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Biomedical subjects

A E Gimson

Publications and source records attributed to A E Gimson.

At least 55 records · Page 3Linked to original sources
PubMed1985

Heparin response and clearance in acute and chronic liver disease.

Patients with liver disease are at risk of bleeding due to abnormalities of the clotting system although they must be anticoagulated if they require haemodialysis or haemoperfusion. The anticoagulant of choice is heparin. In this study we have investigated heparin kinetics in patients with fulminant hepatic failure (FHF) after a single intravenous dose of heparin (2,500 units) and found there was an increased clearance of heparin whether measured by its anti-Xa effect (t 1/2 = 27.8 +/- 2.9 min compared to t 1/2 = 50.2 +/- 2.7 min in normal controls p less than 0.001) or by the whole blood activated clotting time (t 1/2 = 23.7 +/- 2.2 min compared to t 1/2 = 37.0 +/- 2.0 min p less than 0.001). There was a decreased peak level of heparin measured by anti-Xa effect (peak level in FHF = 0.48 +/- 0.05 u/ml and in controls = 0.69 +/- 0.04 u/ml, p less than 0.02), but an increased sensitivity to heparin (sensitivity in FHF = 0.072 +/- 0.011 sec/unit, in controls 0.033 +/- 0.003 sec/unit, p less than 0.001). Patients with FHF had very low levels of antithrombin III (AT III), but there was no correlation between this and any parameters of heparin effect or clearance. In a group of patients with chronic liver disease heparin kinetics did not differ from controls despite low levels of AT III. The changes in heparin kinetics in FHF are likely to be complex with the balance between the proteins that act as cofactors, (e.g. AT III) and the proteins that have heparin neutralising activity, controlling the response of added heparin.

Acute Disease↗
PubMed1985

Effect of liver and renal dysfunction on circulating methionine-enkephalin immunoreactivity.

Plasma methionine-enkephalin (Met-Enk) immunoreactivity has been determined in 24 patients with varying degrees of renal impairment and 14 patients with hepatic failure. Plasma Met-Enk immunoreactivity correlated inversely with creatinine clearance (r = -0.71, P less than 0.001) but was not affected by even severe hepatic failure in the absence of renal impairment. In two patients, with renal failure and elevated plasma prolactin, administration of naloxone (16 mg) had no effect on circulating prolactin concentrations. These studies indicate that the kidney has a major role in Met-Enk metabolism while the liver does not, and further suggest that elevated circulating endogenous opiates are not responsible for the increased production of prolactin found in renal failure.

Enkephalin, Methionine↗
PubMed1985

Lactic acidosis in fulminant hepatic failure. Some aspects of pathogenesis and prognosis.

To obtain further evidence of tissue hypoxia in fulminant hepatic failure, we have measured the mixed venous lactate concentration and the acid-base status of 32 patients at the time of their admission, in grade III or IV encephalopathy. The mixed venous lactate was elevated in 26 of the 32 patients (median 5.0 mmol/l, range 0.8-21.1 mmol/l), and, in 17 patients, this was associated with evidence of a metabolic acidosis. Mixed venous lactate levels correlated inversely with the mean arterial pressure (r = 0.56, P less than 0.005), systemic vascular resistance (r = 0.62, P less than 0.001) and the oxygen extraction ratio (r = 0.44, P less than 0.02). The 17 patients with a raised mixed venous lactate and metabolic acidosis had a significantly reduced systemic vascular resistance and oxygen extraction ratio compared with the other 15 (median systemic vascular resistances 944 and 1710 dyne X s/cm5/m2, respectively, P less than 0.05, median oxygen extraction ratios 19 and 23%, respectively, P less than 0.05). Survival was markedly reduced in the patients with hyperlactataemia and a metabolic acidosis, and only one out of the 17 survived compared with 12 of the remaining 15, P = 0.0002. These results suggest that lactic acid accumulation may be in part the consequence of tissue hypoxia that develops as a result of arteriovenous shunting, reflected in the reduction in systemic vascular resistance. This tissue hypoxia may occur despite apparently adequate systemic blood pressure, flow and oxygenation.

Acidosis↗
PubMed1985

Fibrinogen derivatives and platelet activation products in acute and chronic liver disease.

1. The concentration in plasma of fibrinogen derivatives fibrinopeptide A (FPA) and B beta 1-42 and the platelet release products beta-thromboglobulin (beta TG) and platelet factor 4 (PF4) have been determined in patients with acute and chronic liver disease. 2. In 21 patients with fulmiant hepatic failure on admission in grade III or IV coma the plasma FPA, B beta 1-42, beta TG and PF4 levels were significantly increased compared with those in normal control subjects. On heparinization before haemoperfusion the FPA levels returned to the normal range and during resin and charcoal haemoperfusion there were no significant changes in the coagulation or platelet factors, except for a small increase in FPA with charcoal haemoperfusion. 3. In ten patients with compensated chronic liver disease there was a significant increase in B beta 1-42 and beta TG levels but not FPA and PF4 as compared with normal controls. 4. Interpretation of the results is complicated by the possible reduced clearance of these proteins as a result of renal failure in some of the patients with fulminant hepatic failure and also by the damaged liver itself. However, these results have confirmed that disseminated intravascular coagulation can occur in both acute and chronic liver disease.

Acute Disease↗
PubMed1985

Tissue hypoxia during fulminant hepatic failure.

To assess the adequacy of tissue oxygenation in fulminant hepatic failure, we measured arterial oxygen delivery, the affinity of hemoglobin for oxygen, mixed venous oxygen tension, and lactate concentration in 32 patients suffering grade IV encephalopathy. In the patients who died, median systemic vascular resistance and oxygen extraction ratio were significantly (p less than .005) lower than in those who survived (1268 vs. 1866 dyne . sec/cm5 . m2 and 20% vs. 25%, respectively) despite a significantly (p less than .01) greater oxygen delivery in the former group (716 vs. 570 ml/min . m2). Furthermore, nonsurvivors had significantly greater in vivo P50 and mixed venous lactate values (31 vs. 29.5 torr [p less than .02], and 5.1 vs 3.0 mmol/L [p less than .05], respectively). Only in survivors was the in vivo P50 related to the oxygen extraction ratio (r = 0.68 and p less than .01, compared with r = 0.03 in nonsurvivors). These results suggest that the fall in systemic vascular resistance is related to some form of arteriovenous shunting and that this is more severe in patients who die. The subsequent development of tissue hypoxia is an important prognostic factor in fulminant hepatic failure that may contribute to the occurrence of irreversible multiple organ failure.

2,3-Diphosphoglycerate↗
PubMed1985

B1 selective adrenoreceptor blockade for the long term management of variceal bleeding. A prospective randomised trial to compare oral metoprolol with injection sclerotherapy in cirrhosis.

Oral metoprolol, in a dose sufficient to reduce resting pulse rate by 25%, was compared with repeated injection sclerotherapy for the long term management of variceal bleeding. The prospective, randomised study was undertaken in 32 patients with biopsy proven cirrhosis and variceal bleeding who were Grade A or B on a modified Child's classification. In the 15 patients receiving metoprolol, portal pressure showed a mean fall of 3.7 mmHg (17.3 +/- 1.2 to 13.6 +/- 1.2 mmHg, p less than 0.01) after four weeks of continuous therapy, as compared with pretreatment levels. Nine of the 15 patients taking metoprolol had further bleeding (total of 21 episodes) compared with six of 17 in the sclerotherapy group (nine episodes). The risk of bleeding per patient/month of follow up was three times higher in the metoprolol group compared with those treated by sclerotherapy (0.14 and 0.04 respectively, p less than 0.025). Rebleeding in the metoprolol group occurred in six of the patients who had a fall in portal pressure of 10% or more.

Clinical Trials as Topic↗
PubMed1984

Effects of converting enzyme inhibitor on hepatic blood flow in man.

The acute effects of the oral angiotension converting enzyme inhibitor captopril on hepatic blood flow and systemic hemodynamics were studied in six patients with essential hypertension. Mean arterial pressure decreased from 141.9 +/- 6.9 mm Hg to 130.2 +/- 6.7 mm Hg (p less than 0.05) one hour after the administration of captopril. There was no significant change in other hemodynamic values, but hepatic blood flow decreased uniformly from 1,127 +/- 115 ml per minute to 841 +/- 93 ml per minute (p less than 0.001).

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Selective and non-selective beta receptor blockade in the reduction of portal pressure in patients with cirrhosis and portal hypertension.

To elucidate the mechanisms by which beta receptor blockade leads to a reduction of portal pressure, 18 patients with cirrhosis and portal hypertension were given comparable doses of propranolol or metoprolol. The fall in portal pressure was more marked with propranolol together with a significant reduction in hepatic blood flow, which was not seen with metoprolol. No correlation between the reduction in cardiac output and the decrease in portal pressure or changes in hepatic blood flow could be elicited in each group, but there was a direct relationship between the decrease in hepatic blood flow and fall in portal pressure in the propranolol treated patients. The difference observed may be related to blockade of beta 2 vasodilator receptors in the splanchnic circulation which will occur only with propranolol and lead to a greater fall in splanchnic blood flow than will be produced by a reduction in cardiac output alone. Metoprolol, by maintaining effective hepatic blood flow, may be preferable to propranolol in patients with severely impaired liver function.

Cardiac Output↗
PubMed1983

Specific serological markers in the diagnosis of fulminant hepatic failure associated with halothane anaesthesia.

The aetiology of massive liver-cell necrosis which developed in 16 patients following halothane anaesthesia was investigated by means of new serological techniques. In eight patients a specific halothane-related antibody was found, indicating that these patients were sensitized to halothane-altered liver-cell membrane components. In four patients, hepatitis A viral infection was responsible and among the remainder one was receiving anti-tuberculous drugs and one had received a blood transfusion, thus raising the possibility of a non-A non-B viral infection. There were no biochemical or histological differences between patients in the three groups.

Acute Disease↗
PubMed1983

Clinical and prognostic differences in fulminant hepatitis type A, B and non-A non-B.

In 73 patients with fulminant viral hepatitis, non-A non-B hepatitis (NANB) was most common (43.8%), with hepatitis type A (HAV) diagnosed in 31.5% and hepatitis type B (HBV) in 24.7%. The non-A non-B group had a significantly longer duration from the onset of symptoms to the appearance of encephalopathy (median 21 days) compared with the HAV and HBV groups (medians 10 and seven days, p less than 0.01 and p less than 0.005 respectively). In the HAV group the severity of liver damage, judged by the maximum prolongation of the prothrombin time, was significantly less than in the HBV group (58 and 150 seconds prolonged respectively, p less than 0.005), and cerebral oedema was significantly less frequent (39% and 72% respectively, p less than 0.05). Consistent with this, the survival rate was higher in the HAV group (43.4%) compared with the HBV group (16.6%) and NANB group (9.3%) (p less than 0.005). These variations in presentation and clinical course may be a consequence of differences in the pathogenesis of the hepatic necrosis.

Adult↗
PubMed1983

Serological markers in fulminant hepatitis B.

Serological markers for hepatitis B virus infection have been examined in 34 patients with acute hepatitis B, 17 of whom developed fulminant hepatic failure. Hepatitis B surface antigen concentrations were significantly lower and hepatitis Be antigen was less frequently detectable in patients with fulminant hepatic failure compared with those with acute hepatitis (median 0.64 micrograms, range 16-0 and median 32 micrograms and range 100-4 micrograms respectively, p less than 0.001; HBeAg detected in 12% and 88% respectively, p less than 0.001). The IgM component of hepatitis B core antibody was significantly higher in the patients with fulminant hepatic failure with median values of 500 IU/ml compared with those with uncomplicated hepatitis (median 202 IU/ml, p less than 0.05 Wilcoxon's rank test). Three patients who developed a fulminant course had detectable levels of either anti-HBs or anti-HBe. These results are consistent with enhanced antibody responses to all three hepatitis B virus antigens and more rapid clearance of the latter during fulminant hepatic failure.

Acute Disease↗
PubMed1983

Effects of serial resin hemoperfusion in fulminant hepatic failure.

Resin hemoperfusion using an albumin coated Amberlite XAD-7 column was performed in 19 patients in coma due to fulminant hepatic failure. The procedure was clinically well tolerated, with good blood compatibility, platelet and white cell levels being 97.3 +/- SE 3.2% and 105 +/- 3.8% of the respective initial values after four hours hemoperfusion. No significant changes were observed in beta-thromboglobulin, screen filtration pressure, plasma electrolytes, calcium, protein or albumin. The total plasma bilirubin fell by a mean of 24 mumol/l, with a reduction in 21 of the 25 perfusions studied of up to 104 mumol/l during perfusion. Mean plasma levels of total bile acids were 137 +/- 19 mumol/l and 115 +/- 16 mumol/l respectively before and after four hours hemoperfusion. The amount of bile acids recovered by elution of the resin column was over three times greater than that apparent from the change in plasma levels. Column chromatography on Sephadex G-25 of material eluted from the resin column showed various peaks to be removed, including substances in the middle molecular weight range (1000-5000 daltons). Of the patients treated, eight (42%) survived to leave hospital.

Acrylic Resins↗
PubMed1982

Fibronectin in fulminant hepatic failure.

Thirteen out of 17 patients with fulminant hepatic failure had plasma fibronectin concentrations below the normal range (194--472 micrograms/ml), the mean concentration in all 17 patients being 117.9 +/- SE 19.4 micrograms/ml. There was a significant negative correlation between plasma fibronectin concentration and aspartate aminotransferase activity, suggesting that fibronectin is consumed during clearance of hepatocyte debris. The reduced availability of fibronectin may be an important factor in the impaired function of Kuppfer cells in patients with fulminant hepatic failure.

Acute Disease↗
PubMed1982

Earlier charcoal haemoperfusion in fulminant hepatic failure.

Charcoal haemoperfusion with a prostacyclin infusion for platelet protection was carried out daily in the treatment of 76 patients with fulminant hepatic failure. in the 31 patients who had been referred early and in whom the serial haemoperfusion was started while signs of grade III encephalopathy were still evident remarkable survival rates were obtained-70% for patients with paracetamol poisoning and 65% for the group overall. Cerebral oedema developed significantly less frequently in this group than in those patients in whom haemoperfusion was started later in the course of the disease, when signs of grade IV encephalopathy were already apparent (49% and 78% respectively, p less than 0.05), and this was likely to have been a major factor in their improved survival. Biocompatibility of the system was excellent, and both platelet and white-cell counts at the end of perfusion periods were the same as pre-perfusion values.

Adult↗
PubMed1982

Bacteraemia in patients with fulminant hepatic failure.

Among 103 patients with fulminant hepatic failure due to viral hepatitis, paracetamol overdose, or halothane anaesthesia, treated over a 2-year period, 23 had bacteraemia. Gram-positive organisms, mainly streptococci and Staphylococcus aureus, were isolated from 61% of patients. Escherichia coli, the main type of gram-negative organism isolated, was found in 26% of patients and was associated with a fatal outcome more often than gram-positive bacteria. The type of organism isolated was not related to the aetiology of the hepatic necrosis, the presence of renal failure, or the clinical outcome. In the 23 patients with bacteraemia the same organism was isolated from other sites of infection, including sputum in four, urine in two, and the central venous catheter and arteriovenous shunt in one. Bacteraemia usually occurred 3 days after admission or on average 2 days after clinical deterioration to grade IV encephalopathy had begun. In 11 patients, the infection had an adverse effect on their clinical course, in three patients being implicated as a cause of the encephalopathy. Although in four patients the development of infection after all signs of encephalopathy had cleared may have been a major factor in their death, two of these patients had evidence of severe sepsis, pneumococcal peritonitis, and renal abscesses from which Candida albicans was cultured. An awareness of infection as a complication both of the acute stage of the illness and during recovery is essential if early detection and treatment are to be effective.

Acetaminophen↗