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Biomedical subjects

J Klempnauer

Publications and source records attributed to J Klempnauer.

At least 19 recordsLinked to original sources

[Multivariate analysis of prognostic factors after resection of ductal pancreatic carcinomas].

At Hanover Medical School 466 patients were operated for ductal pancreatic cancer from 1971 to 1993. In 192 cases the pancreatic tumor could be resected, which amounts to a resection rate of 41%. These patients were subjected to uni- und multivariate factorial analysis in order to evaluate factors of significant prognostic value. Extended pancreatic resection because of vascular involvement or invasion of adjacent organs was performed in 40% (n = 77) of the cases. A curative R0 resection was possible in 85% of patients. The operative lethality dropped with time and from 1985 to 1993 was 3.5%. Patient survival at 5 years was 13.4% with a median survival time of 10.9 months. According to the univariate analysis the prognosis deteriorated with increasing tumor size and lymphatic and hematogenic metastases. There was a significant correlation between tumor stage according to the UICC and prognosis. The prognosis after resection was also significantly influenced by the residual tumor state and tumor grading. Extended pancreatic resections, however, had no significant prognostic impact. The multivariate analysis showed that only three factors were of independent significant relevance: residual tumor state, tumor size and tumor grade. The presence or absence of lymphatic and hematogenic metastases had no independent prognostic significance after resection of ductal pancreatic carcinomas.

Adult

[Requirements for a surgical documentation system and its realization].

Adequate documentation of all surgical procedures is now essential. High demands in terms of quality and quantity mean that computerized databases and evaluation procedures are required. In the Department of Abdominal and Transplantation Surgery within Hanover Medical School a standardized but individually adaptable documentation system has been greated using standard hardware and software. A hierarchical code system has been established for surgical procedures, and this also offers the options of automatic online coding and translation into the coding used in the International Classification of Procedures in Medicine. The advantages and limitations of this system are discussed.

Database Management Systems

Insulin cells in rat whole-pancreas isografts display heterogeneous immunoreactivities and ultrastructure.

It has already been shown that insulin cells studied under experimental conditions exhibit differences in insulin immunoreactivity and insulin release. The aim of this study, therefore, was to investigate whether insulin cells themselves exhibit morphological abnormalities after transplantation. Insulin cells in rat pancreas isografts with preserved or suppressed exocrine secretion were studied immunocytochemically and ultrastructurally and compared with those of unoperated rats. In isografts with preserved exocrine secretion, cortical insulin cells connected to the exocrine parenchyma or to glucagon or somatostatin cells expressed mostly dense immunoreactivities for insulin and amylin. In addition, medullary insulin cells connected only to other insulin cells displayed faint immunoreactivities for both constituents as found in unoperated animals. After duct ligation, however, pancreatic ducts and elongated capillaries extended into the islets. Corresponding to the stages of islet fragmentation, the heterogeneity among insulin cells underwent changes and was finally abolished. Ultrastructurally, differences in the number of secretory granules paralleled the heterogeneity in insulin immunoreactivity. It is interesting to note that the heterogeneity among insulin cells is preserved after transplantation, indicating that this phenomenon might be of physiological relevance. The heterogeneity may implicate differences in insulin storage and release as found in insulin cells under normal conditions.

Amyloid

Differential response of kidney and pancreas rejection to cyclosporine immunosuppression.

Immunological interferences between kidney and pancreas transplants were investigated in a genetically defined rat model of combined kidney and pancreas transplantation. Kidney and whole-pancreas grafts were transplanted microsurgically either as individual grafts or in a combined technique. Whole pancreas grafts were grafted into streptozotocin diabetic recipients (55 mg/kg bodyweight i.v.) three days after induction of diabetes. The exocrine secretion was suppressed by duct ligation. Rejection of the grafts was defined by recurrence of diabetes in pancreas-grafted recipients and renal failure after kidney transplantation. There were marked differences in the efficacy of identical short-term cyclosporine immunosuppression (15 mg/kg intramuscularly for 14 days): DA kidneys survived indefinitely in LEW rats (MST greater than 100 days), while DA pancreas allografts underwent prolonged but not permanent survival (P less than 0.01) either as individual grafts (MST 27.3 +/- 1,9 days) or when transplanted simultaneously together with the kidney (44 +/- 16 days) (P less than 0.01). LEW rats carrying a DA kidney for 100 days also rejected a subsequent donor-specific pancreas transplant within 30 days. The histological alterations in the kidney were more pronounced than after cyclosporine-induced DA kidney long-term survival alone. By contrast to the rejecting subsequently transferred pancreas, a metachronous second DA kidney was permanently accepted (greater than 100 days) without further immunosuppression after removal of the first graft, while unrelated LEW. 1U kidneys were acutely rejected. In summary, the results indicate that there are not only quantitative differences of kidney and pancreas allograft survival but also differences concerning the state of immunological unresponsiveness induced by identical cyclosporine immunosuppression. While CsA induces donor-specific immunological unresponsiveness after kidney transplantation, pancreas transplants are all eventually rejected after some differential prolongation of survival. Further investigations on the effects of different MHC and minor alloantigens may provide more insight into the complex immunological situation of individual and combined kidney and pancreas transplantation.

Animals

Progressive deterioration of endocrine function after intraportal but not kidney subcapsular rat islet transplantation.

In inbred streptozocin-induced diabetic rats, the long-term function of different endocrine pancreatic isografts was compared. Isolated islets transplanted into the portal vein showed a progressive deterioration of function over time. In contrast, islets under the kidney capsule sustained a constant long-term function controlling all clinical signs of diabetes. Recipients of kidney subcapsular islets displayed normal growth rate, peripheral serum glucose and insulin levels, and metabolic parameters. However, their functional reserve was markedly reduced as revealed by diminished glucose tolerance and reduced insulin-secreting capacity after an intravenous glucose challenge. Vascularized whole-organ pancreatic grafts with portal venous drainage led to complete normalization of all parameters determined in this study. This study showed that the long-term function of islets transplanted under the kidney capsule is superior compared with islets transplanted into the portal vein.

Animals

[Suppression of exocrine secretion does not lead to disruption of endocrine function of pancreas transplants].

The adequate management of the exocrine secretion of vascularized pancreas transplants is still controversial. Basically, the exocrine graft secretion may either be suppressed by obstruction of the pancreatic ducts or preserved by drainage into the recipient's enteric or urinary tract. In a model of isogenic pancreas transplantation in streptozotocin diabetic rats the impact of preserved versus suppressed exocrine secretion on the quality of endocrine graft function was investigated. Preservation of the exocrine secretion was accomplished by pancreaticoduodenal transplantation, while duct ligation was used to suppress the exocrine secretion. Endocrine graft function was monitored by determination of non-fasting blood glucose levels, intravenous glucose tolerance tests, peripheral insulin levels, water and food intake as well as urine and faeces production. Suppression of the exocrine graft secretion induced acinar atrophy, proliferation of pancreatic ducts, interstitial cell infiltration and fragmentation of islets of Langerhans, while drainage of the exocrine graft secretion completely preserved the architecture of the transplant. Despite the fundamental structural changes induces by exocrine suppression no deterioration of endocrine graft function was noted within the observation period of one year. Both techniques were equally effective in ameliorating the diabetic hyperglycemia, hypoinsulinemia, reduced glucose tolerance, polydipsia, polyphagia, polyuria and restored normal growth rate and general health of diabetic pancreas graft recipients. Thus it can be concluded that suppression of the exocrine secretion does not impair the quality of endocrine function of pancreas transplants.

Animals

Comparison of graft morphology and endocrine function after vascularized whole-pancrease transplantation in the rat by different surgical techniques.

Graft morphology and endocrine function following vascularized pancreas transplantation by different surgical techniques were determined in streptozotocin-diabetic rats. Eight different surgical techniques were studied. Intestinal drainage of exocrine secretion was accomplished by pancreaticoduodenal transplantation or by utilizing only a patch of the donor duodenum for duodenojejunostomy. Following pancreaticoureterostomy and pancreaticocystostomy, the graft's exocrine secretion was drained to the recipient's urinary tract. The exocrine secretion was allowed to drain freely into the recipient's peritoneal cavity following transverse or longitudinal incision of the common bile duct. Exocrine secretion was suppressed either by duct ligation or by retrograde ductal injection of prolamine. Following enteric or urinary exocrine graft drainage, the architecture of both the endocrine and exocrine pancreas was perfectly preserved. Pancreatic juice had remarkably few adverse effects on the recipient's urinary tract. Obstruction of the exocrine secretion induced atrophy of the acinar cells, proliferation of small pancreatic ducts, and a typical fragmentation of the islets of Langerhans. Prolamine was biologically degraded within 28 days. Following free intraperitoneal drainage, spontaneous suppression of the exocrine graft function occurred early after transplantation. Metabolic signs of diabetes mellitus including hypoinsulinemia, hyperglycemia, polydipsia, polyuria, and impaired glucose tolerance were completely normalized by pancreas transplantation irrespective of the surgical technique used. Despite fundamental differences in graft architecture no alteration of endocrine graft function was noted following vascularized pancreas transplantation by different surgical techniques.

Animals

Significance of portal venous drainage after whole-organ pancreas transplantation for endocrine graft function and prevention of diabetic nephropathy.

The significance of portal venous drainage after whole-pancreas transplantation both for metabolic control and development of diabetic nephropathy was investigated. Streptozotocin-diabetic inbred LEW rats received a duct-ligated pancreas graft with either systemic or portal venous drainage and were followed for up to one year. Normal and untreated diabetic rats (n=18 in each group) served as controls. Irrespective of the route of venous drainage pancreas transplants normalized the diabetic polyuria, polyphagia, and polydipsia. Growth rates and general health did not differ from normal rats. Pancreas transplantation with portal venous drainage furthermore normalized nonfasting blood glucose and peripheral insulin levels, and intravenous glucose tolerance. Pancreas transplantation with systemic venous drainage, however, was associated with peripheral hyperinsulinemia, slightly elevated nonfasting blood glucose levels, and supranormal K-values in intravenous glucose tolerance tests. Though portal venous drainage was associated with better metabolic control than systemic venous drainage, both techniques of pancreas transplantation proved equally effective to prevent the development of diabetic glomerular membrane thickening determined 6 and 12 months posttransplant.

Animals

Identical pattern of acute rejection after isolated islet and vascularized whole-pancreas transplantation in the rat.

The course of acute rejection of major histocompatibility complex (MHC)-incompatible isolated rat pancreatic islets transplanted under the kidney capsule was monitored functionally and histologically from day 1 to 10. The patterns observed were compared to those of vascularized whole-pancreas transplants with preserved and suppressed exocrine secretion. In addition the morphologic reactions after isogenic transplantation of islets or whole-pancreas transplants are described. The sequential patterns of acute rejection were found to be essentially identical in isolated islet and whole-pancreas allografts. This was also true for the process of I-A-like class II MHC antigen induction. Endocrine cell necrosis and reduced insulin content of beta cells were detected in isolated islets but not in whole-organ isografts. Thus ischemic damage may have occurred to be transplanted islets on days 1 and 2 because connections to the renal vasculature were not demonstrated before day 3. Islet cell loss was, however, functionally compensated by beta cell proliferation beginning on day 4. From the first day after transplantation, an altered spacial distribution of insulin- and glucagon-containing cells was present in islet isografts. This phenomenon was, however, not unique to islets, but also occurred in duct-ligated whole-organ isografts on days 6 to 10.

Acute Disease