Biomedical subjects
Publications and source records attributed to S G Hubscher.
We report a patient who developed hypercalcaemic metastatic cutaneous calcification in association with a cytomegalovirus infection after a liver transplant. The skin nodules disappeared as the hypercalcaemia resolved and the cytomegalovirus infection subsided.
The distribution of major histocompatibility complex (MHC) class 1 antigens was studied in the liver after transplantation by immunoperoxidase staining for beta-2-microglobulin (beta 2m), a subunit of the class 1 antigen system. Paraffin wax sections were examined from 25 "time zero" biopsy specimens, taken immediately after insertion of the graft, and 87 biopsy specimens taken after transplantation in seven diagnostic categories: acute cellular rejection (n = 22); resolving acute rejection (n = 8); chronic rejection (n = 22); pure cholestasis (n = 14); ischaemia/infarction (n = 5); biliary obstruction (n = 8); massive haemorrhagic necrosis (n = 8). Staining was graded semiquantitatively on a scale of 0-3+ in bile ducts, hepatocytes, sinusoidal lining cells and vascular endothelium. Using the "time zero" biopsy specimens as a baseline for comparison, increased expression of beta 2m was seen in bile ducts, hepatocytes, and endothelial cells after transplantation. These changes were most pronounced in cases of rejection but also occurred in other graft conditions. The degree of hepatocyte and endothelial staining was significantly higher in cases of rejection and massive haemorrhagic necrosis than in the other categories. These findings may have implications for the pathogenesis and diagnosis of rejection of the transplanted liver.
The Birmingham liver transplant programme started in 1982. Forty-six patients have been transplanted with a follow-up of 3 months or longer. Twenty-seven patients are still alive, of whom sixteen have lived for more than one year. The 30 day hospital mortality was 30.4 per cent and the actuarial predicted one year survival 55.5 per cent. Four patients have been regrafted for chronic rejection and graft failure. Thirteen patients have required surgery in the postoperative period for: bleeding (two), removal of abdominal packs (four), biliary leaks and obstruction (five), duodenal perforation (one) and small bowel obstruction (one). Acute rejection was common, occurring in 30 patients and progressing to chronic rejection in 4. Ten patients developed renal failure with an 80 per cent mortality and eleven patients developed grand mal fits. Severe bleeding (greater than 70 units) was associated with previous abdominal surgery and a high mortality (88.9 per cent). Opportunistic fungal infection carried a 100 per cent mortality. Although more than half of all transplanted patients will survive for more than one year, the postoperative period is still one of high morbidity and mortality.
Granulomatous mastitis is a recently described, rare condition of unknown aetiology. It occurs in young, parous women as a tender extra-areolar breast lump and therefore needs to be differentiated from carcinoma. Histologically, a discrete granulomatous lobulitis is seen and because of morphological similarities to granulomatous thyroiditis it has been suggested it may be immunologically mediated. We present a patient in whom granulomatous mastitis presented with periarthritis and erythema nodosum, an association not previously described.
Features of rejection were found in 21 needle biopsies obtained from seven patients after liver transplantation. Wedge biopsies taken peroperatively were used as a baseline for comparison. Rejection was diagnosed by excluding other known causes of graft dysfunction using appropriate methods. In cases in which these criteria were fulfilled a consistent picture of rejection was seen, and this was useful in clinical management. Two features constantly present in cases of acute rejection were: a dense mixed portal inflammatory infiltrate; and polymorphonuclear infiltration of biliary epithelium.
beta 2-Microglobulin, which is associated with HLA class 1 antigens, was assayed in bile and serum from 19 patients following 22 liver transplants. Serum levels were elevated in all posttransplant patients irrespective of the presence of rejection. In contrast, biliary levels were significantly higher during episodes of acute rejection compared with posttransplant cholangitis (p less than 0.01), stable graft function (p less than 0.0001) and nontransplant samples (p less than 0.0001). When bile/serum ratios were studied, the difference between the rejection and the other groups was even more significant, and if a ratio of 0.2 was considered diagnostic of rejection, the test had a sensitivity of 96%, a specificity of 87% with an accuracy of 90%. Therefore, these results suggest that the measurement of bile/serum ratios of beta 2-microglobulin following liver transplantation may be useful in diagnosing acute rejection. When bile/serum ratios of beta 2-microglobulin were compared with those for other proteins, there was strong evidence to suggest that local release accounted for most of the increased biliary beta 2-microglobulin during rejection. These results provide further evidence that HLA class 1 antigens on the biliary epithelium may be important in liver allograft rejection.
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We describe three females who since childhood and puberty have presented with several relapsing episodes of acute or chronic LKM positive hepatitis. Many episodes resolved spontaneously with recovery of normal liver function, although treatment with steroids, steroids/azathioprine was used at occasions. No clear pattern of precipitating factors has emerged though in some cases possible temporal relationship of episodes to menarche, oral contraceptives use or pregnancy has suggested a role for female sex hormones. We discuss briefly the possible mechanisms of LKM positive hepatitis, particularly in terms of drugs as possible trigger factors.