Francis Dudley - Academia.edu (original) (raw)

Papers by Francis Dudley

Gut, 1979

The effect of alcoholic patient sera on in vitro lymphocyte transformation was studied using mito... more The effect of alcoholic patient sera on in vitro lymphocyte transformation was studied using mitogen-induced uptake of 3H-thymidine to measure blastogenesis. With pokeweed mitogen as the stimulus, transformation of normal lymphocytes in sera of alcoholics with either normal or fatty livers was not significantly different from that obtained in pooled human serum (PHS). However, in sera of patients with either alcoholic hepatitis or inactive cirrhosis mean transformation was significantly reduced (P <0001, <0*02 respectively). With phytohaemagglutinin-P or concanavalin A as mitogens, suppression of transformation was not as marked but followed the same pattern. A significant negative correlation was observed between the magnitude of transformation and serum bilirubin and aspartate aminotransferase levels. An intra-patient comparison of the effects on transformation of normal lymphocytes by simultaneously collected peripheral and portal venous sera, and of peripheral sera obtained before and after portasystemic shunt surgery, indicated that the factor(s) responsible did not originate in the splanchnic circulation nor did it accumulate in the serum because of failed hepatic clearance. By performing transformation experiments in the presence of inhibitory patient sera diluted with PHS it was possible to show that these sera caused true inhibition of transformation rather than suppression due to failure to sustain cell culture because of nutritional deficiencies. Inhibitory sera did not contain high levels of the enzyme thymidine phosphorylase and did not significantly inhibit binding of 125I-labelled mitogens to the lymphocyte surface. These findings indicate that the inhibitory effect of sera from alcoholics is of potential in vivo importance, that the effect increases with the degree of heptocyte damage, and that it is unrelated to the nonhepatic metabolic affects of chronic alcoholism.

J Viral Hepatitis, 1997

In patients with hepatitis C who have cirrhosis the rate of sustained response following interfer... more In patients with hepatitis C who have cirrhosis the rate of sustained response following interferon therapy is less than half that of patients without cirrhosis. It has been suggested, however, that a higher dose regime in patients with cirrhosis may improve response. The results of a recent Australian study of cirrhotic patients who were given an intense interferon programme of 4.5 MIU daily for 24 weeks were compared with previous studies of patients with hepatitis C. In the Australian study, 14% of patients had a sustained response at 6 months after end of therapy. Of 11 studies of interferon response in chronic hepatitis C comparison of pretreatment variables showed considerable differences. Identification of predictors of response by univariate and multivariate analysis regularly indicated the importance of age and fibrosis. Analysis of six studies with either a poor (5% or less) or a reasonable (14-19%) sustained response rate to interferon in patients with cirrhosis suggested that a higher dose or longer duration of therapy was associated with better results. The experience of the Australian study, where 14% of patients had a sustained biochemical response to interferon and side-effects were reasonably tolerated with careful monitoring, suggests that future studies in cirrhosis should be carried out exploring higher doses and longer durations of therapy.

Australian and New Zealand journal of medicine

Scintisplenoportography (SSP) was used to assess shunt patency in 15 patients with surgically cre... more Scintisplenoportography (SSP) was used to assess shunt patency in 15 patients with surgically created portasystemic venous shunts and proved to be a simple, safe and accurate technique for demonstrating the patency of both mesocaval "H" grafts and distal lienorenal shunts. SSP was as accurate as angiography in confirming shunt patency but was simpler to perform and resulted in less radiation exposure to the patient. The direction and distribution of blood flow within the splanchnic venous system was different to that obtained by angiography. It is postulated that SSP may well reflect portal haemodynamics more accurately than angiography. In patients with patent mesocaval "H" grafts SSP demonstrated the complete diversion of splanchnic venous blood through the shunt into the systemic venous circulation. This suggests that the mesocaval "H" graft is haemodynamically similar to other side to side portacaval shunts.

Clinical & Experimental Immunology

Both the humoral and cellular immune response to haemocyanin was measured in normal subjects and ... more Both the humoral and cellular immune response to haemocyanin was measured in normal subjects and patients with liver disease including primary biliary cirrhosis, other forms of cholestasis, and cryptogenic cirrhosis. Significant differences in antibody titre were found 2 weeks after immunization being highest in normal subjects, less in cryptogenic cirrhosis and least in primary biliary cirrhosis. The incidence of positive skin tests, indicating the development of delayed hypersensitivity to haemocyanin, was significantly less in patients with primary biliary cirrhosis and cryptogenic cirrhosis than in those with cholestasis or the normal subjects. It is suggested that the poor antibody response seen in primary biliary cirrhosis, could be related to impaired T cell function and hence lack of the T and B cell co-operation necessary for antibody formation to some antigens.

Clinical & Experimental Immunology

Sera from 134 HAA positive patients have been studied for the presence of a variety of autoantibo... more Sera from 134 HAA positive patients have been studied for the presence of a variety of autoantibodies. The patients were divided into groups dependent on the clinicopathological severity of the associated liver disease. Both smooth muscle antibody and rheumatoid factor were found in all groups of patients. However, their incidence and titre was higher in the groups of patients who had clinical and pathological evidence of the more active liver cell damage. As autoantibodies in viral infections may be an index of the presence of cell mediated immunity to the causative infective agent these results could support the hypothesis that cell mediated immunity is important in the pathogenesis of liver cell damage in HAA positive patients.