Reduced amplitude and slowed latency of the acoustic startle response in adolescents and adults with 22q11.2 deletion syndrome.

Background: 22q11.2 deletion syndrome (22q11DS) is one of the most robust genetic predictors of psychosis and other psychiatric illnesses. In this study, we examined 22q11DS subjects' acoustic startle responses (ASRs), which putatively index psychosis risk.

Deep psychophysiological phenotyping of adolescents and adults with 22q11.2 deletion syndrome: a multilevel approach to defining core disease processes.

Background: 22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal interstitial-deletion disorder, occurring in approximately 1 in 2000 to 6000 live births.

Estimation of Early Graft Function Using the BETA-2 Score Following Clinical Islet Transplantation.

Little is known about how early islet graft function evolves in the clinical setting. The BETA-2 score is a validated index of islet function that can be calculated from a single blood sample and lends itself to frequent monitoring of graft function. In this study, we characterized early graft function by calculating weekly BETA-2 score in recipients who achieved insulin independence after single transplant (group 1, = 8) compared to recipients who required a second transplant before achieving insulin independence (group 2, = 7).

Pancreatic islet transplantation in type 1 diabetes: 20-year experience from a single-centre cohort in Canada.

Background: Islet transplantation offers an effective treatment for selected people with type 1 diabetes and intractable hypoglycaemia. Long-term experience, however, remains limited. We report outcomes from a single-centre cohort up to 20 years after islet transplantation.

Comparison of metabolic responses to the mixed meal tolerance test vs the oral glucose tolerance test after successful clinical islet transplantation.

Following islet transplantation, mixed meal tolerance tests (MMTs) are routinely utilized to assess graft function, but how the 90-minute MMTT glucose value relates to a 120-minute glucose concentration of ≥11.1 mmol/L used to diagnose diabetes following a standardized 75 g-OGTT, is not known. We examined this relationship further.

Sitagliptin plus pantoprazole can restore but not maintain insulin independence after clinical islet transplantation: results of a pilot study.

Aims: Resuming insulin use due to waning function is common after islet transplantation. Animal studies suggest that gastrointestinal hormones, including gastrin and incretins may increase β-cell mass. We tested the hypothesis that pantoprazole plus sitagliptin, would restore insulin independence in islet transplant recipients with early graft insufficiency and determined whether this would persist after a 3-month washout.

Validation of the BETA-2 Score: An Improved Tool to Estimate Beta Cell Function After Clinical Islet Transplantation Using a Single Fasting Blood Sample.

The beta score, a composite measure of beta cell function after islet transplantation, has limited sensitivity because of its categorical nature and requires a mixed-meal tolerance test (MMTT). We developed a novel score based on a single fasting blood sample. The BETA-2 score used stepwise forward linear regression incorporating glucose (in millimoles per liter), C-peptide (in nanomoles per liter), hemoglobin A1c (as a percentage) and insulin dose (U/kg per day) as continuous variables from the original beta score data set (n = 183 MMTTs).

Islet oxygen consumption rate dose predicts insulin independence for first clinical islet allotransplants.

Background: Human islet allotransplantation for the treatment of type 1 diabetes is in phase III clinical trials in the U.S. and is the standard of care in several other countries.

Single-donor islet transplantation and long-term insulin independence in select patients with type 1 diabetes mellitus.

Background: Islet transplantation is a recognized treatment option for select patients with type I diabetes mellitus. However, islet infusions from multiple donors are often required to achieve insulin independence. Ideally, insulin independence would be achieved routinely with only a single donor.

Successful treatment of brittle diabetes following total pancreatectomy by islet allotransplantation: a case report.

Context: Allotransplantation of islets can successfully treat subjects with type 1 diabetes complicated by severe hypoglycemia and erratic glycemic control. Insulin independence is often lost over time due to several factors, including recurrent autoimmunity. Brittle diabetes (frequent hypoglycemia and labile glycemic control) is common after pancreatectomy.

Clinical islet isolation outcomes with a highly purified neutral protease for pancreas dissociation.

Background: Pancreas dissociation is a critical initial component of the islet isolation procedure and introduces high variability based on factors including the enzyme type, specificity and potency. Product refinement and alterations to the application strategies have improved isolation outcomes over time; however, islet utilization from donor organs remains low. In this study we evaluate a low endotoxin-high activity grade neutral protease in clinical islet isolation.

Long-term follow-up of hepatic ultrasound findings in subjects with magnetic resonance imaging defined hepatic steatosis following clinical islet transplantation: a case-control study.

Hepatic steatosis is one complication patients may experience following clinical islet transplantation (CIT), yet the cause and consequences of this are poorly understood. The purpose of this case-control study was to examine the relationship between hepatic steatosis, metabolic parameters and graft function in an Albertan cohort of CIT recipients. Hepatic steatosis was detected by magnetic resonance imaging (MRI) in n = 10 cases age-matched with n=10 MRI-negative controls.

Three cases of alopecia following clinical islet transplantation.

Successful clinical islet allotransplantation requires control of both allo- and autoimmunity by using immunosuppressant drugs which have a number of side effects. The development of the autoimmune condition alopecia areata following successful islet transplantation is therefore unexpected. Three cases of alopecia affecting female islet transplant recipients are described.

Comparison of human islet isolation outcomes using a new mammalian tissue-free enzyme versus collagenase NB-1.

Background: After the discontinuation of the manufacturing Liberase HI because of a small potential for prion disease transmission, Roche Diagnostics (Indianapolis, IN) developed a new enzyme product (Liberase MTF [mammalian tissue free]), which is similar to Liberase HI with the exception that no mammalian tissue is used in the manufacture of the collagenase component. We report our experience using the MTF enzyme in clinical islet isolations compared with Serva NB-1 with modified enzyme delivery method.

Methods: Islets were isolated from 41 pancreata using MTF enzyme (n=17) or NB-1 enzyme (n=24).

Insulin-heparin infusions peritransplant substantially improve single-donor clinical islet transplant success.

Background: Successful islet transplantation can result in insulin independence in many patients with type 1 diabetes mellitus, but it often requires more than one islet infusion. The ability to achieve insulin independence with a single donor is an important goal in clinical islet transplantation due to the limited organ supply.

Methods: We examined factors that may be associated with insulin independence after islet transplantation with islets from a single donor, using univariate and multivariate analysis.

Supplemental islet infusions restore insulin independence after graft dysfunction in islet transplant recipients.

Background: The ability of supplemental islet infusions (SII) to restore insulin independence in islet transplant recipients with graft dysfunction has been attributed to the coadministration of exenatide. However, improving islet transplant outcomes could explain the success of SII. We aimed to determine the effect on islet graft function and insulin independence of SII using these new protocols, without the use of exenatide.

Histologic graft assessment after clinical islet transplantation.

Background: An accurate monitoring would help understanding the fate of islet grafts after transplantation.

Methods: This work assessed the feasibility of needle biopsy monitoring after intraportal islet transplantation (n=16), and islet graft morphology was studied with the addition of autopsy samples (n=2). Pancreas autopsy samples from two nondiabetic individuals were used as control.

Nonsimultaneous administration of pancreas dissociation enzymes during islet isolation.

Background: Successful islet isolation relies heavily on enzyme products. Among them, Liberase was used in islet transplantation programs until the islet community was notified of the use of a bovine brain component during the manufacturing process. To minimize potential risk of prion disease transmission, many islet isolation facilities switched to Serva enzyme, which is considered to pose less risk.

Islets isolated from donors with elevated HbA1c can be successfully transplanted.

Clinical islet transplantation is limited by the availability of donor organs. We report two cases where islets were isolated from donors with elevated HbA1c (6.3% and 7.

High risk of sensitization after failed islet transplantation.

Human Leukocyte Antigen (HLA) antibodies posttransplant have been associated with an increased risk of early graft failure in kidney transplants. Whether this also applies to islet transplantation is not clear. To achieve insulin independence after islet transplants multiple donor infusions may be required.

Long-term graft function after allogeneic islet transplantation.

Islet transplants are emerging as a viable option for the treatment of type 1 diabetes mellitus. From 1989 to 1995 we conducted a series of simultaneous islet-kidney transplants in six uremic type 1 diabetic patients. We report two of these patients who have shown persistent islet graft function over many years.

Pretransplant HLA antibodies are associated with reduced graft survival after clinical islet transplantation.

Despite significant improvements in islet transplantation, long-term graft function is still not optimal. It is likely that both immune and nonimmune factors are involved in the deterioration of islet function over time. Historically, the pretransplant T-cell crossmatch and antibody screening were done by anti-human globulin--complement-dependent cytotoxicity (AHG-CDC).

Long-Term Graft Function after Allogeneic Islet Transplantation.

Islet transplants are emerging as a viable option for the treatment of type 1 diabetes mellitus. From 1989 to 1995 we conducted a series of simultaneous islet-kidney transplants in six uremic type 1 diabetic patients. We report two of these patients who have shown persistent islet graft function over many years.

Islet isolation and transplantation outcomes of pancreas preserved with University of Wisconsin solution versus two-layer method using preoxygenated perfluorocarbon.

Background: Previous small clinical trials indicate that the two-layer method (TLM) for pancreas preservation improves islet isolation outcome. However, the effect of TLM has not been evaluated in large-scale study. In addition, a direct benefit of TLM on islet transplantation outcome has not been addressed in the setting of any randomized controlled trials.