bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized trial with two anti‐CMV hyperimmune globulins in the prevention of CMV disease in CMV‐negative renal transplant patients
Authors: Pakkala Seppo , Salmela Kalja , Lautenschlager Irmeli , Hirvonen Marjatta , Ahonen Juhani , Häyry Pekka 
Published: September 2024

Abstract:Cytomegalovirus (CMV) causes marked morbidity in renal transplant patients which may be prevented by passive immunization. We studied the effect of two different hyperimmune globulins in the prevention of CMV disease in seronegative patients receiving renal transplants from seropositive donors. Thirty patients were randomized to receive either anti‐CMV i.v. Ig (pH 4‐pepsin treated), or CytotectR (beta‐propiolactone treated) 1.5 ml/kg on day 1, 1.0 mg/kg on d 14 and 28, 0.5 ml/kg on d 42, 56, 84 and 112 post‐transplantation. As controls, 15 patients transplanted without CMV prophylaxis immediately before (12 patients) and after (3 patients) the randomization period, were included. All patients and controls received same basic immunosuppression and sulfa‐trimethoprime prophylaxis. Of the 30 patients on prophylactic anti‐CMV globulin, 21 (70%) became CMV‐positive and 11 patients (37%) developed virologically confirmed CMV disease. Two additional patients had fever without other signs of CMV disease. Two patients developed interstitial pneumonitis (IPn). Eleven (37%) patients developed acute rejection and had symptomatic CMV disease after transplantation. CMV disease developed earlier in patients treated for rejection with antithymocyte globulin (ATG) than in patients treated with methylprednisolone. In the historical control group, 5 patients (33%) developed CMV disease and 1 of them had pneumonitis. Seven patients (47%) underwent episodes of acute rejection and 3 of them had CMV disease at the same time. There were no opportunistic infections in cither group.
Association of kidney graft failure with a positive flow cytometric crossmatch
Authors: Berteli A. J. , Daniel V. , Möhring K. , Staehler G. , Opelz G. 
Published: September 2024

We examined the pretransplant sera of 154 cadaver kidney recipients for anti‐donor antibodies against T lymphocytes using the flow cytometry technique. All patients had negative routine lymphocytotoxic crossmatches. 31 of the 154 (20%) patients were positive in the flow cytometric T‐cell crossmatch (FACS‐T‐XM). A positive FACS‐T‐XM was associated with irreversible rejection (p < 0.01 at 14 days, p < 0.001 at 30 d, p < 0.001 at 1 year). The 1‐yr graft survival rate of FACS‐T‐XM‐negative patients was 85% in contrast to 58% for FACS‐T‐XM‐positive patients (p < 0.001). 84% of the irreversible rejections in FACS‐T‐XM‐positive patients occurred within the 1st month after transplantation. These results suggest that a positive FACS‐T‐XM should be considered a contraindication for transplantation. We developed a flow cytometric assay to determine the complement‐fixing capacity of antibodies causing a positive FACS‐T‐XM. Of 14 patients who were examined, 10 had noncomplement‐fixing and 4 complement‐fixing antibodies. All 10 patients with noncomplement‐fixing antibodies experienced acute rejections, which were irreversible in 4. These results demonstrate that noncomplement‐fixing anti‐T cell antibodies, which cannot be detected in the lymphocytotoxic crossmatch assay, are clinically relevant.
Fatal lymphoma in association with OKT3 antibody therapy diagnosed by allograft biopsy
Authors: Murray Brian M. , Venuto Rocco C. , Kohli Romesh K. , Brentjens Johannes R. , Anthone Sidney , Cunningham Eugene E. , Gerbasi Joseph R. 
Published: September 2024

We report two renal transplant recipients who died of rapidly fatal lymphoma within 3 months of transplantation. Both presented with fever and deteriorating graft function during the 2nd week of OKT3 therapy for rejection and the removed allograft showed lymphomatous infiltrates. OKT3 may have enhanced in vivo EBV infection in these patients predisposing to lymphomatous transformation. Retrospective review of renal transplants done since July 1986 showed that the incidence of lymphoma in patients receiving OKT3 was 4% and lymphoma has not been seen in patients who did not receive OKT3. Clearly, the risks of OKT3 therapy must be carefully weighed in the aggressively immunosuppressed patient.
Mycobacterium tuberculosis after liver transplantation: Management and guidelines for prevention
Authors: Higgins Robert S. D. , Kusne Shimon , Reyes Jorge , Yousem Sam , Gordon Robert , Van Thiel David , Simmons Richard L. , Starzl Thomas 
Published: September 2024

During a 9‐year period, from January 1981 to December 1989, 6 mycobacterial infections were diagnosed among 2380 orthotopic liver transplants performed at the University of Pittsburgh. These infectious complications, although rare, were a major source of morbidity and mortality (40%). There were several associated risk factors in these patients, including extensive travel through or birth in endemic areas, severe pretransplant illness, post‐transplant rejection requiring adjunct (i.e., OKT3) immunosuppression, and HIV infection. Five patients had M. tuberculosis (MTB) infections; the 6th patient developed a solitary pulmonary nodule which grew mycobacterium avium intracellulare (MAI). Invasive diagnostic studies were usually necessary to document MTB infection and tissue samples often revealed early granuloma formation. Multiple drug regimens (INH, Rifampin, Ethambutol, and Pyrazinamide) were initiated early in the clinical course and effective therapy was judged by resolution of the clinical illness and/or radiographic resolution. The patient with MAI had no pulmonary or infectious symptoms. He was observed without anti‐tuberculous therapy and the pulmonary nodule decreased in size 3 months after the diagnosis was made. We recommend that all patients have pre‐operative PPD skin tests. Only those patients who fall into high‐risk categories, demonstrating x‐ray evidence of pulmonary disease or those who have a documented recent skin conversion, should receive INH prophylaxis in the peri‐operative period because of the associated risk of INH hepatotoxicity in these patients. MAI infection in asymptomatic patients may be managed with expectant observation. If the patient develops pulmonary symptoms, or the lesion persists, pulmonary nodule resection and antituberculous chemotherapy guided by culture sensitivities may be appropriate.
OKT3 treatment of acute renal allograft rejection in children
Authors: Pescovitz Mark D. , Breen Nancy , Book Benita K. , Leapman Stephen B. , Milgrom Martin L. , Pollard Stephen G. , Filo Ronald S. 
Published: September 2024

Although the monoclonal antibody OKT3 has been shown to be highly effective in the treatment of acute cellular renal allograft rejection in adults, there are only a few reports of its use in children. We have analyzed our experience with OKT3 in pediatric renal transplantation to determine its effectiveness and toxicity. Twenty‐four children (10 female, 14 male, age 1 to 17 years) received an initial course of OKT3 as either primary (n = 15) or rescue (n = 9) treatment of acute cellular rejection of 11 cadaver and 13 living‐related renal transplants. Baseline immunosuppression consisted of azathioprine, steroids, and cyclosporine (CyA). Fourteen patients had the CyA stopped during treatment with OKT3. Seven to 16 doses (11.8 ± 2.5, mean ± S.D.) of OKT3 were given, 5 mg for patients over 30 kg and 2.5 mg for those under 30 kg: 22/24 (92%) of the rejections were reversed: 7/22 (32%) had an early re‐rejection within 2 months (33.2 ± 10.5 days). Antibody to OKT3 (OKT3Ab) following the initial course was detected in 7 of the 22 patients tested. Toxicity included a febrile reaction, an increase in the serum creatinine, two late seizures, and one episode of hypotension. Infections requiring extended or repeat hospitalization within 2 months developed in 12/24 patients following OKT3. Patients who received high‐dose steroids (> 5 mg/kg, 26 ± 8 mg/kg, mean ± S.D.) on the 1st d of OKT3 therapy had a blunted febrile response and a blunted creatinine rise when compared to the low steroid group (< 5 mg/kg, 1 ± 0.5 mg/kg). OKT3 was reused for rejection in 8 patients, 4 of whom had developed OKT3Ab following their first course of OKT3. Half (4/8) responded to the second course with reversal of rejection: 3/4 without OKT3Ab responded but only 1/4 with OKT3Ab responded. OKT3Ab developed in 3/4 who were originally OKT3Ab‐negative; it increased in 3/4 who were positive and decreased in 1. No case of anaphylaxis or severe OKT3 reaction occurred during second course therapy. In summary, OKT3 is highly effective in reversing renal allograft rejection in children. Its use is not complicated by severe toxicity nor by an inordinate frequency of re‐rejection or OKT3Ab development. In children without previous OKT3Ab, a second course of OKT3 is usually effective, and can occasionally be effective with a history of previous OKT3Ab development.
A successful second renal allograft across positive B‐cell crossmatch due to IgG anti‐HLA DR5 antibody
Authors: Panajotopoulos Nicolas , Ianhez Luiz E. , Neumann Jorge , Rosales Claudia , Sabbaga Emil , Kaill Jorge 
Published: September 2024

The role of antibodies specific to donor B‐cell antigens in renal transplantation remains to be firmly established. We have used, in a sensitized patient awaiting his second transplant, reduction with dithiothreitol (DTT), platelet absortion and panel reactivity analysis to identify imunoglobulin class and specificity of the antibody causing positive B‐cell crossmatch. The results show that the antibody was an IgG anti‐HLA DR5. The transplant was performed using the recipient's mother, specifically mismatched for DR5, as donor. The graft has excellent function 18 months after transplantation. The experience with this patient raises questions about the clinical significance of anti‐DR antibodies, and of anti‐B cells antibodies in general, in kidney transplantation.
Impact of chronic corticosteroid administration on intraocular pressure in renal transplant recipients
Authors: Perell H. Frederick , Friedman Robert , Burnett Henry W. , Weir Matthew R. , Klassen David K. , Shen Steve Y. , Kittur Dilip 
Published: September 2024

Chronic corticosteroid use has been associated with elevation of intraocular pressure. Intraocular pressure was determined in 46 renal transplant recipients who had received chronic corticosteroid therapy (range 45‐5500 days), with a total cumulative dose of 2.3 to 81 grams. No significant positive correlation was observed between intraocular pressure and either total corticosteroid dose or duration of therapy. Contrary to prior data, there was a trend toward lower intraocular pressure with higher total corticosteroid exposure. Although our data did not demonstrate a correlation between steroid dosage and durations and elevations in IOP in this kidney transplant population, individual pressure elevation requiring treatment was recorded, and the physician needs to be aware of the complication of IOP elevations.
Two distinct patterns of post‐transplantation lymphoproliferative disorder (PTLD): Early and late onset
Authors: Alfrey E. J. , Friedman A. L. , Grossman R. A. , Perloff L. J. , Naji A. , Barker G. F. , Montone K. T. , Tomaszewski J. E. , Chmielewski C. , Holland T. , Zmijewski C. , Dafoe O. C. 
Published: September 2024

In our multi‐organ transplant program, we have noted two distinct patterns of PTLD: 1) potentially treatable PTLD appearing in the early post‐transplant period (≤ 90 days); and 2) fatal insidious PTLD of late onset. Between 1965 and 1990, 1662 transplants were performed and 16 patients developed PTLD. PTLD represented 18% of all malignancies during this time interval. Fourteen PTLDs occurred in kidney transplant recipients (KTxp) and 2 in liver transplant recipients (LTxp). Six of the 16 patients with PTLD presented within 90 d of transplantation (mean time 5 weeks) and 10 presented 4 months to 8 years after transplantation (mean time 152 wk). In the early‐onset PTLD group there was a disproportionate number of allografts well‐matched at DR loci. Four of 6 cases of early‐onset PTLD had evidence of recent Epstein‐Barr virus (EBV) infection. Five of these patients had also received OKT3. In the late‐onset group, 4 of 10 patients had received anti‐lymphocyte globulin (ALG). Three of 6 patients with early‐onset PTLD underwent transplant nephrectomy and survived, whereas all patients with late‐onset PTLD expired. Based on this small experience, it appears that early PTLD was associated with DR match, vigorous immunosuppression and EBV infection.
Experience with posttransplant lymphoproliferative disorders in solid organ transplant recipients
Authors: Nalesnik Michael A. , Locker Joseph , Jaffe Ronald , Reyes Jorge , Cooper Mark , Fung John , Starzl Thomas E. 
Published: September 2024

Nearly 6000 solid organ transplants have been performed at the University of Pittsburgh since 1981. Posttransplant lymphoproliferative disorders (PTLD) have occurred in 131 patients, at a frequency of 2.2%. The majority of cases manifest within 6 months following allograft, but individual lesions may arise several years thereafter. From 1981 to 1989, cyclosporine‐A (CsA) served as the primary immunosuppressant in this population. In March of 1989, FK506 was introduced for clinical trials. Since that time, 1421 patients have received FK506 either for primary immunosuppression or as rescue therapy. The frequency of PTLD in this subpopulation is 1.5%. PTLD arising under FK506‐containing regimens have clinicopathologic features similar to those arising with CsA immunosuppression. The frequency of PTLD at this point in time is approximately 1% in kidney allograft patients, 2.7% in liver, 3.3% in heart and 3.8% in heart/lung or lung recipients. An understanding of the range of histologic appearance is important for the diagnosis of PTLD, especially when it involves the allograft itself. Immunoglobulin heavy chain gene analysis shows that lesions with no rearrangements or with a rearrangement in only a small proportion of cells are more likely to respond to reduced immunosuppression than are those with clonal rearrangement involving a high proportion of cells. However, this distinction is not absolute, and a trial of reduced immunosuppression appears to be indicated regardless of clonal status.
Incidence of malignancies in renal and cardiac transplant recipients in relation to treatment with biologic agents
Authors: Hardy Mark A. , Benvenisty Alan I. , Cohen David , Barr Marc , Rose Eric , Suciu‐Foca Nicole 
Published: September 2024

An 8‐year review was conducted of 1077 transplanted patients at Columbia Presbyterian Medical Center with the specific aim of analyzing the incidence of malignancies in immunosuppressed patients carrying a graft for more than 1 month. The patients studied included 589 renal allograft recipients and 488 cardiac allograft recipients. There was a 3.04% incidence of malignancies following grafting, of which 15 were in the renal and 17 in the cardiac allograft recipients resulting in equal incidence in both groups. Of the 120 renal allograft recipients who were treated with OKT3, 4 were diagnosed as having cancer and only 1 developed lymphoproliferative polyclonal B‐cell disease. More hematopoietic malignancies were found in cardiac allograft recipients (12/488) but only 1 of 56 patients treated with OKT3 developed lymphoma. This study concludes that there is no relationship between the use of OKT3 and development of malignancies in renal or cardiac allograft recipients and that the overall degree of immunosuppression along with the presence of a graft and perhaps viremia relates best to the incidence of lymphoid malignancies.
De novo lymphoma after liver transplantation
Authors: Klintmalm Goran B. 
Published: September 2024

A total of 482 liver transplants were performed in 416 consecutive liver transplant recipients between December 1984 and November 1990. The maintenance immunosuppression protocol was based on cyclosporine and prednisolone. Azathioprine was added only after first rejection. Rejections were treated with steroids. OKT3 was then used for rescue therapy, 5 mg q day for 10‐14 d. A total of 8 lymphomas were diagnosed. There were 2 in 164 patients who had not had a rejection. In 43 patients who had received only steroid therapy for rejection 1 lymphoma was found and in 109 patients who had received OKT3 treatment for rejection 5 lymphomas were seen. However, in 6 patients who received 2 courses of anti‐lymphocytic therapy, either consisting of OKT3 twice or OKT3 and anti‐lymphocytic globulin, 4 lymphomas were found (p < 0.000). Two of the 8 patients survived their lymphomas. In these 2 patients all immunosuppression had been immediately discontinued at the diagnosis of lymphoproliferative disorder. They were maintained only on prednisolone, 10 mg q d. Immunosuppression was later gradually reinstituted after immunological reconstitution with disappearance of the lymphomas and the commencement of rejection. It is concluded that post‐transplant lymphoma seems to be related to the amount of immunosuppression given, and more than 1 course of OKT3 for rescue should not be used. In cases of unrelenting rejection unresponsive to OKT3 re‐transplantation should be contemplated or some of the newer immunosuppressants such as FK 506 or RS‐61443.
Rejection episodes after liver transplantation during primary immunosuppression with FK506 or a cyclosporine‐based regimen: A controlled, prospective, randomized trial
Authors: Jonas S. , Kling N. , Bechstein W. O. , Blumhardt G. , Lohmann1 R. , Lobeck H. , Neuhaus P. 
Published: September 2024

As part of a European multicenter study to investigate the potency of FK506 in primary immunosuppression after liver transplantation, this comparison with our conventional cyclosporine‐based quadruple regimen was carried out as a controlled, prospective, randomized trial. The 121 patients entering the study were randomly assigned to receive immunosuppressive regimens consisting either of FK506 and prednisolone (FK/n=61) or of cyclosporine, prednisolone, azathioprine, and a 7‐day course of rabbit antithymocyte globulin (CsA/n=60). Rejection was suspected in the case of scant production of light bile or biochemical graft dysfunction, without evidence of vascular, biliary, or infectious complications. A liver biopsy for confirmation of the diagnosis was obtained each time. Initial therapy entailed a 3‐d course of high‐dose methylprednisolone. Steroid resistant rejections were treated with OKT3 monoclonal antibody or, in the group of primary CSA administration, conversion to FK506 as another treatment option. One‐year patient (FK: 90.2%; CsA: 96.7%) and graft survival (FK: 88.5%; CSA: 91.7%) did not differ significantly. Overall, 41 patients (33.9%) experienced 50 acute, cellular rejection episodes (RE) [FK: 25 RE in 21 patients (34.4%); CSA: 25 RE in 20 patients (33.3%)]. The histological grading ranged from mild (FK: 14/25; CSA: 8/25) to moderate (FK: 9/25; CsA: 16/25) and severe (FK: 2/25; CSA: 1/25): not significantly different between the two groups. In the CSA‐based group, three additional rejection episodes were classified as early chronic (n=1) and chronic rejection (n=2). A higher share of late‐onset rejections in the CSA‐group (FK: 1/25, 617d; CsA: 6/25, 164±66d) as well as a more frequently observed occurrence of light bile (FK: 8/25; CsA: 4/25) and overlapping cholangitis (FK: 9/25; CSA: 3/25) in the FK‐group were not significant either. In each group, 10 RE were steroid‐resistant. In the FK‐group, all of them resolved under OKT3; in the CSA‐group, I patient was directly switched to FK506, 6 RE resolved during the OKT3 course, whereas 3 RE were resistant to OKT3. Two OKT3 non‐responders were successfully converted to FK506, the other was suffering from early severe rejection and underwent retransplantation. After another retransplantation for severe hepatitis C reinfection, concomitant findings of chronic rejection type changes were evident and the patient was switched to FK506.These results reflect a comparable low incidence of RE in both groups. Safety in terms of patient and graft survival was high. FK506 as a reported rescue agent seems to hold further potential in reducing late‐onset, ductopenic, and histologically higher‐degree cellular rejections.
Does re‐exposure to mismatched HLA antigens decrease renal re‐transplant allograft survival?
Authors: Farney Alan C. , Matas Arthur J. , Noreen Harriet J. , Reinsmoen Nancy , Segall Miriam , Schmidt Wally J. , Gillingham Kristin , Najarian John S. , Sutherland David E. R. 
Published: September 2024

We analyzed 420 kidney retransplants at the University of Minnesota, 87 of which did and 333 which did not share HLA mismatches with the previous transplant. There was no difference in outcome. We conclude that exceptions to routine HLA matching policies do not have to be made for kidney retransplants.ObjectiveTo determine if the kidney graft functional survival rate for retransplants is influenced by presence of HLA mismatches in common with the previous (failed) transplant.Summary background dataKidney retransplants have a lower function. rate than primary grafts. An anamnestic response to HLA antigens shared with the previous donor could be one factor responsible, but reports in the literature are conflicting.MethodsOf 420 kidney retransplants with HLA information done at the University of Minnesota, 87 shared ≥1 HLA antigens specifically mismatched with the previous donor (63 cadaver and 24 living donor retransplants), while 333 did not (247 cadaver, 86 living donor). Patient and graft survival rates were calculated by life‐table analysis for recipients with vs. without repeat mismatches, with the significance of differences determined by the Lee‐Desu statistic.ResultsPatient and kidney graft retransplant survival rate curves were not significantly different (p≥0.41) for those exposed or not exposed to the same HLA mismatches as before. At 2 years, 70% vs. 61%, respectively. of cadaver grafts and 71% vs. 78%, respectively, of living donor grafts were functioning.ConclusionsThe probability of a successful outcome with a kidney retransplant is no different for patients who do than for those who do not receive an organ sharing HLA mismatches with the previous donor. Exceptions to routine HLA matching policies do not need to be made for kidney retransplants.
A prospective study of rapid methods of detecting cytomegalovirus in the blood of renal transplant recipients in relation to patient and graft survival
Authors: Eriksson Britt‐Marie , Wirgart Benita Zweygberg , Claesson Kerstin , Tufveson Gunnar , Magnusson Göran , Tötterman Tomas , Grillner Lena 
Published: September 2024

AbstractEighty‐five renal transplant recipients were prospectively monitored for CMV infection up to 4 months post‐transplantation by virus isolation from leukocytes, CMV antigen detection (pp65) in peripheral blood leukocytes (PBL), polymerase chain reaction (PCR) of alkaline treated plasma (P‐PCR), PCR of extracted DNA from PBL (L‐PCR) and serology. Additionally univariate and multivariate analyses of risk factors for patient and graft survival up to 4 yr post‐transplantation were performed. The incidence of CMV infection was 78% and of CMV disease 33%. Antigen detection in PBL was positive before or at onset of symptoms in 23/24 (96%) evaluable patients with CMV disease. The corresponding figures for virus isolation were 22/24 (92%), PPCR 21/24 (88%) and for L‐PCR 18/24 (75%). The percentage of negative samples in patients without CMV disease was 89% for the antigen test, 92% for L‐PCR and 83% for virus isolation and P‐PCR. One rapid test (antigen test, P‐PCR or L‐PCR) was positive at a median of 16 d before the onset of symptoms. The antigen test was generally the first rapid test to become positive. CMV disease did not affect graft survival in the multivariate analysis but was associated with decreased patient survival.