The detoxification experience of alcoholic in-patients and predictors of outcome.

This paper reports the detoxification experience and outcome at 6 months and 1 year following detoxification from alcohol in 160 patients admitted to a south-east London in-patient detoxification unit. Patients' socio-demographic characteristics are also described. The sample was predominantly middle-aged, mainly male, and highly dependent on alcohol. Subjects had been drinking heavily for many years and suffered physical and social complications in consequence. The rate of convulsions was 3.1% and of delirium tremens 1.25%. The details of the level of drug usage during detoxification and the assessment of severity of the withdrawal syndrome are also reported. The severity of the withdrawal syndrome and the incidence of significant complications of withdrawal were higher in those with a previous history of four or more episodes of detoxification, a previous history of withdrawal fits or evidence of high levels of tolerance and dependence assessed either by the Severity of Alcohol Dependence Questionnaire (SADQ) or by drinking on a typical heavy drinking day in excess of 24 U of alcohol. It is suggested that subjects with one or more of these attributes should be treated on an in-patient, rather than an out-patient, basis unless adequate support and monitoring systems are in place. Overall, patients made improvements on a wide range of social and psychological variables, but the 'abstinent' and 'controlled drinking' groups made significantly higher improvements on all variables in both follow-up periods. When patients improved their drinking status and reduced the levels of drink-related physical and social complications, in both time periods, their use of social and health resources decreased significantly. Living circumstances at intake were predictive of drinking status at both follow-up stages. The amount drunk on a heavy drinking day, at both follow-up stages, was predicted by severity of withdrawal, SADQ and living circumstances at intake in that order of importance.

Frontal glioma presenting as anxiety and obsessions: a case report.

A 53-year-old gentleman is described, who presented with acute onset of anxiety and obsessional symptoms. The clinical picture was complicated by the presence of mild alcohol withdrawal symptoms and history of excessive drinking for 20 years. A month later, he developed right hemiparesis. CT scan revealed a left frontal tumour, and on histology this was found to be Grade 4 astrocytoma.

Alcoholism: a long-term follow-up study of participants in an alcohol treatment programme.

This paper reports the results of a long-term follow-up study of 112 alcoholic patients admitted to an intensive 1-month residential programme. Outcomes at the 6-month and 1-year stages were reported in an earlier paper [G. K. Shaw et al. (1990) British Journal of Psychiatry 157, 190-196]. The length of the follow-up period in this study was an average of 9 years. Eighteen patients had died before the long-term follow-up stage, and of the remaining 94 a total of 60 patients were followed up. This study shows that major improvements on social, psychological and drinking behaviour measures, made at 6 months and 1 year follow-up, were, on the whole, maintained and there was a progressive improvement on most variables at each follow-up stage. Major improvements were achieved by those patients whose drinking was categorized as 'abstinent', 'controlled' and 'improved'. The proportion of patients categorized as 'unchanged' dropped from 43% at 6 months to 33% at 1 year and to 15% at 9 years. By the 1-year follow-up stage, the unchanged group showed deterioration on psychological variables such as neuroticism, self-esteem and satisfaction with life situations, continued to make use of health service resources, and the high level of alcohol-related physical and social complications remained unchanged. This group had similar results at long-term follow-up with the exception of neuroticism, which was significantly lower in all drinking categories.

Thiamine pyrophosphate effect and normalized erythrocyte transketolase activity ratio in Wernicke-Korsakoff patients and acute alcoholics undergoing detoxification.

Thiamine deficiency may be assessed clinically by an abnormally low specific erythrocyte transketolase activity and/or by abnormally large activation by thiamine diphosphate in vitro (or 'TPP effect'). In the present investigation, we report erythrocyte transketolase activation by TPP in acute alcoholics and Wernicke-Korsakoff patients undergoing detoxification. A new age-dependent parameter was used to improve the reliability of transketolase activity as an indicator of marginal thiamine deficiency. Thus normalized transketolase activity ratio (NTKZ), primary activation ratio (PAR) and further activation ratio (FAR) were measured in 29 acute alcoholics and 12 Wernicke-Korsakoff patients upon admission, and also on 47 control subjects. It was possible to follow up 14 of the 29 acute alcoholics after 7 days of treatment. Twenty-one per cent of the acute alcoholics and 33% of the Wernicke-Korsakoff patients, on admission to the detoxification Unit, had NTKZ values beyond the defined critical conditions for thiamine deficiency, whereas 7% of the former and 25% of the latter had PAR values beyond these critical conditions. Furthermore, all three parameters were significantly different in the Wernicke-Korsakoff patients compared to the other groups. The pattern of improvement of the different parameters on follow-up varied considerably and is difficult to explain, as only the NTKZ was statistically significant. Hence, only eight out of 14 acute alcoholics showed improvement in NTKZ, seven showed improvement of PAR and six showed improvement of FAR after treatment. Five patients showed improvement of both NTKZ and PAR and none of the patients showed improvement of all three parameters. We conclude that our findings confirm previous reports and that this modified transketolase activation test improves its reliability as an indicator of marginal thiamine deficiency.

Detoxification: the use of benzodiazepines.

The use of benzodiazepines in the management of alcohol withdrawal in chemically dependent alcoholics is reviewed. Benzodiazepines are safer than earlier sedative drugs used for this purpose, such as barbiturates, chloral hydrate and paraldehyde. Differences in efficacy between individual benzodiazepines are slight, but benefits and disadvantages of longer acting (diazepam and chlordiazepoxide) drugs and shorter acting (lorazepam and oxazepam) are compared. Long-term outcome is commented on.

Tiapride in the prevention of relapse in recently detoxified alcoholics.

BACKGROUND: The aim was to investigate the effect of tiapride (100 mg three times a day for at least one month) on outcome following detoxification. METHOD: The setting was a tertiary referral centre. The study design was randomised, double-blind, and placebo-controlled. One hundred routinely admitted alcohol-dependent patients were entered, and 54 completed the trial. Outcome was assessed by considering drinking status at three months and six months follow-up, and by comparing psychological status at intake and follow-up using the Crown-Crisp Experiential index, the Litman Self-esteem scale and a Satisfaction with Life Situations scale. We also compared performance over the six months before admission with the three and six months of follow-up on measures of health, social and drinking variables. RESULTS: Tiapride proved better (usually at statistically highly significant levels) than placebo at promoting: abstinence, self-esteem, and satisfaction with life situations; and at reducing: alcohol consumption, use of health service resources, and levels of neuroticism. CONCLUSIONS: Tiapride merits serious consideration in the longer-term treatment of alcoholic patients.

Alcoholism: a follow-up study of participants in an alcohol treatment programme.

One hundred and twelve alcoholic patients treated by an intensive one-month residential programme were followed up for one year. As a group, they were socially disadvantaged and highly dependent on alcohol. Outcome of treatment was assessed at six months and one year following discharge by multiple measures which included assessments of drinking behaviour, measurements of social stability, neuroticism and self-esteem, and self-ratings of satisfaction with important aspects of day-to-day living. During the first six months following treatment, 37% were abstinent or drinking in controlled fashion; during the second six months, 53% achieved this status. Improvement in drinking status was positively related to improvements in all other outcome variables.

The genesis of alcoholic brain tissue injury.

1. Acetaldehyde has been implicated in the pathogenesis of alcohol-related liver damage by two mechanisms. Adduct formation with many tissue constituents, especially proteins, makes them immunologically foreign or reduces enzyme activity and formation of cytotoxic free radicals from acetaldehyde metabolism. Adduct formation damage to microtubule associated proteins and to hepatocyte membranes impedes protein movement into, out of and around the cell. 2. Evidence that these mechanisms also have a role in alcoholic brain damage includes raised blood acetaldehyde in alcoholics, especially in those chemically dependent, or in other abnormal states; effects of extra-hepatic free radical toxicity, including induction of superoxide dismutase activity and damaged, abnormal variants of the thiamin-dependent enzyme transketolase and extrahepatic acetaldehyde-adduct formation with haemoglobin. That acetaldehyde-mediated impairment of microtubule systems also damages the brain is suggested by its importance for the maintenance by protein transport of often greatly extended brain cell processes. 3. Oxygen-derived free radicals can damage brain tissue, the effects including cerebral oedema, neuronal loss and damage to the blood-brain barrier, all changes also reported in the brains from alcoholic patients. Alcohol-related pathology in the brain differing from that in the liver, shows sharper regional variations in vulnerability and adverse effects due to nutritional deficiencies, especially of B-group vitamins. Even though some such deficits are capable of causing encephalopathy in the non-alcoholic, the strong association between them and chronic alcoholism points to possible aggravation by metabolic interactions at various levels between acetaldehyde and thiamin or other B-vitamins. Selective regional vulnerability may reflect differences in ease of acetaldehyde access or to important metabolic differences. Alteration of animal behaviour by acetaldehyde points to a need to correlate clinical evidence of acetaldehyde central nervous cytotoxicity with the incidence of different types of cognitive defect.

The age dependence of the activity and activation of human red blood cell transketolase.

Erythrocyte transketolase has been measured in normal controls and non-alcoholic patients not at risk from nutritional deficiency and without signs of brain damage. The enzyme activity declines steadily with age over a range from 18 to 90 years with a statistically significant fall of 25% over this period. Since this decline is apparent whether or not thiamin diphosphate is added in vitro to activate the apoenzyme, the activation ratios are independent of the age effect. The decline is seen in both sexes in patients and normal subjects. It is concluded that the reliability of the specific transketolase activity as an indicator of marginal thiamin deficiency will be improved if the results are expressed as a percentage of the mean normal value corrected for age with values less than 60% of the age adjusted mean taken to indicate possible deficiency.

Relationship between plasma adrenocorticotrophic hormone and cortisol concentrations in chronic alcoholic patients with depression.

In 20 hospitalized male chronic alcoholic patients, plasma adrenocorticotrophic hormone (ACTH) levels were estimated by radioimmunoassay and cortisol levels by the competitive protein binding (CPB) method with radioactive selenium-75 on admission and during abstinence along with rating of the degree of depression immediately after the acute phase of the ethanol withdrawal syndrome was over. Duration of drinking ranged from 5 to 25 years and average daily ethanol intake was between 100 and 150 g. Plasma ACTH levels were found to be raised in drinking chronic alcoholics. There was a positive and statistically significant correlation between depression ratings and plasma ACTH concentrations (r = + 0.379; P less than 0.05). In chronic alcoholism the negative feedback mechanism seems to be disturbed between plasma ACTH and cortisol levels which are not normalised after 1 week of total abstinence. Chronic ethanol ingestion might have a direct stimulatory effect on the adrenal cortex leading to dysregulation of the hypothalamo-pituitary-adrenocortical axis.

Superoxide dismutase in the erythrocytes of acute alcoholics during detoxification.

The activity of erythrocyte superoxide dismutase in acute alcoholic patients on admission does not form a single population but clusters in two groups either above or below the normal range. The values in both groups revert towards the normal after a week of treatment. The divergent activities of this free radical scavenging enzyme between the two groups could not be explained by differences in age, haematology or liver function tests but are likely to be acute responses, possibly to diverse drinking patterns in the period immediately preceding admission.

Alcohol and brain damage.

1. The safe limits of alcohol intake are difficult to define because of individual variations in susceptibility to damage. The present recommendations are based largely on epidemiological studies of liver damage. 2. Recent investigations indicate that alcoholic brain damage is much more common than previously suspected. More information is required about its natural history and the characteristics of individuals most likely to suffer damage. 3. Thiamin (vitamin B1) deficiency has long been associated with brain damage and may result from a number of additive causes in the alcoholic patient. New information indicating damage to the protein moeity of some of the thiamin-using enzymes has been reviewed, as have possible mechanisms of brain cell necrosis.

The dexamethasone suppression test in chronic alcoholics with and without depression and its relationship to their hepatic status.

Fifty consecutively admitted male alcoholics (mean age = 42.8 +/- 8.5 years) were selected. This study shows objectively that 31/50 chronic alcoholics (62%) were found to be severely depressed (Hamilton Depression Rating Scale (HRS) greater than 22); 12/50 (24%) moderately depressed (HRS = 16-22); and 7/50 (14%) were not depressed (HRS less than 15). According to dexamethasone suppression test (DST) results, 8 out of 50 patients showed escape from suppression with 2 mg dexamethasone while 42/50 showed normal suppression. Depression in alcoholics may be of neurotic type or it may be ethanol-induced reactive depression. Raised cortisol levels and abnormal DST response showed a definite tendency towards normalisation after total abstinence accompanied by clinical improvement of depressive symptomatology. The DST showed improvement on improvement of mood and sleep in these patients during total abstinence. An abnormal DST response in chronic alcoholics seems to be state-related and not trait-dependent; it seems to be a non-specific test for depression in alcoholics. Hepatic status was affected equally in both suppressors and non-suppressors of DST. It is therefore suggested that abnormal DST in alcoholics may be due to the abnormality of the hypothalamo-pituitary-adrenocortical (HPA) axis and not due to abnormal hepatic function or histological status.

The activation of red blood cell transketolase in groups of patients especially at risk from thiamin deficiency.

Erythrocyte transketolase activation by thiamin diphosphate has been studied in elderly patients with moderate or severe chronic dementia, acute alcoholic admissions and chronic alcoholics with evidence of brain damage, mostly of the Wernicke-Korsakoff type. Significantly more patients in each group than controls showed abnormal activation of transketolase, not only by 0.3 mM thiamin diphosphate (TDP) but also in further activation by increase to 3 mM. This indicated the presence in a proportion of the alcoholic and the demented patients of an abnormal enzyme variant, similar to that previously found in vitro. The modified transketolase activation test may warn not only of marginal thiamin deficiency but also independently, of susceptibility to brain damage in patients at risk.

Tiapride in the long-term management of alcoholics of anxious or depressive temperament.

Thirty-two chemically dependent alcoholics with significant levels of anxiety or depression were admitted to a double-blind randomised study in which the effect of the substituted benzamide tiapride was compared with that of placebo over a 6-month period. Twenty patients completed the study. Assessments included relevant biochemical and haematological tests, drinking levels and associated behaviour, expressed satisfaction with various areas of life, the Crown-Crisp Experimental Index of neurotic symptoms and questionnaires on self-esteem and alcohol dependence. The results indicated that in comparison with the placebo group, patients treated with tiapride drank less and had longer periods of abstinence. This was associated with improvements in laboratory tests, reduction in neurotic symptoms, gains in self-esteem and increased levels of expressed satisfaction with life situation. The drug was well tolerated and no deleterious effects were noted, suggesting its potential usefulness for this patient group.

Nutrition and alcoholic encephalopathies.

An assessment has been made of metabolic factors possibly causing or contributing to the brain damage associated with chronic alcoholism, especially thiamin lack or disturbance of amino acid metabolism. Abnormalities in the thiamin-dependent enzyme, transketolase, provide evidence of a high incidence of thiamin deficiency as well as of disturbed thiamin metabolism in chronic alcoholics, which are likely to be caused by reduced vitamin intake as well as impaired absorption. A grossly disturbed pattern of amino acids in the blood of patients undergoing treatment for alcohol withdrawal syndromes is likely to be caused by loss of hepatic function and may well aggravate brain damage caused by B group vitamin deficiency. A hypothesis is proposed of how chronic thiamin lack can lead to brain damage.

Changes in the activation of red blood cell transketolase of alcoholic patients during treatment.

Erythrocyte transketolase activation by thiamin diphosphate has been studied in alcoholic patients on admission and after treatment, which included vitamin therapy. The high proportion of the patients who showed an abnormal activation of transketolase, not only by 0.3 mM thiamin diphosphate but also further activation by increasing the thiamin diphosphate to 3 mM, was reduced considerably after treatment. A few patients, however, still showed continuing abnormalities even after treatment. Further study of the enzyme activation in vitro confirmed the presence of an enzyme variant, abnormal both in the ease with which the thiamin diphosphate could be removed and in requiring a high concentration of thiamin diphosphate for activation. Since the modified transketolase activation test appears not only to monitor the effectiveness of thiamin therapy but also independently to warn of persisting enzyme abnormalities, it could prove to be of general use in alcohol detoxification units.

Palmitoyl-catechin for alcoholic liver disease: results of a three-month clinical trial.

A prospective randomized double-blind trial of 3-palmitoyl-(+)-catechin at a dose of 1500 mg daily (500 mg t.d.s.) for 3 months vs placebo has failed to demonstrate statistically significant clinical, biochemical or histological benefit in patients with biopsy-proven alcoholic liver disease. Nevertheless, this trial has confirmed the beneficial effect of a reduction in the rate of alcohol consumption on alcoholic liver disease. Apart from clinical evidence of a higher rate of alcohol consumption by patients receiving the active drug during the trial, no adverse side-effects were identified and for this reason, it is suggested that a further trial should be considered with the daily dosage so far used in man (20 mg/kg) increased toward that (100 mg/kg) employed with benefit in animal experiments.

Reduced stability of rat brain transketolase after conversion to the apo form.

The stability of rat brain transketolase, whether measured at 37 or 0 degree C, was reduced after conversion to the apo form by removal of thiamine diphosphate, as shown by a decline in the activity recovered when assayed in the presence of thiamine diphosphate. Both the shape of the breakdown curve and the failure to recover the full activity, even after incubation with thiamine diphosphate, showed that the breakdown of the apotransketolase was complex. The initial rate of breakdown of the apoenzyme was sharply pH dependent, being minimal at 37 degrees C at a pH value of 7.6, close to that likely to exist in vivo. The rate rose sharply with deviation of the pH in either direction. The stability of the enzyme on storage at 0 degree C showed a similar pattern of pH dependence, provided that allowance is made for temperature effects on dissociation constants. These findings provide further support for the hypothesis that differences in brain transketolase may play a part in the etiology of Wernicke-Korsakoff's syndrome.