Biomedical subjects
Publications and source records attributed to S I Cho.
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We undertook a prospective randomized trial to examine whether an intravenous cytomegalovirus (CMV) immune globulin would prevent primary CMV disease in renal-transplant recipients. Fifty-nine CMV-seronegative patients who received kidneys from donors who had antibodies against CMV were assigned to receive either intravenous CMV immune globulin or no treatment. The immune globulin was administered in multiple doses over the first four months after transplantation. The incidence of virologically confirmed CMV-associated syndromes was reduced from 60 percent in controls to 21 percent in recipients of CMV immune globulin (P less than 0.01). Fungal or parasitic superinfections were not seen in globulin recipients but occurred in 20 percent of controls (P = 0.05). Only 4 percent of globulin recipients had marked leukopenia (reflecting serious CMV disease), as compared with 37 percent of the controls (P less than 0.01). There was a concomitant but not statistically significant reduction in the incidence of CMV pneumonia (17 percent of controls as compared with 4 percent of globulin recipients). A significant reduction in serious CMV-associated disease was observed even when patients were stratified according to therapy for transplant rejection (P = 0.04). We observed no effect of immune globulin on rates of viral isolation or seroconversion, suggesting that treated patients often harbored the virus but that clinically evident disease was much less likely to develop in them. We conclude that CMV immune globulin provides effective prophylaxis in renal-transplant recipients at risk for primary CMV disease.
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.
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At 295 K, crystals of form I of cholesteryl cis-9-hexadecenoate (palmitoleate) and cholesteryl trans-9-hexadecenoate (palmitelaidate) are difficult to distinguish by X-ray diffraction. Both form monoclinic thin plates, space group P21 with two molecules (C43H74O2) A and B in the asymmetric unit. Unit cell dimensions for cholesteryl palmitelaidate (I) are a = 12.827(4), b = 9.075(4), c = 35.67(1) A, beta = 93.42(3) degrees, very similar to those of the palmitoleate crystals. Other crystals (form II) of the palmitelaidate ester are described. The crystal structure of form I of cholesteryl palmitelaidate has been determined from 3657 reflections (sin theta/lambda less than 0.46 A-1) measured at 295 K using CuK alpha X-radiation and refined to give Rw(F) = 0.095. The molecular packing arrangement is isostructural to that of the previously determined crystal structure of cholesteryl palmitoleate. In both crystals, the fatty acid chains of the A molecules are kinked at the double bond but are nearly straight. The chains of B molecules have more complicated dislocations and are bent. It is remarkable that, neglecting their detailed conformations, corresponding fatty acid chains in the two crystal structures have similar overall shapes, although palmitoleate chains have cis-ethylenic groups and palmitelaidate chains have trans groups.
Optimal infrainguinal revascularization should provide limb salvage for the longest duration of time. It is not known whether limb salvage is longer with an initial below-knee popliteal or tibial in situ saphenous vein graft or with staged bypasses; that is, an initial above-knee popliteal prosthetic bypass if feasible, followed by a more distal vein graft should the above-knee prosthetic graft fail. A retrospective review of 197 lower extremity vascular reconstructions performed since 1976 utilizing polytetrafluoroethylene (PTFE), umbilical vein, or in situ saphenous vein was completed. The data were analyzed for differences in limb salvage and prevention of limb threatening ischemia among three subgroups: above-knee prosthetic bypass, below-knee or tibial in situ saphenous vein bypass, and staged reconstructions (above-knee prosthetic bypass with subsequent in situ bypass). The groups were similar with respect to severity of limb threatening ischemia as indicated by mean preoperative ankle-brachial indices. Cumulative secondary limb salvage at 36 months was 73 percent for prosthetic grafts in the above-knee position, 78 percent for in situ saphenous vein grafts in the below-knee or tibial position, and 87 percent for staged reconstruction with an initial prosthetic graft to the above-knee position followed by a distal in situ vein bypass when the prosthetic graft fails.
One hundred thirty two patients who received cadaver kidney transplants in three Boston transplant centers were analyzed to demonstrate the immunosuppressive effect of cyclosporine and steroid therapy versus conventional immunosuppression. Of these, 35 patients received the cyclosporine and steroid regimen and 97 received conventional immunosuppression. The number of patients with preformed reactive antibody was greater in the cyclosporine group; however, a greater number of patients were diabetic in the conventional group. The incidence of acute tubular necrosis was significantly higher in the cyclosporine group. There was no significant difference in transplant or patient survival between these groups.
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Three hundred forty-seven recipients of primary cadaver kidney transplants were analyzed in relation to ATG therapy, pretransplant transfusion, HLA-A, -B and -DR antigen matches, and level of PRA to the panel. Prophylactic ATG treatment increased transplant survival significantly when compared with the non-ATG group. The beneficial effect of pretransplant blood transfusions was not apparent when the recipients received prophylactic ATG treatment. No correlation was noted between HLA-A and -B antigen matches and transplant survival. There was no significant difference in the transplant survival between patients with zero DR antigen match kidneys and those with one DR antigen-match kidney. The number of transplants with two DR antigen-match kidneys was too small to be conclusive. The recipients in whom PRA did not develop despite pretransplant blood transfusions seemed to have better transplant survival than those in whom PRA did develop in response to blood transfusions.