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F Pfeffer

Publications and source records attributed to F Pfeffer.

At least 37 records · Page 2Linked to original sources

Ischemia/reperfusion injury of the pancreas: a new animal model.

BACKGROUND: Ischemia/reperfusion is thought to play an important role in the development of postimplantation pancreatitis after pancreas transplantation and also in the transition of edematous pancreatitis into necrotizing pancreatitis. Previous studies have suggested that impairment of microcirculation and hence tissue oxygenation and energy metabolism may be critical steps in this process. MATERIALS AND METHODS: In landrace pigs vascular isolation of the pancreatic tail was performed. Morphological alterations, tissue oxygenation, and energy metabolism were assessed in response to 3 h of global warm ischemia and the following reperfusion. RESULTS: A rapid onset of morphological alterations immediately after reperfusion was noted. Oxygen consumption and ATP levels were markedly decreased, and tissue oxygenation was severely impaired especially during the first hour after reperfusion. ATP tissue levels and oxygen consumption 10 min after reperfusion correlated significantly with the morphological changes at the end of the experiment. CONCLUSION: These findings can be explained by a failure of nutritive capillary perfusion and concomitant shunt perfusion. Therefore an impaired microcirculation rather than an impaired oxygen utilization shortly after reperfusion is of major relevance in the development of the ischemia/reperfusion injury of the pancreas.

Adenine Nucleotides↗

Impairment of pancreatic microcirculation in the early reperfusion period during simultaneous pancreas-kidney transplantation.

The most likely cause of graft pancreatitis is the ischemia/reperfusion injury which can be a major problem in simultaneous pancreas-kidney transplantation. Animal experiments suggest the important role in this process of an impaired microcirculation after reperfusion. We have investigated pancreatic microcirculation in the early reperfusion period during clinical pancreas-kidney transplantation. Tissue PO2 (PO2ti) was monitored by a PO2-sensitive electrode. After reperfusion (a.r.) samples were taken from the venous effluent of the pancreas and simultaneously from the radial artery. After an initial peak a transient fall of PO2 was found. Total blood flow and hemoglobin oxygen saturation (sHbO2) in the venous effluent increased until 90 min a.r. (107 ml/min, 97.1%) High venous sHbO2 and high PO2ti correlated with good graft outcome. These findings can be explained by an impairment of capillary perfusion (no reflow) and concomitant shunt perfusion. The data suggest the considerable relevance of pancreatic microcirculation in the early reperfusion period during clinical pancreas transplantation.

Humans↗

Modulation of 72-kilodalton type IV collagenase (Matrix metalloproteinase-2) by ascorbic acid in cultured human amnion-derived cells.

Extensive research has been done to investigate the effects of nutrients on placental and fetal development. It is now evident that environmental factors such as diet may exert a profound effect on gene expression during pregnancy. A low intake of vitamin C during pregnancy has been linked to a higher risk of premature rupture of the membranes (PROM) because of its well-known role in collagen biosynthesis. Here we report a new effect of ascorbic acid acting as a modulator of the 72-kDa type IV collagenase (matrix metalloproteinase-2; MMP-2). MMP-2 expression/activity is down-regulated by vitamin C in human amnion cultured cells. The regulatory effect is exerted at the transcriptional level and is specific for MMP-2. Matrix metalloproteinases are implicated in tissue remodeling, and our results allow us to suggest a molecular mechanism that relates poor availability of vitamin C during pregnancy and the development of PROM.

Amniotic Fluid↗

[Influence of the extrinsic nervous system on exocrine pancreatic secretion in the human].

Exocrine pancreatic secretion is regulated by gastrointestinal hormone and the autonomic nervous system. The interaction of both systems is still unclear. In humans CCK mediated regulation of exocrine pancreatic secretion requires a cholinergic tonus. The CCK receptor is thought to be localized on the acinuscell and modulated by cholinergic neurons. Pancreas transplantation and percutaneous diversion of the pancreatic juice offers the opportunity to investigate pancreatic secretion under the condition of complete extrinsic denervation. In the present study the influence of denervation on exogene CCK stimulation and simultaneous cholinergic stimulation or suppression with atropine, respectively, was investigated. CCK stimulation alone showed a reduced, dose dependent increase in enzyme secretion. Simultaneous stimulation with bethachenol resulted in a 2-fold increased secretion. Atropine suppressed the low dose CCK effect completely. Whereas CCK at high doses caused a 1.5 fold increase despite atropine. After extrinsic denervation the human pancreas remains sensitive to exogene stimulation. The intrinsic system remains also intact and is sensitive to cholinergic stimulation. The extrinsic nervous system seems to be necessary for an adequate CCK response. The results are in line with the hypothesis that CCK receptors are only partly localized on the acinuscell, whereas the majority is localized in extrinsic cholinergic neurons.

Adult↗

[Initial applications of a new trochar system for non-laparoscopic intraluminal surgery].

Instruments that have been used in flexible endoscopy have always been confined to the working channel of the endoscope. We have therefore developed a device that allows transabdominal manipulation in the stomach under gastroscopic control with a device similar to a percutaneous endoscopic gastrostomy (PEG). For the first clinical application of this device it was used in order to perform pseudocystogastrostomy in patients with pancreatic pseudocysts.

Drainage↗

Liposoluble antioxidants are not consumed in the pancreas after reperfusion in human simultaneous pancreas-kidney transplantation.

There is considerable evidence that under experimental conditions, oxygen free radicals (OFRs) are decisive in the pathogenesis of ischemia-reperfusion injury. Normally OFRs are scavenged by antioxidants such as alpha-tocopherol. Thus, in the following study we investigated whether antioxidants are consumed locally in human pancreatic grafts after reperfusion. A series of ten patients receiving bladder-drained pancreaticoduodenal and renal allografts were studied. Sequential blood samples were drawn locally from the venous outflow of the graft and simultaneously from the radial artery after reperfusion. alpha-Tocopherol, retinol, lycopene, and alpha- and beta-carotene levels were determined. After reperfusion these levels remained largely unchanged. Hence, in our study a consumption of antioxidants locally in the pancreatic graft after transplantation was not demonstrated. Therefore, the antioxidant capacity seems not to be exhausted at that time. This suggests that in clinical pancreatic transplantation oxidant stress in the initial reperfusion period might not have the relevance suggested by animal models.

Antioxidants↗

Determinants of a normal (versus impaired) oral glucose tolerance after combined pancreas-kidney transplantation in IDDM patients.

After successful pancreas transplantation, insulin-dependent diabetic patients are characterized by a normal or at worst impaired oral glucose tolerance (World Health Organisation criteria). It is not known which pathophysiological mechanisms cause the difference between normal and impaired oral glucose tolerance. Therefore, we studied 41 patients after successful combined pancreas-kidney transplantation using stimulation in the fasting state with oral glucose (75 g), intravenous glucose (0.33 g/kg) and glucagon bolus injection (1 mg i.v.). Glucose (glucose oxidase), insulin and C-peptide (immunoassay) were measured. Repeated-measures analysis of variance and multiple regression analysis were used to analyse the results which showed: 28 patients had a normal, and 13 patients had an impaired oral glucose tolerance. Impaired oral glucose tolerance was associated with a greatly reduced early phase insulin secretory response (insulin p < 0.0001; C-peptide p = 0.037). Age (p = 0.65), body mass index (p = 0.94), immunosuppressive therapy (cyclosporin A p = 0.84; predniso(lo)ne p = 0.91; azathioprine p = 0.60) and additional clinical parameters were not different. Reduced insulin secretory responses in patients with impaired oral glucose tolerance were also found with intravenous glucose or glucagon stimulations. Exocrine secretion (alpha-amylase in 24-h urine collections) also demonstrated reduced pancreatic function in these patients (-46%; p = 0.04). Multiple regression analysis showed a significant correlation of 120-min glucose with ischaemia time (p = 0.003) and the number of HLA-DR mismatches (p = 0.026), but not with HLA-AB-mismatches (p = 0.084). In conclusion, the pathophysiological basis of impaired oral glucose tolerance after pancreas transplantation is a reduced insulin secretory capacity. Transplant damage is most likely caused by perioperative influences (ischaemia) and by the extent of rejection damage related, for example, to DR-mis-matches.

Adult↗

Vitamin C status, cervico-vaginal infection and premature rupture of amniotic membranes.

A prospective study to evaluate the role of vitamin C and cervico-vaginal infection in the premature rupture of amniotic membranes (PROM) was designed. The leukocyte vitamin C levels of 44 pregnant women that did not consume vitamin supplements was evaluated at weeks 20, 28 and 32 of pregnancy. On each evaluation the presence of cervico-vaginal infection was diagnosed and treated. The leukocyte vitamin C level throughout gestation showed a decrease towards week 28 and then it recovered at the end of pregnancy. Six of every ten women had normal flora in their vaginal secretion cultures. Eleven cases had PROM (0.24), no association was found between cervico-vaginal infection and PROM. The leukocyte vitamin C levels on week 20 of gestation showed an association with PROM. (chi 2 = 6.34, p < 0.05, odds ratio 6.75 [CI 1.26-26.03]).

Adult↗

Simultaneous pancreas/kidney transplantation--the optimal therapy for type I diabetics with end-stage renal disease in Europe, too?

Contrary to the situation in the USA, the number of pancreatic transplantations declined during the last year in the Eurotransplant region. Whether the high postoperative morbidity and unsatisfactory graft function rates reported by many European centres can be overcome was investigated in a single centre study. In a consecutive series of 80 patients with simultaneous pancreas/kidney transplantations, postoperative morbidity due to graft pancreatitis and recurrent rejections was significant. Both of these complications, however, were treated successfully in the vast majority of patients. Graft thrombosis was almost completely prevented. Excellent function rates of the pancreatic grafts of 88% after 1 year and 83% after 5 years were achieved. Thus, simultaneous pancreas/kidney transplantation can be recommended as the optimal therapy for type I diabetics with end-stage renal disease in Europe, too.

Adult↗