与非震颤谵妄患者DNA氧化损伤的比较,为临床早发现早治疗提供理论依据。方法将176例慢性酒精中毒患者按入院后是否出现震颤谵妄分为震颤谵妄组及非震颤谵妄组,采用酶联免疫吸附法(ELISA)检测血清8-OHd G水平,采用酒精戒断状态评定量表(CIWA-Ar)评定两组戒断严重程度。结果震颤谵妄组8-OHd G水平高于非震颤谵妄组,差异有统计学意义[(0.58±0.12)ng/ml vs.(0.35±0.13)ng/ml,P0.01];8-OHd G水平与酒精戒断状态评定量表CIWA-Ar评分呈正相关(r=0.84);逐步Logistic回归分析显示8-OHd G(OR=6.3)是震颤谵妄的独立危险因素。结论检测外周血8-OHd G水平可能有助于酒精戒断所致震颤谵妄的早期诊断及病情判定。     

Circadian variation in plasma 5-hydroxyindoleacetic acid level during and after alcohol withdrawal: phase advances in alcoholic patients compared with normal subjects

Alcohol withdrawal symptoms in 19 male alcoholics were objectively evaluated and classified and circadian variation in their plasma 5-hydroxyindoleacetic acid (5-HIAA) concentrations was determined at 3 different intervals after cessation of drinking. Circadian variations in plasma 5-HIAA level exhibited phase advances in alcoholic patients compared with normal controls and were different depending on the severity of alcohol withdrawal symptoms. Plasma 5-HIAA in patients with delirium tremens showed significantly higher levels during the abstention period, possibly suggesting peculiarity in their serotonergic metabolism.     

Diagnostic and prognostic value of additional neurologic diagnosis in alcohol withdrawal delirium

A severe course of alcohol withdrawal has been observed in 28% of patients in a neurological intensive care unit due to complicating central nerve system (CNS) diseases. In any atypical alcoholic delirium, especially with focal neurological signs, partial seizures, or decreased level of consciousness, CNS diseases like meningoencephalitis, intracranial hemorrhage, or central pontine myelinolysis must be diagnosed by computed tomography (CT) scan and cerebral spinal fluid (CSF) tap. The diagnostic and prognostic value of CT scan and CSF analysis was examined in 32 persons with alcohol withdrawal syndrome or delirium tremens. Neurological complications and cerebral convulsions at the beginning of delirium tremens appear to predispose the patient to a protracted clinical course and necessary mechanical ventilation. Blood-CSF barrier permeability is increased in 70% of alcohol withdrawal patients and that also seems to be a marker of a prolonged clinical course. Cerebral atrophy as shown in CT scan does not play a role in predicting clinical course. In our experience, CT examination or lumbar puncture is not necessarily recommended if clinical signs are typical for alcohol delirium.     

A genotype-controlled analysis of plasma dopamine beta-hydroxylase in healthy and alcoholic subjects: evidence for alcohol-related differences in noradrenergic function.

BACKGROUND: Norepinephrine and dopamine mediate important aspects of alcoholism and alcohol withdrawal. Dopamine-beta-hydroxylase (DbetaH) converts dopamine to norepinephrine. A recent study demonstrated a strong association between variance in plasma DbetaH activity and a novel polymorphism (DBH-1021C-->T) at the structural locus (DBH) encoding DbetaH protein. METHODS: Our study investigated whether the DBH-1021C-->T polymorphism and plasma DbetaH activity were associated with alcoholism or with delirium tremens (DT) during alcohol withdrawal by analyzing 207 German alcoholic and 102 healthy control subjects. We also examined the influence of the polymorphism on enzyme activity. RESULTS: Mean (+SD) plasma DbetaH activity measured in alcoholic subjects abstinent was significantly lower than that observed in control (27.7 + 16.7 vs. 35.6 + 18.8; p =.01). It did not differ between subjects with DT during withdrawal and subjects with mild withdrawal symptoms. The T allele of the DBH-1021C-->T polymorphism was significantly associated with lower plasma DbetaH activity. None of the alleles or genotypes were associated with alcoholism or DT. CONCLUSIONS: The data indicate that the alcoholism-related reduction in plasma DbetaH activity is independent of genotype at DBH-1021C-->T and replicate the finding that DBH-1021C-->T is strongly associated with plasma DbetaH activity in a native Western European population.     

Diagnostischer und prognostischer Wert neurologischer Zusatzdiagnostik beim Alkoholdelir

A severe course of alcohol withdrawal has been observed in 28% of patients in a neurological intensive care unit due to complicating central nerve system (CNS) diseases. In any atypical alcoholic delirium, especially with focal neurological signs, partial seizures, or decreased level of consciousness, CNS diseases like meningoencephalitis, intracranial hemorrhage, or central pontine myelinolysis must be diagnosed by computed tomography (CT) scan and cerebral spinal fluid (CSF) tap. The diagnostic and prognostic value of CT scan and CSF analysis was examined in 32 persons with alcohol withdrawal syndrome or delirium tremens. Neurological complications and cerebral convulsions at the beginning of delirium tremens appear to predispose the patient to a protracted clinical course and necessary mechanical ventilation. Blood-CSF barrier permeability is increased in 70% of alcohol withdrawal patients and that also seems to be a marker of a prolonged clinical course. Cerebral atrophy as shown in CT scan does not play a role in predicting clinical course. In our experience, CT examination or lumbar puncture is not necessarily recommended if clinical signs are typical for alcohol delirium.     

Cerebral blood flow during delirium tremens and related clinical states studied with xenon-133 inhalation tomography

The regional cerebral blood flow of 12 patients with severe alcohol withdrawal reactions (delirium tremens or impending delirium tremens) was measured during the acute state before treatment and after recovery. Greater cerebral blood flow was significantly correlated with visual hallucinations and agitation during the acute withdrawal reaction. The results suggest that delirium tremens and related clinical states represent a type of acute brain syndrome mainly characterized by CNS hyperexcitability.     

Inappropriate vasopressin secretion in severe alcohol withdrawal.

Forty-one male alcoholics suffering from alcohol withdrawal syndrome were investigated to assess the relationship between vasopressin (ADH), water homeostasis and alcohol withdrawal. During 10 d, we found a significant decrease in serum vasopressin, from 3.08 +/- 0.61 to 1.71 +/- 0.22 pg/nl. There were no concomitant changes in osmolality, so that a general dysregulatory state of vasopressin secretion during alcohol withdrawal cannot be assumed. Only patients with delirium tremens (8/41) had higher vasopressin levels despite lowered serum osmolalities. These findings support the hypothesis of an inappropriate rebound secretion of vasopressin in severe alcohol withdrawal. Furthermore, they may contribute to the pathogenesis of focal alcoholic brain damage, because rapid and/or profound changes in osmolality are suspected to cause circumscribed cerebral demyelinization.     

Comparative simultaneous measurement of cerebrospinal fluid 5-hydroxyindoleacetic acid and blood serotonin levels in delirium tremens and clozapine-induced delirious reaction.

Cerebrospinal fluid 5-hydroxyindoleacetic acid and total blood serotonin levels were measured simultaneously in 11 female patients with delirium tremens and nine schizophrenic women with clozapine-induced acute delirium. Both groups had significantly raised levels of 5HIAA in CSF and significantly reduced blood 5HT levels as compared with normal control subjects, symptom-free alcoholics, or clozapine-treated schizophrenics. The two delirious groups were not distinguishable from each other in respect of their CSF 5HIAA or blood 5HT values. After clinical recovery both values returned to normal levels.     

Barbital and diazepam plasma levels during treatment of delirium tremens.

Plasma concentrations of barbital and diazepam were measured daily during a double-blind study of the efficacy of the two drugs in the treatment of delirium tremens and less severe clinical states. Treatment was estimated as satisfactory in the majority of cases; the present study deals with the satisfactory groups only. Both in the barbital group and in the diazepam group the same plasma level was seen in different clinical states. This result is discussed in relation to the theories about the aetiology of delirium tremens, and it is concluded that the data fits best with the assumption that delirium tremens is released from a withdrawal state, but once established, the delirious state is not interrupted by the drugs. The barbital concentrations were rather high, many at a level where non-alcoholics would show pronounced intoxication symptoms not seen in the present material. The diazepam concentrations on the other hand were low, often below a level where a cerebral effect is measurable in normal subjects. On this basis it is concluded, that the two drugs have different modes of action. Barbital may act by its cross-dependence properties with alcohol and thus diminish the withdrawal reaction, whereas diazepam may act by its anti-anxiety effect, but not in the doses here applied, by cross-dependence properties with alcohol. Finally, this hypothesis is discussed in relation to clinical experience in the treatment of delirium tremens.     

Platelet and fibroblast monoamine oxidase in alcoholism

Monoamine oxidase (MAO) activity has been reported to be low in platelets (MAO B) and brain (MAO A and B) of some patients with alcoholism compared to control subjects. Whether the decreased platelet MAO activity found in alcoholism is secondary to the effect of alcohol or exists before alcohol abuse is not clear. The hypothesis that altered MAO A activity is determined by an abnormality in the genetic regulation of the enzyme can be tested by measuring MAO A activity in human fibroblasts cultured under controlled conditions. We first studied the kinetic parameters of platelet MAO B activity in patients hospitalized for treatment of alcoholism. Vmax was 38% lower in the patients (n = 14) than in normal controls (n = 22), but the enzyme affinity (Km) for the substrate tyramine was unchanged. Patients with the five lowest levels of platelet MAO activity had MAO activity measured from fibroblasts cultured from skin punch biopsies. Their fibroblast MAO activity was within the normal range, showing a dissociation between platelet MAO B and fibroblast MAO A activities and suggesting that MAO A activity is not low for genetic reasons in alcoholic subjects who do have low platelet MAO B activity.     

慢性酒精中毒酒戒断的震颤谵妄发作危险因素探析

目的探讨慢性酒精中毒患者发生震颤谵妄(DT)的高危因素。方法把148例慢性酒精中毒患者按入院后是否出现震颤谵妄分为震颤谵妄组(DT)和非震颤谵妄组(NDT),观察他们的人口学资料(如性别、年龄、民族、婚姻状态等)、饮酒依赖史(饮酒的年限、饮酒品种、饮酒量、戒酒史等)、既往史、个人史、家族史、入院时的体征和症状(包括生命体征、戒断症状等)和身体状况等项目,描绘其临床特征,并对23项变量进行Logistic回归分析,筛选出慢性酒精中毒患者发生震颤谵妄的高危险因素。结果148例慢性酒精中毒患者在住院期间发生震颤谵妄者共28例(占18.92%)。Logistic regression model结果显示慢性酒中毒者入院后发生震颤谵妄的具有显著相关意义的5个解释变量,即入院时观察指标中的急性感染疾病、心动过速、紧张焦虑状态、精神运动性兴奋和肝功能异常。结论出现震颤谵妄的慢性酒精中毒患者与未发生震颤谵妄的慢性酒精中毒患者在入院时的临床特征存在差异,对慢性酒精中毒患者入院时及之后监测急性感染疾病、心动过速、精神运动性兴奋、紧张焦虑状态和肝功能异常等5个高危因素,有利于及时有效的干预。     

Measurement of Platelet Monoamine Oxidase Using Three Different Substrates in Patients with Alcoholism and Schizophrenia

Abstract: The platelet monoamine oxidase (MAO) activities in alcoholism and schizophrenia were investigated by means of the simultaneous determination, using β-phenyl-ethylamine, tryptamine and serotonin as substrates. No significant difference was found between the MAO levels in the alcoholic and schizophrenic groups, when tryptamine was used as a substrate, but both groups showed lower values than the controls. On the other hand, β-phenylethylamine, a specific substrate for MAO B used as a substrate, showed no significant difference between the alcoholic and control groups in the activities. These two groups showed higher values in MAO activity than the schizophrenic group, whereas when MAO activity was estimated using serotonin, platelet enzyme was found to be inhibited significantly in alcoholism, and the level of activities in the schizophrenics was similar to that of the controls. Moreover, the β-phenylethylamine inhibition curve obtained serotonin as the substrate in the pooled platelets of 50 normal human subjects, and the MAO activity could not be inhibited by higher concentrations than the Km value of serotonin. These findings suggested that there might be two interacting catabolic sites having different substrate affinities in blood platelet MAO. Thus, it could be speculated that serotonergic catabolic sites of MAO in the platelets are disturbed in the alcoholics, while β-phenylethylaminergic catabolic sites of platelet MAO are inherently vulnerable in schizophrenia.     

Measurement of platelet monoamine oxidase using three different substrates in patients with alcoholism and schizophrenia

The platelet monoamine oxidase (MAO) activities in alcoholism and schizophrenia were investigated by means of simultaneous determination, using beta-phenyl-ethylamine, tryptamine and serotonin as substrates. No significant difference was found between the MAO levels in the alcoholic and schizophrenic groups, when tryptamine was used as a substrate, but both groups showed lower values than the controls. On the other hand, beta-phenylethylamine, a specific substrate for MAO B used as a substrate, showed no significant difference between the alcoholic and control groups in the activities. These two groups showed higher values in MAO activity than the schizophrenic group, whereas when MAO activity was estimated using serotonin, platelet enzyme was found to be inhibited significantly in alcoholism, and the level of activities in the schizophrenics was similar to that of the controls. Moreover, the beta-phenylethylamine inhibition curve obtained serotonin as the substrate in the pooled platelets of 50 normal human subjects, and the MAO activity could not be inhibited by higher concentrations than the Km value of serotonin. These findings suggested that there might be two interacting catabolic sites having different substrate affinities in blood platelet MAO. Thus, it could be speculated that serotonergic catabolic sites of MAO in the platelets are disturbed in the alcoholics, while beta-phenylethylaminergic catabolic sites of platelet MAO are inherently vulnerable in schizophrenia.     

酒精所致震颤谵妄患者血液相关指标的对照研究

目的:对酒依赖患者进行血液相关指标的观察与分析,探讨慢性酒精中毒患者发生震颤谵妄(delirium tremens,DT)的高危因素. 方法:对近4年142例首次住院的男性酒依赖住院患者按照是否出现DT分组进行血液相关指标比较. 结果:出现震颤谵妄(DT)的17例酒依赖患者与非震颤谵妄组相比,在谷草转氨酶[(183.53±174.55) U/L;(95.83±118.38) U/L]、谷氨酸转氨酶[(647.26±618.27)U/L; (250.48±313.91) U/L]、及肌酸激酶[(738.85±1023.72)U/L;(330.59±433.42) U/L]及钙[(2.34±0.91) mmol/l;(2.22±0.14) mmol/l]显著升高;而血红蛋白[(126.00±17.77) g/l;(135.38±17.85) g/l]、红细胞[(3.55±0.64)×1012/L; (3.93±0.60)×1012/L]、血小板[(86.41±31.56)×109/L;(173.78±79.44)×109/L]、钾[(3.45 ±0.75)mmol/l;(3.88±0.55) mmol/l]及氯[(100.94±5.02) mmol/l;(104.46±6.64) mmol/l]则显著降低,差异均有统计学意义(P＜0.05或P＜0.01).Logistic回归分析显示,戒酒患者发生DT的危险因素有:血小板减少和血钾降低. 结论:酒依赖患者血液相关指标对DT预测具有一定参考意义.     

Cerebrospinal fluid acid-base and lactate changes after seizures in unanesthetized man II. Alcohol withdrawal seizures.

Acid-base changes in arterial blood and lumbar cerebrospinal fluid were correlated with simultaneously determined lactate levels in patients admitted after alcohol withdrawal seizures. Arterial and cerebrospinal fluid lactate was elevated in association with a marked respiratory alkalosis in 13 patients studied 5 to 12 hours after the seizure. Similar elevations of arterial and cerebrospinal fluid lactate were found in five patients during delirium tremens without antecedent withdrawal seizure. The cerebrospinal fluid lactate determined on admission appeared to correlate best with the length and severity of the alcohol withdrawal syndrome that developed in patients after a withdrawal seizure.     

Delirium tremens. Some clinical features. Part II

Twenty patients with delirium tremens (grade 3) and a less severe clinical state (grade 2) were investigated thoroughly from the time of admission until recovery from the acute state. A lumbar puncture was performed in the majority of the patients immediately after admission and then repeated after recovery from the acute state. The cerebrospinal fluid was found to be both macroscopically and microscopically normal, as was the spinal fluid pressure. The clinical course was without complication, none of the patients were severely dehydrated. All the patients were treated with barbital, a long acting barbiturate. The duration of the acute state and the total amount of drug necessary in the treatment were equal in the two groups of severity. However, patients with proper delirium tremens needed significantly fewer barbital doses during the first hours after treatment was initiated than did patients with a less severe clinical state. The opposite was seen about 12 hours later. These findings are discussed in relation to the high blood alcohol concentration seen at the time of admission in the majority of the patients with proper delirium tremens, but not in patients with grade 2. It is concluded that barbital exerts its effect due to cross-dependence properties with alcohol. The majority of the patients had moderately elevated blood pressure, pulse rate and rectal temperature at the time of admission; these variables were to a great extent normalized within 48 hours after admission. No differences in those physical signs were seen between patients with fully developed delirium tremens and patients with less severe clinical states. The patients' condition during the acute state was followed by means of a delirium tremens rating scale. Physical symptoms were similar in various degrees of severity of the clinical condition. 18-24 hours after admission the differences in mental symptoms between patients with grade 3 and patients with grade 2 had disappeared, 48 hours after admission the patients' condition was to a large extent normalized. Methodological problems in using a rating scale in conditions as delirium tremens are discussed. The results are discussed in relation to aetiology and pathogenesis of delirium tremens. It is concluded that it may be that a qualitative, and not only a quantitative, difference exists between a severe withdrawal reaction and fully developed delirium tremens, and a hypothesis about a "point of no return" is suggested.     

Cerebrospinal fluid amine metabolites in delirium tremens

Cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA) and tryptophan (TRY) were measured in 14 male alcohol-dependent patients with delirium tremens. Lumbar punctures were performed immediately after admission following a standardized psychiatric examination and symptom rating in a drug-free state. Results were compared with a control group consisting of 32 neurological patients with only peripheral disorders, excluding spinal processes and abnormal routine CSF findings. All three substances were significantly increased in delirium tremens; 5HIAA showed the most marked and TRY the least pronounced increase. The statistical correction for age, height and body weight did not decrease but somewhat increased the differences. Duration of alcohol abuse did not account for the observed metabolic changes; severity of delirium tremens, however, correlated significantly with the 5HIAA and to a lesser degree with the HVA level. The further analysis revealed a differential relationship of the amine metabolite concentrations to some prominent symptoms: agitation was significantly dependent only on the HVA level while disorientation and hallucination seemed to be determined mostly by the serotonin metabolite 5HIAA in the CSF. TRY concentration proved to be unrelated to either global severity or any of these symptoms.