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Biomedical subjects

D I Sherman

Publications and source records attributed to D I Sherman.

7 recordsLinked to original sources
PubMed1994

Alcohol and acetaldehyde dehydrogenase gene polymorphism and alcoholism.

Inherited variations in alcohol and aldehyde dehydrogenases, the principal enzymes of ethanol metabolism, have been implicated in determining susceptibility to alcoholism and alcohol-related organ damage. An association between an RFLP for the alcohol dehydrogenase-2 (ADH2) gene and alcohol-induced liver damage was demonstrated in a Caucasian population. Genotyping studies revealed an increase in the ADH3(2) allele in patients with alcohol-induced cirrhosis. PCR studies of the ALDH5 gene have demonstrated diverse polymorphism within a short segment of its coding region, with marked inter-racial variation in allele frequencies. In addition, the Caucasian alcohol-induced flushing reaction has been characterised and its relationship with phenotypic polymorphism of ALDH1 examined.

Alcohol Dehydrogenase↗
PubMed1994

Liver damage: mechanisms and management.

Despite recent advances in our knowledge of the mechanisms of alcohol-induced liver damage, abstinence from alcohol and supportive measures remain the mainstays of management for the majority of patients. Progress has been made in our understanding of ethanol metabolism, the role of acetaldehyde, and both genetic and environmental factors responsible for the variation in individual susceptibility to alcoholic liver disease. Evidence for the involvement of the immune system and the effects of alcohol on hepatic fibrosis are also reviewed. Recent therapeutic trials of corticosteroids in acute alcoholic hepatitis have confirmed their benefit in patients who have a high risk of mortality. For patients with end-stage cirrhosis, orthotopic liver transplantation is now an accepted therapy in selected patients who have a good prognosis for future abstinence.

Acetaldehyde↗
PubMed1994

Identification and characterisation of alcohol-induced flushing in Caucasian subjects.

The prevalence of the alcohol-flushing reaction was assessed in a group of healthy Caucasian medical students (200) by self-reporting and was found to occur in approximately 50% of female and 8% of male subjects. In most of the alcohol flushers there were other family members similarly affected. The presence of this side-effect after a small quantity of alcohol did not necessarily decrease the amount of alcohol consumed. A test dose of ethanol (0.4 g/kg body weight) confirmed the presence of the alcohol-induced flushing, which was of much shorter duration and intensity than that of the Oriental alcohol-induced flusher, as measured by laser Doppler velocimetry, and was not associated with high circulating concentrations of acetaldehyde. Topical administration of 5 M acetaldehyde showed an enhanced erythema in Caucasian flushers compared to non-flushing controls. This effect was not observed with topical ethanol. Low erythrocyte ALDH1 activity was found in all Caucasians (n = 30) who showed the alcohol-induced flushing reaction.

Acetaldehyde↗
PubMed1993

Total pancreatic and salivary serum iso-amylase activities in alcohol misusers in relapse and remission and in alcoholic liver disease.

By means of immunoinhibition by specific salivary monoclonal antibodies in combination with a chromogenic substrate, assays of serum amylase were performed in control subjects, in chronic alcohol misusers in relapse or remission and in patients with alcoholic liver disease (ALD). There was a selective increase in the salivary isoenzyme in the ALD group. There were no significant changes in either of the alcohol misusing groups, compared with control subjects. It is suggested that the increase in salivary iso-amylase observed in patients with ALD is related to the previously reported functional and histological abnormalities in the parotid glands of this group of patients. It is also suggested that assay of pancreatic iso-amylase may be more discriminatory than total amylase levels in detecting pancreatic disease in patients with alcoholic cirrhosis.

Adult↗
PubMed1993

Association of restriction fragment length polymorphism in alcohol dehydrogenase 2 gene with alcohol induced liver damage.

OBJECTIVE: To investigate the role of genetically determined differences in the enzymes of alcohol metabolism in susceptibility to liver damage from misusing alcohol. DESIGN: Use of pADH36 probe to study PVU II restriction length fragment polymorphism in alcohol dehydrogenase 2 gene in white alcohol misusers and controls. SETTING: Teaching hospital referral centres for liver disease and alcohol misuse. SUBJECTS: 45 white alcohol misusers (38 with alcoholic liver disease) and 23 healthy controls. MAIN OUTCOME MEASURES: Alcohol misuse, the presence and severity of alcoholic liver disease, alcohol dependency, and family history of alcohol misuse. RESULTS: A two allele polymorphism (A and B) was identified. In control subjects the allele frequencies were 85% for A and 15% for B compared with 37% and 63% respectively in alcohol misusers (p < 0.001). B allele was significantly associated with severe liver damage (p < 0.05) as well as alcohol dependency and family history of alcohol misuse compared with controls. CONCLUSION: Inherited variation in enzymes of ethanol metabolism may contribute to the pathogenesis of alcohol induced liver damage. This supports the presence of a genetic component in alcohol misuse.

Adult↗