Zinc abnormalities in fulminant hepatic failure.

Zinc is an important trace metal and, in liver disease, abnormal zinc metabolism has been reported. In this study of patients with fulminant hepatic failure progressing to grade IV encephalopathy, plasma zinc concentrations fell during the illness to reach levels significantly below normal; during this time urinary zinc excretion was markedly elevated.

Potential toxins of acute liver failure and their effects on blood-brain barrier permeability.

The effects of potentials toxins of hepatic coma on the blood-brain barrier (BBB) permeability of the rat have been examined using the Oldendorf technique. Classical toxins of hepatic failure such as ammonia, methyl octanoate, mercaptans, and phenol caused significant increases in BBB permeability. A slight increase in permeability occurred following infusion of peroxidized linoleic acid and unconjugated bilirubin but no increase after infusion of bile acids. E. coli endotoxin infused into rats following partial hepatectomy also increased the BBB permeability.

A two-year prospective controlled study of maintenance cimetidine and gastric ulcer.

The aim of the study was to determine the effectiveness of cimetidine in a dose of 400 mg twice daily in the prevention of gastric ulcer recurrence over a 2-yr period. The trial was double-blind and placebo-controlled; 24 patients received cimetidine and 25 received placebo. All had had a gastric ulcer within the prior 6 wk, and healing was demonstrated by endoscopy or by barium meal. The patients were contacted at monthly intervals, and if symptoms were present, investigations were performed. Annual barium meal examinations or endoscopy were also performed in all except 7 patients. In the placebo group, there was rapid recurrence within the first 12 mo; 12 of the 13 recurrences that occurred in this group over the 2-yr period took place within the first 12 mo. In the cimetidine-treated group, there were eight recurrences over the 2-yr period, five of which occurred in the first year. Log rank comparison showed a significant benefit due to cimetidine at 1 yr, but not over the 2-yr period.

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.

Controlled trial of dexamethasone and mannitol for the cerebral oedema of fulminant hepatic failure.

A controlled trial of 44 patients was undertaken to evaluate the use of dexamethasone (32 mg stat, 8 mg qds) in preventing, and intravenous mannitol (1 g/kg) in reversing the cerebral oedema of fulminant hepatic failure. Diagnosis of cerebral oedema was based on intracranial pressure recordings or the presence of defined clinical signs. Cerebral oedema developed in 34 patients with similar frequency in those treated with and without dexamethasone (16 of 21 and 18 of 23 respectively). In those 34 patients episodes of cerebral oedema resolved significantly more frequently in the 17 patients who received mannitol than in the 17 patients who did not (44 of 53 and 16 of 17 respectively, p less than 0.001). Dexamethasone did not affect survival but among patients who developed cerebral oedema those who received mannitol had a significantly better survival than those who did not receive it (47.1% and 5.9% respectively, p 0.008, Fisher's one-tail test).

Reticuloendothelial system and hepatocytic function in fulminant hepatic failure.

Kupffer cell and hepatocyte function were studied in 36 patients with fulminant hepatic failure by measurement of clearance of 125I microaggregated albumin (125IMAA) and galactose, respectively. Both were impaired but there was no correlation with final outcome, although on sequential testing 48 hours later, those patients who survived had a significantly greater improvement in Kupffer cell and hepatocyte function. In six other patients with similar hepatocyte dysfunction but no encephalopathy, Kupffer cell function was not significantly different from that of controls. This is additional support for a possible relation between encephalopathy and damage to Kupffer cell function. The latter was also shown to correlate with renal failure; this is consistent with the suggestion that endotoxaemia is important in the pathogenesis of this complication.

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.

Budd-Chiari Syndrome: clinical patterns and therapy.

Retrospective analysis of 36 patients (25 women, 11 men) with the Budd-Chiari syndrome diagnosed between 1971 and 1980 showed a wide range in aged at presentation (12 to 68 years) with the peak incidence in the third decade for women and in the fourth for men. The 11 patients below the age of 30 were women and six of these had been taking oral contraceptive preparations. There was also a wide range in duration of illness before establishment of diagnosis ranging from eight weeks or less in 20 patients, to up to six years in the other 16. Those in the former group had a high incidence of the 'classical' clinical features (tender hepatomegaly with ascites) and most severe abnormalities in liver function tests. Liver scintiscanning showed the characteristic pattern of maximum colloid uptake in the caudate lobe in only 46 per cent of patients. Mistaken diagnosis in eight cases led to early exploratory laparotomy with serious deterioration in four. One year survival of 58.3 per cent was unrelated to age, sex, or aetiology and little benefit was seen in the few cases treated early with fibrinolytic agents. Of the surgical measures employed only hepatic transplantation has proven worthwhile with three out of four cases alive at 14, 16 and 52 months respectively from the time of operation.

Impaired phagocytic function and increased immune complexes in diabetics with severe microangiopathy.

An increase in circulating immune complexes (AgAb) of medium size has been observed in diabetics with late complications. This increase may be related either to an increased formation or reduced clearance. Alternatively, both mechanisms may be involved. As medium-sized AgAb determined by the C1q solid phase method are mainly removed from circulation by the fixed phagocytes of the reticulo-endothelial system, we investigated the function of these cells using a colloid clearance test in diabetics with various degrees of microangiopathy. Microaggregated iodinated human serum albumin was injected into 30 diabetic volunteers with severe (group 1), moderate (group 2), and absent (group 3) microangiopathy, and into 40 normal volunteers. The colloid clearance was significantly reduced in diabetics with severe microangiopathy in comparison with patients who had no sign of microangiopathy, or with normal subjects. A significant correlation was found between reduced colloid clearance and increased levels of circulating AgAb determined by C1q solid phase method. Results of this study suggest that the increase in circulating AgAb observed in patients with severe microangiopathy may result from an impaired function of mixed phagocytes.

Circulating immune complexes in patients with fulminant hepatic failure.

Circulating immune complexes were found in 15 of 16 patients with fulminant hepatic failure due to viral hepatitis and all of six patients who had had halothane anaesthesia; however, they were found in only five of 32 patients with paracetamol-induced hepatic necrosis. The levels of circulating immune complexes were not related to the severity of the clinical course, development of renal failure, final outcome, or severity of hypocomplementaemia. All the patients had depressed reticuloendothelial function as assessed by the clearance of 125I microaggregated albumin. These findings show that circulating immune complexes in fulminant hepatic failure are not simply a reflection of an immune response to liver antigens released as a result of the hepatic necrosis; nor are they a reflection of the failure of the reticuloendothelial system. This supports the view that circulating immune complexes are associated with immune mediated liver injury and may contribute to the process.

Factors contributing to mortality in paracetamol-induced hepatic failure.

Fifty patients with fulminant hepatic failure from paracetamol overdose were reviewed retrospectively to determine whether there had been any avoidable delays in treatment with protective agents, or other preventable factors which could contribute to the high mortality. Only nine were admitted to the local hospital early enough (within 12 hours) to benefit from protective agents, and only three of these were treated. Treatment was delayed in two patients while the results of plasma paracetamol concentrations were awaited. Signs of grade 3 hepatic encephalopathy were never found until 72 hours after the overdose, and sudden deterioration in consciousness at an earlier stage was due either to the sedative effects of drugs or to hypoglycaemia, which in one patient went unrecognised for 24 hours. A rapid deterioration in prothrombin time, which became prolonged by at least 25 seconds at 48 hours, preceded the onset of grade 3 encephalopathy, and this is the time at which transfer should be arranged to avoid the danger of brain-stem coning. This occurred more rapidly in those transferred at a later stage of their illness.

Prostacyclin to prevent platelet activation during charcoal haemoperfusion in fulminant hepatic failure.

Adverse effects associated with hypotension and the appearance of platelet aggregates in the circulation complicate charcoal haemoperfusion of patients with fulminant hepatic failure. In an attempt to avoid these difficulties the platelet protective effect of prostacyclin (PGI2) given intravenously before and continuously during haemoperfusion was evaluated with an improved charcoal column design. Two of the six patients who underwent haemoperfusion without PGI2 had hypotension, which in one was associated with a striking rise in Swank screen filtration pressure necessitating discontinuation of haemoperfusion after an hour. No platelet losses were observed in the six patients treated with haemoperfusion and PGI2 infusion, and there was significant protection from platelet activation, as assessed by the prevention of release into plasma of the platelet-specific protein beta-thromboglobulin.

Gastric mucosal proteins in patients with chronic peptic ulcer.

As ulcerogenesis could be explained by a defect in the mucosal proteins, a study of soluble proteins extracted from human gastric mucosa was made. The proteins were fractionated by gel electrophoresis. 7--8 major bands and several minor bands were present on polyacrylamide tube gels and 30 bands were visible on isoelectric focusing gels. No reproducible differences were found between body and antral mucosa or between the mucosa of gastric ulcer, duodenal ulcer and gastric carcinoma patients.