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Biomedical subjects

E S Woodle

Publications and source records attributed to E S Woodle.

At least 19 recordsLinked to original sources
PubMed2001

Primum non nocere: avoiding harm to vulnerable wait list candidates in an indirect kidney exchange.

BACKGROUND: One proposal to increase kidney transplantation is to exchange kidneys between pairs of ABO-incompatible (or cross-match-incompatible) living donors and their recipients. One variation that has greater potential exchanges living donor kidneys for cadaveric donor kidneys (indirect exchanges). A primary concern with indirect exchanges is the potential to disadvantage blood group O wait list candidates. Using wait list modeling, we examine whether this proposal would disadvantage cadaveric kidney blood group O wait list candidates, and present an approach for neutralizing these negative effects. METHODS: A probability model estimated the total number and blood type frequencies of donor-recipient pairs that would participate in indirect exchanges. A supply-to-demand model for the cadaveric kidney wait list estimated the mean wait time under different allocation policies and donor selection mechanisms for candidates on the wait list classified according to the candidates' race and blood type. RESULTS: Indirect exchanges will reduce the mean wait time for cadaveric kidney wait list candidates. The mean wait time of blood group O cadaveric kidney wait list candidates increases when the participating living donors self-select and when kidney allocation is determined by efficiency. This is neutralized when the transplant team preferentially selects blood group O living donors and cadaveric kidney allocation is determined by need. CONCLUSION: Indirect exchange programs will significantly shorten the wait times for cadaveric kidney wait list candidates. The wait times of blood group O candidates will not be affected adversely if blood group O living donors are selected preferentially and if allocation is based on need.

ABO Blood-Group System↗
PubMed2001

Transmission of donor cancer into cardiothoracic transplant recipients.

BACKGROUND: The demand for transplantable organs exceeds donor supply. Patients with central nervous system (CNS) or other tumors are controversial donors, and the donor cancer transmission rates in cardiothoracic transplant recipients have not been determined. The Israel Penn International Transplant Tumor Registry (IPITTR) was queried to define the risk of donor cancer transmission in cardiothoracic transplant recipients. METHODS: All heart, lung, or heart-lung recipients of organs from donors with a history of malignancy were reviewed. Donor and recipient demographics, histologic findings, and recurrence were reviewed. RESULTS: Twenty-two patients received 17 hearts, 3 lungs, and 2 heart-lung transplants from donors with known CNS or other malignancies. No malignancy transmissions were noted with astrocytomas (n = 3) or glioblastomas (n = 1), except a medulloblastoma that recurred at 6 months. The transmission rate for CNS tumors was 17% (1 of 6), and 1- and 3-year survivals were 67% and 50%, respectively. The most common non-CNS donor cancer was renal cell carcinoma (n = 5). Two renal cell cancer transmissions occurred, both when vascular extension was present. The most aggressive tumor transmission was choriocarcinoma (n = 2) and melanoma (n = 2). Two of 3 choriocarcinomas metastasized with 67% mortality, and both melanomas were transmitted and resulted in death. Other donor cancers included angiosarcoma (n = 2), cervical (n = 1), lung (n = 1), prostate (n = 1), and a liver adenocarcinoma. The transmission rate for all non-CNS groups was 56% (9 of 16) with a 2-year survival of 40%. CONCLUSIONS: The IPITTR experience indicates that tumor transmission is high (10 of 22, 45%) in cardiothoracic transplant recipients. Similar to intra-abdominal organ recipients in the IPITTR, (1) renal cell carcinomas without capsular invasion appear safe with no transmission, (2) vascular invasion in renal cell carcinoma appears to result in early tumor transmission, and (3) melanoma and choriocarcinoma have high rates of transmission with early and almost universal death.

Brain Neoplasms↗
PubMed2001

Are concerns over right laparoscopic donor nephrectomy unwarranted?

OBJECTIVE: To examine the ability of several large, experienced transplantation centers to perform right-sided laparoscopic donor nephrectomy safely with equivalent long-term renal allograft function. SUMMARY BACKGROUND DATA: Early reports noted a higher incidence of renal vein thrombosis and eventual graft loss. However, exclusion of right-sided donors would deprive a significant proportion of donors a laparoscopically harvested graft. METHODS: A retrospective review was performed among 97 patients from seven centers performing right-sided laparoscopic donor nephrectomy. Surgical and postoperative demographic factors were evaluated. Complications were identified and long-term renal allograft function was compared with historical left-sided laparoscopic donor nephrectomy cohorts. RESULTS: Right laparoscopic donor nephrectomy was performed for varying reasons, including multiple left renal arteries or veins, smaller right kidney, or cystic right renal mass. Mean surgical time was 235.0 +/- 66.7 minutes, with a mean blood loss of 139 +/- 165.8 mL. Conversion was required in three patients secondary to bleeding or anatomical anomalies. Mean warm ischemic time was limited at 238 +/- 112 seconds. Return to diet was achieved on average after 7.5 +/- 2.3 hours, with mean discharge at 54.6 +/- 22.8 hours. Two grafts were lost during the early experience of these centers to renal vein thrombosis. Both surgical and postoperative complications were limited, with few long-term adverse effects. Mean serum creatinine levels were higher than open and left laparoscopic donor nephrectomy on postoperative day 1, but at all remaining intervals the right laparoscopic donors had equivalent creatinine values. CONCLUSIONS: These results confirm that right laparoscopic donor nephrectomy provides similar patient benefits, including early return to diet and discharge. Long-term creatinine values were no higher than in traditional open donor or left laparoscopic donor cohorts. These results establish that early concerns about high thrombosis rates are not supported by a multiinstitutional review of laparoscopic right donor nephrectomies.

Adolescent↗
PubMed2000

Combined liver and kidney transplantation in children.

BACKGROUND: Preexisting renal dysfunction has been reported to significantly increase the morbidity and mortality associated with orthotopic liver transplantation (OLT). OLT alone has been recommended for adults and children with end-stage liver disease and reversible causes of renal failure (i.e., hepatorenal syndrome), whereas combined liver and kidney transplantation (LKT) has been shown to be an effective treatment for adults with combined end-stage liver and kidney disease. The purpose of this study was to examine the role of LKT in children. METHODS: Between October of 1984 and 1997, 385 children less than 18 years of age underwent OLT at the University of Chicago. During this same time period 12 patients underwent LKT. Data were gathered by retrospective review of the patients medical records and by interviews conducted with the patients' families. RESULTS: Actuarial patient survival was comparable for children who underwent OLT alone and LKT (69% versus 67% at 5 years). All allograft losses in the LKT group were the result of patient death and occurred within the first 90 postoperative days. Factors associated with decreased patient survival included severity of illness as reflected by United Network of Organ Sharing status and LKT after failed OLT or cadaveric renal transplant. CONCLUSIONS: In children with concomitant endstage liver and kidney disease, LKT can be considered an effective therapeutic option in selected patients. Long-term patient survival in patients undergoing LKT is comparable to that of patients with normal renal function undergoing OLT alone.

Child↗
PubMed2000

Ethical issues in increasing living kidney donations by expanding kidney paired exchange programs.

INTRODUCTION: In 1997, Ross et al. proposed to increase the supply of living kidney donations by using kidneys from living ABO-incompatible donors through an exchange arrangement between two living kidney donor-recipient pairs. Although many transplant centers are exploring this option, only a small fraction of potential donor-recipient pairs are eligible for an exchange on the basis of ABO incompatibility. In this article, we explore three variations that have potentially great clinical relevance. METHODS: The three potential variations discussed are: (1) altruistically unbalanced living donor-recipient exchanges; (2) an indirect exchange (an exchange between a living donor-recipient pair with a cadaveric donor-recipient pair) on the basis of a positive crossmatch; and (3) an indirect exchange on the basis of ABO incompatibility. DISCUSSION: The goal of kidney paired exchange programs is to increase the supply of kidneys available for transplantation ethically. We acknowledge that all exchanges increase the potential for coercion, and we currently reject the proposal of altruistically unbalanced exchanges because of the potential for coercion. However, we believe that voluntary consent can be achieved for indirect exchanges. The indirect ABO-compatible exchange creates no new ethical concerns to our original living paired exchange program and we support its implementation. The indirect ABO-incompatible exchange does create a new ethical concern because it may increase the vulnerability of O blood group recipients. If mechanisms can be developed to avoid increasing the waiting time for blood group O recipients, we would support the implementation of the indirect ABO-incompatible exchange.

ABO Blood-Group System↗
PubMed2000

Programmed cell death signaling via cell-surface expression of a single-chain antibody transgene.

BACKGROUND: The monoclonal antibody, 5H7, is specific for a monomorphic determinant on the a3 domain of human class I MHC (A, B, C). Immobilized 5H7 delivers programmed cell death (PCD) signals to human lymphoid tumor cells as well as peripheral blood mononuclear cells. METHODS: The potential clinical utility of 5H7 was addressed by design of a single-chain variable antibody (scFv), termed 5H7scFv, which was coupled to glycophosphotidylinostitol (GPI), thereby providing membrane expression of the 5H7 idiotype (5H7scFv-GPI). Membrane expression of 5H7scFv-GPI conferred PCD-inducing properties to cells that do not normally have the capability to process and express whole antibody molecules. The initial construction was undertaken in a bacterial expression system, and appropriate protein folding was determined by binding to class I MHC-expressing cells. RESULTS: 5H7scFv-GPI-transfected Chinese hamster ovary cells demonstrated reconstitution of the 5H7 idiotype and binding to soluble HLA-A2. Cross-linking of class I MHC, via membrane expression of the scFv, provided effective PCD signaling in B and T lymphocyte tumor cells. Peripheral blood mononuclear cells were susceptible to 5H7scFv-GPI-induced PCD, and augmentation of PCD signals was noted with anti-CD3 and anti-CD28 preactivation. Responder cells demonstrated typical histologic features of PCD and Annexin V-fluorescein isothiocyanate binding. CONCLUSIONS: Cell surface anchorage of scFv thus provides effective delivery of immune modulatory signals, which may be manipulated for various therapeutic strategies.

Animals↗
PubMed2000

New scoring system identifies kidney outcome with radiation therapy in acute renal allograft rejection.

PURPOSE: To evaluate the role of radiation therapy for acute refractory renal rejection after failure of medical intervention, and to identify risk factors that influence graft survival following radiation therapy. METHODS: Between June 1989 and December 1995, 53 renal transplant recipients (34 men and 19 women) were treated with localized radiation therapy for acute renal allograft rejection. Graft rejection was defined as an increase in serum creatinine with histologic evidence of rejection on renal biopsy. Ninety-one percent were cadaveric transplant recipients. The majority of patients who experienced acute graft rejection initially received corticosteroid therapy, except for 25% who were referred for radiation therapy and steroids for the first rejection. In more recent years, patients with moderate or severe steroid-resistant or recurrent rejection received OKT3, a polyclonal antilymphocyte antibody (ATGAM), tacrolimus (FK506), or mycophenolate mofetil (MMF). Patients who failed to respond to medical treatment were then referred for radiation therapy. Ultrasound was performed for kidney localization. Treatment consisted of a dose of 600 cGy given in 3 or 4 fractions using 6 MV photons, delivered AP or AP/PA. RESULTS: The overall actuarial graft survival from the initiation of RT was 83% at 1 month, 60% at 1 year, and 36% at 5 years. The median follow-up from the date of transplant to the last follow-up was 22 months. The median time from the date of transplant to the initiation of radiotherapy was 3 months, and the median time from the initiation of radiotherapy to the last follow-up was 10 months. Variables evaluated were as follows: human leukocyte antigen matching on HLA-A, HLA-B, and HLA-DR, the transplant panel-reactive antibodies (PRA) at transplantation, number of acute rejection episodes, interval from the date of the transplant to the first rejection, serum creatinine levels at the time of the first radiation treatment, number of transplants, and concomitant immunosuppressive therapy. Independent factors examined by Cox regression modeling were: gender (p = 0.005), creatinine levels (p = 0.000), HLA-DR (p70% (p = 0.014). Each factor was scored using integral coefficients to generate four different groups. The Kaplan-Meier survival analyzed by group produces an interpretable separation of the risk factors for graft loss. CONCLUSIONS: The outcome in patients treated with radiation therapy for acute renal graft rejection can be predicted by a novel scoring system. Patients with scores of three or less are able to achieve 100% renal graft salvage, while patients who have scores of 12 or higher are not able to be salvaged with the current radiation therapy regimen. Future studies should be directed toward identifying more effective treatment for patients who have a high score based on our criteria. The scoring system should be utilized to identify patients at risk who could benefit from radiation therapy. Further study with a randomized trial utilizing this scoring system is needed to confirm the validity of the scoring system in predicting graft survival and the efficacy of radiation in patients who receive radiation therapy for acute graft rejection.

Acute Disease↗
PubMed2000

Primary living-donor liver transplantation at the University of Chicago: technical aspects of the first 104 recipients.

OBJECTIVE: To evaluate the impact of technical modifications on living-donor liver transplants in children since their introduction in 1989. SUMMARY BACKGROUND DATA: Although more than 4,000 liver transplants are performed every year in the United States, only approximately 500 are performed in children. Living-donor liver transplantation has helped to alleviate the organ shortage for small children in need of liver transplantation. Few centers have amassed a sufficient number of cases to evaluate the impact of the different techniques used in pediatric living-donor liver transplantation. METHODS: From 1989 through 1997, 104 primary living-donor liver transplants were performed at the University of Chicago. Three phases of the living-donor liver transplant program can be defined based on the techniques of vascular reconstruction: phase 1, November 1989 to November 1994 (n = 78); phase 2, November 1994 to January 1996 (n = 6); and January 1996 to present (n = 20). The patients' charts were reviewed retrospectively. The incidence and type of vascular complications and patient and graft survival rates were analyzed. RESULTS: Although the demographics of the patients have not changed during the three phases of the living-donor liver transplant program, the outcomes have improved. Without the use of conduits, the incidence of portal vein complications has significantly decreased from 44% to 8%. The incidence of hepatic artery thrombosis has decreased from 22% to 0% with the use of microvascular techniques. The combined use of both techniques has led to a significant increase in graft survival, from 74% to 94%. CONCLUSIONS: The living-donor liver transplant recipient operation has undergone significant technical changes since its introduction in 1989. These changes have decreased the vascular complications associated with this type of graft. Avoiding the use of vascular conduits and performing microvascular hepatic artery anastomoses are the critical steps in improving graft survival.

Anastomosis, Surgical↗
PubMed2000

Coadministration of tacrolimus and mycophenolate mofetil in stable kidney transplant patients: pharmacokinetics and tolerability.

The tolerance and pharmacokinetics (PK) of tacrolimus (T) by the addition of mycophenolate mofetil (MMF) in stable kidney transplant patients (6/group) on long-term tacrolimus-based therapy were investigated. Patients received combination T and MMF therapy at three MMF doses: 1, 1.5, and 2 g/day administered twice daily. A 12-hour blood PK profile for T was obtained prior to MMF dosing; concomitant 12-hour profiles for T, mycophenolic acid (MPA), and mycophenolic acid glucuronide (MPAG) were obtained after 2 weeks of administration. Tolerance was monitored through 3 months. The intra- and intergroup PK of T were variable. The mean AUC0-12 of T for each group was increased after 2 weeks of concomitant MMF administration, but the increase was not statistically significant. Both drugs were well tolerated. Gastrointestinal events were of interest as such have been attributed to both T and MMF. Events reported were diarrhea, nausea, dyspepsia, and vomiting. Other common adverse events were headache, hypomagnesemia, and tremors. Most were mild, although a few were considered to be moderate. There was no apparent relationship between the incidence of any adverse event and MMF treatment group. In the present study, the coadministration of T and MMF did not significantly alter T pharmacokinetics.

Adult↗
PubMed1999

Epstein-Barr virus-induced posttransplant lymphoproliferative disorders. ASTS/ASTP EBV-PTLD Task Force and The Mayo Clinic Organized International Consensus Development Meeting.

Epstein-Barr virus-induced posttransplant lymphoproliferative disease (EBV-PTLD) continues to be a major complication after solid organ transplantation in high-risk patients. Despite the identification of risk factors that predispose patients to develop EBV-PTLD, limitations in our knowledge of its pathogenesis, variable criteria for establishing the diagnosis, and lack of randomized studies addressing the prevention and treatment of EBV-PTLD hamper the optimal management of this transplant complication. This review summarizes the current knowledge of EBV-PTLD and, as a result of two separate international meetings on this topic, and provides recommendations for future areas of study.

Epstein-Barr Virus Infections↗
PubMed1999

Phase I trial of a humanized, Fc receptor nonbinding OKT3 antibody, huOKT3gamma1(Ala-Ala) in the treatment of acute renal allograft rejection.

BACKGROUND: HuOKT3gamma1(Ala-Ala) is a genetically-engineered derivative of the parental murine OKT3 monoclonal antibody, in which the six complementarity-determining regions have been grafted within a human IgG1 mAb, and whose C(H)2 region has been altered by site-directed mutagenesis to alter FcR-binding activity, thereby eliminating T cell activation properties. This report describes the results of a phase I trial of huOKT3gamma1(Ala-Ala) treatment of acute renal allograft rejection. METHODS: Acute renal allograft rejection in kidney and kidney-pancreas transplant recipients was treated with huOKT3gamma1(Ala-Ala). huOKT3gamma1(Ala-Ala) dosing consisted of daily 5- or 10-mg doses adjusted initially to achieve target levels of 1000 ng/ml. RESULTS: A total of seven patients, five kidney transplant and two kidney-pancreas transplant recipients, were treated with the monoclonal antibody for first rejection episodes. Corticosteroids (500 mg i.v. Solumedrol) were given 2 hr before the first huOKT3gamma1(Ala-Ala) dose only. Banff classification of treated rejections were the following: grade I, 1 patient, grade IIA, 1 patient, grade IIB, 4 patients, and grade III, 1 patient. Median time from transplant to rejection was 15 days, and median follow up 12 months (range 10-17 months). HuOKT3gamma1(Ala-Ala) therapy was given for 10.1+/-2.5 days, and mean total dose was 76+/-27 mg. Rejection was reversed in five of seven patients, and recurrent rejection was observed in one patient. Serum creatinine values peaked on day 1 of huOKT3gamma1(Ala-Ala) therapy, and thereafter demonstrated a progressive decline. Rejection reversal (return of creatinine to baseline) occurred at a median of 4 days and a mean of 4.1+/-2 days. Renal allograft biopsies obtained during huOKT3gamma1(Ala-Ala) therapy provided evidence of rapid rejection reversal. Patient and graft survival were both 100%. First dose reactions were minimal, and anti-OKT3 antibodies were not detected. Elevations in serum IL-10, but not IL-2 levels were observed after the first huOKT3gamma1(Ala-Ala) dose. Marked reductions in circulating CD2+, CD4+, and CD8+ T cells were observed after the first huOKT3gamma1(Ala-Ala) dose, followed by a slow progressive return of cell counts toward pretreatment values. Pharmacokinetic analysis revealed a half-life of 142+/-32 hr. CONCLUSIONS: HuOKT3gamma1(Ala-Ala) possesses the ability to reverse vigorous rejection episodes in kidney and kidney-pancreas transplant recipients, and in comparison to murine OKT3, possesses minimal first dose reactions and does not seem to induce antibodies that bind the OKT3 idiotype. These results support the conduct of additional clinical trials with the huOKT3gamma1(Ala-Ala) antibody.

Acute Disease↗
PubMed1999

Drug-induced acute interstitial nephritis in renal allografts: histopathologic features and clinical course in six patients.

Drug-induced acute interstitial nephritis is a common cause of dysfunction in native kidneys, but is rarely reported in renal allografts. This report describes six renal transplant recipients with acute renal allograft dysfunction or delayed allograft function in whom a renal transplant biopsy showed histopathologic features of drug-induced interstitial nephritis with no diagnostic evidence of acute rejection, cyclosporine or tacrolimus nephrotoxicity, or other lesion that could account for the graft dysfunction. In five of the six patients, interstitial nephritis occurred within 4 weeks of transplantation. All the patients were receiving trimethaprim-sulfamethoxazole and/or other drugs associated with interstitial nephritis. After discontinuation of these drugs and short-term corticosteroid treatment, all patients showed improvement in renal function, although the time course of this improvement varied considerably, with three patients showing a return to baseline serum creatinine level within 2 weeks and two patients showing a gradual improvement over 8 weeks. Four of the five patients followed up for more than 1 year (range, 14 to 33 months) after the episode of interstitial nephritis had good allograft function (serum creatinine level </= 1.6 mg/dL) at most recent follow-up, with one patient who had graft loss because of severe rejection 7.5 months after the development of interstitial nephritis. These findings suggest drug-induced interstitial nephritis may be an infrequent cause of graft dysfunction in kidney transplant recipients. Drug-induced interstitial nephritis is a reversible lesion that should be considered in the differential diagnosis of acute renal allograft dysfunction.

Acute Disease↗
PubMed1999

Smooth muscle-specific actin levels in the urine of renal transplant recipients: correlation with cyclosporine or tacrolimus nephrotoxicity.

Cyclosporine A (CSA) and tacrolimus (FK506) are powerful immunosuppressive agents that have proven useful for antirejection therapy in patients with solid organ transplants, including kidney. However, both drugs are nephrotoxic, each producing similar histological patterns of injury to renal tubules and preglomerular arterioles, and this toxicity is a major cause of renal allograft dysfunction. A renal transplant biopsy presently represents the most reliable means of diagnosing nephrotoxicity caused by CSA or tacrolimus and distinguishing it from acute rejection. Because CSA and tacrolimus nephrotoxicity often involve arteriolar smooth muscle, whereas vascular smooth muscle is rarely involved in acute rejection, we investigated if the appearance of a smooth muscle-specific isoform of alpha-actin (SMA) in the urine of renal transplant recipients about to undergo a biopsy for graft dysfunction correlated with biopsy evidence of CSA or tacrolimus toxicity. Eighty-nine urine samples from 61 patients, plus 6 samples from healthy control subjects, were analyzed in a blinded manner by enzyme-linked immunosorbent assay using a specific anti-SMA monoclonal antibody. For the patient samples, the results of these assays were then correlated with the biopsy findings. Those 40 cases in which the biopsy showed evidence of CSA or tacrolimus nephrotoxicity had a significantly (P < 0.01) greater SMA level in the corresponding urine samples (0.089 +/- 0.126 microgram/mL; mean +/- SD) than the 49 cases without toxicity (0.018 +/- 0.027 microgram/mL) or 6 control subjects (0.003 +/- 0.007 microgram/mL), although there was considerable overlap of SMA values among these groups. The greatest SMA levels were seen in patients with CSA or tacrolimus nephrotoxicity that was likely to be relatively acute, namely those with thrombotic microangiopathy and those without previous biopsy evidence of toxicity. SMA levels correlated significantly with the estimated severity of arteriolopathy on biopsy. In patients with tubular but not arteriolar lesions of CSA or tacrolimus toxicity, the mean SMA level was not significantly greater than that in patients without toxicity. Urine SMA levels in patients with a biopsy specimen showing acute rejection were not significantly different from those in patients without rejection, and there was no correlation between urine SMA level and severity of rejection. Whereas the degree of overlap of SMA levels in patients with and without nephrotoxicity was far too great to consider this assay as a potential alternative to renal transplant biopsy for the diagnosis of nephrotoxicity, the assay may have potential as a marker for active arteriolar injury in renal transplant recipients and other patients receiving CSA or tacrolimus therapy.

Actins↗
PubMed1999

The relationship of untreated borderline infiltrates by the Banff criteria to acute rejection in renal allograft biopsies.

The relationship of borderline infiltrates to acute rejection by Banff criteria in renal allografts of patients receiving only maintenance immunosuppression is not clear. Renal allograft biopsies with borderline lesions that were not treated with additional anti-rejection therapy were retrospectively studied. Sixty-five such biopsies were identified from 50 patients, and their outcome was determined by serum creatinine and/or histologic findings in subsequent biopsies, up to 40 d after the initial biopsy. In addition to the borderline infiltrates, there was evidence of acute cyclosporine or tacrolimus toxicity (58%), acute tubular necrosis (12%), and urinary obstruction (12%). Forty-day follow-up after 30 (46%) biopsies revealed serum creatinine < 110% of baseline, and repeat biopsies were not indicated. In 17 (26%), the serum creatinine initially decreased, then increased, and follow-up biopsies showed acute rejection in nine. In 18 (28%), the creatinine remained elevated and follow-up biopsies revealed acute rejection in nine. The untreated borderline infiltrates were thus nonprogressive after 47 biopsies (72%) and progressed to histologic acute rejection after 18 (28%). When there was increasing or persistently elevated creatinine after the initial biopsy, 51% of cases (18 of 35) progressed to acute rejection. Infiltrates that progressed to rejection had more frequent glomerulitis (7 of 18 versus 3 of 47, P = 0.003) and Banff acute score indices (i+t+v+g) >2 (16 of 18 versus 29 of 47, P = 0.03). A majority (72%) of borderline infiltrates not given additional anti-rejection therapy did not progress to acute rejection over 40 d of follow-up, suggesting that conservative management of these lesions, at least in the short term, may be more appropriate than routine treatment as acute rejection.

Adolescent↗
PubMed1998

Programmed cell death.

Programmed cell death (PCD) is currently one of the most intensively studied areas in cell biology. Substantial evidence now exists demonstrating the integral role of PCD in many fundamental immunologic processes; therefore, understanding the mechanisms of PCD may provide advances with broad implications in immunobiology. This Overview provides a definition of PCD, a description of known PCD biochemical pathways, and finally a discussion of the implications of PCD in transplantation.

Animals↗
PubMed1998

Liver transplantation in the first three months of life.

BACKGROUND: Pediatric liver transplant recipients have traditionally been grouped according to age. Age-based classification schemes are useful in identifying clinical problems in selected age groups and also for developing solutions to these problems. Although infants in the first 3 months of life have not traditionally been considered a distinct age group, several features of these infants may distinguish them from other pediatric liver transplant recipients. METHODS: The experience with liver transplantation in infants during the first 3 months of life in three large pediatric liver transplant programs (University of Chicago, Stanford University, and UCLA) was analyzed in order to characterize this group. RESULTS: A total of 23 liver transplants were performed at these three centers in children younger than 3 months of age. This group of patients comprised approximately 37% of the U.S. experience between 1988 and 1994 according to United Network for Organ Sharing statistics. Age distribution at the time of transplantation included the following: <1 month, 28%; 1-2 months, 35%; and 2-3 months, 36%. Median age at the time of transplantation was 37 days (range, 7-90 days), and mean age was 57+/-30 days. Mean weight at the time of transplantation was 3.8+/-1.0 kg. Etiology of liver disease included idiopathic hepatitis, 52%; iron storage disease, 17%; and other causes, 31%. Types of liver allografts used included cadaveric, 85% (reduced size, 60%, and full-size, 25%); living donor, 15%; ABO-identical, 65%; and ABO-compatible, 35%. Actuarial patient and graft survival rates were 60% and 60% at 1 year and 60% and 42% at 2 years, respectively. Median follow-up was 1.5 years. Rejection occurred in 42% of patients, with a median time to first rejection of 13 days. Of these patients, 28% required steroids only and 14% required OKT3. Three patients (14%) were retransplanted at a median time to retransplantation of 1.6 years. Vascular thrombosis occurred in three patients (14%). CONCLUSIONS: Liver transplantation performed in infants younger than 3 months of age (1) provides acceptable short- and long-term patient and graft survival, (2) is associated with significant rates of rejection, and (3) is not associated with excessive rates of vascular thrombosis. The etiology of end-stage liver disease occurring in the first 3 months of life is distinct from that in other pediatric liver transplant recipient age groups. These infants should be referred promptly for liver transplantation as reasonable survival can be expected.

Antilymphocyte Serum↗