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Biomedical subjects

Marion M Aw

Publications and source records attributed to Marion M Aw.

9 recordsLinked to original sources
PubMed2006

Comparison between effects of cyclosporine and tacrolimus on glomerular filtration rate in pediatric post-orthotopic liver transplant patients.

Tacrolimus (FK506) and cyclosporine, synonymous with immunosuppressive therapy in organ transplantation, are not spared of potential adverse effects such as nephrotoxicity. We retrospectively compared their effects on cGFR in a post-OLT pediatric population. cGFRs of 32 patients from the LTUNUHS either on tacrolimus (group 1) or cyclosporine (group 2) from pretransplantation, transplantation and 3, 6, 9, 12, 18, 24, 30 and 36 months post-transplantation were compared. 95% CI and p-values were calculated for comparison with p < 0.05 considered significant. Longitudinal data analysis revealed no significant cGFR difference between groups 1 and 2 (p = 0.154). However, there was a significant difference in cGFR with time after transplantation (p < 0.0001). The mean difference score between both treatment groups was 277.92 (95% CI = 88.13-643.97). The survival rate post-OLT was 84.4%. In this retrospective sex-matched case controlled study of LTUNUHS patients, there was no difference between tacrolimus and cyclosporine on renal function. However, there was significant difference in cGFR with time post-OLT (p < 0.0001). The reason for this observation could be multifactorial.

Adolescent↗
PubMed2003

Transplant immunology.

The immune response to an allogeneic transplanted organ is T-cell dependent. It is governed partially by the context in which the T-cell encounters the antigen and can range from apoptosis, anergy, and neglect to full activation. The current armamentarium of immunosuppressive agents acts to inhibit the various steps of this T-cell activation pathway; at the level of the T-cell receptor (monoclonal antibodies such as OKT3), intracellular signally (calcineurine-inhibitors), DNA synthesis (azathioprine), or to cause lymphocyte depletion (ATG, ALG). Most protocols use a combination of agents for induction and maintenance immunosuppression. Although successful in preventing and treating allograft rejection, they are not without side effects. With improved patient and graft survival rates, adverse events such as hypertension, nephrotoxicity, hyperglycaemia, and lymphoproliferative disease become increasingly important issues. Newer drugs (IL-2 receptor antagonists, mycophenolate mofetil, rapamycin) have been introduced in an attempt to spare or avoid these adverse effects. Inducing graft tolerance and long-term drug-free survival is the goal of transplant immunologists. Postulated mechanisms include clonal deletion, anergy, and immunoredirection. Although a number of methods have been tested experimentally, none has been proven to induce tolerance for routine clinical use. Immunosuppression remains the cornerstone of the success of organ transplantation. Until investigators are able to induce tolerance in their transplant recipients or develop a tolerance assay, they would need to continue to tailor their immunosuppressive therapy according to the risk profile of the individual recipient.

Graft Rejection↗
PubMed2003

Mycophenolic acid pharmacokinetics in pediatric liver transplant recipients.

The aim of this study is to study mycophenolic acid (MPA) pharmacokinetics in stable pediatric liver transplant recipients and determine which times best represent the area under the concentration versus time curve (AUC) of MPA plasma concentrations. MPA pharmacokinetic profiles were determined in 21 liver transplant recipients (age, 2 to 15 years; 12 boys) administered mycophenolate mofetil (MMF) for at least 6 months. Ten patients were coadministered cyclosporine A (CsA), and 11 patients were coadministered tacrolimus (Tac). Plasma MPA levels were analyzed by enzyme-multiplied immunoassay technique in blood samples at 0, 0.33, 0.67, 1.25, 2, 3.5, 5, and 7 hours after MMF administration. The AUC of plasma concentrations to 7 hours (AUC(0-7)) was calculated using the linear trapezoidal rule. MPA plasma trough concentration (C(0)), maximal concentration, and AUC(0-7) values ranged 9- to 14-fold at a median of 1.81 mg/L (range, 0.4 to 3.7 mg/L), 10.5 mg/L (range, 2.8 to 40.0 mg/L), and 30.2 mg/L.hr (range, 9.3 to 80.3 mg/L.hr), respectively. AUC(0-7) correlated significantly with MMF dose (r = 0.552; P =.010) and C(0) (r = 0.844; P <.001). Median AUC(0-7) (29.6 v 31.4 mg/L.hr; P =.918) was similar in children comedicated with CsA or Tac. Median MMF dose was greater in the CsA group (500 v 250 mg; P =.006). Consequently, median AUC(0-7) was significantly lower in the CsA group when equalized for dose and body weight (2.02 v 3.85 microg/L.hr per mg of MMF dose per kg of weight; P =.002). Variations of MPA pharmacokinetics in pediatric liver transplant recipients suggest that monitoring MPA plasma levels is required. C(0) correlates closely with AUC. Comedication with CsA increased MMF dosage requirements compared with children on Tac therapy.

Area Under Curve↗
PubMed2003

Human hepatocyte isolation and relationship of cell viability to early graft function.

Hepatocyte transplantation is emerging as an additional modality of treatment for patients with acute liver failure or liver-based metabolic disorders. The procedure requires isolation of high-quality hepatocytes from unused donor livers. Hepatocytes were isolated from 20 donor livers (11 right lobes, 3 left lateral segments, 6 whole livers) using a collagenase perfusion technique. Cell viability (median 56%, range 13-95%) and yield (median 1.4 x 10(9) cells, range 2.0 x 10(6)-1.8 x 10(10) cells) varied according to the tissue available. Fatty livers rejected for transplantation gave lower cell viability (median 45%, range 25-59%). There was a significant correlation between age of donor (median 21 years, range 7-66 years) and viability of isolated hepatocytes in vitro (r = -0.683, p = 0.001). The 13 segments of livers were from reduced/split grafts used for clinical transplantation in 9 children and 4 adults. There was no significant correlation between in vitro cell viability and clinical parameters including intensive care stay, serum aspartate aminotransferase,and international normalized ratio (in the first 7 days), and allograft rejection or other early posttransplant complications, in patients transplanted with the corresponding tissue.

Adolescent↗
PubMed2002

Acute liver failure.

Acute liver failure (ALF) is a rare condition in the pediatric population. Patients who present with severe failure of liver synthetic function have a high mortality with medical therapy alone. The main causes of death are cerebral edema, hemorrhage, renal failure and sepsis. The etiology of ALF is age specific, with a significant number due to inborn errors of metabolism especially in neonates and infants. Treatment of children with ALF is supportive, aimed at preventing and managing associated complications until the native liver recovers or liver transplantation. Sedation should not be administered unless a decision for artificial ventilation has been made. As all children are potential transplant candidates, transfer to and management in a liver transplant centre is recommended. Prognostic criteria for mortality are less well defined compared to the adult population, although a significantly elevated INR > or = 4 carries a high chance of death, and liver transplantation should be considered at this stage. Auxiliary transplantation is an attractive option in selected individuals and provides the chance to stop immunosuppression should sufficient hepatic regeneration occur. The use of various liver assist devices and hepatocyte transplantation as a bridge to liver transplantation show promise, although when used in isolation, they do not have an impact on overall patient survival.

Child↗
PubMed2002

Mycophenolic acid and mycophenolic acid glucuronide pharmacokinetics in pediatric liver transplant recipients: effect of cyclosporine and tacrolimus comedication.

Determinants of the wide interindividual variability of the pharmacokinetics of mycophenolic acid (MPA) in 21 stable pediatric liver transplant recipients were investigated in relation to the kinetics of the drug's major phenolic glucuronide metabolite (MPAG), cyclosporin (CsA), or tacrolimus (Tac) co-medication and liver and renal function. Trough concentrations (C(0) ) most reliably predicted the area under the curve (AUC) of 0-7 hours MPA plasma concentrations (r (2) = 0.650). Co-medication with CsA demanded higher MPA mofetil (MMF) doses to achieve equivalent trough levels than Tac (362 vs. 178 mg per mg/L, P= 0.004). Median MPA C(0) (range) was significantly lower during CsA co-therapy when corrected for MMF dose (2.8 vs. 5.6 mg MPA/L for Tac, P= 0.006). The AUC of MPAG was correspondingly higher during CsA co-medication (229 vs. 94 mg/L/h for Tac, P = 0.012) with the MPA-to-MPAG ratio at C(0) correspondingly lower (0.10 vs. 0.14, respectively, P = 0.04). This suggested contrasting effects of CsA and Tac on MPA glucuronidation or its excretion and enterohepatic recirculation. MPAG AUC was correlated to body weight and creatinine clearance. Children with elevated aspartate transaminase (AST; but with no evidence of rejection on liver biopsy, n = 7) had significantly lower MPA trough levels compared with those in whom AST was normal (0. 77 vs. 1.76 mg/L, P = 0.05), but there was no difference in the MMF dose per body weight. Examination of the MPA profiles in these subjects showed significantly lower MPA concentrations from 120 minutes after dose until the end of the 7-hour profile and suggest an accelerated clearance or decreased enterohepatic recirculation.)

Adolescent↗