Form Of Rejection Research Articles

Renal transplantation in children and adolescents: the 1992 Annual Report of the North American Pediatric Renal Transplant Cooperative Study

From January 1987 to January 1992 the North American Pediatric Renal Transplant Cooperative Study registered and followed 2,037 children and adolescents 17 years of age or less who received 2,197 renal transplants at 75 participating centers in the United States and Canada. The cumulative experience over 5 years of data collection demonstrated trends in renal transplantation practice for pediatric patients. The percentage of live donor organ recipients receiving donor-specific blood transfusions decreased from 40% in 1987 to less than 12% in 1991; random blood transfusions also were used less frequently during the most recent 2 years of the study. Immunosuppressive therapy on posttransplant day 0 or 1 with polyclonal and monoclonal antilymphocyte agents was used in over 40% of transplants. There was also a notable preference for the combined use of prednisone, azathioprine and cyclosporine as maintenance immunosuppression. The percentage of live donor source graft recipients receiving cyclosporine increased from 78% in 1987 to 90% in the most recent year, and considered together, nearly 90% of live donor and cadaver organ recipients received cyclosporine. The observed graft survival probabilities for live donor grafts were 88%, 83%, 81% and 76% at years 1-4 post transplantation, respectively. The 1st through 4th year graft survival probabilities for cadaver grafts were 74%, 68%, 63% and 58%, respectively. The five most common causes of pediatric end-stage renal disease have remained as: hypoplastic-dysplastic kidney, obstructive uropathy, focal segmental glomerulosclerosis, reflux nephropathy and systemic immunological diseases throughout the 5 years of this study. There has been a decrease in children 2 years of age or less undergoing transplant surgery. On average, 50% of graft failures were due to the various forms of rejection. Vascular thrombosis (14%) and recurrence of primary renal disease (7%) were the next most frequently encountered causes of graft failure. Poor linear growth was identified as a problem affecting the majority of children both before and after transplantation. Post transplant linear growth was best among recipients less than 6 years of age at transplantation and recipients of all ages who received alternate-day prednisone. A total of 16 malignancies were reported during the 5 years of study. A total of 105 deaths were reported, with infection (41%) the most common primary cause of death. The 2-year patient survival probabilities were 95.5% and 93% for recipients of live donor and cadaver grafts, respectively.

The immunopathology of cardiac xenograft rejection in the guinea pig-to-rat model.

The mechanisms underlying rejection by rats of vascularized guinea pig xenografts have been controversial. The aim of this study was to define, using sequential immunopathologic analysis, the contributions of xenoreactive antibody, complement, and effector cells to the rejection of guinea pig cardiac xenografts by Lewis rats. In untreated recipients, hyperacute rejection of guinea pig cardiac xenografts occurred in 20 +/- 10.2 min and was characterized by focal endothelial deposition of IgM and by diffuse deposition of C3. IgG was not localized to endothelial surfaces, but was present in the same locations as albumin, suggesting that the accumulation of IgG might reflect nonspecific leakage of plasma proteins from blood vessels. No polymorphonuclear or monocytic infiltrate was observed. Depletion from rats of xenoreactive antibody to undetectable levels prolonged the survival of guinea pig cardiac xenografts, but did not prevent hyperacute rejection; the rejected xenografts contained deposits of C3 along the microvasculature but no deposits of IgM or IgG. No cellular infiltrate was observed. Depletion of complement with cobra venom factor prolonged the survival of xenografts up to 96 hr. Xenograft tissues from complement-depleted animals had diffuse deposits of IgM along the microvasculature, but no detectable deposits of C3 or IgG were noted. Graft tissues obtained at various times after transplantation into complement-depleted animals revealed cellular infiltrates consisting of granulocytes, monocytes, and lymphocytes, but few cells bearing an NK cell phenotype. Our findings are consistent with the concept that complement activation is essential for the hyperacute rejection of discordant xenografts, and that in this particular model complement activation can proceed without the involvement of antibody. However, our findings also suggest that xenoreactive antibody contributes to hyperacute rejection and, along with effector cells, contributes to the later rejection of a xenograft when hyperacute rejection has been averted. Finally, we show that when hyperacute rejection is avoided, a form of vascular rejection occurs in which certain of the pathologic features--i.e., interstitial hemorrhage, interstitial edema, and thrombosis--are very similar to those observed in hyperacute rejection. Whether this form of rejection is a delayed form of the process that leads to hyperacute rejection or a novel pathologic process of graft rejection has yet to be determined.

Vascular rejection in cardiac transplantation: Histologic, immunopathologic, and ultrastructural features

Although the majority of rejection found in cardiac transplant biopsies is cellular in type, a variety of vascular alterations occur in cardiac biopsies, constituting different forms of rejection that can be recognized using light microscopic and immunopathologic criteria. In this report, pathologic aspects of the vascular alterations associated with vascular and mixed rejection of cardiac allografts are described in detail. Methods and controls used in this report are identical to those previously reported. The histologic, immunopathologic, and ultrastructural findings associated with vascular rejection and other vascular processes in cardiac allografts are discussed. The relationship of these findings to chronic allograft rejection and potential pathogenetic mechanisms of these vascular changes are also detailed.

Going public as an AIDS family caregiver

Images of AIDS invoke fears of contagion, disability and formidable death, and moral overtones directed toward drug use, sexuality and sexual identity and freedom. Responses to these images are both private and public, and have profound consequences for individuals whose lives have been touched by the disease, both the person with AIDS and the family caregiver. The purpose of this paper is to analyze in detail ‘going public,’ one category of a substantive theory of AIDS family caregiving. This category was developed from a grounded theory study of 53 AIDS family members who were asked to describe their experiences as an AIDS family caregiver during an indepth interview. Data were content analyzed using constant comparative analysis. Going public referred to how AIDS family caregivers let others know that they were caring for a PWA. Specifically, going public entailed selecting appropriate persons and audiences to tell, formulating approaches to communicating information, and considering the risks and benefits of the possible choices. The description of going public as an AIDS family caregiver details the assertiveness involved in political action and social change, contrasted with the isolation and secrecy involved in maintaining relationships with others under the condition of a stigmatizing illness. Data revealed a particular emphasis on the phenomenon of ‘guilt by association’. Because of their close relationship to a person with AIDS, caregivers were obligated to share the stigma of AIDS and were likewise discredited. Findings from our study emphasize the tremendous personal suffering experienced by caregivers which was associated with AIDS stigma in the form of rejection, loss of friends and harassment. Data also revealed the strong commitment of many caregivers to social activism which ranged from participating in educational efforts to marching in demonstrations. The rationale for the apparent increased activism among AIDS family caregivers compared to other groups of caregivers is explored. Going public highlights both the personal suffering and social manifestations of AIDS, significant issues to consider in planning health services for the second decade of the AIDS epidemic.

SOLUBLE HLA ANTIGENS, ANTI-HLA ANTIBODIES, AND ANTIIDIOTYPIC ANTIBODIES IN THE CIRCULATION OF RENAL TRANSPLANT RECIPIENTS

Chronic rejection represents the major threat to long-term survival of organ allografts. It is presumed that this form of rejection is mediated by antibodies against mismatched HLA antigens of the graft. The presence and specificity of anti-HLA-antibodies in posttransplantation sera are, however, difficult to document. We have explored the possibility that anti-HLA antibodies form immune complexes with soluble HLA antigens released from the injured graft and/or that they are blocked by antiidiotypic, anti-anti-HLA-antibodies. Our data demonstrate that the long-term survival of renal allografts is significantly lower in patients who develop anti-HLA-antibodies following transplantation than in patients who do not form antibodies. Following depletion of soluble HLA antigens by magnetic immunoaffinity, we could identify anti-HLA-antibodies in 57% of the sera obtained from patients undergoing chronic rejection of kidney allografts, compared with 41% prior to antigen depletion. In patients tolerating the graft for 4 years or more, the corresponding frequencies of antibody-positive sera was 2% and 5% prior and following depletion of HLA antigens. The presence of HLA antigen/anti-HLA-antibody immune complexes in patients' sera was positively associated with chronic humoral rejection (P less than 0.0001). Patients who tolerated the graft in spite of having developed antibodies against one of its mismatched HLA antigens show specific antiidiotypic (anti-anti-HLA-antibodies). Such antiidiotypic antibodies were not found in sera from patients with chronic rejection (P = 0.005). This indicates that antiidiotypic antibodies may delay the progression of chronic humoral rejection.

ST-segment depression after cardiac transplantation and its usefulness as an indicator of acute rejection

The so-called Hannover classification of rejection in cardiac allografts 1 describes degrees of acute rejection with different frequencies of conversion into the forms of rejection that require therapy, where A0, A1, A2, A3, A4, A5a and A5b denote no rejection, mild rejection, mild rejection with premyocytolysis, moderate rejection, severe rejection, early-resolving phase and lateresolving phase, respectively. During episodes of acute rejection, the small coronary vessels frequently show an inflammatory response. The presence of the more severe degrees of concomitant vasculopathy implies an augmented risk of conversion into the form of acute rejection that requires therapy in the resolving and the late-resolving phases. 2 Various and different vasoactive mechanisms are obviously involved in the process of rejection, especially during the acute phase. Mediators of the eicosanoid pathway 3 and of α-adrenergic stimulation 4 might be responsible for episodes of reduction in blood flow. ST-segment depression after transplantation should therefore be expected, especially during active infiltrating processes in the myocardium. Based on these hypotheses, we studied heart transplant recipients using 24-hour ambulatory electrocardiographic recordings to determine the frequency and time of ST-segment depression after heart transplantation in relation to postoperative intervals, and to reveal a possible correlation with active rejection-related processes (acute rejection at various histologic stages).

Problems of Korean Immigrant Entrepreneurs

This article analyzes major problems of Korean immigrant entrepreneurs in the United States. It is based on interviews with 557 Korean immigrants in Los Angeles, ethnic newspaper articles and personal observations of the Korean community. Korean entrepreneurs’ long hours of work are detrimental to their physical and psychological well-being. Also, because of their business concentration in low-income, minority areas, Korean entrepreneurs are subject to frequent armed robberies, shoplifting, strikes, boycotts and other forms of rejection. Korean entrepreneurs are vulnerable to exploitation because of their dependence upon outgroup members for supplies of merchandise and their dependence on landlords for leases of store buildings. Korean immigrants are engaged in low level, blue collar businesses, and thus most Korean entrepreneurs face the problem of status inconsistency. Finally, Korean immigrants’ segregation into the ethnic sub-economy, while enhancing ethnic attachment and ethnic solidarity, hinders cultural and social assimilation.

Irradiation for xenogeneic transplantation

Xenogeneic transplantation (XT) is the transplantation of organs or tissues from a member of one species to a member of another. Mammalian species frequently have circulating antibody which is directed against the foreign organ irrespective of known prior antigen exposure. This antibody may lead to hyperacute rejection. There is no reliable means to avert hyperacute rejection once it ensues so efforts must be directed towards eliminating the pre-existing antibody. In those species in which hyperacute rejection of xenografts does not occur, cell-mediated rejection, similar to allograft rejection, may occur. It is in the prevention of this latter form of rejection that radiation is most likely to be beneficial in XT. Both total lymphoid irradiation (TLI) and selective lymphoid irradiation (SLI) have been investigated for use in conjunction with XT. TLI has contributed to the prolongation of pancreatic islet-cell xenografts from hamsters to rats. TLI has also markedly prolonged the survival of cardiac transplants from hamsters to rats. A more modest prolongation of graft survival has been seen with the use of TLI in rabbit-to-rat exchanges. Therapy with TLI, cyclosporine, and splenectomy has markedly prolonged the survival of liver transplants from hamsters to rats, and preliminary data suggest that TLI may contribute to the prolongation of graft survival in the transplantation of hearts from monkeys to baboons. SLI appears to have prolonged graft survival, when used in conjunction with anti-lymphocyte globulin, in hamster-to-rat cardiac graft exchanges. The current state of knowledge of the use of irradiation in experimental XT is reviewed.

Tubulointerstitial nephritis caused by the antiviral agent foscarnet

The antiviral agent foscarnet has long been used in our unit to treat cytomegalovirus (CMV) infections in renal transplant patients. The clinical effect has been convincing and, apart from changes in serum calcium levels, very few side effects have been noted. We have, however, observed a nephrotoxic reaction in a series of patients with initially good renal function who therefore received high doses of foscarnet. Transplant biopsies performed in five of those patients revealed degenerative changes in the tubular epithelial cells as well as tubular calcium deposits and an infiltration of the interstitium by mixed mononuclear and polymorphonuclear leucocytes. Renal insufficiency was accompanied by high fever. After withdrawal of the drug, the temperature rapidly normalized, whereas serum creatinine continued to rise for about 3 days and then fell back towards previous levels. We conclude that transplant biopsies are of great value in distinguishing between a foscarnet nephrotoxic effect and CMV nephritis, various forms of rejection, and other causes of impaired renal function.

Are we marketing the right message: Can kids “just say ‘no’” to smoking?

Two hundred sixty‐eight adolescents from two Southern California schools participated in a study designed to assess the compliance‐resisting strategies children use when rejecting pressure to smoke. Participants were asked to indicate how they would respond to eight hypothetical situations varying in relationship (friend vs. acquaintance), number of people present (dyad vs. group), and amount of pressure (first vs. second exertion of pressure). The influence of risk for future smoking on compliance‐resisting strategies was also assessed. Results indicate that contrary to the popular view, children do not always “just say no.”; Their strategies vary with the conditions mentioned above. Moreover, high risk adolescents appear to have difficulty using strong forms of rejection. These results suggest that researchers should consider the influences of situational variations and risk status for future smoking when developing interventions to teach children to resist smoking and other forms of substance abuse.

Monitoring of renal allografts by duplex ultrasound

Deterioration of renal transplant function due to rejection is accompanied by changes in renal blood flow that can be measured by duplex ultrasound (DU). In the present study, 60 transplanted patients were followed up. A total of 233 duplex examinations, 68 percutaneous biopsies, 44 renal scintigraphies, and 6 transplant nephrectomies were performed on these patients. Diagnoses were made on the basis of clinical and histological data. Renal perfusion was calculated by means of DU. In addition, the arterial Doppler signals were quantified using a pulsatility index (PI). Mean perfusion of normal renal allografts was 0.47 l/min. A decrease in blood flow could be found in acute vascular and chronic rejection but not in acute cellular rejection. A lack of renal perfusion due to acute vascular rejection was observed in four patients. Mean PI, used as a parameter of DU, rose significantly in all forms of rejection, which could be diagnosed with a sensitivity of 93% and a specificity of 86%. Cyclosporin overdosage did not alter the Doppler flow shape.

Duplex Doppler sonography of renal transplants. Correlation with histopathology.

The correlation of histopathologic findings with duplex Doppler sonography (DDS) in 24 biopsies in 21 patients was studied. The resistive indices (RI) of the acute rejection group were statistically different (p = .04) from those that were negative for rejection or clinical controls. Although the number of cases of moderate to severe interstitial and/or vascular rejection was relatively small compared to the mild group, patients with the more severe forms of rejection (moderate to severe interstitial with or without vascular rejection) tended to have higher RIs (.89 +/- .04) than those with the milder forms of rejection (.75 +/- .05).

Tubulointerstitial nephritis caused by the antiviral agent foscarnet

Abstract. The antiviral agent foscarnet has long been used in our unit to treat cytomegalovirus (CMV) infections in renal transplant patients. The clinical effect has been convincing and, apart from changes in serum calcium levels, very few side effects have been noted. We have, however, observed a nephrotoxic reaction in a series of patients with initially good renal function who therefore received high doses of foscarnet. Transplant biopsies performed in five of those patients revealed degenerative changes in the tubular epithelial cells as well as tubular calcium deposits and an infiltration of the interstitium by mixed mononuclear and polymor-phonuclear leucocytes. Renal insufficiency was accompanied by high fever. After withdrawal of the drug, the temperature rapidly normalized, whereas serum creatinine continued to rise for about 3 days and then fell back towards previous levels. We conclude that transplant biopsies are of great value in distinguishing between a foscarnet nephrotoxic effect and CMV nephritis, various forms of rejection, and other causes of impaired renal function.

ANALYSIS OF HISTOINCOMPATIBILITY IN A NATURAL POPULATION OF THE BISEXUAL WHIPTAIL LIZARD CNEMIDOPHORUS TIGRIS

Histoincompatibility was analyzed to describe as precisely as possible the sequence of gross morphological events taking place during allograft rejection among closely related conspecifics from a natural population of the bisexual lizard Cnemidophorus tigris. Two types of rejection were noted, depending on whether the grafts were sloughed or not. Abrupt rejection was typically characterized by hemorrhaging of the graft site, scale dissolution, and eventual sloughing of the graft. This process occurred in a graded sequence. Acute rejection occurred from 15 to 20 days, subacute from 30 to 45, and subchronic from 60 to 90. In the gradual form of rejection, the allografts were gradually replaced by host tissue during a period ranging from approximately 100 to 350 days post-transplantation. Such a gradation observed in both the abrupt and gradual categories suggests that large numbers of genes and/or alleles are responsible for the antigenic properties of skin in these lizards.

Differential Rejection of Neurones and Neuroglia in Canine Cardiac Allografts

USING a free-grafting technique, Barnes1 demonstrated that brain tissue is at least as antigenic as skin allografts in mice. After the grafting procedure the neuronal cells become necrotic in his experiments, whereas the associated neuroglia, being more resistant to ischaemic anoxia, survived. A second-set form of rejection was found on subsequent skin grafting. He concluded that in this type of brain allograft, antigenicity is dependent on viable glial tissue. Such free-grafting experiments however, give no indication of the reactions invoked by viable neurones. An answer to this problem is important in the consideration of integrated neural allografting as in whole nerve, heart and brain grafts, for example.

Why do teachers reject change?

He identifies the forms of rejection and discusses ways in which the administrator might cope with each in order to promote greater and more rapid acceptance of change. Mr. Eichholz is director of educational resources and assistant professor of education at the University of South Florida.