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T Berney

Publications and source records attributed to T Berney.

At least 19 recordsLinked to original sources
PubMed2004

Immunosuppression for pancreatic islet transplantation.

Protocols for islet transplantation have to take into account the diabetogenicity/islet toxicity of the immunosuppressive agents, namely corticosteroids and calcineurin inhibitors, most notably tacrolimus. The development by the Edmonton group of a sirolimus-based, steroid-free, low-tacrolimus regimen was a significant breakthrough that allowed the rate of insulin independence after islet transplantation to increase from 13% to 80% at 1 year. Drawbacks include the side effects of sirolimus and the reduction in insulin independence to 50% at 3 years, the latter being attributed to prolonged tacrolimus exposure. Currently explored alternatives to tacrolimus include cyclosporine, mycophenolate mofetil, and the novel agent FTY 720. Perspectives for the near future involve the achievement of "prope tolerance" by strategies using lymphocyte-depleting antibodies (anti-thymocyte globulin, campath-1H, hOKT3gamma1 [ala,ala]), or costimulatory blockade (anti-CD154 mAbs, CTLA4-Ig).

Cyclosporine↗
PubMed2004

Five-year follow-up after pediatric living related small bowel transplantation between two monozygotic twins.

Two 13-year-old monozygotic twins were used for living related small bowel transplantation (SBTx). The recipient presented with short gut syndrome secondary to complicated abdominal surgery. The indication for SBTx was based on a failure to thrive and a poor tolerance of TPN. The donor was an identical twin, as demonstrated by skin graft acceptance, which allowed performance of SBTx without immunosuppression. Growth charts were used to follow intestinal absorption functions and body composition. The donor was used as a control for the recipient. The recipient, who was transplanted with 160 cm of donor ileum, was discharged on postoperative day 62 on a regular diet. Before SBTx the recipient was 10 kg lighter in body weight than the donor, a gap that was progressively reduced over the follow-up period. A height deficit of 3 cm reversed within 1 year after SBTx. A 10-kg deficit in fat-free body mass was completely extinguished within 18 months. By 18 months posttransplant, recipient serum albumin and prealbumin were normal and comparable to donor values. d-Xylose absorption in the recipient remained lower than that in the donor. Within 6 months fecal fat excretion normalized in the recipient. d-Xylose absorption and fecal fat excretion were always within a normal range in the donor.

Adolescent↗
PubMed2004

Short-term immunosuppression reduces fibrotic cellular infiltration around barium-M-alginate microbeads injected intraportally.

INTRODUCTION: One of the major barriers affecting the viability of encapsulated islets is pericapsular fibrotic infiltration (PFI). This study aimed to design strategies to reduce PFI around intraportally injected alginate microbeads. METHODS: Empty, highly purified, barium-M-alginate microbeads (400 microm) were injected intraportally into Lewis rats (3000 beads/rat). Rats (n = 9/group) were treated daily with either rapamycine (RAPA; 1 mg/kg/d p.o.), tacrolimus (TAC; 2 mg/kg/d p.o.), a combination of both, or gadolinium-chloride (GdC13, 20 mg/kg/d i.v., at day -1 and day +4). Treatment was discontinued at 10 days. Three rats/group were sacrificed at 3, 7, and 42 days after transplantation. Cellular composition of PFI was evaluated by immunohistochemistry. Severity of the reaction to the beads was determined by measuring the thickness of PFI on histology. RESULTS: The main cellular components of PFI in the liver were macrophages and myofibroblasts. There was a significant (P <.05) reduction in the thickness of PFI in all treated groups, even 6 weeks after transplantation. Encapsulated rat islets showed excellent insulin response to glucose in vitro, with a stimulation index of 3.6 +/- 2.0. CONCLUSION: Combination of highly purified alginate with short-term immunosuppression reduces fibrotic overgrowth around microbeads injected intraportally.

Alginates↗
PubMed2004

Morbidity associated with intraportal islet transplantation.

INTRODUCTION: Complications associated with intraportal islet infusion have been reported. In this study, we analyzed the relationship between occurrence of complications and islet preparation characteristics/infusion technique. METHODS: We reviewed all intraportal islet infusions from 1992 to 2003. RESULTS: Sixteen islet autotransplantations were performed without infusion-related complications. The tissue volume injected was 13 +/- 11 mL with basal and peak portal pressures of 13 +/- 6 and 21 +/- 6 mm Hg. Seventy-seven intraportal islet allotransplantations were performed in 51 patients. Fifteen islet infusions were done by laparotomy during simultaneous islet/kidney transplantation without complication. Among 62 percutaneous transhepatic injections, nine complications (two portal branch thrombosis and seven intra-abdominal hemorrhages) were recorded. Rise in portal pressure was related to tissue volume injected (P <.05). Basal and peak portal pressures were 14 +/- 5 and 18 +/- 6 mm Hg in uncomplicated infusions, 14 +/- 9 and 18 +/- 9 mm Hg in the thrombosis group, and 13 +/- 7 and 18 +/- 5 mm Hg in the hemorrhage group (P >.05). Complications occurred only after percutaneous islet infusion (P <.03). CONCLUSIONS: Procedure-related morbidity of intraportal islet infusion is low. Changes in portal pressure are related to volume of tissue injected but do not seem to be associated with the occurrence of complications. Percutaneous infusion is a minimally invasive procedure, but this advantage must be balanced by the higher rate of complications.

Hemorrhage↗
PubMed2004

Serva collagenase NB1: a new enzyme preparation for human islet isolation.

INTRODUCTION: Advances in the rate of success of human islet isolation are due in part to the availability of new purified enzyme blends. In this study we evaluated a new enzyme preparation composed of a highly purified collagenase that can be reproducibly blended with predetermined amounts of separately packaged neutral protease. METHODS: Nine human islet isolations were performed with collagenase NB1 supplemented with neutral protease (Serva Electrophoresis GMbH, group I). Yields, purity, morphology, in vitro function and islet cell apoptosis were assessed. The results were compared to those of nine human islet isolations performed with Liberase (Roche, group II) and matched for donor age, BMI, and circumstances of death. RESULTS: Islet yields were similar in both groups. However, islet equivalents (IE) per gram of pancreas and IE number to islet number were higher in group I (P <.05). Stimulation indices after insulin response to glucose (static incubation) were similar in both groups. Islet cell apoptosis rate was statistically significantly lower in group I. Islet morphology was significantly improved in group I with a higher proportion of intact islets. CONCLUSION: This new enzyme preparation (collagenase NB1 with neutral protease adjunct) was as effective as Liberase in terms of islet yields and function. Islet morphology was improved and rate of islet cell apoptosis was lower with this new collagenase. The absence of lot-to-lot variability in terms of neutral protease to collagenase ratio makes collagenase NB1 a promising enzyme for human islet isolation.

Body Mass Index↗
PubMed2004

Optimization of neutral protease to collagenase activity ratio for islet of Langerhans isolation.

AIM: The optimal neutral protease to collagenase activity ratio has not been determined for islet isolation. We evaluated a new highly purified collagenase that can be blended with predetermined amounts of neutral protease (NP). METHODS: Islets were isolated from 7 groups of Sprague-Dawley rats. In group I, collagenase type XI (Sigma) at 2 mg/mL, and, in group II, Liberase at 0.6 mg/mL (2.4 PZ- U/mL; Roche) were used as controls. In groups III to VII, collagenase NB1 0.6 mg/mL (2.4 PZ-U/mL; Serva Electrophoresis) was used with increasing amounts of added NP. The NP to collagenase activity ratio (DMC-U/PZ-U) increased from 0.5% in group III to 2.0% in group VII. RESULTS: Mean islet equivalent (IE) yields per rat were 1367, 1755, 597, 895, 1712, 1043, and 905 in groups I to VII. IE yields were maximal at DMC-U/PZ-U = 1.2%. Islet morphology was influenced by NP concentration with decreasing numbers of trapped islets and increasing numbers of fragmented islets as NP contents increased. Cytokine release, islet cell apoptosis, and in vitro function were significantly better in groups III to VII as compared with groups I and II. CONCLUSION: NP is a crucial additive to collagenase for islet isolation. Optimization of the NP to collagenase activity ratio (1.2% in this model) improves yields and morphology after islet isolation.

Animals↗
PubMed2004

Microbial surveillance during human pancreatic islet isolation.

OBJECTIVES: The study aim was to investigate the microbiological safety of islet isolation and transplantation. MATERIALS AND METHODS: Between 1996 and 2002, prospective microbiological screening was performed on all pancreata procured for islet transplantation. Pancreas transport media and postpurification preparations were screened for microbiological contamination. Prior to isolation, pancreata were washed with either Hanks solution (group I, n = 170) or decontaminated with antiseptic and antimicrobial drugs (group II, n = 45). RESULTS: Microbiological contamination of the pancreas preservation media was shown in 62%. Analysis of the contaminants showed 74% gram-positive, 21% gram-negative organisms, and 5% fungi. The donor condition or procurement center did not influence the contamination rate. Longer pancreas transport duration was significantly associated with bacterial contamination (P <.05). In group I, 16 (9.4%) of 170 islet preparations presented microbial contamination at the end of the isolation procedures. Gram-positive organisms were present in 10 (6%), gram-negative organisms in 4 (2.4%), and fungi in 2 (1.2%) preparations. Four islet preparations (2.4%) from pancreata with noninfected transport medium were positive on postpurification cultures, all with gram-positive organisms. In group II, only 2 of 45 islet preparations (4.4%) presented microbial contamination at the end of the isolation process. CONCLUSIONS: The rate of microbial contamination during pancreas procurement and transport is high. Significant contaminants present when beginning islet isolation become undetectable by the conclusion of isolation. Diminishing the bio-burden by pancreas decontamination reduces the risk of contamination of the final islet preparation.

Animals↗
PubMed2004

Islet autotransplantation for the prevention of surgical diabetes after extended pancreatectomy for the resection of benign tumors of the pancreas.

OBJECTIVE: The objective of this article is to report a single-center experience with islet autotransplantation after extensive pancreatic resection for benign tumors of the pancreas. MATERIALS AND METHODS: Seven patients underwent extensive left pancreatectomy for benign lesions located at the neck of the pancreas. Once an unequivocal diagnosis of a benign nature was ascertained, the rest of the specimen was processed and the unpurified pancreatic digest was infused into the portal vein. The results were compared with those of 8 autotransplantations performed for chronic pancreatitis over the same period. RESULTS: Tumors were 4 cystadenomas, 2 insulinomas and 1 neuroendocrine tumor. Mean islet yields were 275,000 islet equivalents (IEQ) versus 129,000 in chronic pancreatitis (P =.04) or 6700 IEQ/g of tissue versus 1900 (P =.002), resulting in transplantation of 4200 IEQ/kg body weight vs 2150 in chronic pancreatitis (P =.03), respectively at 4-month to 7.5-year follow-up, all patients are alive and 6 of 7 are off insulin. All patients off insulin after at least 1 year currently have a normal IVGTT, with K values ranging between -1.19 and -2.36 (normal < -1.00). All patients, including 1 on insulin, display positive basal and glucagon-stimulated C-peptide levels. CONCLUSIONS: Compared with chronic pancreatitis tissue resected for benign tumors is more likely to achieve good islet yields, and thus insulin independence after autotransplantation. Islet autotransplantation should be considered when extensive pancreatectomy is required for resection of a benign tumor, and only if the benign nature of the lesion is demonstrated unequivocally.

Aged↗
PubMed2004

Islet of Langerhans allogeneic transplantation at the University of Geneva in the steroid free era in islet after kidney and simultaneous islet-kidney transplantations.

AIMS: We report a single-center experience of islet allogeneic transplantation in islet after kidney (IAK) and simultaneous islet-kidney (SIK) type 1 diabetic recipients using a steroid-free immunosuppressive regimen. METHODS: Eight patients received 12 islet infusions in 5 IAK and 3 SIK procedures. Median age was 51 years (range, 30-58 years) with a male:female ratio of 2:6. IAK was considered only for patients with a stable kidney function and a creatinine clearance level >60 mL/min. SIK was considered for patients with a counterindication for simultaneous kidney-pancreas transplantation. Immunosuppression was based on sirolimus/tacrolimus combined with daclizumab induction. Two consecutive infusions of >5000 islet equivalents (IEQ)/kg were planned. RESULTS: Five patients completed the transplantation course, whereas 3 patients received only 1 islet infusion. All patients have functional grafts (C-peptide >166 pmol/L) at 6-month median follow-up. Of 5 patients who completed their transplantation course 4 became insulin independent. HbA1c and fructosamine decreased over time, showing improved metabolic control. Severe adverse events were observed in 4 patients. One SIK patient died after OKT-3 treatment of severe kidney rejection. CONCLUSIONS: The Edmonton immunosuppressive protocol can be applied for patients undergoing either IAK or SIK procedures, with a high rate of graft function and insulin independence. Morbidity is higher than among patients undergoing solitary islet transplantation for type 1 brittle diabetes.

Adult↗
PubMed2004

Urinary compounds in autism.

BACKGROUND: Although earlier claims to identify specific compounds in the urine of people with autism had been discredited, it was subsequently suggested that there might be biochemical characteristics that were specific to early childhood, particularly in those who also did not have a severe degree of intellectual disability This study was to establish whether autism might have a distinctive chromatographic profile on urinary analysis. METHOD: Thirty-four prepubertal boys with autism were matched with two groups of boys without autism--one on ability and chronological age and the other on chronological age alone, being within the normal range of ability. Laboratory analysis of their urine samples was carried out blind as to the clinical diagnosis. RESULTS: The analysis correctly identified 53% of the autism group as against misidentifying 33% and 18% of the other two groups. When children with a severe learning disability (both with and without autism) were excluded from the comparisons, the laboratory then identified 77% of the 13 boys left in the autism group and misidentified 8% and 18% of the other two groups. CONCLUSIONS: The results would support the idea of a biological marker in prepubertal children and that it may be absent in, or obscured by the presence of severe LD.

Autistic Disorder↗
PubMed2004

Pioglitazone and sodium salicylate protect human beta-cells against apoptosis and impaired function induced by glucose and interleukin-1beta.

Decreased functional beta-cell mass in type 1 and type 2 diabetes is due to beta-cell apoptosis and impaired secretory function suggested to be mediated, in part, by immune- and/or high-glucose-induced production of IL-1beta acting through the nuclear factor kappaB (NFkappaB)/Fas pathway. The aim of this study was to determine whether two drugs believed to block NFkappaB activation, the thiazolidinedione (glitazone) pioglitazone and the nonsteroidal antiinflammatory drug sodium salicylate, can protect human beta-cells against the toxic effects of IL-1beta and high glucose in vitro. Human islets were maintained in culture 2-4 d at 100 mg/dl (5.5 mm) glucose with or without (control) IL-1beta or at 600 mg/dl (33.3 mm) glucose. IL-1beta and 600 mg/dl glucose increased beta-cell apoptosis and abolished short-term glucose-stimulated insulin secretion. Both drugs protected partially against loss of glucose-stimulated insulin secretion and prevented completely increased apoptosis caused by IL-1beta or 600 mg/dl glucose. IL-1beta secretion from islets was increased by 4-d culture at 600 mg/dl, and this was blocked by pioglitazone. Both drugs prevented activation of beta-cell NFkappaB by high glucose. Pioglitazone and sodium salicylate thus protect human islets against the detrimental effects of IL-1beta and high glucose by blocking NFkappaB activation and may therefore be useful in retarding the manifestation and progression of diabetes.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Sirolimus therapy in orthotopic liver transplant recipients with calcineurin inhibitor related chronic renal insufficiency.

UNLABELLED: Calcineurin inhibitor-related renal toxicity affects patient and graft survival in transplant recipients. Our clinical experience has revealed sirolimus to be an effective agent in treating renal insufficiency related to calcineurin inhibitor toxicity. METHODS: We performed a retrospective review of the medical records of OLT recipients suffering from chronic renal insufficiency and treated with sirolimus at the University of Miami. RESULTS: Fourteen patients (nine men and five women) of mean age 57 years who had been treated with tacrolimus for at least 30 days were converted to sirolimus after developing nephrotoxicity. Mean creatinine clearances collected on day 0, 30, 60, and 90 after conversion were 40.1 mL/min, 49.6 mL/min, 53.9 mL/min, and 51.4 mL/min, respectively. Episodes of acute cellular rejection were not increased during the sirolimus conversion. CONCLUSION: This retrospective review suggests that OLT patients suffering from tacrolimus-related renal insufficiency successfully converted to sirolimus may benefit from this therapy.

Creatinine↗
PubMed2003

Islet of Langerhans transplantation for the treatment of type 1 diabetes.

Islet of Langerhans transplantation is gaining recognition as a therapy for type 1 diabetes. The procedure involves enzymatic digestion of the pancreatic tissue, purification of the islets from the exocrine tissue, infusion of the islets into the portal vein and implantation in the liver. Until 1999, and overall rate of insulin independence of 14% at one year was reported in the International Islet Transplant Registry. The results of the "Edmonton protocol" since 2000 were a breakthrough in the field, with reports of 80% insulin independence at 1-year after solitary islet transplantation in non uremic patients with brittle type 1 diabetes. A rapamycin-based, steroid-free, islet-sparing immunosuppressive regimen was designed and the problem of the insufficient islet mass was tackled by sequential infusions of islets isolated from at least two pancreatic. The University of Geneva has been involved in clinical islet transplantation since 1992, and has performed 51 allogeneic and 17 autologous. Twenty-one patients have been transplanted in Geneva since 2002. They were five solitary islet transplants, 14 islet after kidney transplants and two simultaneous islet-kidney (SIK) recipients. Insulin independence was achieved in 67%.

Diabetes Mellitus, Type 1↗
PubMed2003

Four year nutritional follow up after living related small bowel transplantation between monozygotic twins.

While small bowel transplantation (SBTX) may allow parenteral nutrition independence in the case of short bowel syndrome, its effects on body composition and growth are unclear. For the first time, a paediatric living related SBTX was performed between monozygotic twins. This case report describes their four year nutritional follow up. The 13 year old recipient and his healthy brother underwent measurements of body composition by 50 kHz bioimpedance analysis and bone mineral density of the femoral neck and total femur by dual energy x ray absorptiometry. Xylose tests and measurements of faecal fat evaluated gut absorption. All tests were performed before and after SBTX. Body weight increased from 34.7 to 51.9 kg in the recipient and from 45.0 to 53.2 kg in the donor within four years. The recipient caught up with the height and fat free mass of his brother within two years. Fat mass, and total femur and femoral neck densities are still lower in the recipient than in the donor four years after SBTX (-1.2 kg, -0.087 g/cm(2), -0.035 g/cm(2)). The xylose test of the recipient was still abnormally low after four years (1.37 mmol/l) and faecal fat was high until two years after SBTX (March 2001: 12 g/24 h). The donor always showed normal xylose tests and faecal fat, except for one episode of high faecal fatty acids about 10 months after SBTX. SBTX improved the nutritional state and growth of the graft recipient although body composition, femoral bone mineral densities, and intestinal absorption had not completely normalised after four years.

Adolescent↗
PubMed2001

Transplantation of islets of Langerhans: new developments.

The clinical results recently reported by the Edmonton group in recipients of allogeneic islet grafts, all of whom achieved at least temporary insulin independence, has rekindled interest in transplantation of islets of Langerhans as a means to cure diabetes. Long-term islet graft survival has been achieved in a non-human primate pre-clinical model with a protocol of T-cell signaling blockade using a new monoclonal antibody. Islet xenotransplantation (namely the use of animal islets, with the aim of transplanting them into humans), or stem cell technology (the controlled differentiation of stem cells to obtain specialised cells for the treatment of diabetes) are other procedures currently being evaluated in animal models. The recent clinical success suggests that, in the near future, diabetes might be treated by islet transplantation early in the clinical course of the disease before the development of complications, and without the risks associated with conventional immunosuppression.

Animals↗
PubMed2001

Patterns of engraftment in different strains of immunodeficient mice reconstituted with human peripheral blood lymphocytes.

BACKGROUND: Models of immunodeficient mice reconstituted with a competent human immune system would represent an invaluable tool for the study of transplantation immunobiology allergy, autoimmunity, and infectious diseases. Severe combined immune deficiency (scid) mice can be successfully reconstituted with human peripheral blood lymphocytes (PBLs), but rates and levels of engraftment are poor. New strains of mice with diverse immunodeficiencies have been recently characterized or developed, which might prove to be advantageous for in vivo studies of human immune reactivity. METHODS: We have compared rates and patterns of human PBL engraftment in four available immunodeficient murine strains; scid-beige, nonobese diabetic (NOD)-scid, NOD-scid-beta2 m- and rag-. T- and B-lymphocyte engraftment, phenotype of engrafted cells, and occurrence of graft-versus-host disease (GVHD) were studied and compared. RESULTS: Successful engraftment of human PBL was readily obtained in the majority of scid-beige, NOD-scid, and NOD-scid-beta2 m- with a single i.p. administration of human PBLs, whereas it was seldom achieved in rag- animals. Human Ig levels were accordingly remarkably low in rag- recipients but, interestingly also in NOD-scid-beta2 m- mice. Engraftment was readily observed not only in peripheral blood but also in spleen and bone marrow of successfully reconstituted animals. Phenotypic analysis of engrafted human cells showed preserved CD4/CD8 ratios and a clear skewing toward an activated phenotype. GVHD was invariably observed in successfully reconstituted animals. CONCLUSIONS: Our data indicate that a high rate of reconstitution with human lymphocytes can be achieved in scid-beige, NOD-scid, and NOD-scid-beta2 m- mice. Human Ig are produced at high levels, except in NOD-scid-beta2 m-, including xenoreactive natural antibodies. Scid-beige and NOD-scid appear therefore better suited than NOD-scid-beta2 m- or rag- for analysis of human immunoreactivity in vivo. An important caveat is the invariable occurrence of GVHD that precludes long-term studies in this model system.

Animals↗
PubMed2001

Early assessment of apoptosis in isolated islets of Langerhans.

BACKGROUND: There is substantial evidence to link early graft loss after islet transplantation to isolation-induced islet cell apoptosis. Measurement of caspase 3 activity and detection of the lost cell membrane asymmetry, revealed by annexin V binding, are newly available assays that allow the analysis of early events of apoptosis. METHODS: In this study, we compared these tests with the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay and analysis of DNA fragmentation after gel electrophoresis in freshly isolated islets obtained from rats, before and after treatment with interleukin-1 beta, interferon gamma, and tumor necrosis factor a, cytokines known to induce islet cell damage. RESULTS: A measurable level of apoptosis was observed the day after isolation when caspase 3 activity and annexin V binding were used as assays, although no substantial DNA fragmentation was detected with TUNEL assay and DNA gel electrophoresis. Baseline caspase 3 activity was 0.8+/-0.3 U/100 islet equivalents and it increased to 1.4+/-0.45 U/100 islet equivalents 3 hr after cytokine stimulation (P<0.05 vs. unstimulated islets). The baseline level of apoptosis, as detected by annexin V binding, was 21.1%+/-5.8%, and it increased to 27.5%+/-8.1% 6 hr after addition of the cytokine cocktail (P<0.01 vs. unstimulated islets). An increase in the number of TUNEL-positive nuclei was detected 24 hr after stimulation and peaked at 48 hr. DNA laddering was also evident 24 hr after cytokine treatment. CONCLUSION: These data suggest that measurement of caspase 3 activity and annexin V binding analysis might represent reliable markers of early events of islet cell apoptosis.

Animals↗