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Biomedical subjects

A B Cosimi

Publications and source records attributed to A B Cosimi.

At least 145 records · Page 8Linked to original sources
PubMed1988

Combined kidney and pancreas transplantation in diabetics.

Kidney and pancreaticoduodenal transplantation were simultaneously performed in 12 insulin-dependent diabetic patients. These patients had advanced secondary complications, including blindness, vascular disease, and disabling neuropathy. Average posttransplant hospitalization and charges were 17.7 days and $42,780 compared with 11.2 days and $29,000 for patients who received renal allografts alone. Following transplantation, blood glucose and glycosylated hemoglobin A levels promptly returned to normal in all patients. Two patients subsequently died, one after five months of a cytomegalovirus infection and one after seven months of a ruptured bladder. After a mean of 11.6 months of follow-up, ten patients (83%) remained independent of insulin and dialysis. The success of pancreas transplantation in diabetics with advanced complications now approaches that of other organ allografts. It therefore appears reasonable to recommend transplantation for diabetics with less severe secondary complications, since these candidates are most likely to realize the potential benefits of long-term normoglycemia.

Adult↗
PubMed1988

Cure of hemophilia A by orthotopic liver transplantation.

A patient with hemophilia A and transfusion-associated end-stage chronic liver disease underwent orthotopic liver transplantation. He had no requirement for exogenous factor VIII replacement during the 27 mo he survived. Although his hemophilia was cured, he had antibodies to the human immunodeficiency virus; ultimately he died of complications arising from acquired immunodeficiency syndrome. Liver transplantation for cirrhotic hemophiliacs can free them of the need for antihemophilic-factor therapy; however, application of this approach may be limited by the high prevalence of human immunodeficiency virus infection in multitransfused hemophiliacs.

Adult↗
PubMed1988

Monoclonal antibody treatment of human allograft recipients.

Antilymphocyte antibody immunosuppression has evolved to the use of therapeutic antibodies which are monoclonal in content. An antibody is termed monoclonal if each immunoglobulin molecule is produced by a single clone of cells and, thus, is identical in both the heavy and light chain structure to every other molecule in the preparation. Monoclonal preparations provide more consistent bioefficacy and predictable toxicity than do polyclonal products. Studies in nonhuman primate allograft recipients have established the immunosuppressive efficacy of several mAb. The results of pilot trial studies using a pan-T-cell mAb, OKT3, either prophylactically or at the time of acute rejection have revealed OKT3 to be remarkably immunosuppressive in man. OKT3 has subsequently been shown in multicenter, randomized trials to be more effective than conventional suppression in reversing renal and hepatic allograft rejection. In uncontrolled trial studies, similar efficacy in reversing cardiac rejection has been reported. Despite these impressive results, several limitations to OKT3 therapy persist. These include febrile and other systemic symptoms after the first or second infusion, a frequency of recurrent rejection episodes and the development of antibodies to the murine protein which may preclude subsequent treatment with the same mAb. Other murine mAb, such as CBL1 and anti-T12, have been noted to produce less side effects; however, these mAb have not been as effective. The next generation of mAb will be selected to minimize these limitations. It is anticipated that future mAb protocols will specifically suppress only selected subsets of T cells, and that these mAb may be chimeric or even human in structure to limit their immunogenicity.

Adult↗
PubMed1987

Plasma interleukin 2 receptor levels in renal allograft recipients.

Shed/soluble interleukin 2 receptor (IL2R) was measured by an enzyme-linked immunosorbent assay (ELISA) in serial samples of plasma from 32 patients with renal allografts. Patients on chronic dialysis (pretransplant) had elevated IL2R levels which fell toward normal after transplantation. Patients with acute rejection and viral infection had significantly higher levels of plasma IL2R than did patients with stable renal function or with cyclosporine nephrotoxicity (all P less than 0.005). Acute renal failure from other causes (renal artery stenosis, hemolytic-uremic syndrome) did not have a comparable rise in IL2R. The assay of shed/soluble IL2R may have diagnostic value in the clinical management of allograft recipients, a possibility that deserves further clinical evaluation.

Antibodies, Monoclonal↗
PubMed1987

The selective use of antilymphocyte serum for cyclosporine treated patients with renal allograft dysfunction.

Eighty-seven adult renal allograft recipients were initially treated with cyclosporine-prednisone immunosuppression. Thirty patients experienced no episode of rejection. Antilymphocyte antibody therapy (ALS) was administered to 21 of the 68 recipients of cadaveric donor allografts for either primary allograft dysfunction or acute rejection, and to 6 of 19 recipients of haploidentical, living-related allografts because of steroid-resistant rejection. The cumulative allograft and patient survival for the entire series (follow-up 9-36 months) was 84% and 95%, respectively. This improvement in the rate of successful transplantation can be attributed to the selective addition of ALS therapy to recipients with specific instances of renal allograft dysfunction. In this report, the indications for the use of ALS preparations following prophylactic CsA immunosuppression are reviewed. Experience with the protocols of the ALS administration is also discussed. In selected cases, the administration of either ATG or OKT3 can significantly benefit CsA recipients who experience either primary allograft nonfunction or an epidose of acute rejection.

Administration, Oral↗
PubMed1987

A randomized clinical trial comparing OKT3 and steroids for treatment of hepatic allograft rejection.

A multiinstitutional randomized trial was undertaken comparing OKT3 with steroids for treatment of hepatic allograft rejection. All patients received baseline immunosuppression with Cyclosporine (CsA) and steroids. At the time of biopsy-confirmed rejection, up to 2 intravenous boluses (250-1000 mg) of methylprednisolone were initially administered. Twenty-eight patients who failed to respond were then randomly assigned to OKT3 or continued steroid therapy. Rescue therapy with the opposite treatment arm was added after 6 days if the primarily allocated protocol failed. Three of 13 patients assigned to the steroid group responded promptly, and continue with good function 7-12 months later. OKT3 rescue was required in 10 patients who failed to improve despite receiving up to 6 g of methylprednisolone (mean: 3.3 g/patient). One patient died of sepsis and hepatic failure. Rejection was reversed in 9 OKT3-rescue patients, 7 of whom are well 1-17 months later. In the OKT3 group, improved allograft function was observed within 72 hr in 11 of 15 patients. Two patients with inadequate response were successfully rescued with steroids; 1 patient underwent retransplantation; and 1 patient developed a biliary fistula that eventually resulted in sepsis and death. In summary, 23 of 28 hepatic recipients (82%) are alive with the original allograft 1-17 (mean 7.8) months after treatment for acute rejection. Another patient is alive 14 months following retransplantation. Eighteen (78%) of the survivors required OKT3 as initial (11) or rescue (7) therapy, whereas only 5 were successfully managed with steroids. OKT3 is superior to steroids for reversing liver allograft rejection and has greatly reduced the need for retransplantation even in recipients selected on the basis of having failed initial steroid therapy.

Antibodies, Monoclonal↗
PubMed1987

OKT3: First-dose safety and success.

Orthoclone OKT3 is a murine monoclonal antibody that has been shown to be effective in reversing acute rejection episodes. In a randomized, multicenter trial, Orthoclone OKT3 reversed 94% of acute rejection episodes; conventional treatments reversed only 75%. However, early trials also disclosed some limitations of OKT3 therapy, such as a severe febrile or bronchospastic response following the initial injection, recurrent rejection episodes after discontinuation of OKT3 administration, or the host's production of antibodies to the murine immunoglobulin. In later experiments modifications and precautions applied to the therapeutic helped to control first-dose reactions and decrease antibody production from 86 to 39%. Furthermore, recurrent rejection episodes occurring after discontinuation of OKT3 therapy in azathioprine-prednisone-treated patients have been shown to be reversible in most cases: a 75% rate of long-term (14- to 26-month) allograft survival has been achieved in these patients. More recently, OKT3 treatment administered to allograft recipients receiving cyclosporin has been shown to benefit 15-20% of patients when administered at the time of rejection. This combination approach not only reverses the rejection, but also seems to significantly reduce the incidence of subsequent rejection episodes. OKT3 has raised clinical immunosuppressive specificity to a higher level than previous therapies such as steroids or cytotoxic agents. OKT3 appears to be safe and effective therapy for patients receiving cyclosporin or azathioprine-prednisone therapy. Despite certain unresolved limitations, it may be a successful prototype for future, even more highly specific, immunosuppressive protocols.

Antibodies, Monoclonal↗
PubMed1987

Psychosomatic aspects of liver transplantation.

Forty patients received orthotopic liver transplants at Massachusetts General Hospital between May 21, 1983 and July 21, 1987 (mean follow-up: 64 weeks, range: 2-186 weeks). Twenty-seven patients (68%) were living as of July 21. Among survivors, 15 (56%) returned to full activity; and 7 (26%) were partially rehabilitated. Five patients were rehospitalized or recently transplanted. Successful outcome occurred most often among those who came to transplant early in the course of illness. All adults experienced preoperative anxiety and 17 (50%) of adults had some degree of hepatic encephalopathy. Following operation, 8 adults (24%) were referred for treatment of depressive disorder typically associated with deterioration of hepatic status, infectious complication or recurrence of cancer. Medical noncompliance required psychiatric intervention in 3 cases. Other psychiatric events an increasingly successful intervention of major scope and affords meaningful survival to many patients whose liver disease allow less than a year of life. Psychiatric consultation is an essential support to the transplant program.

Adjustment Disorders↗
PubMed1987

Mononuclear cells in acute allograft glomerulopathy.

A distinctive glomerular lesion of renal allografts, acute allograft glomerulopathy (AAG), is characterized by hypercellularity and endothelial cell hypertrophy and injury. For elucidating the pathogenesis of this lesion, the infiltrating cells were analyzed by light- and electron-microscopic immunoperoxidase techniques with monoclonal antibodies and compared with those in cellular rejection without AAG (non-AAG). Substantial numbers of T lymphocytes (CD3+,Leu-4+) were detected in the glomeruli in AAG (11.4 +/- 2.4 cells per glomerular cross-section), whereas very few were found in non-AAG (1.4 +/- 1.8, P less than 0.001). In AAG the CD8+ (Leu-2a) subset accounted for essentially all of the intraglomerular T cells, which had a lower CD4/CD8 ratio than the corresponding peripheral blood lymphocytes (P less than 0.03). AAG also differed from non-AAG by the accumulation of intraglomerular mononuclear cells that expressed HNK-1 antigen (Leu-7) and mononuclear phagocytes, which were identified by the presence of the monocyte fibronectin receptor (A6F10). Intraglomerular mononuclear cells were positive for the interleukin-2 receptor (IL2R) and HLA Class II antigens (HLA-DR). The glomeruli in AAG stained more intensely for HLA Class I antigens than the tubules, in contrast to non-AAG cases (P less than 0.03). The interstitial infiltrates in AAG grafts were less intense than in non-AAG of similar duration (P less than 0.01) and had a lower CD4/CD8 ratio, whereas arterial intimal infiltrates were more severe in AAG (P less than 0.03) and consisted of CD8+, but not CD4+, cells. Pathologic features that correlated with poor graft survival were increased numbers of intraglomerular CD8+ cells (both AAG and non-AAG), fewer interstitial T cells (AAG), and more interstitial CD8+ cells (non-AAG) (all P less than 0.05). Cytomegalovirus (CMV) infection was detected in all (8/8) patients with AAG who were studied for infection before or within 3 weeks after the biopsy, compared with 3 of 9 patients with non-AAG. It is proposed that acute allograft glomerulopathy is a distinct form of T-cell-mediated allograft rejection, sometimes associated with CMV infection, in which the glomerular endothelium, often with the arterial endothelium, becomes the principal target of CD8+ T cells.

Adult↗