PubMed Health⌕ Search

Biomedical subjects

L Bühler

Publications and source records attributed to L Bühler.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Recurrence of diabetic disease following pancreas transplantation].

Type-I diabetes is considered an autoimmune disease, directed against pancreatic beta cells. Diabetes recurrence after pancreas transplantation is theoretically possible, and some cases have been reported after isotransplantation of segmental grafts in HLA-identical twins, where no rejection phenomenon is possible and where no immunosuppression was used. Diabetes recurrence has never been observed in a cadaveric allograft recipient, probably because immunosuppression efficiently blocks the autoimmune mechanism. Autoreactivity against beta cells exists life-long in type-I diabetes, and the immunosuppression used after transplantation becomes an advantage y preventing the recurrence of the disease.

Autoimmune Diseases↗
PubMed1995

[Islets of Langerhans allografts in the pig: initial results].

Islet of Langerhans transplantation represents a promising treatment of diabetes. Use of porcine islets for xenotransplantation could offer a solution to shortage of organ donors. However, isolation of pig islets remains a real challenge because of their marked fragility. Using a modified automated method for islet isolation, we performed 10 intraportal islet allografts in pigs. Surgically pancreatectomized pigs were transplanted with purified islet preparations pooled from pancreases of 3 donors (slaughter-house pigs, age 5-8 months). Six recipients were not immunosuppressed and four received an immunosuppressive treatment of Cyclosporine and Azathioprine. In the first group (non-immunosuppressed recipients), insulin secretion was observed for a mean of 4.8 days after transplantation. In the second group (with immunosuppressive treatment) the recipients sustained an insulin secretion for 6-9 days. However, in both groups liver biopsies showed signs of acute rejection and destruction of the transplanted islets. Pig islet allotransplantation, using as recipients surgically pancreatectomized pigs, can be considered as a suitable model to assess the functional results of mass islet isolation. We were able to reverse diabetes transitory in a large animal, by transplantation of purified pig islet preparations. However, even when an immunosuppressive treatment was administered to the recipients, rejection seemed to represent an important factor in the functional outcome of the islet grafts.

Animals↗
PubMed1995

[Mechanism of rejection of islet of Langerhans xenografts].

For immediately vascularised xenografts, the presence of preformed antibodies associated with the activation of the complement induces a hyperacute humoral rejection in discordant combinations. For neovascularised xenografts, such as the islets of Langerhans, the absence of an initial vascularisation prevents the acute humoral rejection and there is some evidence to suggest that the rejection is cell mediated. To analyse the influence of species response to cellular transplantation, we compared the functional outcome and the immunohistochemical analysis of concordant and discordant xenotransplated islets with allotransplanted islets of Langerhans. In the concordant xenotransplantation experiment, rat (Sprague Dawley) purified islets (N = 600) were transplanted under the kidney capsule of streptozotocin diabetic mice. In the discordant experiment, purified human islets (N = 1000), in the allotransplantation model Balb mouse islets (N = 600) were transplanted under the kidney capsule of C57BL/6 mice. Daily blood glucose levels were monitored until rejection occurred (blood glucose > 11 mMol/L) and kidney biopsies were taken every second day for immunohistological examination. In allotransplanted mice, rejection occurred after a mean of 15 +/- 4 days, in concordant xenotransplanted mice after a mean of 10 +/- 3 days and in the discordant xenotransplanted mice after a mean of 8 +/- 1 days. The immunohistological analysis showed in both xenotransplantation models a deposit of IgM and C3 surrounding the grafted cells, starting at day 1 and persisting until rejection, associated with the presence of Mac-1 positive cells. The intensity of the humoral response was moderate to important in the concordant group, but very strong and unchanged until rejection in the disconcordant group. An invasion with CD4+ and CD8+ cells started between day 4 and 6 in both groups, progressively increasing until rejection. In the allotransplantation model, no humoral response was detectable and the cellular response started between day 10 and 12 after transplantation. We conclude, that a cellular response is involved in the rejection process of both concordant and discordant xenotransplanted islets of Langerhans. Compared to an allotransplantation model, the humoral response does not destroy the function of transplanted islets, but could trigger or accelerate the cell-mediated response.

Animals↗
PubMed1994

[Prevention of viral recurrence following liver transplantation for post-hepatitis B and B-delta cirrhosis].

The incidence of recurrence of hepatitis B virus (HBV) following orthotopic liver transplantation (OLT) is as high as 80% when no attempt at prevention has been considered. HBV reinfection is associated with the reappearance of hepatitis B surface antigen (HBsAg) and HBV DNA in serum and, in most cases, with rapid severe graft damage. Immunoprophylaxis using polyclonal anti-HBs immunoglobulins reduces the risk of recurrence but this long-term therapy remains highly expensive. In this report, we use fresh frozen plasma (FFP) with high titers of anti-HBs immunoglobulins in an attempt to reduce HBV recurrence. From July 1987 to September 1993, 11 patients underwent OLT for HBV-related liver disease (18% of our OLT patients). FFP were administered to 6 patients continually for 7 to 46 months. Only one patient, under long-term immunosuppressive treatment before OLT, was reinfected 7 months after OLT. Rapid development of graft failure was observed with histologic manifestations of a fibrosing cholestatic hepatitis, leading to patient death after 12.5 months with concomitant bacterial infection. In this protocol, the rate of reappearance of HBsAg was 17%, a figure which can be favorably compared with other reports. All patients were subsequently tested for HCV and HIV and remained negative. In conclusion, FFP with high titers of anti-HBs immunoglobulins is at least as effective as polyclonal anti-HBs immunoglobulins in reducing the rate of HBV recurrence following OLT. The estimated cost of this new immunoprophylaxis method is less than 10% of the classical prophylaxis based on purified human polyclonal anti-HBs immunoglobulins.

Graft Rejection↗
PubMed1993

[Islet of Langerhans transplantation in humans].

Islet of Langerhans transplantation is an alternative to whole pancreas transplantation for type I diabetic patients, in whom exogenous insulin therapy has not prevented the occurrence of systemic complications. Thanks to a new isolation technique of human islets, 45 patients have been transplanted worldwide since 1988, of whom only 7 have become totally insulin-independent. Rejection and quality of the islet preparations are problems which remain to be solved. Autotransplantation of islets has been proposed in patients undergoing a pancreatectomy for benign disease. The present report concerns two of our patients who had a pancreatectomy with islet autotransplantation. Both patients are insulin-independent 3 and 11 months postoperatively, with satisfactory metabolic tests. Islet autotransplantation can be proposed when pancreatectomy for non-malignant disease is performed. This method may prevent the development of insulin-dependent diabetes, known to be particularly labile. Because of the sophisticated technical procedures required, human islet isolation is at present only performed in a small number of medical centers and still is in the field of medical experimentation.

Adult↗
PubMed1993

Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor.

A complementary DNA for a glucagon-like peptide-1 receptor was isolated from a human pancreatic islet cDNA library. The isolated clone encoded a protein with 90% identity to the rat receptor. In stably transfected fibroblasts, the receptor bound [125I]GLP-1 with high affinity (Kd = 0.5 nM) and was coupled to adenylate cyclase as detected by a GLP-1-dependent increase in cAMP production (EC50 = 93 pM). Two peptides from the venom of the lizard Heloderma suspectum, exendin-4 and exendin-(9-39), displayed similar ligand binding affinities to the human GLP-1 receptor. Whereas exendin-4 acted as an agonist of the receptor, inducing cAMP formation, exendin-(9-39) was an antagonist of the receptor, inhibiting GLP-1-induced cAMP production. Because GLP-1 has been proposed as a potential agent for treatment of NIDDM, our present data will contribute to the characterization of the receptor binding site and the development of new agonists of this receptor.

Amino Acid Sequence↗
PubMed1993

Hepatic function during general hypothermia in the pig: assessment by aminopyrine breath test.

We investigated the influence of pre-harvesting general hypothermia on liver metabolic activity by means of Aminopyrine Breath Test (ABT). This study was conducted in pigs which were anesthetized, curarised and cooled on an ice bed. Each animal received labelled aminopyrine and 14CO2 in expired air was measured between 37.5 and 25.5 degrees C. The liver metabolic activity at 31.5 degrees C represents 53.3% of the normothermic value. At 25.5 degrees C, this activity is reduced by 75.1%. The mean decreasing rate is 6.2%/degrees C for a fall in temperature of 12 degrees C. A change of slope occurred at 31.5 degrees C. The first decreasing rate is 7.47 +/- 1.62%/degrees C and the second one is 4.48 +/- 2.27%/degrees C. Thus, use of general hypothermia during liver harvesting should improve the quality of organ preservation: the important reduction of metabolism should decrease the oxygen debt resulting from anaerobic cold perfusion.

Aminopyrine↗
PubMed1993

[Transplantation of islets of Langerhans in man].

Islet of Langerhans transplantation is an alternative to whole pancreas transplantation for type I diabetic patients, in whom exogenous insulin therapy has not prevented the occurrence of systemic complications. Thanks to a new isolation technique of human islets, 45 patients have been transplanted worldwide since 1988, of whom only 7 have become totally insulin-independent. Rejection and quality of the islet preparations are problems which remain to be solved. Autotransplantation of islets has been proposed in patients undergoing a pancreatectomy for benign disease. The present report concerns two of our patients who had a pancreatectomy with islet autotransplantation. Both patients are insulin-independent 3 and 11 months postoperatively, with satisfactory metabolic tests. Islet autotransplantation can be proposed when pancreatectomy for non-malignant disease is performed. This method may prevent the development of insulin-dependent diabetes, known to be particularly labile. Because of the sophisticated technical procedures required, human islet isolation is at present only performed in a small number of medical centers and still is in the field of medical experimentation.

Adult↗
PubMedDate not supplied

Treatment of gastrointestinal hemorrhage.

BACKGROUND: We assessed the value of selective arteriography in the diagnosis and management of acute gastrointestinal hemorrhage. METHODS: We reviewed the records of 107 consecutive patients who had gastrointestinal hemorrhage and underwent selective arteriography between January 1992 and October 2003: 10 had upper gastrointestinal bleeding, 79 had lower gastrointestinal bleeding, and 18 had varicose bleeding with portal hypertension. Selective embolization was attempted in 15 patients to obtain hemostasis. Angiographic findings were reviewed and prospective reports were compared with the final diagnosis and outcome. RESULTS: Of 129 angiographic studies, 36 correctly revealed the bleeding site and 93 were negative. Extravasation was seen in 24 cases at the level of stomach (n = 2), duodenum (n = 1), small bowel (n = 5), or colon (n = 16). Indirect signs of bleeding sources were identified in 12 patients (stomach in one, small bowel in four, large bowel in four, liver in three). Transcatheter embolization induced definitive hemostasis in 11 of 15 patients (73%), namely in the stomach (n = 2), small bowel (n = 3), colon (n = 7), and liver (n = 3). Three patients required surgery after embolization. CONCLUSION: Abdominal arteriography may localize gastrointestinal bleeding sources in approximately one-third of cases. Selective embolization may provide definitive hemostasis in most instances.

Adolescent↗