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A S Daar

Publications and source records attributed to A S Daar.

102 records · Page 6Linked to original sources

Organ-specific IgM autoantibodies to liver, heart and brain in man: generalized occurrence and possible functional significance in normal individuals, and studies in patients with multiple sclerosis.

In this paper we use a sensitive, 125I-anti-immunoglobulin-binding assay, recently adapted for use with tissue homogenates as targets, to demonstrate autoantibodies to brain, liver and heart in the sera of normal persons. Quantitative absorption analyses demonstrated that the autoantigens detected were in each case organ-specific, and the brain autoantigen was shown to be present in equal amounts on cerebral cortex, cerebral white matter and cerebellar cortex. The autoantibodies were shown to be IgM in nature by gel filtration studies and experiments where IgM was reduced to monomers, and were found to bind equally well at 4, 20 and 37 degrees C. Cross-reactions with brain, liver and heart of rat and dog were unpredictable and usually weak. Parallel studies with kidney homogenates failed to detect anti-kidney autoantibodies, but immunofluorescence studies on frozen sections revealed large amounts of immunoglobulin in normal kidneys, mainly on glomerular and tubular basement membranes, raising the possibility that autoantibodies to kidney are present but that the autoantigen sites are situated in vivo. Sera from patients with multiple sclerosis were indistinguishable from normal sera in their binding to brain homogenate, and CSF from five patients with multiple sclerosis did not bind at all to brain homogenate. The theoretical and practical significance of multiple IgM autoantibodies in normal persons, and the organ specificity of the autoantibodies, is discussed.

ABO Blood-Group System↗

Graft avulsion: an unreported complication of axillofemoral bypass grafts.

A case of avulsion of a unilateral axillofemoral Dacron bypass graft 3 weeks after insertion is reported. Surface measurements on healthy volunteers suggest that when the thoracolumbar spine is in full lateral flexion the length of the graft may increase by up to 21 per cent. Such movements should be restricted during the early postoperative period.

Aged↗

Leucocytosis is not a manifestation of rejection.

The leucocyte response to allograft rejection was retrospectively analysed in 80 rejection episodes that occurred in 50 patients. There was no significant change in leucocyte count in 32 rejection episodes. In 27 there was a fall in leucocyte count of more than 20% and in only 21 was there a rise in count of more than 20%. Thus leucocytosis seems not to be a manifestation of rejection; indeed, it is the least common response, a fall in the count being commoner. The results also suggest that the prognosis for the graft is poorer when the leucocyte count falls significantly.

Graft Rejection↗

Prevalence of antibodies to hepatitis C virus among Omani patients with renal disease.

The prevalence of hepatitis C virus (HCV) infection in Omani patients with renal disease was determined using a second-generation enzyme immunoassay which detects antibodies to three HCV antigens. Based on the results of this assay, 27 of 102 (26.5%) sera from patients on haemodialysis, 11 of 82 (13.4%) sera from kidney transplant patients, and 1 of 103 (1%) sera from non-dialysed, non-transplanted patients with various renal diseases had antibodies to HCV. Among healthy subjects, none of 134 medical students and 5 of 564 (0.9%) blood donors were anti-HCV positive. Thus, the prevalence of HCV infection in dialysis and renal transplant patients was significantly higher than that found in patients with renal disease who had been neither dialysed nor transplanted (p < 0.05). In the latter group of patients, the frequency of anti-HCV was low, and comparable to that of healthy Omani subjects.

Adolescent↗

Ethics of xenotransplantation: animal issues, consent, and likely transformation of transplant ethics.

The shortage of organs, breakthroughs in research, involvement of biotechnology companies, absence of ethically more acceptable alternatives, and a vaguely perceived "time to put man on the moon" feeling have contributed to the current reawakening of interest in xenotransplantation. The focus of ethical attention has changed from the moral correctness of using animals for research/therapy to an increasingly appreciated danger of the establishment and spread of xenozoonoses in recipients, their contacts, and the general public. The United Kingdom has established an embargo on clinical trials and has set up a national regulatory authority to oversee and coordinate the development of research, establish guidelines, and decide on when trials can proceed. In the United States, on the other hand, the overall attitude is to "proceed with caution," and the Food and Drug Administration has approved a number of xenotransplant studies. The Public Health Service guidelines on reducing infection risk are still evolving and are likely to end up being more cautions than they are currently. There are a number of reasons for not using subhuman primates for xenotransplantation, including their closeness to humans, the likelihood of passing on infections, their depletability (gorillas, chimpanzees), their slow breeding, and the expense of breeding them under specified-pathogen free conditions. The pig, although domesticated and familiar, is too distant to evoke the same feelings we have for primates, has the correct-size organs, is probably less likely to pass on infections, breeds rapidly, and is not endangered; moreover, millions of them are eaten every year. Although drawing ethical conclusions is difficult, at this stage of knowledge and debate it seems acceptable to manipulate pigs genetically and to proceed to using their organs for xenotransplantation trials when infection control measures and the scientific base justify it. The question of informed consent is likely to be a vexing one. It might end up more of a binding legal contract than consent as we understand it now. Xenotransplantation is also unlikely to cost less than, or significantly alleviate the shortage of, cadaveric organs in the short term. The international dimension of the risk of infection is becoming obvious, but there has so far been no effort to convene an international forum to agree on universally acceptable guidelines.

Advisory Committees↗