Biomedical subjects

Rodolfo Alejandro

Publications and source records attributed to Rodolfo Alejandro.

24 records · Page 2Linked to original sources

PubMed2004

Twenty years of clinical islet transplantation at the Diabetes Research Institute--University of Miami.

Transplantation of allogeneic pancreatic islets for the treatment of patients with Type 1 diabetes mellitus (T1DM) is now a reality. The steady progress that has allowed for the recent successful clinical trials world-wide follows a steep learning curve and the perseverance of the international islet transplantation community. The Clinical Islet Transplant Program at the Diabetes Research Institute - University of Miami has contributed to the progress in the field with a 20-year track record. It has been a long journey and despite the intermediate success, more work is needed in order to achieve the ultimate goal of a safe and long-lasting treatment for patients with T1DM.

Academies and Institutes↗

PubMed2003

Pancreatic islet transplantation: the radiographic approach.

BACKGROUND: Successful pancreatic islet transplantation (PIT) has resulted in several transplant centers wanting to start PIT programs. PIT remains experimental and must be performed safely for its continued use. We describe the radiographic techniques used at our center and their results. METHODS: Between January 17, 2002, and December 16, 2002, 17 percutaneous transhepatic PITs were performed by two interventional radiologists. Ultrasound localization of and guidance to the portal vein (PV) were used. Portosplenography confirmed the position of the PV islet infusion catheter, and PV pressure was documented before, during, and at the completion of PIT. To prevent PV thrombosis, heparin (17.5 U/kg) through the PV infusion catheter and subcutaneous enoxaparin (Lovenox, Aventis Pharmaceuticals, Parsippany, NJ) were administered after PIT. At the completion of PIT, thrombin-saturated Gelfoam (Johnson and Johnson, Summerville, NJ) was embolized into the hepatic parenchymal tract. RESULTS: Percutaneous PV access was achieved in all cases (median number of seeker needle passes=2, range: 1-6), and PIT was performed. In no case was any extrahepatic organ punctured, and sustained PV hypertension was not seen. No patient required transfusion, and it was documented by Doppler ultrasonography that PV thrombosis did not result from PIT. In addition, intraparenchymal and intraabdominal bleeding did not complicate any PIT; 71% and 59% of the patients experienced moderate posttransplant abdominal pain and nausea, respectively. All patients demonstrated a self-limited, asymptomatic posttransplant transaminitis. CONCLUSIONS: We believe that PIT should be performed by a small number of experienced interventional radiologists using ultrasound guidance and posttransplant embolization of the hepatic parenchymal tract.

Diabetes Mellitus, Type 1↗

PubMed2003

Improved human islet isolation outcome from marginal donors following addition of oxygenated perfluorocarbon to the cold-storage solution.

Last year, from the approximately 6,000 organ donors, only approximately 1,500 pancreata were used for clinical transplantation. Factors that contribute to this poor pancreas use include strict donor selection criteria and the requirement for short cold-ischemia time (CIT). Numerous pancreata have not been used because of long ischemia times postprocurement. Given the oxygen-rich environment of the islets in the native pancreas, it is conceivable that islets are highly susceptible to irreversible damage following prolonged ischemia. The use of continuously oxygenated perfluorohydrocarbons (PFCs), known for their high oxygen-solubility coefficients, in a two-layer culture with standard University of Wisconsin preservation media, has extended the acceptable range CIT, and, furthermore, there has been no evidence of adverse effects from PFCs on the outcome of transplanted cells, whereas they often enhance islet cell function. The purpose of this study was to use the two-layer culture method to improve donor-organ use from marginal donors. Fifteen organs were procured using the two-layer method, and 18 without using it, from donors greater than 50 years of age. Despite nonsignificant differences in age, weight of the donors, weight of the organ and CIT, the PFC group yielded an average of twofold more islet equivalents than those harvested from the control group. As a result, from the control group, only 2 of 18 organs were used for clinical islet transplantation, whereas 8 of 15 were used from the PFC group. To this end, the two-layer method may help clinicians overcome the problem of organ underuse.

Adenosine↗

PubMed2003

The bag method for islet cell infusion.

As islet cell transplantation gains increasing interest following results published by the Edmonton group, results that have been successfully reproduced by several centers nationwide and abroad, the need of guidelines to standardize the procedure becomes highly important. We detail the key steps of the infusion procedure utilizing a closed gravity fed bag system utilized at our institution since 1990, which consists of a 600-ml transfer bag and a 150-ml rinse bag connected via sterile tubing. The use of gravity allows for a control rate of infusion as well as providing a safety mechanism through natural reduction of flow that parallels any increase in portal pressure, therefore allowing the operator to prevent precipitous pressure rises. Reports on significant rise in portal pressures during islet cell infusion as well as portal vein thrombosis have been published. Infusion at these centers was carried out using a syringe method. Using our technique, portal vein thrombosis (partial or complete) was not detected in any of the infusions performed at our institution. This method may be of assistance to minimize some of the observed complications associated with islet transplant procedures and has now been adapted by most centers performing clinical islet transplantation.

Infusions, Intravenous↗

PubMed2002

Achievement of insulin independence in three consecutive type-1 diabetic patients via pancreatic islet transplantation using islets isolated at a remote islet isolation center.

BACKGROUND: As a result of advances in both immunosuppressive protocols and pancreatic islet isolation techniques, insulin independence has recently been achieved in several patients with type 1 diabetes mellitus via pancreatic islet transplantation (PIT). Although the dissemination of immunosuppressive protocols is quite easy, transferring the knowledge and expertise required to isolate a large number of quality human islets for transplantation is a far greater challenge. Therefore, in an attempt to centralize the critical islet processing needed for islet transplantation and to avoid the development of another islet processing center, we have established a collaborative islet transplant program between two geographically distant transplant centers. PATIENTS AND METHODS: Three consecutive patients with type 1 diabetes mellitus with a history of severe hypoglycemia and metabolic instability underwent PIT at the Methodist Hospital (TMH), Houston, Texas, using pancreatic islets. All pancreatic islets were isolated from pancreata procured in Houston and subsequently transported for isolation to the Human Islet Cell Processing Facility of the Diabetes Research Institute (DRI) at the University of Miami, Miami, Florida. Pancreatic islets were isolated at DRI after enzymatic ductal perfusion (Liberase-HI) by the automated method (Ricordi Chamber) using endotoxin-free and xenoprotein-free media. After purification, the islets were immediately transported back to TMH and transplanted via percutaneous transhepatic portal embolization. Immunosuppression consisted of sirolimus, tacrolimus, and daclizumab. RESULTS: After donor cross-clamp in Houston, donor pancreata arrived at DRI and the isolation process began within 6.5 hr in all cases (median, 5.4 hr; range, 4.8-6.5 hr). At the completion of the isolation process, the islets were immediately transported back to TMH and transplanted. All three patients attained sustained insulin independence after transplantation of 395,567, 394,381, and 563,206 pancreatic islet equivalents (IEQ), respectively. Despite insulin independence, the first two patients received less than 10,000 IEQ/kg; therefore, to increase their functional pancreatic islet reserve, they underwent a second islet transplant with 326,720 and 768,132 IEQ, respectively. Posttransplantation follow-up for these three patients is 4, 3, and 0.5 months, respectively. The mean glycosylated hemoglobin values have been dramatically reduced in the first two patients. In addition, the mean amplitude of glycemic excursions have also been reduced in all three recipients (patient 1: before transplantation 197 mg/dL vs. after transplantation 61 mg/dL; patient 2: before transplantation 202 mg/dL vs. after transplantation 52 mg/dL; patient 3: before transplantation 245 mg/dL vs. after transplantation 58 mg/dL) after PIT. All pancreatic islet allografts demonstrated the ability to respond to an in vitro glucose stimulus at the DRI before shipment and at TMH after shipment and final processing with a median stimulation index of 2.1 and 2.2, respectively. None of the transplant recipients have had a hyper- or hypoglycemic episode since PIT and no complications have occurred. CONCLUSIONS: These early data demonstrate that (1) pancreatic islets remain viable after shipment to remote transplant sites; (2) pancreatic islet isolation techniques and experience can be concentrated at a small number of regional facilities that could supply islets to remote transplant centers; and (3) insulin independence via PIT can be achieved using a remote pancreatic islet isolation center.

Adolescent↗

PubMed2002

Use of oxygenated perfluorocarbon toward making every pancreas count.

The past few years have seen significant advancement in the clinical relevance of intraportal islet cell transplantation for treatment of type 1 diabetes mellitus. The implementation of novel protocols, such as the one developed by the group of Shapiro and collaborators in Edmonton, has revitalized the enthusiasm for cellular transplantation as a treatment for diabetes by improving the success rates and long-term function of islet grafts. Improved results in clinical islet transplantation reported by the groups in Edmonton, Miami, and Minneapolis have re-proposed the much simpler outpatient cell transplant procedure as an alternative to the more risky and technically challenging whole-organ pancreas transplantation.

Fluorocarbons↗