Alcohol policy and aviation safety.

Aviation provides an environment which is almost uniquely unforgiving of mistakes. Accordingly, impairment of aircrew performance by alcohol can, and occasionally does, lead to catastrophic mistakes. That such disasters are rare, is a credit to the responsibility of aircrew themselves and to the effectiveness of aviation industry policies. Similarly, maintenance of this exemplary record depends upon continued attention to alcohol policy in the future. The aviation industry thus provides a useful model for the study of alcohol policies within a safety critical environment. Surprisingly, this model appears not to have been subjected to critical research and evaluation. Based upon previous research on alcohol and aviation, and in consideration of findings from the wider field of alcohol policy, suggestions are made here as to a promising framework for future alcohol policy formation in the aviation environment.

Alcohol and aviation.

Aviation accidents due to alcohol consumption by aircrew appear to be rare, especially in commercial aviation. However, a small proportion of general aviation accidents are attributable to alcohol use by aircrew, and aircrew are not well informed about the metabolism of alcohol and its effects on performance. Furthermore, there is evidence that aircrew performance may be impaired by alcohol consumption even after their Blood Alcohol Concentration has returned to "zero" (i.e. < 5 mg/dl). Accidents caused by impairment of aircrew performance by alcohol may therefore not be attributed to alcohol use at all. Aviation safety relies upon faultless human performance and is thus highly sensitive to alcohol-related impairment of performance. This paper provides a review of research regarding aircrew alcohol consumption, impairment of aircrew performance by alcohol, incidence of aviation accidents attributable to alcohol use by aircrew, and other related subjects.

The efficacy of disulfiram: a review of outcome studies.

Twenty-four studies of outcome following oral disulfiram and 14 following implanted disulfiram were identified for review from MEDLINE and PsycINFO databases and by manual searching for the period 1967-95. The methodological rigour of these studies was generally poor, albeit not as poor as that of earlier studies (not reviewed here). An overall assessment of the results of research in this field is hampered by the diversity of both the methods used and the subject populations studied. However, it is clear that support for the general use of oral disulfiram is equivocal, mostly being found in the form of reduced quantity of alcohol consumed and a reduced number of drinking days. Evidence for an effect in increasing the proportion of patients who achieve abstinence is surprisingly lacking. Where it is prescribed, disulfiram use should be supervised and it should be employed as one part of a comprehensive treatment programme. There is no good evidence in favour of implanting disulfiram tablets, but the possibility of a depot injection is intriguing.

Knowledge and experience of drug use amongst church affiliated young people.

A large and growing proportion of young people in the UK are using drugs. Research from the US suggests a protective effect of church affiliation or 'religiosity', but this has not been investigated in British young people. In the present study, the prevalence of drug use was estimated amongst 7666 church affiliated young people in the UK in 1995, using a self report questionnaire survey. In the 12-16 year old age group, 23.4% had been offered at least one of a list of drugs, and 9.7% had tried such drugs. In those aged 17-30 years the figures were 46.1% and 23.3%, respectively. These figures are perhaps slightly less than, those obtained in secular surveys. Those who gave more positive responses to questions on Christian commitment were less likely to have been offered any of the listed drugs, or to have used them, as compared with those who gave no such responses. A lifetime history of ever having smoked demonstrated a far stronger association, with smokers being 15-20 times more likely to have used one of the listed drugs.

Effect of supplements on the nutrient intake of children.

Daily intakes of nutrients were calculated from records of food eaten at home, as school lunches, and morning milk, of boys and girls in second and sixth grades. Vitamin/mineral supplementations were also calculated. Comparisons were made (with and without supplementation) with the Recommended Dietary Allowances (RDAs). Analyses of variance between sexes and between grade levels showed second graders consumed better diets than sixth and boys better diets than girls. Although many received supplements, intakes of several nutrients were below the 67 per cent level. The milk program played a significant role in calcium consumption. Excessive amounts of vitamin A and ascorbic acid were consumed by some children.

Ascertainment of families for a linkage study of alcoholism.

Traditionally, researchers working in the field of genetics and alcoholism have used treatment centres and clinics to try and recruit suitable subjects for research purposes. The current study considered a diverse range of possible sources to recruit suitable families for a linkage study of alcoholism. These sources included the press, personal contacts and circular letters to alcohol treatment centres and members of the Substance Misuse Section of the Royal College of Psychiatrists. Only 9-14% of families contacted from any source were suitable for inclusion in the study, due to the strict selection criteria. Press contacts were found to be the most productive source of suitable families willing to participate in the study, accounting for over 50% of contacts and eventual subjects recruited. There appeared to be no bias in the affection status of subjects recruited from the different sources. For future genetic studies of alcoholism it might be worthwhile to utilize this source more fully. Reasons for exclusion from the study are also considered, with the most common reasons being non-co-operation and no family history.

The D2 dopamine receptor gene and alcoholism: a genetic effect in the liability for alcoholism.

Three of five recent association studies have demonstrated an increased frequency of the A1 allele of the TaqI Restriction Fragment Length Polymorphism (RFLP) of the DRD2 locus in alcoholics compared to controls. One of three family studies has shown preliminary results in favour of linkage of this locus with alcoholism and heavy drinking. The possible mechanism of a genetic effect of the DRD2 locus in alcoholism remains open to speculation, but many involve personality characteristics such as impulsiveness or spontaneity. The applications of the findings of research in this field offer much potential for the prevention and treatment of alcoholism, but also raise certain ethical issues when applied to screening programmes. Future research will be assisted by the development of new, and more informative, genetic markers which are now available at this locus.

Psychiatric aspects of alcohol misuse.

Alcohol and psychiatric disorder have a complicated relationship. Certain important psychiatric syndromes arise from the toxic effects of alcohol and thiamine deficiency. Liver disease and hypoglycaemia are also associated with their own psychiatric syndromes. Many psychiatric patients also turn to alcohol as an easily available 'medication'.

Consumption of oxygen: a mitochondrial-generated progression signal of advanced cancer.

Changes in mitochondrial genome such as mutation, deletion and depletion are common in cancer and can determine advanced phenotype of cancer; however, detailed mechanisms have not been elucidated. We observed that loss of mitochondrial genome reversibly induced overexpression and activation of proto-oncogenic Ras, especially K-Ras 4A, responsible for the activation of AKT and ERK leading to advanced phenotype of prostate and breast cancer. Ras activation was induced by the overexpression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), the rate-limiting enzyme of the mevalonate pathway. Hypoxia is known to induce proteasomal degradation of HMGR. Well differentiated prostate and breast cancer cells with high mitochondrial DNA content consumed a large amount of oxygen and induced hypoxia. Loss of mitochondrial genome reduced oxygen consumption and increased in oxygen concentration in the cells. The hypoxic-to-normoxic shift led to the overexpression of HMGR through inhibiting proteasomal degradation. Therefore, reduction of mitochondrial genome content induced overexpression of HMGR through hypoxic to normoxic shift and subsequently the endogenous induction of the mevalonate pathway activated Ras that mediates advanced phenotype. Reduction of mitochondrial genome content was associated with the aggressive phenotype of prostate cancer in vitro cell line model and tissue specimens in vivo. Our results elucidate a coherent mechanism that directly links the mitochondrial genome with the advanced progression of the disease.

Prevention and treatment of Wernicke-Korsakoff syndrome.

Wernicke's encephalopathy (WE) is both common and associated with high morbidity and mortality and yet there is evidence that appropriate and effective prophylaxis and treatment are often not given. Effective treatment and prophylaxis may only be achieved by use of parenteral vitamin supplements, since oral supplements are not absorbed in significant amounts. Although there are rare anaphylactoid reactions associated with the use of parenteral thiamine preparations, the risks and consequences of inadequate prophylaxis and treatment, in appropriately targeted groups of patients, are far greater. It is therefore proposed that all in-patient alcohol withdrawal should be covered by prophylactic use of parenteral thiamine, that there should be a low threshold for making a presumptive diagnosis of WE, and that there is a need for guidelines to assist physicians in appropriate management of this common clinical problem.

Alcohol withdrawal and hypokalaemia: a case report.

A case is presented where a 25-year-old man developed a serious hypokalaemia (K(+) 2.2 mmol/l) during alcohol withdrawal, despite intravenous saline treatment and normal feeding. As hypokalaemia can be symptom-free, we want to draw attention to the combination of vomiting, malnutrition and alcohol withdrawal, as these can cause lethal complications. We therefore recommend that potassium serum level should be routinely monitored during alcohol withdrawal, even when this is being managed in the community.

B-complex vitamins in the prophylaxis and treatment of Wernicke-Korsakoff syndrome.

Wernicke-Korsakoff syndrome, which is associated with high morbidity and mortality, is a more common neuropsychiatric sequela of alcohol misuse than is widely realized. It is easily prevented and treated with parenteral B-complex vitamins, although this treatment is widely under-utilized.

Parenteral thiamine and Wernicke's encephalopathy: the balance of risks and perception of concern.

Wernicke's encephalopathy, a disorder with significant mortality and high morbidity, is common amongst alcohol-dependent patients. Thiamine deficiency appears to play a key role in its aetiology, and parenteral high-dose thiamine is effective in prophylaxis and treatment. Unfortunately, reports of rare anaphylactoid reactions have led to a dramatic reduction in the use of parenteral thiamine, and it is possible that this change in treatment has led, or will lead, to an increase in morbidity and mortality. There is a need for education of doctors who treat alcohol-dependent patients, in order to ensure appropriate use of parenteral thiamine in prophylaxis and treatment of this disorder.

Obesity as a cause of "false-positive" alcohol misuse laboratory investigations.

Three patients are reported with a prior history of alcohol misuse accompanied by abnormal liver toxicity tests and other indices of alcohol misuse. A decreased but persistently raised serum gamma-glutamyl transferase activity during subsequent abstinence or controlled drinking was interpreted incorrectly as due to continued alcohol misuse whereas obesity-related fatty liver was the probable cause. The value of serum carbohydrate deficient transferrin assays in the differential diagnosis of abnormal liver toxicity tests is emphasized.