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PubMedDate not supplied

Amelioration of weight gain after heart transplantation by corticosteroid-free maintenance immunosuppression. UTAH Cardiac Transplant Program.

After heart transplantation, recipients frequently become obese. Although the cause is undoubtedly multifactorial, administration of corticosteroids may contribute to posttransplant obesity. To test this hypothesis, we retrospectively reviewed the change in body weight with respect to corticosteroid use after transplantation in all 110 recipients surviving 1 year in the UTAH Cardiac Transplant Program. Fifty-two recipients (47%, group 1) were unable to be withdrawn from maintenance corticosteroids, and 58 recipients (53%, group 2) were successfully withdrawn, the latter group requiring only cyclosporine and azathioprine long-term maintenance immunosuppression. The change in weight from the time of transplantation to 1 year after transplantation in group 1 was 8.7 +/- 1.1 kg; group 2 patients gained only 4.9 +/- 0.9 kg (p = 0.009). In conclusion, successful withdrawal of maintenance corticosteroids after heart transplantation decreased posttransplant weight gain, suggesting that posttransplant obesity is in part related to use of corticosteroids.

Adrenal Cortex Hormones↗
PubMed1989

[Technology assessment of liver transplantation; a study of the liver transplantation program in Groningen 1977-1987].

The liver transplantation programme of the University Hospital of Groningen, the Netherlands, was evaluated on behalf of the Dutch Sick Fund Council. From 1978 to 1987 561 patients were put forward for liver transplantation (LTX). During this period, 76 orthotopic liver transplants were carried out, 8 of which were retransplantations. Survival proved to depend on, among other things, diagnosis and age. One-year survival was 100% in children with biliary atresia and 60% in other diagnosis and age groups. The number of life-years gained by LTX depends on the stage of disease. After LTX the quality of life improves quickly. One year after LTX most survivors experience a virtually normal quality of life. The need of LTX in the Netherlands was estimated to be in the range of 25 to 69 transplantations on an annual basis. The annual supply of donor livers is expected to be about adequate. Costs amount to approx. Hfl 250,000.--per transplanted patient including costs of follow-up for up to five years. The cost-effectiveness ratio for all forms of cirrhosis was estimated at Hfl 47,000.--to 133,000.--per life year gained. The results of this first technology assessment on liver transplantation proved relevant for clinicians as well as health politicians.

Adolescent↗
PubMed1987

Pediatric liver transplantation: patient evaluation and selection, infectious complications, and life-style after transplantation.

Liver transplantation is an increasingly accepted treatment for children with end-stage liver disease. Evaluation of the patient and appropriate patient selection for transplantation will become increasingly important issues as more and more children come to transplantation and compete for available organs. Numerous complications occur after transplantation, including infections. We have summarized our experience with bacterial, fungal, and viral infections in these patients and emphasize the need for continued improvement in immune suppressive drugs and regimens to minimize such complications. And finally, information presented on 65 pediatric patients followed 2 to 5 years suggests that, despite numerous complications and often prolonged hospitalization for transplantation, life-style after transplantation appears to be significantly improved.

Biliary Atresia↗
PubMed1983

Intensive therapy followed by bone marrow transplantation for patients with acute lymphocytic leukemia in second or subsequent remission: determination of prognostic factors (a report from the University of Minnesota Bone Marrow Transplantation Team).

Fifteen patients with acute lymphocytic leukemia (ALL) in second or subsequent remission received intensive therapy with cyclophosphamide and single dose, rapid rate (26 cGy/min) total body irradiation (TBI) followed by bone marrow transplantation (BMT) from a histocompatible sibling match. Outcome was compared to that of 23 conventionally treated control patients in second ALL remission who presented to the same institution during the same time period but had no available transplant donor. The 15 BMT patients and 23 control patients had similar characteristics, with the exception that the BMT patients were significantly older at the time of ALL diagnosis (12.6 yr versus 5.7 yr, p = 0.01). BMT patients had a significantly increased chance of remaining disease-free for 36 mo from time on study (43% actuarial versus 5%, p = 0.004) and a greater overall survival rate at 48 mo (47% actuarial versus 9%, p = 0.27) than the conventionally treated patients. In all, 5 of the bone marrow transplant patients (33%) remain alive and free of disease 24-48 + mo from transplantation. Several pre- and posttransplant characteristics were analyzed to determine predictive factors for a successful BMT outcome for patients with ALL in second or subsequent remission. Significant risk factors for predicting leukemic relapse included initial white blood count (WBC) greater than 50,000/microliters at ALL diagnosis (100% relapse rate versus 37% for patients with lower WBCs, p = 0.001) and presence of any extramedullary disease pre-BMT (100% relapse rate versus 37% for patients without extramedullary disease, p = 0.03). All 5 disease-free BMT survivors had initial WBCs less than 50,000/microliters and no evidence of extramedullary disease pretransplantation. Maintenance chemotherapy with 6-mercaptopurine (6MP) and methotrexate was given to four patients starting 100 days after bone marrow transplantation. Use of maintenance chemotherapy was associated with a significantly increased chance of remaining disease free (100% of patients surviving leukemia-free versus 17% for patients not receiving maintenance chemotherapy, p = 0.02). Presence of graft-versus-host disease (GVHD) did not influence leukemia-free survival. These results confirm that intensive therapy followed by bone marrow transplantation is the treatment of choice for patients with ALL in second or subsequent remission who have a histocompatible sibling match. Furthermore, the data suggest that a controlled trial to evaluate the efficacy of maintenance chemotherapy post-BMT for ALL patients is warranted.

Adolescent↗
PubMed1984

Role of bone marrow transplantation in the treatment of hematologic malignancies and solid tumors: critical review of syngeneic, autologous, and allogeneic transplants.

Intensive chemoradiotherapy and bone marrow transplantation is effective for selected patients with acute or chronic leukemia, lymphoma, or solid tumors. This paper will summarize the results of treatment utilizing syngeneic transplants from identical twins, allogeneic transplants from HLA identical and nonidentical donors, and the use of the patient's own bone marrow cells in autologous bone marrow transplantation. The potential complications of marrow transplantation are described and the current results of bone marrow transplantation are compared with recent advances in alternative forms of treatment for these malignancies.

Bone Marrow Transplantation↗
PubMed1978

[Significance of the hemodynamics for the extent of the rejection. Comparison of immunological reactions in artery transplantation in high pressure and vein transplantation in low pressure systems in matching inbred rat strain combinations].

Systemic sensitization is induced by arterial transplants in the high pressure system and by venous transplants in the low pressure system. In aorta transplantation the severity of the rejection corresponds directly to the immunogenetic differences between donor and recipient; the efferent limb is triggered into action. For application of allogeneic veno-venous transplants this is not the case: despite systemic sensitization, even strongly allogeneic venous transplants are maintained over long periods. A threshold value is not reached unless there is presensitization with strong antigens, after which morphologically comprehensible rejection reactions, i.e. round cell infiltration, are demonstrated even in veno-venous transplants.

Animals↗
PubMed1995

A national minority organ/tissue transplant education program: the first step in the evolution of a national minority strategy and minority transplant equity in the USA.

1. These successful education programs initially aimed at the AA community are being expanded into other minority groups such as Native American (Alaskan and American Indian), Hispanic (Latino), and Asian-Pacific Islander populations; and if the same modus operandus, ie, a minority-targeted message delivered by ethnically and culturally similar and sensitive messengers is used, this will have equal applicability to the majority population. MOTTEP, the first grass roots national transplant education program, while directed first to the minority population, can when presented to the majority population help all groups address the number one problem in transplantation today--the shortage of donors. 2. Active inclusion and involvement of minorities at all levels of problem resolution (resource allocation, research, and education), emphasizing community participation, education, and empowerment are the important next steps to allow for minority transplant equity in America. 3. The emergence of ASMHTP as the responsible brain trust for future minority-related efforts along with MOTTEP, a community based, empowering transplant education program, highlights the importance of a national strategy necessary for the survival of minority communities. This will enhance the interaction between minority transplant health professionals and the minority community and requires minority inclusion at all decision making levels of problem resolution within the transplant community.

Black or African American↗
PubMed1995

Lung transplantation in Louisiana: report of the first twenty lung transplants performed in the state.

Lung transplantation is a successful alternative treatment for a variety of end-stage lung diseases. The first 20 lung transplants performed in Louisiana between November 1990 and July 1994 are reported from Ochsner Foundation Hospital. Transplant procedures included 1 heart-lung, 11 bilateral sequential lung, and 8 single-lung transplants in 8 males and 11 females (1 retransplantation). The average age was 38 years (range 7-60), and the median waiting time was 34.5 days (range 1-329). Indications for transplant included emphysema, pulmonary fibrosis, pulmonary hypertension, cystic fibrosis, bronchiectasis, and bronchiolitis obliterans. Overall 1-year and 3-year survival were 65.0% and 58.5%, respectively. Infection was the major cause of morbidity and mortality. Rejection episodes were observed but treated successfully in all 20 patients. Lung transplantation has proved to be a successful treatment for a variety of severely limiting and terminal pulmonary conditions for patients in our state.

Adolescent↗
PubMedDate not supplied

Antiendothelial antibodies after heart transplantation: the accelerating factor in transplant-associated coronary artery disease?

Although the precise cause of transplant-associated coronary artery disease is unknown, immune mechanisms have been implicated. Using the techniques of SDS-PAGe and Western immunoblotting, we have previously shown that a strong positive correlation exists between the development of coronary artery disease and the presence of antiendothelial antibodies reactive with a doublet of polypeptides of approximately 60 and 62 kDa. We have now extended this study to investigate the temporal pattern of antiendothelial antibody formation after transplantation and its association with cellular rejection episodes. The original study used patients in whom coronary artery disease had developed early after transplantation, that is at 1 or 2 years. Here we investigate whether antiendothelial antibodies are also made in patients in whom the disease does not develop until 5 to 10 years after heart transplantation and whether the antibodies are found in patients with severe nontransplant atherosclerosis. We confirm the 60 to 62 kDa antigens are membrane bound, and recalculation of their molecular mass makes the doublet 56 and 57.5 kDa. The results show that antibodies specific for the doublet of endothelial antigens are rarely produced by patients other than those in whom rapidly progressing coronary artery disease develops early after transplantation. The antibodies are unrelated to cellular rejection episodes. We believe their production may be an accelerating factor for the rapid development of transplant-associated coronary artery disease.

Adolescent↗
PubMedDate not supplied

Isolated lung transplantation; initial experience at the University Hospitals Leuven. Leuven Lung Transplant Group.

Lung transplantation nowadays has become a therapeutic modality in the treatment of patients with a variety of end-stage lung diseases. Between July 1991 and December 1992, twelve patients received an isolated lung transplant (eight single lungs and four double lungs) at the University Hospitals of Leuven. The indication for transplantation was emphysema in five patients, pulmonary fibrosis in three, cystic fibrosis in three and primary pulmonary hypertension in one. There were four early, in-hospital deaths (30%): two from sepsis and multi-organ failure, one from anoxia following a bronchial dehiscence and another patient exsanguinated following stent insertion for a partial bronchial dehiscence. Three more patients have died during follow-up: two from chronic respiratory failure secondary to the development of obliterative bronchiolitis (one at 8 months and one at 17 months), and one from a late bronchovascular fistula 4 months following transplantation. The overall actuarial one and two year-survival was 50.0% and 41.6% respectively. All patients discharged from hospital were oxygen free with an improved lung function and exercise capacity. We conclude that lung transplantation is a viable therapeutic option for selected patients with end-stage, irreversible lung disease. In our experience, the bronchial anastomosis remains an important keystone in the early success. Lung transplantation provides a good quality of life in patients free from infection and rejection. Nevertheless, chronic rejection resulting in obliterative bronchiolitis is a major problem in long-term survivors.

Adult↗
PubMed1994

Umbilical cord blood progenitor cell transplantation. The International Conference Workshop on Cord Blood Transplantation, Indianapolis, November 1993.

Haemopoietic progenitor cells are present in umbilical cord blood (UCB) and have been used to restore haemopoiesis in children after myeloablative therapy. UCB may possess a number of advantages over bone marrow and peripheral blood as a source of allogeneic progenitor cells, e.g. a lower incidence of graft-versus-host disease and a decreased risk of transmission of infection and there is considerable interest in the establishment of large cord blood banks for use in unrelated transplants. The International Conference Workshop on Cord Blood Transplantation was held in Indianapolis in November 1993 and provided a timely opportunity to review the clinical and laboratory data relating to the use of UCB in transplantation. The results from 34 UCB transplants have been reported to the International Cord Blood Transplant Registry. Engraftment was achieved in 27 of 31 evaluable patients. Graft-versus-host disease > grade 1 occurred only in children transplanted from a one haplotype matched donor; 22 patients survive at a median of 1.5 years. Further sessions at the meeting reviewed the haemopoietic cell content of UCB, the capacity for expansion of early cells and the origin (fetal and/or maternal) and function of lymphoid cells within the graft. The conference ended with a discussion of the practicalities of cord blood banking including collection, cryopreservation, storage, HLA-typing and screening for genetic and infectious diseases.

Adolescent↗
PubMedDate not supplied

Matching the heart donor and heart transplant recipient. Clues for successful expansion of the donor pool: a multivariable, multiinstitutional report. The Cardiac Transplant Research Database Group.

Little information is available regarding donor-specific parameters that predict success or failure after heart transplantation. Furthermore, with increasing numbers of patients awaiting heart transplantation, there is tremendous pressure to expand the donor pool by stretching the margins of donor acceptability. To gain insight into donor-related and donor-recipient interrelated predictors of death after transplantation, 1719 consecutive primary transplantations performed at 27 institutions between Jan. 1, 1990, and June 30, 1992, were analyzed. Mean follow-up of survivors was 13.9 months, and actuarial survival was 85% at 1 year. By multivariable analysis, risk factors for death included younger recipient age (p = 0.006), older recipient age (p = 0.0005), ventilator support at time of transplantation (p = 0.0006), higher pulmonary vascular resistance (p = 0.02), older donor age (p < 0.0001), smaller donor body surface area (female donor heart placed into larger male patient) (p = 0.003), greater donor inotropic support (p = 0.01), donor diabetes mellitus (p = 0.01), longer ischemic time (p = 0.0003), diffuse donor heart wall motion abnormalities by echocardiography (p = 0.06), and, for pediatric donors, death from causes other than closed head trauma (p = 0.02). The overall 30-day mortality rate was 7% but increased to 11% when donor age exceeded 50 years and was 12% when inotropic support exceeded 20 micrograms/kg/min dopamine plus dobutamine and 22% with diffuse echocardiographic wall motion abnormalities. The interaction of donor risk factors was such that the heart of a smaller female donor given high-dose inotropes placed into a larger male recipient produced a predicted 30-day mortality rate of 26% and the heart of a 25-year-old male donor given high-dose inotropes with diffuse echocardiographic wall motion abnormalities transplanted into a 50-year-old male recipient led to a predicted 30-day mortality rate of 17%. This analysis supports cautious extension of criteria for donor acceptance but with an anticipated greater risk in the presence of diffuse echocardiographic wall motion abnormalities and long anticipated ischemic time, particularly in older donors given inotropic support.

Actuarial Analysis↗
PubMed1994

Effect of donor age on outcome of kidney transplantation. A two-year analysis of transplants reported to the United Network for Organ Sharing Registry.

The shortage of cadaveric donors coupled with a rapidly growing number of potential recipients has resulted in an increased use of older donors. In 1992, 10.7% of all cadaveric kidney transplants were from donors above the age of 55 compared with 5.4% in 1988. The present investigation serves as a follow-up of a prior study of the effect of donor age on outcome with a 2-year analysis of more than 30,000 cadaveric kidney transplants performed in the United States between October 1, 1987, and December 31, 1991, that were reported to the United Network for Organ Sharing. There was no difference between the graft survival at 1 and 2 years comparing donors aged 56-65 versus 65 and older, but the older donors (aged 56 and greater) had a 1- and 2-year graft survival that was approximately 10% and 14% less than that for recipients from the ideal age group of donors (16-45 years). There was no practical adverse interaction between donor age and recipient age, gender, diabetic status, peak PRA (panel reactive antibody activity) level of mismatch, cold ischemia time, or recipient race on outcome. The kidneys from older donors had poorer graft survival than the kidneys from younger donors when transplanted into recipients of repeat transplants, though the impact of repeat transplant and donor age on graft survival are independent of one another. These data suggest that kidneys from donors over the age of 55 overall have reduced functional reserve, which has an adverse effect on long-term function. Thus, attempts should be made to better estimate functional reserve among the older age group, but age alone should not be the sole factor for exclusion of a potential donor. The use of older donors appears to present an increased but acceptable risk of graft loss 2 years after transplant.

Adolescent↗
PubMed1993

[Danish experience with physical and occupational rehabilitation after heart transplantation. The heart transplantation group at Rigshospitalet].

Heart transplantations have been carried out for one year (1.9.1990-1.9.1991) in Denmark. Twenty-three out of 27 patients survived at the end of this period. Prior to transplantation, all of the patients were in NYHA groups III or IV. On discharge, all of the patients could manage a 45-60 minutes training programme followed by a stair test (two to six floors up). Prior to transplantation, 17 patients received financial aid in one form or another and one child received special schooling. On an average 165 days (1.9.1991) after transplantation, nine patients were in full or part-time employment, two were students, seven received financial aid and five were still in hospital. A correlation between the duration of financial aid before transplantation and return to work after transplantation was found. In addition, age was found to be of significance. It is concluded that physical status and return to work are satisfactory.

Adolescent↗
PubMed1993

Bless the babies: one hundred fifteen late survivors of heart transplantation during the first year of life. The Loma Linda University Pediatric Heart Transplant Group.

There is a rapid growth of interest in heart transplantation therapy during early infancy. From 10% to 25% of the infants who are listed for transplantation annually have died while awaiting a donor heart. There has been no significant trend in this variable. Since November 1985, 140 consecutive orthotopic transplantation procedures were performed in 139 infants who were from 3 hours to 12 months of age. Indications for transplantation included hypoplastic left heart syndrome (63%), other complex structural anomalies (29%), myopathy (6.5%), and tumors (1.5%). Most recipients had ductus-dependent circulation and received continuous infusion of prostaglandin E1. Heart donors were usually victims of trauma, sudden infant death, or birth asphyxia. A donor-recipient weight ratio of 4.0 or less was found to be acceptable. The amount of time the graft underwent cold ischemia, ranged from 64 to 576 minutes. The procurement process was facilitated by a single dose of cold crystalloid cardioplegic solution and cold immersion transport. Profound hypothermic circulatory arrest was used for graft implantation. One hundred twenty-four (89%) recipients survived transplantation and were discharged from the hospital. There were 9 late deaths, which resulted in an 83% overall survival. The 5-year actuarial survival is 80%. The survival among newborn recipients (n = 60) at 5 years is 84%. Chronic immunomodulation was cyclosporine-based and steroid-free. Surveillance was noninvasive and relied heavily on echocardiography, electrocardiography, and clinical intuition. There was one documented late lethal infection, tumor was not encountered, and coronary occlusive disease was known to exist in only one long-term survivor. We concluded that transplantation results in excellent life quality and is a highly effective and durable therapy when applied during early infancy.

Actuarial Analysis↗
PubMed1993

Impact of time-interval after transplantation and therapy with fibrates on serum cholesterol levels in renal transplant patients.

It is unclear to what extent different immunosuppressive regimens contribute to increased serum cholesterol levels observed in renal transplant patients after prolonged periods of immunosuppression (i.e. 3 and 5 years following kidney grafting). Therefore 2 groups of renal transplant patients were evaluated with respect to serum cholesterol 3 years (n = 103) and 5 years (n = 66) after transplantation: Group 1: prednisone (Pred)/azathioprine (Aza) [3 years (y): n = 52; 5 y: n = 49; mean prednisone dose 12 +/- 1 mg/day]; group 2: cyclosporine A (CsA) alone or in combination with Pred (3 y: n = 51; 5 y: n = 17; prednisone dose 4 +/- 2 mg/day, p < 0.001 vs group 1). The groups were similar with respect to age, sex, body mass index, time interval after transplantation, underlying kidney diseases and concomitant drug therapy. Serum cholesterol levels were persistently higher in patients of group 2 when compared to group 1 (3 years: 7.3 +/- 0.2 vs 6.7 +/- 0.2 mmol/l, p < 0.01; 5 years: 7.5 +/- 0.1 vs 6.6 +/- 0.3 mmol/l, p < 0.01) despite 75% lower daily doses of Pred (p < 0.001) in CsA treated patients (group 2). Before transplantation, patients exhibited a similar distribution of serum cholesterol levels when compared to age, sex and body mass index matched healthy subjects. In contrast 3 and 5 years following transplantation 72% of the patients had serum cholesterol levels above 6.5 mmol/l, whereas in normal subjects, 60% had serum cholesterol levels below 6.5 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group.

Mycopehenolate mofetil (MMF) is a powerful immunosuppressant that inhibits the proliferation of T and B lymphocytes by blocking the enzyme inosine monophosphate dehydrogenase. MMF has been shown to prevent acute graft rejection in animal experiments and may have an important role in clinical renal transplantation. We conducted a prospective, double-blind, multi-center trial to compare the efficacy and safety of MMF and azathioprine within standard immunosuppressive regimen for patients receiving a first or second cadaveric renal graft. A total of 503 patients were randomized to groups receiving MMF 3 g (n=164), MMF 2 g (n=173), or azathioprine (AZA) 100-150 mg (n=166) daily. All were treated simultaneously with equivalent doses of cyclosporine and oral corticosteroids and followed for 12 months. The primary endpoint was treatment failure, defined as the occurrence of biopsy-proven graft rejection, graft loss, patient death, or discontinuation of the study drug during the first 6 months after transplantation. Treatment failure occurred in 50.% of patients in the AZA group by 6 months after transplantation, compared with 34.8% in the MMF 3g group (P=0.0045) and 38.2 % in the MMF 2g group (P=0.0287). Biopsy-proven rejection occurred in 15.9% of patients in the MMF 3 g group and 19.7% in the MMF2 g group, compared with 35.5% in the AZA group. Rejection of histologic severity grade II or more developed in 6.1 %, 10.4% and 19.9% of patients in the MMF 3 g, MMF 2 g, and AZA groups, respectively. Patients receiving MMF required less frequent and less intensive treatment for acute rejection: 24.4% of patients on MMF 3 g and 31.0% on MMF 2 g were tested for acute rejection, compared with 47.5% on AZA. Only 4.9% on MMF 3 g and 8.8% on MMF 2 g required antilymphocyte antibodies for treatment of severe or steroid-resistant rejection, compared with 15.4% of the patients on AZA. At 1 year after transplantation, graft survival in the MMF groups was marginally superior to that in the AZA group, although this difference was not statistically significant. Gastrointestinal toxicity and tissue-invasive cytomegalovirus infection were more common in the MMF 3 g group. Noncutaneous malignancies occurred in six patients on MMF 3 g, three patients on MMF 2 g, and four patients on AZA. Lymphoproliferative disorders occurred in two patients per MMF group, compared with one patient receiving AZA. MMF appears to be an important advance in prophylaxis following renal transplantation. It is associated with a significantly lower rate of treatment failure compared with AZA during the first 6 months after renal transplantation and produces a clinically important reduction in the incidence, severity, and treatment of acute graft rejection. These differences persist throughout the first year of follow-up. Clinical benefit was greatest with a dose of MMF 3 g/day, but gastrointestinal effects, invasive cytomegalovirus infection, and malignancies were slightly more common at that dose. The appropriate dose may lie between 2 g and 3 g per day and may require individualization depending on clinical course or other factors.

Adult↗
PubMedDate not supplied

Improvement in quality of life after lung transplantation: a preliminary study. The University of Washington Medical Center Lung Transplant Study Group.

BACKGROUND: Lung transplantation is an expensive therapeutic option for a number of endstage conditions. Improving health-related quality of life is an important objective of transplantation. METHODS: We report quality of life measurements in 21 waiting list patients and 23 patients after transplantation with seven different pulmonary conditions using two standardized instruments: the Sickness Impact Profile and the standard gamble. RESULTS AND CONCLUSIONS: This cross-sectional study indicates the following: (1) overall quality of life improves significantly after transplantation; (2) although most dimensions of functional disability improve after transplantation, some aspects may suffer; (3) quality of life gains after transplantation may not be equal for all pretransplantation conditions.

Activities of Daily Living↗