1. Serum carnosinase activity was assayed in a group of alcoholic patients with and without histologically proven atrophy of type II skeletal muscle fibres, and in control subjects. No significant activity was detected in muscle biopsy samples or washed erythrocytes. 2. Serum carnosinase activity was significantly lower in chronic alcoholic patients compared with a group of age-matched controls. Alcoholics with abnormal muscle biopsies had significantly lower enzyme activities than either those patients with normal muscle biopsies or the controls. Serum enzyme activities in patients with normal muscle biopsies were not significantly different from controls. 3. Serum carnosinase activity was inversely correlated with the degree of muscle atrophy as measured by the type II fibre atrophy factor. There was a positive correlation between the enzyme activity and skeletal muscle mass as reflected by the creatinine-height index. Furthermore, the enzyme activity significantly increased, with resolution or improvement in the myopathy, in patients who abstained from alcohol. 4. Kinetic studies showed that the reduced carnosinase activity was due mainly to a decrease in the apparent V max . The apparent K m was significantly higher in the myopathic compared with non-myopathic alcoholics. Mixing serum from controls and patients with myopathy gave the expected values, indicating the absence of a serum enzyme inhibitory factor. Acute alcohol loading had no effect on the serum carnosinase activity. 5. The decrease in serum carnosinase activity in alcoholics was not related to the severity of their liver disease. Assays of serum carnosinase in chronic alcoholics can thus be used as a marker of their associated myopathy.

1. Chronic alcoholism is associated with a selective atrophy of type II skeletal muscle fibres. We studied the glucocorticoid status of chronic alcoholics with and without myopathy to determine if hypercortisolism is responsible for the myopathy. 2. Twenty-four hour urinary Cortisol excretion and diurnal serum Cortisol measurements were not significantly different in chronic alcoholics, with and without atrophy of type II skeletal muscle fibres. 3. Diurnal serum Cortisol variation was normal for both groups of alcoholics studied. None of the patients with myopathy had raised serum Cortisol levels. 4. We conclude that chronic alcoholic myopathy is not due to alcohol-related pseudo-Cushing's syndrome.

1. A micro-technique was developed to measure fatty acid oxidation in vitro and to investigate its possible derangement in alcoholic fatty liver disease. 2. Percutaneous liver biopsy specimens were obtained from nine control subjects and 28 alcoholic patients with mild to severe fatty liver. Fresh tissue (10–15 mg) was incubated at 37°C for 90 min in a sealed reaction flask containing 1.92 mmol/l [l- 14 C]palmitic acid (1–2 μCi) and 1% essentially fatty acid free albumin in Krebs-Henseleit buffer, pH 7.4. Radiolabelled CO 2 and perchloric acid-soluble ketone bodies were isolated and counted. 3. CO 2 production was markedly reduced in alcoholic patients with mild and severe fatty liver compared with controls. This depression was reversed by the addition of malate to the reaction flask but not by carnitine or coenzyme A. 4. Ketone body production was similar in controls and patients with mild and severe fatty liver. 5. After the incubation in vitro , the tissue was extracted with chloroform/methanol and the triglyceride fraction isolated by thin layer chromatography and counted for radioactivity. The rate of palmitic acid incorporation into triglyceride was higher in alcoholic patients, particularly those with severe fatty infiltration, compared with controls. 6. It is suggested that alcoholic fatty liver is accompanied by a progressive reduction in palmitic acid oxidation with the major defect occurring in the tricarboxylic acid cycle. In contrast, the rate of palmitic acid esterification into ‘triglyceride is enhanced.

1. Disulfiram has long been used in the treatment of chronic alcoholism. It is in vivo partially reduced to diethyldithiocarbamate, which is an efficient inhibitor of Cu, Zn-containing superoxide dismutase both in vitro and in vivo. The recently described extracellular superoxide dismutase is even more sensitive to diethyldithiocarbamate than Cu, Zn-superoxide dismutase. 2. To test for the possibility that long term treatment with disulfiram leads to inhibition of the superoxide dismutases, plasma extracellular superoxide dismutase and erythrocyte Cu, Zn-superoxide dismutase were determined in 12 disulfiram-treated alcoholics, and compared with 11 non-treated alcoholics and 19 healthy controls. 3. Plasma extracellular superoxide dismutase was moderately reduced (about 20%) in the disulfiram-treated alcoholics as compared with the non-treated alcoholics and the healthy controls. No effect of disulfiram treatment on erythrocyte Cu, Zn-superoxide dismutase activity was demonstrated.

1. Respiration during sleep was studied in 16 withdrawn alcoholic patients and in 12 control subjects. 2. The alcoholic patients had increased numbers of central ( P < 0.01) and of obstructive ( P < 0.05) apnoea and of hypopnoea episodes ( P < 0.01) as compared with controls. 3. Significant positive associations were found between the frequencies of central apnoea ( P < 0.05) or hypopnoea ( P < 0.01) and clinical evidence of central nervous system damage in the alcoholic patients. Hypopnoea also showed a significant association with vagal neuropathy ( P < 0.05), assessed by tests of cardioreflexes. 4. We conclude that abnormal respiratory events are common in abstinent alcoholic patients and that they are likely to be at least partly related to nervous damage.

1. Plasma catecholamine, blood pressure and heart rate responses to standing were measured in ten alcoholics during withdrawal, ten alcoholics after 2–7 weeks of abstinence from alcohol, six abstinent alcoholics with orthostatic hypotension and ten normal control subjects. 2. Withdrawing alcoholics had supine and standing heart rates and plasma noradrenaline and adrenaline concentrations that were higher than in abstinent alcoholics or control subjects. Supine blood pressures were also higher in withdrawing alcoholics than in abstinent alcoholics or control subjects, but on standing blood pressures in withdrawing alcoholics fell, four patients having a fall of more than 30/5 mmHg. 3. Abstinent alcoholics without orthostatic hypotension had higher basal and standing concentrations of noradrenaline than control subjects but normal heart rates and adrenaline concentrations. 4. Abstinent alcoholics with orthostatic hypotension showed a wide range of basal plasma noradrenaline concentrations and were found to have variable plasma noradrenaline responses to standing, three subjects having normal responses and three subjects having no or little increase in plasma noradrenaline on standing. 5. It is concluded that alcohol withdrawal is associated with increased sympathetic nervous activity, as reflected by raised supine and standing plasma concentrations of catecholamines, and that even after 2–7 weeks of abstinence from alcohol plasma noradrenaline concentrations may be higher than in control subjects. Despite increased sympathetic nervous responses to standing, alcoholics during withdrawal have impaired blood pressure control and some may exhibit orthostatic hypotension. Orthostatic hypotension may also be observed in alcoholics during continuing abstinence from alcohol; in some of these patients failure of reflex noradrenaline release in response to standing may contribute to orthostatic hypotension.

1. Needle biopsy specimens of liver were obtained from six control subjects with histologically normal liver and 11 chronic alcoholics with fatty liver. 2. Micro- and macro-lipid droplet fractions were isolated by differential flotation. These fractions, together with the sedimenting membranes, were assayed for cholesterol, cholesteryl ester, phospholipid, free fatty acids and triglyceride. 3. Electron microscopy demonstrated marked differences in the range of lipid droplet sizes in the two fractions and biochemical analysis suggested that the microdroplet lipid corresponded to pre-very low density lipoprotein (VLDL) particles. 4. Studies on biopsies from patients with alcoholic fatty liver showed a 2–3-fold increase in triglyceride in both lipid droplet fractions but most of the accumulating triglyceride was sedimentable and membrane-bound. 5. Needle biopsy specimens from two patients with alcoholic fatty liver were fractionated with a vertical pocket re-orientating rotor. The principal organelles were separated and the subcellular distribution of triglyceride, phospholipid and free cholesterol determined. Triglyceride showed a bimodal distribution to a particulate fraction tentatively located to Golgi particles and to droplet-lipid remaining in the sample layer.

1. The relationship between the content of hepatic reduced glutathione (GSH) and the length of abstinence was investigated in 45 chronic alcoholic patients. 2. Hepatic GSH levels were significantly correlated ( r = 0.58; P <0.001) with the length of alcohol withdrawal in the whole group. According to liver histology patients were divided into two groups, with and without hepatic necrosis. Subjects without necrosis showed a significant positive correlation ( r = 0.71; P <0.001) between GSH values and the length of abstinence; no correlation ( r = −0.22; P <0.40) was observed in the group with necrosis. 3. According to the period of abstinence patients were separated into two groups, with a short (≪ 5 days) and a prolonged (> 5 days) alcohol withdrawal. Patients with and without necrosis exhibited comparable mean levels of liver GSH (2.04 ± sem 0.21 and 1.74 ± 0.23 μmol/g respectively; P <0.30) when studied after short periods of abstinence. Alcoholics without liver necrosis showed significantly higher hepatic GSH levels than those with necrosis (3.23 ± 0.30 and 1.60 ± 0.33 respectively; P < 0.01) after prolonged periods of alcohol withdrawal. Similar results were obtained when liver GSH levels were expressed as a function of the mean surface area of hepatocytes, which was not significantly different between patients with and without hepatic necrosis. 4. Parameters assessing the nutritional status of patients with and without necrosis were not significantly different. Steatosis, histologically scored and irrespective of the period of abstinence, was higher in patients with liver necrosis and it did not correlate with hepatic GSH ( r = −0.17; not significant). Fibrosis was observed in 20 cases and it did not modify the positive correlation between liver GSH content and the period of abstinence (with fibrosis: r = 0.57; P < 0.01; without fibrosis: r = 0.58; P < 0.01). 5. The changes observed in liver GSH content might be of pathogenic importance in alcoholic liver disease through alterations in lipoperoxidative processes in the hepatocyte.

1. Percutaneous needle biopsy specimens of liver were obtained from alcoholic, diabetic and control patients. Micro-methods of lipid separation and quantification were employed to determine the detailed nature of hepatic lipid. 2. Triglyceride is the major accumulating liver lipid in both alcoholic and diabetic patients. Cholesteryl ester levels were raised in both alcoholic and diabetic patients but only diabetic patients had significantly increased free cholesterol and phospholipid levels. Determination of phospholipid/free cholesterol ratios revealed a significant decrease in alcoholic cirrhosis compared with controls. 3. Fatty acid ester analysis of hepatic phospholipid and triglyceride revealed significant differences between alcoholic patients and controls but not between diabetic patients and controls. An increased ratio of non-essential/essential fatty acids was found in the patients with alcoholic liver disease whereas those of diabetic patients were similar to the controls.

1. Of 96 alcoholics admitted for detoxification, 48% were hypertensive (systolic blood pressure > 140 mmHg and/or diastolic pressure > 90 mmHg). 2. Elevation of both systolic and diastolic blood pressures was related to the severity of alcohol-withdrawal symptoms. 3. After these symptoms had abated only 9% of patients remained hypertensive. 4. Blood pressure remained normal if patients abstained from alcohol after discharge but rose in those who started drinking again. 5. Hypertension was not consistently related to the presence or severity of alcoholic liver disease. 6. Alcohol-related hypertension may be the result of the alcohol-withdrawal syndrome; increased noradrenergic activity is suggested as the likely mechanism.