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...on Substance Abuse
--Medical Aspects--

www.ProjectCork.org

Summer 2002

A case of reversible azoospermia following withdrawal from alcohol consumption.

Vicari E; Arancio A; Giuffrida V; D'Agata R; Calogero AE. Journal of Endocrinological Investigation 25(5): 473-476, 2002. (30 refs.)
Chronic alcohol intake is associated with male reproductive function impairment. However, no longitudinal studies have been carried out to determine the recovery of alcohol-related spermatogenetic failure subsequent to moderate periods of abstinence. The present report describes the achievement of a pregnancy 3 months after withdrawal from alcohol consumption in the partner of a patient with azoospermia secondary to heavy alcoholic intake (mean daily alcohol consumption: 90 g). Alcoholism was the putative cause of the infertile condition of this patient because, during alcohol consumption, he first had teratozoospermia characterized by a never reported high percentage of spermatozoa with large heads (associated with a nonmegaloblastic macrocytic anaemia in the blood smear), and subsequently azoospermia.

Accelerated metabolism of nicotine and cotinine in pregnant smokers.

Dempsey D; Jacob P III; Benowitz NL. Journal of Pharmacology and Experimental Therapeutics 301(2): 594-598, 2002. (43 refs.)
Cigarette smoking is the foremost modifiable risk factor for adverse pregnancy outcomes. Nicotine is a suspected fetal neuroteratogen. There is concern that nicotine may achieve toxic levels during pregnancy if nicotine replacement therapies are prescribed at doses used in the nonpregnant state. Ten healthy, volunteer, pregnant smokers received infusions of deuterium-labeled nicotine and cotinine during pregnancy and again post-partum. From blood and urine measurements, the following were determined: clearance (renal and nonrenal) of nicotine and cotinine, clearance of nicotine via the cotinine pathway (an indicator of CYP2A6 activity), and daily intake of nicotine from smoking. The clearance of nicotine and cotinine was significantly higher (60 and 140%, respectively), and the half-life of cotinine was much shorter (8.8 versus 16.6 h, P < 0.01) during pregnancy. Although plasma levels of cotinine were lower during pregnancy (119 versus 202 ng/ml, P < 0.05), daily intake of nicotine from smoking was similar during pregnancy and postpartum. For a given level of intake, the pharmacologic and toxicologic effects of nicotine during pregnancy are anticipated to be less than expected from nicotine metabolism data in nonpregnant women. Our data indicate that no downward dose adjustment needs to be made for nicotine replacement therapy during pregnancy. Conversely, higher than usual doses of nicotine may be necessary to optimize efficacy. Lower cotinine levels observed during pregnancy do not necessarily reflect less smoke exposure, and cut-off levels used to classify nonsmokers, passive smokers, and active smokers need to be established for pregnancy.

Acute renal failure following ingestion of wild mushrooms.

Mount P; Harris G; Sinclair R; Finlay M; Becker GJ. Internal Medicine Journal 32(4): 187-190, 2002. (14 refs.)
We describe three cases of acute renal failure in young men who ingested wild mushrooms with the intent of producing hallucinations. Two cases remained dialysis dependent and, in these cases, renal biopsy revealed tubulointerstitial nephritis and fibrosis. Similar cases have been reported in other countries, but not in Australia. The most recognized mushroom nephrotoxin is orellanine, however the causative mushroom species and the actual toxin involved in these cases are unknown.

Alcohol consumption and risk of ischemic stroke: The Framingham Study.

Djousse L; Ellison RC; Beiser A; Scaramucci A; D'Agostino RB; Wolf PA. Stroke 33(4): 907-912, 2002. (46 refs.)
Background and Purpose-Stroke is a major cause of death in the United States. The association between alcohol consumption and ischemic stroke (IS) remains controversial. Methods-We used data collected on participants in the Framingham Study to assess the association between total alcohol intake and type of alcoholic beverage and development of IS, overall and according to age. Results-A total of 196 men and 245 women developed IS during three 10-year follow-up periods. In the categories of never drinkers, drinkers of 0.1 to 11, 12 to 23, and greater than or equal to24 g/d of ethanol (a "typical drink" is approximate to 12 g of ethanol), and former drinkers of 0.1 to 11 and greater than or equal to 12 g/d, crude incidence rates of IS were 6.5, 5.9, 4.9, 5.0, 6.7, and 17.8 cases per 1000 person-years, respectively, for men and 5.9, 4.1, 4.1, 4.3, 8.3, and 7.1, respectively, for women. Overall, compared with never drinkers in a multivariate Cox regression, current alcohol consumption was not related significantly to IS in either sex. Former drinking of greater than or equal to 12 g/d of alcohol was associated with a 2.4 times higher risk of IS among men but not among women. When stratified by age, alcohol intake was associated with lower risk of IS among subjects aged 60 to 69 years. In beverage-specific analysis, only wine consumption was related to a decreased risk of IS. Conclusions-Our data showed no significant association between total alcohol and IS overall but showed a protective effect of alcohol among subjects aged 60 to 69 years.

Auditory and visual sustained attention in adolescents prenatally exposed to alcohol.

Coles CD; Platzman KA; Lynch ME; Freides D. Alcoholism: Clinical and Experimental Research 26(2): 263-271, 2002. (34 refs.)
Background: Sustained attention problems and impulsivity are reported in association with prenatal alcohol exposure and fetal alcohol syndrome, but research in this area is limited and contradictory. Methods: Auditory and visual sustained attention were investigated in 265 low-income, predominantly African-American, adolescents (mean age, 15.12 years; SD, 0.92). Included were 53 unexposed controls and 128 exposed to alcohol and other drugs prenatally, with 46 of these exhibiting dysmorphic features and growth retardation, as well as a special-education contrast group (n = 84). Sustained attention was measured with "AK" subtests from a commercially available Continuous Performance Task program. Outcomes included total correct, total errors, omissions, commissions, preservations, hit rate, false alarms, reaction time, and response sensitivity (d'). A repeated- measures multivariate analysis of variance procedure was used with the exposure group (four groups) as the independent variable and presentation mode (visual or auditory) and trial block (four blocks) as within-subject repeated measures. Results: There was an interaction of group with presentation mode for total correct, errors, error type, hit rate, and d'. Most groups processed visual information more effectively than auditory information. In contrast, dysmorphic adolescents performed as effectively when presented with auditory stimuli but were less efficient in processing visual information. Significantly higher error rates, particularly omission errors [17(3,261) = 7.16; p < 0.000], as well as lower d' [17(3,261) = 5.77; p < 0.001], were noted in this group. Conclusions: These results suggest that there may be specific patterns to the effect of prenatal alcohol exposure on cognitive performance that can be identified during adolescence. In this study of sustained attention, processing in the visual modality was more affected than that in the auditory modality. Deficits in visual processing seemed to result from insensitivity to target stimuli.

Effects of alcohol consumption and restriction on home blood pressure in hypertensive patients: Serial changes in the morning and evening records.

Kawano Y; Pontes CS; Abe H; Takishita S; Omae T. Clinical and Experimental Hypertension 24(1/2): 33-39, 2002. (23 refs.)
To study the time course of alcohol effects on blood pressure (BP), we examined morning and late evening home BP for 4 weeks in a regular alcohol consumption period and for 4 weeks in a alcohol restriction period in 30 Japanese men with essential hypertension (52 +/- 2 years, m +/- SE) in a randomized crossover study. Mean daily intake of alcohol were 66.5 +/- 4.7 and 10.2 +/- 1.9 ml, respectively. At the end of the regular alcohol period, morning BP had increased by 4.4 +/- 1.1/2.9 +/- 0.8 mmHg but evening BP had decreased by 7.4 +/- 1.9/5.7 +/- 1.7 mmHg. The depressor effect of alcohol on the evening BP was evident from day 1 to week 4, while the pressor effect on the morning BP was significant from week 2 regardless of the order of the two periods. These results confirm the biphasic effect of alcohol on BP, and suggest that the status of alcohol intake may markedly influence the morning-evening BP difference.

Ethanol modulates the growth of human breast cancer cells in vitro.

Izevbigie EB; Ekunwe SI; Jordan J; Howard CB. Experimental Biology and Medicine 227(4): 260-265, 2002. (36 refs.)
The role of ethanol or its metabolites on breast neoplasm has not been characterized. We hypothesized that ethanol may alter the growth rate of human breast tumor epithelial cells by modulating putative growth-promoting signaling pathways such as p44/42 mitogen-activated protein kinases (MAPKs). The MCF-7 cell line, considered a suitable model, was used in these studies to investigate the effects of ethanol on [H-3]thymidine incorporation, cell number, and p44/42 MAPK activities in the presence or absence of a MAPK or extracellular signal-regulated kinase ERK-1, and (MEK1) inhibitor (PD098059). Treatment of MCF-7 cells with a physiologically relevant concentration of ethanol (0.3% or 65 mM) increased p44/42 activities by an average of 400% (P < 0.02), and subsequent cell growth by 200% (P < 0.05) in a MEK1 inhibitor (PD098059)-sensitive fashion, thus suggesting that the Ras/MEK/MAPK signaling pathways are crucial for ethanol-induced MCF-7 cell growth.

Metadoxine in acute alcohol intoxication: A double-blind, randomized, placebo-controlled study.

Shpilenya LS; Muzychenko AP; Gasbarrini G; Addolorato G. Alcoholism: Clinical and Experimental Research 26(3): 340-346, 2002. (15 refs.)
Background: At present there are only intriguing and preliminary clinical results regarding the efficacy of metadoxine (pyridoxol L-2- pyrrolidone-5-carboxylate) in acute alcohol intoxication. The present study was planned with the aim of investigating the effectiveness of metadoxine in the management of patients affected by acute ethanol intoxication. Methods: A double-blind, randomized, multicenter, placebo-controlled trial was carried out on 58 patients of both sexes with acute ethanol intoxication. Patients were treated with a single dose of 900-mg intravenous metadoxine (n = 29) or with placebo (n = 29). Patients were clinically and biochemically evaluated at 0.5, 1.2, 3, 6, 9. and 12 hr after treatment. Results: Treatment with metadoxine significantly decreased the half-life of ethanol in blood (from 6.70 +/- 1.84 to 5.41 +/- 1.99 hr: p < 0.013) and showed a faster rate of ethanol elimination. The effects on ethanol half-life in blood were accompanied by a faster onset of recovery from intoxication, defined as the time of the transition of blood ethanol levels to the immediately lower range defined by intoxication categories (in g/liter: 0 to 0.5, absent; 0.51 to 1.0, mild; 1.1 to 2.5, moderate; >2.5, severe). Thus the median time to onset of recovery was 0.95 hr with metadoxine and 2.34 hr with placebo (p = 0.013). The effects of treatment on blood alcohol levels were paralleled by a significant decrease in the rating of the toxic clinical symptomatology. At 2 hr the improvement of toxic symptoms (in percent of maximum possible) was 68 +/- 28 vs. 44 +/- 27% in controls (p < 0.002). Conclusions: In patients with acute ethanol intoxication metadoxine accelerated the elimination of ethanol from blood, which led to faster recovery from intoxication, and improved the behavioral toxic symptomatology. Metadoxine could be helpful in the management of acute ethanol intoxication.

Moderate alcohol intake during pregnancy and the risk of stillbirth and death in the first year of life.

Kesmodel U; Wisborg K; Olsen SF; Henriksen TB; Secher NJ. American Journal of Epidemiology 155(4): 305-312, 2002. (45 refs.)
The authors evaluated the association between alcohol intake during pregnancy and risk of stillbirth and infant death in a cohort of pregnant women receiving routine antenatal care at Aarhus University Hospital (Aarhus, Denmark) between 1989 and 1996. Prospective information on alcohol intake, other lifestyle factors, maternal characteristics, and obstetric risk factors was obtained from self- administered questionnaires and hospital files, and 24,768 singleton pregnancies were included in the analyses (116 stillbirths, 119 infant deaths). The risk ratio for stillbirth among women who consumed 5 drinks/week during pregnancy was 2.96 (95% confidence interval: 1.37, 6.41) as compared with women who consumed <1 drink/week. Adjustment for smoking habits, caffeine intake, age, prepregnancy body mass index, marital status, occupational status, education, parity, and sex of the child did not change the conclusions, nor did restriction of the highest intake group to women who consumed 5-14 drinks/week (risk ratio = 3.13, 95% confidence interval: 1.45, 6.77). The rate of stillbirth due to fetoplacental dysfunction increased across alcohol categories, from 1.37 per 1,000 births for women consuming <1 drink/week to 8.83 per 1,000 births for women consuming greater than or equal to 5 drinks/week. The increased risk could not be attributed to the effect of alcohol on the risk of low birth weight, preterm delivery, or malformations. There was little if any association between alcohol intake and infant death.

MRI findings in children with school problems who had been exposed prenatally to alcohol.

Autti-Ramo I; Autti T; Korkman M; Kettunen S; Salonen O; Valanne L. Developmental Medicine and Child Neurology 44(2): 98-106, 2002. (67 refs.)
This study examined 17 children (nine males, eight females; mean age 13 years) with prenatal alcohol exposure of various durations. The aim of the study was to detect specific brain morphological alterations by means of MRI and to see if findings correlated with particular cognitive deficits. Of the 17 children, five had been exposed to heavy maternal consumption of alcohol (over 10 drinks/week) during the first trimester only; four had been exposed during the first and second trimester; and eight had been exposed throughout pregnancy. Five children had alcohol related neurobehavioural disorder, seven were diagnosed as having foetal alcohol effects and five were diagnosed as having foetal alcohol syndrome. Hypoplasia of the vermis was observed in 10 children and malformed posterior vermis in one additional child. Five children had hypoplastic cerebellar hemispheres. Hypoplasia of the corpus callosum was observed in two children. Small hippocampi were observed in three children and wide cortical sulci in six. No specific structural anomaly correlated with a particular neuropsychological deficit. In this study, deviations in the development of the vermis was the most sensitive morphological indicator of the effects of prenatal alcohol exposure. It was seen in every diagnostic group including children who had been exposed during only the first trimester of pregnancy.

Brain maturation may be arrested in chronic cocaine addicts.

Bartzokis G; Beckson M; Lu PH; Edwards N; Bridge P; Mintz J. Biological Psychiatry 51(8): 605-611, 2002. (50 refs.)
Background: Animal and human newborn studies suggest that exposure to cocaine in utero delays glial maturation and white matter myelination. Postmortem data show that in the frontal and temporal lobes, white matter myelination continues into middle age. Recent magnetic resonance imaging (MRI) data have confirmed continued white matter volume increase in these regions, reaching a maximum at age 47. Methods: Thirty-seven male cocaine dependent (CD) and 52 normal control subjects between ages 19 and 47 were evaluated with MRI. Coronal images focused on the frontal and temporal lobes were acquired using pulse sequences that maximized gray/white matter contrast. Results: Highly significant positive correlations between white matter volume and age were observed in both the frontal and temporal lobes of the control group (r = .52, p = .0001 and r = .54, p = .0001, respectively); however, CD subjects did not demonstrate any age-related increase in white matter volume of the frontal (r = -.001; p = .99) and temporal (r = -.07; p = .67) lobes in this age range. Conclusions: The age-related expansion in white matter volume occurring in normal control subjects was absent in CD subjects. The findings suggest that in adults, cocaine dependence may arrest normal white matter maturation in the frontal and temporal lobes of addicts who continue using cocaine.

...on Substance Abuse --Medical Aspects--