Heparin therapy and bone fractures.
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Biomedical subjects
Publications and source records attributed to J A Buckels.
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The shortage of paediatric liver donors has led to the use of reduced size hepatic allografts. Between July 1987 and July 1990, 30 reduced size orthotopic liver transplantations were performed in 24 children aged between 3 months and 7 years. All patients were in advanced chronic or acute liver failure and were considered unlikely to survive for long enough for a size-matched donor to become available. The most common indication was biliary atresia. The median intraoperative blood loss was 75 (range 13-1015) ml kg-1. Nine patients have died and seven have undergone retransplantation, four successfully. Seven patients had portal vein hypoplasia with a high graft failure rate due to ischaemic infarction. There was significant morbidity from biliary tract complications, leading to further operations in four cases. The 1-year actuarial survival rate was 62 per cent.
The association of sclerosing cholangitis, retroperitoneal fibrosis, and Riedel's thyroiditis has been reported twice before, and on both occasions the authors successfully used steroids to control the fibrotic process. A further case of fibrosis with this triad of organ involvement in which a combination of surgery and steroid treatment has arrested disease progression is described. This suggests an inappropriate immune response in this type of fibrotic overlap syndrome.
A leporine model to investigate tumour necrosis factor alpha (TNF alpha) secretion after peripheral vein or mesenteric vein lipopolysaccharide injection was devised. Mesenteric vein injection provoked lower arterial concentrations after 90 minutes (median (range), 2.81, (0.75-11.96) ng/ml) than peripheral vein injection (7.00 (4.27-14.95) ng/ml (p less than 0.05)). Mesenteric vein injection after 10 minutes' warm hepatic ischaemia, which impairs hepatic clearance, provoked higher median arterial TNF alpha values at 90 minutes (7.98 (2.85-21.48) ng/ml) than in normal animals (p less than 0.05). Portal vein endotoxaemia induced less TNF alpha production than systemic endotoxaemia unless hepatic clearance was impaired, thus the major source of TNF alpha in systemic endotoxaemia is probably extrahepatic.
A simple modification of choledochoenterostomy is described. Using continuous suture and pull through technique, the posterior line of the anastomosis is completed without immediate approximation of the two structures. By improving the access, good control of the posterior suture line is ensured, the risk of anastomotic leakage is minimized and the use of stent or T tube is unnecessary.
A 21-year-old man who had an HLA-identical sibling donor BMT for chronic myeloid leukaemia developed grade IV acute GVHD of the liver that was unresponsive to corticosteroids and anti-IL2 receptor monoclonal antibody. He was treated with an orthotopic liver transplant and is currently well 6 months later with normal liver function and no evidence of GVHD in the transplanted liver.
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During the 1980s the results of liver replacement in children improved dramatically, with 12-month survival rates rising from around 20% to over 85% at the most experienced centres. This improvement has been due to several factors, including better patient selection and timing of transplantation, advances in immunosuppressive therapy, and developments in liver preservation. Moreover, the learning curve effect has contributed with advances both in surgical technique and in the rapid diagnosis and treatment of complications, including the need to retransplant patients in whom the first graft has been irreversibly damaged. One major development is the refinement of the anatomically reduced grafts where a larger, usually adult, graft is cut down to fit a child. This has allowed a greater number of children to be grafted, including emergency cases such as fulminant hepatic failure in whom there is insufficient time to wait for a size-matched donor.
Loss of bile ducts is a characteristic feature of chronic rejection in the liver allograft (also known as irreversible rejection and vanishing bile-duct syndrome). Typically, this occurs as a progressive lesion resulting in irreversible damage and graft failure requiring retransplantation. In this study, we describe 6 patients who developed a transient loss of bile ducts following liver transplantation. This occurred in a series of 138 patients who underwent the first 160 liver transplant operations in the Birmingham Liver Transplant Programme (incidence = 4.4% of patients, 3.7% of grafts). Forty needle biopsies were obtained from the 6 patients between 6 and 1303 days after transplantation. Thirteen specimens, taken between 8 and 1253 days posttransplant (median 98 days) showed an absence of bile ducts in more than 50% of portal tracts. Other histologic features of chronic rejection, inflammatory bile-duct lesions, perivenular cholestasis, and hepatocyte dropout were also seen in these biopsies, and severe cholestasis was present biochemically (median serum bilirubin level 240 mumol/L). The histologic and biochemical changes were thought to be compatible with a diagnosis of chronic/irreversible rejection, but the decision to carry out retransplantation was deferred on the basis of stable and, subsequently, improving biochemistry. Follow-up biopsies showed recovery of duct loss and other histologic abnormalities. All 6 patients are currently alive and well with good graft function. It is concluded that a transient, reversible bile-duct loss can occur after liver transplantation and that cases with this condition are indistinguishable from those who subsequently develop irreversible graft damage. In view of the risks associated with additional immunosuppression and/or retransplantation, caution is advocated in the interpretation of ductopenia in posttransplant liver biopsies. We suggest that the term "early chronic rejection" might be appropriate to describe cases in which a definite diagnosis of irreversible graft damage cannot be made.
Twelve of 178 (7%) liver transplant patients underwent endoscopic retrograde cholangiopancreatography (ERCP) after transplantation. The indications for ERCP were persistent or late onset cholestasis, recurrent cholangitis, and suspected biliary leaks or strictures. The time between transplantation and ERCP ranged from 44 to 330 days (median 153 days). Biliary complications diagnosed by ERCP included biliary sludge in the form of casts, calculi, or debris (n = 7); bile leaks (n = 2); a biliary stricture (n = 1), and complete biliary obstruction (n = 1). One patient had a normal cholangiogram after transplantation. Biliary sludge was detected by ultrasound before ERCP in only one of six patients. Eight patients underwent endoscopic papillotomy, followed by clearance of biliary sludge in four and dilatation of a biliary stricture in one. Two patients bled after papillotomy but neither required surgical intervention. At a median follow up of 1.2 years (range 0.5-2.8 years), nine patients are well and three have died. ERCP provides both accurate diagnosis of biliary complications after liver transplantation and treatment that obviates the need for additional surgery in selected patients.
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Between January 1982 and April 1989, 134 patients with a suspected liver neoplasm were referred to the liver unit, Queen Elizabeth Hospital, Birmingham. In 105 (78 per cent), a primary hepatic neoplasm was histologically confirmed, and 47 patients (45 per cent) proved to have primary hepatocellular carcinoma. Twenty-nine orthotopic liver transplants were performed in 28 of these patients (27 per cent). Twenty patients (71 per cent) survived 30 days or longer (median 11.5 months; range 2-87 months), of whom nine are currently alive. We retrospectively analysed our data to determine the influence of preoperative evaluation, histological type and staging on outcome. Computed tomography proved to be superior to intraoperative assessment (86 versus 58 per cent) in diagnosing tumour positive nodes. Patients with tumour negative lymphadenopathy had a better prognosis. Postoperative stage I/II had a median survival of 16 months (range 3-87 months) compared with 7.5 months (range 2-20 months) for stage III. Non-cirrhotic patients with hepatocellular carcinoma had the best prognosis; cholangiocellular carcinoma and cirrhotic patients with hepatocelluar carcinoma had the worst outcome with no survivors beyond 1 year. Because of the advanced stage of disease at the time of presentation, the value of liver transplantation in primary liver cancer is limited. For those presenting with advanced disease confined to the liver (stage I/II) in whom conventional hepatic resection is not possible, significant benefit can be achieved in selected cases.
All patients with primary biliary cirrhosis referred to this unit for consideration for transplantation between April 1981 and January 1989 were analysed retrospectively to assess whether disease stage at referral affects the outcome after grafting and whether greater awareness of the benefits of the procedure means that patients are now being referred at an earlier stage. Seventy of the 107 patients have been grafted, with an overall one year actuarial survival of 62%. A better prognosis at the time of referral, as assessed by both serum bilirubin concentration and a mathematically derived prognostic index, was associated with a greater probability of survival after grafting. Patients in the tertile with the best prognosis (median serum bilirubin concentration at referral 84 mumol/l and estimated survival in the absence of transplantation of more than nine months) had a 78% one year actuarial survival after transplantation, whereas those in the tertile with the worst prognosis (median serum bilirubin concentration 467 mumol/l and estimated survival of less than four months) had a one year actuarial survival of only 50%. No trend towards earlier referral of patients, however, was shown using either of these two markers. This retrospective analysis suggests that many patients are being referred too late for an optimal outcome. We recommend that patients with primary biliary cirrhosis who are potential candidates for liver grafting should be referred to a transplant centre before the serum bilirubin concentration approaches 150 mumol/l.
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