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Drug Toxicity (drug + toxicity)
Selected AbstractsIntra-arterial chemotherapy with mitomycin C in gallbladder cancer: A follow-up studyJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2005Michaela K. Bode MD Abstract Background and Objectives There is only limited and somewhat controversial information available on hepatic artery infusion of cytotoxic agents in gallbladder cancer. We report the results of 5-year follow-up of all gallbladder cancer patients treated with surgery and intra-arterial mitomycin C or mitomycin C alone in our hospital during 15 years. Methods Thirty-five patients with gallbladder cancer were treated with superselective intra-arterial chemotherapy (SIAC) with mitomycin C during 1981,1996. Survival was measured from diagnosis, and all patients were followed up until death or the end of January 2002. Cumulative survival rates and median survival times were calculated for all patients, according to response to treatment and staging. The data are presented as 5-year survival. Results Median survival times after SIAC for all patients, responders, and non-responders were 48, 60+, and 8.5 months, respectively. Overall response rate was 60%. Survival was significantly better for tumors limited to the gallbladder wall, as expected. Drug toxicity occurred in half of the patients, requiring cessation of chemotherapy in 25% of the cases. Conclusions The median survival of gallbladder cancer patients treated with surgery and SIAC seems to be significantly better compared to the previously reported outcome of surgical treatment alone. Drug toxicity limits the use of i.a. chemotherapy and requires careful monitoring for early side-effects. J. Surg. Oncol. 2005;91:102,106. © 2005 Wiley-Liss, Inc. [source] Mitochondrial toxicity associated with HAART following liver transplantation in an HIV-infected recipientLIVER TRANSPLANTATION, Issue 5 2004Charalambos Antoniades Antiretroviral therapy is not uncommonly associated with drug toxicities, and hepatotoxicity occurs in approximately 20% of individuals prescribed antiretroviral therapy. Mitochondrial toxicity causing lactic acidosis is a rare but fatal complication that has been described in some HIV-infected patients treated with nucleoside analogue reverse transcriptase inhibitors. In this report, we describe the course of an HIV-infected patient receiving antiretroviral therapy who developed lactic acidosis after liver transplantation for HCV-induced liver disease. (Liver Transpl 2004;10:699,702.) [source] Application of Genomics in Preclinical Drug Safety EvaluationBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2006Peter G. Lord Toxicologists have traditionally gathered pathological, morphological, chemical and biochemical information from in vivo studies of preclinical species in order to assess drug safety and to determine how new drugs can be safely administered to the human patient population. In recent years the emerging "-omics" technologies have been developed and integrated into preclinical studies in order to better assess drug safety by gaining information on the cellular and molecular events underlying adverse drug reactions. Genomics approaches in particular have become readily available and are being applied in several stages of drug development. The burgeoning literature on what has become known as "toxicogenomics" has for the most part highlighted successful applications of gene expression profiling in predictive toxicology, enabling decisions to be made on the developability of a compound early in the drug development process. It is also becoming apparent that toxicogenomic approaches are good starting points to develop experiments designed to gain a mechanistic insight into drug toxicities within and across species. Gene expression arrays permit the measurement of responses of essentially all the genes in the entire genome to be monitored, and knowledge of the function of the genes affected can identify the potential mechanisms to then be confirmed using conventional biochemical, toxicological and pathological approaches. As toxicologists put these technologies into practice they build up a knowledge base to better characterize toxicities at the molecular level and to make the search for much needed, novel biomarkers of toxicity more achievable. [source] Current treatment of non-alcoholic fatty liver diseaseDIABETES OBESITY & METABOLISM, Issue 3 2009Mohamed H. Ahmed Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in Western World and frequently associated with insulin resistance and overweight and occurs often with type 2 diabetes. Interestingly, NAFLD is not only regarded as a hepatic component of the metabolic syndrome but also as an independent risk factor and a marker for increase in cardiovascular disease (CVD). Significantly, NAFLD is associated with an increased risk of all-cause mortality and predicts future CVD events independent of age, sex, LDL-cholesterol and features of metabolic syndrome. Although there was initial concern about drug toxicity with NAFLD, increasing evidence suggests that commonly used drugs such as metformin and statins do not cause harm and the thiazolidinediones (TZDs) may even confer a therapeutic benefit in NAFLD. Interestingly, medical and surgical treatments of obesity show potential benefit in treating NAFLD. In this review, we have focused on the safety and therapeutic impact of TZDs, statins, metformins and obesity medications in NAFLD. The potential benefit of bariatric surgery and the role of weight loss per se in treating NAFLD are also discussed. [source] Spectrum of chronic kidney disease in HIV-infected patientsHIV MEDICINE, Issue 6 2009LJ Campbell Objectives The aim of the study was to investigate the prevalence and aetiology of chronic kidney disease (CKD) and trends in estimated glomerular filtration rate (eGFR) in HIV-infected patients. Methods Ascertainment and review of CKD cases among patients attending King's College and Brighton Hospitals, UK were carried out. CKD was defined as eGFR <60 mL/min for ,3 months. Longitudinal eGFR slopes were produced to examine trends in renal function before, during and after exposure to indinavir (IDV) or tenofovir (TFV). Results CKD prevalence was 2.4%. While HIV-associated nephropathy accounted for 62% of CKD in black patients, 95% of CKD in white/other patients was associated with diabetes mellitus, hypertension, atherosclerosis and/or drug toxicity. Exposure to IDV or TFV was associated with an accelerated decline in renal function (4.6-fold and 3.7-fold, respectively) in patients with CKD. In patients initiating IDV, age ,50 years increased the odds of CKD [odds ratio (OR) 4.9], while in patients initiating TFV, age ,50 years (OR 5.4) and eGFR 60,75 mL/min (OR 17.2) were associated with developing CKD. Conclusion This study highlights the importance of metabolic and vascular disease to the burden of CKD in an ageing HIV-infected cohort. In patients who developed CKD, treatment with IDV or TFV was associated with an accelerated decline in renal function. [source] Clinical benefit of interventions driven by therapeutic drug monitoringHIV MEDICINE, Issue 5 2005AL Rendón Background Adequate plasma concentrations of antiretroviral drugs are key to achieving and maintaining long-term suppression of HIV replication. Multiple factors may influence drug levels, causing increases or reductions that may, respectively, result in toxicity or virological failure. Therapeutic drug monitoring (TDM) might help to detect and correct such abnormalities. Objective To evaluate the usefulness of TDM in the care of HIV-infected patients in an out-patient clinical setting. Methods All the requests for TDM of protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) for patients attending our HIV out-patient clinic from October 2000 to August 2003 were analysed. Blood samples were collected before the morning dose. Drug concentrations were measured by high performance liquid chromatography by ultraviolet waves (HPLC-UV). Results A total of 151 requests from 137 patients were assessed. The reasons for requesting TDM were drug toxicity (59%), virological failure (39%) and possible drug interactions (2%). NNRTI levels were more often requested because of toxicity, while PI levels were more often requested because of virological failure. Elevated drug levels were confirmed in 36% of patients with suspected drug toxicity, while subtherapeutic levels were found in 37% of patients failing virologically. Based on the results of TDM, dose modifications were made in 37% of patients, allowing correction of such abnormalities in 80% of cases. Moreover, adequate plasma concentrations were confirmed in 79% of patients whose levels were assessed again. Conclusions Therapeutic drug monitoring may be a useful tool to identify toxic levels of NNRTI and subtherapeutic concentrations of PI. Dose adjustments following TDM may ameliorate drug-related toxicities or improve virological response rates. [source] Age-related differences in susceptibility to cisplatin-induced renal toxicity,,JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2010P. Espandiari Abstract Limited experimental models exist to assess drug toxicity in pediatric populations. We recently reported how a multi-age rat model could be used for pre-clinical studies of comparative drug toxicity in pediatric populations. The objective of this study was to expand the utility of this animal model, which previously demonstrated an age-dependent sensitivity to the classic nephrotoxic compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis). Sprague,Dawley rats (10, 25, 40 and 80 days old) were injected with a single dose of Cis (0, 1, 3 or 6,mg,kg,1 i.p.). Urine samples were collected prior and up to 72,h after treatment in animals that were , 25 days old. Several serum, urinary and ,omic' injury biomarkers as well as renal histopathology lesions were evaluated. Statistically significant changes were noted with different injury biomarkers in different age groups. The order of age-related Cis-induced nephrotoxicity was different than our previous study with gentamicin: 80 > 40 > 10 > 25 day-old vs 10 , 80 > 40 > 25-day-old rats, respectively. The increased levels of kidney injury molecule-1 (Kim-1: urinary protein/tissue mRNA) provided evidence of early Cis-induced nephrotoxicity in the most sensitive age group (80 days old). Levels of Kim-1 tissue mRNA and urinary protein were significantly correlated to each other and to the severity of renal histopathology lesions. These data indicate that the multi-age rat model can be used to demonstrate different age-related sensitivities to renal injury using mechanistically distinct nephrotoxicants, which is reflected in measurements of a variety of metabolite, gene transcript and protein biomarkers. Published in 2009 by John Wiley & Sons, Ltd. [source] Comparison of genetic polymorphisms of the NAT2 gene between Korean and four other ethnic groupsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2009T. S. Kang MS Summary Background and objective:,N -acetyltransferase 2 (NAT2) is responsible for the acetylation of numerous drugs and in the transformation of aromatic and heterocyclinc amines into carcinogenic intermediates. Polymorphism of NAT2 may contribute to interindividual variability in such acetylation. The aim of this study was to determine the allele frequencies of polymorphisms of the NAT2 gene, analyse linkage disequilibrium (LD) block and haplotypes in Koreans and compare them with those of other ethnic groups. Methods:, We analysed genetic polymorphisms in all functional promoter and exons of the NAT2 gene by direct sequencing of genomic DNA from 192 healthy Korean subjects. The LD and haplotype blocks of these subjects were constructed from genotype data using an expectation,maximization algorithm. We compared these allele frequencies, LD block and haplotype structure with those of other ethnic groups registered on the International HapMap database. Results and discussion:, We identified 33 polymorphisms including six novel single nucleotide polymorphisms, ,10778T>C, ,10777A>G, ,10351A>G, ,10199C>T and ,10104G>T in promoter and 578C>T in exon2 (T193M) in the Korean subjects tested. All allele frequencies reported in the Koreans were similar to those of Asians except for one allele (rs4345600, ,9306A>G), whereas African and European groups had different frequencies in exon2. The haplotype structure and LD block among the five groups also revealed significant differences. Conclusion:, Ethnic differences in the NAT2 genotype frequencies may be one of the important factors explaining variability in cancer incidence and drug toxicity. Our observations could be useful in assessing the susceptibility of different populations to cancer and contribute to better predictions of the pharmacokinetics and pharmacodynamics of drugs that are metabolized by NAT2, in different populations. [source] Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horsesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009R. L. LINARDI Methadone hydrochloride is a synthetic ,-opioid receptor agonist with potent analgesic properties. Oral methadone has been successfully used in human medicine and may overcome some limitations of other analgesics in equine species for producing analgesia with minimal adverse effects. However, there are no studies describing the pharmacokinetics (PK) of oral opioids in horses. The aim of this study was to describe the PK of orally administered methadone (0.1, 0.2 and 0.4 mg/kg) and physical effects in 12 healthy adult horses. Serum methadone concentrations were measured by gas chromatography/mass spectrometry at predetermined time points for 24 h, and PK parameters were estimated using a noncompartmental model. Physical effects were observed and recorded by experienced clinicians. No drug toxicity, behavioural or adverse effects were observed in the horses. The disposition of methadone followed first order elimination and a biphasic serum profile with rapid absorption and elimination phases. The PK profile of methadone was characterized by high clearance (Cl/F), small volume of distribution (Vd/F) and short elimination half-life (t1/2). The mean of the estimated t1/2 (SD) for each dose (0.1, 0.2 and 0.4 mg/kg) was 2.2 (35.6), 1.3 (46.1) and 1.5 (40.8), and the mean for the estimated Cmax (SD) was 33.9 (6.7), 127.9 (36.0) and 193.5 (65.8) respectively. [source] Late hepatic allograft dysfunctionLIVER TRANSPLANTATION, Issue 11B 2001Professor of Medicine Russell H. Wiesner MD Key Points 1Lifelong monitoring of graft function, immunosuppressive levels, and screening for drug toxicity is required in all liver recipients. 2Late hepatic allograft dysfunction is common and is caused by a variety of etiologies including rejection, infection, biliary/vascular abnormalities, recurrence of disease, and drug hepatotoxicity. 3In all patients with late hepatic allograft dysfunction, liver biopsy should be performed to assess for the presence of rejection, and to thus avoid excessive use of bolus corticosteroid therapy and guide appropriate immunosuppressive management. 4Recurrence of disease is the most common cause of late hepatic allograft dysfunction. 5Hepatitis C universally reinfects the hepatic allograft, and is associated with decreased patient and graft survival and leads to the recurrence of cirrhosis in 28% of patients within 5 years of transplantation. 6Major advances have been made in preventing recurrence of hepatitis B by the use of hepatitis B immune globulin in combination with lamivudine therapy. 7Autoimmune liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis have a recurrence rate of approximately 20% to 30%. 8In patients developing recurrence of autoimmune hepatitis, steroid withdrawal is the most common cause. 9Recurrent hepatocellular cancer can be markedly reduced if strict guidelines are adhered to in selecting patients. 10Drug hepatotoxicity must always be considered in the differential diagnosis of late hepatic allograft dysfunction. [source] Management of membranous nephropathyNEPHROLOGY, Issue 4 2000Daniel Cattran SUMMARY: The Management of membranous nephropathy requires a recognition of its natural history and an ability to predict those pationts with the worst prognosis. Treatment of those at risk of progression with immunosuppressive drugs should be accompanied by additional conservative risk reduction strategies such as dietary protein restriction, blood pressure reduction, angiotensin-converting enzyme inhibitors and lipid-lowering agents. Anticoagulants should also be considered as well as medications to reduce drug toxicity. [source] A bicistronic SIN-lentiviral vector containing G156A MGMT allows selection and metabolic correction of hematopoietic protoporphyric cell linesTHE JOURNAL OF GENE MEDICINE, Issue 9 2003Emmanuel Richard Abstract Background Erythropoietic protoporphyria (EPP) is an inherited disease characterised by a ferrochelatase (FECH) deficiency, the latest enzyme of the heme biosynthetic pathway, leading to the accumulation of toxic protoporphyrin in the liver, bone marrow and spleen. We have previously shown that a successful gene therapy of a murine model of the disease was possible with lentiviral vectors even in the absence of preselection of corrected cells, but lethal irradiation of the recipient was necessary to obtain an efficient bone marrow engraftment. To overcome a preconditioning regimen, a selective growth advantage has to be conferred to the corrected cells. Methods We have developed a novel bicistronic lentiviral vector that contains the human alkylating drug resistance mutant O6 -methylguanine DNA methyltransferase (MGMT G156A) and FECH cDNAs. We tested their capacity to protect hematopoietic cell lines efficiently from alkylating drug toxicity and correct enzymatic deficiency. Results EPP lymphoblastoid (LB) cell lines, K562 and cord-blood-derived CD34+ cells were transduced at a low multiplicity of infection (MOI) with the bicistronic constructs. Resistance to O6 -benzylguanine (BG)/N,N,-bis(2-chloroethyl)- N -nitrosourea (BCNU) was clearly shown in transduced cells, leading to the survival and expansion of provirus-containing cells. Corrected EPP LB cells were selectively amplified, leading to complete restoration of enzymatic activity and the absence of protoporphyrin accumulation. Conclusions This study demonstrates that a lentiviral vector including therapeutic and G156A MGMT genes followed by BG/BCNU exposure can lead to a full metabolic correction of deficient cells. This vector might form the basis of new EPP mouse gene therapy protocols without a preconditioning regimen followed by in vivo selection of corrected hematopoietic stem cells. Copyright © 2003 John Wiley & Sons, Ltd. [source] Experience with a Novel Efalizumab-Based Immunosuppressive Regimen to Facilitate Single Donor Islet Cell TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010N. A. Turgeon Islet transplantation is an experimental therapy for selected patients with type 1 diabetes (T1DM). It remains limited by immunosuppressive drug toxicity, progressive loss of insulin independence, allosensitization and the need for multiple islet donors. We describe our experience with an efalizumab-based immunosuppressive regimen as compared to the prevailing standard regimen, the Edmonton protocol. Twelve patients with T1DM received islet transplants: eight were treated with the Edmonton protocol; four were treated with daclizumab induction, a 6-month course of tacrolimus, and maintenance with efalizumab and mycophenolate mofetil. The primary endpoint was insulin independence after one islet infusion. Only two Edmonton protocol treated patients achieved the primary endpoint; six required islets from multiple donors, and all experienced leukopenia, mouth ulcers, anemia, diarrhea and hypertransaminasemia. Four became allosensitized. All patients treated with the efalizumab-based regimen achieved insulin independence with normal hemoglobin A1c after a single islet cell infusion and remained insulin independent while on efalizumab. These patients experienced significantly fewer side effects and none became allosensitized. Trial continuation was terminated by withdrawal of efalizumab from the market. These data suggest that this efalizumab-based regimen prevents islet rejection, is well tolerated, and allows for single donor islet transplantation. [source] Antibody-Mediated Microcirculation Injury Is the Major Cause of Late Kidney Transplant FailureAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009G. Einecke We studied the phenotype of late kidney graft failure in a prospective study of unselected kidney transplant biopsies taken for clinical indications. We analyzed histopathology, HLA antibodies and death-censored graft survival in 234 consecutive biopsies from 173 patients, taken 6 days to 31 years posttransplant. Patients with late biopsies (>1 year) frequently displayed donor-specific HLA antibody (particularly class II) and microcirculation changes, including glomerulitis, glomerulopathy, capillaritis, capillary multilayering and C4d staining. Grafts biopsied early rarely failed (1/68), whereas grafts biopsied late often progressed to failure (27/105) within 3 years. T-cell-mediated rejection and its lesions were not associated with an increased risk of failure after biopsy. In multivariable analysis, graft failure correlated with microcirculation inflammation and scarring, but C4d staining was not significant. When microcirculation changes and HLA antibody were used to define antibody-mediated rejection, 17/27 (63%) of late kidney failures after biopsy were attributable to antibody-mediated rejection, but many were C4d negative and missed by current diagnostic criteria. Glomerulonephritis accounted for 6/27 late losses, whereas T-cell-mediated rejection, drug toxicity and unexplained scarring were uncommon. The major cause of late kidney transplant failure is antibody-mediated microcirculation injury, but detection of this phenotype requires new diagnostic criteria. [source] Early treatment of a quetiapine and sertraline overdose with Intralipid®,ANAESTHESIA, Issue 2 2009S. D. H. Finn Summary We describe the initial management and subsequent recovery of a 61 year-old male patient following attempted suicide by oral ingestion of a potentially fatal overdose of quetiapine and sertraline. Intravenous Intralipid® was given soon after initiation of basic resuscitation. There was a rapid improvement in the patient's level of consciousness. No other clinical signs of drug toxicity were observed. Intralipid may have reversed the deep coma associated with ingestion and prevented other manifestations of drug toxicity occurring, thus expediting this patient's recovery. [source] Seizures in HIV/AIDS: a southern African perspectiveACTA NEUROLOGICA SCANDINAVICA, Issue 2005A. I. Bhigjee South Africa, with a population of 44.8 million, has over 5 million human immunodeficiency virus (HIV)-infected individuals. Over 70% of HIV-infected patients will present with clinically relevant neurologic disease at some stage during the course of their disease. New onset seizures occur in 3,11% of these patients. The mechanism of seizure production in HIV-positive patients includes incidental association, HIV itself, opportunistic infections (OIs), neoplasia, cerebrovascular disease, drug toxicity, and metabolic derangements. In developing countries, OIs constitute the largest group presenting with seizures. Seizure management in HIV-positive patients presents special problems, especially with respect to drug,disease and drug,drug interactions. The older antiepileptic drugs (AEDs) are protein-bound and largely depend on the cytochrome p450 system for their metabolism. The newer AEDs may be safer in patients on antiretroviral drugs. However, they are expensive, an important consideration in developing countries. [source] Multidrug resistance-associated proteins and implications in drug developmentCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1 2010Ya-He Liu Summary 1.,The multidrug resistance-associated proteins (MRPs) belong to the ATP-binding cassette superfamily (ABCC family) of transporters that are expressed differentially in the liver, kidney, intestine and blood,brain barrier. There are nine human MRPs that transport a structurally diverse array of endo- and xenobiotics as well as their conjugates. 2.,Multidrug resistance-associated protein 1 can be distinguished from MRP2 and MRP3 by its higher affinity for leukotriene C4. Unlike MRP1, MRP2 functions in the extrusion of endogenous organic anions, such as bilirubin glucuronide and certain anticancer agents. In addition to the transport of glutathione and glucuronate conjugates, MRP3 has the additional capability of mediating the transport of monoanionic bile acids. 3.,Both MRP4 and MRP5 are able to mediate the transport of cyclic nucleotides and confer resistance to certain antiviral and anticancer nucleotide analogues. Hereditary deficiency of MRP6 results in pseudoxanthoma elasticum. In the body, MRP6 is involved in the transport of glutathione conjugates and the cyclic pentapeptide BQ123. 4.,Various MRPs show considerable differences in tissue distribution, substrate specificity and proposed physiological function. These proteins play a role in drug disposition and excretion and thus are implicated in drug toxicity and drug interactions. Increased efflux of natural product anticancer drugs and other anticancer agents mediated by MRPs from cancer cells is associated with tumour resistance. 5.,A better understanding of the function and regulating mechanisms of MRPs could help minimize and avoid drug toxicity and unfavourable drug,drug interactions, as well as help overcome drug resistance. [source] Practical tests for clinical diagnosis of kidney allograft dysfunctionCLINICAL TRANSPLANTATION, Issue 2008Masayoshi Miura Abstract:, Graft dysfunction after renal transplant occurs due to a variety of causes. Graft biopsy is a mainstay in the diagnosis of graft dysfunction, including rejection, infection, glomerulonephritis and drug toxicity. Clinical tests including regular laboratory tests, antibody tests and imaging studies, however, are also important in the process of diagnosis. The possible causes of graft dysfunction are different depending on the period after transplantation. Pre-transplant donor factors may also affect the early graft function. Perioperative graft dysfunction is mainly related to hemodynamic factors and surgical complications. Early acute rejection may occur in immunologically high-risk cases. Later graft dysfunction may be related to infection, acute and chronic rejection or drug toxicity. Clinical tests to differentiate these factors are discussed in this paper. [source] Establishing pediatric immune response zones using the Cylex® ImmuKnowTM assayCLINICAL TRANSPLANTATION, Issue 6 2005E Hooper Abstract:, For all transplant patients, the transplant physician must balance the risk of rejection caused by under-immunosuppression against the risk of drug toxicity, secondary infections and post-transplant lymphoproliferative disorder with over-immunosuppression. A Food and Drug Administration (FDA)-approved in vitro assay, the Cylex® ImmuKnowTM assay, provides a global assessment of cellular immune function to help monitor the immune status of immunosuppressed patients. This assay uses the plant lectin phytohemagglutinin to stimulate lymphocytes; an ATP assay is then used to measure the degree of activation of CD4+ T cells. However, the normal values for this assay were developed with healthy adult patients. In this study, we determined the normal ranges for the ImmuKnowTM assay in healthy children and compared those values to levels obtained in healthy adults and in stable pediatric renal transplant patients. We found that healthy children 12 yr of age and older showed immune function levels indistinguishable from adults, while healthy children under 12 had significantly lower immune function levels than adults. For adults, the ImmuKnowTM assay zones (in ng/mL ATP) of strong, moderate and low immune function correspond to >525, 225 to 525, and <225. In children under 12, we found the corresponding zones to be >395, 175,395 and <175 ng/mL. The median value for normal adults is 415, whereas it is only 295 for children <12 yr of age and this value decreases to 165 in stable renal transplant patients <12 yr of age (compared with 258 for stable adult renal transplant patients). Thus, this study provides critical information necessary to utilize the ImmuKnowTM assay with pediatric patients. In adults, the degree of immune function as assessed by the ImmuKnowTM assay helps to predict patients at risk for infection or rejection. If further studies in pediatric patients document the same and is true for children, then the ImmuKnowTM assay will provide a useful adjunct tool to prevent over- or under-immunosuppression as newly developed drugs are utilized or drug treatment is altered because of drug side effects, toxicity, concurrent illnesses or rejection. [source] | ||||||||||||||||||||||