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This paper describes smoking and drinking patterns during pregnancy amongst a cohort of 2266 women who enrolled at a London antenatal clinic 1982-1983. Only 12% of mothers were non-drinkers before pregnancy, but 44% abstained in the first trimester, 38% in the second and 50% in the third. Before pregnancy 20% of mothers were drinking more than the recommended 10 units of alcohol per week. This dropped to 6% during pregnancy. Mean consumption at each of the three stages of pregnancy was highest amongst those mothers who were the heaviest drinkers before pregnancy. The heaviest pre-pregnancy drinkers were also the least likely to abstain at any point in pregnancy. Of those mothers who were drinking less than 10 units of alcohol per week before pregnancy, 3% increased during pregnancy. Wine was the most popular beverage choice but heavier drinkers were more likely to drink beers and spirits in addition. Before pregnancy 29% of mothers smoked. This dropped to 23% in pregnancy. Consumption levels fell amongst those who continued smoking. The heaviest pre-pregnancy smokers were the most likely to reduce but the least likely to stop. Smoking was positively associated with the level of both pre-pregnancy and pregnancy drinking. The most commonly cited reasons for changes in drinking and smoking habits in pregnancy were concern for the child, concern for self or concern for both. Feeling sick or ill was a more commonly stated reason for reduction of drinking than smoking. Social pressures were important in reducing smoking, but the mass media were quoted as a more important influence in reducing drinking. Mothers who drank more than 10 units of alcohol per week during pregnancy were more likely to be older, of higher social status and primiparous. In contrast those who smoked in pregnancy were more likely to be younger, of lower social status and multiparous. This has important implications for planning antenatal health education.
Alcohol Alcohol 1989
PMID:Drinking and smoking patterns amongst women attending an antenatal clinic--II. During pregnancy. 278 5

The so-called Oriental flushing reaction associated with ingestion of small amounts of alcohol was antagonized by combined antihistamine administration. In stage one of the study, the flushing reaction to low doses of alcohol was produced in Orientals. Most subjects experienced a cutaneous flush, increase in skin temperature, decrease in blood pressure, increase in pulse rate and subjective symptoms such as dizziness, sleepiness, anxiety, headache, generalized weakness and nausea. One half of the group of subjects was then given diphenhydramine, 50 mg (H1 receptor antagonist) and cimetidine, 300 mg (H2 receptor antagonist) and the second half received placebo tablets before the administration of alcohol. The clearest difference between the antihistamine group and placebo group was in the skin flushing reaction. The antihistamine group showed a statistically significant reduction in the skin flush. The antihistamines also neutralized the systolic hypotension induced by the administration of alcohol.
Alcohol Alcohol Suppl 1987
PMID:Combined antihistamine antagonism of the flushing reaction to alcohol. 289 99

The opioid agonist-antagonists are a heterogeneous group of compounds capable of providing analgesia sufficient to treat moderate to severe acute pain. Pentazocine, butorphanol and nalbuphine produce subjective effects which are quite different from those of morphine. Lack of mood elevation and occasional dysphoria may contribute to a lower level of patient acceptance, but all of these analgesics are significantly safer than the pure agonists. Doses in the therapeutic range are unlikely to produce dangerous levels of respiratory depression in most patients. Other opioid side-effects such as nausea, constipation and biliary spasm appear to be less frequent as well. The mu partial agonist buprenorphine shares many of the safety advantages of the older drugs, and its subjective effects appear more morphine-like. It is not clear whether mu partial agonists have real clinical advantages over kappa-type analgesics. All of these drugs are opioid antagonists and are able to precipitate abstinence in individuals with significant prior exposure to opiates. Neither absolute potency nor the ratio of agonist to antagonist effect are predictors of therapeutic usefulness. There is now an enormous amount of clinical experience with the agonist-antagonists. In many, but not all, clinical situations they are acceptable alternatives to the morphine-like drugs.
Drug Alcohol Depend 1987 Dec
PMID:The clinical usefulness of agonist-antagonist analgesics in acute pain. 289 87

We have studied the interaction of viqualine, a 5-hydroxytryptamine (5-HT) uptake inhibitor, with ethanol in 16 healthy men aged 20 to 34 years. The subjects were randomly assigned to receive ethanol dosed to maintain blood alcohol concentrations of 17-22 mmol.l-1 (n = 8) or orange juice (n = 8) on each of two test days one week apart and preceded, in random order, by 3 days of viqualine 75 mg bd or placebo. Ethanol had no effect on steady-state viqualine concentrations or the inhibition of 5-HT uptake. Viqualine did not affect acetaldehyde concentrations or cause an aversive alcohol-sensitizing reaction. The deleterious effects of ethanol on word recall, manual tracking, body sway, and self-ratings of intoxication, sedation, and performance were not modified by the presence of viqualine. Within each beverage group performances and self-ratings on viqualine and placebo days were not different. The first dose of viqualine was associated with transient nausea. Viqualine and ethanol do not interact kinetically or dynamically on the variables examined in this study.
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PMID:Kinetic and dynamic interactions of oral viqualine and ethanol in man. 291 97

4-Methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, is a possible future drug for the treatment of methanol and ethylene glycol intoxications and the severe ethanol-disulfiram reaction. Therefore a placebo-controlled, double-blind, single-dose, randomized, sequential, ascending-dose "Phase I study" was performed in healthy volunteers in order to determine the tolerance of 4-MP at dose levels of 10 (n = 4), 20 (n = 4), 50 (n = 4), and 100 mg/kg (n = 3). Along with each dose group, there were two placebos except with the 100 mg/kg group where there was only one placebo. In the 10 and 20 mg/kg group there were no side-effects in any subject. At the 50 mg/kg level, three out of four subjects experienced slight to moderate nausea and dizziness from 0 to 2.5 h after dosing. In the 100 mg/kg group all three subjects reported side-effects like nausea, dizziness, and vertigo, that were short-lived in two subjects, but lasted up to 30 h in one subject. The study was stopped after evaluation of the latter subject, so fewer subjects were completed in this last group. Despite these subjective side-effects, there were no significant changes in objective clinical parameters like pulse, blood pressure, body temperature, or blood and urine chemistries. We conclude that at a single dose of 4-MP (10-20 mg/kg) producing plasma levels within a probable therapeutic range, no side-effects were attributed to 4-MP.
Alcohol Clin Exp Res 1988 Aug
PMID:4-Methylpyrazole: a controlled study of safety in healthy human subjects after single, ascending doses. 305 73

Under ultrasound guidance, we treated 25 cases of renal cyst with 99% ethanol instillation to prevent the recurrence of this disease from January 1985 to June 1987. Patients' age was from 17 to 85 years old with the average age of 63 years. Twelve cases were men, and 13 cases were women. Among the 25 cases, eleven were asymptomatic and 14 showed clinical features of lumbago, microhematuria, hypertension or proteinuria. The aspirated site was the right side in 9, left side in 14 and bilateral kidneys in 2 cases. Subsequently, cyst puncture was carried out 27 times. We encountered 12 complications following puncture. These complications were derived from the puncture itself or caused by the ethanol instillation. Flank pain caused by the injection of ethanol, nausea, causalgia or a feeling of drunkenness appeared immediately after the inoculation procedure. However, no serious complications such as pneumothorax, perirenal hematoma or infection were recognized. Some complications arose in 7 cases of 9 examples (77.8%) following more than 50 ml of ethanol injection, but the complications were observed in only 5 cases of 18 examples (22.8%) following less than 50 ml of administration. Based on these findings, ethanol injection in renal cysts appears to be useful for the treatment of this disease. In case of huge cysts when more than 50 ml of ethanol, is instilled the case should be followed up carefully after the instillation procedure.
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PMID:[Renal cyst puncture under ultrasound guidance: complications of ethanol injection]. 306 4

Differences in the pharmacokinetics of alcohol absorption and elimination are, in part, genetically determined. There are polymorphic variants of the two main enzymes responsible for ethanol oxidation in liver, alcohol dehydrogenase and aldehyde dehydrogenase. The frequency of occurrence of these variants, which have been shown to display strikingly different catalytic properties, differs among different racial populations. Since the activity of alcohol dehydrogenase in liver is a rate-limiting factor for ethanol metabolism in experimental animals, it is likely that the type and content of the polymorphic isoenzyme subunit encoded at ADH2, beta-subunit, and at ADH3, the gamma-subunit, are contributing factors to the genetic variability in ethanol elimination rate. The recent development of methods for genotyping individuals at these loci using white cell DNA will allow us to test this hypothesis as well as any relationship between ADH genotype and the susceptibility to alcoholism or alcohol-related pathology. A polymorphic variant of human liver mitochondrial aldehyde dehydrogenase, ADLH2, which has little or no acetaldehyde oxidizing activity has been identified. Individuals with the deficient ALDH2 phenotype do not have altered ethanol elimination rates but they do exhibit high blood acetaldehyde levels and dysphoric symptoms such as facial flushing, nausea and tachycardia, after drinking alcohol. Because acetaldehyde is so reactive, it binds to free amino groups of proteins including a 37 kilodalton hepatic protein-acetaldehyde adduct and may elicit an antibody response. We would predict that individuals who have low ALDH2 activity because of liver disease or because they have the inactive ALDH2 variant isoenzyme might form more protein-acetaldehyde adducts and elicit a greater immune response. These adducts may represent good biological markers of alcohol abuse and may also play a role in liver injury due to chronic alcohol consumption.
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PMID:Genetic polymorphism of enzymes of alcohol metabolism and susceptibility to alcoholic liver disease. 306 25

Hyperacetataemia during acetate haemodialysis has been associated with the development of a variety of unpleasant symptoms, although a direct toxic effect of acetate is hard to prove. Acetaldehyde, which is produced during the metabolism of ethanol to acetate, has various toxic effects including some of those reported during acetate dialysis such as nausea, headache and palpitations. Using a novel, recently developed method we studied blood acetaldehyde concentrations during acetate dialysis in 15 patients and found significant increases in five, with a mean peak value in these patients of 1.36 mumol/l (normal less than 0.4 mumol/l). These five patients also developed high blood acetate concentrations during a subsequent acetate dialysis and showed a significant correlation between blood acetaldehyde and acetate concentrations (r = 0.55, P less than 0.05). Blood acetaldehyde did not change during bicarbonate dialysis in these patients. Our results suggest that significant accumulation of acetaldehyde may occur during acetate dialysis, especially in those patients whose metabolic capacity for acetate is somehow impaired, and that acetaldehyde may contribute to some of the symptoms previously ascribed to 'acetate' intolerance.
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PMID:Changes in blood acetaldehyde concentrations during acetate haemodialysis. 314 21

The so-called Oriental flushing reaction associated with ingestion of small amounts of alcohol was antagonized by combined antihistamine administration. In stage one of the study, the flushing reaction to low doses of alcohol was produced in Orientals. Most subjects experienced a cutaneous flush, an increase in skin temperature, a decrease in blood pressure, an increase in pulse rate and subjective symptoms such as dizziness, sleepiness, anxiety, headache, generalized weakness and nausea. Before the administration of alcohol, one-half of the subjects were given 50 mg of diphenhydramine (H1 receptor antagonist) and 300 mg of cimetidine (H2 receptor antagonist). The second half received placebo tablets. The clearest difference between the antihistamine group and placebo group was in the skin flushing reaction. The antihistamine group showed a significant reduction in the skin flush. The antihistamine also neutralized the systolic hypotension induced by the administration of alcohol. The possible importance of histamine in the expression of sensitivity to alcohol is considered. The relevance to genetic susceptibility for development of alcoholism is discussed.
J Stud Alcohol 1988 Jan
PMID:Antihistamine blockade of alcohol-induced flushing in orientals. 334 71

A double-blind, placebo-controlled study in eight healthy male volunteers was conducted to study possible disulfiram-type reactions and hypoprothrombinemia associated with cefotetan administration. Three doses of cefotetan (2 g) or of placebo were administered at 12-h intervals. Ethanol (0.5 g/kg of total body weight) was ingested 1 h after the third dose. Blood ethanol, serum acetaldehyde, and prothrombin times were measured throughout the study. Heart rate, blood pressure, and clinical signs as well as symptoms suggestive of a disulfiram-type reaction were also noted. Five of eight volunteers that received cefotetan showed significant flushing. A significant increase in heart rate also was noted. No change in mean arterial pressure was observed during the cefotetan phase, and no one experienced nausea or vomiting. No statistical differences were observed between phases with respect to ethanol area under the time-concentration curve, elimination rate, or serum acetaldehyde concentrations. A slight but statistically significant increase in prothrombin time also was observed with cefotetan. This study suggests that patients receiving cefotetan might be at risk to develop disulfiram-type reactions and hypoprothrombinemia.
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PMID:Cefotetan-induced disulfiram-type reactions and hypoprothrombinemia. 347 45


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