Pharmacokinetic profiling of cyclosporine microemulsion during the first 3 weeks after simultaneous pancreas-kidney transplantation.

The optimal effect of therapy with cyclosporine (CsA) seeks to minimize undesirable side effects while maximizing immunosuppression. This balance, depends on CsA exposure, which may be characterized by the area under the concentration-time-curve (AUC). Therefore, we tested the pharmacokinetic profile of microemulsion CsA as a superior approach to guide clinical immunosuppression after de novo simultaneous pancreas-kidney transplantations. We examined 10 consecutive pancreas-kidney recipients with type 1 diabetes and end-stage renal disease. All patients were treated with a regimen consisting of CsA, mycophenolate mofetil (MMF), and prednisone. Full (9-point) pharmacokinetic studies (C0, C1, C2, C3, C4, C6, C8, C10, C12) were performed on week 1 and during week 3 to examine CsA pharmacokinetic profiles. Mean AUC0-12 of 4431 +/- 2400 microg x h/L at week 1 remained stable at week 3 (5119 +/- 1190 microg x h/L). The C6 sampling time displayed the best correlation with AUC0-12 (r2 = 0.881), followed by C3 (r2 = 0.758). Our preliminary data after simultaneous pancreas-kidney transplantation support the hypothesis that C3 or C6 sampling is a more accurate predictor of the AUC0-12 than C0. The combination of two samplings, namely C3 + C6 (r2 = 0.938) or C2 + C6 (r2 = 0.955) proved excellent prediction of exposure after simultaneous pancreas-kidney transplantation.

[Gallstones--surgical aspects]. / Gallensteinleiden--chirurgische Aspekte.

Between 10% to 15% of the adult population develop gallstones. Therefore, cholecystectomy is among the most common operations in general surgery. The diagnosis of cholelithiasis depends on the patient's history, clinical findings, laboratory tests and ultrasound examination. Once diagnosis of symptomatic gallbladder disease has been confirmed, laparoscopic cholecystectomy is the treatment of choice. Its advantages in comparison with open surgery are decreased morbidity, costs and hospital stay. Open cholecystectomy is still the treatment of choice for complicated gallstone disease (i.e. cancer, Mirizzi's syndrome, severe inflammation) and in high-risk patients. In case of acute cholecystitis, early laparoscopic cholecystectomy is a safe procedure and is associated with the same benefits as for symptomatic disease.

[Intraoperative fluid management in pancreatic resections--the surgeon's view]. / Intraoperative flüssigkeitstherapie bei pankreasresektionen--die sicht des chirurgen.

Even though intraoperative fluid management during major intraabdominal surgery has frequently been addressed in the past, there is a lack of evidence-based recommendations. This report elucidates the topic from the surgeon's view. For the surgeon, the influence of larger fluid amounts on wound and anastomotic healing, bleeding complications and postoperative outcome (time of extubation, postoperative gastrointestinal function, hospital stay, etc.) is of interest. To clarify the question as to what a perioperative fluid regime should be composed of from a surgical point of view, data from the literature and our own studies were evaluated. The retrospective analysis of 98 pancreas resections that had been performed in our hospital revealed no significant differences concerning the occurrence of postoperative bleeding (8.2 %), wound infection (4.1 %), pancreatic fistula (9.4 %) and mortality (2.0 %) based on the administered intraoperative fluid amount. These results were comparable to those of other authors. The average intraoperatively infused fluid amount was 13.9 +/- 0.9 mL / kg / h. Catecholamines were administered in 74 % of all operations, while noradrenaline was used in 54 % of all cases. Although other factors might play a role in this setting, we can deduce from these data that application of a volume of 10-15 mL / kg / h has no negative influence on the outcome following pancreas resections and that the intraoperative fluid therapy should be targeted at these values.

Octreotide hardens the pancreas.

BACKGROUND AND AIMS: Leakage from pancreaticojejunostomy and development of pancreatic fistulas are the major postoperative complications in patients undergoing duodenopancreatectomy. The risk of developing these complications is higher when surgery is performed on a soft pancreas. A recent report suggests that octreotide hardens the pancreas when given intraoperatively. The present study aims at verifying this observation by measuring tissue hardness of the pancreas by a commercially available durometer in pigs with and without octreotide pretreatment. METHODS: Three groups of pigs were investigated: Group 1 (n=6) received no treatment; group 2 (n=6) was treated with 3x100 microg octreotide for 1 day; group 3 (n=6) for 5 days. Thereafter, animals were killed and the pancreas was harvested for performing measurements: Tissue hardness was assessed by a commercially available durometer, and a suture holding test was performed using a Newton dynamometer. RESULTS: There was a significant increase in tissue hardness between untreated control animals [26.3+/-2.5 S.U. (shore units)] and animals with 1 day octreotide pretreatment (29.8+/-2.6 S.U.; p=0.04) as well as between the groups treated for 1 and 5 days (34.8+/-2.8 S.U.; p=0.01). Suture holding capacity was higher in animals treated for 5 days. CONCLUSION: The present study agrees with a recent report suggesting that octreotide hardens the pancreas. Octreotide pretreatment may therefore be an advantage when performing surgery on a soft pancreas, i.e., in patients scheduled for duodenopancreatectomy for ampullary carcinomas or circumscript pancreatic tumors not associated with chronic pancreatitis.

Glutathione depletion with L-buthionine-(S,R)-sulfoximine demonstrates deleterious effects in acute pancreatitis of the rat.

A common pathway in the pathogenesis of acute pancreatitis is the generation of free oxygen radicals. The most important defense mechanisms are free radical scavengers, especially glutathione. This study evaluates the influence of the inhibition of glutathione synthesis with L-buthionine-(S,R)-sulfoximine (BSO) on the course of experimentally induced acute pancreatitis in rats and the effects on isolated pancreatic acini and their secretion pattern. Thus acute necrotizing pancreatitis was induced with intraductal infusion of low-dose glycodeoxycholic acid and subsequent hyperstimulation with cerulein with and without pretreatment with BSO. In vitro pancreatic acini were isolated and stimulated with different concentrations of cerulein with and without BSO. The BSO-treated group showed a significantly reduced survival, more necrosis, and a decreased secretion of amylase in vivo. No effect on secretion pattern in either groups was seen in vitro and BSO did not exert toxic effects. Based on the data presented, this study demonstrates deleterious effects of scavenger depletion on the course of experimental pancreatitis. This is due to the systemic effects of free oxygen radicals rather than to local effects.