Transketolase abnormality in cultured fibroblasts from familial chronic alcoholic men and their male offspring.

We have investigated a thiamine-dependent enzyme, transketolase, in cultured fibroblasts from 41 human subjects, including patients with alcoholism-associated Wernicke-Korsakoff syndrome (n = 3), familial chronic alcoholic males (n = 7), their sons (n = 7), nonalcoholic men (n = 7), their male offspring (n = 7), and three generations of an Amish family (n = 10) without any history of alcoholism. This study was undertaken to delineate whether transketolase abnormality (i.e., high Michaelis Menton constant (Km) for thiamine pyrophosphate), previously reported in patients with Wernicke-Korsakoff syndrome is prevalent among familial chronic alcoholic men and their sons without prior history of alcohol abuse but who are at high risk for alcoholism. Our data suggest that an inborn error (i.e., high Km of transketolase for thiamine pyrophosphate) predisposing to thiamine deficiency diseases similar to those reported in Wernicke-Korsakoff syndrome may occur in the general population. However, for some as yet unexplained reason(s) this variant seems to occur more frequently among familial chronic alcoholic men and their male offspring without any history of alcoholism. The inheritance pattern of this enzyme variant as revealed from an Amish pedigree study may be autosomal recessive as previously suggested.     

Wernicke-Korsakoff syndrome complicating T-cell lymphoma: unusual or unrecognized?

Malnutrition rather than alcohol abuse is the common element in most cases of WKS. Our report may be the first to identify both the clinical and neuropathologic features of the syndrome in a patient with T-cell lymphoma. The coincidence of these two illnesses underscores a need to consider Wernicke's encephalopathy in debilitated individuals with malignancy or other chronic illnesses, highlights an atypical presentation of acute Wernicke's encephalopathy, and demonstrats the precipitation of that syndrome by glucose feeding. Attention to a patient's nutritional status and the liberal use of thiamine may prompt early recognition of the syndrome or prevent it entirely.     

Low Distress Tolerance and Hyperarousal Posttraumatic Stress Disorder Symptoms: A Pathway to Alcohol Use?

Research on substance use suggests that distress tolerance mediates the relationship between posttraumatic stress disorder (PTSD) symptoms and alcohol use; however, given that distress tolerance may represent vulnerabilities for both PTSD symptoms and alcohol use, it may in fact facilitate PTSD and subsequent alcohol use. The present study investigated the relationship between distress tolerance, and alcohol consumption and alcohol-related consequences, with PTSD hyperarousal, re-experiencing, avoidance, and numbing symptoms as mediating variables. A community based North-American sample (n = 146, 81 % = women) completed measures online as part of a larger ongoing study. Results demonstrated that distress tolerance had an indirect effect on alcohol consumption through hyperarousal symptoms but no other PTSD symptoms. No significant relationships were demonstrated with alcohol-related consequences. Findings suggest interventions promoting distress tolerance following trauma exposure may help decrease hyperarousal symptoms and subsequent risk of alcohol-use disorders. Comprehensive results, implications, and future research are discussed.     

Intrauterine growth retardation caused by dietary biotin and thiamine deficiency in the rat

The effects on fetal development of maternal biotin deficiency, alone and in conjunction with thiamine deficiency, were investigated in rats. Fetuses from dams given biotin-deficient diet throughout gestation demonstrated only some characteristics of intrauterine growth retardation (IUGR) including abnormal liver weight and a higher brain/liver ratio. However, fetuses from dams given biotin-thiamine-deficient diet and daily pyrithiamine (a thiamine antagonist used to insure thiamine deficiency) injections demonstrated severe IUGR along all of the fetal parameters investigated. We conclude that biotin and thiamine deficiency during intrauterine growth of the fetus may be partially responsible for the development of IUGR, a frequent concomitant of fetal alcohol syndrome.     

Detection and incidence of B and C vitamin deficiency in alcohol-related illness.

The activity of the red blood cell enzymes transketolase, glutathione reductase, and aspartate transaminase, and their activation by the coenzymes thiamine, riboflavin, and pyridoxine, the pyruvate tolerance test, the leucocyte vitamin C concentration, and the activity in serum of gamma-glutamyl transferase were measured in a series of 35 patients with alcohol-related illness. The incidence of thiamine deficiency was 31% as assessed by the activation of transketolase, and 55% as assessed by the pyruvate tolerance test. The incidence of riboflavin deficiency was 23% and of ascorbic acid deficiency 91%. No cases of pyridoxine deficiency were detected. The pyruvate tolerance test was found to be a more sensitive test of thiamine deficiency than the transketolase activation, and the activation of red blood cell aspartate transaminase was found to be a poor indicator of pyridoxine deficiency. There was a poor correlation of the gamma-glutamyl transferase activity with the degree of vitamin deficiency, suggesting that alcohol exposure is only partly responsible for the observed vitamin deficiency.     

Alcohol and pregnancy--embryopathy and alcohol effects

Fetal alcohol syndrome (FAS) is a specific polydystrophic pattern of malformations with the following diagnostic criteria: 1. Maternal alcohol dependence or alcohol abuse during pregnancy. 2. Pre- and postnatal deficiency of growth in weight, height and head circumference. 3. Multiple minor and major anomalies recognizable mainly at a typical face. 4. Structural injuries and changes at the central nervous system with complex brain dysfunction combining elements of cognitive impairments, behavioral disturbance and neurological damage. Fetal alcohol effects (FAE) or so-called "alcohol-related neurodevelopmental disorders" (ARND) with predominant neurotoxic effects and a large spectrum of cerebral dysfunctions are manifold more frequent than the full-blown FAS. These remain mostly unrecognized, overlooked and they are difficult to be diagnosed, the symptoms being unspecific. Alcohol in pregnancy is nowadays the most important and the most frequent toxic substance for the embryo and the fetus and one of the most frequent causes of mental retardation. The longlasting and irreversible consequences refer to school development, social maturation, social behaviour and later life-style. The diagnosis is based on the careful maternal history and on the clinical findings; there are no biochemical parameters of assessment. The risk of addiction development in these children is assumed to be more than 20 percent.     

Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease

Despite the targeting of traditional risk factors for cardiovascular disease, disease burden has not been completely eliminated. Thiamine is an essential cofactor in carbohydrate metabolism and individuals with diabetes are thiamine deficient. The pathophysiology of recognised complications of thiamine deficiency is similar to that underlying atherosclerosis and the metabolic syndrome, namely oxidative stress, inflammation and endothelial dysfunction. This review examines the mechanisms by which thiamine deficiency occurs in individuals with diabetes, how this deficiency leads to hyperglycaemic-induced damage, and the effect of thiamine replacement on vascular disease, endothelial function and oxidative stress. Thiamine administration can prevent the formation of harmful by-products of glucose metabolism, reduce oxidative stress and improve endothelial function. The potential benefit of long-term replacement in those with diabetes is not yet known but may reduce cardiovascular risk and angiopathic complications.     

The association of long-term alcohol biomarkers with risk for alcohol-related injury: Implications for screening

Alcohol misuse is a leading risk factor for serious injury and death. For those experiencing trauma in emergency care settings, recent alcohol misuse history is typically assessed via self-report measures. Since underreporting may be a problem in these settings, objective indicators like long-term biomarkers may be useful for identifying hazardous drinkers who may need intervention. Recognizing this, we investigated (1) whether hazardous drinking was linked to reports of alcohol-related injury in a probability sample of over 600 college students from a large, Midwestern, urban university; (2) whether elevated long-term biomarkers showed similar associations in the same sample. Associations derived from responses to the Alcohol Use Disorder Identification Test-C (AUDIT-C) as well as from hair and fingernails tested for ethyl glucuronide, a direct alcohol biomarker, suggested that hazardous drinking is significantly associated with elevated risk for alcohol-related injury. Implications for screening and intervention in health care settings are discussed.     

Alcohol-related emergency department attendances: is preloading a risk factor? Cross-sectional survey

Introduction

‘Preloading’ is a phenomenon where people drink alcohol at a private residence before going out. We aimed to identify whether preloading is a risk factor for alcohol-related emergency department attendance. We also wanted to identify where people became injured or unwell.

Methods

We conducted a cross-sectional, anonymous, survey at peak drinking times in our emergency department. We interviewed adult patients who presented to our emergency department with an alcohol-related presentation over an 8-week period.

Results

We approached 1,079 patients. One hundred sixty-one had suffered an alcohol-related problem while out drinking; 27% of women and 14% of men had their first drink at home. There was no particular presentation or age group that was associated with preloading. Seventy percent of patients stated that they had drunk most of their alcohol at a public place; 76% of patients suffered their alcohol-related problem at a site different from where they had drunk most of their alcohol or where they had had their first drink.

Conclusion

Preloading is more common in women than men. Preloading is common in alcohol-related emergency department attendances. The proportions of patients preloading in this study are lower than in other studies conducted in different environments. Preloading is not a risk factor for alcohol-related emergency department attendance. Polices to reduce alcohol-related harm should continue to focus on bars, nightclubs and pubs.     

Wernicke's encephalopathy

Wernicke's encephalopathy should be considered as a possible diagnosis in comatose and hypothermic patients. The classic triad of confusion, ophthalmoplegia (or nystagmus) and ataxia may be absent, and the history of alcohol abuse or other causes of thiamine deficiency may be unknown. Left untreated, acute Wernicke's encephalopathy has a 17 percent mortality rate. Since the morbidity from Wernicke's encephalopathy is potentially reversible with parenteral thiamine, and large doses of thiamine can be given without documented ill effects, it is recommended that all comatose or hypothermic patients, as well as those with more classic presentations of Wernicke's encephalopathy, be given parenteral thiamine before administration of glucose.     

Differential Effects of Maternal and Paternal Alcoholism and Gender on Drinking, Alcohol-Related Self-Cognition, and Psychopathology

Familial alcoholism is associated with various types of psychopathology in offspring, yet most studies do not differentiate maternal from paternal alcoholism. The purpose of this study was to examine the influence of maternal and paternal alcoholism and gender on alcohol consumption, an alcohol-related self-cognition, and four types of psychopathologic symptoms in young adults. Data were drawn from a study designed to examine the role of the self-concept in alcoholism and recovery. The sample included young adults with a current DSM-IV diagnosis of alcohol dependence (n = 25), those with a history of DSM-IV alcohol dependence who were abstinent for at least 12 months (n = 18), and nonalcoholic controls (n = 23). Regression analyses showed that 1) alcoholism on the paternal side of the family independently predicted drinking behavior and symptoms of social phobia over and above the effects of current alcohol dependence, 2) neither alcoholism on the maternal nor paternal side of the family predicted the alcohol-related self-cognition score, and 3) alcoholism on the maternal side of the family predicted symptoms of major depression, generalized anxiety disorder, and obsessive-compulsive disorder, with women having more major depressive symptoms, and men with alcoholism on the maternal side having more anxiety symptoms. These findings suggest that maternal and paternal alcoholism may confer different risks to the offspring, and that risk may vary depending on the gender of the offspring. Results highlight the importance of examining the effects of maternal and paternal alcoholism separately in research, and have important implications for assessing risk for high levels of alcohol consumption and psychopathology.     

Alcohol age of initiation and long-term impact: a cross sectional survey of adults in England

Background: Worldwide alcohol consumption is involved in 2.5 million deaths annually. Worryingly, the age of alcohol initiation may be decreasing; evidence suggests an inverse correlation between initiation and prevalence of alcohol use. European data are limited.

Methods: Data are from a survey (n?=?2638) on alcohol consumption of ≥18?y in England. Univariate and multivariate associations are reported between demography, last year alcohol consumption, historic drinking including having regularly drank alcohol <18?y (drank at least monthly), and experience of at least one serious alcohol-related problem (self-defined).

Results: Lifetime alcohol consumption was reported by 93.2% of participants. Of these, 36.1% reported regular consumption <18?y; 18–30?y had a threefold greater odds of reporting alcohol consumption <18?y than 61–75?y. In total, 5.2% reported at least one serious alcohol-related problem; those who had regularly consumed alcohol <18?y had a twofold greater odds of reporting this than those who had not.

Conclusion: Our sample supports a potential increase in the proportion of those reporting underage alcohol initiation. As those who regularly consumed alcohol <18?y were at risk of experiencing alcohol-related problems, incidence of harm could increase over time as early initiators start to experience harms, supporting the need for interventions to delay alcohol consumption in underage groups.     

Alcohol consumption and suicide

About 90% of people in Western countries use alcohol at some time in their lives, and 40% experience temporary or permanent alcohol-related impairment in some area of life as a result of drinking. Multiple sociocultural and environmental factors influence suicide rates, and thus studies conducted in one nation are not always applicable to other nations. Impulsivity and aggression are strongly implicated in suicidal behaviour. Constructs related to aggression and impulsivity confer additional risk for suicidal behaviour in people with alcohol dependence. Lower serotonin activity is tied to increased aggression/impulsivity, which in turn may enhance the probability of suicidal behaviour. Acute alcohol use is associated with suicide. Suicide completers have high rates of positive blood alcohol. Intoxicated people are more likely to attempt suicide using more lethal methods. Alcohol may be important in suicides among individuals with no previous psychiatric history. Alcohol dependence is an important risk factor for suicidal behaviour. Mood disorder is a more powerful risk factor for suicide among problem drinkers as age increases. All individuals with alcohol use disorders should be assessed for suicide, especially at the end of a binge or in the very early phase of withdrawal. Middle-age and older men with alcohol dependence and mood disorders are at particularly high risk.     

Effect of intravenous infusions of thiamine on the disposition kinetics of thiamine and its pyrophosphate

BACKGROUND: Thiamine supplementation is necessary in patients with thiamine deficiency syndromes. Experimental evidence suggests that tissue uptake and the elimination of thiamine are dose-dependent. AIM: The aim of the present study was to investigate the effect of different i.v. infusion rates of thiamine on blood concentrations of thiamine and its active metabolite thiamine pyrophosphate (TPP) and on renal excretion of thiamine. METHODS: Twelve healthy subjects received in a two-period block randomized study 150 mg thiamine intravenously over either 1 or 24 h. RESULTS: The maximum blood concentrations (Cmax) of thiamine were significantly higher after the more rapid infusion (RI; 2300 ng/mL) than after the slower infusion (SI; 177 ng/mL). The AUC of thiamine was identical after both infusion protocols. There was a slightly (10%) increased AUC of TPP (P < 0.08) after SI, whereas C(max) values were comparable. Urinary excretion of thiamine was significantly decreased from 83.6% of the applied dose after RI to 57.6% after the SI. CONCLUSIONS: Our data suggest an increased tissue uptake of thiamine when it is given as an SI compared with a RI of the same dose. It is concluded, therefore, that an SI of thiamine may be superior to RI or bolus injections to treat severe deficiency syndromes.     

Prevalence of folate deficiency in emergency department patients with alcohol-related illness or injury.

To assess the prevalence of folate deficiency in emergency department patients with alcohol-related illness or injury, a prospective, nonconsecutive case series with nonrandomized controls was used. All patients presenting to a 60,000-visit public hospital emergency department with alcohol-related illness or injury were eligible; patients were excluded if they had received folate in our health care facility within the previous 4 months. An alcohol and brief dietary history was obtained, and a complete blood cell count and red blood cell folate level was performed on each patient. Analysis was undertaken by chi 2 to evaluate the prevalence of folate deficiency in the alcohol-related versus the control population. One hundred three patients were entered into the study. Three patients were subsequently excluded from analysis. Of 52 study patients, three (5.8%) were found to be folate deficient. Of 48 controls, two (4.2%) were found to be folate deficient. This difference is not statistically significant (P greater than .05, chi 2; mean difference 1.6%, 95% confidence interval -6.9% to 10.1%). The prevalence of folate deficiency in patients presenting to this emergency department with alcohol-related illness or injury is low, and does not differ from the general emergency department population. Empiric folate therapy in these patients is not indicated.     

Fatal metabolic acidosis caused by thiamine deficiency

Acute thiamine deficiency, an uncommon cause of hemodynamic instability in Western countries, may be manifested by acute heart failure and neurological deficits. Severe metabolic acidosis is one of its least recognized features. We present a report of foreign workers who complained of weakness and lower limb edema and were found to have acute thiamine deficiency. One died of refractory metabolic acidosis and shock, and the diagnosis was reached post mortem. Thiamine deficiency should be considered in every case of severe lactic acidosis without an obvious cause, especially in high-risk populations (malnourished, alcoholics, Far-East workers, etc). Whenever it is suspected, empiric treatment with thiamine should be initiated immediately. Physicians who care for populations at risk should be familiar with the clinical spectrum of nutritional deficits, and monitor the nutritional habits of these patients carefully. The treatment is inexpensive and devoid of adverse effects. Moreover, delaying thiamine administration in patients with deficiency may cause severe life-threatening metabolic acidosis and affect recovery. The prophylactic use of thiamine in a high-risk population, even before blood levels are received, may be cost effective.     

Alcohol and trauma

Countermeasures to alcohol-related trauma are essential. The public perception that there is low risk of detection and punishment for alcohol-precipitated violence is being addressed. Current legislation is aimed at decreasing the availability of alcohol (e.g., adjusting legal drinking age, decreasing the serum alcohol intoxication limit, restricting the sale of alcoholic beverages at public events), increasing detection (e.g., greater driver surveillance, increased number of dedicated personnel), strengthening legal penalties for alcohol-related offenses, and mandating rehabilitative therapy. Physicians can intervene in the alcohol-trauma cycle. Unfortunately, they are notably poor in detecting the patient with alcohol-related injury. Moreover, physicians infrequently refer these patients to facilities and personnel that are expert in alcohol detoxification and rehabilitation. Recidivism can be positively impacted by physicians who are sensitive to and versed in the medical and social patterns of alcohol abuse.     

Wernicke Encephalopathy—Clinical Pearls

Wernicke encephalopathy (WE) was first described by Carl Wernicke in 1881. WE is caused by thiamine deficiency. Alcoholism is the most common etiologic factor associated with WE in the United States, but it can occur in any patient with a nutritional deficiency state such as hyperemesis gravidarum, intestinal obstruction, and malignancy. WE is a clinical diagnosis. The common findings include mental status changes, ocular dysfunction, and a gait apraxia, present in only 10% of cases. Only a few cases of WE are diagnosed before death. Approximately 80% of patients with untreated WE have development of Korsakoff syndrome, which is characterized by memory impairment associated with confabulation. The initial clinical diagnosis of WE is critical, keeping in mind that the classic triad of symptoms is often absent. Recognition of nutritional deficiency and any portion of the classic triad should prompt treatment. Additionally, hypothermia, hypotension, and coma should raise clinical suspicion for the disease. Primary treatment includes timely administration of thiamine, for which the route and dosage remain controversial. Clinical judgment should be exercised in diagnosis and treatment (dosage, frequency, route of administration and duration) in all cases of WE. Overdiagnosis and overtreatment may be preferred to prevent prolonged or persistent neurocognitive impairments given the excellent safety profile of thiamine. Further prospective research is warranted to better understand the disease biology, risk factors, and treatment recommendations.     

Wernicke's encephalopathy — causes to consider

Wernicke's encephalopathy (WE) is a thiamine deficiency disorder and is characterized clinically by the triad of ocular abnormalities, ataxia and disturbances of consciousness. We report on 3 patients with WE, of whom 2 had insufficient thiamine substitution. In the first patient symptoms disappeared during thiamine substitution. In the second patient acute WE was the terminating event in the sequence of parenteral nutrition, lactic acidosis and cardio-pulmonary decompensation. Possibly due to heriditary deficits WE developed in the third patient despite sufficient thiamine substitution. Attention to thiamine deficiency should be paid in all patients with history of alcoholism, malnutrition, malabsorption, tumors, inflammation, other severe diseases and in parenteral hyperalimentation. In order to prevent WE thiamine should be substituted with at least 100 mg/day i.v. or i.m.