No abstract

The shift from a predominantly portal-based process toward lobular graft damage represents the early transition of AR to CR, for which a modification of immunosuppression might be necessary to prevent graft loss.

Bacterial sepsis remains a frequent complication after liver transplantation. We previously reported the results of a pilot study that suggested that low expression of HLA‐DR on monocytes is a predictive marker for the occurrence of sepsis. We have studied the value of this marker in an additional cohort of patients, and have analyzed the relation of HLA‐DR expression with the use of immunosuppressive agents. 20 adult liver transplantation patients were prospectively monitored during the first 4 weeks after transplantation. All were treated according to standard protocols. The percentage of monocytes expressing HLA‐DR was measured by flow cytometry. In addition, the effects of incubation of monocytes with prednisolone in vitro on the expression of HLA‐DR was determined in 7 healthy volunteers. Seven patients developed bacterial sepsis after a median 15 (range 10–20) days after transplantation. HLA‐DR expression was significantly lower in these patients on days 7, 14, 21, and 28 after transplantation compared with non‐septic patients. The percentage of HLA‐DR positive monocytes was 30% or less, 3 (1–8) days before onset of sepsis. On day 7 after transplantation, HLA‐DR expression on 50% or less of monocytes had a positive predictive value for sepsis of 71%, whereas the negative predictive value was 85%. Patients who developed sepsis received significantly more prednisolone. Incubation with prednisolone in vitro lowered the expression of HLA‐DR in a dose‐dependent manner. We conclude that low HLA‐DR expression on monocytes is a marker for a high risk of subsequent sepsis in liver transplantation patients. This high risk may be (at least partly) related to the dose of prednisolone.

The lytic response of lymphoid cells to glucocorticoid hormones (GC) is prototypical of the induction of apoptosis: a special form of cellular demise for the removal of unwanted or redundant cells. Initiation and execution of a death programme are therefore major checkpoints in GC-sensitivity. Although Bcl-2 protein can prevent or delay apoptosis of lymphoma and leukemia cells, exposed to multiple cytotoxic agents, its antagonism of GC-induced apoptosis appears most critical in conferring resistance to corticosteroids. Moreover, Bcl-2 may modulate GC-signalling to apoptosis through its association with fundamental cellular processes such as energy state, Ca2+ homeostasis and transmembrane transport. However, this signalling pathway can also be interrupted by Bcl-2- independent mechanisms. This review discusses the various cellular and oncogenetic factors that control GC sensitivity of leukemia/lymphoma cells and proposes a hypothesis of how GC may induce a death programme, sensitive to blockade by Bcl-2.

Forty acute gastric ulcers were created in 10 rabbits. The bleeding was controlled by monopolar electrocoagulation in 20 ulcers, the remaining ulcers were left untreated as controls. Spontaneous intravascular thrombosis was precluded by heparinization. A histological assessment in the acute stage revealed significant morphological alterations in electrocoagulated ulcers, with fibrin deposition, decreased tissue stainability and swelling of the vessel walls, indicating heat-induced damage including cells of the vessel walls. An intravascular occlusive fibrin thrombosis demonstrated in all coagulated ulcers is suggested to be the probable mechanism of hemostasis.