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Biomedical subjects

F Saudek

Publications and source records attributed to F Saudek.

At least 37 records · Page 2Linked to original sources

The effect of bone marrow transplantation on survival of allogeneic pancreatic islets with short-term tacrolimus conditioning in rats.

OBJECTIVE: Specific immune tolerance achieved by induction of lymphocyte chimerism could reduce the need for immunosuppressive therapy in pancreatic islet transplantation. The aim of the experiment was to assess the effect of pre-treatment with donor specific bone marrow on the function of allogeneic islets under the conditions of a short-term immunosuppression. METHODS: Male Lewis-Brown Norway and female Brown Norway rats were used as donors and recipients, respectively. In all recipients diabetes was induced by streptozotocin. In Group 1, 5 animals were treated only by islet transplantation. In Group 2, 7 rats underwent islet transplantation after previous 45-day therapy with tacrolimus 1 mg/kg and hydrocortisone 2 mg/kg, which was stopped 6 days after islet transplantation. Recipients in Group 3 (n = 16) were treated as Group 2 (n = 7) and, in addition, underwent transplantation of 10(8) bone marrow cells 10 days after initiation of immunosuppressive therapy. RESULTS: In Group 1, islets were rejected after a median survival time of 11 days. In Groups 2 and 3, islet function has been demonstrated for more than 70 days in all animals. CONCLUSIONS: Short-term immunosuppressive therapy prevented islet rejection for at least 70 days. Longer follow-up period is needed to show whether peripheral microchimerism induced by bone marrow transplantation will further improve islet survival in non-immunosuppressed recipients.

Animals↗

Increased glucagon-stimulated insulin secretion of cryopreserved rat islets transplanted into nude mice.

Cryopreservation is the only available technique for long-term storage of pancreatic islets. The freezing/thawing protocol may cause considerable loss of viable islet tissue and impair its function in vivo. The aim of this study was to investigate glucose and insulin levels after transplantation of fresh and cryo/thawed rat islets. Rat pancreatic islets were isolated following intraductal collagenase injection and Ficoll gradient purification. After isolation, islets were cultured for 24 h and then either transplanted or frozen after stepwise addition of DMSO according to Rajotte et al. and stored in liquid nitrogen. After rapid thawing islets were stepwise transferred into RPMI medium and cultured for another 24 h. The recipients were athymic mice with streptozotocine-induced diabetes. Two hundred fresh (n=13) or cryo/thawed (n=15) islets were transplanted beneath the renal capsule. Glucose levels were measured for 14 days and blood samples for insulin determination were obtained 15 min after i.p. glucagon (10 mg/kg) administration on day 14. Glucose levels were normalized (<9 mmol/l) in all recipients within 3 days since transplantation. On day 14, mean fasting values+/-SE in fresh and cryo/thawed islet groups were 4.0+/-0.6 and 4.4+/-0.4 mmol/l, respectively (P>0.05). Fasting insulin levels were higher in the cryo/thaw than in the fresh islet group (1.67+/-0.33 vs 0.57+/-0.13 ng/ml; P<0.01). Post-glucagon levels did not differ significantly (1.45+/-0.24 vs 0.86+/-0.24 ng/ml; P=0.06). While glucagon significantly increased insulin levels (P<0.01) in the fresh islet group, no change in insulin levels was observed (P>0.05) in the cryo/thaw group. Immunohistochemical staining demonstrated fragmentation of viable islet tissue which was more apparent in the cryo/thaw group. We conclude that in a short-term study cryo/thawed rat islets produce higher insulin levels than fresh islets transplanted into nude mice. This may be due to better islet survival or loss of feed-back regulation.

Animals↗

[Conversion of drainage of a pancreatic transplant from the urinary bladder to the intestine in a recipient].

The most frequently used surgical technique in transplantations of the pancreas is to connect the duodenum of the graft with the urinary bladder of the recipient. Introduction of this method led during the last five years to marked improvement of results. On the other hand duodenocystoanastomosis is a frequent cause of metabolic and urological complications in patients after transplantation. The authors present the case-record of a female patient after combined transplantation of the pancreas and kidney where surgical conversion of the drainage of pancreatic juice from the urinary bladder to the gut was necessary.

Anastomosis, Surgical↗

Effect of successful combined renal and pancreatic transplantation on diabetic retinopathy.

UNLABELLED: The treatment of diabetic retinopathy (DR) is one of the most challenging problems in ophthalmology. The possibility of modulating DR by successful combined kidney and pancreas transplantation thus holds an attractive promise for the ophthalmologist. From June 1983 until April 1997, a total of 86 combined kidney and pancreas transplantation procedures were performed at the Prague-based Institute for Clinical and Experimental Medicine. All recipients are on close follow-up in terms of their ophthalmic status. However, evaluation of the effect of transplantation is problematic because of the advanced status of DR prior to the procedure. We divided the transplant recipients into two groups according to type of transplantation. In Group I (segmental transplantation), proliferative DR was present in 100% eyes, 70% had undergone vitrectomy, and there were 21% of blind eyes. All eyes had been treated by laser. In this group, long-term stabilization of the finding was observed in three patients. In Group II (whole pancreas transplantation), proliferative and non-proliferative DR was diagnosed in 86% and 14%, respectively. There were 12% of blind eyes, and 70% had been treated by laser prior to transplantation. After a successful transplantation, stabilization was found in 60%, improvement in 18%, and deterioration in 22% of eyes in this group. The stabilization and improvement can be explained by subsequent normoglycemia (HbAlc 5.6%). By contrast, we were unable to provide a satisfactory explanation for the deterioration and progression of these findings. While the effect of immunosuppression on DR remains unclear, it obviously accelerates the existing cataract. CONCLUSION: Successful combined transplantation has a beneficial effect on DR and is worthwhile even for patients at the end stage on account of its beneficial psychosocial effect and prevention of dolorous glaucoma. However, many effects of the procedure on the eye of diabetics remain to be identified in future studies.

Adult↗

[Metabolic sequelae of pancreatic transplantation using two different surgical techniques].

BACKGROUND: By transplantation of the pancreas in diabetics type 1 long-term-term independence on exogenous insulin can be achieved. The extent of normalization of the carbohydrate metabolism can depend on the applied surgical technique. The objective of the submitted work was to compare indicators of compensation of diabetes one year after combined transplantation of the kidney and pancreas, using the method of transplantation of a segment of the pancreas with obliteration of the pancreatic duct by a polymer and the method of transplantation of the whole pancreas with drainage of the pancreatic duct into the urinary bladder. METHODS AND RESULTS: The authors examined two groups of recipients, 13 subjects each with full function of the pancreatic graft one year after transplantation where a combined transplantation of the kidney and pancreatic segment (group SP) had been performed or of the kidney and whole pancreas (group CP). The authors investigated the blood sugar level, glycated haemoglobin, intravenous glucose tolerance test, free insulin level and C-peptide as well as some indicators of the lipid metabolism and acid base balance. In both groups normal blood sugar levels were achieved, though the mean values in the course of the day were higher in group SP than in group CP (mean +/- SE 5.48 +/- 0.11 as compared with 4.98 +/- 0.09; p < 0.01). Glycated haemoglobin declined in group SP from the pretransplantation value of 9.31 +/- 0.09 to 6.40 +/- 0.10% and in group CP from 9.49 +/- 0.15 to 4.92 +/- 0.08%. In group CP the glycated haemoglobin after transplantation was significantly lower (p < 0.01), similarly as the coefficient of glucose assimilation (1.83 +/- 0.03 as compared with 1.25 +/- 0.15; p < 0.05). Indicators of the acid base balance did not differ. Recipients in group CP were however permanently treated with bicarbonate. CONCLUSIONS: With both transplantation method it is possible to achieve compensation of diabetes close to normal. The carbohydrate tolerance is however better after transplantation of the whole pancreas.

Adult↗

[Use of the circular stapler for duodenal-cystic anastomosis in pancreas transplantation].

The number of combined transplantations of the pancreas and kidney in type I diabetics with chronic renal failure is increasing every year. The authors present their experience with a new technique of duodenocystostomy during this transplantation. The use of a circular stapler to create the duodenocystoanastomosis can hasten the surgical procedure and reduce at the same time the risk of development of a pancreatic fistula.

Anastomosis, Surgical↗

[Large-scale isolation of islets of Langerhans in dogs and human].

BACKGROUND: Transplantation of isolated islets of Langerhans is a perspective method of treating type 1 diabetes. The first prerequisite for its implementation is to obtain sufficient amounts of vital islets. The objective to the authors' experiments was to introduce a method of massive isolation of islets of Langerhans from dogs which would serve as a model pro obtaining islets of Langerhans from humans and would permit to use them in future in clinical practice. METHODS AND RESULTS: After excision of the dog pancreas the authors injected into the ducts a 1% collagenase solution and the tissue was deposited in a specially developed semi-automatic isolation system which consisted of a vibrating isolation chamber in which an isolation solution with controlled temperature circulated. As soon as the islets started to be released, the system was cooled and the disintegrated tissue was collected. The islets were separated from the acinar mass by centrifuging in a ficoll mass gradient. The islet function was tested by transplantation to athymic diabetic mice. A total of 15 isolations of dog islets was performed, incl. 5 which were evaluated quantitatively. In a similar way twice isolation from a human cadaverous pancreas was implemented. On average 6336 +/- 745 (+/-SD) purified dog islets were obtained. Their function was tested by normalization of the blood sugar after transplantation to diabetic mice. The authors obtained also vital highly purified human islets. CONCLUSIONS: The authors developed a method of isolation of dog and human islets of Langerhans which makes it possible to obtain sufficient amounts of vital islet tissue which could be used for transplantation. A further task will be to standardize the process and adjust it to hygienic norms essential for clinical use.

Animals↗

[Long-term treatment of diabetes with transplantation of a pancreatic segment].

BACKGROUND: Successful transplantation of the pancreas is at present the only way how to ensure on a long-term basis an almost physiological regulation of the carbohydrate metabolism in type 1 diabetics. So far it is, however, indicated mainly in patients with already advanced microangiopathy where at the same time also renal transplantation is planned and long-term experience is so far limited. The objective of the submitted paper is to report on the development of metabolic compensation and its impact on the development of microangiopathic changes in type 1 diabetics where the complete function of both grafts persisted more han five years. METHODS AND RESULTS: From a group of 34 combined transplantations of a pancreatic segment with an obliterated duct and a kidney, implemented in 1983-1988 in the Institute of Clinical and Experimental Medicine, a group of nine type 1 diabetics was followed up where the independence on exogenous insulin and haemodialyzation treatment persisted for or still persists for 5-8 years. After annual intervals the blood sugar level was examined, the intravenous glucose to tolerance test, free insulin levels, glycosylated haemoglobin, an ophthalmological and neurological examination was made, incl. the peripheral and autonomous system, and by means of a standard questionnaire the quality of life before and after transplantation was assessed. In all examined subjects normal blood sugar levels were recorded. The fasting insulin levels in transplant recipients were higher than in healthy subjects (22 vs. 10.2 microU/ml, p < 0.01) while in the course of the blood sugar curve corresponding levels were recorded. Glycosylated haemoglobin remained after 5 years quite or almost normal (4.2-7.2%). The coefficient of glucose assimilation after 5 years varied in the range from 0.7 to 1.9% min. Hypoglycaemic states were not recorded. In none of the recipients in the course of the investigation deterioration of the ophthalmological finding was observed and in three patients improvement was recorded. Symptoms of somatic polyneuropathy improved in all patients but signs of vegetative neuropathy remained unchanged. In all recipients psychic, physical and social rehabilitation as well as the general quality of life improved markedly. CONCLUSIONS: Although the group of investigated patients is so far small, the authors provided evidence that combined transplantation of the pancreas and kidney can influence in a very favourable way the quality of life and development of microangiopathic complications. As the success rate of transplantations of the pancreas in increasing and the risk of surgical complications is declining due to improving surgical techniques, the authors conclude that combined transplantation of the pancreas and kidney is at present the optimal therapeutic procedure in type 1 diabetics with chronic renal insufficiency and that indication for transplantation of the pancreas could be moved to earlier stages of diabetes when it would be possible to influence the development of diabetic microangiopathy more favourably.

Adult↗

[Treatment of a pancreatic fistula after pancreatic transplantation using the obliterative technic].

The authors present the case-record of a patient after combined transplantation of the pancreas and kidney who developed a chronic duodenocutaneous fistula. The case was resolved by elimination of the duodenocystoanastomosis of the transplanted pancreas and by obliteration of the pancreatic duct of the graft by a polymer. One year after surgery the patient has no complaints and the function of both transplanted organs is satisfactory.

Adult↗