Biomedical subjects
Publications and source records attributed to D K Cooper.
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An enzyme-linked immunosorbent assay (ELISA) was developed to estimate the amount of material carrying blood group A activity in biologic samples. A soluble synthetic form of the A antigenic determinant (A trisaccharide, ATS) conjugated to peroxidase competes with the blood group A substance present in a biologic sample for anti-A attached to a solid phase by a second antibody coating the plastic micro-wells. A reference curve is constructed by using known quantities of ATS to compete with a fixed amount of ATS-peroxidase conjugate. The A substance activity in a sample is obtained by extrapolating the degree of inhibition of the binding of the ATS-peroxidase conjugate to an equivalent amount of ATS in the reference curve. The assay is reproducible, specific, and sensitive. It has been used in pharmacologic studies to estimate the concentration of ATS in the blood and urine of rats, rabbits, and baboons and in a study with human samples, testing the potential clinical use of ATS to neutralize anti-A when therapeutically indicated. It is also useful for the detection of ABO natural products in secretions, thus allowing the accurate classification of secretor and nonsecretor individuals.
As the medical results of heart transplantation steadily improve, the social rehabilitation of patients, in particular, their ability to return to some form of employment, is becoming increasingly important. Two-hundred fifty patients were therefore surveyed at 7 heart transplant centers (5 of which were Medicare certified) from different geographic regions in the U.S.A. Over all, 45% were employed, 36% were unemployed, 13% were medically disabled, and 6% were retired. Of those employed, 87% had returned to their previous employment, and only 13% had secured new employment. Of the unemployed, 16% had made job applications, and no fewer than 63% had no current plan to seek employment. Factors found to negatively influence a return to work included the following: (1) length of medical disability prior to transplantation; (2) a patient's self-perception of being physically unable to work; and (3) the potential loss of health insurance and/or disability income. At 2 centers, where there was a definite policy of not supporting a patient's claim for medical disability in the absence of an absolute indication, there were significantly increased numbers who (1) secured new employment and (2) planned to seek employment. More serious attention must be paid to aspects of employment if heart transplant recipients are to become fully productive members of the community.
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There is evidence to suggest that long-term survival of discordant xenografts may be possible if the organ is transplanted at a time when the host natural anti-species (xenoreactive) antibodies are temporarily absent or otherwise inhibited from reacting with the donor antigens. There is also evidence that the target antigens on pig organs may be carbohydrate structures, as are the human A and B blood group antigens. The intravenous infusion of synthetic A or B trisaccharides in hyperimmunized baboons, coupled with pharmacologic immunosuppression, has prolonged ABO-incompatible cardiac allograft survival from a mean of 19 minutes to several days, and even to several weeks in one animal. The nature of the carbohydrate structures of the pig antigens against which human xenoreactive antibodies are directed has been investigated. Two of the most important of these would appear to be alpha galactosyl structures, referred to as linear B. If the central role of these carbohydrates can be confirmed, then it may be possible to adsorb out or inhibit human anti-pig antibodies in the same way as anti-A and anti-B antibodies. It may then be possible to offer organ transplantation to all suitable recipients under elective conditions without the restriction of donor availability.
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As the results of organ transplantation show steady improvement, we have seen a marked increase in the number of potential organ recipients. During this time however, the number of donor organs becoming available has remained little changed. The reasons for this phenomenon and some potential solutions for improving the supply of donor organs are reviewed.
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Two groups of dogs were subjected to a 15-minute period of regional myocardial ischemia by snaring the left anterior descending coronary artery proximal to its first diagonal branch. After release of the snare, the dogs were given either placebo (group 1: n = 7) or triiodothyronine (T3) therapy (group 2: n = 6). The dose of T3 given was 0.2 microgram/kg at 30-minute intervals to a total of six doses. Plasma free T3 level fell significantly during the ischemic period in both groups and continued to fall after reperfusion in group 1. In both groups, cardiac function deteriorated significantly during the period of ischemia and rapidly returned to control level after reperfusion. After 90 minutes of reperfusion, however, deterioration of left ventricular function was observed in group 1 and was significantly worse than in group 2, in which hemodynamic function was maintained and, in fact, improved to levels superior to control. It is suggested that T3 therapy may be worthy of trial in patients in whom reperfusion of the myocardium takes place after a relatively short ischemic period (the "stunned myocardium").