The effect of heterologous immune serum on canine renal homografts.
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Biomedical subjects
Publications and source records attributed to A G Sheil.
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Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are the most common cholestatic disorders in adulthood requiring hepatic transplantation. Although they run similar courses, they may have different problems before and after transplantation. The aim of this study was to compare pre- and post-transplant complications and outcomes in these two similar but distinct patient groups. One hundred and seventeen adult patients underwent liver transplantation at our institution over a 6 year period, including 19 with PSC and 20 with PBC. Pre-transplant there were no significant differences in age, liver biochemistry, haematology or Child-Pugh scores between the two groups. The mean duration of disease before transplant was longer in PSC patients (11.7 vs 6.5 years; P < 0.05). The prevalence of septic cholangitis was greater in PSC (58 vs 5%; P < 0.01) as was the requirement for surgical or radiological interventional procedures, excluding cholecystectomy (53 vs 0%; P < 0.01). At transplantation, four patients with PSC had previously unrecognized cholangiocarcinoma. In the pre-transplant period these four patients had uncontrolled biliary sepsis at the time of transplant vs five of 15 PSC patients without cholangiocarcinoma. Postoperatively, PSC patients had a greater prevalence of intra-abdominal sepsis requiring surgical or radiological intervention (42 vs 5%; P < 0.05). In comparison, patients with PBC had a high prevalence of skeletal complications (30 vs 10%; P < 0.05) particularly avascular necrosis (15 vs 0%). The prevalence of chronic rejection was similar in both groups (15%). Overall survival was higher in PBC patients (85 vs 63%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Although hepatic transplantation is now a well-accepted treatment modality for end-stage liver diseases there are little detailed data on the clinical profile of patients who survive beyond 1 year following transplantation. The aim of this study was to develop a cross-sectional profile on 53 adults who have survived beyond 2 years following liver transplantation. These patients have been followed for a mean of 43.5 months (range 24-84) since the time of transplant. Nineteen patients had persisting liver enzyme abnormalities, 11 due to chronic viral hepatitis (seven hepatitis C virus, three hepatitis B virus), four due to biliary disease. Two had post severe rejection, one steatosis secondary to obesity while in one the aetiology was unclear. Nineteen (36%) of patients required anti-hypertensive medications. The median doses of Prednisone, Cyclosporin and Imuran were 7.5, 300 and 50 mg daily, respectively. The mean serum creatinine was 117 +/- 27 mumol/L. However 22 (41%) had an elevated serum creatinine (> 120 mumol/L) but in only seven was the serum creatinine > 150 mumol/L. Fourteen (26%) of patients were obese (body mass index > 30) whilst 46% had a higher than recommended serum cholesterol (mean level 5.6 +/- 1.5 mumol/L). There has only been one case of internal malignancy (lymphoma) although 19 patients attend regular dermatological review for skin cancer surveillance. Forty-eight patients had a Karnofsky Score > 80. In conclusion, the vast majority of these patients have excellent clinical function but some caution is required with respect to renal function, hypertension, obesity and mild hypercholesterolaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Cells from primary porcine hepatocytes (PPH) and the immortalized human hepatoma cell line C3A are both used in bioartificial liver support systems (BALSS). In this work the viability and metabolic capacity of PPH and C3A cells cultured in different media were compared. Also, because the cells come into direct or indirect contact with human blood components in BALSS, the effects of human complement on survival and functions of the cells was evaluated. For short-term culture, maintenance of PPH viability was essential for retention of P450IA1 activity (r = 0.882, p < 0.01) and effective ammonia clearance (r = -0.791, p < 0.01). When cell viability was below 60% P450IA1 activity could not be recorded and nitrogen elimination activity significantly diminished. In contrast to PPH, ammonia levels were markedly increased for C3A cells in all culture media tested (p < 0.01). Ammonia increase correlated with C3A viability (r = 0.896, p < 0.05). PPH metabolic function was superior to that of the C3A cell line when evaluated by P450IA1 activity, ammonia removal, and amino acid metabolism. When PPH were incubated in human plasma (HP) or human serum (HS) there was rapid and irreversible deterioration of viability occurring within 9 h. This toxic effect could be prevented by the inactivation of complement. When sodium citrate dissolved in dextrose was added to medium, there was considerable damage to both PPH and the C3A cell line. However, there was no demonstrable toxic effect when hepatic cells of either type were exposed to heparin. We conclude that PPH cultivated in complement-inactivated HP or HS are to be preferred to C3A for clinical application of BALSS, and that heparin should be preferred for anticoagulation in BALSS.
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