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PubMed1990

Survival analysis of 1563 renal transplants in Brazil: report of the Brazilian Registry of Renal Transplantation.

Little is known about renal transplantation activity in developing countries. The objective of this study was to evaluate patient and graft survival among the different types of renal transplant recipients in Brazil. The study population consisted of 1563 patients receiving renal grafts for the first time between 1 October 1987 and 31 December 1989 in 49 transplant centres in Brazil. Data were prospectively collected through individual patient questionnaires. Of the 1563 transplantations performed, 1051 (67%) were from living donors, 467 (30%) from cadaver donors, and 45 (3%) unspecified. A total of 963 (62%) transplants came from living related donors (10% HLA-identical, 45% HLA-haploidentical and 6% HLA-distinct). Among the transplant recipients, only 7% were more than 55 years old, 5% were younger than 15 and 4% had diabetes mellitus. Blacks accounted for 24% of patients receiving transplants. An immunosuppressive regimen, including cyclosporin was used in 75% of cadaver kidney recipients, in 42% of living donor kidney recipients; and in 43% and 75% of HLA-haploidentical and HLA-distinct living related donor recipients, respectively. At 2 years, patient survival for living donor and cadaver donor transplant recipients was 89% and 80% respectively, and graft survival was 76% and 61% respectively. Patient survival for recipients of HLA-identical, haploidentical, and distinct living related donor kidneys was respectively 94%, 90%, and 81% at 2 years, and graft survival was 90%, 75%, and 65% respectively. Graft survival for recipients of HLA-distinct living related donor and non-related donor kidneys compared to cadaver donor kidneys was not significantly different at 2 years (63% vs 61%, P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Definition and classification of negative outcomes in solid organ transplantation. Application in liver transplantation.

OBJECTIVE: This study defined negative outcomes of solid organ transplantation, proposed a new classification of complications by severity, and applied the classification to evaluate the results of orthotopic liver transplantation (OLT). SUMMARY AND BACKGROUND DATA: The lack of uniform reporting of negative outcomes has made reports of transplantation procedures difficult to interpret and compare. In fact, only mortality is well reported; morbidity rates and severity of complications have been poorly described. METHODS: Based on previous definition and classification of complications for general surgery, a new classification for transplantation in four grades is proposed. Results including risk factors of the first 215 OLTs performed at the University of Toronto have been evaluated using the classification. RESULTS: All but two patients (99%) had at least one complication of any kind, 92% of patients surviving more than 3 months had grade 1 (minor) complications, 74% had grade 2 (life-threatening) complications, and 30% had grade 3 (residual disability or cancer) complications. Twenty-nine per cent of patients had grade 4 complications (retransplantation or death). The most common grade 1 complications were steroid responsive rejection (69% of patients) and infection that did not require antibiotics or invasive procedures (23%). Grade 2 complications primarily were infection requiring antibiotics or invasive procedures (64%), postoperative bleeding requiring > 3 units of packed red cells (35%), primary dysfunction (26%), and biliary disease treated with antibiotics or requiring invasive procedures (18%). The most frequent grade 3 complication was renal failure, which is defined as a permanent rise in serum creatinine levels > or = twice the pretransplantation values (11%). Grade 4 complications (retransplantation or death) mainly were infection (14%) and primary dysfunction (11%). Comparison between the first and last 50 OLTs of the series indicates a significant decrease in the mean number of grade 1 and 2 complications. This was partially a result of better medical status of patients at the time of transplantation. Using univariate and multivariate analyses of risk factors, the best predictor of grade 1 complications was donor obesity; for grade 2 complications, the best predictor was a donor liver rewarming time of > 90 minutes, and for grade 3 and 4 complications, the best predictor was the APACHE II scoring system and donor cardiac arrest. CONCLUSIONS: Standardized definitions and classifications of complications of transplantation will allow us to better evaluate and compare results of transplantation among centers and over time, and better compare effectiveness of new therapies. Orthotopic liver transplantation still is a procedure with high morbidity that requires careful analysis of risk factors to optimize selection of patients and organ sharing.

Adolescent↗
PubMed1992

Analyses of the UNOS Scientific Renal Transplant Registry at three years--early events affecting transplant success.

The success of cadaveric renal transplants in the first year is determined largely by events that transpire during the transplant hospitalization. This conclusion is based upon analyses of data on 19,525 cadaver donor renal transplants performed since October 1987 and reported to the UNOS Scientific Renal Transplant Registry from more than 200 centers nationwide. Graft survival rates at 1 year differed by 20-30% depending upon whether or not the transplanted kidney functioned immediately and upon whether the patient required dialysis during the first week posttransplant, experienced rejection, or was discharged with a kidney that was functioning well. Recipients whose discharge serum creatinine level was less than 2.6 mg/dl or whose graft was functioning well at the time of discharge had 88% 1-year graft survival. A multistep logistic regression analysis showed cold ischemia time, transfusions, donor age and cause of death, HLA-DR mismatches, and peak sensitization to be significant factors in the first week. Prophylactic antilymphocyte antibodies (ALG/OKT3) reduced the incidence of rejection from 30% to 20% during the transplant hospitalization, but apparently only delayed rejection. By 6 months there was only a 3% reduction with ALG and a 5% reduction with OKT3 in the incidence of reported rejection and a 2% difference in 1-year graft survival. Although graft and patient survival are important measures of transplant success, graft survival is predicted upon both early and late events. The course of the transplant during the initial hospitalization and the quality of function at discharge were the strongest determinants of 1-year graft survival.

Adolescent↗
PubMed2003

Incidence of cancer after kidney transplant: results from the North Italy transplant program.

BACKGROUND: Patients undergoing kidney transplantation demonstrate a higher risk of developing cancer as the result of immunosuppressive treatment and concurrent infections. METHODS: The incidence of cancer in a cohort of patients who underwent kidney transplantation between 1990 and 2000, and who survived the acute phase (10 days), was analyzed as part of the North Italy Transplant program. RESULTS: A total of 3,521 patients underwent transplantation during a 10-year period in 10 of 13 participating centers; the length of follow-up after kidney transplant was 67.7+/-36.0 months. During the follow-up, 172 patients developed cancer (39 with Kaposi sarcoma, 38 with lymphoproliferative diseases, and 95 with carcinomas [17 kidney, 11 non-basal cell carcinoma of the skin, 10 colorectal, 8 breast, 7 gastric, 7 lung, 6 bladder, and 3 mesothelioma]). The average time to cancer development after transplant was 40.1+/-33.4 months (range 0-134 months). Twenty-four patients developed cancer within 6 months from the transplant (10 with carcinomas, 7 with Kaposi sarcoma, and 7 with lymphoproliferative diseases). Three patients demonstrated a second primary cancer. The average cancer incidence was 4.9%. The incidence of cancer was 0.01 per year. Independent determinants of cancer development were age, gender, and immunosuppressive protocol including induction. Ten-year mortality was significantly higher in patients with cancer (33.1%) than among patients without cancer (5.3%). The relative risk of death in subjects with cancer was 5.5 (confidence interval 4.1-7.4). CONCLUSIONS: These preliminary data underline the importance of long-term surveillance of transplant recipients, choice of immunosuppressive treatment, and careful donor selection.

Actuarial Analysis↗
PubMed2005

Logistics and transplant coordination activity in the GRAGIL Swiss-French multicenter network of islet transplantation.

BACKGROUND: Since the Edmonton trial in 2000, increasing numbers of transplant centers have been implementing islet transplantation programs. Some institutions have elected to associate in multicenter networks, such as the Swiss-French GRAGIL (Groupe Rhin-Rhône-Alpes-Genève pour la Transplantation d'Ilots de Langerhans) consortium. METHODS: All pancreata offers to the University of Geneva Cell Isolation and Transplantation Center from within the network in 2002 and 2003 were reviewed. Islet preparations were attributed to the most suitable recipient on a centrally managed waiting list. All shipments were performed by ambulance in less than 5 hr. RESULTS: Over the period of study, 260 pancreata were offered, from a total of 1,304 cadaveric donors in the four allocation regions (20%). Fifty-two patients were on the waiting list at any time during this 2-year period. The percentage of organs offered varied in the range of 0.5% to 42%, depending on region of origin, with a correlation with number of patients on the waiting list in each region. Of these, 104 (40%) were accepted for processing. Ninety-two pancreata were actually processed, resulting in 42 islet preparations being transplanted. The number of international equivalents of transplanted preparations was 378,500+/-16,000 versus 165,400+/-15,400 (P<0.0001) for nontransplanted preparations. Total cold ischemia time was 6+/-0.3 hr for transplanted preparations versus 6.7+/-0.4 hr for nontransplanted preparations (not significant). CONCLUSIONS.: A high rate of pancreas offers, successful isolation, and islet transplantation can be achieved in multicenter networks such as GRAGIL. Such an approach can expand both the donor pool and the recipient population.

Adult↗
PubMed2004

Treatment of Budd-Chiari syndrome in a liver transplant unit, the role of transjugular intrahepatic porto-systemic shunt and liver transplantation.

BACKGROUND: Budd-Chiari syndrome is an uncommon cause of liver failure usually associated with an underlying hypercoagulable state. AIM: To evaluate current trends in management of Budd-Chiari syndrome at our institution. METHODS: Twenty-two patients with Budd-Chiari syndrome underwent transjugular intrahepatic porto-systemic shunt, liver transplantation, or both in between 1992 and 2001. We analysed underlying diagnosis, medical therapy, complications, follow-up and overall outcomes. RESULTS: Five patients (17%) presented with fulminant liver failure and 17 patients (83%) with new-onset ascites or chronic liver disease. Seventeen patients (74%) underwent transjugular intrahepatic porto-systemic shunt: improvement or stabilization occurred initially in 14 (82%), whereas the other three patients died within a month. At a mean 3 years follow-up eight patients (47%) continued to do well clinically and four have died (23.5%); seven have required transjugular intrahepatic porto-systemic shunt revisions (mean 2.3 interventions), five have experienced transjugular intrahepatic porto-systemic shunt occlusion managed with new transjugular intrahepatic porto-systemic shunt placement and five patients underwent subsequent transplantation. Of the 10 patients who underwent liver transplantation, patient and graft survival are 80% at a mean 5.7 years of follow-up. No patient developed post-transplant Budd-Chiari syndrome. CONCLUSIONS: Transjugular intrahepatic porto-systemic shunt is usually feasible in patients with Budd-Chiari syndrome, and is best suited as a bridge to more timely liver transplantation. Long-term success of transjugular intrahepatic porto-systemic shunt is limited and usually requires revision, placement of a new shunt or liver transplantation. Liver transplantation with chronic anticoagulation offers excellent short- and medium-term patient and graft survival. In our series, there was no recurrence of Budd-Chiari syndrome after liver transplantation.

Adolescent↗
PubMed1984

Bone marrow transplantation for acute lymphoblastic leukaemia: a survey of the European Group for Bone Marrow Transplantation (E.G.B.M.T.).

Between 1979 and 1982, 192 patients with acute lymphoblastic leukaemia were given allogenic bone marrow transplants from HLA-identical siblings. Data on 57 patients transplanted in first remission were compared with the results in 96 patients transplanted in second remission, and 39 in third or subsequent remission. The majority of these patients were of the non-B non-T-ALL and T-ALL subtypes. The 2-year actuarial survival for non-B non-T-ALL was 58% for patients transplanted in first remission, 34% for second remission patients and 33% for patients transplanted in third or subsequent remission (P = 0.60). For patients with T-ALL, the survivals at 2 years for first and second remission transplant patients were 61% and 10%, respectively (P = 0.04). Multifactorial analysis demonstrated a significantly higher probability of survival for patients grafted in first remission (compared with more advanced remission states) and with bone marrow from young (age less than or equal to 20 years) donors. The 2-year actuarial risk of relapse for patients with non-B non-T-ALL transplanted in first remission was 0%, 32% and 69% for second and third or subsequent remission patients, respectively (P = 0.04). For T-ALL the actuarial risk of relapse at 2 years is 10% for first remission grafts and 48% for second remission grafts (P = 0.07). Only patients (with both non-B non-T/and T-ALL) transplanted in first remission have a high and stable probability of remaining in remission.

Actuarial Analysis↗
PubMed1996

Cardiac pacemakers in pediatric heart transplant recipients: incidence, indications, and associated factors. Pediatric Heart Transplant Group-Loma Linda.

This study was undertaken to assess the incidence, indications, and predisposing factors for pacemaker placement in a pediatric heart transplant population. From November 1985 to May 1994, 246 pediatric patients have undergone cardiac transplantation at Loma Linda University Medical Center. Seven (2.8%) have received pacemaker placement with an 8-50 month follow-up period. Median age at transplant was 462 days (0 days to 2.5 years). The median time to pacemaker placement was 190 days (18-1,672 days) after transplantation. Indications were sick sinus syndrome (SSS) in 5 and heart block in 2 patients (1 during acute rejection). Three patients with SSS underwent electrophysiology studies (EPS); 1 was normal and 2 showed sinus node dysfunction. The mode of pacing was VVIR in 6 patients and VVI in 1 patient. All 6 survivors are doing well and 5 patients' pacemakers still provide support. These 7 patients were compared with 185 pediatric patients (0 days to 12-years-old) transplanted during 1985 through 1993 who survived at least 6 months after transplantation. There was no correlation between the receipt of a pacemaker and graft cold ischemic time, rejection history, donor age, or recipient age at transplantation. The 5 patients with SSS had significantly lower average heart rates in the first month after transplantation (108 +/- 16 vs 130 +/- 12; P = 0.0002). The need for permanent pacemakers in this population is uncommon. Pacemakers, however, can be safely performed when necessary with excellent clinical results.

Case-Control Studies↗
PubMed1998

Pre-transplant gingival hyperplasia predicts severe cyclosporin-induced gingival overgrowth in renal transplant patients.

The relationship between the pre-transplant periodontal status and the development of post-transplant gingival overgrowth was investigated in a longitudinal study. The periodontal condition of 35 patients was examined on 2 occasions while they were on the transplant waiting list and then at 4-6, 10-12, 16 and 20 weeks post-transplant. At each visit the plaque index, the bleeding index and a pocket index (CPITN) were measured. Dental impressions were taken of the pre- and post-transplant gingival condition and used to make stone models which were used to score the gingival overgrowth index (GOI). The patients divided into 3 distinct groups having severe (n=13), mild (n=16) or no post-transplant gingival overgrowth (n=6). Only 1 of the patients had taken cyclosporin prior to inclusion into the study. All the patients who developed severe overgrowth had evidence of gingival hyperplasia before the transplant. There was no difference in the serum cyclosporin levels between the three groups (chi2<2.28, p>0.319). Furthermore, there was no statistical difference for any of the periodontal indices. This study indicates that the hyperplastic gingival inflammatory response of some individuals appears to be potentiated by cyclosporin resulting in severe post-transplant overgrowth. In other patients the same reaction may allow the fibroblastic activity to occur to an extent where it produces a mild clinically apparent overgrowth.

Chi-Square Distribution↗
PubMed1990

Recombinant human growth hormone treatment in short children with chronic renal disease, before transplantation or with functioning renal transplants: an interim report on five European studies.

Growth retardation is common in children with chronic renal disease. Final adult height is often reduced, even in children with a functioning renal transplant. The five European studies considered here aim to investigate the efficacy and safety of recombinant human growth hormone therapy (rhGH) in two groups of short children with chronic renal disease. The first group comprises 29 prepubertal children with preterminal chronic renal failure (i.e. before renal transplantation), and the second group comprises 39 prepubertal and pubertal children with functioning renal transplants. The median bone age retardation in the groups at the start of treatment was between 2.2 and 3.7 years; this did not change during the first year of treatment. This interim report concentrates on patients who have been treated for at least 1 year (i.e. 22 children from the first group, and 28 children from the transplant group (15 prepubertal and 13 pubertal children). The median height velocity increased from 4.8 cm/year to 10.0 cm/year in the first group (the chronic renal failure group), from 2.6 cm/year to 6.2 cm/year in prepubertal children with renal transplants and from 3.8 cm/year to 6.7 cm/year in pubertal children with renal transplants. The corresponding changes in height velocity SDS were from -1.3 to 5.1 for the chronic renal failure group and -2.8 to 2.3 for the prepubertal children with renal transplants. Renal function declined in the chronic renal failure group but this decline corresponded to expected progression of the disease. Some of the children with renal transplants showed a decreased renal function, which in most cases was explained by non-compliance or chronic rejection.

Adolescent↗
PubMed2000

Effect of receiving a heart transplant: analysis of a national cohort entered on to a waiting list, stratified by heart failure severity. Comparative Outcome and Clinical Profiles in Transplantation (COCPIT) Study Group.

OBJECTIVE: To determine whether there is a survival benefit associated with cardiac transplantation in Germany. DESIGN: Prospective observational cohort study. SETTING: All 889 adult patients listed for a first heart transplant in Germany in 1997. MAIN OUTCOME MEASURE: Mortality, stratified by heart failure severity. RESULTS: Within 1 year after listing, patients with a predicted high risk had the highest global death rate (51% v 32% and 29% for medium and low risk patients respectively; P<0.0001), had the highest risk of dying on the waiting list (32% v 20% and 20%; P=0.0003), and were more likely to receive a transplant (48% v 45% and 41%; P=0.01). Differences between the risk groups in outcome after transplantation did not reach significance (P=0.2). Transplantation was not associated with a reduction in mortality risk for the total cohort, but it did provide a survival benefit for the high risk group. CONCLUSION: Cardiac transplantation in Germany is currently associated with a survival benefit only in patients with a predicted high risk of dying on the waiting list. Patients with a predicted low or medium risk have no reduction in mortality risk associated with transplantation; they should be managed with organ saving approaches rather than transplantation.

Acute Disease↗
PubMed2001

Epstein-Barr virus infection in paediatric liver transplant recipients: detection of the virus in post-transplant tonsillectomy specimens.

AIMS: Post-transplant lymphoproliferative disease (PTLD) is an important and serious complication in transplant patients. Recent studies have suggested that quantitative assessment of Epstein-Barr virus (EBV) infection in transplant patients might help to identify those at risk of developing PTLD. Therefore, tonsils from paediatric liver transplant recipients were studied for evidence of EBV infection. METHODS: Tonsils were studied by in situ hybridisation for the detection of the small EBV encoded nuclear RNAs (EBERs). The phenotype of EBV infected cells was determined by double labelling in situ hybridisation and immunohistochemistry. The expression of viral latent and lytic antigens was determined by immunohistochemistry. Tonsils from patients without known immune defects were studied as controls. RESULTS: Tonsils from transplant patients showed pronounced follicular hyperplasia and minor paracortical hyperplasia. In situ hybridisation revealed variable numbers of EBV infected B cells in the tonsils from transplant patients (range, 2-1000/0.5 cm(2); mean, 434/0.5 cm(2); median, 105/0.5 cm(2)). Lower numbers were detected in the control tonsils (range, 1-200/0.5 cm(2); mean, 47/0.5 cm(2); median, 9/0.5 cm(2)). The latent membrane protein 1 (LMP1) of EBV was not detected and there were only rare cells in two cases showing expression of the EBV encoded nuclear antigen 2 (EBNA2). There was no evidence of lytic infection. None of the patients developed PTLD within a follow up period of up to five years. CONCLUSIONS: These data indicate that tonsillar enlargement in paediatric liver transplant patients does not necessarily imply a diagnosis of PTLD. Furthermore, the presence of increased numbers of EBV infected cells in tonsils from liver transplant recipients by itself does not indicate an increased risk of developing PTLD.

Antigens, Viral↗
PubMed1995

Serial renal transplant surgery: technical reflections concerning third transplants.

From 1972 to 1993, we carried out 803 consecutive renal transplants including 8 third transplants. Exclusively cadaveric, these third renal transplants were implanted by intraperitoneal approach in right iliac position, without previous homolateral transplantectomy in 5 cases. The arterial anastomoses were common (7) or external iliac and hypogastric (1), and the venous anastomoses external (1) and common iliac (3), or inferior vena cava (4). Restoration of urinary continuity was by ureteronecystostomy (Politano-Leadbetter = 4, Grégoir-Lich = 3) or ureteroureteric anastomosis (1). The level of HLA compatibility varied from 2 to 5 identities (mean 3.1) and 4 of the 7 patients explored were hyperimmunized with lymphocytotoxic antibody levels > or = 80%. With the exception of the first of these third transplants, the immunosuppressive protocol associated azathioprine, prednisolone, antilymphocytic serum and cyclosporin. Postoperative sequels were marked by 3 vascular rejections and 1 death from hyperkalemia. Moreover, 1 urinary fistula on ureteroureteric anastomosis settled after percutaneous nephrostomy and placing of an uteric stent endoprosthesis. With a postoperative follow-up of 8-32 months (mean 24), 5 of the transplanted patients (62.5%) have a functional renal transplant with a serum creatinine from 120 to 180 microM/l (mean 140). This brief series, whose failures are exclusively immunological, reveals the remarkable technical reliability for these third renal transplants in right iliac implantation, by median transabdominal approach and above a former transplant site.

Adult↗
PubMed1995

Selection and treatment of candidates for heart transplantation. A statement for health professionals from the Committee on Heart Failure and Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association.

Improved outcome of heart failure in response to medical therapy, coupled with a critical shortage of donor organs, makes it imperative to restrict heart transplantation to patients who are most disabled by heart failure and who are likely to derive the maximum benefit from transplantation. Hemodynamic and functional indexes of prognosis are helpful in identifying these patients. Stratification of ambulatory heart failure patients by objective criteria, such as peak exercise oxygen consumption, has improved ability to select appropriate adult patients for heart transplantation. Such patients will have a poor prognosis despite optimal medical therapy. When determining the impact of individual comorbid conditions on a patient's candidacy for heart transplantation, the detrimental effects of each condition on posttransplantation outcome should be weighed. Evaluation of patients with severe heart failure should be done by a multidisciplinary team that is expert in management of heart failure, performance of cardiac surgery in patients with low left ventricular ejection fraction, and transplantation. Potential heart transplant candidates should be reevaluated on a regular basis to assess continued need for transplantation. Long-term management of heart failure should include continuity of care by an experienced physician, optimal dosing in conventional therapy, and periodic reevaluation of left ventricular function and exercise capacity. The outcome of high-risk conventional cardiovascular surgery should be weighed against that of transplantation in patients with ischemic and valvular heart disease. Establishment of regional specialized heart failure centers may improve access to optimal medical therapy and new promising medical and surgical treatments for these patients as well as stimulate investigative efforts to accelerate progress in this critical area.

Adolescent↗
PubMedDate not supplied

Validity of standard gamble utilities as measured by transplant readiness in lung transplant candidates.

PURPOSE: To evaluate the validity of standard gamble (SG) utilities, by comparing utilities with decision-making behavior in a group of lung transplant candidates facing a risky health decision. METHODS: The authors elicited SG utilities for current health from 57 transplant candidates. They assessed the concordance between utility scores and patients' self-reported readiness to be placed on the transplant waiting list ("listed"). Because transplantation represents a real-life gamble with a short-term survival probability of 85%, the authors defined their minimum validity criterion as utility for current health < or = 0.85 in transplant-ready patients. RESULTS: Utilities were significantly higher in patients who were not ready for listing (n = 22, median utility = 0.79, range 0.06-1) than in those who were ready or listed (n = 35, median utility = 0.50, range 0-0.85, P < 0.00005). All transplant-ready patients had utilities < or = 0.85 for current health. CONCLUSIONS: Low SG utilities were associated with transplant readiness in this population of lung transplant candidates. These results provide one line of evidence supporting the validity of SG utilities as a measure of health-related quality of life, using the criterion of decision-making behavior.

Adult↗
PubMed1998

Metallothionein expression in human lung and its varying levels after lung transplantation. Toulouse Lung Transplantation Group.

The aim of this study was to determine the lung levels of metallothionein (MT), a free radical scavenger, because oxygen-derivated free radicals (ODFRs) have been involved both in reperfusion injury of transplanted lungs and in cardiac or renal allograft destruction. First, MT localization was evaluated in 14 normal human lung biopsy specimens. Then, in lung transplant recipients, MT content in BAL fluid (BALF) and its transcription rate in alveolar macrophages (AMs) were determined. The BALFs of 69 patients were separated into six groups: lung transplant recipients in clinically stable condition (CSR), those with acute rejection (AR), asymptomatic cytomegalovirus infection (ACMV), cytomegalovirus pneumonitis (CMVP), bronchiolitis obliterans syndrome (BOS), and patients without transplants who served as control subjects (NTCs). In normal lungs, 83% of AMs were positively stained. MT staining was also observed in pleural endothelial cells and basal cells from bronchial epithelium. In lung transplant recipients, MT levels in BALF were significantly higher in patients with CSR, AR, ACMV, and CMVP compared with NTCs, while during BOS, MT had a significantly lower level compared with other lung transplant groups. However, no difference among groups was found concerning MT-II messenger RNA expression in AMs, showing that, as in normal lung, AMs are not the only cells that produce MT. These data report for the first time to our knowledge MT cell distribution in human lung with specific emphasis on its enhanced levels after lung transplantation, even in the absence of complication. Possible correlation among MT levels, ODFRs, cytokine levels, and corticosteroid treatment during complications of lung transplantation are discussed.

Acute Disease↗
PubMed1998

Pharmacokinetics of mycophenolic acid (MPA) and determinants of MPA free fraction in pediatric and adult renal transplant recipients. German Study group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients.

Dosage guidelines for mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), are still preliminary in children. This study compares the pharmacokinetics of MPA and its major metabolite MPA glucuronide (MPAG) in pediatric renal transplant recipients receiving 600 mg MMF/m2 body surface area twice a day to those of adults on the currently recommended oral dose of 1 g of MMF twice a day. Concentration-time profiles of 18 children (age, 10.7+/-0.72 yr; range, 5.9 to 15.3 yr) and 10 adults were investigated 1 and 3 wk after transplantation. Plasma concentrations of MPA and MPAG were measured by reverse-phase HPLC. Because MPA is extensively bound to serum albumin and only the free fraction is presumed to be pharmacologically active, the MPA free fraction was also analyzed by HPLC after separation through ultrafiltration. The areas under the concentration-time curves (AUC0-12) of total and free MPA throughout the 12-h dosing interval in children were, in general, comparable to the corresponding data in adult patients. The mean AUC0-12 of MPA and free MPA did not change significantly over the first 3 wk after transplantation, but there was substantial intra- and interindividual variation. MPAG-AUC0-12 values in children with primary renal transplant dysfunction were threefold higher than in those with functioning transplants. Renal impairment had no consistent effect on total MPA-AUC0-12 values, but the MPA free fraction in children (median, 1.65%; range, 0.40 to 13.8%) was significantly (r2=0.46) modulated by renal transplant function and serum albumin levels. In conclusion, concentration-time profiles of pediatric renal transplant recipients administered 600 mg MMF/m2 body surface area twice a day are comparable to those in adults on 1 g MMF twice a day in the first 3 wk after transplantation. Renal impairment and decreased serum albumin levels led to an increase in the free fraction of MPA and the free MPA-AUC0-12 values. Because the pharmacologic activity of MPA is a function of unbound drug concentration, these findings might be relevant for the pharmacodynamic effects of MPA.

Adolescent↗
PubMed1995

New techniques for liver transplantation: reduced-size, split-liver, living-related and auxiliary liver transplantation.

Mortality among patients on a waiting list for orthotopic liver transplantation continues to be 10-15%; this is of particular concern in the pediatric population and may become more problematic in adult patients as longer waiting lists for cadaveric transplantation accrue. The longer cold ischemia times afforded by use of University of Wisconsin (UW) solution and improved hepatic surgery techniques have allowed the development of reduced-size liver transplantation (RSLT), split-liver transplantation (SLT), and living-related liver transplantation (LRLT). These new surgical techniques have been predominantly employed in children, up to 40% of whom may be candidates for one of these modified procedures. With the exception of SLT, these approaches have been associated with comparable rates of biliary tract and vascular complications, rejection episodes and graft and patient survival when compared to whole organ transplantation. Right hepatic lobe graft recipients have approximately 15% decreased graft survival rates, limiting the acceptance of SLT as a standard approach to decrease waiting list times. Application of LRLT to the adult population, where 5-10% of recipients are potential candidates, is expected to increase. Over 100 LRLTs have been performed worldwide and while recipient survival with LRLT is excellent, concerns about donor morbidity and mortality, psychosocial factors and reimbursement issues remain obstacles. Living-unrelated liver transplantation and auxiliary orthotopic partial liver transplantation are developing approaches to be considered only in highly selected cases.

Humans↗