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Biomedical subjects

J Neuberger

Publications and source records attributed to J Neuberger.

At least 37 records · Page 2Linked to original sources
PubMed1989

Drug-induced jaundice.

A large number of drugs may be associated with impaired bile flow. Drug-associated cholestasis presents like other forms of cholestasis with pale stools, dark urine, pruritus and jaundice. Abdominal pain may be present in some instances and can be so severe as to lead to a false diagnosis of acute cholecystitis. Biochemically, drug-associated cholestasis resembles other forms of cholestasis although the presence of eosinophilia may suggest drug involvement. Many types of drug-induced cholestasis run a benign course with resolution of signs and symptoms within 3 months but occasionally the jaundice can take a year or more to resolve. Progression to cirrhosis is uncommon. Some patients may develop a syndrome resembling primary biliary cirrhosis. The mechanisms of drug-associated cholestasis are uncertain but may arise from alteration of bile formation within the hepatocyte or bile excretion at the level of the canaliculus or the extrahepatic ducts. Histological examination of the liver may be helpful in classifying the types of jaundice but the diagnosis of drug-induced cholestasis is usually one of temporal association and exclusion of other causes.

Cholestasis↗
PubMed1989

Prognosis after liver transplantation for primary biliary cirrhosis.

Timing of transplantation for patients with primary biliary cirrhosis (PBC) requires identification not only of individual risk factors for the operation but estimation of survival with and without transplantation. To identify those risk factors and develop a prognostic model, 82 patients grafted for PBC since 1980 in the Birmingham and Cambridge/King's College Hospital series have been analyzed. Using logrank tests it was found that treatment with diuretics, hemoglobin above 10 g/dl, prothrombin time less than 5 sec prolonged, serum sodium above 130 mmol/L and serum bilirubin less than 350 mumol/L were all individually associated with a better prognosis. Using Cox regression analysis to identify independent variables, it was found that year of transplant, serum bilirubin, serum urea, and diuretic responsive ascites had a significant association with survival. Using these four variables, it was possible to develop a model to identify those patients with a good and a poor probability of survival after transplantation.

Bilirubin↗
PubMed1989

Immune mechanisms in tienilic acid associated hepatotoxicity.

In order to investigate the mechanisms underlying the hepatotoxicity associated with tienilic acid (Ticrynafen) ingestion we have looked for evidence of sensitisation to drug altered liver cell determinants using an indirect antibody dependent, cell mediated cytotoxicity assay (ADCC). As targets, hepatocytes were isolated from rabbits pretreated with either tienilic acid or its isomer with or without previous enzyme induction with either phenobarbitone or B-naphthoflavone (BNF). Sera from 16 of 36 patients with presumed tienilic acid hepatotoxicity induced significant cytotoxicity to hepatocytes isolated from rabbits pretreated with BNF and subsequently tienilic acid. Three of 10 sera from patients receiving tienilic acid but without overt liver damage also induced significant cytotoxicity to these hepatocytes, however, although none of 20 normal controls or of 16 patients with other liver diseases did so. Non-organ specific autoantibodies, classified as anti-LKM2, were also detectable. These were present in association with tienilic acid associated antibodies: of the 36 patients with presumed tienilic acid hepatotoxicity, 38% had both antibodies, 18% had only anti-LKM2 antibodies and 9% only tienilic acid associated antibodies. These results suggest that this drug reaction is associated with sensitisation to drug altered liver cell antigens and autoantigens. If ticrynafen associated hepatotoxicity is immune mediated, then one possible mechanism is that the drug induced antigens break tolerance, leading to an immune attack on normal liver cell components.

Adult↗
PubMed1989

Massive haemorrhagic necrosis of the liver after liver transplantation.

Six of the first 85 patients who received the first 100 liver transplantations carried out in Birmingham developed a syndrome of fulminant liver failure with distinctive clinical and pathological features. The typical clinical presentation was of an uneventual initial postoperative period, followed by a sudden deterioration in graft function, progressing rapidly to graft failure. All six patients died. The characteristic pathological changes were those of massive haemorrhage and hepatocyte necrosis with only mild inflammation and without occlusive lesions in large arteries or veins. These distinctive features differed from other recognised patterns of graft damage and seemed to comprise a specific post-transplant syndrome. The pathogenesis was not clear and in the absence of any definite aetiology it is suggested that the term "massive haemorrhagic necrosis" be used to describe these cases. Additional findings seen in five of the six cases were venoocclusive lesions (n = 4) and a combination of ductopenia and foam cell arteriopathy (n = 2). The presence of these associated lesions suggests that there may be an overlap with other types of graft damage.

Adult↗
PubMed1988

Transplantation of the liver in adults and children with fulminant hepatic failure.

Fulminant hepatic failure has a high mortality rate despite intensive medical treatment. Urgent hepatic transplantation was considered over a 3 year period in 26 (36%) of 73 patients with the worst prognostic features of fulminant hepatic failure. The criteria for patient selection were based on the duration of advanced hepatic coma and the deterioration of liver function. Sixteen patients were transplanted, and 9 (56%) are currently alive. The median duration of follow-up is 16 months and actuarial 1 year survival 55%. Six patients died because of the absence of offers of organ donation. Twenty-two (85%) of the 26 patients considered were referred with advanced encephalopathy or hepatorenal syndrome. Of the 57 patients not transplanted, 18 (95%) of 19 patients with grade I/II encephalopathy survived compared to 13 (34%) of 38 patients with grade III/IV encephalopathy. Transplantation does improve the chance of survival in selected patients with fulminant hepatic failure, early referral and availability or organ donation being important factors.

Adolescent↗
PubMed1988

Halothane hepatitis.

Hepatitis following halothane anaesthesia may take two forms: a mild self-limiting disease or a more severe hepatitis with a high mortality. Whether these two forms represent two distinct entities or ends of a spectrum is unclear. Severe hepatitis is commoner after multiple exposures and has many of the characteristics of an immune-mediated hypersensitivity reaction. The incidence is very low; the best, albeit unsatisfactory, estimate of the incidence is about 1 in 3,700 patients with multiple halothane exposures. The mechanism of liver damage is uncertain: in some circumstances halothane may be directly hepatotoxic, but it remains to be conclusively proved that immune mechanisms are responsible. Studies from our unit have suggested that halothane hepatitis can positively be diagnosed by demonstration of antibodies reacting with halothane-altered liver cell determinants. The incidence of the condition can be reduced by taking a full anaesthetic history and avoiding the use of halothane in the high-risk patients, namely those who have had recent previous halothane anaesthesia and those who have had jaundice or unexplained post-operative pyrexia following earlier halothane anaesthetics. When halothane hepatitis has occurred, treatment is purely supportive with the possibility of transplantation for those in grade IV encephalopathy.

Adult↗
PubMed1988

Kidney pathology in liver allograft recipients after long-term treatment with cyclosporin A.

Organ transplant recipients given immunosuppressive treatment with cyclosporin A are at risk of injury due to nephrotoxicity. Eight liver allografted patients whose renal function became impaired during therapy with cyclosporin A for up to 4.5 years were investigated by renal biopsy. Ischemic changes in glomeruli were found to be greater than in controls, and there was focal tubular atrophy, but an excess of lesions in small arteries could not be demonstrated. In one patient there were glomerular changes suggestive of thrombotic microangiopathy. Interstitial fibrosis and cellular infiltration were slight. The pathogenesis of the ischemia remains to be elucidated, but reasons are advanced for favoring the view that the mechanism of cyclosporin A nephrotoxicity is primarily vasomotor, causing a reduction of renal blood flow and glomerular filtration rate without permanent organic arterial narrowing; nephrons become damaged irreversibly nevertheless.

Adult↗
PubMed1987

Halothane hepatitis in children.

It is often stated that halothane hepatitis in children is nonexistent or extremely rare. This syndrome occurred in seven children aged between 11 months and 15 years, one of whom, a 3 1/2 year old boy, died with fulminant hepatic failure. All the children had received multiple halothane anaesthetics (range 2-6, median 3). In all cases other causes of liver diseases were excluded, and in all but one the diagnosis was confirmed serologically by antibodies to halothane altered liver cell membrane antigens. These findings suggest that halothane hepatitis occurs in children, and the risk of halothane hepatitis should therefore be considered when choosing which agents to use in children who require multiple anaesthetics.

Adolescent↗
PubMed1987

Evidence for an immune response to HLA class I antigens in the vanishing-bileduct syndrome after liver transplantation.

The relation between donor and recipient status for HLA class I and II antigens in 62 patients undergoing liver transplantation was examined with particular reference to a well-defined variant of chronic rejection, the vanishing-bileduct (VBD) syndrome. A complete mismatch for class I antigens was more common in those with the VBD syndrome than in those with normal graft function or chronic graft malfunction unrelated to the syndrome (p less than 0.025). In contrast, a complete mismatch for class II antigens was considerably less common in those with the VBD syndrome than in those without (p less than 0.02). The association of a complete mismatch for class I and a partial or complete match for class II antigens with the VBD syndrome was highly significant (p less than 0.0005). These findings support the hypothesis that in the VBD syndrome both class I antigen expression on bileduct epithelium and immunological interaction at the level of class II antigens are required for the rejection process to occur. In addition, high-titre donor-specific antibodies to class I antigen, which were present in 6 of 14 of those with the VBD syndrome but in none of those without (p less than 0.0005), may be involved in the pathogenesis of bileduct damage.

Adolescent↗