Reinhard Feneberg

University of Iowa Children's Hospital, Iowa City, Iowa, United States

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Publications (55)171.15 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Biomarker-based post-transplant immune monitoring for the prediction of impending graft rejection requires validation in specific patient populations. Serum of 28 pediatric renal transplant recipients within the framework of a well-controlled prospective randomized trial was analyzed pre- and post-transplant for soluble CD30 (sCD30), a biomarker reflecting mainly T-cell reactivity, and anti-human leukocyte antigen (anti-HLA) antibody reactivity, a biomarker for B-cell activation. A sCD30 concentration ≥40.3 U/ml on day 14 was able to discriminate between patients with or without biopsy-proven acute rejection (BPAR) with a sensitivity of 100% and a specificity of 76%. Six of seven patients (86%) with BPAR showed a sCD30 above this cut-off, whereas only 3/21 patients (14%) without BPAR had a sCD30 above this cut-off (P = 0.004). For pre- and post-transplant anti-HLA class II reactivities by enzyme-linked immunosorbent assay, a cut-off value of 140 optical density was able to discriminate rejecters from nonrejecters with a sensitivity of 86% or 71% and a specificity of 81% or 90%, respectively. Withdrawal of steroids was associated with a approximately twofold higher serum sCD30 compared to controls, but did not affect anti-HLA reactivities. An increased post-transplant sCD30 serum concentration and positive pre- and post-transplant anti-HLA class II reactivities are informative biomarkers for impending BPAR in pediatric renal transplant recipients. (TWIST, Clinical Trial No: FG-506-02-43).
    Transplant International 12/2012; · 3.16 Impact Factor
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    ABSTRACT: Background. The epidemiology and morbidity of Epstein-Barr virus (EBV) infection in pediatric renal transplant recipients have been characterized insufficiently.Methods. In a prospective, multicenter study among 106 pediatric kidney allograft recipients, aged 11.4±5.9 years, we investigated the epidemiology of EBV infection, the relationship between EBV load, EBV serology and EBV-related morbidity (PTLD or symptomatic EBV infection defined as flu-like symptoms or infectious mononucleosis).Results. EBV primary infection occurred in 27 of 43 (63%) seronegative, and reactivation/reinfection in 28 of 63 (44%) seropositive patients. There was no association between the degree or duration of EBV load and EBV-related morbidity: The vast majority (17 of 18 (94%) patients) with a high, persistent EBV load remained PTLD-free throughout a follow-up of 5.0±1.3 years, while 2 of 3 (66%) patients with EBV-related PTLD exhibited only a low EBV load beforehand. Eight of 18 (44%) patients with a high, persistent EBV load remained asymptomatic during a follow-up of 5.3±2.9 years. Multivariate analysis identified the EBV high-risk (D+/R-) serostatus (OR 7.07, P<.05), the presence of HLA-DR7 (OR 5.65, P<.05), and the intensity of the immunosuppressive therapy, (OR 1.53, P<.01) as independent risk factors for the development of a symptomatic EBV infection.Conclusions. Presence of EBV high-risk seroconstellation, HLA-DR7, and intensity of immunosuppressive therapy are significant risk factors for a symptomatic EBV infection, while there is no close association between the degree or duration of EBV load and EBV-related morbidity.
    Clinical Infectious Diseases 10/2012; · 9.37 Impact Factor
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    ABSTRACT: Epstein-Barr virus (EBV) primary infection constitutes a serious risk for pediatric transplant recipients, particularly as regards the development of EBV-related post-transplant lymphoproliferative disease (PTLD). Currently, there is no established prophylactic regimen. We investigated the association between chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) and the incidence of EBV viremia in EBV-naïve pediatric renal transplant recipients (R-) who had received a graft from an EBV-positive donor (D+) and are therefore at high risk of EBV primary infection. In a prospective, multicenter trial (n = 114), we compared a cohort on chemoprophylaxis (n = 20) with a similar control cohort without chemoprophylaxis (n = 8). Over the 1-year study period, antiviral prophylaxis with VGCV/GCV was associated with a significantly decreased incidence of EBV primary infection: 9/20 patients (45%) in the prophylaxis group experienced an EBV primary infection compared to 8/8 controls (100%) (P < 0.0001). Chemoprophylaxis was associated with a significantly lower EBV viral load (P < 0.001). Type or intensity of immunosuppressive therapy did not influence the occurrence of EBV primary infection or the level/persistence of EBV viral load. Chemoprophylaxis with VGCV/GCV is associated with a reduced incidence of EBV viremia in high-risk pediatric kidney allograft recipients in the first year post-transplant. (ClinicalTrials.gov number: NCT00963248).
    Transplant International 04/2012; 25(7):723-31. · 3.16 Impact Factor
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    ABSTRACT: Since many drug targets and metabolizing enzymes are developmentally regulated, we investigated a potential comparable regulation of inosine 5'-monophosphate dehydrogenase (IMPDH) activity that has recently been advocated as a pharmacodynamic biomarker of mycophenolic acid (MPA) effects in the paediatric population. Since the field of pharmacodynamic monitoring of MPA is evolving, we also analyzed the response of IMPDH activity on MPA in children vs adolescents after renal transplantation. We analyzed IMPDH activity in peripheral blood mononuclear cells (PBMCs) in 79 healthy children aged 2.0-17.9 years in comparison to 106 healthy adults. Pharmacokinetic/pharmacodynamic profiles of MPA and IMPDH over 6 or 12 h after mycophenolate mofetil dosing were performed in 17 paediatric renal transplant recipients. IMPDH activity was measured by HPLC and normalized to the adenosine monophosphate (AMP) content of the cells, MPA plasma concentrations were measured by HPLC. Inosine 5'-monophosphate dehydrogenase activity displayed a high inter-individual variability (coefficient of variation 40.2%) throughout the entire age range studied. Median IMPDH did not differ significantly in healthy pre-school children (82 [range, 42-184] μmol/s/mol AMP), school-age children (61 [30-153]), adolescents (83 [43-154]) and healthy adults (83 [26-215]). Similar to adults, IMPDH activity in children and adolescents was inversely correlated with MPA plasma concentration. In conclusion, our data do not show a pronounced developmental regulation of IMPDH activity in PBMCs in the paediatric population and there is a comparable inhibition of IMPDH activity by MPA in children and adolescents after renal transplantation.
    European Journal of Clinical Pharmacology 01/2012; 68(6):913-22. · 2.74 Impact Factor
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    ABSTRACT: Peritonitis is a common complication of chronic peritoneal dialysis (CPD) and can be associated with technique failure. Enterococcus is an uncommon peritoneal pathogen in children receiving CPD but represents a potential therapeutic challenge due to its innate resistance to cephalosporins and emerging resistance to glycopeptides. The International Pediatric Peritonitis Registry is a global consortium of 47 paediatric dialysis centres designed to address validation of the International Society for Peritoneal Dialysis paediatric peritonitis treatment guidelines. Between 2001 and 2004, peritonitis episodes were assessed in 392 participating children receiving CPD. Among the 392 patients, 340 episodes of culture-positive peritonitis were evaluated. Twenty of these episodes were due to Enterococcus species (5.9%). There were no clinical characteristics uniquely associated with enterococcal peritonitis at presentation. After 3 days of therapy, 75% of patients were pain free, 95% had decreased effluent cloudiness and 90% were afebrile. Only one patient required a catheter exchange, and all patients experienced full functional recovery. Despite broad in vitro resistance to cephalosporins and 21% resistance to glycopeptides, neither in vitro resistance pattern nor choice of empiric antibiotic regimen affected short- or long-term outcomes. Enterococci are likely responsible for ∼6% of culture-positive peritonitis episodes in children receiving CPD. Although it was not possible to identify patients with enterococcal peritonitis based on presentation, clinical response was not associated with in vitro resistance patterns, and patients who initially received a cephalosporin-based empiric regimen until culture results are available are likely to respond quickly and have full functional recovery.
    Nephrology Dialysis Transplantation 12/2010; 25(12):4048-54. · 3.37 Impact Factor
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    ABSTRACT: Pharmacokinetic monitoring of CsA is unsatisfactory, because at comparable CsA blood concentrations, the frequency and severity of adverse effects vary considerably among patients. We have therefore recently developed a precise, reliable, and robust whole-blood pharmacodynamic assay that measures the suppression of CsA-target genes in T lymphocytes. Because of the different characteristics of CsA pharmacokinetics in children and the higher propensity for infectious complications, this assay requires validation in the pediatric patient population. We therefore quantified in a prospective study of 45 pediatric renal transplant recipients the residual expression of NFAT-regulated genes in lymphocytes by RT-PCR and correlated these findings with the frequency of recurrent infections in the maintenance period post-transplant. Patients with recurrent infections showed a significantly stronger inhibition of NFAT-regulated gene expression (18.2%) than patients without recurrent infections (31.7%; p = 0.012). This difference was specific, because various PK parameters of CsA and the concomitant immunosuppressive therapy were comparable between patients. Multivariate regression analysis showed that patient age and residual NFAT-regulated gene expression were the only independent determinants of recurrent infections. By ROC curve analysis, a cutoff value of 23% residual NFAT-regulated gene expression had the highest sensitivity (71.1%) and specificity (65.4%) for the discrimination of patients with and without recurrent infections. Pharmacodynamic monitoring of CsA by measurement of residual NFAT-regulated gene expression in T lymphocytes has the potential to identify over-immunosuppressed pediatric renal transplant recipients and is therefore a useful tool for the optimization of CsA therapy.
    Pediatric Transplantation 11/2010; 14(7):844-51. · 1.50 Impact Factor
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    ABSTRACT: Ethical concerns and disadvantages of newborn screening (NBS) for cystic fibrosis (CF) related to genetic testing have raised controversies and impeded implementation of CF NBS in some countries. In the present study, we used a prospective and sequential immunoreactive trypsinogene (IRT)/pancreatitis-associated protein (PAP) strategy, with IRT as first and PAP as second tier, and validated this biochemical approach against the widely used IRT/DNA protocol in a population-based NBS study in southwest Germany. Prospective quantitation of PAP and genetic analysis for the presence of four mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene most prevalent in southwest Germany (F508del, R553X, G551D, G542X) were performed in all newborns with IRT > 99.0th percentile. NBS was rated positive when either PAP was ≥1.0 ng/mL and/or at least one CFTR mutation was detected. In addition, IRT > 99.9th percentile was also considered a positive rating. Positive rating led to referral to a CF centre for testing of sweat Cl(-) concentration. Out of 73,759 newborns tested, 98 (0.13%) were positive with IRT/PAP and 56 (0.08%) with IRT/DNA. After sweat testing of 135 CF NBS-positive infants, 13 were diagnosed with CF. Detection rates were similar for both IRT/PAP and IRT/DNA. One of the 13 diagnosed CF newborns had a PAP concentration <1.0 ng/mL. Sequential measurement of IRT/PAP provides good sensitivity and specificity and allows reliable and cost-effective CF NBS which circumvents the necessity of genetic testing with its inherent ethical problems.
    Journal of Inherited Metabolic Disease 10/2010; 33(Suppl 2):S263-71. · 4.07 Impact Factor
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    ABSTRACT: Imexon [AOP99.0001 (4-imino-1,3-diazobicyclo[3. 1. 0]-hexan-2-one)] belongs to a novel class of promising anticancer agents that induce tumor apoptosis through oxidative stress. Clinical experience since the late 1960s has provided initial evidence for a clinical antitumor activity. Our open-label, multicenter phase I clinical trial was designed to further investigate the adverse event (AEs) profile and pharmacokinetics of AOP99.0001 in pretreated myeloma patients and collect initial data on the potential clinical efficacy in this indication. Thirty-six patients with relapsed or refractory myeloma, who had been pretreated with at least two lines of therapy earlier, were included. Imexon was applied intravenously on 5 consecutive days for 2 weeks (d1-5 and d8-12) for a 3-week cycle. The plasma half-life of AOP99.0001 and its active metabolite AOP99.0002 was found to be approximately 1.2 and 2.6 h, respectively. The mean duration of treatment with Imexon was 6.8 weeks in a dose range between 50 and 1000 mg/m without reaching dose-limiting toxicity. Drug-related AEs occurring with a frequency of greater than 10% were fatigue, nausea, constipation, headache, asthenia, anemia, thrombocytopenia, leukopenia and creatinine increase. A total of nine severe adverse events occurred in three patients. No mortality was encountered when patients were on treatment with Imexon. Preliminary antimyeloma efficacy of AOP99.0001 was observed with 1 minimal response, 12 (36%) stable disease responses, and all other evaluable patients had progressive disease. Remarkably, the patient with minimal response also experienced a complete clinical resolution of myeloma-associated polyneuropathy. Overall, Imexon was safe and well tolerated in the dose range investigated. Imexon showed minor clinical activity as a single agent in heavily pretreated myeloma patients. On account of its unique mechanism of action, favorable toxicity profile, initial clinical evidence for antimyeloma activity, and its known synergistic activity in combination with approved agents for myeloma treatment, AOP99.0001 is recommended for future clinical studies in combination regimens in multiple myeloma.
    Anti-cancer drugs 08/2010; 21(7):708-15. · 2.23 Impact Factor
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    ABSTRACT: The International Pediatric Peritonitis Registry (IPPR) was established to collect prospective data regarding peritoneal dialysis (PD)-associated peritonitis in children. In this report, we present the IPPR results that pertain to relapsing peritonitis (RP). This was an online, prospective entry into the IPPR of data that pertain to peritonitis cases by participating centers. Of 490 episodes of nonfungal peritonitis, 52 (11%) were followed by a relapse. There was no significant difference between RP and non-RP in distribution of causative organisms and antibiotic sensitivities. Initial empiric therapy-ceftazidime with either first-generation cephalosporin or glycopeptide (vancomycin or teicoplanin)-was not associated with relapse. Switching to monotherapy with a first-generation cephalosporin on the basis of culture results was associated with higher relapse rate (23%) than other final antibiotic therapies (0 to 9%). Culture-negative RP was less likely to have a satisfactory early treatment response than non-RP (82 versus 98%). Young age, single-cuff catheter, downward-pointing exit site, and chronic systemic antibiotic prophylaxis were additional independent risk factors for RP in the multivariate analysis. Compared with non-RP, RP was associated with a lower rate of full functional recovery (73 versus 91%), higher ultrafiltration problems (14 versus 2%), and higher rate of permanent PD discontinuation (17 versus 7%). This is the largest multicenter, prospective study to date to examine RP in children. In addition, this is the first report in the literature to examine specifically the relationship of postempiric antibiotic treatment regimens to the subsequent risk for relapse.
    Clinical Journal of the American Society of Nephrology 06/2010; 5(6):1041-6. · 5.07 Impact Factor
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    ABSTRACT: BACKGROUND: Long-term corticosteroid treatment impairs growth and increases cardiovascular risk factors. Hence, steroid withdrawal constitutes a major topic in paediatric renal transplantation and maintenance immunosuppression. METHODS: The lack of data from randomised controlled trials caused us to conduct the first prospective, randomised, multicentre study on late steroid withdrawal among paediatric kidney allograft recipients treated with standard-dose cyclosporine microemulsion (CsA) and mycophenolate mofetil (MMF) for 2 years. Forty-two low- or regular-immunologic risk patients were randomly assigned, >or=1 year post-transplant, to continue taking or to withdraw steroids over 3 months. RESULTS: Two years after steroid withdrawal, they showed a longitudinal growth superior to controls [mean height standard deviation score (SDS) gain, 0.6 +/- 0.1 SDS versus -0.2 +/- 0.1 SDS (P < 0.001)]. The prevalence of the metabolic syndrome declined significantly (P < 0.05), 2 years after steroid withdrawal, from 39% (9/23) to 6% (1/16). Steroid-free patients had less frequent arterial hypertension (50% versus 93% (P < 0.05)) and required fewer antihypertensive drugs [0.6 +/- 0.2 versus 1.5 +/- 0.3 (P < 0.05 versus control)]. Additionally, they had a significantly improved carbohydrate and lipid metabolism with fewer hypercholesterolaemia and hypertriglyceridaemia (P < 0.05 versus control). Patient and graft survival amounted to 100%. Allograft function remained stable 2 years after steroid withdrawal. The incidence of acute rejections was similar in the steroid-withdrawal group (1/23, 4%) and controls (2/19, 11%). CONCLUSION: Late steroid withdrawal in selected CsA- and MMF-treated paediatric kidney transplant recipients improves growth, mitigates cardiovascular risk factors and reduces the prevalence of the metabolic syndrome, at no increased risk of acute rejection or unstable graft function.
    Nephrology Dialysis Transplantation 02/2010; · 3.37 Impact Factor
  • Clinical Journal of the American Society of Nephrology. 01/2010; 5(6):1041-1046.
  • Nephrology Dialysis Transplantation. 01/2010; 25(12):4048-4054.
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    ABSTRACT: Long-term corticosteroid treatment impairs growth and increases cardiovascular risk factors. Hence, steroid withdrawal constitutes a major topic in paediatric renal transplantation and maintenance immunosuppression. The lack of data from randomised controlled trials caused us to conduct the first prospective, randomised, multicentre study on late steroid withdrawal among paediatric kidney allograft recipients treated with standard-dose cyclosporine microemulsion (CsA) and mycophenolate mofetil (MMF) for 2 years. Forty-two low- or regular-immunologic risk patients were randomly assigned, >or=1 year post-transplant, to continue taking or to withdraw steroids over 3 months. Two years after steroid withdrawal, they showed a longitudinal growth superior to controls [mean height standard deviation score (SDS) gain, 0.6 +/- 0.1 SDS versus -0.2 +/- 0.1 SDS (P < 0.001)]. The prevalence of the metabolic syndrome declined significantly (P < 0.05), 2 years after steroid withdrawal, from 39% (9/23) to 6% (1/16). Steroid-free patients had less frequent arterial hypertension (50% versus 93% (P < 0.05)) and required fewer antihypertensive drugs [0.6 +/- 0.2 versus 1.5 +/- 0.3 (P < 0.05 versus control)]. Additionally, they had a significantly improved carbohydrate and lipid metabolism with fewer hypercholesterolaemia and hypertriglyceridaemia (P < 0.05 versus control). Patient and graft survival amounted to 100%. Allograft function remained stable 2 years after steroid withdrawal. The incidence of acute rejections was similar in the steroid-withdrawal group (1/23, 4%) and controls (2/19, 11%). Late steroid withdrawal in selected CsA- and MMF-treated paediatric kidney transplant recipients improves growth, mitigates cardiovascular risk factors and reduces the prevalence of the metabolic syndrome, at no increased risk of acute rejection or unstable graft function.
    Nephrology Dialysis Transplantation 09/2009; 25(2):617-24. · 3.37 Impact Factor
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    ABSTRACT: : Many transplant centers practice late steroid withdrawal after pediatric renal transplantation, but evidence-based data on the overall risk-to-benefit ratio in this patient population are lacking. : We therefore conducted the first prospective, randomized, open-label multicenter study to validate this strategy: 42 low-immunologic risk pediatric kidney allograft recipients, aged 10.3+/-4.3 years, on cyclosporine microemulsion, mycophenolate mofetil, and corticosteroids were randomly assigned, more than or equal to 1-year posttransplant, to continue steroids or to withdraw over 3 months. This report contains the 1-year results. : In response to steroid withdrawal, patients experienced a significant catch-up growth with a mean standardized height gain of 0.3+/-0.1 standard deviation score (SDS) per year (P<0.05 vs. control), whereas mean height SDS in the control group did not change (0.0+/-0.1 SDS). Standardized body mass index declined significantly by 0.68+/-0.23 SDS after steroid withdrawal, but rose significantly by 0.26+/-0.34 SDS in the control group. Patients off steroids had less frequent arterial hypertension (50% vs. 87.5% (P<0.05) and significantly lower serum cholesterol (by 21%) and triglyceride values (by 36%) than control patients. Patient and graft survival were 100%. The incidence of acute rejection episodes in the steroid-withdrawal group was 1 of 23 (4%) compared with 1 of 19 (5%) in controls. Transplant function remained stable in both groups. : Late steroid withdrawal in low-immunologic risk European pediatric kidney transplant recipients on cyclosporine microemulsion and mycophenolate mofetil is not associated with an increased rate of acute rejection episodes, enables catch-up growth and ameliorates cardiovascular risk factors.
    Transplantation 03/2009; 87(6):934-41. · 3.78 Impact Factor
  • Bone 01/2009; 45. · 3.82 Impact Factor
  • Bone 01/2009; 45. · 3.82 Impact Factor
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    ABSTRACT: The proportion of gram-negative causative organisms in peritoneal dialysis-associated peritonitis is increasing. Little published information for this complication exists in children. The objective of this study is to evaluate the clinical presentation, early and late response to treatment, and identification of factors influencing the outcome of gram-negative peritonitis (GNP) in children. Case series. 104 children (aged 7.9 +/- 5.9 years) with 121 GNP episodes reported to the International Pediatric Peritonitis Registry from October 2001 through December 2004. Patient, clinical, bacteriological, and treatment features. Initial response to empirical treatment was assessed after approximately 72 hours of therapy. Final outcome was judged according to the occurrence of death, technique failure, relapse, need for catheter exchange, and a composite end point defining full functional recovery. 44% of episodes of GNP occurred in children younger than 5 years. Causative organisms included Pseudomonas species, 21%; Klebsiella species, 18%; Escherichia coli, 17%; and Acinetobacter species, 12%. Thirty-two percent of organisms classified as gram-negative were not identified further. Clinical manifestations were severe and uniform for all causative gram-negative agents. A substantial proportion (20%) of organisms were resistant to ceftazidime, with resulting suboptimal response to empirical therapy. By day 3 of initial empiric treatment, 85% of children with GNP had improved clinically (39%, complete resolution; 46%, improvement in symptoms), 10% showed poor response, and 5% had worsening of symptoms. Multivariate analysis identified severe abdominal pain, use of a single-cuff catheter, and intermittent (versus continuous) intraperitoneal ceftazidime administration as independent predictors of worse initial response to treatment. Full functional recovery was achieved in 86% of episodes. Nineteen patients (16%) required catheter removal, 11 (9%) experienced a relapse, 7 (6%) discontinued peritoneal dialysis therapy permanently, and 3 died. Lack of clinical improvement after 72 hours of therapy (odds ratio, 5.39; P < 0.01) and the presence of an exit-site infection (odds ratio, 7.69; P = 0.01) independently increased the risk of an incomplete functional recovery. The study was not designed to assess absolute incidence figures or risk factors for the development of GNP in children. GNP is a significant complication of long-term peritoneal dialysis therapy in children, and a substantial proportion of affected children are at risk of permanent sequelae. Because results of empiric treatment with ceftazidime are suboptimal in the setting of this infection, alternative antimicrobial agents should be reconsidered.
    American Journal of Kidney Diseases 03/2008; 51(3):455-62. · 5.29 Impact Factor
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    ABSTRACT: Peritonitis is the most common cause of dialysis failure in children on chronic peritoneal dialysis. We performed a prospective study of 501 peritonitis episodes in 44 pediatric dialysis centers located in 14 countries that examined peritonitis etiology, efficiency of opinion-based management guidelines, and final outcomes. Culture-negative incidence varied significantly from 11% in North America to 67% in Mexico. Argentina and North America had the highest rate of Gram-negative episodes. Pseudomonas-based peritonitis was eightfold more common in the United States than in Europe, and correlated with the frequency of exit site cleansing and topical mupirocin administration. Significant regional variation in antibiotic susceptibility was noted for the first generation cephalosporins and aminoglycosides. Initial response rates to standardized empiric antibiotic treatment did not differ between regions; however, final outcomes were significantly less favorable in Eastern Europe. The wide regional variation in culture-negative peritonitis, and the distribution and antibiotic susceptibilities of causative bacteria needs to be taken into consideration when the guidelines for empiric therapy of pediatric dialysis-associated peritonitis are revised.
    Kidney International 01/2008; 72(11):1374-9. · 7.92 Impact Factor
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    ABSTRACT: The study aimed to evaluate differences between EEG and MEG analysis of early somatosensory evoked activity in patients with focal epilepsies in localizing eloquent areas of the somatosensory cortex. Twenty-five patients (12 male, 13 female; age 4-25 years, mean 11.7 years) were included. Syndromes were classified as symptomatic in 17, idiopathic in 2 and cryptogenic in 6 cases. 10 patients presented with malformations of cortical development (MCD). 122 channel MEG and simultaneous 33-channel EEG were recorded during tactile stimulation of the thumb (sampling rate 769 Hz, band-pass 0.3-260 Hz). Forty-four hemispheres were analyzed. Hemispheres were classified as type I: normal (15), II: central structural lesion (16), III: no lesion, but central epileptic discharges (ED, 8), IV: lesion or ED outside the central region (5). Analysis of both sides including one normal and one type II or III hemisphere was possible in 15 patients. Recordings were repeated in 18 hemispheres overall. Averaged data segments were filtered (10-250 Hz) and analyzed off-line with BESA. Latencies and amplitudes of N20 and P30 were analyzed. A regional source was fitted for localizing S1 by MRI co-registration. Orientation of EEG N20 was calculated from a single dipole model. EEG and MEG lead to comparable good results in all normal hemispheres. Only EEG detected N20/P30 in 3 hemispheres of types II/III while MEG showed no signal. N20 dipoles had a more radial orientation in these cases. MEG added information in one hemisphere, when EEG source analysis of a clear N20 was not possible because of a low signal-to-noise ratio. Overall N20 dipoles had a more radial orientation in type II when compared to type I hemispheres (p=0.01). Further N20/P30 parameters (amplitudes, latencies, localization related to central sulcus) showed no significant differences between affected and normal hemispheres. Early somatosensory evoked activity was preserved within the visible lesion in 5 of the 10 patients with MCD. MEG should be combined with EEG when analyzing tactile evoked activities in hemispheres with a central structural lesion or ED focus. At time, MEG analysis is frequently applied without simultaneous EEG. Our results clearly show that EEG may be superior under specific circumstances and combination is necessary when analyzing activity from anatomically altered cortex.
    Clinical Neurophysiology 09/2007; 118(8):1721-35. · 3.14 Impact Factor
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    ABSTRACT: In children who are on chronic peritoneal dialysis, peritonitis is the primary complication compromising technique survival, and the optimal therapy of peritonitis remains uncertain. An Internet-based International Pediatric Peritonitis Registry was established in 47 pediatric centers from 14 countries to evaluate the efficacy and safety of largely opinion-based peritonitis treatment guidelines in which empiric antibiotic therapy was stratified by disease severity. Among a total of 491 episodes of nonfungal peritonitis entered into the registry, Gram-positive organisms were cultured in 44%, Gram-negative organisms were cultured in 25%, and cultures remained negative in 31% of the episodes. In vitro evaluation revealed 69% sensitivity of Gram-positive organisms to a first-generation cephalosporin and 80% sensitivity of Gram-negative organisms to a third-generation cephalosporin. Neither the risk factors assumed by the guidelines nor the choice of empiric therapy was predictive of either the early treatment response or the final functional outcome of the peritonitis episodes. Overall, 89% of cases achieved full functional recovery, a portion after relapsing peritonitis (9%). These data serve as the basis for new evidence-based guidelines. Modification of empiric therapy to include aminoglycosides should be considered.
    Journal of the American Society of Nephrology 08/2007; 18(7):2172-9. · 8.99 Impact Factor

Publication Stats

451 Citations
171.15 Total Impact Points

Institutions

  • 2004–2012
    • University of Iowa Children's Hospital
      Iowa City, Iowa, United States
  • 2010
    • Children's Memorial Hospital
      Chicago, Illinois, United States
  • 2008
    • Medical University of Gdansk
      • Department of Pediatrics, Nephrology and Hypertension
      Gdańsk, Pomeranian Voivodeship, Poland
  • 2007
    • Children's Mercy Hospital
      Kansas City, Missouri, United States
  • 1998–2006
    • Universität Heidelberg
      • • Department of Pediatric Neurology
      • • Institute of Pharmacology
      Heidelberg, Baden-Wuerttemberg, Germany