Search PubMed⌕ Search

Biomedical subjects

J B Saunders

Publications and source records attributed to J B Saunders.

At least 73 records · Page 4Linked to original sources
PubMed1985

The role of salsolinol in alcohol intake and withdrawal.

We studied the urinary excretion of the tetrahydroisoquinoline (TIQ) salsolinol, formed from acetaldehyde and dopamine, in both severely and moderately dependent alcoholics during withdrawal from alcohol and subsequent challenge with an acute dose of alcohol and L-dopa, and compared these results with controls. Plasma acetaldehyde and alcohol levels in a sub-population of severely dependent withdrawn alcoholic and control subjects following an acute dose of alcohol were also determined. Salsolinol excretion during the first 4 days of alcohol withdrawal was variable but 10 out of 14 alcoholics showed an increasing trend from day 1 to day 3 and 4 of alcohol withdrawal. L-dopa administration raised salsolinol excretion in controls and withdrawn alcoholics to a uniform extent. Loading of the withdrawn alcoholics with an acute dose of alcohol did not cause an increase in urinary salsolinol concentration (despite increased plasma acetaldehyde). Indeed, 24 h following acute alcohol administration, salsolinol excretion rates were depressed in the alcoholics but not in the controls.

Acetaldehyde↗
PubMed1984

Effect of alcohol withdrawal on blood pressure, plasma renin activity, aldosterone, cortisol and dopamine beta-hydroxylase.

Sixty-five alcoholic patients admitted for detoxification had blood pressure, withdrawal symptoms, plasma cortisol (PC) and plasma aldosterone (PA) levels, plasma renin activity (PRA), and serum dopamine beta-hydroxylase (DBH) levels measured on the first and fourth days after admission. On the morning after admission blood pressure was elevated (greater than 140/90) in 32 patients (49%) and was 160/95 mmHg or more in 21 (32%). PRA was initially elevated in 41 patients, PA levels in 14, and 13 patients had raised PC levels. By the fourth day, blood pressure and biochemical measures had fallen significantly while urine volume and sodium output, low on admission, had increased significantly. On admission urinary metanephrine levels were raised in four out of the 31 patients who had them measured. The height of both the systolic and diastolic blood pressures was significantly related to the severity of the alcohol withdrawal symptoms. Of the biochemical parameters measured, PC level correlated with systolic but not diastolic pressure, and urinary volume was inversely correlated with the height of the diastolic pressure. No relationship was found between blood pressure and PRA or PA level. The pressor effect of alcohol withdrawal could be due to sympathetic nervous system overactivity, or possibly to hypercortisolaemia . The first hypothesis seems more likely.

Adult↗
PubMed1984

Antibodies to alcohol altered liver cell determinants in patients with alcoholic liver disease.

Circulating antibodies reacting specifically with hepatocytes isolated from ethanol pretreated rabbits have been demonstrated by two techniques - induced cytotoxicity and immunofluorescence. In the cytotoxicity assay antibodies were found in seven of 19 (39%) of patients with alcoholic fatty liver (with or without fibrosis), six of 13 (46%) of those with alcoholic hepatitis, 15 of 36 (43%) of those with cirrhosis, and seven of 14 patients (50%) of those with hepatitis and cirrhosis. In the immunofluorescence studies, nine of 15 sera induced a granular pattern of fluorescence on the ethanol pretreated hepatocytes; two sera which induced significant cytotoxicity did not induce immunofluorescence. No ethanol related antibodies were found in normal individuals or in patients with other types of acute or chronic liver disease. These results show that antibodies directed against ethanol altered liver cell determinants are present in the serum of 43% of patients with alcoholic liver disease, and suggest a mechanism whereby chronic alcohol consumption may, by inducing antigenic changes in hepatocyte membranes, trigger a cell damaging immune reaction.

Adult↗
PubMed1984

The clinical nature and detection of psychiatric disorders in patients with alcoholic liver disease.

To determine the clinical nature of psychiatric disorders and their detection in patients with alcoholic liver disease we interviewed 71 randomly sampled subjects using two well-validated techniques: (i) the Schedule for Affective Disorders and Schizophrenia (SADS-L) and (ii) the General Health Questionnaire (GHQ), a self-administered screening questionnaire. We also interviewed a similar number of controlled subjects with non-alcoholic liver disease of comparable severity. Forty-seven (66%) of those with alcoholic liver disease had psychiatric disorder compared with 23 (32%) of the control group (P less than 0.001). The commonest problems encountered in both groups were affective disorders, neuroses and anti-social personality, the latter was commoner in male alcoholics (33%) than in non-alcoholics (13%; P less than 0.02). In nearly half of the alcoholic group, psychiatric disorder antedated the onset of heavy drinking; nearly half of them had psychiatric disorders at the time of interview. Thirty-five (74%) of the alcoholics with positive psychopathology assessed by SADS-L were identified as psychiatric cases by the GHQ (score greater than 5), and the mean GHQ score was significantly higher in the alcoholics than in the controls (13.2 +/- 2.1 and 6.2 +/- 1.3, P less than 0.01). These results demonstrate the high frequency of psychiatric disorders in patients with alcoholic liver disease and suggest that psychiatric intervention is needed in many patients to improve their likelihood of remaining abstinent from alcohol.

Adult↗
PubMed1983

Psychiatric morbidity in patients with alcoholic liver disease.

Seventy one patients with alcoholic liver disease and an equal number with non-alcoholic liver disease were interviewed using the schedule for affective disorders and schizophrenia. Forty seven (66%) of the group with alcoholic liver disease had or had had psychiatric illnesses compared with 23 (32%) of the control group (p less than 0.001). Affective disorder, particularly major depression, neurotic disorders, and antisocial personality, were all more common among the patients with alcoholic liver disease than the controls. No patient had schizophrenia or other forms of psychosis. Among the patients with alcoholic liver disease 11 men (24%) and 14 women (54%) had an affective or a neurotic disorder that had antedated their heavy drinking, and 30 (77%) of those who had had such a problem at any time had symptoms at the time of interview. Abstinence from alcohol is essential for patients with severe alcoholic liver disease. In view of the high prevalence of psychiatric disorders in these patients psychiatric assessment is important to increase the patients' likelihood of complying with such advice.

Adult↗
PubMed1983

Severity of alcohol dependence in patients with alcoholic liver disease.

To determine the severity of dependence on alcohol in patients with alcoholic liver disease the severity of alcohol dependence questionnaire was administered to 193 patients with various types of alcoholic liver disease established histologically, in whom a detailed history of lifetime alcohol consumption was also obtained. Only 34 patients (18%) were classified as being severely dependent compared with 56% of patients without overt liver disease who were attending a neighbouring alcohol treatment unit. There was a significant correlation between the severity of dependence and mean daily alcohol consumption (r = 0.45 and 0.39 for men and women, respectively) but not duration of drinking. Dependence scores tended to be lower in patients with cirrhosis than in those with precirrhotic liver disease, but this difference reached significance only in women. These findings confirm that patients who develop chronic alcoholic liver disease are usually only mildly dependent on alcohol and support the hypothesis that patients who escape florid symptoms of alcohol dependence are at greater risk of developing liver damage because they are able to sustain a continual consumption of alcohol over many years.

Adult↗
PubMed1983

Importance of markers of hepatitis B virus in alcoholic liver disease.

To determine the importance of the presence of serological markers of hepatitis B virus infection in patients with alcohol related liver disease we compared cumulative alcohol intake and clinical and histological features in patients with markers of hepatitis B virus infection and in those without. Hepatitis B surface antigen (HBsAg) was detected in five (2%) out of 285 patients studied and antibody to HBsAg (anti-HBs) in 41 (14%); one patient had antibody to hepatitis B core antigen alone. The combined prevalence of markers of hepatitis B virus infection was similar in patients with alcoholic cirrhosis (18%) and precirrhotic liver disease (13%). Two patients positive for HBsAg had histological features of both alcoholic liver disease and chronic active hepatitis, with stainable HBsAg. Patients with anti-HBs were, however, histologically indistinguishable from patients without markers, and the mean cumulative alcohol intake of patients with anti-HBs was similar to or even higher than that of patients with liver disease of comparable severity who had no evidence of previous infection. The presence of markers of hepatitis B virus infection was related to former residence in countries with a high prevalence of the infection and to previous parenteral treatment and blood transfusions. Infection with hepatitis B virus does not enhance the development of chronic liver disease in heavy drinkers, except in the small number who remain positive for HBsAg.

Adult↗
PubMed1983

Effects of ethanol and acetaldehyde on hepatic plasma membrane ATPases.

To elucidate possible causes of the hepatocyte swelling and necrosis found in alcoholic liver disease, the effects of ethanol and acetaldehyde on the activities of two hepatic plasma membrane ATPases--(Na+K+) ATPase and Mg2+ ATPase--were investigated. The activity of another plasma membrane-bound enzyme, 5' nucleotidase, was also determined to assess the specificity of these effects. Over concentrations ranging from 8 to 90 mM ethanol did not cause significant inhibition of any of the three enzymes. At 120 mM ethanol (Na+K+) ATPase activity was inhibited by 20% (P less than 0.01) and at higher concentrations there was progressive inhibition of all three enzymes that was non-competitive in type. Acetaldehyde produced non-competitive inhibition of (Na+K+) ATPase and Mg2+ ATPase at concentrations of 6 and 56 mM respectively and 5' nucleotidase activity was also inhibited at these concentrations. We conclude that ethanol and acetaldehyde inhibit (Na+K+) ATPase and Mg2+ ATPase activities as part of a generalised effect on the liver plasma membrane. Because the inhibitory concentrations of both substances are higher than are usually found in alcoholic subjects or in experimental animals after alcohol feeding, it seems unlikely that direct suppression of ATPase activity by ethanol or acetaldehyde is responsible for the morphological abnormalities of alcohol-induced liver disease. It could, however, be implicated in the development of hepatocellular necrosis in severe ethanol poisoning.

5'-Nucleotidase↗
PubMed1983

Identification of alcohol dehydrogenase and aldehyde dehydrogenase isoenzymes in human liver biopsy specimens.

A sensitive method for detecting isoenzymes of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in human liver biopsy specimens by simultaneous starch gel electrophoresis is described. All the currently recognised hepatic isoenzymes of ADH and ALDH which are concerned with ethanol metabolism can be identified. The method is suitable for amounts of liver biopsy material weighing as little as 2.5 mg and also allows spectrophotometric assay of ADH activity (at pH 8.8 and 11.0) and of ALDH.

Alcohol Oxidoreductases↗
PubMed1983

Isolation and preliminary toxicological evaluation of arsenobetaine - the water-soluble arsenical constituent from the hepatopancreas of the western rock lobster.

The water soluble arsenic compound present in the hepatopancreas of the western rock lobster (Panulirus cygnus George) has been isolated as the reineckate salt and has been identified as arsenobetaine. Intraperitoneal injection of arsenobetaine into mice at 500 mg kg-1 did not result in mortality, and no symptoms of poisoning were observed. Mice treated with arsenobetaine at 360 mg kg-1 rapidly eliminated the compound in their excreta and no evidence was obtained for metabolic alteration. When tested in the Ames' Salmonella typhimurium system for chemical mutagens, both in the presence and absence of liver microsomal oxidase fraction, arsenobetaine gave consistently negative results.

Animals↗
PubMed1983

Hepatic ADH and ALDH isoenzymes in different racial groups and in chronic alcoholism.

A method has been developed for simultaneous analysis of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isoenzymes in small (2.5 mg) liver biopsy cores by starch gel electrophoresis. All the currently recognized hepatic isoenzymes coded by ADH1, ADH2, ADH3 and ADH4 can be detected as can the five ALDH isoenzymes. Using this technique we have investigated the isoenzyme composition of liver samples from English and Chinese subjects and a group of chronic alcoholics. Pronounced racial differences in frequency of ADH2 and ALDH phenotypes were found--only 2 (4%) of English controls had the "atypical" ADH2 variant whereas this was present in 42 (84%) of Chinese subjects, and whereas all the English subjects had the rapidly migrating mitochondrial isoenzyme of ALDH, this was absent in 27 (54%) of Chinese. No differences in ADH or ALDH phenotype were seen in the chronic alcoholics, all of whom were of English origin, compared with the English controls, but there was a reduction in overall ALDH activity and particularly in the mitochondrial isoenzyme in those with cirrhosis. The reduction in ALDH activity is probably acquired; by limiting acetaldehyde oxidation it could be responsible for the rapid deterioration in liver function in patients who continue drinking excessively.

Alcohol Dehydrogenase↗
PubMed1983

Blood pressure and pressor mechanisms during alcohol withdrawal.

Blood pressure, alcohol withdrawal symptoms and plasma levels of cortisol, aldosterone and renin activity and serum dopamine beta-hydroxylase concentrations were measured in 65 alcoholics on the first and fourth days after admission for detoxification. On the day after admission blood pressure was elevated (greater than 140/90 mmHg) in 32 patients (49%) and was 160/95 mmHg or more in 21 (32%). Plasma renin activity was elevated in 41 patients and plasma aldosterone concentration in 14, but neither correlated with blood pressure. Plasma cortisol levels were elevated in 13 patients and were positively correlated with systolic blood pressure. Blood pressure and all biochemical measures fell significantly by the fourth day while urine volume and sodium output, low on admission, increased significantly. Urinary metanephrine levels were elevated in four of 31 patients in whom they were measured on admission. Alcohol withdrawal was accompanied by raised blood pressure and high plasma concentrations of cortisol, renin and aldosterone but only plasma cortisol concentrations and withdrawal symptoms were significantly related to blood pressure.

Alcoholism↗
PubMed1982

Accelerated development of alcoholic cirrhosis in patients with HLA-B8.

To test whether the increased prevalence of HLA-B8 reported in patients with alcoholic cirrhosis is due to the antigen being a genetic marker of susceptibility to liver damage from alcohol, patients who had cirrhosis of comparable clinical and histological severity were investigated for HLA-B8 status and cumulative alcohol intake. Both male and female cirrhotics with HLA-B8 had been drinking greater than 40 g alcohol/day for a shorter period of time (16.6 +/- 1.4 men, and 9.4 +/- 2.0 years, women) than their counterparts without this antigen (23.7 +/- 1.7, p less than 0.005, and 15.8 +/- 2.0 years, p less than 0.05, respectively), but the mean daily alcohol intake was similar whether patients had HLA-B8 or not. These results suggest that genetic determinants linked to HLA-B8 enhance the rate of development of liver damage in those who drink potentially hepatotoxic amounts of alcohol.

Adult↗