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Biomedical subjects

U T Hopt

Publications and source records attributed to U T Hopt.

At least 91 records · Page 5Linked to original sources
PubMed1998

The nitric oxide donor sodium nitroprusside is protective in ischemia/reperfusion injury of the pancreas.

BACKGROUND: The role of nitric oxide in the ischemia/reperfusion injury of the pancreas is still unclear. In other organs, protective as well as aggravating effects have been described. We have, therefore, investigated the effect of the nitric oxide donor sodium nitroprusside on pancreatic ischemia/reperfusion injury. METHODS: In Landrace pigs, after transsection of the pancreas, complete vascular isolation of the pancreatic tail was performed. The tail was subjected to 3 hr of warm ischemia and thereafter reperfusion (6 hr). The animals were divided into a control group (n=7) and a treatment group (n=7) that received 15 mg of sodium nitroprusside after reperfusion intra-arterially into the splenic artery. RESULTS: The morphological tissue damage and lipase activity in the venous effluent of the pancreas were significantly lower in the treatment group. Partial oxygen tension in the tissue after reperfusion was markedly reduced in the control group, indicating an impairment of microcirculation. In the treatment group, however, partial oxygen tension in the tissue was significantly higher (43 vs. 20 mmHg; P<0.014). Furthermore, total blood flow through the pancreatic tail in the treatment group was found to be significantly higher in the late reperfusion period (14 vs. 9.5 ml/min at 5 hr after reperfusion; P<0.05). CONCLUSION: There is a marked impairment of pancreatic microcirculation after reperfusion. Sodium nitroprusside counteracts this impairment and has a protective effect on ischemia/reperfusion injury of the pancreas.

Adenosine Triphosphate↗
PubMed1998

Successful islet auto- and allotransplantation in diabetic pigs.

BACKGROUND: Because of its anatomical and physiological similarities to humans, the pig appears to be a suitable large animal model for preclinical studies of islet transplantation. The aim of this study was to investigate islet auto- and allotransplantation in a pig model with diabetes induced by total pancreatectomy. METHODS: Porcine islets were isolated by a continuous digestion-filtration device at 32 degrees C and purified by a discontinuous iso-osmolar Ficoll-sodium-diatrizoate gradient on a Cobe 2991. The purified islets were autografted into the liver or the renal subcapsular space. The liver appears to be a more suitable site for the islet grafts than the renal subcapsular space, and the minimal amount of islets for reversal of diabetes is >5 microl/kg of body weight. RESULTS: Persistent normoglycemia (fasting blood glucose level: 72.4+/-44.38 mg/dl) with a normal insulin secretion response to glucose stimulation was successfully achieved in five of six diabetic pigs by implanting a sufficient islet mass into the liver. Triple-drug immunosuppressive therapy with cyclosporine, azathioprine, and prednisolone did not prevent porcine islet allografts from experiencing early failure. However, the addition of 15-deoxyspergualin to the triple-drug immunosuppressive regimen significantly prolonged the function of the islet allografts. When antithymocyte globulin was added to the above-mentioned immunosuppressive drug regimen, the normoglycemic period was prolonged to more than 1 month (fasting blood glucose level: 75.4+/-17 mg/dl). CONCLUSION: We conclude that autotransplantation with a sufficient islet mass can induce normoglycemia with a normal insulin secretion response to glucose stimulation in pancreatectomized diabetic pigs and that allotransplantation can be successfully achieved when 15-deoxyspergualin and antithymocyte globulin are combined with the triple-drug immunosuppression described above. However, this immunosuppressive protocol results in a high rate of infectious complications.

Animals↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

[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↗
PubMed1998

[Risk and benefits of pancreas transplantation].

Because of exocrine secretions of the gland, pancreas transplantation carries its own specific risks. Perioperative morbidity is significantly higher than after isolated kidney transplantation. The incidence, however, has been greatly reduced the last few years. The patient survival rate and graft function rate are excellent. By drainage of the graft into the small bowel and venous connection with the portal system, an almost completely physiological status can be restored. The effect on diabetic late complications vastly depends on the extent of damage induced by the long-standing diabetes mellitus. Physical capacity and quality of life increase dramatically in almost all patients after a successful pancreas transplantation. Thus, almost all patients urgently request retransplantation when the graft is lost.

Diabetes Mellitus, Type 1↗
PubMed1998

[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↗
PubMed1997

[Programmed lavage as a basic principle in therapy of diffuse peritonitis].

The therapeutic concept of programmed lavage has been established in the treatment of severe diffuse peritonitis. This treatment was given to 30 patients from January 1995 to February 1997. The total lethality rate was 30% (11/30 patients). Ten patients had organ failure of three or four organ systems at the time of first laparotomy. In this group the lethality rate was 50%. On average 9.2 programmed relaparotomys were performed per patient. As early complications, small bowel fistulas were observed in three patients, bleeding in three patients and problems due to the laparostomy in four patients.

Female↗
PubMed1997

[Surgical relevance of diagnostic imaging of abdominal tumors--decision making in pancreatic tumor].

Imaging of tumors of the pancreas may have a series of significant implications for surgical decision making. First of all verification and localization of a suspected tumor is crucial. Later on, accurate staging of local tumor extent and of distant metastases is necessary for evaluating the indications for surgical intervention. If histologic proof of malignancy of a pancreatic lesion is needed, different imaging techniques can be used for percutaneous biopsy of the tumor. Finally imaging is required in patients with a pancreatic tumor if an obstruction of the common bile duct is treated with palliative intent by endoscopy or transhepatic intervention. A rational and efficient selection from all the imaging techniques currently available requires a clear-cut definition of what is needed for surgical decision making in each individual case. Thereby one has to take into account whether the tumor arises from the exocrine or from the endocrine tissue of the pancreas.

Biopsy↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1994

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↗