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The purpose of this study is to identify factors in the sera of highly sensitized (HS) patients (pts) that inhibit T-cell alloresponses. An in vitroassay was used to measure HLA class I and class II-like antiidiotypic antibodies (anti-ids). The stimulation index (SI) was used to measure PBL and T-cell responses to alloantigens. All HS sera (32 pts) and the IgG fraction inhibited PBL and CD4T-cell responses to alloantigens. The SI with HS IgG was 7.9 ± 1.7 as compared to 31.5 ± 5.9 with normal IgG (p 0.0003). In a subset of pts who were transiently sensitized, the SI was 6.6 ± 1.0 with a high panel reactive antibody (PRA), but when their PRA was zero, the SI was 17.8 ± 1.3 (p 0.0000001). Anti-ids were found in 100 of 17 pts with a high PRA. The T-cell inhibitory factors reduced CD4T-cell responses of HS pts to alloantigens in the presence of autologous anti-ids, were MHC restricted and were inactivated by in vitrogenerated antibodies to HLA class II-like anti-ids. The HLA class II-like anti-id IgG molecules bind to the TCR of CD4T cells and may impair their ability to help in the downregulating antibody response to anti-ids.

Until recently, most transplant units required that a negative crossmatch using all available sera was an essential criterion which would ensure the best use of a donor kidney. This policy was accepted without clinical trial until 1982 when it was suggested that a donor kidney will function successfully in the majority of recipients with a negative crossmatch using current sera and a positive crossmatch with one or more non-current sera, i. e., sera taken 3 or more months prior to the time of the transplant. In the 14 reported series addressing this question, the average 1-year graft survival ranges between 53% and 100% in these highly sensitized patients who receive a primary graft, and between 0% and 100% in those who receive a secondary graft. Controversy does exist as to whether a positive crossmatch in non-current sera is an additional risk factor, i.e., that it decreases graft survival significantly when compared with a similar group of highly sensitized patients who were transplanted with a negative crossmatch on all available pre-transplant sera. Of the published studies on this subject, the majority, but not all, find that there is no difference between controls and positive crossmatch patients who receive a primary graft, but those that receive a secondary graft may be at increased risk. The reasons for the different results from these studies may be related to differences in the many variables which influence graft outcome between various study groups.

The mean first exit time is logarithmically equivalent to the exponential of the smallest total free energy barrier separating metastable from stable states for a general class of discontinuous Markov processes in the thermodynamic limit. This asymptotic principle of minimum relative free energy difference constitutes a generalization of the corresponding entropy principle to systems in thermal contact with their environment and formalizes the results of a number of previous authors. The overwhelmingly most probable path of exit, in the thermodynamic limit, is the mirror image in time of the causal path. Along the anticausal path the free energy is an increasing function of time and hence does not provide any criterion of evolution. The kinetic mean-field model of a ferromagnetic serves for illustration.

Abstract: Well-contained abdominal abscesses developed in two renal transplant patients ten years and six months, respectively, after transplantation. Investigations including gastrointestinal series and CT scan demonstrated cystic collections within the abdominal cavity. Laparotomy in each case revealed an infected cystic mass arising from the sigmoid colon. In both patients deroofing the abscess and, in one patient, defunctioning colostomy were performed. Both patients did well in the postoperative period.

Variable experience is documented for pregnancy in renal transplant patients. Furthermore, little information is available that compares graft function and graft survival of cadaver transplant patients who undergo pregnancy with those of a similar group of patients who do not undergo pregnancy. From 1970 to 1979, 30 patients of childbearing age were identified who were first-time recipients of cadaver-donor kidneys. Long-term follow-up was from 32 to 136 months. Five patients have undergone seven pregnancies that resulted in six viable infants and one therapeutic termination. Pregnancy complications included severe preeclampsia, spontaneous premature rupture of membranes, and proteinuria. One infant was small for gestational age. There were no neonatal problems, and no congenital anomalies. Rejection episodes were more common in the postpartum than in the antepartum period (four of six versus one of six). Chronic rejection that led to graft loss occurred in two patients. Ten patients who did not undergo pregnancy were identified for comparison of graft function and graft survival. Late graft rejections occurred in four patients, two of whom eventually suffered graft loss. Survival rates of the grafts by actuarial analysis for the two groups were not significantly different.

Effects of two calcium antagonists on hemodynamics and on cyclosporine pharmacokinetics were studied in eight transplant patients (four heart-transplant and four kidney-transplant patients) by use of a single-blind, randomized, crossover, and placebo-controlled design. Patients received, at least 1 week apart, either 90 mg diltiazem, 20 mg nifedipine (in tablet form), or placebo, given 1 hour before cyclosporine. Cyclosporine and its main metabolite (metabolite 17) were measured in plasma (separated at 25° C) by use of HPLC. Both calcium antagonists tended to increase absorption rate and elimination rate, but none of the pharmacokinetic parameters of cyclosporine were significantly altered. Moreover, the area under the curve of plasma concentrations of metabolite 17 did not change. On the other hand, both nifedipine and diltiazem significantly altered the hemodynamics, but to a different extent in the two groups of patients. The heart-transplant patients showed larger decreases in systolic and diastolic blood pressure than the kidney-transplant patients after administration of both nifedipine and diltiazem, but they showed smaller increases in cardiac index and heart rate with nifedipine. In contrast, diltiazem caused small decreases in heart rate and cardiac index in heart-transplant patients and small increases in heart rate and cardiac index in kidney-transplant patients. We conclude that a single dose of either nifedipine or diltiazem does not affect, to a clinically significant extent, the pharmacokinetics of cyclosporine. In addition, heart-transplant patients show different hemodynamic responses to these two calcium antagonists than the responses shown by kidney-transplant patients, probably because of cardiac denervation.

IMMUNE complexes contribute to tissue damage in a variety of experimental and human diseases. Immune complexes induce arthritis1and nephritis2,3in laboratory animals while lupus glomerulonephritis4and possibly rheumatoid arthritis5are examples of their effects in man. The mechanisms by which damage is initiated and perpetuated are poorly understood. In the acute stage of inflammation resulting from immune complexes many granulocytes are present. These cells have abundant lysosomes rich in acid hydrolases which when released can degrade various tissue components. Enzyme release may result from cell death or exocytosis of granules from viable cells. Henson6and others7,8have shown that granulocytes exposed to immune complexes in vitro release lysosomal enzymes while remaining viable, and presumably the same happens in Arthus reactions in vivo.