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Biomedical subjects

F H Wright

Publications and source records attributed to F H Wright.

At least 19 recordsLinked to original sources

Consensus statement on the live organ donor.

OBJECTIVE: To recommend practice guidelines for transplant physicians, primary care providers, health care planners, and all those who are concerned about the well-being of the live organ donor. PARTICIPANTS: An executive group representing the National Kidney Foundation, and the American Societies of Transplantation, Transplant Surgeons, and Nephrology formed a steering committee of 12 members to evaluate current practices of living donor transplantation of the kidney, pancreas, liver, intestine, and lung. The steering committee subsequently assembled more than 100 representatives of the transplant community (physicians, nurses, ethicists, psychologists, lawyers, scientists, social workers, transplant recipients, and living donors) at a national conference held June 1-2, 2000, in Kansas City, Mo. CONSENSUS PROCESS: Attendees participated in 7 assigned work groups. Three were organ specific (lung, liver, and kidney) and 4 were focused on social and ethical concerns (informed consent, donor source, psychosocial issues, and live organ donor registry). Work groups' deliberations were structured by a series of questions developed by the steering committee. Each work group presented its deliberations to an open plenary session of all attendees. This information was stored and shaped into a statement circulated electronically to all attendees for their comments, and finally approved by the steering committee for publication. The term consensus is not meant to convey universal agreement of the participants. The statement identifies issues of controversy; however, the wording of the entire statement is a consensus by approval of all attendees. CONCLUSION: The person who gives consent to be a live organ donor should be competent, willing to donate, free from coercion, medically and psychosocially suitable, fully informed of the risks and benefits as a donor, and fully informed of the risks, benefits, and alternative treatment available to the recipient. The benefits to both donor and recipient must outweigh the risks associated with the donation and transplantation of the living donor organ.

Health Status↗

Effects of tacrolimus on hyperlipidemia after successful renal transplantation: a Southeastern Organ Procurement Foundation multicenter clinical study.

BACKGROUND: Tacrolimus has been shown to have a less adverse effect on the lipid profiles of transplant patients when the drug is started as induction therapy. In order to determine the effect tacrolimus has on lipid profiles in stable cyclosporine-treated renal transplant patients with established hyperlipidemia, a randomized prospective study was undertaken by the Southeastern Organ Procurement Foundation. METHODS: Patients of the 13 transplant centers, with cholesterol of 240 mg/dl or greater, who were at least 1 year posttransplant with stable renal function, were randomly assigned to remain on cyclosporine (control) or converted to tacrolimus. Patients converted to tacrolimus were maintained at a level of 5-15 ng/ml, and control patients remained at their previous levels of cyclosporine. Concurrent immunosuppressants were not changed. Levels of total cholesterol, triglycerides, total high-density lipoprotein, low-density lipoprotein (LDL), very-low-density lipoprotein, and apoproteins A and B were monitored before conversion and at months 1, 3, and 6. Renal function and glucose control were evaluated at the beginning and end of the study (month 6). RESULTS: A total of 65 patients were enrolled; 12 patients failed to complete the study. None were removed as a result of acute rejection or graft failure. Fifty-three patients were available for analysis (27 in the tacrolimus group and 26 controls). Demographics were not different between groups. In patients converted to tacrolimus treatment, there was a -55 mg/dl (-16%) (P=0.0031) change in cholesterol, a -48 mg/dl (-25%) (P=0.0014) change in LDL cholesterol, and a -36 mg/dl (-23%) (P=0.034) change in apolipoprotein B. There was no change in renal function, glycemic control, or incidence of new onset diabetes mellitus in the tacrolimus group. CONCLUSION: Conversion from cyclosporine to tacrolimus can be safely done after successful transplantation. Introduction of tacrolimus to a stable renal patient does not effect renal function or glycemic control. Tacrolimus can lower cholesterol, LDL, and apolipoprotein B. Conversion to tacrolimus from cyclosporine should be considered in the treatment of posttransplant hyperlipidemia.

Adult↗

Induction of heat shock protein 27 in rat embryos exposed to hyperthermia.

Previously we reported that eight proteins were reproducibly induced in postimplantation rat embryos exposed to a brief heat shock (43 degrees C, 15 min). The major heat-inducible rat embryo protein has now been identified as heat shock protein 72 (Hsp 72). In addition, the induction of Hsp 72 is temporally correlated with induction of thermotolerance. One of the other rat embryo proteins previously shown to be induced by elevated temperature is a heat shock protein of approximately 27 kilodaltons (Hsp 27). In this report we show that this protein is recognized by an antibody directed against a conserved peptide sequence of Hsp 27. Unlike Hsp 72, Hsp 27 is constitutively expressed in the rat embryo in the absence of any thermal stress; however, the level of Hsp 27 is increased approximately 2-3-fold after thermal stress (43 degrees C, 10 min). Immunohistochemical analysis revealed that the constitutively expressed Hsp 27 is localized primarily to cells of the heart, cells that are uniquely resistant to the cytotoxic effects of hyperthermia. After thermal stress, Hsp 27 is expressed in all tissues of the embryo. Finally, our data show that Hsp 27 exists in the rat embryo as three major isoforms indicative of different phosphorylation states. Furthermore, most Hsp 27 in the heart is phosphorylated, whereas in the rest of the embryo, nonphosporylated Hsp 27 predominates. After thermal stress, levels of phosphorylated isoforms increase dramatically in nonheart tissues of the embryo. Together, these results suggest that Hsp 27 may play a role in the development of thermotolerance in the postimplantation mammalian embryo.

Animals↗

Single pediatric donor kidneys for adult recipients: the San Antonio experience.

Early, sustained and significant growth occurs in single kidneys from donors < or = 4 years of age transplanted into adult recipients who are receiving CsA therapy. Early and late renal function of single kidneys from donors < or = 4 years of age transplanted into adult recipients is more than adequate. Allograft loss from surgical complications (5%) is not excessive. Allografts from donors < or = 4 years of age are very vulnerable to early rejection. Allograft survival of single kidneys from donors < or = 4 years of age is equal to that reported for cadaveric kidneys from donors > 50 years of age. Single kidneys from donors < or = 5 years of age have an allograft survival equal to that for kidneys from donors of the same age that are transplanted en-bloc. One-year allograft survival among recipients of kidneys from donors < or = 4 years of age receiving 14 days of induction therapy and aggressive treatment of rejection (75%) approaches that of the ideal donor (83%). Kidneys from donors < or = 4 years of age represent an underutilized resource.

Adolescent↗

Function of pancreas allografts more than 1 year following transplantation.

At the University of Iowa, Iowa City, 75 pancreas transplant procedures were performed for type I diabetes mellitus from March 1984 to September 1988. Forty-seven of these transplants were performed simultaneously with kidney transplants from the same donor; 23 followed previous kidney transplants, and 5 were preuremic pancreas-only transplants. The 1-year patient survival rate is 85% and pancreas graft survival rate is 54%. The simultaneous kidney and pancrease group had a 1-year patient survival rate of 82%, a pancreas graft survival rate of 59%, and a renal graft survival rate of 73%. Thirty-one of 70 kidney and pancreas recipients had a functioning pancreas 1 year post transplantation and 26 of 31 currently have a functioning pancreas and are insulin free. Patient symptoms of neuropathy and gastroenteropathy are improved with long-term graft function. Some patients may develop type II diabetes post transplantation with impaired glucose tolerance despite high insulin production by the graft. Pancreas transplantation is the only therapy that achieves a euglycemic state as indicated by glycosylated hemoglobin and glucose tolerance testing. Centers must continue to follow up patients on a long-term basis to determine the final effects on the secondary complications of diabetes.

Diabetes Mellitus, Type 1↗

Increased frequency of posttransplant lymphomas in patients treated with cyclosporine, azathioprine, and prednisone.

We have documented seven B cell lymphomas over a six-month period in 132 (5.3%) kidney and heart allograft recipients immunosuppressed with cyclosporine, azathioprine, and prednisone (triple therapy). This is a significant increase (P less than 0.0001) over the number of such tumors seen by us previously. Only 2 lymphomas had occurred in 669 cadaver and 29 living-related kidney allografts treated with azathioprine and prednisone alone (0.3%). In 160 cadaver kidney recipients treated with cyclosporine and prednisone there have been no lymphomas. Similarly in 14 living-related kidney recipients who were transplanted since the introduction of triple therapy for cadaver grafts, but continued to receive only azathioprine and prednisone, no lymphomas occurred. There seemed to be a clear relationship between this increase and the use of triple therapy. This led us to examine other possible contributing factors. A case control study has not shown any other factor that differs in patients in whom lymphomas developed. We have only been able to demonstrate Epstein Barr virus nuclear antigen in the cells of one tumor. Four of these 7 tumors were monoclonal, one polyclonal, and two indeterminate. All patients had their immunosuppression withdrawn and six received intravenous acyclovir. Three patients have shown some response but four patients died. Triple therapy is being used by many centers to reduce the level of cyclosporine toxicity. We wish to sound a note of caution that this may result in an increased incidence of posttransplant lymphomas.

Adult↗

Appearance of type II diabetes mellitus in type I diabetic recipients of pancreas allografts.

To determine the cause of hyperglycemia appearing after pancreas transplantation in type I diabetic recipients, we performed 65 oral glucose tolerance tests with serum insulin and C-peptide determinations in 32 patients with pancreas grafts functioning two or more months following transplantation. We correlated these results with estimates of graft size obtained by magnetic resonance imaging (MRI) and values of urinary amylase as a measure of pancreatic exocrine function. A total of 33 studies were obtained in 20 patients at times of normal glucose tolerance, and normal ranges for serum insulin and C-peptide levels were established; 32 studies in 17 patients during periods of glucose intolerance revealed values of serum insulin and C-peptide that were within the normal range, though the time to peak values was delayed to 2 hr, characteristic of type II diabetes. Only 3 of 17 patients examined by MRI had significant pancreatic allograft atrophy. These patients also had low urinary amylase excretion, and the only values for serum C-peptide that were below the normal range. The other 14 hyperglycemic patients had normalized pancreas grafts, normal urinary amylase excretion, and normal values for serum insulin and C-peptide. In our experience, then, in 76% of patients with hyperglycemia more than 2 months following pancreas transplantation, the cause was appearance of type II diabetes rather than destruction of the allograft with recurrence of type I diabetes. This observation has important implications for the definition of pancreas allograft failure and for the management of pancreas allograft recipients with hyperglycemia.

Amylases↗

Pancreatic transplants: evaluation with MR imaging.

Eighty-eight magnetic resonance (MR) imaging studies of 31 pancreas transplants in 30 patients were performed. The postoperative graft usually appears enlarged and inhomogeneous, with patchy areas of increased signal intensity on T2-weighted images that may last 3-4 weeks. During acute rejection, T1-weighted images of graft abnormalities show a decrease in signal intensity, similar to that of muscle, and T2-weighted images show an increase in signal intensity, equal to or higher than that of the bladder. The pattern of abnormal signal is most frequently multifocal but can be diffuse, and the graft may be enlarged. During recovery from rejection, the graft parenchyma shows a decrease in signal intensity (less than that of the bladder) on T2-weighted images when compared with that of acute rejection. During chronic rejection the graft is small and shows low signal intensity, slightly higher than or similar to that of muscle, on both T1- and T2-weighted images. MR imaging appears to be useful for detection of early pancreas allograft rejection and complications in conjunction with clinical findings, laboratory data, and other radiologic procedures.

Acute Disease↗

Application of magnetic resonance imaging in pancreas transplant.

Various imaging methods have been used in the differential diagnosis of pancreas-transplant dysfunction. As early as 1977, angiography and radionuclide studies ([75Se]seleno-DL-methionine) were used to evaluate pancreas allografts. More recently, the use of 99mTc-labeled DTPA, computed tomography, and ultrasonography has been described, and abnormal findings associated with rejection have been reported with these imaging methods. However, no attempt has been made to determine the ability of each method to detect rejection and to differentiate graft dysfunction caused by rejection from dysfunction by other causes. We summarize our experience with the application of magnetic resonance imaging (MRI) in pancreas transplantation and a comparative study of radionuclide 99mTc-DTPA scans, ultrasonography, and MRI in the detection and differentiation of pancreas-graft dysfunction.

Adult↗