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Background Budd–Chiari syndrome carries significant mortality, but factors predicting this outcome are uncertain. Aim To determine factors associated with 3-month mortality and compare outcomes after surgical shunting or liver transplantation. Methods From 1985 to 2008, 51 patients with Budd–Chiari syndrome were identified. Results By logistic regression analysis, features associated with higher risk of 3-month mortality were Rotterdam class III, Clichy >6.6, model for end-stage liver disease (MELD) >20 and Child–Pugh C. Rotterdam class III had the best performance to discriminate 3-month mortality with sensitivity of 0.89 and specificity of 0.63, whereas Clichy >6.60 had sensitivity of 0.78 and specificity of 0.69; MELD >20 had sensitivity of 0.78 and specificity of 0.75 and Child–Pugh C had sensitivity of 0.67 and specificity of 0.72. Eighteen patients underwent surgical shunts and 14 received liver transplantation with no significant differences in survival (median survival 10 ± 3 vs. 8 ± 2 years; log-rank, P = 0.9). Conclusions Rotterdam score is the best discrimination index for 3-month mortality in Budd–Chiari syndrome and should be used preferentially to determine treatment urgency. Surgical shunts constitute an important therapeutic modality that may help save liver grafts and prolong transplantation-free survival in a selected group of patients with Budd–Chiari syndrome. [ABSTRACT FROM AUTHOR]

Islet transplantation offers the prospect of good glycemic control without major surgical risks. After our initial report of successful islet transplantation, we now provide further data on 12 type 1 diabetic patients with brittle diabetes or problems with hypoglycemia previous to 1 November 2000. Details of metabolic control, acute complications associated with islet transplantation, and long-term complications related to immunosuppression therapy and diabetes were noted. Insulin secretion, both acute and over 30 min, was determined after intravenous glucose tolerance tests (IVGTTs). The median follow-up was 10.2 months (CI 6.5-17.4), and the longest was 20 months. Glucose control was stable, with pretransplant fasting and meal tolerance-stimulated glucose levels of 12.5+/-1.9 and 20.0+/-2.7 mmol/l, respectively, but decreased significantly, with posttransplant levels of 6.3+/-0.3 and 7.5+/-0.6 mmol/l, respectively (P < 0.006). All patients have sustained insulin production, as evidenced by the most current baseline C-peptide levels 0.66+/-0.06 nmol/l, increasing to 1.29+/-0.25 nmol/l 90 min after the meal-tolerance test. The mean HbA1c level decreased from 8.3+/-0.5% to the current level of 5.8+/-0.1% (P < 0.001). Presently, four patients have normal glucose tolerance, five have impaired glucose tolerance, and three have post-islet transplant diabetes (two of whom need oral hypoglycemic agents and low-dose insulin (<10 U/day). Three patients had a temporary increase in their liver-function tests. One patient had a thrombosis of a peripheral branch of the right portal vein, and two of the early patients had bleeding from the hepatic needle puncture site; but these technical problems were resolved. Two patients had transient vitreous hemorrhages. The two patients with elevated creatinine levels pretransplant had a significant increase in serum creatinine in the long term, although the mean serum creatinine of the group was unchanged. The cholesterol increased in five patients, and lipid-lowering therapy was required for three patients. No patient has developed cytomegalovirus infection or disease, posttransplant lymphoproliferative disorder, malignancies, or serious infection to date. None of the patients have been sensitized to donor antigen. In 11 of the 12 patients, insulin independence was achieved after 9,000 islet equivalents (IEs) per kilogram were transplanted. The acute insulin response and the insulin area under the curve (AUC) after IVGTT were consistently maintained over time. The insulin AUC from the IVGTT correlated to the number of islets transplanted, but more closely correlated when the cold ischemia time was taken into consideration (r = 0.83, P < 0.001). Islet transplantation has successfully corrected labile type 1 diabetes and problems with hypoglycemia, and our results show persistent insulin secretion. After a minimum of 9,000 IEs per kilogram are provided, insulin independence is usually attained. An elevation of creatinine appears to be a contraindication to this immunosuppressive regimen. For the subjects who had labile type 1 diabetes that was difficult to control, the risk-to-benefit ratio is in favor of islet transplantation. [ABSTRACT FROM AUTHOR]

Purified human islets and a kidney from the same donor were transplanted into four patients with Type 1 (insulin-dependent) diabetes mellitus. Two of the patients received additional islets that were isolated from multiple donors, cryopreserved, and stored in a tissue bank. The islets were embolized into the liver via the portal vein. Immunosuppression was induced with antilymphocyte globulin and maintained with azathioprine, prednisone and cyclosporine. In the first two patients, fasting serum C-peptide rose to levels of 0.5-2.0 ng/ml during the first 4-8 weeks and mixed meal feeding elicited increases to 2-3 ng/ml. C-peptide secretion persisted for 8 months, but at progressively lower levels and insulin therapy could not be withdrawn. In the next two patients who received cryopreserved islets in addition to fresh islets, serum C-peptide levels (fasting/post-meal) rose to 4-7 ng/ml and serum glucose was more stable, allowing withdrawal of insulin therapy after 69 days in one patient, and reduced insulin doses in the other. The insulin-independent patient has maintained normal fasting glucose, glycosylated haemoglobin, and oral glucose tolerance at 1 year following cessation of daily insulin therapy. Episodes of renal graft rejection occurred in three patients, including the insulin-independent patient. High-dose steroid therapy reversed the rejection in all instances, with apparent preservation of C-peptide secretion. These data show that transplantation of purified freshly-prepared and cryopreserved islets into Type 1 diabetic patients results in prolonged insulin secretion, and that sufficient function could be provided in one patient to sustain euglycaemia in the absence of insulin therapy at 1 year of follow-up. [ABSTRACT FROM AUTHOR]

Purified islets of Langerhans and a kidney were transplanted into a 36-year-old patient who suffeded from renal failure secondary to a 25 year history of Type 1 (insulin-dependent) diabetes mellitus. The islet graft contained 243 000 fresh islets (mean islet diameter 150 μm) that were syngeneic with the kidney fraft and 368 000 cryopreserved islets that had been collected from four other donors. The total of 10 000 islets/kg body weight was infused into the liver via the umbilical vein. Immunosupperession was induced with antilymphocyte globulin and maintained with prednisone, cyclosporine and azathioprine. Serum C-peptide levels (ng/ml) during fasting and after standard mixed metal feeding (Sustacal) were <0.12 preoperatively. Postoperatively, insulin secretion was restored: fasting C-peptide rose during the first 4 weeks to levels of 4 to 5 and Sustacal elicited a further rise to 6 to 7. Transplant renal function was stable. Dialy fasting glucose (mmol/l, mean±SD) was 5.6±1 and 5.3±0.6 during the first and second months respectively and post-Sustacal glucose was 5.7+-0.8. Exogenous insulin therapy was progressively withdrawn and stopped duting the ninth week. Thereafter, fasting glucose was 4.7+-0.5, 24 h mean glucose was 6.6+-0.5, and normoglycaemia was maintained after Sustacal. These data show that this mass of freshly isolated and cryopreserved islets from multiple donors provided sustained function (3 months) that reversed insulin-dependence in an immunosuppressed Type 1 diabetic patient treated with simultaneous islet-kedney transplantation. [ABSTRACT FROM AUTHOR]

Many lower vertebrates (reptilian and amphibian species) are capable of surviving natural episodes of hypoxia and hypothermia. It is by specific metabolic adaptations that anurans are able to tolerate prolonged exposure to harsh environmental stresses. In this study, it was hypothesized that livers from an aquatic frog would possess an inherent metabolic ability to sustain high levels of ATP in an isolated organ system, providing insight into a metabolic system that is well-adapted for low temperature in vitro organ storage. Frogs of the species, R. pipiens were acclimated at 20 °C and at 5 °C. Livers were preserved using a clinical preservation solution after flushing. Livers from 20 °C-acclimated frogs were stored at 20 °C and 5 °C and livers from 5 °C-acclimated frogs were stored at 5 °C. The results indicated that hepatic adenylate status was maintained for 96 h during 5 °C storage, but not longer than 4–10 h during 20 °C storage. In livers from 5 °C-acclimated animals subjected to 5 °C storage, ATP was maintained at 100% throughout the 96-h period. Warm acclimation (20 °C) and 20 °C storage resulted in poorer maintenance of ATP; energy charge values dropped to 0.50 within 2 h and by 24 h, only 24% of control ATP remained. Lactate levels remained less than 25 μ mol/g dry weight in all 5 °C-stored livers; 20 °C-stored livers exhibited greater accumulation of this anaerobic end-product (lactate reached 45–50 μ mol/g by 10 h). The data imply that hepatic adenylate status is largely dependent on exposure to hypothermic hypoxia and although small amounts of ATP were accounted for by anaerobic glycolysis, there must have been either a substantial reduction in cellular energy-utilization or an efficient use of low oxygen tensions. [ABSTRACT FROM AUTHOR]