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Biomedical subjects

J Neuberger

Publications and source records attributed to J Neuberger.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1987

Specific antibodies to halothane-induced liver antigens in halothane-associated hepatitis.

Antibodies to halothane-altered liver cell determinants (halothane antibodies) have previously been detected in serum of patients with fulminant hepatic failure after halothane anaesthesia. However, their diagnostic value has not been reported in patients with non-fulminant hepatitis. Sera from 39 patients who developed hepatitis following halothane anaesthesia between January 1983 and December 1985 were tested for antibodies to halothane-induced liver antigens using an ELISA; 22 of these patients had hepatitis without encephalopathy. Nineteen of the sera were from patients anaesthetized during 1985; four of the patients were aged 15 yr or less. All patients had undergone previous anaesthesia 17 days to 13 yr (median 3 yr) earlier. In 19 of the patients the final operation was a minor surgical procedure, lasting less than 45 min. In 13 patients a previous adverse reaction to halothane was documented in the case records. Twelve of the patients died. Halothane antibodies were detected in 12 of the 16 (75%) patients with hepatic encephalopathy and 16 of the 23 (70%) who did not develop encephalopathy, demonstrating that halothane antibodies are detectable in a wider spectrum of halothane-associated liver damage than previously appreciated.

Adolescent↗
PubMed1987

Identification by immunoblotting of three halothane-induced liver microsomal polypeptide antigens recognized by antibodies in sera from patients with halothane-associated hepatitis.

Previous studies have demonstrated that sera from patients with severe liver damage after halothane anesthesia ("halothane hepatitis") contain antibodies reacting with novel antigenic determinants expressed on hepatocytes from rabbits exposed previously to halothane. To determine the structure of the halothane-induced antigen(s), immunoblotting experiments were performed using patient sera and rabbit liver subcellular fractions. Three polypeptide antigens (Mr 100,000, 76,000 and 57,000) expressed in liver fractions from animals sacrificed 16 hr after exposure to 1% halothane in oxygen for 45 min, but not in fractions from unexposed animals, were identified. Analysis of fractions prepared by differential and sucrose density gradient centrifugation, and characterized by enzyme marker analysis, localized all three antigens to a microsomal subfraction relatively enriched in glucose-6-phosphatase activity, therefore, presumably derived from the endoplasmic reticulum. Antibodies to these antigens were detected in 19 of 24 sera from patients with halothane hepatitis, and four distinct patterns of antibody specificity were observed: 100,000 + 76,000 (seven patients), 100,000 alone (seven patients), 76,000 alone (three patients) and 57,000 alone (two patients). Such antibodies were not detectable in sera from 24 normal blood donors or 36 control patients. Thus, halothane induces expression of three distinct polypeptide antigens in liver, and patients with halothane hepatitis differ in patterns of recognition of these antigens by circulating antibodies.

Animals↗
PubMed1986

Oral contraceptives and hepatocellular carcinoma.

A series of 26 white women aged under 50 who developed hepatocellular carcinoma in a non-cirrhotic liver were studied for the possible role of oral contraceptives. Eighteen of the women had used the "pill" for a median of eight years. Over 1300 women whose use of the pill had been determined in another study served as controls. Patients and controls were divided into five age and four calendar groups and the relative risks associated with oral contraceptives calculated by multivariate analysis. Short term use of the pill was not associated with an increased risk of tumour development; nevertheless, use for eight years or more was associated with a 4.4-fold increased risk (p less than 0.01). When patients with markers of hepatitis B virus infection were excluded the relative risk was 7.2 (p less than 0.01). In both instances the absolute risk for developing hepatoma remained low.

Adult↗