Total Lifetime Dose Of Ethanol Research Articles

Evaluation of Subclinical Left Ventricular Systolic Dysfunction in Chronic Asymptomatic Alcoholics by Speckle Tracking Echocardiography.

By using two-dimensional speckle tracking echocardiography, we aimed to investigate the structural and functional changes on myocardium in chronic asymptomatic alcoholics without any cardiovascular disease. Forty-one consecutive asymptomatic male alcoholics who were admitted to the outpatient alcoholism unit and 30 age matched healthy male volunteers selected as the control group were enrolled in the study. The study group were investigated by using standard two-dimensional echocardiography and speckle tracking echocardiography. The left ventricular (LV) global longitudinal strain and LV global circumferential strain were significantly lower in alcoholics when compared with control subjects. There was no difference in global radial strain between the two groups. To demonstrate the effect of total life time dose of ethanol (TLDE) on echocardiographic abnormalities, we assessed the correlation analysis. There was a nonsignificant weak correlation between global LV circumferential strain and TLDE (r = 0.27, p = 0.083). Speckle tracking echocardiography derived left ventricular systolic function was impaired in chronic alcoholic patients when compared with healthy controls.

Left atrial function by speckle-tracking echocardiography in chronic asymptomatic alcoholic patients.

Although the effects of chronic alcoholism on left ventricular (LV) systolic function are well established, diastolic impairment has been evaluated partially. In addition, there are scarce data available about the relation of LV diastolic function to either or both duration and quantity of drinking among alcoholics. The aim of the study was to evaluate the left atrial (LA) function in chronic asymptomatic alcoholic patients by using two-dimensional speckle-tracking echocardiography (2D-STE). We enrolled 30 healthy subjects (age 34.8 ± 5.8 years) and 75 asymptomatic male alcoholics (age 39.8 ± 6.5 years) divided into two groups, according to total lifetime dose of ethanol: group I, <15 kg/kg and group II, ≥15 kg/kg. In the 2D-STE analysis of the LA, strain during ventricular systole (LA-Res), during late diastole (LA-Pump) and strain rate during ventricular contraction (LA-SRs), during passive ventricular filling (LA-SRe), during active atrial contraction (LA-SRa) were obtained. Deceleration time was longer, E/A and V(p) were smaller, and E/E(m) was higher in alcoholics. Although parameters of diastolic dysfunction were comparable in alcoholic groups, LA-Res and LA-Pump were found significantly different among the alcoholics. However, there were no differences in LA-SRs and LA-SRe between the controls and alcoholic groups. LA function is reduced in chronic alcohol abuse, and heavy alcohol consumption may play an important role in LA function impairment.

Peripheral neuropathy in chronic alcoholism: a retrospective cross-sectional study in 76 subjects.

A consecutive sample of 76 chronic alcoholic patients was studied clinically, biochemically and electrophysiologically to assess clinical and/or subclinical signs of alcohol-related neuropathy as well as the most important and disputed risk factors for neuropathy such as age, parental history of alcoholism, nutritional status, alcoholic disease duration and total lifetime dose of ethanol (TLDE). The results show that alcohol-related neuropathy, especially when subclinical, seems to be frequent and mostly characterized by axonal degeneration of peripheral nerve fibres with earlier and more frequent involvement of sensory fibres and lower limbs. Moreover, positive family history of alcoholism, but above all alcoholic disease duration and TLDE, could be more important factors than malnutrition in determining neuropathy.

Gender And Peripheral Neuropathy In Chronic Alcoholism: A Clinical‐Electroneurographic Study

In some alcohol‐related pathologies of chronic alcoholism women are more vulnerable than men. A consecutive sample of 62 chronic alcoholics was studied, 18 females and 44 males, aged between 28 and 69 years to assess the incidence and distribution of peripheral neuropathy with regard to gender. All patients underwent clinical and neurological observations, laboratory tests, and electroneurography. Total lifetime dose of ethanol (TLDE) and other risk factors for neuropathy (disease duration, age, nutritional status) were calculated and correlated to sural nerve sensory‐evoked potential (SEP) amplitude. In 42 patients (67.7%), we observed the presence of clinical and/or infraclinical neuropathy, mostly axonal, in 29 males (65.9%) and 13 females (72.2%). In women, compared to men, TLDE and disease duration were significantly inversely correlated to sural nerve SEP amplitude, i.e in women, SEP amplitude is significantly reduced in relation to TLDE and disease duration increase. These data indicate a higher sensitivity of females towards the toxic effects of ethanol, other than malnutrition, on peripheral nerve fibres.

GENDER AND PERIPHERAL NEUROPATHY IN CHRONIC ALCOHOLISM: A CLINICAL-ELECTRONEUROGRAPHIC STUDY

In some alcohol-related pathologies of chronic alcoholism women are more vulnerable than men. A consecutive sample of 62 chronic alcoholics was studied, 18 females and 44 males, aged between 28 and 69 years to assess the incidence and distribution of peripheral neuropathy with regard to gender. All patients underwent clinical and neurological observations, laboratory tests, and electroneurography. Total lifetime dose of ethanol (TLDE) and other risk factors for neuropathy (disease duration, age, nutritional status) were calculated and correlated to sural nerve sensory-evoked potential (SEP) amplitude. In 42 patients (67.7%), we observed the presence of clinical and/or infraclinical neuropathy, mostly axonal, in 29 males (65.9%) and 13 females (72.2%). In women, compared to men, TLDE and disease duration were significantly inversely correlated to sural nerve SEP amplitude, i.e. in women, SEP amplitude is significantly reduced in relation to TLDE and disease duration increase. These data indicate a higher sensitivity of females towards the toxic effects of ethanol, other than malnutrition, on peripheral nerve fibres.

Chronic alcohol consumption increases serum levels of circulating endothelial cell/leucocyte adhesion molecules E-selectin and ICAM-1.

A group of 30 chronic alcoholics without alcohol-related diseases and 30 controls (teetotallers) were selected to measure serum levels of endothelial adhesion molecules (AMs) (ICAM-1, VCAM-1, and E-selectin). ICAM-1 and E-selectin serum levels were higher in alcoholics, whereas VCAM-1 serum levels were similar in both groups. There was a significant correlation between daily alcohol intake and serum level of ICAM-1 (r = 0.49, P = 0.003) and E-selectin (r = 0.41, P = 0.02). A significant positive correlation between E-selectin and total lifetime dose of ethanol was also observed (r = 0.52, P = 0.003). These changes in serum levels of endothelial AMs of chronic alcoholics may reflect endothelial and/or immune activation, and could interfere with the reactions between immune cells and the endothelium.

Activated lymphocytes (CD25+ CD69+ cells) and decreased CD19+ cells in well-nourished chronic alcoholics without ethanol-related diseases.

To assess lymphocyte subsets and expression of activation antigens in peripheral blood lymphocytes (PBLs) in chronic alcoholism, a cross-sectional study with 30 well-nourished chronic alcoholics and 30 controls was performed. Studies included detailed clinical and laboratory evaluation, nutritional status assessment, and determination of lymphocyte subpopulations, as well as activation antigens. A significant decrease of B cells (CD19+) was observed in chronic alcoholics, compared with controls (p < 0.001). A significant increase of PBLs expressing CD69 and CD25 (p < 0.01, both) in chronic alcoholics was also detected, whereas CD71 expression was unaffected. In addition, T lymphocytes expressing HLA-DR were significantly higher in chronic alcoholics than controls (p < 0.05). The serum level of soluble interleukin-2 receptor was also significantly higher in the alcoholic group, compared with controls (p = 0.04). Moreover, the estimated total lifetime dose of ethanol consumed correlated positively with the percentage of PBLs expressing CD25 (r = 0.48; p = 0.01) and negatively with PBLs expressing CD71 (r = -0.39; p = 0.04). By contrast, the changes were not related to age, nutritional status, or the presence of other ethanol-related diseases. In conclusion, chronic alcoholics present a significant decrease of B cells and an "incomplete activation state" of PBLs that depends on the dose of ethanol consumed.

Serum and Muscle Levels of α‐Tocopherol, Ascorbic Acid, and Retinol Are Normal in Chronic Alcoholic Myopathy

Some authors have suggested a possible loss of antioxidant factors in alcoholic skeletal myopathy. To assess the relationship between ethanol consumption and serum and muscle levels of alpha-tocopherol, ascorbic acid, and retinol in chronic alcoholics with and without skeletal myopathy, a prospective cross-sectional study was performed in the Alcohol Unit of a 1000-bed university hospital. Twenty-five chronic male alcoholic patients (10 with skeletal myopathy) and 15 male controls of similar age were included. Evaluation of daily and lifetime ethanol consumption, assessment of anthropometric and protein nutritional parameters, and open biopsy of the left deltoid muscle were performed, as well as determinations of serum and muscle levels of retinol, alpha-tocopherol, and ascorbic acid by HPLC analysis. Ten of the 25 chronic alcoholic patients presented histological criteria of skeletal myopathy. Four alcoholics presented caloric malnutrition and three protein malnutrition. All of the muscle biopsies of the control group were entirely normal, as were their nutritional studies. The serum and muscular levels of alpha-tocopherol, ascorbic acid, and retinol were normal and were similar in both alcoholics and controls. Except for serum retinol, these values were also similar in alcoholic patients with or without skeletal myopathy. In the univariate analysis, we identified the total lifetime dose of ethanol (p < 0.003), the muscle arm area (p < 0.05), and serum levels of prealbumin (p < 0.03) and retinol-binding protein (p < 0.05) as factors influencing the development of alcoholic myopathy. However, in multivariate analysis, the total lifetime dose of ethanol was the only independent factor in relation to alcoholic myopathy (p < 0.003). Serum and muscle levels of the antioxidants alpha-tocopherol, ascorbic acid, and retinol do not influence the presence of skeletal myopathy in chronic alcoholic patients.

Comparison of Alcoholic Cardiomyopathy in Women Versus Men

To compare the prevalence and cardiac status of male and female alcoholics with alcoholic cardiomyopathy during a 5-year period, all chronic alcoholics with dilated cardiomyopathy who had clinical symptoms of heart failure were included. Alcoholic cardiomyopathy was diagnosed in 10 chronic alcoholic women and in 26 men; the prevalence of alcoholic cardiomyopathy was similar in both sexes. No significant differences were observed in age, nutritional parameters, and clinical and radiologic data of heart failure between the 2 groups. Alcoholic women reported a significantly lower daily dose of ethanol (p = 0.002), a shorter duration of alcoholism (p = 0.017), and a lower total lifetime dose of ethanol consumption (p = 0.001), and had a lower New York Heart Association functional class than men. Women also had lesser ventricular dysfunction than men. In a multivariate analysis, left ventricular systolic dysfunction was related to the total lifetime dose of ethanol consumption (p <0.04), but not to gender. Finally, when patients were matched for left ventricular ejection fraction, women had consumed a lower total lifetime dose of ethanol than men (p <0.001). The prevalence of alcoholic women with dilated cardiomyopathy was found to be similar to that of alcoholic men, although women required a lower total lifetime dose of ethanol to develop the disease.

Atrophy of the corpus callosum in chronic alcoholism

To determine the prevalence of corpus callosum atrophy in chronic alcoholics and its relationship to cognitive function and brain atrophy, a prospective clinicoradiologic study was carried out in 28 right-handed male patients with chronic alcoholism and 14 age- and sex-matched right-handed control subjects. Clinical evaluation, neuropsychological testing and measurement of the midsagittal corpus callosum area and thickness (genu, truncus and splenium), as well as the frontal lobe index and the width of the cortical sulci on T 1- and T 2-weighted magnetic resonance images were performed. Compared to controls, alcoholics had significantly decreased corpus callosum area and thickness, mainly in the genu. Two-thirds had a corpus callosum area 2 SD below the mean of the control group. The sagittal area of the corpus callosum body correlated negatively with the degree of frontal and cortical atrophies ( r = −0.5579 and −0.6853, respectively p < 0.01, both). Alcoholics with corpus callosum atrophy exhibited impairment of visual and logical memories ( p < 0.05 both) and those with reduced thickness of the genu showed impairment of frontal lobe tasks ( p < 0.05). The reduction of corpus callosum indices (age-corrected) also correlated with the total lifetime dose of ethanol consumed ( r = 0.6107, p < 0.001), but was not related to nutritional status or electrolyte imbalance. Atrophy of the corpus callosum is common among alcoholic patients and may reflect the severity and pattern of cortical damage. The degree of this atrophy also correlated with the severity of ethanol intake. © 1997 Elsevier Science B.V. All rights reserved.

Testicular Function in Asymptomatic Chronic Alcoholics: Relation to Ethanol Intake

To evaluate the effect of ethanol on testicular function in chronic alcoholics without chronic liver disease, we studied 38 asymptomatic chronic alcoholics and 19 age-matched controls. Detailed clinical history, nutritional status, hormonal analysis, and seminal studies were conducted in each case and control. Alcoholic patients had an average of 39 +/- 2 years old (range: 26 to 60) and reported a daily ethanol consumption from 100 to 350 g (mean: 198 +/- 15) over a period of 18.0 +/- 1.2 years. Alcoholics exhibited a significant increase of the luteinizing hormone (p < 0.001) and a decrease of the Free Androgen Index, compared with controls (p < 0.05) that related significantly with the total lifetime dose of ethanol (p < 0.01, both). Seminal studies indicate that 39.4% of alcoholics had significantly reduced their spermatozoa count (p < 0.01), whereas significant morphological abnormalities were observed in 44.7% of the alcoholics (p < 0.01). Spermatozoa motility from alcoholics was also found to be altered in half of the patients (p < 0.01). A significant increase of serum luteinizing hormone, follicle-stimulating hormone, and sex hormone binding globulin levels, and a decrease of Free Androgen Index were observed in alcoholics with morphology and motility abnormalities (p < 0.05, all). In multivariate analysis, the only independent factor that determined the alterations in sperm (count, morphology abnormalities, and motility alterations) was the total lifetime of ethanol intake (p < 0.001, all). We conclude that alcoholics frequently develop a situation of primary hypogonadism related to a lifetime of ethanol consumption.

The Greater Risk of Alcoholic Cardiomyopathy and Myopathy in Women Compared With Men

To compare the cardiac and muscular status of male and female alcoholics to determine if the response of women to alcohol is different from that of men. Cross-section study. An ambulatory alcoholism treatment unit in the Hospital Clínic of Barcelona. Fifty asymptomatic alcoholic women, 100 asymptomatic alcoholic men, and 50 female nonalcoholic controls. Studies included clinical assessment of muscle strength, muscle biopsy, echocardiography, radionuclide cardiac angiography, and treadmill exercise electrocardiographic recording test. The mean strength of the deltoid muscle in alcoholic women was significantly lower than that in controls (P < .001) and half suffered clinical weakness (muscle strength > or = 2 SD below controls). Muscle biopsy specimens from half of all asymptomatic women showed histologic evidence of myopathy. Left ventricular ejection fractions tended to be depressed, and a third of the alcoholic women had evidence of cardiomyopathy. Muscular strength and ejection fractions in women were inversely correlated with the total lifetime dose of ethanol, whereas the left ventricular mass showed a direct correlation. Of the alcoholic men, 39% suffered clinical weakness, and 45% had histologic evidence of myopathy. Evidence of cardiomyopathy was found in almost a third of the men, and their ejection fractions also correlated inversely with the total lifetime dose of ethanol. However, the threshold dose for the development of cardiomyopathy was considerably less in women than in men, and the decline in the ejection fraction with increasing alcohol dose was significantly steeper (P < .001). Despite the fact that the mean lifetime dose of alcohol in female alcoholics was only 60% that in male alcoholics, cardiomyopathy and myopathy were as common in female alcoholics as in male alcoholics. This finding, together with a more pronounced response of the ejection fraction to the dose of ethanol, indicates that women are more sensitive than men to the toxic effects of alcohol on striated muscle.

Significance of type II fiber atrophy in chronic alcoholic myopathy

To determine the significance of type II fiber atrophy in alcoholic myopathy and its relationship with ethanol-related diseases a prospective study was carried out in 100 chronic alcoholics who showed clinical suspicion of skeletal myopathy. Measurement of muscle strength, laboratory analysis, nutritional assessment and open biopsy of deltoid muscle were performed in each case, as well as electrophysiological testing for peripheral neuropathy. Hepatic ultrasonography and liver biopsy, echocardiography and radionuclide cardiac scanning were carried out in selected subjects. According to histomorphometric analysis, type II fiber atrophy was found in 33 cases (33%), being selective for type II B fiber in 23 (70%). Skeletal myopathy was diagnosed in 61 cases, alcoholic cardiomyopathy in 26, peripheral neuropathy in 23 and cirrhosis in 12. Patients with type II fiber atrophy had a significantly higher total lifetime dose of ethanol, presented a greater incidence of skeletal myopathy and peripheral neuropathy, and exhibited significantly lower values of percentage of ideal body weight and lean body mass than their counterparts. However, the only independent factors for developing type II fiber atrophy were the coexistence of caloric malnutrition ( p = 0.004) and the presence of skeletal myopathy ( p = 0.043). Selective type II fiber atrophy is a non-specific finding in alcohol-induced muscle damage appearing, overall, in the patients with caloric malnutrition as well as in those with histologic evidence of myopathy.

Alcoholic cardiomyopathy.

Chronic alcoholism is one of the most important causes of dilated cardiomyopathy, and a large proportion of chronic alcoholics demonstrate impairment of cardiac function. The development of cardiac dysfunction is apparently related to the total lifetime dose of ethanol. Studies in experimental animals have demonstrated that both acute and chronic ethanol administration impair cardiac contractility. However, the relationship, if any, between the acute effects of alcohol and the development of irreversible cardiomyopathy remain to be elucidated.

NUTRITIONAL STATUS IN CHRONICALLY ALCOHOLIC MEN FROM THE MIDDLE SOCIOECONOMIC CLASS AND ITS RELATION TO ETHANOL INTAKE

To determine the relationship between nutritional status and ethanol consumption, 250 chronically alcoholic men (mean age 41 +/- 11 years) entering an alcoholism treatment program were studied. A control group of 100 male volunteers (mean age 40 +/- 10 years) was also evaluated. Detailed clinical history, laboratory analysis and nutritional status assessment were carried out in each case and control. In addition, ethanol-related diseases such as liver disease, chronic pancreatitis, cardiomyopathy, myopathy and peripheral neuropathy were ruled out in all patients. The mean daily ethanol consumption of the alcoholics was 235 +/- 62 g over an average of 19 years. All of them belong to a very stable, middle-class working group of men. Only 25 (10%) alcoholics showed evidence of energy malnutrition, 15 (6%), of protein malnutrition, and 6 (2%) of both. In the multivariate analysis, the only independent factors for the development of malnutrition were the total lifetime dose of ethanol and calorie intake (ethanol excluded) (P < 0.01; both), as well as cirrhosis (P < 0.01) when protein malnutrition was considered. Alcoholic cirrhosis was diagnosed in 20 cases, skeletal myopathy in 117, dilated cardiomyopathy in 20 and peripheral neuropathy in 41. When patients with ethanol-related diseases were excluded, no significant differences in nutritional parameters were observed between chronic alcoholics and controls. We conclude that malnutrition is not as frequent as previously thought in middle socioeconomic class male alcoholics and its existence may be considered as another consequence of ethanol intake or secondary to the alcohol-related diseases.

RELATIONSHIP BETWEEN ETHANOL-RELATED DISEASES AND NUTRITIONAL STATUS IN CHRONICALLY ALCOHOLIC MEN

Two-hundred and fifty chronically alcoholic men (mean age, 41 +/- 11 years) entering an alcoholism treatment program were studied. Detailed clinical history, nutritional assessment and measurement of muscle strength by electronic myometer were performed in each case. In addition, hepatic ultrasonography and liver biopsy, echocardiography and radionuclide cardiac scanning, and electrophysiologica testing of peripheral nerves were performed when there was clinical evidence of liver disease, cardiomyopathy or neuropathy, respectively. Alcoholic cirrhosis was diagnosed in 20 cases, skeletal myopathy in 117, dilated cardiomyopathy in 20 and peripheral neuropathy in 41 cases. No patients with chronic myopathy or cardiomyopathy showed either clinical or laboratory evidence of malnutrition. Patients with cirrhosis showed a significantly lower lean body mass than controls (P = 0.03) and significantly lower nutritional protein levels than those alcoholics without cirrhosis. Alcoholics with peripheral neuropathy had significantly lower anthropometric parameters and nutrition protein levels than their counterparts (P < 0.001). However, in the multivariate analysis, the only independent factor for developing these complications of alcoholism was the total lifetime dose of ethanol (P < 0.001). We conclude that alcohol-related diseases are common in asymptomatic alcoholic men and these diseases appear to be due to an accumulative toxic effect of ethanol. Age and nutritional status do not seem to play a part in the development of such diseases.

The effects of alcoholism on skeletal and cardiac muscle.

To determine the prevalence of alcoholic myopathy and cardiomyopathy, we studied a group of 50 asymptomatic alcoholic men (mean age, 38.5 years) entering an outpatient treatment program. Studies performed included an assessment of muscle strength by electronic myometer, muscle biopsy, echocardiography, and radionuclide cardiac scanning, with comparison to healthy control subjects of similar age. The patients' mean (+/- SEM) daily alcohol consumption was 243 +/- 13 g over an average of 16 years. These patients had no clinical or laboratory signs of malnutrition or electrolyte imbalance. Forty-two percent of the patients, as compared with none of the controls, had strength of less than 20 kg as measured in the deltoid muscle. Muscle-biopsy specimens from 23 patients (46 percent) had histologic evidence of myopathy. In the cardiac studies, when the alcoholic patients were compared with 20 healthy controls, the patients had a significantly lower mean ejection fraction (59 vs. 67 percent), a lower mean shortening fraction (33 vs. 38 percent), a greater mean end-diastolic diameter (51 vs. 49 mm), and a greater mean left ventricular mass (123 vs. 106 g per square meter of body-surface area). One third of the alcoholics had an ejection fraction of 55 percent or less, as compared with none of the controls. Endomyocardial biopsy specimens from six patients with ejection fractions below 50 percent showed histologic changes of cardiomyopathy. The estimated total lifetime dose of ethanol correlated inversely with muscular strength (r = -0.65; P less than 0.001). In an analysis that also included six patients with symptomatic alcoholic cardiomyopathy, the estimated total lifetime dose of ethanol correlated inversely with the ejection fraction (r = -0.58; P less than 0.001) and directly with the left ventricular mass (r = 0.59; P less than 0.001). We conclude that myopathy of skeletal muscle and cardiomyopathy are common among persons with chronic alcoholism and that alcohol is toxic to striated muscle in a dose-dependent manner.