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Biomedical subjects

A G Sheil

Publications and source records attributed to A G Sheil.

At least 55 records · Page 3Linked to original sources
PubMed1998

Paradoxical early immune activation during acceptance of liver allografts compared with rejection of skin grafts in a rat model of transplantation.

Liver allografts in many animal models are often spontaneously accepted across a complete histocompatibility barrier without requirement for immunosuppression. In contrast, skin allografts are usually rejected, even across minor histocompatibility barriers. To identify the mechanism of liver allograft acceptance we have compared skin rejection with liver acceptance in DA rat strain recipients of PVG donors, a major histocompatibility complex (MHC) class I plus II mismatch. In spite of the established role of draining lymph nodes (LN) in induction of rejection of skin allografts, there was much greater involvement of LN after liver than after skin transplantation. Few donor cells migrated to these organs from transplanted skin but many cells migrated from transplanted liver. There was also a paradoxical increase in interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) mRNA in LN and spleen of liver allograft recipients that greatly exceeded their expression in skin allograft recipients. For example, there were 2. 7+/-1.6x104 molecules of IFN-gamma per 106 molecules of beta-actin mRNA in the LN draining liver allografts 1 day after transplantation compared with 2.0+/-0.3x103 molecules/106 beta-actin in LN draining skin allografts and 8.1+/-1.8x102 molecules/106 beta-actin in LN draining skin isografts. Examination of the graft showed that infiltration and cytokine mRNA up-regulation occurred more slowly in the transplanted skin than in liver but progressed inexorably in skin grafts until rejection. These results show that liver acceptance is associated with a paradoxical marked early activation then subsequent decline of the immune response.

Animals↗
PubMed1998

Evaluation of the loin pain/hematuria syndrome treated by renal autotransplantation or radical renal neurectomy.

Some patients with the loin pain/hematuria syndrome suffer incapacitating flank pain. No effective therapy has been reported. Uncertainty persists concerning the authenticity of the pain and the role of surgery in treatment. Forty-six patients with loin pain/hematuria syndrome and intractable pain were evaluated following treatment either by renal autotransplantation (30 patients, 10 bilaterally) or by renal denervation (20 patients, four bilaterally) over a 13-year period. All patients had concomitant renal nerve excision and ligation and capsulotomy. There were 37 (80%) women and nine men aged 18 to 61 years (mean age, 33 years). Excretion urography and angiography were normal in all patients. Nineteen of 25 (76%) patients in whom renal autotransplantation was successfully accomplished and who completed a follow-up questionnaire were free of pain, including eight of 10 with bilateral procedures. The follow-up periods ranged from 1 to 13 years (mean, 8.4 years). Six patients have been free of pain for 10 to 13 years. Of 18 patients treated with renal neurectomy who were available for follow-up examination, 12 (67%) developed recurrent renal pain, including four who had pain relief on the other side following previous renal autotransplantation. The follow-up period for these patients ranged from 6 to 9.9 years (mean, 8.0 years). Three of four patients with recurrent renal pain following neurectomy were treated successfully by renal autotransplantation. The loin pain/hematuria syndrome is a rare cause of incapacitation, predominantly of relatively young females. The pain of the syndrome is organic. Renal autotransplantation achieves pain relief in three quarters of patients, but the procedure is often (30%) required bilaterally and has significant complications. Renal neurectomy is followed by an excessive incidence of recurrent renal pain.

Adult↗
PubMed1998

Cadaveric liver procurement using aortic perfusion only.

BACKGROUND: To test the effectiveness of a simpler surgical technique for cadaveric liver procurement for liver transplantation, a prospective randomized study was carried out between August 1994 and December 1995, to compare aortic perfusion only (APO) for flush-preservation of the liver with the conventional combined aortic and portal perfusion (APP) technique. METHODS: Forty multiple organ donors were enrolled with 20 in each arm of the trial. Donor parameters (age, bodyweight, liver function tests), surgeons performing the operations, the involvement of other procurement teams and the total ischaemic times were similar in the two groups. The liver recipients had a wide range of native liver pathology but were of similar age, sex and bodyweight in the two groups. RESULTS: The mean procurement operation times for the APO and APP groups were 126.7+/-38.6 and 137.8+/-55.9 min, respectively (P=ns). The perfusion took longer to complete in the APO group (10.2+/-1.7 vs 7.2+/-1.4 min (APP), P < 0.001). The liver temperature fell to its lowest level (12.5+/-3.4 degrees C (APO) vs 11+/-3 degrees C (APP), P=ns) in a similar time (11.9+/-3.8 min (APO) vs 9.3+/-3.4 mins (APP), P=ns). There was no graft primary non-function or graft arterial injury in either group. There was no significant difference between the APO and APP initial graft outcomes. The 3-month patient survival rate was identical in the two groups (95%); 81% of renal grafts from the APO donors functioned well from the time of transplantation as did 76% of those from APP donors. CONCLUSIONS: It is concluded that the APO procurement technique produces equivalent results to those achieved with the APP method. The simplicity of the APO technique makes it the preferred technique.

Adult↗
PubMed1998

Positive biochemical effects of a bioartificial liver support system (BALSS) in a porcine fulminant hepatic failure (FHF) model.

This study describes biochemical changes in the plasma and blood of pigs with devascularised livers treated in a bioartificial liver support system (BALSS). Porcine hepatic cells were incubated with collagen-coated dextran microspheres (CDM) for 3 hours and the medium tested to determine cellular metabolic activity. Incubation continued for a further 18 hours during which the hepatic cells attach to the CDM. The CDM-attached cells were inoculated into a hollow fibre bioreactor which was part of an extracorporeal support system. Hepatic cell content of the bioreactor was 6 x 10(9) cells. The system was tested in a controlled trial in pigs prepared in a surgical model of fulminant hepatic failure (FHF). When plasma from FHF pigs was circulated through the device containing hepatic cells, there was significantly less increase in the accumulation of ammonia and most amino acids, together with a decrease in plasma lactate and of one amino acid, compared to control experiments when hepatic cells were excluded. We conclude that primary porcine hepatocytes can contribute beneficial metabolic function in a BALSS.

Adenosine Triphosphate↗
PubMed1997

Liver transplantation for hepatitis C-associated cirrhosis in a single Australian centre: referral patterns and transplant outcomes.

During the study period, 63 patients with hepatitis C virus (HCV) cirrhosis were referred to our unit for liver transplantation. All cases referred and transplanted were retrospectively examined. Eighty-six per cent of referred patients were male, 35% consumed alcohol in the harmful/hazardous range, 13% were infected with hepatitis B and 7% had hepatocellular carcinoma. Patients with sporadic infection were more likely to be born outside Australia and were an average of 10 years older than those with HCV acquired via intravenous drug use (P < 0.001). However, patients were an average of 12 years younger at referral if they consumed harmful amounts of alcohol than if they abstained (P = 0.002). We examined the impact of HCV on the outcome of 28 patients who underwent liver transplantation (mean follow up 25 months; range 3-76 months). The use of OKT3, HCV genotype and hepatitis B status were examined for their effect on HCV-related graft dysfunction. Three year survival was 84%, equivalent to a control group. Chronic HCV-related graft dysfunction occurred in 15 (56%) patients, of whom 10 had an asymptomatic elevation in serum amino transferase, two had cholestatic hepatitis and three had severe hepatitis C that progressed onto chronic rejection. Hepatitis C virus genotype 1b tended to be associated with HCV graft dysfunction (5/6 type 1b vs 10/16 in non-type 1b). In conclusion, HCV is an increasingly common indication for liver transplantation. Alcohol and hepatitis B were frequently occurring cofactors in the referral cohort. Most patients referred were male, although the reason why is not clear. Transplantation offers a good medium-term outcome, despite the high incidence of HCV-associated graft dysfunction.

Adult↗
PubMed1997

ABO blood group incompatibility in liver transplantation: a single-centre experience.

BACKGROUND: For most organ transplantation (Tx), ABO blood group incompatibility (ABOI) is an absolute contraindication because of the high incidence of hyperacute rejection (HAR). While HAR occurs in ABOI liver Tx (LTx), it is known that some liver grafts can be accepted. METHODS: ABO-incompatible (ABOI) liver allografts were used in seven of 355 orthotopic LTx operations performed at our institution over a 10-year period. All seven recipients were in fulminant hepatic failure (FHF) prior to Tx. RESULTS: Following Tx, all grafts functioned immediately. One patient died without recovering consciousness. Six patients recovered consciousness following Tx but three patients subsequently required re-transplantation (with ABO-compatible grafts (ABOC)) because of severe acute rejection (2) and chronic rejection (1). Hyper-acute rejection did not occur. All six patients are now well, with a mean survival of 61.5 months. When compared to 36 other FHF patients who received ABOC grafts, graft survivals were 3/7 (43%) for ABOI versus 23/36 (64%) for ABOC (P = not significant (NS)). Patient survivals were 6/7 (85.7%) for ABOI patients and 23/36 (64%) for ABOC (P = NS). The re-transplantation rate was significantly higher in the ABOI group (P = 0.001). CONCLUSIONS: The results confirm that ABOI liver grafts should be used in urgent circumstances when compatible grafts are not available. Some grafts function indefinitely, while those that fail may function for sufficient time to allow successful retransplantation with ABOC grafts.

ABO Blood-Group System↗
PubMed1997

A liver transplantation technique in a patient with a thrombosed portal vein and a functioning renal-lieno shunt.

A liver transplant technique is described in a patient with a thrombosed portal vein and a functioning surgically created renal-lieno shunt. Permanent portal inflow to the graft was provided by division of the left renal vein (LRV) at its junction with the inferior vena cava and anastomosis of the LRV end-to-end with the donor portal vein. Although this results in splanchnic blood traversing a 360 degree roundabout from the superior mesenteric vein via the splenic and disconnected left renal veins to the donor portal vein, the anastomosis lay well and the procedure was successful.

Anastomosis, Surgical↗
PubMed1997

Simple and reliable methods to assess hepatocyte viability in bioartificial liver support system matrices.

New assays were compared with tritiated thymidine (3HTdR) and trypan blue dye exclusion for evaluating hepatocyte viability on cytodex 3 beads and in microcapsules, the matrices used in bioartificial liver support systems. They were the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) 5 min qualitative assay and the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4 -sulfophenyl)-2H -tetrazolium, inner salt (MTS) 1 h quantitative assay. Both tetrazolium salts are cleaved in active mitochondria, the reaction occurring, therefore, in living cells only. After bathing at 39 degrees C with MTT for 5 min, porcine or rat hepatocytes on cytodex 3 beads were detached by collagenase while those in microcapsules were released by citrate treatment or passage through a fine needle. Cell viability was determined directly by microscope. The MTT 5 min metabolic inclusion test and MTS 1 h quantitative assay results correlated closely with those obtained by the 3HTdR, trypan blue dye exclusion, and fluorescein diacetate (FDA) methods. Both the new assays are sensitive, accurate, simple, and time-saving.

Animals↗
PubMed1996

Tolerance to rat liver allografts: IV. Acceptance depends on the quantity of donor tissue and on donor leukocytes.

Liver allografts in some rat strains are often spontaneously accepted across a complete major histocompatibility barrier without the requirement for immunosuppression while other nonliver allografts are rejected. In previous studies, we have shown that spontaneous acceptance is dependent on liver passenger leukocytes. Depletion of passenger leukocytes by donor irradiation allows rejection, with DA recipients of irradiated PVG livers having a median survival time (MST) of 16 days. Here we show that, in this model, spontaneous acceptance is reconstituted by intravenous injection of donor leukocytes. Intravenous injection of 3-5x10(7) PVG liver leukocytes significantly prolonged DA survival time (MST=96 days, P=0.026), as did 5x10(7) spleen leukocytes (MST>100 days, P=0.002). Deletion of T cells from the reconstituting inoculum reduced survival time (MST=78 days, P=0.039), whereas deletion of B cells or monocytes/macrophages had no effect on survival time. In contrast, PVG hearts are regularly rejected by DA recipients, and PVG liver or spleen leukocytes, even at doses of greater than 3x10(8) cells/recipient, were unable to induce heart acceptance. To investigate the possibility that acceptance of the irradiated liver but not the heart might be due to the large mass of the liver, two kidneys and two hearts of PVG origin were transplanted to each DA recipient together with 1.5x10(8) PVG leukocytes. These organs survived for greater than 200 days, thereby showing that a large mass of donor tissue, in association with donor leukocytes, leads to acceptance of organs that are rejected if transplanted singly. It appears likely that spontaneous liver transplant tolerance is a high-dose or activation-associated immune phenomenon.

Animals↗
PubMed1996

Retrieval of organs for transplantation: experience of the Australian National Liver Transplantation Unit.

The Australian National Liver Transplantation Unit carried out 251 multiple organ-retrieval procedures between January 1986 and December 1994: 53% were in the Sydney metropolitan area, 22% in country New South Wales and the Australian Capital Territory, 21% interstate and 4% in New Zealand; mean total procurement times were, respectively, 4 hours 57 minutes, 6 hours 58 minutes, 9 hours 20 minutes and 12 hours 20 minutes. Donor operation times steadily decreased over the nine years. One-year patient and graft survival rates were 77.1% and 70.3%, respectively; primary non-function occurred in only one case. The importance of coordination of donor organ procurement and efficient organ retrieval to the success of transplantation programs is discussed.

Adolescent↗
PubMed1996

Tolerance to rat liver allografts. III. Donor cell migration and tolerance-associated cytokine production in peripheral lymphoid tissues.

The aim of this work was to investigate the mechanism of spontaneous rat liver allograft tolerance. Liver allografts from a LEW donor into DA recipient (LEW-->DA) or of PVG-->DA were spontaneously tolerated (TOL) across a complete MHC mismatch. In contrast, DA-->LEW or PVG-->LEW liver allografts were rejected in 10 to 15 days (REJ). We examined whether donor cell migration to recipient lymphoid tissues might be associated with TOL. Many donor cells were observed in draining (celiac) lymph nodes (LN) and spleen, reaching a peak on day 1 and then decreasing rapidly thereafter. Irradiation of liver donors, which we have previously shown to delete tolerance, significantly reduced the number of donor leukocytes in recipient lymphoid tissues. While this suggested an association between donor cell migration and tolerance, the number, distribution, and type of donor cells in recipient lymphoid tissues of REJ was similar to those of TOL. Expression of cytokine mRNA in LN and spleen showed an early increase in the expression of IL-2 and IFN-gamma mRNA on day 1 and then a rapid decrease to constitutive levels. Spleen and LN levels of IL-6, IL-10, TNF-alpha, or TGF-beta mRNA showed much less up-regulation than IL-2 or IFN-gamma. Paradoxically, there was greater expression of IL-2 and IFN-gamma mRNA in TOL lymphoid tissues than in REJ, and this superinduction was partially prevented by donor irradiation. Superinduction of IL-2 and IFN-gamma was, therefore, more closely associated with TOL than was donor cell migration. This was confirmed by treatment of TOL recipients with a short course of methylprednisolone, which reduced survival of subsequent donor strain skin grafts. This finding has implications for treatment of human liver transplants and is evidence for a novel pathway of transplant tolerance.

Animals↗
PubMed1996

Hepatic resection with vascular isolation and routine supraceliac aortic clamping.

BACKGROUND: Hepatic resection with total vascular isolation has been reported to reduce hemorrhage. Addition of supraceliac aortic clamping putatively avoids hemodynamic instability, but may increase morbidity. METHODS: This technique was used in 99 major liver resections utilizing scalpel division and suture hemostasis. RESULTS: Livers were normal in 86 patients, cirrhotic with no portal hypertension in 5, and cirrhotic with portal hypertension in 8. There was 1 death in 91 patients with no portal hypertension due to hepatic failure or bleeding esophageal varices. There were 59 hemihepatectomies and 40 segmentectomies. Median operating time was 145 and 110 minutes, respectively, and mean transfused blood was 4 and 0 units, respectively, with minimal morbidity. CONCLUSIONS: Use of total hepatic vascular isolation with routine supraceliac aortic clamping is a safe and expedient method of hepatic resection that limits blood loss and maintains hemodynamic stability, but does not increase morbidity. However, the presence of portal hypertension precludes safe resection.

Adult↗