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Biomedical subjects

L L Bailey

Publications and source records attributed to L L Bailey.

At least 37 records · Page 2Linked to original sources

Genotyping the baboon ABO histo-blood group locus by two-color fluorescence SSCP.

The use of baboons in experimental medicine, especially as organ and tissue donors, would be facilitated by the availability of ABO histo-blood group O animals, which are currently rare. To meet our need in breeding and identifying such animals, we have developed a single-stranded conformational polymorphism (SSCP)-based genotyping assay using fluorescence detection. Various buffers and labeling schemes were evaluated to optimize allele discrimination. Through the use of a nested PCR protocol, single-cell sensitivity was achieved, making the assay applicable to preimplantation diagnosis following in vitro fertilization. We discuss the comparative advantages of SSCP vs. alternative methodologies for genotyping.

ABO Blood-Group System↗

Heart transplantation among 233 infants during the first six months of life: the Loma Linda experience. Loma Linda Pediatric Heart TransplantGroup.

Two hundred thirty-three heart transplantations were performed in infants during their first 6 months of life at Loma Linda University between November, 1985 and June, 1999. Survival has now exceeded 13 years. Nearly 70% of infants are expected to live at least 10 years. Those transplanted during the first 30 days of life have about a 15% survival advantage at 10 years. Scarcity of donors continues to limit the transplantation effort. While acute rejection is the most common cause of late mortality, posttransplant coronary artery disease (PTCAD) is the leading cause of graft loss affecting 22 recipients (9.5%). The majority of patients are asymptomatic prior to diagnosis of PTCAD and are either retransplanted or dead within 6 months. Retransplantation (9 of 11 retransplantations for PTCAD) has been highly successful, with 10 year actuarial survival of 91%. Posttransplant lymphoproliferative disease (PTLD) has been found in only 7 patients (3%), most commonly in lymph nodes. Causes of late mortality include acute rejection (n = 16), PTCAD (n = 9), infection (n = 7), PTLD (n = 2), chronic graft dysfunction (n = 2), arrhythmia (n = 1), recurrent pulmonary vein stenosis (n = 1), and other noncardiac causes (n = 4). Infant psychomotor development is mildly delayed although cognitive development is normal. School-age children are performing at the level of their peers with average achievement and low average intelligence testing. Heart transplantation is durable therapy for newborns and infants with structurally incurable and end-stage myopathic heart disease.

Brain Death↗

Cardiac retransplantation for graft vasculopathy in children: should we continue to do it?

BACKGROUND: Cardiac transplantation (CTx) has been established as an effective therapy for a variety of inoperable cardiac conditions in infants and children. However, graft vasculopathy (GV) has emerged as the main limiting factor to long-term survival of CTx recipients. The only treatment of severe GV is cardiac retransplantation (re-Tx). Controversy exists regarding the use of scarce donor organs for cardiac re-Tx. OBJECTIVE: To compare the outcome of cardiac re-Tx for GV with that of primary CTx in children. DESIGN: A 12-year retrospective cohort review. SETTING: A university-affiliated children's hospital. PATIENTS: All infants and children who underwent CTx (group 1, n = 322) had complete follow-up of 1389.7 patient-years. Graft vasculopathy was confirmed in 32 recipients (1.1-8.2 years after undergoing CTx). Thirteen patients died suddenly, 3 died waiting for cardiac re-Tx (1-17 days after relisting), 4 are pending cardiac re-Tx, and 12 (group 2) underwent cardiac re-Tx. INTERVENTION: Cardiac re-Tx at a mean (+/- SD) interval from the first CTx of 6.3 +/- 1.8 years (range, 2.2-9.4 years). Two patients required additional aortic arch aneurysm repair with cardiac re-Tx. RESULTS: When group 1 was compared with group 2, there was no significant difference in operative mortality (9.0% vs 8.3%; P = .9), rejection rate (0.98 vs 0.86; P = .1), and hospital stay (23.0 +/- 18.8 days vs 20.5 +/- 11.6 days; P = .65). Actuarial survival for groups 1 and 2 at 1 and 4 years was 84.3% vs 83.3% (P = .59) and 74.4% vs 83.3% (P = .85), respectively. CONCLUSIONS: The surgical outcome and intermediate survival of cardiac re-Tx for GV and primary CTx are similar. Children with severe cardiac GV are at risk of sudden death and can benefit from early cardiac re-Tx.

Child, Preschool↗

Facile minimally invasive cardiac surgery via ministernotomy.

BACKGROUND: The public's and surgeons' perception of minimally invasive operations are frequently at odds. Nevertheless, real or perceived benefits may result from limiting skin and skeletal trauma. METHODS: Beginning in January 1996, we began approaching most infant and pediatric open heart procedures through an upper sternal split incision using a 1- to 3-inch skin opening and then extended this technique using a 2.5- to 3.5-inch incision for adult aortic and mitral valve replacement. RESULTS: A total of 82 patients, 57 infants and children and 25 adults, have been operated on using this approach (age range, newborn to 81 years). Operations accomplished through ministernotomy have included aortic valvotomy, arterial switch, tetralogy of Fallot, atrial or ventricular septal defect closure, aortic valve replacement, mitral valve replacement and repair, redo aortic or mitral valve replacement, double valve replacement, aortic root replacement, and complex arch reconstruction. In adults, the sternum was divided and then a T incision was made at the second, third, or fourth intercostal space. The mitral valve was reached through the roof of the left atrium. In children, a lower sternal split was used for atrial septal defect repairs. All cannulas were introduced through the ministernotomy incision, eliminating femoral cannulation. No new instruments, retractors, or ports were used. Mediastinal drainage was accomplished through a Blake drain connected to Heimlich-valved grenade suction. All but 2 patients were extubated immediately. Hospital stay was from 1 to 20 days (median 2 days). Patient and family acceptance is very high. CONCLUSIONS: On the basis of this initial experience, we attempt all congenital cardiac and isolated adult valve operations through ministernotomy.

Adolescent↗

Intermediate survival in neonates with aortic atresia: a multi-institutional study. The Congenital Heart Surgeons Society.

OBJECTIVE: Controversy persists with regard to the treatment of patients with aortic atresia. Staged reconstructive operations and primary transplantation have been advocated as treatment strategies, but in many instances no treatment is undertaken. A multi-institutional study was undertaken for the purpose of characterizing this challenging patient group, comparing the prevalence and outcomes of the various treatment strategies, and identifying potential predictors of success or failure with each. METHODS AND RESULTS: A total of 323 neonates with aortic atresia were entered into a 21-institution prospective, nonrandomized study between January 1, 1994, and January 1, 1997. Three protocols were used, nonexclusively in many institutions: (1) staged reconstructive surgery with initial palliation by a Norwood procedure and eventual Fontan operation, (2) heart transplantation as initial definitive therapy, and (3) nonsurgical management. Analysis was based on initial protocol assignment: staged reconstructive surgery in 253 patients, heart transplantation in 49 patients, and nonsurgical management in 21 patients. For all patients initially entered into the 2 surgical treatment protocols, survival at 1, 3, 12, 24, and 36 months after entry was 67%, 59%, 52%, 51%, and 50%, respectively. A multivariable analysis found incremental risk factors for death at any time after entry to be lower birth weight (P=.04), associated noncardiac anomaly (P=.007), and entry into the nonsurgical protocol (P < .0001) or the staged reconstructive surgery protocol (P=.03). Four institutions had higher survival statistics; 2 used a heart transplantation protocol and 2 used a staged reconstructive surgery protocol. For the 113 patients treated at these 4 institutions, survival at 1, 3, 12, 24, and 36 months after entry was 77%, 70%, 64%, 62%, and 61%, respectively. Survival among the 4 institutions was similar (P=0.1). CONCLUSIONS: Among patients with aortic atresia, other features of cardiac structure including aortic size, degree of left ventricular hypoplasia, and degree of mitral hypoplasia or atresia are not predictive of survival from 2 surgical protocols. The highest survival was achieved with either treatment strategy at institutions strongly committed to the use of one or the other surgical management protocol.

Aortic Valve↗

Seven-year follow-up of coronary artery bypasses performed with and without cardiopulmonary bypass.

BACKGROUND: There has been resurgent interest in coronary revascularization performed on the beating heart. Heretofore, there has been no long-term comparison of this technique to traditional coronary artery bypass with cardioplegia. OBJECTIVE: The purpose of this study was to provide a comparison of long-term survival and intervention-free outcome between patient groups subjected to coronary bypass accomplished with or without the use of cardiopulmonary bypass. METHOD: From June 1989 to July 1990, all patients treated for coronary revascularization by three surgeons were considered for coronary revascularization with the heart beating: 107 patients underwent coronary bypass on the beating heart, and 112 patients underwent revascularization with the aid of bypass with cardioplegia. Mean ages (65 +/- 10 years) and risk factors were identical. Patients operated on with the heart beating had 2.4 +/- 0.9 grafts versus 3.2 +/- 1.1 grafts for patients having cardiopulmonary bypass with cardioplegia. RESULTS: At 7-year follow-up, 86 of 107 (80%) patients operated on with the heart beating were alive versus 88 of 112 (79%) patients in whom cardiopulmonary bypass with cardioplegia was used. Cardiac deaths occurred in 13 of 107 (12%) patients in the former group versus 10 of 112 (9%) patients in the latter group. However, 32 of 107 patients operated on with the heart beating (30%) needed catheterization for their symptoms versus 18 of 112 (16%) patients in the bypass with cardioplegia group (p = 0.01). This results in 21 of 107 (20%) patients in the beating heart group needing angioplasty or a second coronary bypass versus only 8 of 112 (7%) patients in the bypass with cardioplegia group. No patient in the bypass with cardioplegia group required reoperation. Most of the reinterventions for the beating heart group were percutaneous transluminal coronary angioplasty (15 of 21 [71%] patients). CONCLUSION: Despite one less graft per patient, survival and cardiac death rates were similar for the two groups. However, twice as many patients in the beating heart group required recatheterization (30% versus 16%), and 20% needed a second intervention. Only 7% of the bypass with cardioplegia group required reintervention. Limited revascularization of the beating heart provides long-term results comparable to full revascularization with cardiopulmonary bypass, but at the cost of a threefold increase in reinterventions.

Aged↗

Prolonged discordant xenograft survival and delayed xenograft rejection in a pig-to-baboon orthotopic cardiac xenograft model.

OBJECTIVE: Our objectives were to study delayed xenograft rejection and the effectiveness of pretransplantation total lymphoid irradiation combined with immunosuppression on rejection in a pig-to-baboon cardiac xenograft model. METHODS: Baboons were treated with pretransplantation total lymphoid irradiation, cyclosporine A (INN: ciclosporin), and methotrexate. Orthotopic pig-to-baboon cardiac transplantations were performed after depletion of circulating xenoreactive natural antibody by pretransplantation donor organ hemoperfusion. Tissue samples were collected for immunologic and immunopathologic evaluation. RESULTS: Pig cardiac xenografts survived more than 18 and 19 days without evidence of hyperacute rejection. Immunologic analysis of serum samples demonstrated that circulating xenoreactive natural antibody levels did not return to pretransplantation levels. The production of xenoreactive natural antibodies from the recipient's splenocytes was inhibited completely. Histologic examination of xenografts showed the feature of acute vascular rejection. Immunohistochemical studies demonstrated infiltration of cardiac xenografts by large numbers of macrophages, small numbers of natural killer cells, and a few T cells. The infiltrating macrophages also showed expression of interleukin-1 and tumor necrosis factor. Diffuse deposition of immunoglobulin G, C1Q, C3, and fibrin on xenograft vasculature was observed. Interleukin-2 expression was not found in rejected cardiac xenografts. Xenograft endothelial cells also showed evidence of activation (expression of cytokines interleukin-1 and tumor necrosis factor). CONCLUSIONS: This study demonstrates prolonged discordant cardiac xenograft survival and delayed xenograft rejection in a pig-to-baboon model. The delayed xenograft rejection is mediated by both humoral and cellular mechanisms. Pretransplantation total lymphoid irradiation combined with cyclosporine A and methotrexate can inhibit xenoreactive natural antibody production but not elicited antipig antibody production and the xenoreactivity of macrophages.

Animals↗

Heart transplantation in infants and children with situs inversus.

BACKGROUND: Recipient situs inversus has always represented a technical challenge during heart transplantation. OBJECTIVE: A simplified operative strategy for heart transplantation in a recipient with atrial situs inversus is described. METHODS: Fifteen pediatric recipients with situs inversus accompanying other complex congenital heart disease or dilated cardiomyopathy having "orthotopic" heart allotransplantation in one center, between 1985 and 1997, were reviewed retrospectively. A nearly uniform, simplified technical approach to transplantation was used and is described. RESULTS: Fourteen of these recipients with complex malformations survived the transplantation. Morbidity relating to surgical technique has been limited to partial (n = 2) or complete (n = 1) late obstruction of superior vena caval drainage; each case was managed successfully by interventional cardiologic techniques. Actuarial survival after transplantation compares favorably with that among 290 infants and children with atrial situs solitus who underwent heart transplantation. CONCLUSIONS: Systemic atrial malposition, including situs inversus, does not limit successful heart transplantation by the simplified method described.

Adolescent↗

Posttransplant recoarctation of the aorta: a twelve year experience.

OBJECTIVES: This study was undertaken to investigate the incidence of posttransplant recoarctation of the aorta, delineate the mode of presentation, identify risk factors that predict recoarctation and examine the results of intervention for posttransplant recoarctation. BACKGROUND: Patients with aortic arch hypoplasia require extended arch reconstruction at transplant, with an inherent possibility of subsequent recoarctation of the aorta. METHODS: This was a retrospective review of all children (age <18 years) who underwent cardiac transplantation over a 10-year period. Collected data included pretransplant diagnosis, details of the transplant procedure and posttransplant data including development of recoarctation of the aorta, interventions for recoarctation and the most recent follow-up assessment of the aortic arch. RESULTS: Two hundred eighty-eight transplants were performed on 279 children (follow-up = 1,075 patient-years; range 0 to 133 months, median 43.7). Thirty-two of 152 patients (21%) who underwent extended aortic arch reconstruction subsequently developed recoarctation. All but one patient developed recoarctation within 2 years after transplant; 87% were hypertensive at presentation. Of 30 patients who underwent intervention for recoarctation (balloon angioplasty [n = 26] and surgical repair of recoarctation [n = 4]), 26 (87%) have remained recurrence-free (follow-up = 133 patient-years; range 8 to 106 months, median 47). CONCLUSIONS: The high frequency of recoarctation after cardiac transplantation with extended aortic arch reconstruction mandates serial echocardiographic evaluation of the aortic arch. Patients typically present with systemic hypertension within the first two years after transplantation. Balloon angioplasty is a safe, effective and durable method of treatment.

Adolescent↗

Heart transplantation for hypoplastic left heart syndrome: modified technique for reducing circulatory arrest time.

BACKGROUND: The surgical technique of heart transplantation as therapy in infants with hypoplastic left heart syndrome was first reported over a decade ago. Since that time, incremental refinements have evolved that both facilitate the operation and potentially reduce the perceived neurologic hazards associated with the use of hypothermic circulatory arrest. METHODS: Minor technical adjustments have permitted infant heart transplantation to be accomplished with relative ease while markedly limiting the need for complete circulatory arrest. Low-flow hypothermic systemic perfusion is used for atrial implantation, reserving circulatory arrest for arch reconstruction only. This is accomplished by use of an active (pump) sucker for venous return. RESULT: Mean circulatory arrest time with the current technique has been 26 minutes. CONCLUSION: Minor technical refinements have resulted in a marked reduction in hypothermic circulatory arrest time during infant heart transplantation for hypoplastic left heart syndrome.

Cardiopulmonary Bypass↗

Prolonged discordant cardiac xenograft survival in newborn recipients.

BACKGROUND: We previously demonstrated very low levels of xenoreactive natural antibodies in newborns, suggesting the possibility of prolongation of xenograft survival in newborn recipients. We used a pig-to-newborn goat heterotopic cardiac xenograft model to examine our hypothesis that hyperacute rejection would be absent in newborn recipients and that both humoral and cellular rejection would participate in the late phase of discordant xenograft rejection. METHODS AND RESULTS: The serum of newborn goats was found to have very low titers of natural anti-pig antibodies. Newborn pig hearts were transplanted heterotopically into the neck of four unmanipulated newborn goats: none of these xenografts underwent hyperacute rejection. Dilation of the xenografts and decreased contractility were observed 4 to 6 days after transplantation, and the xenografts eventually ceased functioning between 6 and 8 days after transplantation. Blood samples collected after transplantation demonstrated a dramatic increase in anti-pig xenoantibody titers and correlated with histological studies demonstrating features consistent with delayed humoral rejection, including reactive vascular endothelial and perivascular stromal cells, marked capillary congestion, and interstitial hemorrhages. Scant to diffuse perivascular and interstitial infiltration of activated lymphoid cells occurred. CONCLUSIONS: Our study demonstrates that hyperacute rejection does not occur, allowing limited prolongation of xenograft survival in a pig-to-newborn goat cardiac xenograft model. We propose that this is attributable, at least in part, to the very low titers of natural antibodies in newborn recipients. Delayed xenograft rejection, however, remains an important problem in these newborn recipients. This delayed xenograft rejection is likely the result of both humoral and cellular rejection mechanisms.

Animals↗

The effect of quick-freezing in ethylene glycol on morphological survival and in vitro development of mouse embryos frozen at different preimplantation stages.

This study was conducted to examine the effect of a quick-freezing protocol on morphological survival and in vitro development of mouse embryos cryopreserved in ethylene glycol (EG) at different preimplantation stages. One-cell embryos were harvested from 6-to 8-wk-old CB6F1 superovulated mice, 20 to 23 h after pairing with males of the same strain and hCG injection. The embryos were cultured in human tubal fluid (HTF) containing 4 mg/ml BSA under mineral oil at 37 degrees C in 5% CO(2) plus 95% room air at maximal humidity. Twenty-four to 96 h after collection, the embryos were removed from culture and frozen at the 2 cell, 4 to 8-cell, compact morula, early blastocyst, expanding blastocyst and expanded blastocyst stages. To perform the quick-freeze procedure, embryos were equilibrated in Dulbecco's phosphate buffered saline (DPBS) + 10 % fetal bovine serum (FBS) + 0.25 M sucrose + 3 M ethylene glycol (freeze medium) for 20 min at room temperature (22 to 26 degrees C) and loaded in a single column of freeze medium into 0.25-ml straws (4 to 5 embryos per straw). The straws were held in liquid nitrogen vapor for 2 min and immersed in liquid nitrogen. Embryos were thawed by gentle agitation in a 37 degrees C water bath for 20 sec and transferred to DPBS + 10 % FBS + 0.5 M sucrose (re-hydration medium) for 10 min at room temperature, rinsed 2 times in HTF plus 4 mg/ml BSA and then cultured for 24 to 96 h. Survival of embryos was based on their general morphological appearance after thawing and their ability to continue development upon subsequent culture in vitro. Survival of blastocysts after thawing also required expansion or reexpansion of the blastocoel after several hours in culture. Significant differences were found in the survival and development of mouse embryos at different developmental stages quick-frozen in ethylene glycol and sucrose: 2-cell embryos 43/84 (51%), 4 to 8-cell embryos 44/94 (47%), morulae and early blastocysts 56/70 (80%; P</=0.05), expanding and expanded blastocysts 10/59 (17%; P</=0.05). Our data indicate that the developmental stage in which mouse embryos are subjected to this quick-freeze protocol affects survival and development in vitro and that most (80%) morula and early blastocyst stage embryos survive the procedure.

Journal Article↗

Sequence comparison of baboon ABO histo-blood group alleles: lesions found in O alleles differ between human and baboon.

Histo-blood group O has only rarely been observed in baboon. Recent discovery of such an animal has provided use the opportunity to investigate the molecular genetics of the ABO locus in baboons. The major baboon prototype O allele, observed in two homozygous and several heterozygous animals, is related to the A allele as is the case in humans. Additional apparent prototype O alleles have been observed in heterozygotes, one of which is related to the B allele. The nucleotide changes conferring the O phenotype in the two known human O alleles have not been observed in any baboon allele. This information will aid the identification of baboons useful for the development of xenotransplantation in humans.

ABO Blood-Group System↗

Echocardiographic recognition of iatrogenic aortic valve leaflet perforation.

BACKGROUND: There is a paucity of literature regarding iatrogenic aortic valve perforation after cardiac operations performed in the vicinity of the aortic valve. This report describes the echocardiographic recognition of iatrogenic aortic valve perforation. METHODS: Among 6 patients who had previously under-gone non-aortic valve cardiac operations, a diagnosis of iatrogenic aortic regurgitation was made by transthoracic two-dimensional echocardiography and Doppler color flow imaging. RESULTS: The location of the aortic valve leaflet perforation varied and depended on the site of the previous intracardiac lesion repair. Repeat operations in 5 patients confirmed the echocardiographic findings. Aortic valve repair was confirmed in 2 patients by transesophageal echocardiography, whereas aortic valve replacement became necessary in 2 other patients. A fifth patient with acquired cardiomyopathy underwent orthotopic heart transplantation. CONCLUSIONS: A detailed two-dimensional echocardiographic examination, along with color flow imaging, should be done to evaluate iatrogenic aortic valve perforation in patients with a new murmur of aortic regurgitation after cardiac operations in proximity to the aortic valve. Precise preoperative diagnosis of this lesion allows optimal surgical planning and treatment.

Adult↗

The optimal Fontan connection: a growing extracardiac lateral tunnel with pedicled pericardium.

OBJECTIVE: The concept of a lateral tunnel for the Fontan operation is now widely accepted. Most lateral tunnels are constructed intraatrially with the use of aortic crossclamping. Construction of extracardiac lateral tunnels with the use of homografts or other nonviable tubes eliminates aortic crossclamping but lacks growth potential in length or width. The native pericardium, which is "sealed" posteriorly along the pulmonary artery, atrium, and inferior vena cava, could be turned down onto the right atrium to form a viable extracardiac lateral tunnel. METHODS: We designed and successfully constructed extracardiac lateral tunnels using viable autologous pericardium, pedicled on its lateral blood supply, in 19 patients aged 9 months to 5 years. All patients had a previous Glenn shunt; five patients had dextrocardia and a midline inferior vena cava. The patients' inferior vena cava-right atrial connection was opened transversely and the right atrial opening was sutured to its back wall, keeping the eustachian valve in the inferior vena cava. The underside of the right pulmonary artery was opened longitudinally; its inferior edge was sewn to the adjacent pericardial reflection. Any "pocket" or depressions in the posterior pericardium along the pulmonary veins were closed with running suture. Two incisions were made in the right pericardium down to the phrenic nerve parallel to the inferior vena caval and pulmonary arterial openings. This pedicled pericardium was trimmed and sewn as a roof to the upper edges of the inferior vena cava and pulmonary artery openings and then sewn longitudinally along the unopened right atrial wall, completing the viable extracardiac lateral tunnel. Although no fenestrations were used, these could be made during construction, or more significantly, owing to the lack of thick walled structures, in the catheterization laboratory in the postoperative period. RESULTS: All 19 patients had respiratory/cardiac pulsations in the pulmonary arteries owing to the compressible lateral tunnel. At follow-up of up to 2 1/2 years, all tunnels are growing and no obstructions have occurred. CONCLUSION: The viable autologous pericardial extracardiac lateral tunnel can be constructed without cardiac ischemia, can be fenestrated in the postoperative period, and forms a compressible, nonthrombogenic conduit capable of growth, which can be constructed early in infancy.

Child, Preschool↗

Reanimation: overcoming objections and obstacles to organ retrieval from non-heart-beating cadaver donors.

Interest in the retrieval of organs from non-heart-beating cadaver donors has been rekindled by the success of transplantation of solid organs and the insufficient supply of donor organs currently obtained from heart-beating cadaver donors. There are currently two retrieval techniques being evaluated, the in situ cold perfusion approach and the controlled death approach. Both, however, raise ethical concerns. Reanimation is a new method which has been used successfully in animals. We believe this new approach overcomes the ethical objections raised to these other methods.

Animals↗

Limitations to survival for infants with hypoplastic left heart syndrome before and after transplant: the Loma Linda experience.

Untreated, hypoplastic left heart syndrome is a lethal cardiac defect. Heart transplant has become an accepted therapeutic option for this condition. However, significant limitations to survival remain for infants with this condition who are referred for heart transplantation. Attention to the prevention, early detection, and management of common problems occurring at each stage of the transplantation process is important for improving survival rates. This study retrospectively reviewed the cases of 195 infants with hypoplastic left heart syndrome registered for heart transplantation at Loma Linda University Medical Center between November 1985 and July 1996 to determine causes of death. During the waiting period, progressive cardiac failure and complications from interventional procedures were the leading causes. In the early postoperative period, technical issues and acute graft failure were most important, whereas late deaths (more than 30 days after transplant) were most often related to rejection and posttransplant coronary artery disease.

California↗