Orthotopic liver transplantation (OLT) is often associated with hemodynamic instability upon reperfusion, recognized as postreperfusion syndrome. Changes in vascular tone due to humoral factors released upon reperfusion of the graft have been suggested as a possible mechanism. In this study, we looked at the perioperative changes in cyclic guanosine monophosphate (cGMP), a mediator of vascular smooth muscle relaxation, and investigated its relationship with hemodynamic parameters. cGMP was measured in the plasma of 14 patients undergoing OLT by radioimmunoassay serially at the preanhepatic and anhepatic phases, and after reperfusion at 30, 60, and 120 min. Hemodynamic data recorded were systemic and pulmonary arterial pressures, cardiac output, and pulmonary and systemic vascular resistance. cGMP decreased markedly after reperfusion from a baseline level of 5.33+/-0.7 ng/ml to 1.63+/-0.5 ng/ml (P<0.01). Pulmonary arterial pressure increased from 17+/-1.21 mmHg to 23.5+/-1.9 mmHg (P<0.05), and pulmonary vascular resistance increased from 62.8 +/-12.9 dynes/sec/cm5 to 135+/-42.7 dynes/sec/cm5 (P<0.01). Changes in cardiac output and systemic vascular resistance were not significant. The changes in cGMP correlated with pulmonary arterial pressure (r=0.74, P=0.005) and pulmonary vascular resistance (r=0.7, P=0.01). These data confirm the occurrence of hemodynamic changes during OLT, and provide evidence to suggest that the reduction in cGMP after reperfusion may mediate the vascular changes.

Osler-Weber-Rendu disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant condition causing systemic fibrovascular dysplasia. It has an incidence of 1-2/100,000. Phenotypic variation is extreme ranging from asymptomatic to severely symptomatic, from cases with no or few mucocutaneous lesions to those with diffuse cutaneous telangiectasia. We discuss a case of Osler-Weber-Rendu disease causing diffuse cutaneous telangiectasia and hemoptysis. The patient presented with complaints of hemoptysis and was extensively examined and investigated before being diagnosed with Osler-Weber-Rendu disease. We successfully managed the patient's hemoptysis by bronchial artery embolization. This case emphasizes the need for careful examination and investigation and to consider such rare diseases when all the common causes of hemoptysis are ruled out. An early and proper diagnosis will lead to more effective management of such a rare disease with few treatment options available.

survival rates for shunted and endoscopically treated patients Methods: Sixty-three consecutive cirrhotic patients with a of 90% and 89%, and 2-year survival rates of 79% and 82%, hemorrhage from esophageal varices were included. Thirtyrespectively. The incidence of clinically significant hepatic two patients were randomly allocated to ES and 31 to TIPS encephalopathy after 1 year was higher in the shunt group groups. Results: One patient in each group died before the (36% vs 18%, P Å 0.011). Interpretation: These results sugtherapeutic procedure could be performed. During a mean gest that the transjugular shunt is more effective than endofollow-up period of 15 months, variceal rebleeding occurred scopic treatment in prevention of variceal rebleeding but has in 51.6% of the patients in the ES group and 23% of those in a considerable risk of hepatic encephalopathy. Survival is simthe TIPS group. Uncontrolled rebleeding occurred in 10 of ilar in the two groups. 31 patients in the ES group, whereas rebleeding did not occur in any patient of the TIPS group. Hepatic encephalopathy was more frequent in TIPS patients (33.3%) than in those treated (3) Cello JP, Ring EJ, Olcott EW, Koch J, Gordon R, Sandhu by ES (13%). However, mortality was similar in both treat-J, Morgan DR, et al. Endoscopic sclerotherapy compared with ment groups. Conclusions: These preliminary results suggest percutaneous transjugular intrahepatic portosystemic shunt that TIPS is more effective than ES in the prevention of vari-after initial sclerotherapy in patients with acute variceal hemceal rebleeding in cirrhotic patients, even though no difference orrhage: a randomized, controlled trial. Ann Intern Med in survival was observed.

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Introduction Hospitalisations from acetaminophen poisoning are increasing (1999, n¼39 045; 2010, n¼52 707. UK, NHS admissions). For the most serious cases there are no effective therapies to assist recovery or prolong survival apart from liver transplantation, which remains a limited resource. We report a clinically-relevant, intensively-managed, model of ALF, which mimics the human condition and has a predictable survival time, for testing of new potential therapies. Methods Nine, 30e40 kg, female pigs were anaesthetised and instrumented for continuous monitoring and management of respiratory and cardiovascular systems and acid-base and electrolyte status, using standardised intensive care protocols and intermittent positive pressure ventilation. Intracranial pressure (ICP) was monitored but not treated. Six animals were induced to ALF with acetaminophen administered via an oroduodenal tube: a loading dose of 0.25 g/kg was followed by hourly doses of 0.5e4.0 g adjusted according to serum acetaminophen concentrations. At irreversible ALF (defined as prothrombin time >3 times normal), continuous renal replacement therapy (CRRT) was initiated. Three animals acted as controls with initiation of CRRT at 20 h and termination at 40 h. Results Following onset of acetaminophen dosing, peak serum acetaminophen concentrations of 367630 mg/l were achieved at 12 h and irreversible ALF at 19.361.8 h. Death occurred predictably 12.662.7 h after irreversible ALF. Development of ALF was associated with progressive hypotension (p<0.001) and metabolic acidosis (p¼0.001), not observed in controls. Mean arterial pressure (MAP) was maintained with aggressive fluid therapy, noradrenaline and terlipressin. Metabolic acidosis was corrected successfully with bicarbonate and CRRT. In ALF, there was significant (p<0.001) rise in ICP compared to controls with sudden marked increase prior to death: at study end, ICP in ALF and controls was 41.268.6 mm Hg and 22.762.5 mm Hg respectively. Death was preceded by abrupt increase in central venous pressure, fall in MAP and bradycardia. Histopathology confirmed moderate to marked acute centrilobular to midzonal hepatocyte degeneration and necrosis in ALF. Conclusion A predictable model of ALF, with death due to multiorgan failure, has been successfully validated for translational studies for therapies designed to prolong survival in man.