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Biomedical subjects

F J Dudley

Publications and source records attributed to F J Dudley.

At least 55 records · Page 3Linked to original sources
PubMed1984

Hyperinsulinaemia and insulin resistance of cirrhosis: the importance of insulin hypersecretion.

The mechanism for the hyperinsulinaemia in cirrhosis was investigated using two different approaches. In the first study, the metabolic clearance rate of insulin was measured at steady state in 13 cirrhotic and 13 weight-matched control subjects. With comparable insulin infusion rates (1.00 +/- 0.19 versus 1.07 +/- 0.15 mU/kg/min), steady-state plasma insulin concentrations (104 +/- 25 versus 87 +/- 12 microU/ml; P greater than 0.5) and MCRIRI (13.6 +/- 1.6 versus 15.4 +/- 2.0 ml/kg/min; P greater than 0.5) were similar. In the second study, fasting and oral glucose stimulated C-peptide/insulin ratios were compared in 16 cirrhotic and 18 weight matched control subjects. Although fasting glucose levels were significantly higher in the cirrhotic groups, all values were in the normal range (5.5 +/- 0.3 versus 4.8 +/- 0.1 mmol/l, P less than 0.02). However, fasting insulin (0.171 +/- 0.02 versus 0.068 +/- 0.004 nmol/l) and C-peptide (1.02 +/- 0.13 versus 0.42 +/- 0.02 nmol/l) were strikingly higher (P less than 0.001) in cirrhotic subjects. On the other hand, fasting C-peptide/insulin ratios were not statistically different in the two groups (6.18 +/- 0.52 versus 6.77 +/- 0.46; P greater than 0.3). This suggests that beta cell hypersecretion was the principal cause of the fasting hyperinsulinaemia, rather than decreased insulin hepatic extraction. Following the glucose load in 13 of the control and seven of the cirrhotic group, the C-peptide/insulin ratio fell in both groups but was significantly lower in the cirrhotic compared to control subjects at 30, 60 and 120 min, consistent with possible impairment of hepatic insulin extraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Insulin resistance in cirrhosis: evidence for a post-receptor defect.

Receptor and post-receptor abnormalities of insulin action and their possible role in the insulin resistance of cirrhosis were examined in eight biopsy-proven cirrhotic subjects and eight age-weight matched healthy volunteers. To this end, oral glucose tolerance tests (OGTT), insulin dose response curves and insulin binding to circulating monocytes were determined for each subject. The dose-response curves for the cirrhotic subjects were significantly shifted to the right compared to the control subjects, indicating the presence of insulin insensitivity (ED50 223 +/- 30 versus 64 +/- 8 mU/l respectively; P less than 0.001). The magnitude of the right shift of the insulin-dose response curves correlated significantly (P less than 0.001) with the OGTT 2 h insulin levels (r = 0.74) and the insulin areas under the OGTT curves (r = 0.86). In contrast, insulin responsiveness was marginally elevated in the cirrhotic group (maximal glucose disposal 680 +/- 47 versus 574 +/- 21 ml/m2/min; P less than 0.05). Insulin binding to circulating monocytes was normal in the cirrhotic subjects. It is concluded that the insulin resistance of cirrhosis is due to a post-receptor defect in insulin action which reduces insulin sensitivity but not insulin responsiveness.

Blood Glucose↗
PubMed1984

Ischemic hepatitis: clinical features, diagnosis and prognosis.

Nineteen episodes of ischemic hepatitis were diagnosed by hepatitic liver function tests and characteristic liver pathology in 17 patients. All patients had an acute illness associated with a likely fall in cardiac output although only five episodes were associated with documented hypotension. Right ventricular failure was severe in only four, mild in six, and absent in nine whilst left ventricular failure was clinically apparent in 16. The hepatitic illness was usually mild. No patient died as a direct result of hepatic damage, prognosis depending on the underlying cardiac or systemic disease. Liver function tests were characterised by a marked rise in serum transaminase levels with a parallel increase in serum lactic dehydrogenase of hepatic origin and a short time course of the enzyme elevation lasting 3 to 11 days. It is concluded that ischemic hepatitis is caused by poor hepatic perfusion associated with an acute fall in cardiac output; is usually a subclinical illness with little influence on prognosis, and may be accurately differentiated from viral hepatitis on clinical and biochemical criteria alone.

Adult↗
PubMed1984

Pulmonary hypertension complicating hepatocellular carcinoma.

A case of primary liver cell carcinoma is presented in which tumor emboli to the pulmonary microvasculature resulted in pulmonary hypertension, documented by clinical, radiologic, electrocardiographic, and cardiac catheter studies. Emboli arose from tumor invading the portal vein and passed via a patent splenorenal shunt to the systemic venous and pulmonary arterial microvasculature. Despite a prolonged clinical course (20 mo) there was no radiologic evidence of pulmonary metastases and, histologically, tumor emboli were seen to undergo organization and recanalization.

Autopsy↗
PubMed1983

Erythrocyte ferritin content in idiopathic haemochromatosis and alcoholic liver disease with iron overload.

The erythrocyte ferritin content was measured in patients with either idiopathic haemochromatosis or alcoholic liver disease and iron overload to define its value as a marker for an excess of tissue iron. The mean erythrocyte ferritin content in patients with untreated idiopathic haemochromatosis was increased 60-fold and fell with phlebotomy. After phlebotomy many patients had an increased red cell ferritin content despite normal serum ferritin concentrations. That this reflected persistent iron overload with inadequate phlebotomy was suggested by the higher serum iron concentrations, percentage transferrin saturation, and urinary excretion of iron after administration of desferrioxamine, together with a lower annual iron loss by phlebotomy in this group compared with patients with treated disease and normal red cell ferritin content. The mean erythrocyte ferritin content in patients with alcoholic liver disease and iron overload was increased only sevenfold, and the ratio of erythrocyte to serum ferritin clearly discriminated these patients from those with idiopathic haemochromatosis. The determination of erythrocyte ferritin content is a useful non-invasive test for diagnosing idiopathic haemochromatosis, monitoring the effect of phlebotomy in this disorder, and distinguishing patients with this disorder from those with alcoholic liver disease with iron overload.

Adult↗
PubMed1983

Coagulopathy of peritoneovenous shunts: studies on the pathogenic role of ascitic fluid collagen and value of antiplatelet therapy.

The role of ascitic fluid collagen in the pathogenesis of the coagulopathy that follows peritoneovenous shunting was examined. Collagen was partially purified from ascitic fluid and infused into rabbits. All animals developed changes in their haemostatic profile consistent with intravascular coagulation. Aspirin therapy, for five days before the collagen infusion, prevented these changes. Seven patients undergoing a total of eight peritoneovenous shunts for intractable ascites received antiplatelet therapy (aspirin and dipyridamole) in the immediate pre- and postoperative period. After six shunts no thrombocytopenia or prolongation of clotting times developed to suggest decompensated consumptive coagulopathy. Complicating factors may have contributed to the deterioration in haemostasis in the other two patients. There was no early shunt occlusion. The results support the hypothesis that ascitic fluid collagen is important in the pathogenesis of intravascular coagulation postascitic fluid infusion and indicate that antiplatelet drugs may be of value in preventing this complication.

Adult↗
PubMed1982

Fentanyl and diazepam in endoscopy of the upper gastrointestinal tract.

To compare the effect of fentanyl, a short-acting narcotic analgesic, with that of diazepam as intravenous premedication for endoscopy of the upper gastrointestinal tract, we allocated at random 200 consecutive outpatients requiring elective endoscopy to receive either fentanyl or diazepam; the procedure was evaluated both by the endoscopist and by the patient. The endoscopists' opinion of the ease of the procedure was significantly better for the group of patients who received fentanyl than for the group who received diazepam (P less than 0.001). The patients' opinion of the procedure was not influenced by the premedication used. No serious side effects were observed in either patient group. We concluded that fentanyl has significant advantages over diazepam as premedication for endoscopy of the upper gastrointestinal tract.

Aged↗
PubMed1981

The aggregation of human platelets by ascitic fluid: a possible mechanism for disseminated intravascular coagulation complicating LeVeen shunts.

To identifiy causative factors responsible for the disseminated intravascular coagulation complicating peritoneovenous (LeVeen) shunts, the ascitic fluid from 12 patients with alcoholic liver disease or peritoneal malignancy was examined for its effects on human platelets. In all patients, concentrated ascitic fluid caused irreversible platelet aggregation. Properties of the aggregating factor suggested that it is collagen, and subsequently, the presence of collagen in ascitic fluid was confirmed. This finding, together with the known effects of collagen on platelets and contact clotting factors, would be sufficient to explain the development of disseminated intravascular coagulation following this procedure. Aspirin by inhibiting collagen-induced aggregation may have a therapeutic role in the management of this problem.

Adenosine↗
PubMed1981

Primary liver cell carcinoma complicating autoimmune chronic active hepatitis.

In a group of 50 patients seen with primary liver cell carcinoma over a period of five years, 38 had cirrhosis. In four patients the cirrhosis was due to autoimmune chronic active hepatitis. None of the patients had markers of hepatitis B virus infection, but in three of the four, serum autoantibodies were present. Coexisting autoimmune disease was present in two. Corticosteroids induced remission in all patients, and the liver disease appeared quiescent at the time primary liver cell carcinoma developed.

Adult↗
PubMed1981

The distal lienorenal shunt: perioperative experience with 30 patients.

During the past 51/2 years, thirty consecutive and unselected patients who bled from oesophageal varices underwent distal lienorenal shunt surgery. Eight deaths occurred in the immediate postoperative period. Three of nine emergency patients died because of continued bleeding and, of the five elective patients who died, four were largely the result of technical problems encountered at surgery. In the immediate postoperative period variceal bleeding recurred in five of eight emergency patients despite shunt patency. This did not occur in the elective group. Shunt blockage was relatively common compared to that following conventional porta-systemic shunt surgery; being documented in five of the 24 patients in whom patency was assessed. No clinical, biochemical or histological criteria were identified as predictors of outcome. In particular, the presence of preoperative ascites gave no indication of postoperative problems. However, if ascites developed in the immediate postoperative period, it was a major management problem in 50% of patients. In conclusion, the distal lienorenal shunt has a high perioperative mortality, is commonly complicated by shunt thrombosis and, in the emergency situation, often fails to control bleeding. The technical difficulties encountered at surgery appear largely responsible for the early morbidity and mortality.

Adolescent↗
PubMed1981

Disseminated intravascular coagulation following peritoneo-venous (LeVeen) shunt.

Ten LeVeen shunts were inserted into nine patients with intractable ascites and coagulation studies were performed to determine the incidence, severity, and clinical importance of disseminated intravascular coagulation (DIC) in the initial post-operative period. Two of the shunts failed to function in the immediate post-operative period and the clotting profiles of these patients were unchanged by surgery. The remaining shunts had good initial flow and in all patients there was a deterioration in the coagulation profile consistent with DIC. In four of these patients this was associated with clinical evidence of impaired haemostasis which required surgical ligation of the shunt in two as an emergency measure. The other two patients died as a direct consequence of their bleeding. Of the eight initially patent shunts, one blocked spontaneously and three others were surgically ligated in the early post-operative period. The clotting abnormalities of all of these patients returned to pre-operative levels with the cessation of flow through the shunts. Four patients had continued shunt patency during their hospital stay and, in all, titres of fibrin degradation products remained elevated. The conclusions reached are that adequate flow through the peritoneovenous shunt causes laboratory evidence of DIC in all patients and this can be of major clinical importance; that monitoring of the coagulation profile is a good index of continued shunt patency at least in the early post-operative period; and that DIC may account for the high spontaneous blockage rate.

Adult↗
PubMed1980

Interaction between oral propranolol and hydralazine.

Seven healthy subjects were given oral propranolol (1 mg/kg) alone or in combination with hydralazine 25, 50, or 100 mg on separate occasions. Hydralazine induced variable increases in the peak concentrations (p less than 0.05) and in the area under the propranolol concentration: time curves (p less than 0.02) without change in the recovery of 14 C-propranolol/metabolites in urine or in the systemic clearance of propranolol; i.e., oral hydralazine enhanced the systemic availability of propranolol by alteration of "first-pass" (hepatic) clearance. The results indicate the possibility of change in presystemic clearance without reciprocal change in systemic clearance and also suggest that propranolol or any other high-clearance drug should be administered in fixed relationship to hydralazine and other drugs capable of altering "first-pass" hepatic extraction (either due to alteration in splanchnic blood flow or competitive inhibition of metabolism) if large variations in plasma concentrations are to be avoided.

Administration, Oral↗