Could the high level of cirrhosis in central and eastern Europe be due partly to the quality of alcohol consumed? An exploratory investigation.

BACKGROUND: The burden of alcohol-related diseases differs widely among countries. Since the 1980s, a band of countries in Central and Eastern Europe have experienced a steep rise in deaths from chronic liver diseases and cirrhosis. A possible risk factor is the consumption of illegally produced home-made spirits in these countries containing varying amounts of aliphatic alcohols and which may be hepatotoxic. However, little is known about the composition of such beverages. AIMS: To compare the concentration of short-chain aliphatic alcohols in spirits from illegal and legal sources in Hungary. DESIGN: Samples taken from commercial retailers and illegal sources were collected and their aliphatic patterns and alcohol concentrations were determined by gas chromatographic/mass spectrometric (GC/MS) analysis. FINDINGS: The concentrations of methanol, isobutanol, 1-propanol, 1-butanol, 2-butanol and isoamyl alcohol were significantly higher in home-made spirits than those of from commercial sources. CONCLUSIONS: The results suggest that the consumption of home-made spirits is an additional risk factor for the development of alcohol-induced cirrhosis and may have contributed to high level of liver cirrhosis mortality in Central and Eastern Europe. Restrictions on supply and sale of alcohol from illicit sources are needed urgently to reduce significantly the mortality from chronic liver disease

Prognostic Modelling Studies of Coronary Heart Disease—A Systematic Review of Conventional and Genetic Risk Factor Studies

This study aims to provide an overview of multivariable prognostic modelling studies developed for coronary heart disease (CHD) in the general population and to explore the optimal prognostic model by comparing the models’ performance. A systematic review was performed using Embase, PubMed, Cochrane, Web of Science, and Scopus databases until 30 November 2019. In this work, only prognostic studies describing conventional risk factors alone or a combination of conventional and genomic risk factors, being developmental and/or validation prognostic studies of a multivariable model, were included. A total of 4021 records were screened by titles and abstracts, and 72 articles were eligible. All the relevant studies were checked by comparing the discrimination, reclassification, and calibration measures. Most of the models were developed in the United States and Canada and targeted the general population. The models included a set of similar predictors, such as age, sex, smoking, cholesterol level, blood pressure, BMI, and diabetes mellitus. In this study, many articles were identified and screened for consistency and reliability using CHARM and GRIPS statements. However, the usefulness of most prognostic models was not demonstrated; only a limited number of these models supported clinical evidence. Unfortunately, substantial heterogeneity was recognized in the definition and outcome of CHD events. The inclusion of genetic risk scores in addition to conventional risk factors might help in predicting the incidence of CHDs; however, the generalizability of the existing prognostic models remains open. Validation studies for the existing developmental models are needed to ensure generalizability, improve the research quality, and increase the transparency of the study

The composition of surrogate and illegal alcohol products in Estonia.

AIM: To identify the composition of illegal and surrogate alcohol products consumed in Estonia. METHODS: The initial source of information was a series of visits made in August 2005 to a soup kitchen in central Tartu, Estonia. Individuals were asked for brief details of their personal circumstances, what they normally drank, and in addition they were asked to bring samples of the substances they usually consumed. In other cases, the substances identified were purchased by the investigators or from informal contacts in north-eastern part of Estonia, an area that is well known for illegal alcohol consumption. Samples were tested for chemical contents. RESULTS: We identified a range of alcohol-containing substances that are consumed, although, not intended for consumption. These comprised medicinal products, aftershaves, illegally produced spirits, and fire-lighting fuel. The medicinal compounds contained, on average, 67% ethanol by volume; the aftershaves contained slightly less. Both were typically pure, with a few containing detectable quantities of isoamyl alcohol. The illegally produced alcohol contained, on average, 43% ethanol by volume, ranging from 32 to 53%. However, many also contained detectable quantities of long chain alcohols. These substances are half the price or less of commercial vodka, with fire lighting fuels especially inexpensive. CONCLUSIONS: There is in Estonia a range of alcohol-containing substances easily available at low cost. Some contain substantially higher concentrations of ethanol than commercial spirits and others also contain toxic long chain alcohols

Aliphatic alcohols of illegally produced spirits can act synergistically on superoxide-anion production by human granulocytes.

CONTEXT: Aliphatic alcohols present in illegally produced spirits in a large number of low and middle income countries have been implicated in the etiology of chronic liver disease and cirrhosis. Previous studies have confirmed that chronic alcoholism can lead to increased susceptibility to infectious diseases. Reduced superoxide-anion (O(2)·(-)) production by granulocytes could provide a mechanism by which antimicrobial defense is impaired in alcoholics. In vitro experiments have also demonstrated that ethanol can inhibit granulocyte O(2)·(-) generation. Aliphatic alcohols consumed as contaminants of illicit spirits may also influence O(2)·(-) production thereby contributing to a decrease in microbicidal activity. OBJECTIVE: The aim of this study was to investigate this possibility. It measured the O(2)·(-) production by human granulocytes following treatment of the cells with aliphatic alcohol contaminants found in illicit spirits. MATERIALS AND METHODS: Granulocytes were isolated from human buffy coats with centrifugal elutriation and then treated with individual aliphatic alcohols and their mixture. The O(2)·(-) production was stimulated with phorbol-12-13-dibutyrate and N-formyl-methionyl-leucyl-phenylalanine (FMLP) and measured by superoxide dismutase inhibitable reduction of ferricytochrome c. RESULTS: Aliphatic alcohols of illegally produced spirits inhibited the FMLP-induced O(2)·(-) production in a concentration dependent manner. They suppressed O(2)·(-) generation at 2.5-40 times lower concentrations when combined than when tested individually. DISCUSSION AND CONCLUSION: Aliphatic alcohols found in illegally produced spirits can inhibit FMLP-induced O(2)·(-) production by granulocytes in a concentration-dependent manner. Due to their synergistic effects, it is possible that, in combination with ethanol, they may inhibit O(2)·(-) formation in heavy episodic drinkers

The prevalence of obesity is increased in patients with late compared with early onset psoriasis.

PURPOSE We compared the clinical and epidemiologic characteristics of early and late onset psoriasis with an emphasis on potential differences in the comorbidities associated with each subtype. METHODS An observational, multicenter study was performed, and associations between the age at the time of diagnosis and binary comorbidity outcomes were evaluated using multiple logistic regression analysis adjusted for age and other relevant confounders. RESULTS An increased prevalence of positive family history, psoriatic arthritis, and depression was observed in patients with early onset psoriasis. On the other hand, late onset psoriasis was more frequently associated with obesity and elevated waist circumference compared with early onset form. Elderly psoriatic patients (at the age of 75 years) with late onset psoriasis are at an especially high risk for obesity compared with individuals at the same age with an early onset disease. CONCLUSIONS The increased frequency of psoriasis in the family of early onset patients may suggest that manifestation of psoriasis at younger age is driven by strong genetic influence. However, such a remarkable association of abdominal obesity with late onset psoriasis may suggest that obesity can be one of the acquired factors that may predispose for the development of psoriasis in the elderly

Multiple common variants for celiac disease influencing immune gene expression.

We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P(GWAS) < 10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (P(combined) < 5 x 10(-8)); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection. There was evidence to suggest associations for a further 13 regions. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P < 0.0028, FDR 5%) with cis gene expression