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We used data from the National Infant Mortality Surveillance project to examine the effect of older maternal age on infant mortality for the 1980 United States birth cohort. The 1,579,854 births and 14,591 deaths of singletons who were black or white and whose mothers were 25-49 years of age were included. Direct standardization was used to calculate birth-weight-adjusted relative risks of neonatal and postneonatal mortality, using the birth weights of infants with maternal age 25-29 as the standard. We found that the risk of infant mortality was nearly equal for infants born to mothers 25-29 and 30-34 years of age; infants born to mothers 35-39 years of age were at a slightly elevated (18% higher) risk, and those born to mothers 40-49 years of age were at a much more elevated (69% higher) risk. Among whites, the higher neonatal mortality associated with a maternal age of 35-39 was mostly due to an increased prevalence of low birth weight; among blacks, it was due to higher birth-weight-specific risks. Neither white nor black postneonatal mortality risks were much elevated until a maternal age of 40-49, and this last elevation was mostly due to higher birth-weight-specific risks. These findings suggest that infertility and fetal mortality aside, and considering only the effect on infant mortality, it is relatively safe for women to postpone childbearing into their middle, and perhaps late, thirties.

Intravascular perfusion of healthy, viable human kidneys either with human sera or with monoclonal antibodies specific for individual HLA-A, B, DR or E-M antigens demonstrated that all of these antigens are exposed to circulating antibodies and thus can serve as stimuli or targets for immunologic mediators of renal transplant rejection. In addition, these antibodies could be recovered from the renal vessels by brief treatment with acid buffer.

Primarily vascularized LBN cardiac allografts transplanted to LEW rats are rejected 6 to 8 days after transplantation. Immunoperoxidase stains for cells producing immunoglobulin (Ig) demonstrate a proliferation of Ig-containing immunoblasts in the splenic red pulp (RP) and peripheral periarterial sheath (PAS) within 2 days after transplantation. These immunoblasts differentiate into plasma cells that triple the RP volume by the time of rejection. By 14 days, the plasma cells are replaced by mitotically active large and small lymphocytes with no demonstrable cytoplasmic Ig. Splenic Ig production is followed by a venous vasculitis in the graft and by the appearance of circulating cytotoxic antibodies 5 days after grafting. Three biological methods of prolonging cardiac graft survival were found to derange this sequence of immunological reactions at different stages. Enhancement by antigen and antibody pretreatment of the recipient elicited a premature production of Ig that subsided and was not reinitiated by cardiac transplantation. Transfer of suppression with thymocytes from enhanced cardiac recipients temporarily inhibited differentiation of splenic B cells into immunoblasts and plasma cells. T cell depletion by thymectomy, irradiation, and bone marrow reconstitution also decreased the plasma cell response, possibly by removing helper cells required to switch IgM production to IgG. These studies reemphasize the importance of Ig production in the complex interaction of immune reactions leading to acute rejection of organ transplants.

Clearly the pioneering studies on hyperacute rejection, which lead to the concept of antibody-mediated injury to transplants, still present challenges to the clinician today. It is obvious that tests for antibodies before and after transplantation must be further refined to more reliably distinguish among destructive, protective and innocuous antibodies. The current crossmatch tests detect antibodies to donor lymphocytes, but lymphocytes may not always represent adequately the antigenic composition of the tissue that will be transplanted. Moreover the distribution of antigens in transplanted tissues must be considered in relation to the functional anatomy of the organs in order to understand the ultimate effects of antibodies on specific transplants. Thus some antibodies that produce a positive crossmatch may be safely ignored because they exert either a beneficial or no effect on the organ that is to be transplanted, while other antibodies that remain undetected by crossmatches on lymphocytes may damage some types of transplants. Moreover, the balance between protective and destructive antibodies is not dynamic; with time potentially dangerous antibody responses may be inhibited by a variety of autoregulatory mechanisms, some of which may be mediated by antibodies. Regulatory as well as cytotoxic antibody production may be actively stimulated by pretransplant blood transfusions. These antibody-mediated immune responses probably are magnified in the clinical setting by our current therapeutic immunosuppressive drugs which have more impact on cell-mediated immunity than on antibody-mediated mechanisms. New immunosuppressive interventions devised to inhibit undesired antibody-mediated immune responses might be of benefit to those patients who fail to respond to current rejection therapy as well as to patients who have pre-existing antibodies and are waiting for transplants.

The Optometric Research Institute has clinically evaluated the effectiveness and efficiency of the Erickson Goniolens System. Operational procedures and interpreting the results are discussed. Advantages, disadvantages and conclusions are expressed.