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T Berney

Publications and source records attributed to T Berney.

At least 37 records · Page 2Linked to original sources
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

Successful islet after kidney transplantations in a distance over 1000 kilometres: Preliminary results of the Budapest-Geneva collaboration.

To overcome critical islet processing and to ensure patient safety and quality care, we have established an international collaboration between two geographically distant transplant centers for islet transplantation. Four pancreata were harvested and immediately preserved by the two-layer method (oxygenated perfluorocarbon+University of Wisconsin) and subsequently transported for the automated method isolation to Geneva. After purification, the islets were cultured overnight and transported the next day back to Budapest. Three consecutive kidney transplant patients with type 1 diabetes mellitus underwent islet transplantation via percutaneous transhepatic portal embolization using the bag-method. The immunosuppression consisted of daclizumab, sirolimus, and low-dose tacrolimus. Mean donor age was 43.7 years, mean body mass index: 26.5. The islet isolation process began within 8 hours from the donor aorta cross-clamp in all cases. The isolation success rate was 80% (4 of 5). In Budapest, the islets were assessed for viability. No complications occurred during the transplantation, and the portal pressure remained within the normal range. The first patient received 12,000 IU/BW from two donors and the insulin requirement decreased from 40 U/d to 10 U/d. The second patient received 7200 IU/BW from a single donor and became immediately insulin free. The third patient was given 7100 IU/BW; the insulin requirement decreased from 39 U/d to 14 U/d. Posttransplant follow-up for the three patients are 7 months, 4 months, and 2 weeks, respectively. All patients achieved metabolic stability. These preliminary results demonstrate the feasibility of an international collaborative islet transplantation program at a distance over 1000 km.

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↗
PubMed2001

Renal transplantation with donors aged over 50: a long-term, single centre experience.

BACKGROUND: Renal transplantation is now considered the best treatment for end-stage renal failure patients. In view of the worldwide growing waiting list, extending donor age is one of the strategies implemented to make more kidneys available for transplantation. METHODS: From October 1983 to February 2000, 324 renal transplantations were performed at Geneva University Hospital, 68 of which were done with kidneys from donors aged over 50 (mean donor age 55.3 + 4.8 years) The following data were analysed at 1, 5 and 10 years and compared between recipients with donors aged over 50 (> 50 years) and under 50 (< 50 years): actuarial patient and graft survival, serum creatinine, causes of graft loss. RESULTS: Patient survival at 10 years was 83% with donors < 50 years and 61% with donors > 50 years (non-significant). Graft survival at 10 years was 61% with donors < 50 years and 48% with donors > 50 years (non-significant). Graft survival at 10 years or death with functioning graft was 69% with donors < 50 years and 68% with donors > 50 years (non-significant). Overall, donor age was not a predictive factor for graft survival, as shown by multiple logistic regression. CONCLUSIONS: Kidneys obtained from donors > 50 years are suitable for renal transplantation and yield acceptable graft survival.

Adolescent↗
PubMed2001

Endotoxin-mediated delayed islet graft function is associated with increased intra-islet cytokine production and islet cell apoptosis.

BACKGROUND: Primary nonfunction resulting in immediate graft loss is responsible for the failure of a large number of islet transplants. Evidence is accumulating to single out endotoxin contamination of the various reagents needed for islet isolation as a major cause of early graft loss. METHODS: Islets isolated with endotoxin-containing (400 endotoxin units/ml) collagenase type V and "endotoxin-free" (3.1 endotoxin units/ml) Liberase were compared. Graft function was assessed using a syngeneic murine model of marginal islet mass transplantation. Pro-inflammatory cytokine production by islets was measured by ELISA in culture supernatants, and quantitative reverse transcriptase-PCR. Islet cell apoptosis was measured using the annexin assay. RESULTS: Graft function was significantly delayed when islets were isolated with endotoxin-containing collagenase. Addition of endotoxin to the Liberase solution similarly delayed graft function. After 18 hr in culture, collagenase-isolated islets released higher amounts of proinflammatory cytokines compared with Liberase-isolated islets (interleukin-6: 2,185+/-1,174 pg/ml vs. 520+/-201 pg/ml; tumor necrosis factor-alpha: 304+/-298 pg/ml vs. 0; IL-1beta: 12.5 pg/ml+/-12.5 vs. 0). This observation correlated with higher cytokine mRNA expression in collagenase-isolated islets. The percentage of apoptotic islet cells immediately after isolation was 17.2%+/-9.4 in collagenase-isolated islets and 7.1%+/-2.1 in Liberase-isolated islets. CONCLUSIONS: We propose that endotoxin contamination is the primum movens of a chain of events that involves intra-islet cytokine production and release and islet cell apoptosis, and endotoxin contamination can ultimately lead to primary nonfunction in vivo. This emphasizes the fact that using endotoxin-free reagents during isolation is a key factor for successful islet transplantation.

Animals↗
PubMed2001

Sexual abuse in children and adolescents with intellectual disability.

The present authors conducted a study of the occurrence of victimization and the perpetration of sexual abuse among 43 in-patients with intellectual disability aged between 9 and 21 years who were admitted to a child and adolescent psychiatric in-patient department over a period of 5 years. A retrospective case-note review was employed that explored the nature and severity of abuse in relation to the age, gender and level of disability. The prevalence of abuse or abusive behaviour, i.e. 14% of 300 admissions, did not change over time. In 13 out of the 43 cases, the issue of sexual abuse was identified after admission. Victimization alone occurred in 21 cases, perpetration alone in six cases, and both victimization and perpetration in 16 cases. Fifty per cent of the victims had been abused by a member of their close or extended family. Most cases (62%) were adolescents. There was only one instance of a victim being abused by a female. However, there were five girls who were perpetrators, all of whom had previously been victims. By contrast, 11 out of the 17 male perpetrators had been victims. Despite difficulties of disclosure, it was possible to establish that severely disabled patients had suffered sexual abuse. The present data support theories which (1) recognize gender differences in sexual abuse patterns and (2) have a developmental perspective, incorporating the influence of adolescence.

Adolescent↗
PubMed2001

Psychopathology of sexual abuse in young people with intellectual disability.

The present study addressed two issues using a sample of child and adolescent victims and perpetrators of sexual abuse: (1) the extent of post-traumatic stress disorder (PTSD) in the sample; and (2) the possible distinction between perpetrators whose motivations were sexually impulsive, and those who were controlling and abuse-reactive. Retrospective case material from 43 cases (21 victims only, and 22 perpetrators, of whom 16 were also victims) provided the data. Post-traumatic symptomatology was not common. Only one case of PTSD was found. Perpetrators could be distinguished by whether they had suffered sexual abuse alone, sexual and physical abuse, or neither. The proposed distinction between perpetrators received support. Sexual abuse directed at younger victims was associated with earlier experience of multiple forms of abuse. The present data does not support the view that post-traumatic symptoms following victimization are a mediator of sexual abuse perpetration. It is argued that an elaboration of the Williams & New developmental model of perpetration better fits the data.

Adolescent↗
PubMed2001

Renal transplantation in the elderly: a long-term, single-centre experience.

BACKGROUND: End-stage renal failure increases with advancing age and renal transplantation should be considered in end-stage renal failure patients older than 60 years. However, there is a paucity of data on long-term patient and graft survival in this population. METHODS: From October 1983 to March 1999, 310 renal transplantations were performed at Geneva University Hospital in 283 patients, of which 49 were done in 48 patients older than 60 years (mean age 65.6+/-4.1 years). The following data were analysed at 1, 5, and 10 years, and compared between the patients >60 years and <60 years old: actuarial patient and graft survival, serum creatinine, causes of graft loss, and patient death. RESULTS: Patient survival at 10 years was 81% for patients <60 years and 44% for patients >60 years. Graft survival at 10 years was 59% for patients <60 years and 32% for patients >60 years. Graft survival at 10 years censored for death with functioning graft was 65% for patients <60 years and 81% for patients >60 years. Main causes of mortality in the older patients were related to cardiovascular events (47%), neoplasia (41%), and sepsis (18%). Overall, recipient and donor age were not predictive factors for graft survival, as shown by multiple logistic regression. CONCLUSIONS: Renal transplantation should be considered in patients older than 60 years, since graft survival is excellent in this population. Although these patients have a shorter life expectancy, they benefit from renal transplantation similarly to younger kidney transplant recipients.

Adolescent↗
PubMed2001

Prolonged islet graft survival in NOD mice by blockade of the CD40-CD154 pathway of T-cell costimulation.

Allorejection and recurrence of autoimmunity are the major barriers to transplantation of islets of Langerhans for the cure of type 1 diabetes in humans. CD40-CD154 (CD40 ligand) interaction blockade by the use of anti-CD154 monoclonal antibody (mAb) has shown efficacy in preventing allorejection in several models of organ and cell transplantation. Here we report the beneficial effect of the chronic administration of a hamster anti-murine CD154 mAb, MR1, in prolonging islet graft survival in NOD mice. We explored the transplantation of C57BL/6 islets into spontaneously diabetic NOD mice, a combination in which both allogeneic and autoimmune components are implicated in graft loss. Recipients were treated either with an irrelevant control antibody or with MR1. MR1 administration was effective in prolonging allograft survival, but did not provide permanent protection from diabetes recurrence. The autoimmune component of graft loss was studied in spontaneously diabetic NOD mice that received syngeneic islets from young male NOD mice. In this combination, a less dramatic yet substantial delay in diabetes recurrence was observed in the MR1-treated recipients when compared with the control group. Finally, the allogeneic component was explored by transplanting C57BL/6 islets into chemically induced diabetic male NOD mice. In this setting, long-term graft survival (>100 days) was achieved in MR1-treated mice, whereas control recipients rejected their grafts within 25 days. In conclusion, chronic blockade of CD154 results in permanent protection from allorejection and significantly delays recurrence of diabetes in NOD mice.

Animals↗