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.

Regulation of neuronal and recombinant GABA(A) receptor ion channels by xenovulene A, a natural product isolated from Acremonium strictum.

Xenovulene A (XR368) is a natural product exhibiting little structural resemblance with classical benzodiazepines yet is able to displace high-affinity ligand binding to the benzodiazepine site of the gamma-aminobutyric acid (GABA)A receptor. We have characterized this compound and an associated congener (XR7009) by use of radioligand binding and electrophysiological methodologies with native neurons and the Xenopus oocyte expression system. Xenovulene A, and the more potent XR7009, inhibited [3H]flunitrazepam binding to rat forebrain with Ki values of 7 and 192 nM, and 1.7 and 42 nM, respectively, each site accounting for approximately 50% of the total specific binding. In cerebellar and spinal cord membranes, these ligands identified only single binding sites. These ligands demonstrated no intrinsic agonist activity at recombinant GABA(A) receptors comprising alpha1beta1gamma2S subunits expressed in Xenopus oocytes, yet at 1 microM both significantly potentiated the GABA-induced response and reduced the GABA EC50 from 10.9 (control) to 5.1 (Xenovulene A) or 2.7 microM (XR7009). The rank potency order for enhancement of the 10 microM GABA response is: XR7009 (EC50, 0.02 microM) > diazepam (0.03) > Xenovulene A (0.05) > flurazepam (0.17). The activity of XR368 and XR7009 was reduced by the benzodiazepine antagonist, flumazenil, and absent in receptors devoid of the gamma2 subunit. These agents exhibited receptor subtype selectivity because alpha3beta1gamma2S receptors were less sensitive to these compounds relative to alpha1 subunit-containing receptors, whereas alpha6beta1gamma2S receptors were completely insensitive. Potentiation of the response to GABA on native GABA(A) receptors in cortical neurons substantiates the profile of the novel structures of Xenovulene A and XR7009 as specific benzodiazepine agonists.

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.

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.

Metabolism of toxic pyrrolizidine alkaloids from tansy ragwort (Senecio jacobaea) in ovine ruminal fluid under anaerobic conditions.

The ability of ovine ruminal fluid to metabolize pyrrolizidine alkaloid (PA) from Senecio jacobaea under anaerobic conditions was evaluated. Four fistulated sheep fed PA served as individual sources of ruminal fluid, which was incubated in a defined minimal salts medium under two different anaerobic conditions, denitrifying and methanogenic. Anaerobic cultures amended with ovine ruminal fluids (20%), PA (100 micrograms/ml), and a defined minimal salts medium were monitored for a period of several days. These cultures revealed that while PA was not depleted in sterile, autoclaved controls or under denitrifying conditions, it was metabolized during periods of active methanogenesis under methanogenic conditions. In addition, samples of ruminal fluid were separated by differential centrifugation under anaerobic conditions, and the resultant supernatants were tested for their ability to metabolize PA as compared with those of the respective uncentrifuged control fluids. Uncentrifuged controls exhibited a PA depletion rate of -4.04 +/- 0.17 micrograms of PA per ml per h. Supernatants 1 (centrifuged at 41 x g for 2 min), 2 (centrifuged at 166 x g for 5 min), and 3 (centrifuged at 1,500 x g for 10 min) exhibited significantly slower depletion rates, with slopes of data representing -1.64 +/- 0.16, -1.44 +/- 0.16, and -1.48 +/- 0.16 micrograms of PA metabolized per ml per h, respectively, demonstrating no statistically significant difference among the supernatant cultures. Microscopic evaluations revealed that protozoa were present in the control whole ruminal fluid and to a lesser extent in supernatant 1, while supernatants 2 and 3 contained only bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterisation of adjustments to the structure of feeding behaviour following pharmacological treatment: effects of amphetamine and fenfluramine and the antagonism produced by pimozide and methergoline.

An observational procedure for examining the micro-structure of eating has been employed to establish the characteristic behaviour patterns displayed after various pharmacological manipulations. Using a double dissociation design it was shown that amphetamine and fenfluramine gave rise to quite distinctive readjustments to the structure of feeding behaviour. Amphetamine anorexia was characterised by a long initial delay, following which feeding was typified by infrequent short bursts of rapid eating. These effects were antagonised by the dopamine receptor blocking agent, pimozide. Fenfluramine exerted a more restricted pattern of action characterised by a marked slowing of the rate of eating. This effect was countered by the serotonin receptor blocking agent methergoline. These data throw light on the way in which pharmacological agents may impede food consumption and upon the neurochemical systems believed to be involved in the expression of feeding behaviour.

Serotonergic influences on food intake: effect of 5-hydroxytryptophan on parameters of feeding behaviour in deprived and free-feeding rats.

Three experiments were carried out to examine the effect of the serotonin precursor, 5-hydroxytryptophan, upon food intake and the micro-structure of eating in deprived rats, and on the pattern of meal taking in free-feeding animals. The study also investigated the capacity of a peripheral decarboxylase inhibitor (MK-486) to antagonise the effect of 5-HTP in order to identify a central or peripheral mode of action. In deprived rats 5-HTP brought about a dose related inhibition of food intake which was midly antagonised by MK-486. A detailed analysis of the behavioural changes occurring during eating showed that the inhibition of food intake by 5-HTP was reflected in a reduced number of eating bouts and a slower rate of eating. MK-486 did not antagonise the effect of 5-HTP on eating rate. In free-feeding rats whose food comsumption was continuously monitored for 24-hr periods, 5-HTP gave rise to reduction in meal size and a slowing of the intra-meal rate of eating. These findings are in keeping with the effects of other serotonergic manipulations on the patterns of feeding in rats.

Differences between the anorexic actions of amphetamine and fenfluramine--possible effects on hunger and satiety.

The inhition of feeding in rats brought about by amphetamine and fenfluramine was continuously monitored for periods of up to 24 h using a pellet detecting eatometer. For rats tested under conditions of food deprivation the two drugs gave rise to distinctive anorexic profiles: amphetamine delayed the onset of eating whereas fenfluramine allowed eating to commence normally but brought about an early termination of the initial bout of feeding. When the drugs were administrated to rats with free access to food, analysis of the meal pattern showed that amphetamine gave rise to a small increase in the inter-meal interval while fenfluramine brought about a clear reduction tion in meal size. It is suggested that the contrasting modes of action of these drugs represent an effect of amphetamine upon hunger and an action of fenfluramine on satiety. This suggestion is in keeping with the proposed mechanisms of action of these drugs, amphetamine acting upon a hpothalamic motivational system and fenfluramine acting by means of a postulated serotoninergic satiety system. Use of the continuous monitoring technique has pointed pointed to certain limitations in the assessment of anorexic drug action by means of discrete food sampling periods.