bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune monitoring of heart transplant patients receiving either one or two cycles of OKT3 prophylaxis. Induced anti‐idiotypic and anti‐isotypic anti‐OKT3 antibodies do not prohibit depletion of peripheral T cells due to second OKT3 treatment
Authors: Hesse C. J. , Heyse P. , Stalk B. J. M. , Vaessen L. M. B. , Balk A. H. M. M. , Mochtar B. , Jutte N. H. P. M. , Weimar W.
Published: September 2024

24 heart transplant recipients were treated with OKT3 together with azathioprine for 7 days as a rejection prophylaxis. The plasma OKT3 concentration ranged from 280 to 1600 ng/ml. During treatment the T cells in peripheral blood disappeared but returned modulated without TcR‐α/β‐chains and with low CD3 expression. Antimurine antibodies were induced and median IgG antimurine antibody concentrations increased from 9.6 mg/l pretransplant to 52.1 mg/l as measured by ELISA. In 13 out of 24 patients, anti‐idiotypic antibodies were present at a level that caused over 50% inhibition of OKT3 binding to T cells. The extent of inhibition was positively correlated with the increase in IgG antimurine antibody levels, both in relative (> 3 times pre‐transplant level, p < 0.05) and in absolute terms (more than 50 mg/l, p < 0.001). In 9 patients, who received two prophylactic courses of OKT3, we found a decrease in anti‐OKT3 antibody levels after the second course of OKT3 which can be caused by the additional cyclosporin A (CsA) immune suppression. The second course also resulted in a rapid depletion of circulating functional T cells despite the presence of anti‐OKT3 antibodies generated after the first course.
Comparison between the effects of cyclosporine and azathioprine on functional and morphologic renal parameters in a randomized study from 12 to 24 months after renal transplantation
Authors: Pedersen Erling B. , Hansen Hans E. , Olsen Steen , Danlelsen Henning , Eiskjær Hans , Jespersen Bente , Kornerup Hans J. , Madsen Søren , Sørensen Arne W. S. , Sørensen Seren S.
Published: September 2024

The use of cyclosporine as an immunosuppressive agent has improved graft survival after transplantation. However, the nephrotoxicity of cyclosporine is a serious clinical problem. After treatment with cyclosporine and prednisolone during the 1st year after renal transplantation, 106 patients were consecutively randomized to either treatment with azathioprine and prednisolone (Group Az) or cyclosporine and prednisolone (Group Cy) in a prospective controlled study during the following 1 yr. 51‐Cr‐EDTA clearance (CEDTA), blood pressure (BP), plasma concentrations of atrial natriuretic peptide (ANP), angiotensin II (Ang II), and aldosterone (Aldo), and urinary excretion rate of prostaglandin E2 (PGE2) were determined at the start of the study and every 6 months. Systematic, blind and semiquantitative histopathologic analyses were performed on biopsies from the renal grafts at the start of the study and after 12 months. Comparison within groups showed that GFR increased in Group Az (44 to 48 ml/min, p < 0.05) and decreased in Group Cy (43 to 39 ml/min, p < 0.05) after 6 months, and that GFR was unchanged after 12 months in Group Az (42 ml/min) and reduced in Group Cy (39 ml/min, p < 0.05) compared to baseline level. Comparison between groups showed a significantly higher GFR in Group Az than in Group Cy after 6 months, but no significant difference in GFR at the start of the study or after 12 months. The extent of arteriolar hyalinosis increased significantly in Group Cy (0.82 to 1.72 score, p < 0.001) after 12 months but was unchanged in Group Az (0.97 to 0.94 score), whereas interstitial fibrosis increased to the same level in both groups. After 12 months, BP was decreased and ANP, PGE2, Ang II and Aldo were unchanged in Group Az. Contrariwise, in Group Cy BP remained unchanged, ANP and PGE2 were increased, and Ang II and Aldo suppressed. The increased arteriolar hyalinosis during cyclosporine treatment most probably results in a higher BP than during azathioprine treatment. The higher ANP and PGE2 during cyclosporine treatment may be compensatory phenomena in order to preserve graft function and reduce BP. Conversion to azathioprine treatment may be superior to continued cyclosporine treatment at least from 12 to 24 months after renal transplantation.
Noncompliance in renal transplant recipients: Experience in Taiwan
Authors: Lal Ming‐Kuen , Huang Chiu‐Ching , Chu Sheng‐Hsien , Chuang Cheng‐Keng , Huang Jeng‐Yi , Chen Hsiao‐Wen
Published: September 2024

Patient compliance is one of the key factors of successful treatment following renal transplantation. Eleven out of 228 renal transplant recipients (4.8%) in our series displayed evidence of medical noncompliance which happened after the recipients had enjoyed good graft function for an average of 53.1 ± 16.9 months after transplantation. In comparison with the control group, these recipients were usually younger (26.3 ±5.49 vs 32.6 ±8.92 years old, p<0.05), had fewer rejection episodes (0% vs 21.4%, p<0.05) and had lower educational level (p<0.01). Nine of these noncompliant patients (81.8%) lost their kidney grafts eventually. Three of them died from complications after kidney graft failure. Noncompliance was responsible for 21.4% of total graft loss, the third leading cause of graft loss after rejection (50.0%) and infection (26.2%). Since there is a severe shortage of donor kidneys in the Taiwan area, great effort much be spent to prevent kidney graft loss from patient noncompliance. Patient education and alertness to the risk factors of noncompliance should be emphasized.
Pseudomonas pulmonary artery graft endocarditis in heterotopic heart transplant: Case presentation and literature review
Authors: Grinstead W. Carter , Noon George P. , Sekela Michael E. , Samo Tobias , Verani Mario S. , Hays John , Young James B.
Published: September 2024

A heterotopic heart transplant patient developed Pseudomonas aeruginosa infection 3 days after transplantation. Pseudomonas infections recurred 4 and 8 months later. During the second recurrence a new systolic murmur was noted. An indium‐111 white blood cell scan showed abundant uptake in the location of the prosthetic pulmonary artery graft and angiography revealed a mobile filling defect near the anastomosis of the graft and the native pulmonary artery. The grossly infected graft was surgically replaced without the need for cardiopulmonary bypass. Cultures from the graft's partially dissected pscudointima grew Pseudomonas aeruginosa. The patient remained free of recurrent Pseudomonas infection 12 months after graft replacement. Timely recognition of this previously unreported complication of heterotopic heart transplantation allowed surgical cure of this potentially devastating infection.
Temporary wound closure with expanded polytetrafluoroethylene in pediatric liver transplantation
Authors: Shun A. , Thompson J. F. , Dorney S. F. A. , Sheil A. G. R.
Published: September 2024

A shortage of donor organs of appropriate size causes lengthy delays for many children awaiting liver transplantation, and results in the death of some children on the active waiting list. A major contribution to overcoming this problem has been the use of reduced livers from adult donors. However, reduced adult livers are frequently too large to be used for small pediatric recipients (<8 kg) because of the serious problems which occur when too light an abdominal closure is attempted. We report a technique which we have used successfully in 2 children, involving the insertion of a temporary patch graft of expanded polytetrafluoroethylene. This allowed comfortable abdominal wound closure, which would not otherwise have been possible. Delayed primary closure of the abdomen 4‐5 days later was achieved without difficulty in each case, the liver grafts having decreased markedly in size by this time. The technique allows greater flexibility in the use of donor livers for pediatric recipients, and thus has the potential to reduce waiting times and deaths on the waiting list for small children requiring liver transplantation.
Fulminant Epstein‐Barr virus‐associated post‐transplant lymphoproliferative disorders following OKT3 therapy
Authors: Canfield Craig W. , Hudnall S. David , II John O. Colonna , Busuttil Ronald W. , Wilkinson Alan H. , Danovitch Gabriel , Shaked Abraham , Goldstein Leonard , Rosenthal J. Thomas
Published: September 2024

Post‐transplant lymphoproliferative disorders (PTLD) are recognized as sequelae of immunosuppression. The clinical spectrum reported ranges from a mononucleosis‐like syndrome to fulminant malignant lymphoma. Prior reports have suggested that PTLD may regress if immunosuppression is withdrawn, and since they are strongly associated with Epstein‐Barr virus (EDV), that they may respond to treatment with acyclovir. We present 6 cases seen recently at our medical center that rapidly progressed to death, despite withdrawal of immunosuppression and prophylactic use of acyclovir in 5 of the 6 cases. Routine peripheral blood smear in all cases identified atypical lymphocytes. All cases were associated with the use of OKT3 monoclonal antibody therapy, with 5 of 6 patients having been treated with two or more courses. The reemergence of these disorders, as OKT3 is becoming widely adopted, serves as a reminder of the price of profound immunosuppression.
Herpes viral hepatitis in liver transplant recipients
Authors: Awad Joseph , Peters Marion G. , Brunt Elizabeth , Hanto Douglas W.
Published: September 2024

The incidence, treatment and outcome of histologically diagnosed herpes viral hepatitides were studied in 58 consecutive patients who received orthotopic liver transplants. Cytomegalovirus hepatitis occurred in 26% of patients, 75% of whom had a self‐limited viral syndrome. Serum liver tests were not helpful in establishing the diagnosis. Liver culture and histology proved valuable in the diagnosis of herpes viral infections. Infection was more frequent in patients who received seropositive organs than in those who did not, but was not more common in those Who required retransplantation. Two patients had Epstein Barr virus hepatitis and 1 had herpes simplex hepatitis. Prophylaxis for cytomegalovirus with acyclovir is important especially in those seronegative patients who receive seropositive organs.
“Growth” of adult kidneys transplanted into small children
Authors: Bunchman Timothy E. , Lynch Robert E. , Garvin Paul J. , Fleming Susan S. , Wood Ellen G.
Published: September 2024

We reviewed the renal allograft length as determined by serial ultrasound examinations in 12 children who underwent renal transplantation at less than 4 years of age (18.1 ± 4.1 months, 9.48 ± 0.78 kg, mean ± SEM) receiving an adult donor kidney. Follow‐up serum creatinines and allograft length, (determined by ultrasounds) were reviewed for a mean of 59.7 ± 7.4 months after transplantation. Nine of 12 children have stable allograft function whereas 3/12 children have functional deterioration with histological evidence of chronic rejection. Compared to baseline, in those children with stable function there was a mean decrease in allograft length (–0.7 ± 0.1 cm) at 1 yr post‐transplantation with return to baseline allograft length at 4 yr (+0.2 ± 0.2 cm). Beyond 4 yr, there is a persistent increase in allograft length of +0.6 ± 0.3, +1.3 ± 0.6 and + 1.9 ± 0.5 cm as compared to baseline at 5, 6 and 7 yr respectively (p < 0.01). This is in contrast to a persistent diminution in allograft length with failure to return to baseline length in those children with chronic rejection. In this small number of young children there appears to be growth potential over time of the donor adult allograft with stable function, which appears to be lacking in those allografts with chronic rejection. The stimulus for the allograft growth may be due to unique growth factors that are yet to be determined.
Alternative technique of pancreas graft arterialization
Authors: Bechstein Wolf O. , Reed Alan I , Sollinger Hans W.
Published: September 2024

Combined liver‐pancreas procurement mostly requires back bench reconstruction of arterial blood supply to the pancreas graft. Anastomosing the mid‐portion of the splenic artery end‐to‐side to a donor illiac artery graft as an alternative method of pancreatic graft arterialization is described.
Cadaveric renal transplantation using kidneys from donors greater than 60 years old
Authors: Vivas Carlos A. , O'Donovan Richard M. , Jordan Mark L. , Hickey David P. , Hrebinko Ronald , Shapiro Ron , Starzl Thomas E. , Hakala Thomas R.
Published: September 2024

Transplantation of kidneys from donors over the age of 60 yr is controversial. However, as the demand for cadaveric kidneys far exceeds the supply, exploration of the usefulness of kidneys outside the currently accepted donor pool is necessary. Between January 1987 and July 1989, 31 (5.5%) of the 558 cadaveric renal transplants performed at the University of Pittsburgh utilized organs from donors older than 60 yr. Median recipient age was 41 yr (range 24‐71 yr); 4 recipients were diabetic and 6 had panel‐reactive antibody levels greater than 20% at the time of transplant. All recipients were treated with cyclosporine, prednisone and azathioprine. The 1‐yr allograft survival was 65% which was less than but not statistically different from the graft survival of 80% in a retrospective selected control group who received grafts from younger donors aged 11 to 50 yr. However, the 1‐yr graft survival of older donor kidneys with cold ischemia time greater than 48 hours was 38%, which was significantly poorer than the 78% 1‐yr graft survival seen with cold ischemia times less than 48 h (p = 0.04 Breslow). The mean serum creatinine was significantly higher in the older donor kidneys at 1, 3, and 12 months posttransplant than in the control kidneys even when kidneys with greater than 48 h of cold ischemia time were excluded. In summary, transplantation of cadaver kidneys from donors older than 60 yr results in acceptable graft survival rates. These kidneys are more susceptible to cold ischemic injury and function with a higher serum creatinine than kidneys from younger donors. Expansion of the donor pool by the use of older donor kidneys in selected recipients could have an impact on alleviating the chronic national cadaver kidney shortage.
Colonic screening prior to renal transplantation and its impact on post‐transplant colonic complications
Authors: McCune Thomas R. , Nylander William A. , Van Buren David H. , Richie Robert E. , MacDonell Robert C. , Johnson H. Keith , Shull Harrison , Cate Clifford K. , Helderman J. Harold
Published: September 2024

Colonic complications after renal transplantation are uncommon but have a high mortality rate. Some have recommended colonic screening in patients over 50 years of age prior to transplantation to lessen the impact of colonic diverticular disease. We report our 9‐year experience of colonic screening for diverticular disease in potential recipients over the age of 50 and compare these results to the overall colonic complication rate in the same time period. From 1981‐1990, 1186 renal transplants in 1019 patients were perormed, during which time all potential recipients over the age of 50 yr were required to undergo colon evaluation prior to transplantation. Twenty cases of diverticular disease were found with more than a quarter of the cases in patients with adult polycystic disease. All underwent renal transplantation without a pre‐transplant colectomy, and none had post transplant symptomatic colon disease. During that same time period a total of 14 colonic complications requiring surgical intervention were encountered with a mortality rate of 40%. Acute diverticulitis occurred in 5 patients, all of whom were over 50 yr of age, on low‐dose immunosuppression, and in most cases it occurred remotely after transplantation. Colonic dysplasia/neoplasia also occurred remotely after transplantation in 2 patients over the age of 50. Cytomegalovirus (CMV) colitis was the next most common complication, accounting for 3 cases. This complication, which occurred in younger patients, was associated with high‐dose steroid immunosuppression and had a high mortality rate, in spite of surgical intervention. Although half of all colonic complications occurred in patients over the age of 50, advanced age was not associated with increase mortality. Mortality rate was lowered by aggressive surgical intervention but remained high when colonic complications were a manifestation of systemic disease. Because of the inability to predict which patients are at risk for colonic complications and, in those patients who had such a complication, the remoteness between occurrence and transplant, we recommend abandoning pre‐transplant colon screening.
A study of autoreactive lymphocytotoxic antibodies in sensitized dialysis patients
Authors: Nicholls C. M. , Grooby W. L. , Russ G. R.
Published: September 2024

Patients awaiting renal transplantation over the 6‐month period from October 1988 to March 1989 were tested for autoreactive lymphocytotoxic antibodies (ALCA) by autologous crossmatch. All patient sera had previously been screened for lymphocytotoxic antibodies against a 40‐member cell panel, and only those with panel reactivity of 10% or more were included in the study (63/88). Lymphocytotoxic crossmatch was performed against autologous B and T lymphocytes using peak and current sera and other historical sera if available. A total of 167 sera from the 63 patients were tested. Fourteen of the 63 patients (22%) had ALCA, 10 of whom were available for further study. There was no apparent difference between race, age and peak or current panel reactivity among the 14 patients with and the 49 without ALCA. A second autocrossmatch was performed using 11 selected sera from the 10 patients with ALCA. Sera used for this crossmatch were depleted of ALCA using three methods; (1) autologous absorption (AA) with EBV‐transformed B‐lymphoblastoid cells. (2) treatment with dithiothreitol (DTT) which dissociates IgM, and (3) absorption with Staphylococcal protein A (PrA) for IgG depletion. In 7 sera, ALCA were removed by AA and DTT treatment but not PrA absorption, inferring an IgM antibody. In 1 serum ALCA was removed by AA and PrA absorption but not DTT treatment, inferring an IgG antibody. In 2 sera, ALCA activity remained after DTT treatment and PrA absorption and was only removed after AA. Alloantibodies were detected by screening AA, DTT‐treated and PrA‐absorbed sera from each patient against a 30‐member lymphocyte panel typed for HLA‐A and ‐B loci. Sera with persisting panel reactivity after AA were considered to contain alloantibodies. These were classified as IgM or IgG on the basis of their reduction or non‐reduction with DTT. Four reaction patterns were observed which identified ALCA (IgM and IgG) and alloantibodies (IgM and IgG). Alloantibodies were present in 5 of the 10 patients with ALCA. All patients identified as having alloantibodies had either a failed kidney graft and/or multiple transfusions (> 10 units). Two of these sera contained IgG alloantibodies alone, and 3 contained mixtures of IgG and IgM alloantibodies. HLA class I‐specific antibodies could be recognized in 3 patients and in each case appeared to be IgG. Some sera remain highly reactive after AA, indicating that high panel reactivity cannot be presumed to be due to ALCA in patients with a positive autocrossmatch. Five patients from this study were transplanted on the basis of a negative crossmatch using AA serum. Four grafts have good function at between 8 and 28 months after transplantation. One patient died with a functioning graft 12 months after transplantation. No patient experienced acute rejection in the 1st week.
Malaria and liver transplantation
Authors: Crafa Francesco , Gugenheim Jean , Fabianl Pascal , Marty Plerre , Loubiere Robert , Gari‐Toussaint Martine , Bourrier Martine , Goubaux Bernard , Moulel Jean
Published: September 2024

Transmission of malaria by liver transplantation has not been previously described. A 45‐year‐old Italian man with hepatocellular carcinoma underwent hepatic transplantation in our center; he had no evidence of prior parasite infection. The donor was an 8‐yr‐old child who had been a resident in an endemic malarial area. Retrospective examination of donor sera by immunofluorescent antibody test showed a high titer (1/10240) to Plasmodium falciparum. Twenty days after liver transplantation the recipient became febrile and neurological disorders appeared. Blood films revealed Plasmodium falciparum. Effective therapy by quinine (Quinoforme) was administred but death occurred 41 days after liver transplantation. Autopsy was not permitted. Retrospective examination of donor liver and spleen specimens (Giemsa staining) showed malarial pigment in both organs, macrophage reaction in the spleen and a suspected intraerythrocytic parasite in a liver biopsy. Transmission of malaria following blood transfusion is well documented but in this case blood products were not contaminated by parasites. We suggest that transmission of malaria in our report may be related to the transplanted liver.
Depletion of natural antibodies in non‐human primates – A step towards successful discordant xenografting in humans*
Authors: Cooper D. K. C.
Published: September 2024

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 xenorcactive antibodies are directed has been investigated. Two of the most important of these would appear to be α 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.
Sulfadiazine‐induced obstructive renal failure in a kidney transplant recipient
Authors: Doutrelepont J. M. , Abramowicz D. , Goldman M. , Vanderwinden J. M. , De Pauw L. , Vanherweghem J. L. , Kinnaert P. , Vereerstraeten P.
Published: September 2024

A kidney transplant recipient on long‐term sulfadiazine and pyrimethamine therapy for recurrent toxoplasmosis chorioretinitis developed acute oliguric renal failure. Ultrasound examination of the graft revealed hydronephrosis caused by radiolucent calculi. The calculi were most probably made of sulfadiazine, as sulfadiazine crystalluria was detected on several occasions prior to the acute obstruction. Although percutaneous nephrostomy was temporarily required, withdrawal of sulfadiazine and alkalinization of the urine led to a prompt dissolution of the calculi. The risks factors and therapeutic measures of sulfadiazine‐induced obstructive nephropathy are reviewed.
Hyperuricemic acute renal failure associated with FK506 nephrotoxicity
Authors: Williams Mark E. , Lewis David
Published: September 2024

Acute renal failure due to severe hyperuricemia is reported in a liver transplant recipient undergoing rescue therapy with FK506. Earlier treatment with cyclosporine had been complicated by gout and uric acid nephrolithiasis. Transplant recipients with symptomatic hyperuricemia on cyclosporine may be at particular risk for marked hyperuricemia when conversion to FK506 results in FK506 toxicity.
Immunosuppression ‐ A contributory factor in lymphoma formation
Authors: Perm Israel
Published: September 2024

Intense immunosuppression is complicated by the development of various neoplasms, many arising in the immune system itself, mainly nonHodgkin's lymphoma (NHL's). This is shown by the evolution of 883 lymphomas among 5737 types of cancer, that arose in 5386 organ transplant recipients, reported to the Cincinnati Transplant Tumor Registry up to June 1991. If nonmelanoma skin cancer and in situ carcinomas of the uterine cervix are excluded, they comprise 22% of neoplasms seen in transplant patients, compared with 5% in the general population. Most NHL's are large cell lymphomas or immunoblastic sarcomas. Immunologically, most (86%) are of B‐cell origin. Most (70%) lesions are extranodal in distribution. They show a remarkable predilection for the brain. Four groups of patients are particularly prone to develop lymphomas: cyclosporine‐treated patients, OKT3‐treated patients, recipients of nonrenal organs, and pediatric recipients. There is a considerable overlap of patients in these four categories. Possible causes of the NHL's include oncogenic viruses; disturbed immune surveillance; chronic antigenic stimulation; impaired immunoregulation; carcinogenic effects of immunosuppressive agents; and genetic susceptibility to lymphomagenesis. Treatment includes drastic reduction or cessation of immunosuppressive therapy, surgical excision, local radiation therapy, antiviral therapy with agents such as acyclovir, immunostimulation with agents such as α‐interferon, and cancer chemotherapy.
Lymphoproliferative disorders in renal transplant recipients: Virologic aspects
Authors: Preiksaitis Jutta K.
Published: September 2024

Most cases of post‐transplant lymphoproliferative disorders are linked to infection with Epstein‐Barr virus (EBV). We examined the relationship between the use of polyclonal and monoclonal anti‐lymphocyte globulins, pretransplant EBV serology and PTLD in cadaveric renal transplant recipients. We found that EBV‐seronegative patients were at significantly increased risk of developing PTLD and this risk was further amplified by the use of anti‐lymphocyte globulins, particularly when they are used for both induction and rejection therapy. The results of a prospective study of quantitative oropharyngeal EBV shedding in renal and cardiac transplant recipients is reported. The relationship between EBV shedding, immunosuppressive regimens, antiviral drugs, serologic responses and the risk of PTLD is examined.
Increased risk of lymphoproliferative disorders following the use of OKT3 in cardiac transplantation
Authors: Swinnen Lode J. , Costanzo‐Nordin Maria R. , Fisher Susan G. , O'Sullivan E. Jeanne , Johnson Maryl R. , Heroux Alain L. , Dizikes George J. , Pifarre Roque , Fisher Richard I.
Published: September 2024

A sudden increase in the incidence of post‐transplant lymphoproliferative disorder (PTLD) in our cardiac transplant program prompted a retrospective study of 154 consecutive patients to identify predictive variables. The increase was found to be temporally and statistically related to the introduction of the immunosuppressive antibody OKT3. While effective in the treatment of refractory rejection, the value of OKT3 used prophylactically at the time of transplantation remains to be clearly established. Among 75 patients who had not received the drug, PTLD developed in 1 (1.3%) compared with 9 of 79 patients who had (11.4%), a ninefold higher incidence (p = 0.01). The following factors were assessed in a multivariate model: sex; race; age; weight; reason for transplant; rejection episodes; mean cyclosporine level; use and cumulative dose of OKT3, ATG, and steroids. Only the use of OKT3 was significantly associated with development of PTLD (p = 0.001). Increasing risk with increasing dose was evident, in that 4 of 65 patients (6.2%) who received one course of OKT3 (≤ 75 mg) developed PTLD, while 5 of 14 patients (35.7%) who received more than 1 course did so (p < 0.001). Over the year since the study was completed, two more cases of PTLD have arisen in the group receiving one course of the drug, resulting in an incidence of 9.2% after a single prophylactic course of OKT3 (p=0.03), and an overall incidence of 13.9%. Withholding cyclosporine during the prophylactic course did not reduce the risk of PTLD. Among patients who had received > 75 mg OKT3, all but one presented with widespread, rapidly progressive disease resulting in early organ failure and death. Among the 14 patients who had received > 75 mg, the interval between courses for those who developed PTLD was much shorter (med 13 days, range 0‐33) than for those who did not (med 115 days, range 8‐884, p = 0.02). There was a strong inverse correlation between total OKT3 dose and the time to appearance of PTLD following transplantation; a mean of 11 ± 4.9 mos. for patients who had received one course, compared to a mean of 1.3 ± 0.45 mos. for those who had received two (p < 0.001). It can be concluded that the addition of OKT3 to a triple drug immunosuppressive regimen increases the incidence of PTLD after cardiac transplantation, and that both the risk and clinical pattern of disease are dose related. No conclusions regarding the mechanism for this increase can be drawn from these data. It is suggested that the risks and benefits of prophylactic OKT3 administration be reassessed, that short intervals between courses be avoided, and that patients who have received the drug be monitored closely for indications of PTLD.
Raised levels of tumor‐necrosis factor alpha (TNFα) in cardiac transplant patients
Authors: Sabokbar A. , Horton J. D. , Bowler K. , Manning R. , Meager A. , Dark J. H.
Published: September 2024

Enzyme immunoassay is used to probe serum and plasma levels of tumor‐necrosis factor‐alpha (TNFα) in human heart transplant patients during the first few months post‐transplantation. Detectability of TNFα was increased by heat‐pretreatmcnt of serum (56°C for 30 minutes), in order to inactivate inhibitors of the immunoassay present in the sera. In EDTA‐treated plasma samples such treatment was not necessary, thus suggesting the possible involvement of complement in such inhibition. Compared with samples from control (healthy) volunteers, transplant patients frequently displayed elevated levels of TNFα, especially in the first few weeks post‐transplantation. However, increased cytokine levels did not correlate with histologically (biopsy)‐determined rejection episodes. We were unable to detect interleukin‐6 (IL‐6) in plasma samples of heart transplant patients.
Liver transplantation for acute Budd‐Chiari syndrome complicated by portal and inferior vena cava thrombosis
Authors: Vera S. R. , Shokouh‐Amiri M. H. , Riely C. , Adamec T. , Jensen S. L. , Gaber A. O.
Published: September 2024

The prognosis of patients suffering from Budd‐Chiari syndrome is poor without treatment. Both medical and surgical treatments have some benefit. Surgical treatment consists cither of portosystemic shunt surgery or liver transplantation. It is still debatable which patients might benefit from either of these procedures. We report a patient with Budd‐Chiari syndrome with extensive thrombotic involvement of both systemic and portal venous systems. The Budd‐Chiari syndrome appeared acutely following a spontaneous abortion in a 33‐ycar‐old woman who was 4 weeks pregnant. The course was fulminant with acute liver failure. Thrombolytic therapy failed to resolve the inferior vena cava thrombosis. Because of the extensive and progressive involvement of both portal and cavai systems, an emergent cavai and portal vein thrombectomy followed by liver transplantation was performed. This was followed by sustained anticoagulant therapy. The patient was discharged 3 weeks after transplantation and has remained asymptomatic since February' 1991. We concluded that orthotopic liver transplantation, with portal and inferior vena cava thrombectomy, can be performed in patients with complete acute hepatocellular necrosis resulting from massive thrombosis of hepatic veins, abdominal vena cava, and portal vein.
Acute dilative cardiomyopathy following liver transplantation for idiopathic hemochromatosis
Authors: Koller J. , Kornberger R. , Wleser C. H. , Dietze O. , Vogel W. , Königsrainer A. , Margreiter R.
Published: September 2024

Liver transplantation was performed in a 29‐year‐old male suffering from end‐stage liver disease due to idiopathic hemochromatosis. History, clinical examination, chest X‐ray and ECG revealed no signs of cardiac dysfunction. Apart from intraabdominal bleedings necessitating relaparotomy on day 1, the immediate postoperative course was entirely uneventful and the patient enjoyed excellent graft function. Six days following transplantation he developed rapidly progressive heart failure which, despite high‐dose catecholamines, led to death only 24 hours later. Postmortem examination revealed acute dilative cardiomyopathy due to iron storage disease of the heart. Iron extraction from the heart in order to meet postoperative iron requirements is discussed as a possible cause. From this observation it is concluded that echocardiographic examination and perhaps endomyocardial biopsy should be included in the pretransplant work‐up of patients with idiopathic hemochromatosis.
The pathogenesis of xenograft rejection
Authors: Makowka Leonard , Cramer Donald V.
Published: September 2024

The transplantation of vascularized organs between species stimulates an intense rejection reaction by the recipient of the graft. The classification of the xenograft rejection reaction on the basis of the degree of genetic disparity between donor and recipient species and the presence or absence of preformed antibody to the donor tissue does not provide for a precise classification schema. We have proposed that xenograft reactions be classified on the basis of the immunological mechanisms responsible for the loss of the graft. The rejection of xenografts would then be divided into those that are antibody‐dependent and mediated by anlidonor antibody, either preformed (i.e. pig‐to‐human xenografts) and present at the time of transplantation or antibody produced in response to placement of the graft (hamster‐to‐rat). A second group of xenograft reactions would consist of those for which the direct activation of the alternative complement pathway results in loss of the graft in the absence of the binding of antidonor antibody from the recipient (guinea pig‐to‐ral). The focus on the pathogenesis of xenograft reactions for classification purposes is a more consistent method of description and is more clearly related to future attempts to prevent rejection with immunosuppressive therapy.
Cell‐mediated xenoresponses: Strong or weak?1
Authors: Auchincloss Hugh
Published: September 2024

Cell‐mediated responses to xenoantigens are different from those to alloantigens. CD4' T cells are especially important in xenoresponses and depletion of CD4* T cells can prolong survival of xenografts better than allografts in some circumstances. The difference between the two responses is due in part to the relative weakness of direct T‐cell responses stimulated by xenogeneic antigen‐presenting cells. Instead. T cells tend to require that donor antigens be processed and presented indirectly in association with the MHC antigens on their own APCs. The defect in direct stimulation is due to failure of some of the several T cell/ A PC interactions when the receptors and ligands of these interactions come from different species. Although the cell‐mediated response to xenografts is different, it remains very strong. The mechanism by which CD4* cells cause xenograft destruction remains to be determined, but a better understanding of this mechanism may help to select the most useful types of immunosuppression for xenogeneic transplantation.
Cytokines and adhesion molecules in chronic rejection
Authors: Azuma Haruhito , Heemann Uwe W. , Tullius Stefan G. , Tilney Nicholas L.
Published: September 2024

Despite the increasing short‐term success of clinical transplantation during recent years, many allografts, regardless of organ type, continue to be lost over the long term due to chronic rejection, despite improvements in immunosuppression and better patient management. Thus, as a long‐term answer to an irreversible disease process, organ transplantation has not lived up to its potential. Although the host mechanisms leading to the process remain obscure, the progressive morphological changes evolving in the afflicted organs are well understood. Chronic rejection has long been thought to be an antibody‐mediated event, as immunoglobulins and other circulating proteins are often associated with areas of vascular damage. It is becoming more clear, however, that a whole array of host defense factors, primarily, cytokines, lymphokines and adhesion molecules, are of critical importance in the process. This review summarizes various cytokines and their individual functions as well as adhesion molecules potentially involved in aspects of immune responsiveness, and placed in the context of chronic rejection.
Veto cells in transplantation tolerance1
Authors: Thomas Judith M. , Verbanac Kathryn M. , Carver F. Melinda , Kasten‐Jolly Jane , Haisch Carl E. , Gross Ulrike , Smith John P.
Published: September 2024

Advances in immunosuppressive management for transplantation have improved graft survival. However, lasting success will probably depend on the induction of donor‐specific unresponsiveness, avoiding chronic immunosuppressive drug therapy and its debilitating side effects. Tolerance strategies have been developed in rodents, but applicability to human organ transplantation has not been achieved. We have established a preclinical allogeneic kidney transplant model in unrelated outbred rhesus monkeys and have investigated a tolerance‐inducing strategy in which posttransplant administration of rabbit antithymocyte globulin and infusion of a subpopulation of donor bone marrow cells yields longterm graft acceptance in the absence of chronic immunosuppressive drugs. Recent studies of the immunological mechanisms by which induction and maintenance of transplant tolerance is achieved in this model are presented within the framework of a veto hypothesis.
Quality of life after combined kidney‐pancreas or kidney transplantation in diabetic patients with end‐stage renal disease
Authors: Kiebert G. M. , van Oosterhout E. C. A. A. , van Bronswijk H. , Lemkes H. H. P. J. , Gooszen H. G.
Published: September 2024

The quality of life after a successful combined kidney‐pancreas transplantation was studied in 17 diabetic patients with end‐stage renal disease (ESRD) and in 11 patients who experienced a failure of one or both grafts. The control group comprised 23 patients who received a kidney transplantation only. The aspects of quality of life chosen for study were: physical, psychological and social wellbeing, daily activities, level of functioning and global quality of life evaluation. Additionally, future expectations, the perceived burden of treatment, and main reason for undergoing organ replacement therapy were evaluated. In only one aspect of quality of life did patients with a successful combined transplantation score significantly better than patients with a kidney transplantation, i.e.. mobility in daily functioning and activities (p = 0.03). Patients with a failure of one or both grafts reported significantly more fatigue (p = 0.02). less energy (p = 0.04), and more social isolation (p = 0.05) than patients who had well‐functioning grafts. The mean duration of hospitalization following combined transplantation is twice that for kidney transplantation only 10 v.v 5 weeks). Although the combined transplantation group found the first 3 months after transplantation more burdensome (p = 0.04) and more often wondered whether it had been worth all the trouble (p = 0.05). they indicated the same willingness as the group with a kidney transplant only to undergo another transplantation under similar circumstances. Although the recipients of a kidney transplant had not been offered the choice of a combined transplantation, their reasons for transplantation did not. in essence, differ from those of recipients of a combined transplantation. In both groups the main motivation to opt for organ replacement therapy was the burden of dialysis, to stop the progressive deterioration of their health, and to experience a belter quality of life.
Hyperlipidemia in long‐term survivors of pediatric renal transplantation
Authors: Sharma Atul K. , Myers Timothy A. , Hunninghake Donald B. , Matas Arthur J. , Kashtan Clifford E.
Published: September 2024

The prevalence of hyperlipidemia in adolescents and young adults who are long‐term survivors of pediatric renal transplantation with stable graft function has not previously been examined. We studied 33 renal transplant recipients aged 5 to 23 years, who were an average of 7.4 years (range 3 to 11 years) post‐transplant. We found hypercholesterolemia in 17 (total cholesterol (TC) > 5.18 mmol/l). Both low‐density lipoprotein cholesterol (LDL‐C) and high‐density lipoprotein cholesterol (HDL‐C) levels were increased, such that the mean TC/HDL‐C and apolipoprotein B/apolipoprotein A1 (Apo B/Apo A1) ratios were below levels associated with increased coronary artery disease risk. Subjects with hypercholesterolemia did not differ from those with normal cholesterol values in current age or age at transplant, serum creatinine, serum albumin, serum triglycerides, HDL‐C, TC/HDL‐C ratio, Apo B/ Apo Al ratio, prednisone dose, body mass index, gender, use of thiazides or β blockers, or family history of premature atherosclerosis. Coronary risk factors appear to cluster in these patients, with hypertension in 53% of those with hypercholesterolemia. Lipid profiles were not different in patients treated with prednisone‐azathioprine vs. prednisone‐azathioprinecyclosporine A immunosuppression. A significant correlation was found between predisone dose (mg/m2) and TC, LDL‐C and TC/HDL‐C. According to National Cholesterol Education Program guidelines, 32% of these long‐term survivors of pediatric renal transplantation warrant at least dietary intervention and 10% are candidates for treatment with lipidlowering drugs. This proportion is likely to increase as the safety of lipidlowering agents is established in younger children.
Pathology and etiology of chronic rejection of the heart
Authors: Billingham Margaret E.
Published: September 2024

As there are other lesions in the cardiac allografts of long‐term survivors, it is best to refer to the vascular lesion as “graft vascular disease”. Graft vascular disease may be evident as early as 3 months after cardiac transplantation and may cause death in the recipient as late as 22 years post‐transplant. The disease affects infants, children, and adults as well as the recipients of combined heart‐lung transplants. It is one of the most discouraging aspects of long‐term survival in combined heart‐lung and heart transplantation, accounting for 18% of the deaths among the 201 cardiac transplants performed at Stanford during the cyclosporine era. The pathology of graft vascular disease is that of a concentric intimai proliferation with minimal damage to the elastic lamina and minimal or no change in the media of the coronary vessel wall. The lesion may affect the entire length of the vessel wall as well as the branches and small branches that penetrate into the myocardium of the coronary system. These changes differ from that of naturally occurring atherosclerosis in that, instead of focal lesions developing, the whole length of the vessel is affected, including the small branches. This precludes optimal treatment with angioplasty and other therapies. Because small vessels are involved, the resulting myocardial infarcts may be patchy and small. Presently, no strong correlation has been made with usual risk factors or transplantation for end‐stage coronary atherosclerosis, cardiomyopathy or congenital heart disease. The etiology of graft coronary disease remains unclear. Studies have suggested vascular cell activation of various kinds, including cytokines. Some of these processes, however, have been found in nontransplant coronary disease as well. A correlation with acute rejection, although suspected, has not been definitively proved; in combined heart‐ lung transplantation, the cardiac graft rarely rejects and yet graft vascular disease develops. The only correlation thus far has been with cytomegalovirus (CVM) infection, in which death from graft vascular disease is higher in infected recipients. More recently, a correlation has been made with the so‐called “Quilty lesion”. Early animal studies with in vivo blockade of tumor necrosis factor (TNF) indicated that it inhibits the development of graft arteriopathy. Such studies are being conducted extensively in America and elsewhere.
Outcome statistics of renal transplants with an emphasis on long‐term survival
Authors: Cecka J. Michael
Published: September 2024

Remarkable increases in cadaveric renal transplant survival rates have been seen following improvements in areas such as immunosuppression, organ preservation, HLA typing and cross‐matching, and blood transfusion protocols. However, while these improvements have influenced survival in the early post‐transplant period up to 6 months, the cumulative rate of graft loss beyond the 1st year has remained constant at about 9% year over the past 25 years. Several factors that affect long‐term survival have been identified through univariate and multivariate analyses. Chief among these is the detrimental effect of HLA‐A and HLA‐B antigen mismatching. Also important are the recipient's race, sex, and age, and presence of diabetes, as well as the donor's age, sex, and cause of death, and long cold ischemia times. Likewise, posttransplant events, including delayed graft function, early rejection episodes, and discharge serum creatinine levels strongly affect long‐term graft survival. Chronic rejection should also be recognized as a major contributor to the long‐term failure rate, but there is currently no reliable way to identify or classify it in the UNOS Scientific Renal Transplant Registry database. Characteristics that define chronic rejection must be identified to allow transplant centers to accurately report its incidence and to enable investigators to analyze and monitor its impact on transplant outcome.
Acute rejection episodes – Best predictor of long‐term primary cadaveric renal transplant survival
Authors: Ferguson Ronald
Published: September 2024

Uniformly high 1‐year primary cadaveric renal transplant survival has prompted an interest in establishing clinical factors associated with longer‐term (i.e., more than 5‐year) graft survival. We have studied 665 consecutive primary transplanted cadaveric kidneys using sequential quadruple immunosuppression with at least 1 year of follow‐up (average 41.4 months). No attempt at HLA matching was made and all rejection episodes were confirmed by histology. Overall, 8‐year patient and graft survival were 78% and 60%, respectively. Death as a cause of graft loss occurred in 103 patients. However, only 14 patients died from complications of immunosuppression. A multivariate analysis was performed using age, sex, blood type, race, presence of diabetes, HLA mismatch, current and maximum panel reactive antibody (PRA), time to first rejection episode, treatment of first rejection episode, and number of rejection episodes (none, one, or more than one). Number of rejection episodes was by far the most important co‐variate (p= <0.00001).

In total, 53% of patients had no rejection episodes, 25% had one, and 22% had more than one. The occurrence of acute rejection did not correlate with the degree of HLA mismatch or PRA. Demographic and immunologic variables were similar for all three groups. Actuarial 8‐year graft survival was negatively affected by rejection history (Fig. 1). Uncensored T2 in the group with no rejection episodes was 16.9 years, compared with 3.9 years in the group that experienced more than one such episode. In conclusion, the predominant factor to dictate long‐term CAD kidney graft survival is the presence or absence of one or more rejection episodes early in the post‐transplant course. These data suggest that chronic rejection occurs almost exclusively in patients successfully treated at one or more time points for acute rejection.