Diversity of autoantibodies in patients with antimitochondrial antibody and their diagnostic value.

A retrospective analysis of clinical and laboratory features of 102 patients, whose sera contained antibody to mitochondria, showed that primary biliary cirrhosis was diagnosed in 50% of them. Immunofluorescence showed that the sera of the patients with primary biliary cirrhosis all had the M2 antimitochondrial antibody staining pattern. A new staining pattern, designated M2(1), which could be mistaken for the M2 pattern, was not found in any patients with either primary biliary cirrhosis or chronic active hepatitis. Other serological variables such as antibody to mitochondria in IgM class, to multiple nuclear dots, and to the XR antigen, were associated with primary biliary cirrhosis, and taken in association with antimitochondrial antibody of M2 type, contribute to the diagnosis of the disease.

Antibodies specific for measles virus envelope antigens and autoantibodies in patients with chronic active hepatitis.

Distinctly increased levels of antibodies to measles virus envelope antigens haemolysin and haemagglutinin were found in the sera of patients with chronic active hepatitis compared with a normal control group, using immunofluorescence and functional tests. Similarly, a higher incidence of smooth muscle antibody of both IgG and IgM classes was observed in the patients and an important correlation was found between haemolysin antibodies specific for measles virus and smooth muscle antibody of IgG and IgM classes. In contrast, there was no such correlation between the virus specific haemolysin antibodies and antinuclear antibodies. The increased levels of antibodies to measles virus envelope antigens and of autoantibodies may reflect defects in immunoregulation rather than persistent infection with measles virus.

Cortisol metabolism in chronic liver disease.

Impairment of cortisol metabolism, evidence of endogenous hypercortism and sensitivity to oral corticosteroids are known to occur in patients with chronic liver disease. Measurements were made of plasma 11-OHCS and urinary cortisol levels and other parameters of adrenal function in a group of such patients. The mean plasma total 11-OHCS was lower in patients than in control subjects, although this difference was not statistically significant and the normal circadian rhythm was maintained. However, in patients with chronic liver disease a greater proportion of the 11-OHCS was in the non-protein bound state resulting in an elevation of this fraction. This elevation of non-protein bound 11-OHCS must represent a resetting of the pituitary-adrenal feedback mechanism in these patients. Corticosteroid binding globulin was lower in patients than in control subjects, although the difference was not statistically significant. Urinary cortisol excretion was significantly reduced as was excretion of 17-ketosteroids. Cortisol secretion rate was found to be normal. It is suggested that elevation of plasma non-protein bound 11-OHCS, resulting from impaired metabolism and reduced protein binding of cortisol in patients with hepatic disease, may explain the features of endogenous hypercorticism seen in such patients. Moreover, in the presence of impaired steroid metabolism and reduced protein binding, these patients may exhibit an increased sensitivity to corticosteroid therapy, and therefore administration of a reduced dosage may be advisable.

The effect of exercise on the venous blood ammonium concentration in man.

Mild muscular exercise did not cause any significant rise in the ammonium concentration of venous blood draining the exercising forearm of control subjects or patients with cirrhosis. However, in both cirrhotic and non-cirrhotic subjects moderate exercise produced significant increases in venous blood ammonium values and these occurred earlier and were more prolonged in cirrhotic patients. Severe exercise caused larger increases in venous blood ammonium concentration in all subjects but there were no significant differences between the mean ammonium concentrations of the cirrhotic and control groups either before or after exercise. All ammonium values returned to their pre-exercise levels within half an hour of resting. The exact mechanism of these phenomena is not fully understood but they are of practical importance in the study of blood ammonium metabolism in normal subjects and in patients with cirrhosis of the liver. The importance of making subjects rest for at least 30 minutes before obtaining blood for ammonium determination is emphasized in order to obviate misleadingly high readings due to muscular activity.

Venous blood ammonium levels in control subjects and in patients with disorders of the liver.

Venous blood ammonium levels were studied in 106 control subjects and 47 patients with varying degrees of liver disorder. The resting venous blood ammonium was normally distributed in both male and female control subjects and was not influenced by either the sex or the fasting state of the subject. In general it was also uninfluenced by age except that the level was found to be a little lower in subjects over 60 years of age probably due to their state of greater muscular inactivity. The mean resting ammonium level in controls was 80.0 mug/100 ml +/- 17.17 mug/100 ml and the range (mean +/- 2 SD) 46-114 mug/100 ml. Raised levels were obtained in 16.7% of patients with subclinical liver disorder, 62.5% with moderate liver disorder, and 85.5% with severe liver disorder, indicating a relationship between the severity of liver disorder and the resting venous blood ammonium level. As the majority of patients with severe liver disorder were known to have varices the raised ammonium levels are likely to have been related to the greater magnitude and incidence of portal systemic shunts in those with severe liver disease.