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Biomedical subjects

J B Whitfield

Publications and source records attributed to J B Whitfield.

At least 19 recordsLinked to original sources

Is alcohol-related flushing a protective factor for alcoholism in Caucasians?

Although alcohol-related flushing seems to be a genetically influenced protective factor for alcoholism in some Asian groups, little is known about whether this is true for Caucasians. The evidence for alcohol-related flushing as a protective factor for the development of alcoholism was examined in a sample of 5831 Australian twins (2041 men, 3790 women) who were administered a structured psychiatric interview. Twin correlations for self-reported adverse alcohol reactions (e.g., "flushing or blushing" and "feeling very sleepy" after drinking 1 or 2 drinks) were modest, suggesting minimal contribution of genetic factors, but when corrected for reliability of measurement, were consistent with moderate heritabilities. In accord with studies examining Asian samples, we found that individuals who experienced adverse reactions after drinking small amounts of alcohol drank less often and slightly less per drinking occasion than those who did not experience adverse reactions. However, those who experienced adverse reactions were more likely to have symptoms of alcoholism and to report a parental history of alcohol problems. We conclude that self-reported alcohol-related flushing is not a protective factor for alcoholism in Caucasians and may be a risk factor.

Adult

Diagnostic tests for alcohol consumption.

A variety of laboratory tests are available to assist in the diagnosis of hazardous alcohol consumption and related disorders. Standard tests, such as serum gamma glutamyltransferase activity and erythrocyte mean cell volume, have limited sensitivity, particularly in detecting non-dependent hazardous consumption. Most also have poor specificity in that results are affected by common diseases and medications. Over the past 10 years a number of new laboratory tests have emerged. One of these, carbohydrate deficient transferrin, has high sensitivity in detecting persons with alcohol dependence, and shows promise for identification of non-dependent hazardous drinking; it is also highly specific. Others such as measurement of bound acetaldehyde, serum beta-hexosaminidase and the ratio of urinary serotonin metabolites offer promise in detecting recent heavy drinking. However, many issues remain unresolved. The newer markers have often been judged by contrasting their values in patients who are clearly alcohol dependent and abstainers or very light drinkers. It is now apparent that some are relatively insensitive markers of hazardous consumption. Future research needs to examine the performance of these markers among subjects with a range of alcohol intakes to fully determine their value in assessing drinking history. In addition, assays which are capable of some degree of automation need to be developed for analysing large numbers of samples.

Alanine Transaminase

Carbohydrate deficient transferrin levels in hazardous alcohol consumption.

Little information is available on the value of carbohydrate deficient transferrin (CDT) in detecting persons with hazardous alcohol consumption. In the present study isoelectric focusing (IEF) and immunofixation were used to examine the sensitivity of CDT in hazardous drinkers compared with control subjects and alcohol dependent persons. Elevated CDT levels (> 100 mg/l) were found in 62% of hazardous drinkers and 67% of alcohol dependent persons compared with only 5% of controls. CDT was more sensitive than serum gamma glutamyltransferase (GGT) activity in detecting hazardous alcohol consumption (sensitivity of GGT 19%; P < 0.001), but was of comparable sensitivity to GGT for alcohol dependence. Neither the transferrin index nor transferrin ratio offered any advantage over CDT in detecting hazardous consumption. We conclude that serum CDT, as measured by IEF and immunofixation, is a sensitive and specific test for hazardous drinking.

Adult

Alcohol consumption and alcohol pharmacokinetics: interactions within the normal population.

We have analyzed the interrelationships between habitual alcohol consumption, peak blood alcohol concentration after a standard dose, and rate of alcohol metabolism in a group of 199 male and 213 female twins. Both peak concentration and rate of metabolism are strongly associated with alcohol consumption levels, even in the range of 0-10 g of alcohol/day. The peak concentration and rate of metabolism were strongly correlated in both men and women; this is not due to their common dependence on alcohol intake nor to experimental error. These results show that the threshold for effects of habitual consumption on alcohol pharmacokinetics is much lower than previously suspected, and that there are factors that reduce preabsorptive or first-pass metabolism but increase postabsorptive metabolism.

Adolescent

Prediction of alcohol-related harm by laboratory test results.

We examined the value of laboratory markers of excessive alcohol (ethanol) intake as predictors of mortality, morbidity, and health-care utilization in a cohort of 330 patients attending an acute ambulatory care service. Among men, all four markers examined--gamma-glutamyltransferase (GGT) and aspartate aminotransferase (AST) activities, high-density lipoprotein cholesterol (HDL-C), and mean corpuscular volume (MCV)--were predictive of medical sequelae and health-care utilization over a 3-year period. In contrast, social problems were more closely related to the amount of alcohol consumption at initial assessment than to any biological marker. Serum GGT and AST activities and MCV were predictive of medical sequelae in women. The predictive value of GGT was an independent risk factor and did not merely reflect recent alcohol intake or the presence of chronic liver disease. We conclude that these readily available laboratory tests provide important prognostic information and should be an integral part of the assessment of persons with hazardous alcohol consumption.

Alcoholism

Effects of increasing the rate of alcohol metabolism on plasma acetate concentration.

Plasma acetate concentration is increased during alcohol metabolism. However, measures which increase the rate of alcohol metabolism do not always increase plasma acetate concentration. Plasma samples from normal male subjects who had been given alcohol and then either fructose or glucose were analysed for acetate. Although each of these carbohydrates increased the mean rate of alcohol metabolism, only fructose increased the plasma acetate concentration. It was concluded that the further metabolism of acetate produced from alcohol may be increased by glucose.

Acetates

Protease inhibitor frequencies: is there a deficit of M subtype heterozygotes?

A large number of reports on human protease inhibitor (PI) type frequencies in various populations have now appeared. A combination of the results of published studies shows that the observed frequencies of the M subtype homozygotes and heterozygotes differ significantly from those predicted by the Hardy-Weinberg equilibrium, especially among Europeans but probably not among Asians or Africans. The M1, M2 and M3 homozygotes are more numerous than would be expected, while the M1M2 and M1M3 heterozygotes are less common than expected.

Africa

The effect of fructose on alcohol metabolism and on the [lactate]/[pyruvate] ratio in man.

Ten male subjects were given alcohol by intravenous infusion and maintained at a constant blood alcohol level. The rate of alcohol metabolism was measured before and after an oral dose of fructose (100 g), as the amount of alcohol required to maintain the steady state. The mean rate of alcohol metabolism increased by 80% after fructose but there was considerable variation among the subjects, which was related to their plasma fructose concentrations. Blood lactate increased after fructose to a greater degree than blood pyruvate, resulting in a significant increase in [lactate]/[pyruvate] ratio. Since fructose increased the [lactate]/[pyruvate] ratio when it increased alcohol metabolism, the action of fructose cannot be explained by a decrease in the liver cytoplasmic [NADH]/[NAD] ratio and some other mechanism must be sought.

Adolescent

Effect of humidification on the airways of cats during high-frequency ventilation.

The effect of humidity on the histologic lesions induced by high-frequency jet ventilation was investigated in 12 healthy cats. After 16 hours of ventilation, the appearance of the tracheal epithelium ranged from normal to necrotic. The damage was considerably more severe in the trachea of cats of the group ventilated without added humidity. Increasing the relative humidity to 63% at 24 C had a protective effect, but further increasing the relative humidity to 92% at 35 C did not appear to provide significantly more protection. The bronchi and distal airways had minimal, if any, damage in all groups.

Animals

Alpha-1-antitrypsin (protease inhibitor) phenotypes and longevity.

We have tested the hypothesis that the protease inhibitor phenotypes MZ and MS are disadvantageous and reduce survival by comparing the prevalence of these phenotypes in a group of 707 very old people (hospital patients) with the prevalences reported in younger populations of blood donors. The MS and MZ phenotypes appear to be no less common among those who have survived to old age, but a highly significant difference was found in the occurrence of the M subtypes. The M1 type was more common in the elderly, and the M heterozygotes were less common than would be predicted from the reported incidence in younger groups and from the Hardy-Weinberg equilibrium. This discrepancy appeared to be smaller in subjects of Mediterranean origin than in those of British or Irish genetic background.

Aged

Effect of diet on [lactate]/[pyruvate] ratios during alcohol metabolism in man.

Ten subjects received alcohol by intravenous infusion on two occasions, after five-day periods on high- or low-carbohydrate diets. Blood [lactate]/[pyruvate] ratios were significantly higher during fasting alcohol metabolism after the low-carbohydrate, high-fat diet. The carbohydrate/fat balance in the diet may affect cytoplasmic-mitochondrial NADH transfer. Dietary composition may modify the metabolic changes caused by alcohol.

Adult

Surgical management of bilateral diaphragmatic paralysis in a dog.

Bilateral diaphragmatic paralysis of uncertain cause developed in a 3-month-old Golden Retriever. A surgical procedure for tightening the diaphragmatic muscle was used to help alleviate the dog's respiratory distress. During thoracotomy, the central tendon of the diaphragm was plicated, using an interlocking suture pattern. The dog improved after surgery, and although complete recovery from paralysis was achieved only on one side, the dog has remained clinically normal 1 year after surgery.

Animals

Effect of oral glucose on the rate of metabolism of ethanol in humans.

We have tested whether the effect of carbohydrate on the rate of alcohol metabolism can be reproduced by glucose alone. Ten male subjects were given ethanol by intravenous infusion until a steady state was established and 100 g glucose in solution was then taken orally. The rate of alcohol metabolism, measured as the rate of infusion required to maintain a constant breath alcohol reading, increased significantly after glucose but there were differences between the subjects. The presence or absence of a change in the rate of alcohol metabolism after glucose was associated with the subject's fasting rate and with their glucose tolerance.

Administration, Oral

Differing effects of carbohydrate, fat and protein on the rate of ethanol metabolism.

The rate of metabolism of ethanol in humans has been assessed by intravenous infusion of ethanol/saline under feedback control to maintain a constant blood alcohol concentration. After equilibration, meals consisting predominantly of carbohydrate, fat or protein were eaten and changes in ethanol metabolic rate were found. Carbohydrate caused a significant increase in this rate and fat or protein caused small but non-significant decreases. Infusion of ethanol/saline resulted in a temporary fall in plasma free fatty acid levels and a steady rise in plasma triglycerides. The changes in alcohol metabolism following carbohydrate cannot be accounted for by changes in insulin, free fatty acid or lactate/pyruvate levels.

Adult

Genetic variation and plasma creatine kinase activity.

The distribution of plasma creatine kinase (CK; E.C.2.7.3.2) is known to be skewed, and this has made it difficult to analyse the sources of variation. We have studied plasma CK in 206 pairs of twins and have analysed the results after separating them into what appear to be two Gaussian frequency distributions. The results in the main distribution (CK less than 300 iu/1) are apparently affected by genetic factors common to both men and women, and by environmental factors which are of much greater effect in men. The tendency for some men to have very high CK values may also have a genetic basis.

Adult