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Biomedical subjects

F J Dudley

Publications and source records attributed to F J Dudley.

At least 73 records · Page 4Linked to original sources
PubMed1980

The mechanism of the carbohydrate intolerance of cirrhosis.

Cirrhosis of the liver is frequently associated with carbohydrate intolerance but it is unknown whether this intolerance is due to increased hepatic glucose production (HGP), decreased glucose utilization, or both. HGP and the MCR of glucose [(MCR)G] were measured at steady state, basally and during an infusion of insulin (25 mU/kg x h) and glucose (11 mumol/kg x min), in 11 cirrhotics and 8 controls using the technique of a primed constant infusion of [3H]3-glucose. HGP was also estimated at nonsteady state during an infusion of glucagon (8 ng/kg x min). Basal HGP was significantly lower in cirrhotics compared to controls (10.2 +/- 0.6 vs. 13.2 +/- 0.6 mumol/kg x min; P < 0.0025). During the insulin/glucose infusion, HGP was suppressed to the same degree in both groups [in controls by 83% (13.2 +/- 0.6 to 2.2 +/- 0.8 mumol/kg x min) and in cirrhotics by 87% (10.2 +/- 0.6 to 1.3 +/- 0.4 mumol/kg x min)]. After the glucagon infusion, HGP rose by a similar degree in cirrhotics and controls. In contrast, basal (MCR)G was significantly lower in the nondiabetic cirrhotics (2.1 +/- .02 ml/kg x min; P < 0.005) and diabetic cirrhotics (1.2 +/- 0.2 ml/kg x min; P < 0.0005) compared to that in the control subjects (2.8 +/- 0.2 ml/kg x min). Moreover, there was a highly significant (P < 0.001) negative correlation between basal (MCR)G and the fasting glucose level (r = 0.82), and the degree of glucose intolerance as expressed by the 2-h glucose level determined by the oral glucose tolerance test (r = 0.87). It is concluded that the glucose intolerance of cirrhosis is due to a defect in peripheral glucose utilization.

Adult↗
PubMed1979

Lymphopenia and lymphocyte transformation in alcoholics.

The basis of peripheral blood lymphopenia observed in patients with chronic alcoholism and liver disease was investigated by examining the effect of sera of these patients on in vitro transformation of normal human peripheral blood lymphocytes. A positive correlation was demonstrated between the serum inhibition of phytohaemagglutinin- and pokeweed mitogen-induced transformation and the degree of lymphopenia. Thus serum factors may contribute to the observed lymphopenia by inhibiting lymphocyte production in vivo.

Alcoholism↗
PubMed1979

Glucagon metabolism in normal subjects and in cirrhotic patients before and after portasystemic venous shunt surgery.

The effect of portasystemic shunt surgery on basal immunoreactive glucagon (IRG) levels, metabolic clearance rate (MCR) and t 1/2 for glucagon decay, and basal systemic delivery rate (BSDR) of glucagon was investigated in paired studies in ten cirrhotic subjects. The degree of hepatocellular dysfunction and extent of portasystemic venous shunting was also recorded. Basal IRG levels were highest in the post-shunt (mean +/- SEM, 382 +/- 73 pg/ml) as compared to the pre-shunt (213 +/- 27 pg/ml; P less than 0.05) cirrhotic and control (53 +/- 13 pg/ml; P less than 0.005) groups. The MCR of glucagon was similar in control (13.0 +/- 1.3 ml/kg/min) and pre-shunt cirrhotic patients (13.3 +/- 1.7 ml/kg/min) but was significantly (P less than 0.02) decreased in the post-shunt cirrhotics (7.6 +/- 1.3 ml/kg/min). The t 1/2 for glucagon decay was similar in the control and cirrhotic groups. The BSDR, an estimate of pancreatic A cell secretion, was increased four-fold (P less than 0.01) in the pre-shunt (3042 +/- 454 pg/kg/min) and post-shunt (2518 +/- 535 pg/kg/min) cirrhotic groups, as compared to controls (750 +/- 244 pg/kg/min). It is concluded that (a) in the presence of cirrhosis, the magnitude of portasystemic shunting is important in determining the degree of hyperglucagonaemia; (b) in preshunt cirrhotics raised basal IRG levels are principally due to A cell hypersecretion of glucagon whereas in post-shunt cirrhotics riased IRG levels reflect both A cell hypersecretion and delayed clearance of glucagon; and (c) acute shunting of splanchnic venous blood away from the liver reduces the clearance of glucagon, suggesting that, in man, the liver contributes to the clearance of circulating glucagon.

Adult↗
PubMed1979

Effect of portasystemic venous shunt surgery on hyperglucagonaemia in cirrhosis: paired studies of pre- and post-shunted subjects.

The effect of liver disease on glucagon metabolism was examined in nine patients with chronic liver disease who were studied both before and after the creation of a surgical portasystemic shunt. Hepatocellular function did not deteriorate after shunt surgery. However, hepatic perfusion with splanchnic venous blood, as determined by scintisplenoportography, decreased after shunt surgery in six subjects but appeared unaltered in three. Basal plasma immunoreactive glucagon (IRG) levels in the pre-shunt cirrhotic group were significantly greater (p <0.005) than in control subjects and further increased (p <0.05) after shunt surgery. Moreover, the increase in basal IRG after shunt was evident only in patients in whom portasystemic shunting was demonstrably increased by surgery. Despite the higher basal IRG levels postoperatively, shunt surgery in the cirrhotics did not alter basal glucose and insulin levels or the glucose and insulin response to a glucose or protein load. Circulating IRG was heterogeneous in the pre-shunt cirrhotic patients: the 9000 molecular weight fraction comprised 27+/-4%, the 3500 mol. wt. fraction 71+/-4%, and the > 40 000 mol. wt. fraction was minimal. After shunt surgery, the relative proportion of the 9000 mol. wt. fraction of IRG (13+/-3%) decreased significantly (p <0.05) and this fall was associated with a corresponding increase in the 3,500 mol. wt. fraction (84+/-4%). It is concluded that, in cirrhosis, hyperglucagonaemia is: (1) dependent on the degree of portasystemic shunting rather than impaired hepatocellular function; (2) predominantly due to increased circulating 3500 molecular weight glucagon; and (3) not a major factor in the pathogenesis of carbohydrate intolerance in liver disease.

Adult↗
PubMed1979

Suppressive effect of alcoholic liver disease sera on lymphocyte transformation.

The effect of alcoholic patient sera on in vitro lymphocyte transformation was studied using mitogen-induced uptake of (3)H-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 <0.001, <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 (125)I-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.

Alcoholism↗
PubMed1978

Repeated shunt surgery in a patient with portal hypertension.

A 45-year-old male with chronic active hepatitis and portal hypertension had a mesocaval interposition graft performed because of repeated uncontrolled bleeding from oesophageal varices. Acute hepatocellular failure, manifested by Grade IV encephalopathy and severe coagulopathy, developed early in the post-operative course despite the absence of hepatic necrosis or other precipitating factors. Both encephalopathy and coagulopathy resolved rapidly following ligation of the shunt. Variceal bleeding recurred and nine months later an emergency distal lienorenal shunt was performed. Post-operatively the shunt was shown to be patent and there has been no encephalopathy or recurrence of variceal bleeding. It is concluded that (1) the splanchnic haemodynamic effects of a mesocaval interposition graft can result in severe hepatocellular failure and this can be reverted by shunt ligation and (2) the distal lienorenal shunt, while effectively reducing the risk of haemorrhage from varices, may be less likely to result in post-operative encephalopathy than more conventional forms of portal decompressive surgery.

Adult↗
PubMed1977

The mesocaval "H" graft: experience with 22 cases.

During the past 32 months, 22 consecutive unselected patients who had bled from oesophageal varices have undergone mesocaval "H" graft operations. There have been nine deaths, three in the early and six in the late postoperative periods. Two deaths were the result of bleeding complicating severe primary fibrinolysis and three were due to disseminated sepsis, one originating from an infected shunt. Continued alcohol intake may have contributed to five of the late deaths. Ten of the 19 patients who left hospital developed some degree of hepatic encephalopathy easily controlled by diet and medical therapy. However, in one case the development of grade IV coma necessitated ligation of the shunt to reverse the coma. Patency of the shunt was demonstrated in all but one patient. Recurrence of bleeding occurred only in this patient and the one in whom the shunt was ligated. Although the operation had a comparatively low operative mortality, the long-term mobidity and mortality were no better than those of the more conventional portacaval anastomosis.

Adolescent↗
PubMed1977

Demonstration of surgical portasystemic venous shunts by scintisplenoportography.

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.

Celiac Artery↗
PubMed1973

Lymphocyte transformation in response to phytohaemagglutinin in primary biliary cirrhosis: the search for a plasma inhibitory factor.

The aim of this study was to determine the importance of plasma inhibitory factors in producing the impaired phytohaemagglutinin (PHA)-induced lymphocyte transformation that is seen in some patients with primary biliary cirrhosis. Twenty-six normal subjects and 12 patients with primary biliary cirrhosis were studied. The lymphocytes from each subject were cultured in the presence of autologous plasma and also in the presence of homologous plasma from a normal subject or from a patient with primary biliary cirrhosis. The results confirm that a proportion of patients with primary biliary cirrhosis are anergic and that the impaired lymphocyte transformation to PHA in vitro can be partially accounted for by the presence of inhibitory factors in the plasma. However, these factors are unlikely to account completely for the impaired transformation, it being probable that there are also abnormalities of the T lymphocytes themselves.

Adult↗
PubMed1973

Serum autoantibodies and immunoglobulins in hepatitis-associated antigen (HAA)-positive and -negative liver disease.

Serum immunoglobulin G, A, and M and serum antinuclear, mitochondrial, and smooth muscle antibody have been measured in 223 patients with hepatitis-associated antigen (HAA)-positive and -negative acute and chronic liver disease. In patients with acute hepatitis, chronic persistent hepatitis, and primary liver cell carcinoma, these indices failed to show any significant differences. However, in the group with chronic aggressive hepatitis the patients who were HAA negative had significantly higher levels of serum IgG, much higher titres of smooth muscle antibody, and often antinuclear and mitochondrial antibodies which were not found in the HAA-positive patients from this group. This suggests that different pathogenic mechanisms may be operative in HAA-positive and -negative chronic aggressive hepatitis.

Acute Disease↗
PubMed1972

Cell-mediated immunity in patients positive for hepatitis-associated antigen.

Cell-mediated immunity to antigens prepared from both serum and liver of patients positive for hepatitis-associated antigen (H.A.A.) was measured by using the leucocyte migration test. Altogether, 43 patients with H.A.A.-positive acute and chronic liver disease, eight with serum antibody to H.A.A., and 13 controls were studied. The cell-mediated immunity detected was specific for H.A.A. or other antigenic determinants of the associated infective agent and could be found only in patients with evidence of previous contact with H.A.A.Cell-mediated immunity to the H.A.A.-positive test antigens was found in all but one of the patients with acute hepatitis, in about half of the patients with chronic aggressive hepatitis or cirrhosis, rarely in those with chronic persistent hepatitis, and in none of the apparently healthy carriers.Our results support the hypothesis that the cellular immune response plays an important part in the clearance of the infective agent from H.A.A.-positive patients and in the pathogenesis of the associated liver cell injury.

Acute Disease↗