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Biomedical subjects

M L Henry

Publications and source records attributed to M L Henry.

At least 73 records · Page 4Linked to original sources

Antibody depletion prolongs xenograft survival.

BACKGROUND: The lack of human organ donors has prompted a renewed interest in xenotransplantation. Xenoantibody is believed to be an initiator of a complex cascade of events ultimately ending in rapid xenograft destruction. METHODS: Cell-free plasma was obtained via plasmapheresis of the recipient canine. This plasma was then perfused in an ex vivo fashion through either the donor (pig) spleen or liver, allowing for specific antidonor antibody deposition in the "screening" organ, and is then returned to the animal. A porcine kidney is then transplanted to the dog, and the outcome is observed. RESULTS: We have used specific antibody depletion to prolong xenotransplant survival. In the untreated pig-to-dog combination, the transplanted pig kidney is destroyed by the dog in 13 minutes (mean). Adsorption using either the donor spleen or liver resulted in an increase of 3.4 hours and 7.8 hours of graft survival, respectively. The histologic picture of rejected kidneys after adsorption shows a modified form of rejection. CONCLUSIONS: In this pig-to-dog xenograft combination, xenoantibody adsorption allows for prolonged graft survival as compared with control animals. Subsequent xenograft destruction occurs but in a modified manner.

Adsorption↗

A randomized, prospective, double-blinded trial of cyclosporine vs. OG37-325 in cadaveric renal transplantation--a preliminary report.

The efficacy of cyclosporine is documented, but it has side effects that are troublesome. Another compound, OG37-325, has been identified that appears to have similar efficacy, but less nephrotoxicity. This study was designed to address the benefits and toxicities of cyclosporine and OG37-325 in a prospective, randomized, double-blinded trial in cadaveric renal transplant recipients. The preliminary results demonstrate similar outcomes in terms of patient and graft survival, but suggest less nephrotoxicity in the OG37-325-treated patients. Longer follow-up will delineate the utility of OG37-325 in solid-organ transplantation.

Adult↗

OKT3 for primary therapy of the first rejection episode in kidney transplants.

The improvement in one-year graft survival has allowed transplant centers to focus on long-term graft survival. A study of 665 primary cadaveric kidney transplants from a single center treated with cyclosporine demonstrated that patients did not develop chronic rejection if there was not an episode of acute rejection. This study is a retrospective review of 314 consecutive kidney transplants from a single center to determine if early, aggressive treatment of the first episode of acute rejection will improve graft survival without increasing recipient morbidity. The course of 314 consecutive kidney transplants performed during a 27-month period (245 CAD and 68 living-related) was studied. Demographic characteristics were equivalent between the two groups, and all patients received sequential quadruple immunosuppression using ALG and CsA. Patient and graft survivals at 2 years were 89.7% and 84%, respectively. At least one rejection episode occurred in 41% of the patients, one-half within 30 days of transplant. Rejection episodes were treated by oral prednisone taper, primary ALG or OKT3, or "rescue" therapy with ALG or OKT3. Graft survival in the 52 recipients treated with OKT3 for primary treatment of first rejection episode was 20% better than the 50 patients treated with PRED (P = 0.0847). Comparing the 39 recipients of primary CAD kidneys treated with primary OKT3 vs. 38 treated with PRED demonstrated a 32% improvement in 2-year graft survival (P = 0.033). There was no increase in second rejection episodes in patients treated with OKT3. Renal function was equivalent in patients with rejection regardless of type of antirejection therapy used. Of patients treated for rejection, 22% had symptomatic CMV infections, which were divided equally between the two groups. Eighty-two patients received a single course of OKT3, 28 received two courses, and 2 patients received OKT3 three times. Only two patients developed antimurine antibodies that required abandoning OKT3 for the treatment of rejection. This study clearly demonstrates that the early use of OKT3 as primary treatment of rejection results in significant improvement of 2-year graft survival in recipients of first CAD kidney transplants. There is no increase in episodes in CMV in patients treated with OKT3 as primary therapy and no increase in patient mortality. Early use of OKT3 does not prevent or decrease incidence of subsequent rejection episodes. Renal function in surviving grafts is not improved in patients treated with OKT3 vs. PRED.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Minimal model analysis of insulin sensitivity and glucose-mediated glucose disposal in type 1 (insulin-dependent) diabetic pancreas allograft recipients.

Decreased insulin sensitivity and glucose-dependent glucose disposal (glucose effectiveness) have been demonstrated in poorly-controlled Type 1 (insulin-dependent) diabetic patients. We have therefore examined the effects of successful pancreas transplantation that results in long-term physiologic normoglycaemia as measured by insulin sensitivity index and glucose effectiveness in 14 Type 1 diabetic recipients (Group 1) using the Bergman minimal model method. Their results were compared with those of five non-diabetic patients with kidney transplant alone (Group 2) and 10 healthy control subjects (Group 3). Mean plasma glucose levels were indistinguishable in Group 1 when compared to Groups 2 and 3. However, mean basal plasma insulin levels were two- and eight-fold greater in Group 1 (36 +/- 6 microU/ml) than in Group 2 (17 +/- 7 microU/ml) and Group 3 (4.5 +/- 0.6 microU/ml), respectively. Following intravenous glucose (t = 0 min) and tolbutamide (t = 20), peak incremental insulin levels were significantly (p less than 0.001) greater in Group 1 vs Groups 2 and 3. Mean insulin sensitivity index was 65% and 50% lower in Group 1 (2.89 +/- 0.45) and Group 2 (4.11 +/- 1.30), respectively, when compared to Group 3 (8.40 +/- 1.24 x 10(-1) min-1 (microU/ml)-1. In contrast, glucose effectiveness was similar in the three groups (Group 1, 2.48 +/- 0.26; Group 2, 2.05 +/- 0.21; and Group 3, 2.10 +/- 0.17 x 10(-2).min-1). We conclude that, despite prednisone-induced insulin resistance, normal glucose tolerance is achieved by hyperinsulinaemia and normalisation of glucose-dependent glucose disposal following pancreas-kidney transplantation in Type 1 diabetic patients.

Adult↗