beth israel deaconess medical center a harvard medical school teaching hospital

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Dr. Martha Pavlakis

Islet Transplantation

Islet Transplantation is at BIDMC as part of the center for Islet Transplantation at Harvard Medical School. The centers involved are BIDMC, and Brigham and Women's Hospital. Dr. Pavlakis serves as the BIDMC PI for this trial. With the development of pancreatic islet isolation techniques, it became apparent that diabetic rodents and other small animals could be "cured" with this procedure. After initial enthusiasm in the late 1980's, the results of human pancreatic islet allografts in type 1 diabetic patients have shown disappointingly low rates of graft survival, and the lack of progress has tempered interest in this minimally invasive approach to the therapy of type 1 diabetes. More recently, advances in islet cell biology and transplant immunology have been instrumental in a resurgence of interest in islet transplantation with very promising data obtained in monkeys showing long-term survival and function of islet allografts after treatment with anti-CD154 antibodies. These results demonstrate that islet transplantation is technically feasible and effective in maintaining normoglycemia. A report from , showed insulin independence in type one diabetics after islet transplantation using a combination of IL-2 receptor antagonist, FK506 and Rapamycin. At BIDMC, we are currently underway enrolling patients with diabetes who have already received a kidney transplant.

Molecular Diagnosis

Drs. Terry Strom, Martha Pavlakis and Xin Xiao Zheng hope to refine and sharpen the diagnostic tools for anticipating/determining the occurrence of rejection. Every transplant is infiltrated by mononuclear leukocytes. Sometimes the infiltrate is very substantial although there is no clinical evidence of rejection. By probing the activities of the infiltrating cells, these researchers have determined whether such infiltrates are benign or actually capable of mediating rejection. Using reverse transcription assisted polymerase chain reaction and renal biopsy specimens, they have determined that gene expression of cytotoxic T lymphocyte (CTL) activation genes is very closely associated with the diagnosis of rejection. In the past year, refined, highly quantitative tools have been employed to address this problem. As rejection proceeds, the number of expressed CTL and other select immune activation transcripts increases. With a refinement in techniques, it has now been determined that expression of these genes can be detected in small peripheral blood and urine leukocyte specimens before and during rejection episodes. These researchers will now test the hypothesis that this information may be useful to anticipate and thereby prevent rejection.

Pre-Transplant Cardiac Screening in Diabetics

Dr. Pavlakis is collaborating with Dr. Michael Johnstone (Cardiology) to determine the best method for screening diabetics for coronary disease before renal transplantation. She is currently supervising a resident doing a retrospective analysis of our center's experience given the high volume of diabetics patients we see with end stage renal disease.