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Background and Objective: Platelet function abnormalities influence the haemostatic defect in patients with liver failure. Patients after orthotopic liver transplantation present thrombocytopaenia associated with bleeding problems, which may be aggravated by the interaction of hydroxyethyl starches with platelets., Methods: From 12 patients after liver transplantation venous blood samples (3 mL) were taken before, 20 and 120 min after infusion of hydroxyethyl starch of medium molecular weight (200 kDa/0.5) 6% 10 mL kg(-1) over a period of 30 min. Surface expression of glycoprotein IIb/IIIa and P-selectin were quantified by flow cytometry as well as the percentage of platelet-leucocyte complexes., Results: A significant decrease of P-selectin expression following administration of hydroxyethyl starch after 120 min (89.1 +/- 4.2%, P = 0.029) and a corresponding significant reduction in the formation of platelet-monocyte complexes (81.1 +/- 7.8%, P = 0.001) were observed. There was no alteration in the glycoprotein IIb/IIIa expression after hydroxyethyl starch infusion., Conclusions: Infusion of hydroxyethyl starch 200 kDa/0.5 in clinically relevant doses does not alter glycoprotein IIb/IIIa expression in thrombocytopaenic patients with pre-existing platelet dysfunction after orthotopic liver transplantation. Accordingly, infusion of hydroxyethyl starch may have a beneficial effect on microvascular graft perfusion through the resulting haemodilution and reduced P-selectin expression with subsequent reduced leucocyte-platelet complexes and endothelial adhesion.

Early postoperative infections and septic complications are predominant causes of morbidity and mortality in patients following orthotopic liver transplantation (OLTx). Prophylactic granulocyte colony-stimulating factor (G-CSF) administration after OLTx was found to decrease the number of sepsis episodes and sepsis-related mortality. Since polymorphonuclear neutrophils (PMNs) are one of the major determinants of antimicrobial defense, alteration of their functions may influence the development of sepsis in these patients. Therefore, we investigated in vitro whether or not priming with G-CSF affects the neutrophils' respiratory burst (RB) in immunosuppressed liver-transplanted patients. Venous blood was drawn from liver allograft recipients (n=12) between the 5th and 15th day postoperatively. Patients without clinical signs of infection or rejection were included in this study. Leukocytes were obtained as supernatant following sedimentation and incubated with 1000 IE ml-1 G-CSF. The RB was measured by the intracellular oxidation of non-fluorescent dihydrorhodamine to the fluorescent rhodamine by flow cytometry. The results were expressed as a percentage of increasing stimulation compared to the control responses, which are made up of the percentage of cells with RB reaction after stimulation with phorbol ester (PMA), bacteria (E. coli), or the combination of a cytokine (TNF-alpha) and a bacterial peptide (FMLP) in the absence of G-CSF. In vitro priming with G-CSF resulted in significantly increased activity of the RB after PMA (from 71.7% to 85.6%) and TNF-alpha/FMLP (from 58.4% to 72.7%) stimulation. These data demonstrate that G-CSF in vitro augments the RB of PMNs, thereby suggesting a possible therapeutic role for G-CSF as immunomodulating agent during bacterial and fungal infections following OLTx.

Objective: Superoxide production by polymorphonuclear neutrophils (PMNs) under cyclosporin A (CsA) therapy following kidney transplantation is impaired. We investigated if the respiratory burst of PMNs is similarly depressed in patients undergoing CsA treatment following orthotopic liver transplantation (OLTx). Additionally, the in vitro influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the superoxide anion production was examined during the respiratory burst., Patients: 10 patients after OLTx and 10 healthy blood donors (control group)., Measurements and Results: PMNs were stimulated with bacteria (Escherichia coli) or a combination of tumour necrosis factor alpha (TNFalpha) and N-formyl-methionyl-leucyl-phenylalanine (FMLP). The respiratory burst was measured by oxidation of non-fluorescent dihydrorhodamine to the fluorescent rhodamine by means of flow cytometry. No differences in respiratory bursts from OLTx patients compared to those from healthy blood donors could be seen. Under TNFalpha/FMLP stimulation, the respiratory burst was significantly increased after in vitro incubation with GM-CSF (500 U ml(-1)) in patients following OLTx (from 58.2 to 74.5 %) as well as in the control group (from 47.4 to 61.9%)., Conclusions: Our results demonstrate that superoxide production is not impaired under CsA treatment following OLTx. The respiratory burst of these patients' PMNs can even be augmented by GM-CSF in vitro.

Unlabelled: Inflammatory bowel disease (IBD) is associated with an increase in colon and rectal carcinoma. Immunosuppression after transplantation increases the incidence of certain types of tumors., Purpose: We reviewed the postoperative course of IBD patients who had undergone hepatic transplantation for primary sclerosing cholangitis to see whether there was an increase in the rate of colorectal neoplasms., Methods: The charts of 44 patients from two institutions who had undergone a hepatic transplant for primary sclerosing cholangitis were reviewed. Of these 44 patients, 33 had IBD (32 chronic ulcerative colitis, 1 Crohn's). Of these 33 patients, 2 had previously undergone total colectomy/proctectomy and 4 died in the perioperative period. The remaining 27 patients had all undergone colonoscopic evaluation just prior to transplant. Postoperatively all patients were given prednisone, cyclosporine, and azathioprine. Minimum follow-up was 12 months; mean follow-up was 39 months., Results: Three of the 27 patients (11.1 percent) developed early colorectal neoplasms (2 cancers, 1 large villous adenoma with severe dysplasia) at 9, 12, and 13 months post-transplant. All three patients were successfully treated with a total colectomy/proctectomy or resection of any remaining colon. These 3 patients had a mean 19-year history of IBD (range, 9-27 years), while the 24 patients without tumors had a mean 18-year history of IBD (range, 6-39 years)., Conclusion: There is a subset of transplant patients with primary sclerosing cholangitis and IBD who rapidly develop colorectal neoplasms. Frequent surveillance is recommended for IBD patients in the post-transplant period.