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Distribution of pulmonary ventilation and perfusion and pulmonary gas exchange were studied in 2 dogs surviving 4 years after bilateral reimplantation and 4 dogs surviving 13-25 months after unilateral allotransplantation of the lung. These studies showed variable degrees of pulmonary dysfunction in all animals but significant levels of function could be demonstrated in all lungs tested. Gas exchange was best when reduction of ventilation was matched by reduction in perfusion. Animals were observed to survive and appear normal with bilaterally reimplanted lungs.

OBJECTIVE: To compare the efficacy, safety, and cost of prophylactic low-dose ganciclovir with that of immunoglobulin in renal transplant recipients at risk for primary cytomegalovirus (CMV) disease. DESIGN AND SETTING: A prospective, randomized trial at a 650-bed tertiary medical center hospital. PATIENTS: Fifty-one consecutive CMV-seronegative patients who received renal allografts from seropositive donors between March 1990 and April 1992. MAIN OUTCOME MEASURES: Patient and allograft survival, and the incidence and severity of CMV disease. INTERVENTION: Cytomegalovirus prophylaxis with seven doses of intravenous immunoglobulin for 6-week periods (group 1, n=27) or low-dose intravenous ganciclovir for 3 weeks (group 2, n=24). Results were compared with those obtained in 23 CMV-seronegative historical positive donors between 1987 and 1989, and who did n-positive donors between 1987 and 1989, and who did not receive prophylaxis for CMV (group 3). RESULTS: Both prophylactic regimens significantly reduced the incidence of invasive CMV infection (P<.05) and were well tolerated. However, the cost of ganciclovir ($350 per patient) was substantially less than that of immunoglobulin ($4000 per patient). CONCLUSIONS: These data suggest that prophylactic ganciclovir therapy provides a cost-effective approach toward significantly improving the outcome of renal transplantation in recipients at risk for primary CMV disease.(Arch Surg. 1994;129:443-447)

• Hydrogen peroxide (100 to 200μM) inhibited the response of human peripheral-blood mononuclear cells (PBMCs) in phytohemagglutinin, concanavalin A, and mixed lymphocyte culture assays by more than 90% without affecting cell viability. The response of PBMCs to pokeweed mitogen was stimulated twofold by 50μM H2O2, but 200μM H2O2 inhibited the pokeweed mitogen response by more than 95%. A 50μM concentration of H2O2 completely blocked the generation of cytotoxic T cells in the mixed lymphocyte culture but did not inhibit the production of interleukin 2. Concentrations of 100μM to 200μM H2O2 inhibited interleukin 2 production by 45% to 57%. The H2O2 appeared to block early events in T-cell activation, since 200μM H2O2 was not inhibitory when added one hour after stimulating the cells with phytohemagglutinin. Treatment of PBMCs with 200μM H2O2 did not decrease the total cellular thiol pool, suggesting that H2O2-mediated inhibition of the proliferative response was not due to thiol oxidation. However, pretreatment of PBMCs with the lipid antioxidants butylated hydroxyanisole, butylated hydroxytoluene, and n-propyl gallate blocked more than 75% of the inhibitory effect of H2O2, suggesting that H2O2 inhibits T-cell activation by inducing lipid peroxidation.(Arch Surg 1987;122:99-104)

• Hydrogen peroxide, a reactive oxygen intermediate produced by activated neutrophils, has been shown to inhibit the response of human T lymphocytes to mitogens and alloantigens. Since hydrogen peroxide is known to react with iron and to induce lipid peroxidation, we compared the effects of hydrogen peroxide and a lipid peroxidation product, malondialdehyde, on the response of human peripheral blood mononuclear cells to T-cell mitogens. Peripheral blood mononuclear cells pretreated with 1 mmol/L of malondialdehyde, washed, and resuspended in fresh medium exhibited no inhibition of phytohemagglutinin responsiveness. Peripheral blood mononuclear cells treated in the same manner but with 200 μmol/L of hydrogen peroxide were inhibited by more than 95%. The addition of ferric edetate did not alter the inhibitory effects of 50 to 100 μmol/L of hydrogen peroxide, nor did the addition of deferoxamine, an iron chelator. These studies suggest that exogenous lipid peroxidation does not affect lymphocyte activation but that hydrogen peroxide has a direct inhibitory effect. Although monocytes are necessary for T-cell mitogenic responses, the effect of hydrogen peroxide was found to be directed at T lymphocytes. Exposure of T cells to a single dose of 200 μmol/L of hydrogen peroxide resulted in more than 71% suppression of the proliferative response measured 48 hours later, but the effect was spontaneously reversed by 72 to 96 hours. Repeated exposure of the cells to hydrogen peroxide resulted in continued inhibition of the proliferative response. These findings suggest that hydrogen peroxide produced by inflammatory phagocytic cells might be capable of suppressing the immune response of nearby T lymphocytes.(Arch Surg 1988;123:300-304)

Forty-five dogs have been treated with varying dosages of nitrogen mustard. Nineteen of these dogs were subjected to cross-clamping of the splenic vessels prior to administration of the drug. No appreciable improvement in mortality or degree of marrow depression has been found with this technic. Exclusion of the spleen and small intestine has been found to be a practical and reliable method for protecting these organs from the effect of intravenous administration of nitrogen mustard.

Preexisting humoral immunity to donor alloantigens was investigated in 67 potential renal transplant patients on chronic hemodialysis on a continuing basis over 28 months by 2,740 cytotoxicity tests. The cytotoxicity tests were enhanced by the use of six concentrations of recipient sera, and other techniques for better assessment of immunity. The six-well crossmatch concentration profile demonstrated 596 discordant results (21.8%) from those obtained by a single-well crossmatch. Among these were 196 positive profiles which were negative in the customary 1λ well. The profile method further demonstrated a low number of false positives (32) and resolved 100 of 116 doubtful reactions. Dilutions appeared more valuable than concentrations in determining the final crossmatch. No cases of hyperacute or accelerated rejection occurred in 20 cadaver and 9 related kidney transplants.