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A new software-based visual search and divided-attention test of cognitive performance was developed and evaluated in an alcohol dose-response study with 24 human subjects aged 21-62 years. The test used language-free, color, graphic displays to represent the visuospatial demands of driving. Cognitive demands were increased over previous hardware-based tests, and the motor skills required for the test involved minimal eye movements and eye-hand coordination. Repeated performance on the test was evaluated with a latin-square design by using a placebo and two alcohol doses, low (0.48 g/kg/LBM) and moderate (0.72 g/kg/LBM). The data on 7 females and 17 males yielded significant falling and rising impairment effects coincident with moderate rising and falling breath alcohol levels (mean peak BrALs = 0.045 g/dl and 0.079 g/dl). None of the subjects reported eye-strain or psychomotor fatigue as compared with previous tests. The high sensitivity/variance relative to use in basic and applied research, and worksite fitness-for-duty testing, was discussed. The most distinct advantage of a software-based test that operates on readily available PCs is that it can be widely distributed to researchers with a common reference to compare a variety of alcohol and drug effects.
Alcohol Clin Exp Res 1996 Dec
PMID:A PC-based software test for measuring alcohol and drug effects in human subjects. 898 7

We investigated specific subjective effects of naltrexone pretreatment or placebo during various intervals on the breath alcohol level (BAL) curve in nonalcoholic volunteers. Fifteen high-risk (social drinkers with an alcoholic father) and 14 low-risk (no alcoholic relatives in at least two generations) subjects were tested in a double-blind placebo-controlled study of the effects of 50 mg oral naltrexone on response to a moderate dose of alcohol. Dependent measures included subjective stimulation and sedation subscales from the Biphasic Alcohol Effects Scale (BAES) and mood subscales from the Profile of Mood States (POMS). At rising BALs, high-risk subjects showed a naltrexone-related attenuation of BAES stimulation. This effect was not evident in low-risk subjects, who directionally showed the opposite effect, although nonsignificant. For both groups, there were no significant naltrexone-related effects for BAES sedation; however, naltrexone did affect several POMS scales on alcohol response, such as decreased vigor, and increased fatigue, tension, and confusion. Confusion was significantly elevated for the high-risk group during rising BALs of the naltrexone session. The results suggest a differential response to naltrexone, based on paternal history of alcoholism and level of stimulation experienced during alcohol drinking.
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PMID:Effect of naltrexone on subjective alcohol response in subjects at high and low risk for future alcohol dependence. 912 58

To assess the association between the economic recession of the 1990s in Finland and sleep behaviour, a longitudinal study was conducted in an adult Finnish population cohort. Baseline data were obtained by means of reports on sleep behaviour, health-related behaviour, health status, and objective laboratory tests in 1983-1987. The second screening conducted in 1992-1995, i.e. during economic recession, repeated data collection by postal questionnaires. The prevalences of various sleep symptoms including insomnia, daytime tiredness, fatigue, parasomnias and the use of hypnotics remained similar in the same age cohorts during economic recession. Alcohol consumption and snoring increased among the middle-aged (30-49 years), though snoring shows the greatest individual stability among various sleep symptoms. Despite some baseline differences in the sleep/health behaviour frequencies, the changes were independent of gender and socioeconomic class. The prevalences over eight years of insomnia and snoring show fair chronicity, whereas daytime tiredness and fatigue seem to be less chronic. Middle-aged participants who were stably employed at the initial screening but became unemployed during economic recession were studied separately. Prospectively unemployed persons suffered more from insomnia and used more hypnotics than the continuously employed. We conclude that the sleep quality of the general Finnish population has not drastically deteriorated during severe economic recession except among unemployed blue-collar workers.
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PMID:Quality of sleep during economic recession in Finland: a longitudinal cohort study. 922 96

Previous studies (Ivester et al., Arch. Biochem. Biophys. 322, 14-21, 1995) have established that periportal and perivenous hepatocytes isolated from ethanol-fed rats demonstrate lower ATP concentrations than those in control preparations when the cells are maintained at very low oxygen tension. In the present investigation, experiments were implemented with periportal and perivenous hepatocytes to determine the effects of chronic ethanol consumption on cellular respiratory and glycolytic activities, since both contribute to maintenance of the energy state of the liver cell. Both periportal and perivenous hepatocytes from ethanol-fed rats demonstrated significantly increased, rather than decreased, respiratory activity when monitored with oxygen concentrations ranging from 16 to 140 microM. Whole liver hepatocytes from control and ethanol-fed animals demonstrated equivalent oxygen utilization, however. Glycolytic activity, monitored by lactate + pyruvate concentrations obtained after both anaerobic and aerobic incubation protocols, was decreased in both cell types from ethanol-fed animals. The glycogen concentrations in freshly isolated periportal and perivenous hepatocytes were also decreased eight- and sevenfold, respectively, as compared with control preparations. Incubation under anaerobic conditions resulted in almost complete depletion of glycogen in both cell types. These observations suggest the possibility that the decreased energy state observed in hepatocytes from ethanol-fed animals is related to a depression in anaerobic glycolysis due to depletion of the endogenous substrate, glycogen.
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PMID:Effect of chronic ethanol consumption on respiratory and glycolytic activities of rat periportal and perivenous hepatocytes. 947 92

Twenty healthy social drinkers (9 women and 11 men) drank either 50 g of ethanol (mean intake 0.75 g/kg) or 80 g (mean 1.07 g/kg) according to choice as white wine or export beer in the evening over 2 h with a meal. After the end of drinking, at bedtime, in the following morning after waking-up, and on two further occasions during the morning and early afternoon, breath-alcohol tests were performed and samples of urine were collected for analysis of ethanol and methanol and the 5-hydroxytryptophol (5-HTOL) to 5-hydroxyindol-3-ylacetic acid (5-HIAA) ratio. The participants were also asked to quantify the intensity of hangover symptoms (headache, nausea, anxiety, drowsiness, fatigue, muscle aches, vertigo) on a scale from 0 (no symptoms) to 5 (severe symptoms). The first morning urine void collected 6-11 h after bedtime as a rule contained measurable amounts of ethanol, being 0.09 +/- 0.03 g/l (mean +/- SD) after 50 g and 0.38 +/- 0.1 g/l after 80 g ethanol. The corresponding breath-alcohol concentrations were zero, except for three individuals who registered 0.01-0.09g/l. Ethanol was not measurable in urine samples collected later in the morning and early afternoon. The peak urinary methanol occurred in the first morning void, when the mean concentration after 80 g ethanol was approximately 6-fold higher than pre-drinking values. This compares with a approximately 50-fold increase for the 5-HTOL/5-HIAA ratio in the first morning void. Both methanol and the 5-HTOL/5-HIAA ratio remained elevated above pre-drinking baseline values in the second and sometimes even the third morning voids. Most subjects experienced only mild hangover symptoms after drinking 50 g ethanol (mean score 2.4 +/- 2.6), but the scores were significantly higher after drinking 80 g (7.8 +/- 7.1). The most common symptoms were headache, drowsiness, and fatigue. A highly significant correlation (r = 0.62-0.75, P <0.01) was found between the presence of headache, nausea, and vertigo and the urinary methanol concentration in the first and second morning voids, whereas 5-HTOL/5-HIAA correlated with headache and nausea. These results show that analysing urinary methanol and 5-HTOL furnishes a way to disclose recent drinking after alcohol has no longer been measurable by conventional breath-alcohol tests for at least 5-10h. The results also support the notion that methanol may be an important factor in the aetiology of hangover.
Alcohol Alcohol
PMID:Urinary excretion of methanol and 5-hydroxytryptophol as biochemical markers of recent drinking in the hangover state. 971 4

Bryostatin 1 is a protein kinase C partial agonist which has both antineoplastic and immune-stimulatory properties, including the induction of cytokine release and expansion of tumour-specific lymphocyte populations. In phase I studies, tumour responses have been observed in patients with malignant melanoma, lymphoma and ovarian carcinoma. The dose-limiting toxicity is myalgia. Sixteen patients (age 35-76 years, median 57 years) with malignant melanoma were treated. All had received prior chemotherapy. In each cycle of treatment, patients received bryostatin 25 degrees g m(-2) weekly for three courses followed by a rest week. The drug was given in PET diluent (10 microg bryostatin ml(-1) of 60% polyethylene glycol, 30% ethanol, 10% Tween 80) and infused in normal saline over 1 h. The principal toxicities were myalgia (grade 2, eight patients and grade 3, six patients) and grade 2 phlebitis (four patients), fatigue (three patients) and vomiting (one patient). Of 15 patients evaluable for tumour response, 14 developed progressive disease. One patient developed stable disease for 9 months after bryostatin treatment. In conclusion, single-agent bryostatin appears ineffective in the treatment of metastatic melanoma in patients previously treated with chemotherapy. It should, however, be investigated further in previously untreated patients.
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PMID:A phase II study of bryostatin 1 in metastatic malignant melanoma. 982 75

An overview of the characteristics of traffic crashes among young, middle-aged and older drivers is presented. The results suggest that the youngest and the oldest drivers were more likely to be considered at-fault. With respect to crash characteristics, older drivers were less likely to have crashes involving driver fatigue, during the evening and early morning, on curved roads, during adverse weather, involving a single vehicle, and while traveling at high speeds. Conversely, older drivers were over-represented in crashes at intersections and/or involving failure to yield the right of way, unseen objects, and failure to heed stop signs or signals. Crashes occurring while turning and changing lanes were also more common among older drivers. Alcohol was less likely to be a factor in traffic crashes involving older adults. Synthesizing these results led to the conclusion that the primary problem with the young is risk-taking and lack of skill. The strength of older drivers lies in their aversion to risk, but perceptual problems and difficulty judging and responding to traffic flow often counterbalance this attribute.
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PMID:Characteristics of traffic crashes among young, middle-aged, and older drivers. 1019 95

A microcapsule suspension, a substitute for animal blood in hemolysis tests, has been developed for evaluation of the absolute hemolytic properties of circulatory artificial organs. The microcapsule suspension was made by dispersing microcapsule slurry into an ethylene glycol sodium chloride solution. The microcapsule slurry was composed of a leuco dye solution and polyurethane membrane made by the reaction between aliphatic poly-isocyanate and polyamine by interfacial polycondensation. The microcapsule was a small particle containing dye inside. The microcapsule suspension was white; the diameter of the microcapsules was from 5 to 100 microns. The specific gravity of the suspension was 1.024, and the membrane was elastic. The fluid showed Newtonian characteristics, different from animal blood, and its viscosity was approximately 5.8 mPa.s. After the microcapsules were destroyed, the leuco dye was extracted with n-hexane from the suspension and was measured by spectroscopy after being colored with acid ethanol. Hemolysis can be regarded as a fatigue fracture of cell membranes rather than a static fracture. The destruction of microcapsules by a Potter type tissue grinder was observed at a low stroke number region and was compared to rat blood. Moreover, hemolysis tests of a commercially available centrifugal blood pump and the prototype of our centrifugal pump for mechanism checks were carried out with bovine blood. The hemolysis level of the prototype pump increased with time while the hemolysis level of the commercial blood pump did not change as much as that of the control when both pumps were tested with the microcapsule suspension. These results are similar to tests utilizing bovine blood. Therefore, hemolysis tests of circulatory artificial organs completed with microcapsule suspension are expected to provide results similar to tests with animal blood.
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PMID:A preliminary study of microcapsule suspension for hemolysis evaluation of artificial organs. 1019 20

The urinary excretion products of serotonin (5-hydroxytryptamine, 5HT) are 5-hydroxyindole-3-acetic acid (5HIAA) and 5-hydroxytryptophol (5HTOL), and the ratio of 5HTOL to 5HIAA is normally very low (< 0.01 ) in man. Intake of foods rich in 5HT (high amounts in banana, pineapple, and walnuts) induces a general increase in the output of 5HT metabolites, without affecting the 5HTOL/5HIAA ratio. In contrast, during metabolism of ethanol there is a shift in the catabolic pattern of 5HT, and the formation of 5HTOL increases appreciably at the expense of 5HIAA. Accordingly, the urinary 5HTOL/ 5HIAA ratio increases and does not recover to baseline levels until several hours after ethanol has been cleared from the body. When 10 healthy subjects ingested a moderate dose of ethanol (0.5 g/kg), the urinary 5HTOL/SHIAA ratio was increased approximately 70-fold on average at 4 h after intake. When the same amount of ethanol was ingested together with 3 bananas (approximately 10 mg 5HT), this ratio was increased approximately 100-fold at 4 h and still significantly higher than baseline levels at 24 h. Starting at 3-4 h after the combined intake of ethanol and banana, 7 subjects experienced one or more unpleasant symptoms (diarrhea, headache, and fatigue) which are associated with the 5HT system. The events were transient but typically lasted for several hours, and the duration correlated with the time period during which 5HTOL levels were raised. Intake of ethanol and banana separately produced much lower increases in 5HTOL output and caused no corresponding effects. This observation indicate that dietary 5HT intake together with even a moderate dose of ethanol can provoke unpleasant physiological symptoms. The symptoms may be attributed to the high concentration of 5HTOL.
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PMID:Dietary serotonin and alcohol combined may provoke adverse physiological symptoms due to 5-hydroxytryptophol. 1096 9

The effects of alcohol ingestion were compared with those of prolonged wakefulness on a simulated driving task. Eighteen healthy, male subjects aged between 19 and 35 years drove for 30 min on a simulated driving task at blood alcohol concentrations of 0.00, 0.05 and 0.08%. Subjective sleepiness was assessed before and after the driving task. Driving performance was measured in terms of the mean and standard deviation (S.D.) of lane position (tracking); the mean and S.D. of speed deviation (the difference between the actual speed and the posted speed limit); and the number of off-road occurrences. Ratings of sleepiness increased with increasing blood alcohol concentration, and were higher following the driving task. With increasing blood alcohol concentration, tracking variability, speed variability, and off-road events increased, while speed deviation decreased, the result of subjects driving faster. The results were compared with a previous study examining simulated driving performance during one night of prolonged wakefulness [Arnedt, J.T., MacLean A.W., 1996. Effects of sleep loss on urban and motorway driving stimulation performance. Presented at the Drive Alert... Arrive Alive International Forum, Washington DC], using an approach adopted by Dawson and Reid [Dawson, D., Reid, K., 1997. Fatigue, alcohol and performance impairment. Nature 388, 23]. For mean tracking, tracking variability, and speed variability 18.5 and 21 h of wakefulness produced changes of the same magnitude as 0.05 and 0.08% blood alcohol concentration, respectively. Alcohol consumption produced changes in speed deviation and off-road occurrences of greater magnitude than the corresponding levels of prolonged wakefulness. While limited to situations in which there is no other traffic present, the findings suggest that impairments in simulated driving are evident even at relatively modest blood alcohol levels, and that wakefulness prolonged by as little as 3 h can produce decrements in the ability to maintain speed and road position as serious as those found at the legal limits of alcohol consumption.
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PMID:How do prolonged wakefulness and alcohol compare in the decrements they produce on a simulated driving task? 1123 95


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