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Biomedical subjects

F P Stuart

Publications and source records attributed to F P Stuart.

At least 55 records · Page 3Linked to original sources

Reexposure to OKT3 in renal allograft recipients.

Between 40% and 80% of patients treated with the monoclonal antibody OKT3 develop blocking antibody against its idiotypic region. Thus a major concern with the use of OKT3 as part of a baseline immunosuppressive regimen is that formation of blocking antibodies might preclude its subsequent use. Between 7/86 and 2/87, 32 patients received prophylactic OKT3 in addition to low-dose prednisone, azathioprine, and cyclosporine. Prophylactic OKT3 did not prevent rejection, as 21 of 32 patients studied developed rejection. Retreatment of 13 patients with OKT3 successfully reversed 12 rejections and lowered the number of T3-positive cells in spite of a low level of blocking antibody in two patients in this group. Of the patients analyzed, 38% developed blocking antibody on initial exposure to OKT3, but OKT3 reuse was denied only 4 patients due to the presence of these antibodies. Three of these had rejections reversed with steroids alone; the other patient lost the allograft. A high frequency of infectious complications occurred in the retreatment group, with viral infections predominating. Only one patient in the retreated group developed antibodies after the second use. Appearance of blocking antibodies after use of OKT3 as part of a base-line prophylactic immunosuppressive regimen did not significantly compromise access to OKT3 for treatment of subsequent rejection episodes, but multiple exposures to OKT3 did increase the frequency of infectious complications.

Antibodies, Anti-Idiotypic↗

OKT3 treatment of steroid-resistant renal allograft rejection.

The monoclonal antibody, Orthoclone OKT3 (OKT3), has been used with great efficacy in a prospective multicenter trial as therapy for first rejection episodes in cadaveric donor (CD) renal allograft recipients treated with azathioprine (AZA) and prednisone (P). However, although almost all rejection episodes were reversed, recurrent rejection occurred in approximately two-thirds of OKT3-treated patients in this earlier trial; infections also occurred in about two-thirds of patients, often related to the additional immunosuppression necessary to reverse the rerejection episodes. In the current series of patients, OKT3 was used to treat rejection in CD renal graft recipients in a protocol differing from the multicenter trial in two respects: baseline immunosuppression was cyclosporine (CsA) and P or CsA, AZA, and P (probably more potent immunosuppressive combinations than the AZA and P in the multicenter trial); and OKT3 treatment was reserved for rejection episodes resistant to 3 bolus infusions of methylprednisolone (MP), 5-10 mg/kg, rather than as primary therapy for first rejection episodes. Using this protocol, 46 of 74 rejection episodes (62%) diagnosed between 3/85 and 3/86 in CD renal allograft recipients were treated successfully with MP. Of the remaining 28 steroid-resistant rejection episodes, 27 (96%) were reversed with a 7-14-day course of OKT3, 5 mg/day. Only 5 recurrent rejection episodes (19%) have been observed in the 2-14-month follow-up period after OKT3 treatment; infections have occurred in 10 patients (36%), and three grafts (11%) have been lost in OKT3 treated patients. These results suggest that recurrent rejection and subsequent infection after OKT3 is used to treat rejection may be reduced in a protocol where CD renal allograft recipients are treated with baseline immunosuppression regimens including CsA and where OKT3 is reserved for steroid-resistant rejection. This approach appears to be both more cost-effective than, and as effective therapeutically as, treating all first rejection episodes with the monoclonal antibody.

Adolescent↗

Potent immunosuppression overcomes immunologic high-risk factors in recipients of cadaveric renal allografts.

With the introduction of more potent immunosuppressive regimens, increasing numbers of kidney transplant recipients traditionally viewed as being at high immunologic risk for rejection and graft loss have been accepted. These include recipients of multiple grafts, sensitized patients as measured by high panel reactive antibody (PRA), and patients with current warm B or historical positive crossmatches. Since November 1983, all recipients of cadaver kidneys have been treated with cyclosporine and prednisone. In addition, most also received a short posttransplant course of antilymphocyte globulin and long-term azathioprine. With these regimens, retransplantation, sensitization, current B-cell crossmatch and historical B- and/or T-cell crossmatch do not affect graft survival.

Antibodies, Monoclonal↗

Elective conversion from cyclosporine to azathioprine in recipients with stable renal function 6 months after kidney transplantation.

The average cost of cyclosporine over the first 6 months after renal transplantation has been $2450/recipient for recipients with stable renal function. Fifty-nine percent of all patients transplanted in 1984 do not have a third-party payment mechanism for outpatient medicines and many cannot afford cyclosporine. The expense of cyclosporine has, thus, mandated developing a protocol for conversion from cyclosporine to azathioprine. Using a protocol, which included a short overlap of cyclosporine and azathioprine and a temporary, modest increase in prednisone dose, 27 renal allograft recipients with stable renal function have undergone conversion of their immunosuppressive regimen approximately 6 months posttransplant with a minimum follow-up of 4 months from conversion. There has been no graft loss or patient death. Mean serum creatinine has been reduced in recipients with stable function after conversion (1.4 mg/dl 3 months postconversion compared to 1.8 mg/dl preconversion). However, acute breakthrough rejection has occurred in four recipients (15%), and, after reversal of rejection, mean serum creatinine is elevated (3.1 mg/dl) in this group. Only a single patient developed an infection during the conversion period. Thus, a policy of conversion from azathioprine appears to be a reasonable compromise for those patients who cannot afford long-term outpatient treatment with cyclosporine.

Adolescent↗

Transplantation.

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Blood Grouping and Crossmatching↗

Properties of liposomes containing 212Pb.

The reverse phase evaporation method was used to prepare lipid bilayer membrane vesicles containing 212Pb and other markers of high specific activity. Electron microscopy and microfiltration were used to measure the sizes of the liposomes. Isotopes were released from the liposomes during exposure to serum and this leakage was prevented by complexing of small molecules with proteins or by precipitating particulate complexes within the liposomes. The in vivo distribution of 212Pb liposomes differed from the distribution of free 212Pb in that the reticuloendothelial system cleared the liposomes. Liposomes with surface dinitrophenol hapten were highly immunogenic and the humoral response to dinitrophenol was nonspecifically suppressed by 212Pb liposomes.

Animals↗

Effect of warm ischemia on segmental pancreas transplantation in the rat.

This study was performed to determine the effect of warm ischemia on post-transplantation endocrine function of rat segmental pancreas transplants. Diabetic (streptozotocin) rats were recipients of syngeneic vascularized grafts in all experiments. Thirty-, 60-, and 90-min periods of absolute ischemia at 37 C in addition to approximately 30 min of anastomosis time did not impair control of glucose metabolism as manifested by daily serum glucose values or response to intravenous glucose challenge when compared with control rats transplanted with freshly harvested pancreata. However, when the ischemic period was lengthened to 120 min, only one of five recipients had normal glucose values post-transplant. Islet morphology in the 30-, 60-, and 90-min ischemia groups was not different from controls. On the other hand, after 120 min of ischemia, islets were decreased in number, appeared smaller in size, and had undergone degeneration. For comparison, renal isografts using kidneys with 90 min of warm ischemia failed. These data suggest that in this model, islets in segmental pancreas transplants are more tolerant of warm ischemia than kidneys.

Animals↗

Gastroduodenal complications in kidney transplant recipients.

Oral antacids taken every two hours while awake provided the only prophylaxis against gastroduodenal ulceration for 167 kidney transplant recipients between 1968 and July 1978. Either perforation or major hemorrhage occurred in eight patients within 30 days after transplantation. Between July 1978 and January 1981, bleeding occurred within 30 days in two of 147 recipients who were treated with both antacids and cimetidine. Of the 147 patients, eleven with a history of ulcers had undergone pretransplant vagotomy; neither perforation nor hemorrhage occurred in any of the eleven patients. Despite reports that cimetidine enhances certain types of immune responses, we observed slightly greater graft survival in the group treated with cimetidine.

Adult↗