bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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.
Evaluation of an organ‐donor‐card campaign in Sweden
Authors: Sanner1 Margareta A. , Hedman Håkan , Tufveson Gunnar 
Published: September 2024

One of the aims of this study was to evaluate an information campaign carried out in three geographical areas of Sweden in the winter of 1992‐93. The campaign was intended to increase public awareness of organ donation and to increase the signing of donor cards. Another objective was to test the effects of different kinds of information. These were: A) an extensive “package” of information including training of key groups, lecturing at meetings and exhibitions, and advertisements of donor cards: B) a brochure to households including two donor cards; and C) a combination of A and B. Yet another aim was to reassess public opinion on transplantation issues, which had been surveyed before in 1987, 1988, and 1990. Random samples of the population in three campaign areas and a control sample were surveyed before and after the campaign, altogether 5600 persons. The average response rate was 69% (1992) and 68% (1993). In the two areas where the brochure had been distributed to the households, the rate of donor card holders had more than doubled (from 3% and 5% to 13% and 12%). In the two areas where the brochure had not been distributed, the rate was unchanged (5%). In the “brochure areas” also a somewhat larger number of people had informed their relatives about their decisions, compared with people in the other areas. In all campaign areas considerably more people were aware of the cards than in the control area. No attitude changes could be shown in any area. Thus, the mailed brochure was the most effective in increasing people's signing of the donor cards and informing their families. The more elaborate campaign could possibly have long‐term effects, but this remains to be studied. The attitudes toward organ donation have been rather constant in Sweden from 1987 to 1993, with only slight variations.A “frankness gradient” was confirmed in this study as well as in an earlier study, where those who were negative toward donation of their own organs had discussed this issue least with their families, followed by those who were undecided, whereas those who were positive (and above all those positive who were card‐holders) had discussed this the most with their relatives.
Cancer incidence in 854 kidney transplant recipients from a single institution: comparison with normal population and with patients under dialytic treatment
Authors: Montagnino G. , Lorca E. , Tarantino A. , Bencini P. , Aroldi A. , Cesana B. , Braga M. , Lonati F. , Ponticelli C. 
Published: September 2024

In this retrospective historical study, we compared the incidences of malignancies observed among 854 renal transplant recipients (RT) with at least 1 yr of follow‐up, with the incidences of neoplasias among patients under regular dialytic treatment (RDT) and a control population from Northern Italy. Cox's proportional hazard model was used in RT recipients in order to evaluate the prognostic factors related to the development of neoplasia. Seventy six out of 854 RT patients (8.9%) developed some malignant neoplasia: 46% of these 76 were cutaneous neoplasias including melanomas, and the remaining 54% non cutaneous cancers: 33% miscellaneous tumors (MT), mostly adenocarcinomas, 17% Kaposi's sarcomas (KS), 4% non‐Hodgkin's lymphomas (NHL). Malignancies had a higher incidence (p<0.01) among RT recipients than among control and RDT patients. However, MT were equally frequent among the three groups. RDT patients on the contrary, had similar incidence of neoplasias when compared to the control population, but showed at lower incidence of squamous cell carcinomas (SCC). The risk ratios (RR) for the most frequent neoplasias among RT recipients vs. control population were: 224.7 for KS, 7.4 for NHL, 6.2 for SCC, 5.7 for basal cell carcinomas (BCC), 4.0 for MT. The risk of developing ade novoneoplasia was of about 13% at 10 yr and of 34% at 20 yr.In RT recipients, Cox's proportional analysis showed that age >40 at transplantation and male sex were the only risk factors associated with an increased incidence of neoplasias, while no difference was observed between conventional (azathioprine+methylprednisolone: Aza+MP) and CSA therapy or in CSA monotherapy vs. double or triple therapy. However, KS occurrence correlated both with CSA dose (RR 15.2 for monotherapy; 12.5 for double therapy; 2.98 for triple therapy) and with 10 or more i.v. methylprednisolone pulses for treatment of rejection (RR 5.2).We conclude that in our series CSA does not increase the risk for development of neoplasias, when compared to conventional immunosuppression.
Heart transplantation for patients over age 60
Authors: Everett Jeffrey E. , Djalilian Ali R. , Kubo Spencer H. , Kroshus Timothy J. , Shumway Sara J. 
Published: September 2024

AbstractAs the proportion of people over age 60 in our society continues to rise, so does the number of potential heart transplant candidates. Advanced recipient age, however, has long been used as an exclusion criterion for transplantation, though the upper age limit remains poorly defined. The purpose of our study was to analyze the outcomes of 31 heart transplant recipients over age 60 at our institution. They were followed with regard to early and late morbidity and mortality. Mean follow‐up time was 50 months. The 1‐ and 5‐ yr survival rates were 90% and 85%. These rates were not significantly different compared with younger (age 18 to 59) recipients transplanted in the same time period. The older recipients more frequently developed osteoporotic changes as well as cutaneous and visceral malignancies, but had infrequent rejection episodes. Overall, heart transplantation is safe and effective for patients over age 60 with end‐stage congestive heart failure. Both 1‐ and 5‐yr survival rates are well within the acceptable range and do not differ significantly from younger recipients. Individualized immunosuppression might help reduce the incidence of malignancy in older recipients, but further studies are needed. Matching donor and recipient age would make the best use of available organs.
The importance of early cyclosporine levels in pediatric kidney transplantation
Authors: Matas Arthur J. , Gillingham Kristen J. , Chavers Blanche M. , Nevins Tom , Kashtan Cliff , Mauer S. Michael , Payne William D. , Gruessner Rainer , Najarian John S. 
Published: September 2024

AbstractWe studied the impact of early cyclosporine (CSA) levels on the incidence of rejection in pediatric transplant recipients. Between 1 January 1984 and 31 December 1994, a total of 234 pediatric patients underwent kidney transplants and received CSA immunosuppression. We analyzed the impact of CSA levels (at 1 wk, 2 wk, 1 month, 2 months, and 3 months) on the incidence of rejection in the first 3 and the first 6 months post‐transplant. We found that CSA levels at all timepoints correlated; i.e. recipients with low levels in the early post‐transplant period tended to have low levels throughout the first 12 months. Multivariate analysis for risk factors for biopsy‐proven rejection in the first 3 months revealed that the CSA trough level was the critical factor (p<0.05). Recipients with CSA trough levels <100 ng/ml had 2.24 times the risk of rejection vs. those with blood levels >100 ng/ml. Similarly, the CSA trough level at 1 month was the critical risk factor for biopsy‐proven rejection within the first 6 months (p<0.05). The major risk factor for graft loss within the first 12 months was a biopsy‐proven rejection episode. We conclude that in pediatric kidney transplant recipients, early CSA trough levels <100 ng/ml are associated with a significantly increased incidence of rejection in the first 6 months post‐transplant.
Cytomegalovirus infection associated accelerated heart allograft arteriosclerosis may impair the late function of the graft
Authors: Koskinen Petri , Lemstrøm Karl , Mattila Severi , Häyry Pekka , Nieminen Markku S. 
Published: September 2024

AbstractCardiac allograft arteriosclerosis is the most important limiting factor of long‐term survival of heart transplant recipients. Several clinical studies have suggested the association between CMV infection and heart allograft arteriosclerosis, chronic rejection. To determine the temporal impact of CMV infection on the development of heart allograft arteriosclerosis we quantitated coronary angiograms obtained from 72 heart transplant recipients followed for 1‐6 yr post‐transplantation. To examine the graft function, echocardiography was evaluated. CMV infection was associated with early development of allograft arteriosclerosis manifested by intense diffuse pruning of the coronary arteries including their smallest branches already after the second post‐transplant year. Even 6 yr post‐transplantation the magnitude of arteriosclerotic changes was significantly higher in recipients with CMV infection compared with patients without infection (P<0.02). No difference in echocardiographic parameters including ejection fraction (EF), left ventricular end diastolic diameter (LVEDD) and left ventricular mass (LVM) between recipients with and without CMV infection was recorded early after transplantation. However, when compared to recipients without CMV, the CMV accelerated chronic rejection seen in coronary angiography associated with impaired late graft function as judged by decreased EF in patients with CMV infection 6 yr post‐transplantation (P<0.02). No differences in LVEDD or LVM between the patient groups occurred. Taken together, these results suggest that CMV infection is associated with intense cardiac allograft arteriosclerosis affecting the whole coronary tree soon after transplantation. The intensity and magnitude of these chronic vascular wall changes increase and persist during subsequent years, indicating that the risk for graft loss and death due to chronic rejection is especially high during the first 5 post‐transplant years in CMV‐infected patients. Echocardiography may not be a sensitive method to distinguish patients with early CMV‐accelerated allograft arteriosclerosis but coronary angiography must be performed.
VCAM‐1 and E‐selectin expression during cytomegalovirus infection in post‐transplant myocardial biopsies
Authors: Allen Margaret D. , King Christine , MacDonald Thomas O. , Himes Victoria 
Published: September 2024

AbstractAdhesion molecule expression may become useful in monitoring cardiac graft rejection, but first the question of whether expression is upregulated by cytomegalovirus (CMV), a common post‐transplant infection, must be answered. To study this, all cardiac biopsies (n=201) on 12 cardiac transplant recipients were examined for rejection grade and VCAM‐1, ICAM‐1, and E‐selectin expression over the first 6‐15 months post‐transplant. Adhesion molecule expression in biopsies taken during documented CMV infections were compared to those taken in the absence of infection, both overall and sorted as to rejection grade.There were 17 CMV infections in this patient group. VCAM‐1 was expressed in 82% of biopsies coincident with CMV infections, compared to 43% of biopsies unrelated to CMV infection, a significant difference (p<0.01). E‐selectin was expressed in 65% of biopsies with CMV infection, compared to 30% of biopsies unrelated to CMV infection, also statistically significant (p=0.01). Both VCAM‐1 and E‐selectin were expressed in 80% of biopsies without rejection taken during CMV infections, significantly greater than the 24% incidence of VCAM‐1 and 14% incidence of E‐selectin expression in biopsies without rejection that were not concomitant with CMV infection. In the absence of CMV infection, both VCAM‐1 and E‐selectin expression correlated significantly with rejection grade, but this relationship became invalid in the presence of CMV infection. ICAM‐1 expression bore no relation to CMV infection.VCAM‐1 and E‐selectin expression in cardiac biopsies can be upregulated with CMV infection in the absence of graft rejection.