bluuebunny/crossref_metadata_2025 huggingface dataset:
Examination of vascular anastomoses during liver transplantation by intraoperative Doppler duplex scanning
Authors: Roberts John P. , Hughes Linda , Goldstone Jerry , Ascher Nancy L.
Published: September 2024

Intraoperative examination of the arterial and portal vein anastomoses was performed in 16 liver transplant patients using duplex scanning. Two major defects and three minor defects were found in 5 arterial anastomoses. Major defects were defined as those associated with an audibly abnormal Doppler signal, a defect greater than 3 mm in length or greater than 50% luminal narrowing. Minor defects were defects visible by ultrasound but not meeting the above criteria. The major defects were repaired and scans following repair were without evidence of defects. The three minor defects were ignored. A nearly occluding thrombus was found in the portal vein of one patient. A thrombectomy was performed successfully. All patients have done well postoperatively. This report suggests that intraoperative duplex scanning may be of value in detecting technical imperfections in the vascular anastomoses during liver transplantation. Detection of a major defect intraoperatively allows immediate repair.
Is the susceptibility to recurrent CMV infection linked to certain HLA antigens in renal transplant patients?
Authors: Salmela Kaija , Höckerstedt Krister , Koskimies Saija , Lautenschlager Irmell , Ahonen Juhani
Published: September 2024

A group of 151 cytomegalovirus (CMV)‐seropositive renal transplant recipients was retrospectively evaluated. CMV disease was verified in 16% of the patients 2 to 24 weeks posttransplant. The 1 year survival rates of the patients and the grafts were not impaired by CMV. Antigens in locus HLA‐B5 in the recipient and HLA‐A3 in the donor were demonstrated to be associated with an increased incidence of posttransplant CMV disease.
Conversion from azathioprine/prednisone to azathioprine/cyclosporin promotes catch‐up growth in pediatric renal allograft recipients
Authors: David‐Neto Elias , Vilares Sandra , Lando Valeria , Nicolau Willian , Ianhez Luiz E. , Sabbaga Emil , Wajchenberg Bernardo L. , Arap Sami
Published: September 2024

Fifteen pediatric renal allografts recipients under azathioprine (AZA) 2–2.5 mg/kg/day and prednisone (PRED) (5.4 $pM 2.9 mg/m2/d) had their immunosuppression switched to AZA/cyclosporin (CSA) to evaluate benefits on linear growth. Before and after conversion, growth hormone (GH) nocturnal spontaneous secretion (GHss) and somatomedin C basal levels were measured. GH stimulation test (GHst) and SMc generation (SMcG) were also measured but only during the AZA/PRED period. GHst was normal in all children. GH levels increased from 2.6 $pM 2.5 to 20.9 $pM 7.9 ng/ml (p $lt 0.005) after hypoglycemia. The SMc levels, during SMcG, increased from 1.12 $pM 0.41 to 3.73 $pM 1.48 (p $lt 0.005), which is considered a normal response in our laboratory. GH nocturnal secretion inversely correlated to PRED dosage (r = 0.6, p $lt 0.02). GHss increased after PRED withdrawal in the 6 children on PRED 7.0 $pM 3.0 mg/m2/d. On the other hand, bSMc levels did not increase after conversion. After conversion, growth rate increased from 0.34 $pM 0.21 to 0.68 $pM 0.20 cm/month (p $lt 0.0004). The group showed a catch‐up growth from – 3.7 $pM 1.6 to – 2.7 $pM 1.7 standard deviation scores (p $lt 0.0001) after 1 year of follow‐up. Serum creatinine increased slightly from 0.9 $pM 0.2 to 1.0 $pM 0.4 mg/dl. AZA/CSA represents a good alternative for the pediatric recipient of a renal allograft since it is safe to both the child and the graft. This immunosuppressive regimen allows linear growth to occur.
Functional characteristics of lymphocytes propagated from a human multivisceral allograft
Authors: Tragar Jonathan D. K. , Zeevi Adriana , Jaffe Ronald , Rowe Marc I. , Todo Satoru , Starzl Thomas E. , Duquesnoy Rene J.
Published: September 2024

We investigated the characteristics of lymphocytes propagated from biopsies of the mesenteric lymph nodes, liver, and ileum of a human multivisceral allograft in order to provide functional evidence for the presence or absence of rejection and graft‐versus‐host disease (GVHD). The recipient was a 39‐month‐old girl with secretory diarrhea due to microvillus inclusion disease and end‐stage liver disease secondary to prolonged parenteral nutrition. She developed a multifocal posttransplant lymphoproliferative disorder (PTLD) and died 37 days after transplantation. Four pairs of sequential mesenteric lymph node and liver biopsies (13, 17, 24, and 33 d posttransplant) and a single ileal biopsy (31 d posttransplant) were placed in culture with recombinant interleukin‐2 (rIL‐2) and phytohemagglutinin (PHA). T‐cell phenotyping of cultured cells showed that CD8 + cells became dominant in all three tissues. The alloreactivity of biopsy‐grown cells was determined using the primed lymphocyte test (PLT) and cell‐mediated lympholysis test (CML). The proliferative and/or cytolytic responses of biopsy‐grown cells to donor but not recipient or third party cells provided evidence for rejection and absence of GVHD. This donor‐specific alloreactivity was detected before there was histologic evidence of rejection and during the period of active lymphoproliferation. This study suggests that the functional characterization of graft‐infiltrating lymphocytes is useful in defining the immunologic events following multivisceral transplantation.
Treatment of metastatic Vipoma by liver transplantation
Authors: Bramley P. N. , Lodge J. P. A. , Losowsky M. S. , Giles G. R.
Published: September 2024

We report the first case of metastatic Vipoma treated by orthotopic liver transplantation. A woman with explosive secretory diarrhea causing hypokalemic acidosis was diagnosed as having a vasoactive intestinal peptide secreting tumor with widespread hepatic metastases. The symptoms were initially controlled for 9 months with increasing doses of long‐acting somatostatin analogue (Sandostatin, Sandoz Ltd, UK.). Alpha interferon was not tolerated, causing an acute paranoid psychosis. Eventually orthotopic liver transplantation was performed with the removal of the primary tumor from the distal pancreas. Postoperatively, complications were associated with the distal pancreatectomy. The patient has no evidence of tumor recurrence on imaging or serum VIP level 12 months posttransplantation.
Increased T suppressor activity in renal transplant recipients with long‐term stable graft function
Authors: Weimer R. , Pomer S. , Staehler G. , Opelz G.
Published: September 2024

There is evidence for differences in B‐cell regulation between renal allograft recipients with long‐term stable graft function (ST patients) and patients undergoing chronic rejection (CR patients). To assess the role of T cells in B‐cell regulation, we tested T‐lymphocyte helper and suppressor functions in 26 ST patients (> 1 year posttransplant) and in 13 CR patients. 34 healthy blood donors served as controls. CD4‐positive or CD8‐positive T lymphocytes were cocultured with B lymphocytes and pokeweed mitogen for 6 days. B‐cell differentiation was assessed in a reverse hemolytic plaque assay and by ELISA determination of IgM and IgG in culture supernatants. We found a diminished T helper function and elevated T suppressor activity in ST patients (immunoglobulin‐secreting cell formation, p < 0.001; IgM secretion, p < 0.002; IgG secretion, p < 0.05) but not in CR patients. Elevated counts of CD4 cells with suppressor activity were responsible for the increased T suppression in ST patients. The percentage of CD45R‐positive CD4 cells (suppressorinducer cells) was unchanged in both ST and CR patients. Whereas all CR patients had T helper function in the normal range, 11 of 26 (42%) ST patients had defective T helper activity (p < 0.005). 62% of the ST patients demonstrated T‐cell suppression of immunoglobulin‐secreting cell formation in contrast to 23% of CR patients (p < 0.05). Our data support a role of T suppressor activity in the maintenance of allograft acceptance in long‐term transplant recipients.
Cytoimmunological monitoring of heart transplant recipients
Authors: Jutte N. H. P. M. , Hop W. C. J. , Daane R. , Essed C. E. , Weimar W. , Simoons M. L. , Bos E.
Published: September 2024

The prognostic value of cytoimmunological monitoring of peripheral blood from heart transplant recipients was investigated with respect to the first rejection episode within the first 3 months after transplantation. The study comprised 371 CIM slides made concurrently with endomyocardial biopsies (EMB) in 70 patients. The number of lymphoblasts and activated lymphocytes counted in the slides was expressed as percentage of the total number of lymphocytes. Histological evaluation of the EMB was used as a “gold standard” for the occurrence of rejection, including myocytolysis. With regard to the absolute values of percentages of lymphoblasts and/or activated lymphocytes or their sum, no significant differences were observed between slides made when rejection was diagnosed or not. This was also the case when different immunosuppressive regimens were analyzed separately. Also, when changes in CIM parameters within individual patients were evaluated, no relation between CIM and rejection was found. In conclusion, for diagnosis of rejection of heart transplant recipients CIM was not useful for our group of patients.
Pediatric hepatic artery thrombosis successfully treated by immediate reoperation associated with selective urokinase injection. A case report
Authors: Yandza T. , De Victor D. , Pariente D. , Takahashi H. , Devictor D. , Gauthier F. , Jacolot D. , De Dreuzy O. , Huault G. , Valayer J.
Published: September 2024

Early hepatic artery thrombosis (HAT) is thought to be associated with a high mortality rate by liver graft or graft bile duct infarction unless followed by retransplantation. We report a case of early HAT immediately operated. After partial thrombectomy and flush with urokinase, a new end‐to‐end anastomosis of the arterial stumps was performed. One year post‐transplant, the child is doing well and hepatic biology is normal. Immediate surgical revision associated with in situ Urokinase injection may avoid serious complications related to early HAT.
Signs of nerve regeneration and repair following pancreas transplantation in an insulin‐dependent diabetic with neuropathy
Authors: Beggs John L. , Johnson Peter C. , Olafsen Astrid G. , Cleary Colleen P. , Watkins C. Jane , Targovnlk Jerome H. , Koep Lawrence J.
Published: September 2024

Neuropathy is a common complication of diabetes mellitus (DM). Myelinated nerve fiber (MNF) abnormalities, microangiopathy of the vasa nervorum, and abnormalities of the perineurium (PN) are frequent pathological findings in the nerves of diabetics. Nerve function in most DM patients with neuropathy improves following successful pancreas transplantation (PT). In this morphometric study of sequential nerve biopsies from a DM patient who experienced a marked improvement in debilitating diabetic neuropathy after PT, we found that the progression of nerve disease was halted during the 2 yr of euglycemia after PT. We also identified signs of tissue repair and regeneration of some nerve components including: a reduction in the frequency of abnormal pericytes associated with endoneurial capillaries, a reduction of MNF abnormalities characteristic of active fiber degeneration, an increase in fiber characteristics associated with regeneration, a two‐fold increase in unmyelinated axons, and a doubling of MNF sprouts. Conclusion: Long‐term euglycemia may prevent progressive nerve disease in DM and provide a neural environment suitable for nerve regeneration and repair.
Immunologic monitoring of steroid withdrawal in renal allograft recipients on triple therapy with cyclosporine‐A, azathioprine and prednisone
Authors: von Kiparski Alexander , Frei Dieter , Fierz Walter , Uhlschmid Georg , Frei Gertrud , Largiadèr Felix , Binswanger Ulrich
Published: September 2024

The lymphocyte subsets in the peripheral blood were examined in 35 stable renal allograft recipients on maintenance triple therapy with cyclosporine‐A (CyA), azathioprine (Aza) and low‐dose prednisone (Pred). In 20/35 recipients, Pred was discontinued. Pred withdrawal was successful in 12 (60%) patients (group A) and unsuccessful in 8 (40%) patients (group B). Group B had a significantly higher CD4/CD8 ratio before Pred withdrawal than group A (2.4 ± 1.4 vs 1.4 ± 0.6; p < 0.05) although only 4/8 patients had a high ratio (> 2.5). After cessation of Pred, Leu3 + (helper/inducer) and Leu2 + (suppressor/cytotoxic) cells increased in group B and Leu3 + cells were significantly higher than in group A (p < 0.02). The Leu2 + /Leu15 – (cytotoxic) subset was responsible for the significant increase of the Leu2 + cells (p < 0.05). However, in 6/12 recipients of group A there was also an increase of Leu3 + and Leu2 + cells but a decrease of these subsets in the other 6 patients. After withdrawal of Pred, group A was compared to the 15 patients with triple therapy who were not withdrawn, 15 patients with conventional therapy (Aza and Pred) and 15 blood donors. B cells (Leu12 +) and Leu11 + NK cells were significantly lower in the transplanted patients compared to the blood donors. Group A and the conventionally treated patients had significantly decreased helper/inducer cells (Leu3 +) with a significantly lower CD4/CD8 ratio than the controls. In the transplant group a reversal of the Leu3 + subsets was observed resulting in higher T‐helper cell values (Leu3 + /Leu8–) and significantly lower T‐suppressor‐inducer cell counts (Leu3 + /Leu8 +) compared to the controls. A similar distribution was seen already pretransplant in 14 uremic patients. In conclusion, patients with a high CD4/CD8 ratio might represent a risk group for Pred withdrawal failure, although the outcome could not be predicted in the individual patient.
Expression of HLA‐class I molecules in human pancreas
Authors: Leprini Arnaldo , Valante Umberto , Barocci Sergio , Cantarella Sebastiana , Fontana Iris , Leprini Alessandra E. G. , Celada Franco , Nocera Arcangelo
Published: September 2024

In the present work we have focused our attention on the distribution of HLA‐class I molecules (A, B, C) in human pancreas. To this end, tissue sections from 12 pancreata, obtained from normal cadaver donors, were studied by means of single and double immunoenzymatic stainings with a battery of monoclonal antibodies. The analysis of 10 out of 12 organs demonstrated that: i) endocrine parenchymal cells expressed very low amounts of HLA‐class I antigens as opposed to exocrine parenchymal cells that were stained with different degrees of clear positivity: ii) within the non‐fibroblastic interstitial cell population of pancreatic tissues, dendritic cells appeared almost negative whereas macrophages stained strongly positive. Changes in the above pattern of class I antigen expression were observed in the remaining 2 pancreata. These organs did not show any histologic tissue alteration but differed from the other 10 because of an increased percentage in the exocrine portions of interstitial mononuclear cells such as monocytes, B and T lymphocytes. In these latter pancreases no differences were detectable between exocrine and endocrine parenchymal cells, both appearing sharply positive for HLA‐class I molecule expression. The inducibility of HLA‐class I antigens on pancreatic parenchymal cells was also demonstrated by in vitro experiments where human purified isolated islets were cultured in the presence of human recombinant tumor necrosis factor‐α.
Role of passenger leukocytes in islet allograft immunity
Authors: Gill Ronald G.
Published: September 2024

The passenger leukocyte concept proposes that a specialized antigen‐presenting cell within the graft is responsible for the induction of allograft immunity. This theory forms the basis for attempting to modify tissue immunogenicity by eliminating or inactivating these cells prior to grafting. Despite considerable work addressing this issue, the contribution of passenger leukocytes to allograft immunity remains a controversial subject. Recent studies challenge the role of passenger leukocytes as the principal inducers of alloimmunity. The goal here is to reassess the role of passenger leukocytes in alloimmunity by focusing on two central questions: (1) What is the role of MHC antigens in inducing graft rejection, and (2) What constitutes an alloantigen‐presenting cell? The evidence presented suggests that MHC alloantigens are not sufficient for the induction of allograft immunity, thus supporting a critical role for passenger leukocytes in the triggering of allograft rejection.
Arteriovenous fistulas after renal allograft biopsy: A serious complication in patients beyond one year1
Authors: Lawen Joseph G. , Van Buren Charles T. , Lewis Richard M. , Kahan Barry D.
Published: September 2024

Cyclosporine (CsA) immunosuppressive therapy has raised the diagnostic dilemma of differentiating drug‐induced renal injury from renal allograft rejection. Renal transplant biopsy has emerged as an important tool to resolve this question. Among 744 patients treated with CsA‐prednisone (P) and 221 patients with azathioprine (Aza)‐P therapy, 352 (47%) and 41 (19%; p < 0.01) respectively, underwent renal transplant biopsy. Of the latter, 81% were needle biopsy (NB). The present reported 6 arteriovenous fistulas (AVF) all occurred in the CsA‐P‐treated group after NB, yielding an incidence of 1.3%. While 37 and 75% of NB were performed within the 1st month and 1st year post‐transplant, respectively, the occurrence of AVF was low, 0 and 2 lesions (0.6%), respectively. Contrariwise, 4 of 6 AVF (3.5%; p = 0.015) developed beyond the 1st yr, all in patients displaying hypertension as well as histopathologic findings of interstitial fibrosis and arteriolopathy in the biopsy specimen. Among a set of 54 NB performed beyond 1 yr after transplantation for renal dysfunction, but not complicated by AVF, fibrosis and arteriolopathy were present in 98% and 73%, respectively, suggesting that the remote time‐frame of the NB associated with this histopathologic picture may predispose to the increased risk of AVF. Two patients with AVF were managed expectantly; while 4 required interventional therapy. One patient in the former group and 3 in the latter lost their grafts within 1–6 months. These findings suggest that CsA‐treated patients undergoing allograft NB beyond 1 year following transplantation are at increased risk of AVF, which was associated with loss of the graft in 4 of 6 cases.
Alloreactivity of lung biopsy and bronchoalveolar lavage‐derived lymphocytes from pulmonary transplant patients: Correlation with acute rejection and bronchiolitis obliterans
Authors: Rabinowich Hanna , Zeevi Adriana , Yousem Samuel A. , Paradis Irvin L. , Dauber James H. , Kormos Robert , Hardesty Robert L. , Griffith Bartley P. , Duquesnoy Rene J.
Published: September 2024

A total of 82 TBB from 28 patients were cultured in the presence of interleukin‐2, a lymphokine that induces proliferation of activated T cells. Lymphocyte growth was almost 100% for biopsies with histological diagnosis of acute rejection or active bronchiolitis obliterans, significantly more than the 29% growth of biopsies with no major abnormalities. On 57 occasions, BAL were sampled simultaneously with TBB. Lymphocyte growth from TBB correlated with donor‐specific alloreactivity of BAL cells as measured by primed lymphocyte testing (PLT); both occurred with high frequency during acute rejection and bronchiolitis obliterans. The PLT activity of BAL cells from clinically quiescent patients with histologically negative biopsies, correlated with a high incidence of subsequent active bronchiolitis obliterans. TBB‐propagated lymphocytes and BAL cells were also studied for donor‐specific cytotoxicity measured by cell‐mediated lympholysis (CML). Significant correlations were found with acute rejection and bronchiolitis obliterans. Regression analysis showed a linear correlation between the PLT and CML reactivity patterns of biopsy and BAL‐derived lymphocytes. These data suggest that the allore‐active T cells in BAL were analogous to those in the cellular infiltrate of the lung allograft. The results of these studies reinforce the usefulness of BAL in assessing in situ immunity within the transplanted lung.
HLA‐D region restriction fragment length polymorphisms in living‐related and cadaver donor renal transplantation
Authors: Ludwin D. , D'Souza M. , Singal D. P.
Published: September 2024

DNA typing was used to examine the restriction fragment length polymorphism (RFLP) for the HLA‐D region and the T‐cell antigen‐receptor genes in donors and recipients of successful and rejected kidney transplants. The results in 15 HLA‐identical MLC‐non‐stimulatory sibling donor‐recipient combinations demonstrate that, in one instance, where the graft was removed due to rejection, the donor had two HLA‐D region gene RFLPs, (Bam HI‐DRB; Eco RV‐DQB), not present in the recipient. In contrast, polymorphism observed with these two restriction endonucleases was identical in two other HLA‐identical donor‐recipient combinations with rejected kidneys, as well as in all cases with functioning allografts. DNA typing was not helpful in distinguishing between 7 HLA‐haploidentical living‐related sibling and parent‐to‐child or 33 unmatched cadaver donor‐recipient pairs with and without functional transplants. When the TcR gene RFLPs were analyzed, all 12 recipients of HLA‐identical sibling allografts with successful transplants were identical or matched for the TcR β chain polymorphism. In contrast, all 3 recipients in this group who had rejected the kidney were mismatched or were not identical for the TcR β chain RFLPs. Extensive analysis of the TcR genes in the 7 haploidentical living‐related and 33 mismatched cadaver allograft donor‐recipient pairs failed to reveal any significant correlations between RFLP matching and clinical outcome. It is likely that DNA typing will be useful only in predicting or explaining rejection in some apparently HLA‐identical donor‐recipient pairs.
Renal transplantation in patients with paraproteinemias1
Authors: Bumgardner Ginny L , Matas Arthur J. , Payne William D. , Dunn David L , Sutherland David E. R. , Najarian John S.
Published: September 2024

Patients with paraproteinemias may have a spectrum of clinical diseases with marked differences in prognosis. We report the course of 3 patients with pretransplant paraproteinemias (1 with multiple myeloma, 1 with light chain deposition disease, 1 with Waldenström's macroglobulinemia) and review 10 patients reported in the literature (6 with multiple myeloma, 4 with light chain deposition disease). Of the 7 patients with multiple myeloma, 2 are alive with functioning grafts. The remaining 5 died with function 14 months to 9.5 years posttransplant; infection was the cause of death in all 5. The patient with Waldenström's macroglobulinemia and 3 of the 5 with light chain disease are alive with function. Although recurrent disease was common, it did not necessarily result in renal dysfunction or graft loss. The collective experience from these 13 patients demonstrates that relatively long patient and graft survival can be achieved in a select group of patients with paraproteinemias. Pretrans‐plant evaluation should exclude the presence of active disease. Patients with “benign monoclonal gammopathy” should undergo serial revaluations for at least 1 yr to exclude the presence of unrecognized multiple myeloma or Waldenström's macroglobulinemia. Posttransplant management should: (1) include a particularly low threshold for detecting infectious complications, especially with fungal pathogens, (2) avoid dehydration, hypercalcemia, hyperuricemia, and nephrotoxic drugs, and (3) maintain close follow‐up for detecting recurrent disease. The data suggests transplantation is an acceptable choice for treating renal failure in patients with paraproteinemias.
Liver transplantation in patients with situs inversus
Authors: Todo Satoru , Hall Roberta , Tzakis Andreas , Starzl Thomas E.
Published: September 2024

Two patients with situs inversus and biliary atresia were treated with hepatic transplantation, one with an auxiliary liver and the other with an orthotopic graft which was placed using a piggy‐back technique. Both transplants functioned well initially. The auxiliary liver was rejected after 1½ months, and the patient died after an attempt at retransplantation many months later. The recipient of the orthotopic liver has perfect liver function 10 months postoperatively.
Diagnosis of pancreatic graft rejection by duplex‐Doppler ultrasonography
Authors: Kubota Keiichi , Billing Hans , Kelter Ulrike , Tibell Anika , Tydén Gunnar , Groth Carl Gustav
Published: September 2024

The utility of duplex‐Dopper ultrasonography (US) in the diagnosis of pancreatic graft rejection was evaluated in 9 patients. The examinations assessed the resistive index (RI) of arteries within the graft parenchyma, the homogeneity and echogenicity of the parenchyma, and the presence of fluid collections around the grafts. For the first 3 days after transplantation, the RI was found to be high. Subsequently, it decreased, and when the graft was in a stable condition, the mean RI was 0.63. With acute rejection episodes, the RI increased to a mean of 0.68 (p = 0.002). Thus the increase in mean RI was small but significant. If serial US examinations were performed then an increase in RI, above an individual stable base‐line level, was more apparent. After successful anti‐rejection treatment, the RI decreased again. In 1 case with chronic rejection, the RI was found to be high, and the parenchyma was non‐homogenous with high echogenicity. With pancreatitis, the RI did not change significantly. In 2 patients, fluid collections – which later resolved spontaneously –were seen around the grafts. In 1 patient, an arterial pulsation, which had been detectable previously, was found to be absent, and arterial thrombosis was confirmed at operation. In conclusion, serial duplex‐Doppler US may be useful for monitoring pancreatic grafts and the RI may assist in the diagnosis of pancreatic graft rejection.
Outpatient use of OKT3 for the treatment of acute renal allograft rejection
Authors: Hricik Donald E. , Bartucci Marilyn R. , Seller Mary C. , Schulak James A.
Published: September 2024

The case of administering the monoclonal antibody OKT3 makes outpatient therapy feasible in patients who are free of side effects during the latter stages of treatment for acute allograft rejection. In our 3‐year experience with OKT3, almost half of our patients have been able to receive a portion of their therapy on an outpatient basis. A retrospective analysis of clinical conditions influencing the decision to discharge patients for outpatient therapy suggests that persistent fever and renal dysfunction are the main factors that preclude outpatient therapy. The substantial economic impact of administering this effective anti‐rejection agent on an outpatient basis has encouraged us to seek means of increasing the proportion of patients who can be treated with OKT3 in the outpatient clinic.
Pneumonia incidence in renal transplantation: Factors associated with declining rates
Authors: Mutgi Anand , Zeitler Rodney , Helms Charles , Goeken Nancy , Flanigan Michael , Corry Robert J.
Published: September 2024

The incidence density and factors associated with pneumonia in a cohort of 769 renal allograft recipients over a 15‐year period were studied. A total of 154 episodes of pneumonia occurred in 133 renal graft recipients. The overall incidence density (ID) of pneumonia was 5.5 cases per 100 patient years at risk. The ID of pneumonia declined from 23.8 per 100 patient years over the first 5 yr of the transplantation program, to 7.8 per 100 patient years over the next 5 yr and has stabilized at 3.0 per 100 patient years in the most recent 5‐yr period. Most of the reduction occurred prior to the introduction of cyclosporine in 1983. A logistic regression analysis indicated this decline to be associated with reduction in the dosage of prednisone (p = 0.007) and male sex (p = 0.02). Pneumonia etiology was identified in 67% of cases. Gram‐negative bacilli were the most common pathogens. Despite decreasing incidence of pneumonia and mortality over time, mortality rates remain high.
Efficacy of local graft irradiation in preventing cadaveric renal transplant rejection: A prospective randomized trial
Authors: Morris Michael , Lloyd George , Badosa Francisco , Om Anil , Yuan Dah‐Lun , Asbell Sucha , Anderson Leonard , Bannett Aaron
Published: September 2024

Successful renal transplantation depends on the modification of the normal immunologic response. The earliest attempts at such modification involved the use of ionizing irradiation. The significant morbidity and mortality of total body irradiation led to its abandonment in favor of the safer technique of local graft irradiation. While still commonly used, the efficacy of this technique has never been evaluated in a prospective, randomized fashion. The present study is a prospective, randomized, double blinded evaluation of the efficacy of the addition of local graft irradiation to our immunosuppressive protocol. One hundred consecutive cadaveric renal transplants were randomized to receive either conventional immunosuppression alone or conventional immunosuppression plus local graft irradiation delivered in doses of 150 rads on the 1st, 3rd and 5th post‐operative days. Patients were followed for a period of 2 years. No significant difference was demonstrated between the groups among any measured parameter. In conclusion, the addition of local graft irradiation in doses of 150 rads on d 1, 3, and 5 does not appear to offer any advantage over standard immunosuppressive therapy and its use cannot be recommended.
Post‐transplant lymphoproliferative disease and triple therapy
Authors: Lopatin William B. , Hickey David P. , Nalesnik Michael A. , Vivas Carlos A. , Flack Charlas E. , Jordan Mark L. , Starzl Thomas E. , Hakala Thomas R.
Published: September 2024

The occurrence of lymphoproliferative disease in the renal transplant patient has been associated with the type of immunosuppression administered. The present retrospective study analyzed the risk of developing post‐transplant lymphoproliferative disease in patients receiving cyclosporine, azathioprine and prednisone triple therapy. Of 296 renal transplant patients treated with triple therapy from 1987 through January 1989, 4 (1%) developed post‐transplant lymphoproliferative disease. This figure is not significantly different from our previous experience. Possible reasons for this are discussed. We concluded that triple therapy as used at our institution is not associated with an increased risk of post‐transplant lymphoproliferative disease, and we recommend its continued use in this patient population.
A critical analysis of morbidity and mortality as it relates to recipient age following cardiac transplantation
Authors: Hosenpud Jeffrey D. , Pantely George A. , Norman Douglas J. , Cobanoglu Adrian M. , Hovaguimian Hagop , Starr Albert
Published: September 2024

Older patients (age greater than 55) are now being accepted as candidates for cardiac transplantation. The outcome following cardiac transplantation in this older age group has been largely limited to an analysis of mortality and rejection and infection incidence. In addition to these factors, this report investigates whether morbidity related to other organ system disease is greater in older patients. Seventy‐eight cardiac transplant operations in patients aged 15 through 64 have been performed using the identical immunosuppression protocol from December 1985 to May 1989. Of these, 58 patients were under the age of 55 (younger), and 20 were 55 years of age or older (older). One‐ and 2‐yr survival tended to be lower in the older group compared to the younger group, but was not statistically significant (1 yr ‐ 87% vs. 77%, respectively; 2 yr ‐ 84% vs. 77%, respectively, p = 0.143). There were no statistical differences between groups in length of initial transplant hospitalization, number of readmissions or total duration of time in hospital (including readmissions) either absolutely or normalized to total months of follow‐up for each patient. Neurologic and vascular problems represented a greater proportion of readmissions and rejection a lower proportion of readmissions in the older group compared to the younger group (p < 0.05). Using hospitalization as a marker for important morbidity, there appears to be little impact of older age on post‐cardiac transplant outcome.
Leucoencephalopathy after cyclosporine in a liver transplant
Authors: Lloveras J.‐J. , Larrue V. , Suc E. , Fourtanier G. , Durand D.
Published: September 2024

Numerous reports have emphasized neurologic manifestations after cyclosporine therapy. Among them, leucoencephalopathy appears as rarely documented. We describe such a case in a liver transplant recipient who presented serious central nervous system complications; clinical feature was essentially confusion and drowsiness. A close relationship existed between neurological signs and administration of cyclosporine during the post‐operative period. A sequential study of computed tomographic (CT) scanning and magnetic resonance (MR) imaging of the head showed partially regressive white matter abnormalities. On one occasion, cyclosporine level was measured in cerebrospinal fluid (CSF) showing a CSF/blood ratio close to 0.5. This case stresses the importance of CT scanning and MR imaging when cyclosporine is incriminated as the cause of neurologic symptoms in transplant patients. Moreover, presence of cyclosporine in CSF suggests the possibility of increasing permeability of the blood brain barrier (BBB) in liver transplants.
Treatment of upper abdominal malignancies with organ cluster procedures
Authors: Mieles Luis , Todo Satoru , Tzakis Andreas , Starzl Thomas E.
Published: September 2024

Upper abdominal exenteration for upper abdominal malignancies was carried out in 15 patients with removal of the liver, spleen, pancreas, duodenum, all or part of the stomach, proximal jejunum and ascending and transverse colon. Organ replacement was with the liver, pancreas and duodenum plus, in some cases, a short segment of jejunum. Eleven of the 15 patients survived for more than 4 months; 2 died, after 6½ and 10 months, of recurrent tumor. Of the 9 patients who are surviving after 6½ to 14 months, recurrent tumor is suspected in only 1 and proven in none. Four patients with sarcomas and carcinoid tumors (2 each) have had no recurrences. The other 5 survivors had duct cell cancers (3 examples), a cholangiocarcinoma (1 example), and a hepatoma (1 example). The experience so far supports further cautious trials with this drastic cancer operation.
Antigen‐specific transplantation tolerance
Authors: Sachs David H.
Published: September 2024

Two animal models are described which are currently being studied in this laboratory in attempts to induce specific transplantation tolerance across major histocompatibility barriers. One model involves the use of minature swine selectively inbred at the MHC. Exposure of these animals to a vascular graft genetically identical to the recipient at class II was found to be sufficient to induce long‐term, specific tolerance to both class I and minor antigens in about one‐third of animals. Tolerance induction in this situation appears to be an active immunologic phenomenon involving a suppressive arm of the immune response. In the second model, induction of mixed lymphohematopoietic chimerism in mice was found to produce specific transplantation tolerance toward the allogeneic bone marrow donor. The mixed chimerism has been induced either by lethal irradiation and reconstitution with mixtures of syngeneic and allogeneic bone marrow, or by treatment with monoclonal antibodies followed by sublethal irradiation and administration of allogeneic bone marrow. Because the latter preparative regimen is non‐lethal, it may be clinically applicable for the induction of specific tolerance to human organ transplants.
HLA compatibility and clinical outcome among cardiac transplant recipients
Authors: Shakin‐Eshleman Susan H. , Cavarocchi Nicholas C. , Zmijewski Chester M.
Published: September 2024

The importance of HLA compatibility between the donor and recipient in determining the clinical outcome of cardiac transplant recipients is not clear. This report examines the relationship between HLA compatibility and clinical outcome in 82 cardiac transplant recipients during the 1st post‐operative year. Both the degree of HLA antigen mismatch and the compatibility of the pre‐transplant crossmatch are considered as parameters of HLA compatibility. Clinical outcome is assessed by comparing rejection rates and 1‐yr survival among different patient groups.
Improved results in elderly renal transplants without prophylactic steroids
Authors: Andreu J. , Campistol J. M. , Oppenheimer F. , Ricart M. J. , Vilardell J. , Talbot R. , Carretero P.
Published: September 2024

Aged patients have been considered as high‐risk recipients for renal transplantation (RT). From June 1980 to December 1989, we performed 82 cadaveric RT in elderly (> 55 years) patients, 23 RT were treated with azathioprine (Aza) and the remaining 59 (transplanted since June 1984) with cyclosporine (CyA) as monotherapy (41 cases) or in low doses with Aza (18 cases). Steroids were introduced at first rejection crisis so that patients without any rejection remained without steroids. Patient survival at 1 and 3 yr was 77.4% and 67.7% in the Aza group. In the CyA group patient survival was 96.6% and 93.7% at 1 and 3 yr. Graft survival at 1 and 3 yr was 73.9% and 52.2% in the Aza group and 92.9% and 90% in the CyA group (p < 0.05). All but 2 recipients in the Aza group had rejection episodes and were treated with high doses of steroids. In the CyA treatment group 54.2% of the recipients were rejection‐free (without steroids). During the same period 453 patients under 55 yr received cadaveric RT, 174 were treated with Aza and the remaining 279 recieved CyA. There were no differences in patient and graft survival among recipients under and over 55 yr in the CyA group. The differences are statistically significant in the Aza group. Mean rejection episodes were significantly lower in aged patients than in younger. In conclusion. RT in patients over 55 yr old treated with CyA had excellent results. CyA used as monotherapy is probably the best immunosuppressive protocol in elderly kidney recipients.
HPV infection in the lower genital tract of women undergoing hemodialysis and women with renal allografts
Authors: Kelly Graham E. , Shell A. G. Ross , Rose Barbara R. , Caterson Robyn , Pearse Elizabeth , Thompson Carol H. , Cossart Yvonne E.
Published: September 2024

The prevalences of both human papillomavirus (HPV) infection and epithelial abnormalities of the lower genital tract (LGT) of 48 immunosuppressed kidney transplant recipients and 24 hemodialysis patients were studied and compared to those in 55 age‐matched controls. Cervival scrapes were examined cytologically and by dot hybridization for the presence of HPV types 6/11 and 16/18; those patients with abnormal cytology and/or positive results for HPV types 16/18 were examined further by colposcopy and cervical biopsies taken for histopathology. The prevalence of abnormal cervical cytology in the control, transplant and hemodialysis patients was 0%, 4% and 13% respectively; the prevalence of HPV DNA was 2%, 46% and 42% respectively. HPV types 16/18 were the predominant types present in transplant recipients, while types 6/11 predominated in hemodialysis patients. Three of 11 transplant recipients examined colposcopically had evidence of HPV infection and one of these had cervical intra‐epithelial neoplasia (CIN); 3 of 5 hemodialysis patients examined had HPV infection and 1 of these had CIN. This study confirms that both sub‐clinical and overt HPV infection of the LGT are more common in female immunosuppressed transplant recipients. It is probable that infection is already present at the time of transplantation. The results confirm the need for regular gynaecological assessment of these high‐risk groups.
HLA antigen expression and cellular infiltrate analysis in rejected and accepted human liver allografts
Authors: Nocera Arcangelo , Pellicci Riccardo , Barocci Sergio , Valento Umberto , Cantarella Sebastiana , Celada Franco , Callea Francesco , Ceppa Paola , Leprini Arnaldo
Published: September 2024

HLA class I (A, B, C) and class II (DP, DQ, DR) antigen expression patterns and mononuclear cell infiltrates were analyzed in liver allograft needle biopsies from 4 acute rejections and 2 stably accepted grafts. Acute rejections were represented by a steroid‐resistant irreversible rejection, by a severe rejection responsive only to OKT3 mAb treatment and by 2 reversible moderate rejections. From one of these latter cases, as well as from another patient, liver biopsies were also available 310 and 275 days after transplantation in the presence of a stable graft acceptance. Paraffin and/or cryostat biopsy sections were studied by means of indirect immunohistological techniques using a battery of monoclonal antibodies. Cell lines were also established in vitro by culturing biopsy fragments in recombinant IL‐2 and were analyzed for phenotype and donor‐specific functions. The results demonstrated that: i) severe rejections were associated with a strong increase of HLA class I antigens on graft parenchymal cells (hepatocytes and bile duct epithelia) and with a DR positivity displayed mainly on bile duct cpithelia. Both portal and lobular areas were found to be infiltrated by mononuclear cells constituted mostly by CD8 + T cells endowed with donor‐specific CTL activity; ii) moderate rejections were characterized by different class I and DR positivity patterns and by portal cell infiltrates containing high numbers of non‐cylotoxic CD4+ T cells expressing in vitro donor‐specific proliferative activity; iii) mononuclear cell infiltrates of lesser intensity, mostly constituted by CD4+ T cells, were also detected in biopsies from accepted grafts, and these appeared almost normal for histology and for HLA antigen expression pattern. In one of the 2 accepted liver grafts, biopsy‐derived non‐cytotoxic CD4+ T cells, capable of donor‐specific proliferation, could also be expanded in vitro. Other molecules, such as DP and DQ, were never detected on hepatocytes in any of the cases and appeared weakly induced on bile duct epithelium only in severe rejections. These data demonstrate that presence and intensity of rejections as well as graft acceptance may be associated in transplanted livers with distinct patterns of HLA antigen expression and with T‐cell infiltrates having different phenotype and function.
A prospective study of quality of life in end‐stage renal disease: Effects of cadaveric renal transplantation
Authors: Christensen Alan J. , Jr. John M. Holman , Turner Charles W. , Smith Timothy W. , Grant Morgan K. , DeVault George A.
Published: September 2024

We prospectively examined quality of life in a sample (n = 35) of end‐stage renal disease (ESRD) patients before and after undergoing renal transplantation. Patients were initially assessed at the time of their pretransplant clinic evaluation. Follow‐up assessment was made an average of 9 months later. Subjects were classified into either a Successful Transplant or Waiting List group based on their treatment status at the follow‐up assessment period. Results indicated that patients receiving a renal graft demonstrated significant posttransplant improvement in terms of physical mobility (e.g., travel outside the home). Patients showed a nonsignificant trend toward improved physical functioning after transplantation on measures of ambulation and body care and movement. The present study did not find significant differences in vocational rehabilitation as a function of transplant status. In terms of psychological indices of quality of life the present results suggest a substantial advantage for renal transplantation. Transplanted patients exhibited a significant decrease in depression relative to the pretransplant period. In addition, patient reports of subjective well‐being (IWB) were significantly more positive after transplantation. Successful transplantation did not appear to reduce patient anxiety.
Solid‐organ transplantation in the pediatric population
Authors: First M. Roy , Schroeder Timothy J.
Published: September 2024

The results of solid‐organ transplantation in children have improved dramatically in recent years with advances in surgical technique and immunosuppressive therapy regimens. Donor organ availability continues to be a limiting factor in the pediatric age‐group, and it has been estimated that 20–30% of children waiting for a heart or liver transplant die before a suitable donor can be found. A number of problems remain for the long‐term pediatric graft recipient, and these will need to be vigorously pursued so that optimal rehabilitation and longevity can be achieved for the transplanted child.
Use of monoclonal antibody immunosuppressive therapy in pediatric renal and liver transplantation
Authors: Ryckman Frederick C. , Schroetter Timothy J. , Pedersen Susan H. , Fisher Robert A. , Farrell Michael K. , Heubi James E. , Ziegler Moritz M. , Balistreri William F.
Published: September 2024

OKT3, a murine monoclonal antibody directed against the human CD3 antigen, has proven effective in treating and preventing acute rejection in pediatric transplant recipients. Rejection reversal rates have ranged from 68‐93% in children receiving kidney transplants and 80‐93% in children receiving liver transplants. Single prophylactic studies with OKT3 in pediatric renal and liver transplants have reported outstanding 87% and 86% 1‐year graft survivals, respectively. Immunological monitoring of OKT3 therapy is essential to determine dosing changes and the ability to re‐use the monoclonal antibody.
Immunological monitoring during and following OKT3 therapy in children
Authors: Schroeder Timothy J. , Ryckman Frederick C. , Hurtubise Paul E. , Pedersen Susan H. , Balistreri William F. , First M. Roy
Published: September 2024

Immunologic monitoring during and following OKT3 monoclonal antibody therapy provides insight into the efficacy of the drug in treating or preventing allograft rejection. Depletion of CD3 + lymphocytes occurred following the first dose in all children treated with OKT3. There was a continued modulation of CD3+ lymphocytes throughout OKT3 therapy. Pre‐OKT3 treatment lymphocyte subsets were higher in younger children than in older children, and higher than previously reported in adults. Trough serum OKT3 concentrations were higher in children being treated for rejection than has been seen in adults. Pediatric transplant patients receiving OKT3 prophylactically had a trend towards lower drug concentrations as therapy progressed, while children being retreated with OKT3 had lower drug levels at the initiation of therapy that required increases in their daily OKT3 dose. Formation of OKT3 antibodies was 33%, which is similar to what we have reported in adults. A large number of pediatric liver recipients required increases in their daily OKT3 dose in order to achieve depletion of CD3+ cells (< 25/mm3) and ensure therapeutic OKT3 serum concentrations (> 800 ng/ml). In conclusion, immunologic monitoring during and following OKT3 therapy in children is necessary to ensure that the drug is being used most effectively and to determine if retreatment is possible.