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The role of mTOR inhibitors, such as EVL, has not been established for pediatric liver transplant recipients up to now, although data from adult solid organ graft transplantation are very promising. Major complications following pediatric liver transplantation in the long-term course include chronic graft rejection and CNIderived nephrotoxicity. The purpose of our study was to report first results using EVL as a rescue therapy in pediatric liver transplant recipients for the following indications: chronic graft dysfunction n = 12, suspected CNI toxicity n = 3, hepatoblastoma n = 2, and recurrence of primary sclerosing cholangitis post-Ltx n = 1. Four patients with chronic graft dysfunction developed completely normal liver function tests using EVL, six patients showed partial improvement, and two patients did not respond at all. One patient with CNIinduced nephropathy showed a slightly improved GFR. Both patients with hepatoblastoma did not develop any metastasis post-Ltx. First experience with EVL in pediatric liver transplant recipients shows promising results in patients with chronic graft failure when standard immunosuppression has failed. The future role of EVL in immunosuppressive protocols for children post-Ltx has to be proven by controlled clinical trials. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics which include "Interpretation of chest radiographs from children with lower respiratory tract infections," by Martin Edwards and colleagues, "Where is the air? A review of paediatric extra-pulmonary air collections," by Fleur Kilburn-Toppin, Owen Arthurs and Anna Gomez, and "Pulmonary infections in immunocompromised children," by Silvia Cacaci and colleagues.

The article presents abstracts on medical topics including the impact of class-3 semaphorins on brain tumors, prevalence of renal dysfunction among children following liver transplantation, and immature platelet fraction for differential diagnosis of thrombocytopenia.

A letter to the editor is presented in response to an article about pediatric transplantation.

The article argues in favor of 2010 German legislation calling for the extension of the "Führungszeugnis," which is a registration background criminal check of a number of personnel related to schools or businesses who deal with the young in order to prevent child sexual abuse. The law is said to extend to school bus drivers, custodial staff, athletic trainers, and workers in youth welfare offices.

The article lists several topics which will be discussed at the 47th Annual Meeting of the European Society of Paediatric Radiology in June 9 and June 10, 2010 which includes reappraisal of the sonographic characteristics of the neonatal kidney, brain malformations in children with syndromic craniosynostosis and the clinical and radiological presentation of preterm cerebellar haemorrhage.

The article presents abstracts related to pediatric radiology which include structural brain abnormalities in children with syndromic craniosynostosis, a study on children reference biometric data of the corpus callosum (CC) in Magnetic Resonance Imaging (MRI), and MRI and neurodevelopmental analysis in children with rhombencephalosynapsis.

Krampe K, Briem-Richter A, Fischer L, Nashan B, Ganschow R. The value of immunoprophylaxis for cytomegalovirus infection with intravenous immunoglobulin in pediatric liver transplant recipients receiving a low-dose immunosupressive regimen. Pediatr Transplantation 2010: 14: 67–71. © 2009 Wiley Periodicals, Inc. The incidence of CMV infection following pediatric Ltx is particularly high, which can be attributed to the increased number of patients at high risk for primary infection (donor CMV+, recipient CMV−). Current approaches to cope with this complication producing post-operative morbidity include prophylactic or preemptive ganciclovir therapy. As the risk for symptomatic CMV infection is directly correlated with the intensity of immunosuppression, the aim of our study was to assess the value of IVIG in order to protect children receiving low-dose immunosuppression from CMV disease. Twenty-eight consecutive children (median age 62.2 months) at high risk prospectively received three infusions of IVIG on days four, 14, and 28 post-transplant and were monitored for six months post-Ltx. Immunosuppression consisted of cyclosporine (initial trough levels 170–200 μg/L) and prednisolone (starting dose 15 mg/m2) as well as basiliximab induction therapy. Patient survival was 100% and graft survival was 92.9%. Two subjects developed laboratory findings of CMV infection (8%) and one child suffered from tissue invasive CMV disease (4%). Three patients were excluded from the study because of protocol violations. We conclude that there was a low incidence of CMV disease among a prospective cohort receiving low-dose immunosuppression and a standard IVIG product. [ABSTRACT FROM AUTHOR]

FHF is characterized by a high percentage of unknown causes leading to acute liver failure and furthermore by an increased morbidity and mortality prior to and post-Ltx. In different transplant centers, the reasons leading to FHF differ significantly as well as outcome. We report our single center experience with 30 pediatric patients receiving a liver transplant for FHF, out of a total of 83 children presenting with FHF. The time to transfer patients to the transplant center after the diagnosis of FHF was long, with a median of 14 days (Ltx group) and 12 days (controls), respectively. In nearly half of the patients (n = 14) in the Ltx group, we were not able to establish an exact diagnosis prior to Ltx: 50% suffered from encephalopathy, and 13 patients were treated in the intensive care unit prior to transplant. Because of the availability of different surgical techniques, all children received a timely transplant [split (n = 18), living donor (n = 9), whole organ (n = 2), and reduced liver (n = 1)]. Patient survival was 93.4%, and graft survival was 83.4% for at least one yr follow-up. Severe complications following Ltx included three cases with aplastic anemia and one child suffering from systemic mitochondrial depletion syndrome. The survival of patients treated medically was 83%. We conclude that a strong focus should be made on early referral to a specialized center and on improvement of diagnostic tools to timely detect the underlying reason for FHF. Results following Ltx for FHF are good. [ABSTRACT FROM AUTHOR]

We present a 4-year-old boy admitted to the hospital due to the typical symptoms of celiac disease with severe dystrophy, anaemia and elevated gliadin IgG antibodies. Upper endoscopy ruled out celiac disease but showed severe Candida esophagitis. Due to an impaired T-cell function especially following Candida antigen stimulation in vitro, plus recurrent Candida infections of the skin, the diagnosis of chronic mucocutaneous candidasis (CMC) was made. Under the treatment with fluconazol, trimethoprim/sulfmethoxazole and IVIG, the child improved impressively. Gliadin antibodies declined steadily. Conclusion: The common symptoms growth retardation, anaemia and elevated gliadin antibodies are suggestive for celiac disease but very unspecific. The rare immunodeficiency CMC may cause elevated gliadin antibodies. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics which include development of regenerated chimeric liver grafts and long-term evaluation of their potential, anxieties and doubts about living kidney donation from the recipient's viewpoint, and inaccuracy of preoperative imaging in case of patients with liver transplantation for hepatocellular carcinoma.

The article presents a program of events for the International Pediatric Transplant Association (IPTA) 5th Congress on Pediatric Transplantation to be held in Istanbul, Turkey on April 18-21, 2009.

We report a 15-year-old boy who developed aseptic meningitis 10 days after administration of the second dose of the COVID-19 vaccine BNT162b2. Although accompanying aphthous mouth ulcers resembling herpetic stomatitis initially led us to suspect an underlying viral infection, broad virological and microbiological screening did not identify any causative pathogen. Gonarthritis and skin lesions, which both developed within three days after admission, extended the clinical presentation eventually resembling an acute Behçet's disease episode. This is the first description of a juvenile patient with aseptic and pathogen-negative meningitis occurring in close temporal association with vaccination against COVID-19, along with a few previously reported adult patients with isolated meningitis and a further case with meningitis and an accompanying Behçet's disease-like multisystem inflammation episode as seen in our patient. With billions of individuals being vaccinated worldwide so far and only a few cases of aseptic pathogen-negative meningitis reported in close temporal relation, causality is unclear. However, aseptic meningitis should be kept in mind in the differential diagnosis of patients with persistent or delayed onset of headache and fever following COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

In adult liver graft recipients, it has been shown that certain chemokine polymorphisms (CCR5Δ32) may correspond to ischemic type biliary lesions leading to chronic graft dysfunction. The aim of our present study was to assess the importance of CCR5Δ32 polymorphism in a cohort of pediatric liver graft recipients with regard to acute or chronic graft dysfunction. A total of 137 children post-liver transplantation have been included for genetic analysis (CCR5Δ32 polymorphism), and the incidence of acute and chronic graft dysfunction was analyzed. The most common diagnosis leading to LTx was biliary atresia (56.2%), the median age was 14 months, and 33.5% of the patients received a living-related graft. In all, 110 of the subjects were found to have the CCR5 wild type, 25 children were heterozygous for CCR5Δ32, and two patients were homozygous. Of 137, 44 (32.1%) developed acute graft rejection, nine out of 137 (6.6%) chronic graft dysfunction (vanishing bile duct syndrome), and 84 (61.3%) children had neither acute nor chronic graft rejection. There was no significant correlation between acute graft rejection or chronic graft dysfunction and the CCR5Δ32 allele in the study population. We conclude that CCR5Δ32 polymorphism may not play a role in acute or chronic liver graft dysfunction in children. [ABSTRACT FROM AUTHOR]

The article presents a schedule for the 4th Congress of the International Pediatric Transplant Association on pediatric transplantation that will be held in Cancun, Mexico on March 17-21, 2007.

Both calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, are widely used in pediatric liver transplant recipients and currently data are limited with regards to long-term results using the one drug or the other in comparable low doses. We conducted the present study to assess the advantages and disadvantages of both drugs in children at least five yr post-liver transplantation. A total of 129 children were enrolled in the study. Thirty-eight of the children were switched to tacrolimus monotherapy for different reasons [steroid resistant graft rejection (n = 15), chronic rejection (n = 5), severe acute rejection (n = 4), repetitive acute graft rejection (n = 5), dysfunction of the transplant (n = 3), insufficient CsA metabolism (n = 3), hypertrichosis (n = 2), and CsA toxicity (n = 1)], four patients had primary tacrolimus therapy, and 87 patients are receiving cyclosporine. Mean trough levels were 5.3 ± 2.3 ng/mL (tacrolimus) and 73.6 ± 44.5 μ/L (cyclosporine), respectively at least five yr post-orthotopic liver transplantation (OLT). There was no significant difference in the calculated glomerular filtration rate between children on cyclosporine and tacrolimus (142.7 + 39.5 mL/min/1.73 m2 vs. 151.1 ± 44.1 mL/min/1.73 m2). The incidence of arterial hypertension was 7.1% vs. 9.2%, that of hepatotoxicity was 0% vs. 2.3%. Cosmetic changes were found in more than one-third of the patients on cyclosporine and in 4.8% of the patients receiving tacrolimus. Quality of life was excellent in both groups (self assessment). The impact of CNIs on chronic graft dysfunction cannot be assessed by our present study. We conclude from the results that cyclosporine and tacrolimus are both excellent drugs for maintenance immunosuppression in the long-term course following pediatric liver transplantation. However, this retrospective analysis is limited by the bias between children on CsA as compared with patients receiving tacrolimus. A prospective randomized controlled trial is needed in order to assess which CNI is the best for children following OLT. [ABSTRACT FROM AUTHOR]

Several factors may contribute to post-transplant cholestatic complications after liver transplantation. These include ischemic reperfusion injury, hypoperfusion, bile duct strictures, and hepatotoxic drugs. Up to now, there have been no publications on tacrolimus cholestatic toxicity in clinical transplantation when the drug was used in therapeutic doses. We describe six pediatric liver graft recipients in whom cholestatic complications developed under a tacrolimus-based immunosuppression following liver transplantation and all of them suffered from previous steroid-resistant graft rejection. The overall incidence of cholestatic syndrome was 5.4% in children receiving tacrolimus. The immunosuppression was switched back to cyclosporine and prednisolone in all six patients resulting in completely resolved clinical signs and laboratory findings. We conclude from our observations that a cholestatic syndrome following pediatric liver transplantation may be caused by tacrolimus therapy following steroid-resistant graft rejection, even if given in therapeutic doses. [ABSTRACT FROM AUTHOR]

An AGS is a dominant inherited multisystem disorder caused by mutations in the Notch signaling pathway ( JAG1). In our center, 5.3% of liver transplantations (OLT) are performed in children with AGS. Some of the affected children fulfilled criteria for OLT, despite the absence of liver cirrhosis. The aim of our present study was to evaluate the indications and outcome for OLT in children with this complex disorder as clear criteria are difficult to establish in clinical practice. A total of 37 patients were included in a retrospective analysis. Twenty-four children underwent OLT for chronic end-stage liver failure (n = 8) or symptomatic liver disease (n = 16). Patient survival post-OLT was 91.7% after 1 yr, that of graft survival was 87.5%, respectively. Significant post-transplant vascular complications included a mid-aortic syndrome (n = 1) and severe lethal bleeding due to suspected vascular malformation (n = 1). Severe hypercholesterolemia (>800 mg/dL) and xanthomata resolved completely in affected patients. We conclude from our data that indications for OLT in AGS should be extended to patients with severe symptomatic liver disease, even in the absence of liver cirrhosis because of the significantly improved outcome after pediatric OLT in the last decade. Future studies must identify underlying mechanisms of hypercholesterolemia and vascular malformation. [ABSTRACT FROM AUTHOR]

It has been shown that an induction therapy with the monoclonal anti-interleukin-2 receptor antibody basiliximab (SimulectTM) is capable to reduce the incidence of acute graft rejection in adult and pediatric liver transplantation (Ltx). However, data on long-term results using basiliximab in children post-Ltx are still pending. Therefore, the objective of our study was to report on the long-term results of basiliximab induction therapy in pediatric liver transplant recipients. A total of 54 children received two single doses of basiliximab in addition to cyclosporine and prednisolone following Ltx. We analyzed the incidence of acute and chronic graft rejection that of post-transplant lymphoproliferative disease (PTLD), and patient and graft survival. The follow-up was 22–46 months. The historical control group (matched controls) consisted of 54 patients treated with a cyclosporine and prednisolone dual therapy. Patient survival was 53 of 54 in the treatment group and 51 of 54 in the controls. One patient was retransplanted in the treatment group vs. three patients in the control group. The incidence of acute graft rejection was 16.6% compared with 53.7% in the control group (p < 0.001), that of chronic rejection was comparable in both groups (one of 54 vs. one of 54). The incidence of steroid resistant rejection was four of 54 vs. six of 54 that of PTLD were one of 54 vs. zero of 54. There were no adverse effects observed, which could be related to the antibody treatment. We conclude that basiliximab provides safe and effective induction immunosuppression in pediatric liver graft recipients. Short- and even long-term results are excellent. [ABSTRACT FROM AUTHOR]

The article presents the subject index of the December 2005 issue of the "Clinical Chemistry & Laboratory Medicine."

The article presents a table of contents of the December 2005 issue of "Clinical Chemistry & Laboratory Medicine."

Ganschow R, Englert C, Grabhorn E, Richter A, Hinrichs B, Broering DC, Rogiers X, Burdelski M. Hypogammaglobulinemia in pediatric liver transplant recipients.Pediatr Transplantation 2005.© 2005 Blackwell MunksgaardHypogammaglobulinemia has been reported after solid organ transplantation in adults, however immunoglobulin replacement [intravenous immunoglobulins (IVIG)] is only necessary in a minority of affected patients. We here present three pediatric patients with severe post-transplant hypogammaglobulinemia following liver transplantation (LTx) receiving a cyclosporine-based standard immunosuppression. Patient 1 was transplanted at the age of 10 months for biliary atresia. Eight weeks post-Ltx the serum IgG was 1.7 g/L. Patient 2 was transplanted at the age of 12 yr for acute liver failure. Four weeks post-Ltx the IgG dropped to 2.6 g/L. Patient 3 was transplanted at the age of 4 months for biliary atresia. Ten weeks post-Ltx severe hypogammaglobulinemia (IgG < 1.48 g/L) was diagnosed during a severe infectious complication. Patients 1 and 3 received a steroid bolus therapy for acute graft rejection. All patients had normal IgG concentrations prior to Ltx and lymphocyte subsets were post-operatively in the normal range. There was no extensive loss of protein by ascites. IGIV were replaced in the three patients monthly without further complications. In two of the patients (1 and 3) IVIG therapy was discontinued 8 and 10 months after Ltx when the immunosuppression has been reduced and serum IgG concentrations were found in the normal range without further immunoglobulin replacement. Severe hypogammaglobulinemia is a rare phenomenon following pediatric LTx and seems to be mainly caused by immunosuppressive drugs, however, the exact underlying mechanisms are unclear. A screening for hypogammaglobulinemia is useful after pediatric LTx, especially in patients with an intensified immunosuppression. Moreover, further immunologic research in affected patients is necessary. [ABSTRACT FROM AUTHOR]

Ganschow R, Richter A, Grabhorn E, Schulz A, von Hugo A, Mir TS, Broering DC, Rogiers X, Hinrichs B, Burdelski M. C2 blood concentrations of orally administered cyclosporine in pediatric liver graft recipients with a body weight below 10 kg. Pediatr Transplantation 2004: 8: 185–188. © 2004 Blackwell Munksgaard Pharmacokinetic studies in adult and pediatric liver transplant recipients have shown that the C2 monitoring is superior to the traditional determination of CsA trough levels (C0) as an estimate of CsA exposure. However, target reference values for C2 in very small infants have not been established yet. The objective of our study was to assess the distribution of C2 levels in the first week following Ltx and to analyze enteral absorption of CsA for this group of patients. We documented CsA C0 and C2 levels in 25 infants with a body weight below 10 kg (median 6.8 kg; range 3.0–9.8 kg) in the first 7 days after Ltx. The infants had a median age at transplantation of 7 months (range 0.3–20.0 months). The underlying diagnoses were biliary atresia (n = 17), acute liver failure (n = 4), metabolic disease (n = 4). All children received CsA microemulsion (NeoralTM, initial 10 mg/kg/day), prednisolone, and two single doses of basiliximab as immunosuppressive drugs. The mean C0 and C2 levels were as follows: day 1: C0 77.0 ± 39.6, C2 340.5 ± 140.0 ng/mL; day 2: C0 135.5 ± 53.2, C2 467.0 ± 168.2 ng/mL; day 3: C0 146.5 ± 70.8, C2 519.0 ± 219.1 ng/mL; day 4: C0 168.5 ± 55.1, C2 570.0 ± 163.7 ng/mL; day 5: C0 156.5 ± 38.0, C2 612.0 ± 132.4 ng/mL; day 6: C0 177.0 ± 41.1, C2 606.0 ± 149.2 ng/mL; day 7: C0 174.0 ± 27.2, C2 622.0 ± 98.8 ng/mL (r = 0.82, p < 0.05). This analysis demonstrates that there is a good enteral absorption of CsA in very small children post-Ltx in the early post-operative period. Based on the C2 levels achieved, we conclude that there is a good correlation between C0 and C2 levels even in very small infants. [ABSTRACT FROM AUTHOR]

Lists events to be held on April 06, 2003 during the 2nd Congress of the International Pediatric Transplant Association. Plenary Session I -- Pediatrics Registries 2003; Chairpersons of Plenary Session II; Schedule of a session on renal transplantation.

Lists events to be held on April 08, 2003 during the 2nd Congress of the International Pediatric Transplant Association. Time of Plenary session VI -- Immunology for the Clinician; Chairpersons in Plenary session VII; Venue for the gala dinner.

Presents abstracts of papers presented in the 2nd Congress of the International Pediatric Transplant Association. Authors of the abstract on a regulatory cell population expressing a peripheral homing receptor; Possibility of existence of an interaction between mycophenolate mofetil and tacrolimus in pediatric liver transplant recipients; 'Long-Term Quality of Life for Living Liver Donors,' presented by David C. Cronin.

A 14-week-old boy with undiagnosed Chediak–Higashi syndrome developed fever with a high temperature and acute cardiac failure after having received a scheduled vaccination. We hypothesize that decreased concentrations and receptor binding of serum and tissue diadenosine polyphosphates, such as AP4 A, AP5 A, or AP6 A, which are stored in various tissues and serve as extra-cellular signaling molecules or are secreted by cells in response to physiologically stressful stimuli, lead to the observed severe tachyarrhythmia. Diadenosine polyphosphates normally have a negative chronotropic and inotropic effect. This is the first report of severe cardiac failure in a child with Chediak–Higashi syndrome and we suggest that cardiac arrhythmias should be considered in such children in the event of high fever. Our hypothesis requires further investigation in other patients. [ABSTRACT FROM AUTHOR]

Alterations of serum immunoglobulins, especially hypogammaglobulinemia (HG), are a frequent finding in steroid sensitive nephrotic syndrome (SSNS). The exact mechanisms are unclear, especially the persistence of HG into remission. Therefore we studied serum immunoglobulins M, A and G including IgG subclasses 1–4 in 44 children with SSNS; 14 were studied during relapse (RL) and 30 in remission (RM). Data were compared with those of 23 healthy controls. In a subgroup of 23 patients (12 in RM and 11 in RL) we also studied IgG-1 specific antibodies to tetanus toxoid and IgG-2 specific antibodies to pneumococcus antigen. Increased serum concentrations of IgM in RL and reduction of serum IgG in RL and RM were confirmed. During relapse, HG was characterized to result from deficiency of IgG-1–3, whereas in early phases of relapse the reduction was due to low IgG-1 only. In RM the deficiency of IgG-2 persisted for 12 months and correlated strongly with the duration of remission (R=0.60, P<0.0001). IgG-4 levels were not altered in SSNS. In addition, IgG-2 specific antibodies to pneumococcus antigen were significantly reduced only in RL compared to RM (P<0.05). In conclusion, hypogammaglobulinemia of SSNS is characterized by a different constitution of IgG subclasses. In RL a reduction of serum levels of IgG-1–3 occurs, while low concentrations of IgG-2 might be the explanation for HG in remission of SSNS. [ABSTRACT FROM AUTHOR]

Background: Data on the oxidative metabolism of polymorphonuclear neutrophils (PMN) after solid organ transplantation are very limited. We hypothesized that immunosuppressive agents reduce the capacity of PMN to produce reactive oxygen species, such as O[sub 2][sup -] , H[sub 2] O[sub 2] , OH, and OCL[sup -] leading to an increased susceptibility to infectious complications after liver transplantation. Methods: A lucigenin-enhanced chemiluminescence (CL) assay was used with soluble and particulate stimuli to study the oxidative metabolism of PMN in pediatric liver graft recipients. Sixteen patients (median age: 2.4 yr) were enrolled in a prospective study and integrated CL response was compared with the CL activity of 29 healthy controls. Results: In the second week post-transplant, we found a significantly reduced CL activity. Pre-operatively, and after lowering steroids and cyclosporin A (CsA) the oxidative burst was normal. Conclusions: Our data suggest that CsA and steroids may not only influence T and B cells but also PMN, which may be a relevant factor for the incidence of infectious complications in pediatric liver graft recipients. [ABSTRACT FROM AUTHOR]

The real incidence and the underlying causes of cholelithiasis in pediatric solid organ recipients is probably not exactly known. In addition to well-established risk factors for cholelithiasis, children after heart, kidney, or liver transplantation may develop gallstones due to drug therapy, sepsis, parenteral nutrition, or surgical complications. For pediatric patients, data are very limited and heterogeneous. However, the incidence in pediatric heart recipients seems to be substantially higher compared with kidney or liver graft recipients. In this review article the present data are discussed focusing on incidence, detection, and management of cholelithiasis in pediatric organ transplantation. In general, surgery is the therapy of choice in symptomatic patients; however, the pharmacological profile of ursodeoxycholic acid and the first results on its clinical impact are promising. The value of prophylactic therapy with ursodeoxycholic acid must be determined in further studies. [ABSTRACT FROM AUTHOR]

Abstract: Several studies have shown a significant reduction of acute cellular graft rejection in adult liver and kidney graft recipients treated with monoclonal anti-interleukin-2 (IL-2)-receptor antibodies. The mechanism was inhibition of activated T-helper cells by blocking the α-chain (CD25) of the IL-2 receptor. The pilot study described here evaluated the use of basiliximab in pediatric liver transplantation (LTx), which is the first report on its use in children. Fifty-two liver-transplanted children were analyzed in this study. A matched-pair historical control group (n = 26) received cyclosporin A (CsA) and prednisolone, and patients in the basiliximab group (n = 26) were treated with low-dose CsA and basiliximab (after reperfusion and on day 4 post-transplant). The incidences were compared of acute graft rejections, infectious complications, and the adverse effects of immunosuppressive medication within the first 6 months post-transplant. The incidence of acute rejection was significantly higher in the control group (61.5% vs. 11.5%, p = 0.0004). The frequency of infectious complications was similar (46.1% vs. 53.8%). Patients in the basiliximab group showed less arterial hypertension; however, the differences were not statistically significant (30.7% vs. 7.7%, p = 0.07). Nephrotoxicity, hepatotoxicity or neurotoxicity were only seen in the control group (7.7%; 3.8%; 3.8%, respectively). Hence, the use of basiliximab in combination with CsA and steroids in pediatric liver transplant recipients is safe and reduces the incidence of acute graft rejection. Further studies are needed to confirm our preliminary results and to analyze long-term effects on post-transplant lymphoproliferative disease, chronic rejection, and patient survival. [ABSTRACT FROM AUTHOR]

Abstract: The use of mycophenolate mofetil (MMF) in combination with cyclosporin A (CsA) and steroids is well established after kidney transplantation (Tx) in children. A 9-yr-old girl with primary hyperoxaluria type 1 and systemic oxalosis underwent a combined kidney and liver Tx at our institution. The post-operative immunosuppression consisted of CsA, prednisolone, and MMF. Four weeks post-transplant the girl suffered from a severe urinary tract infection caused by Pseudomonas aeruginosa, when the serum immunoglobulin G (IgG) concentration was found to be critically low (< 1.53 g/L). Additionally, there was an isolated B-cell depletion (240/µL) at that time. In the following course, the B-cell count was significantly diminished until the MMF was stopped 13 weeks post-transplant. As a result of the very low serum IgG concentration, intravenous immunoglobulin (IVIG) substitution was necessary. There was no significant loss of immunoglobulins in the ascites and urine and no other medication with possible side-effects on B cells was given. We suggest that MMF can lead to suppressed IgG production by B cells and can cause a defective differentiation into mature B cells. In vitro studies demonstrated these effects of MMF on B cells, but no in vivo cases of this phenomenon have been reported. B-cell counts and serum IgG concentrations returned to normal values after discontinuing the MMF. As we can assume that the observed B-cell dysfunction and depletion were MMF related, we suggest that serum IgG concentrations should be monitored when MMF is used after solid-organ Tx. [ABSTRACT FROM AUTHOR]

Abstract: A retrospective study was conducted to determine the significance of intensive care management on outcome after liver transplantation (LTx) in children. Of 195 transplants performed in 162 children, factors affecting morbidity and mortality were documented during the post-operative intensive care unit (ICU) stay. To assess the gain in experience of ICU management, we compared mean ventilation time and stay in the ICU as well as mortality, incidence of surgical complications, infections, and rejection episodes, during three different time-periods (October 1991–August 1994, September 1994–July 1996, and August 1996–February 1998). The time spent by patients in the ICU (9.7 days vs. 7.9 days vs. 4.7 days, p < 0.001) and time on ventilation (5.2 days vs. 3.1 days vs. 1.2 days, p < 0.001) were significantly reduced over the duration of the study. The overall mortality was 18.0% (n = 30) and 76.7% (n = 23) of these deaths occured during the early post-operative period in the ICU. The incidence of severe surgical complications decreased significantly over time, and the application of intra-operative Doppler ultrasound since 1994 led to detection of 27 correctable vascular complications. The overall incidence of acute cellular rejection episodes in our center was 64.1%: 43.5% of the infectious episodes occured in the ICU (bacterial 70.2%, viral 12.3%, and fungal 17.5%). The main side-effect from immunosuppressive drugs was arterial hypertension in 29% of the patients. We conclude that our efforts to improve intensive care management and monitoring were the key elements in reducing morbidity and mortality after pediatric LTx. [ABSTRACT FROM AUTHOR]

Abstract: Acute graft rejection is one of the most frequent complications after pediatric liver transplantation (LTx). In clinical practice, it is sometimes difficult to differentiate acute cellular graft rejection from other complications because clinical and chemical findings are often non-specific. We therefore investigated the value of cytokine quantification in drained ascites, in addition to quantification of cytokine concentrations of serum, in 30 children in the first 2 weeks after orthotopic liver transplantation (OLT). Six of 30 patients showed acute graft rejection, with rising levels of alanine aminotransferase (ALT) and α-glutathione-S-transferase (α-GST) in serum up to 24 h prior to biopsy-proven rejection. There were no significant elevations of interleukin-2 receptor (IL-2r) and interleukin-6 (IL-6) in serum and ascites. In contrast to these findings, the concentration in ascites of the interleukin-1 receptor antagonist (IL-1ra) increased 48 h before rejection was proven by liver biopsy (p < 0.01, in comparison with the non-rejecting group, n = 24). The IL-1ra concentration in ascites was up to 11-fold higher than in serum during rejection (15.43 vs. 1.38 ng/mL). Two children with early infectious complication showed no significant increase in ascitic IL-1ra concentration. We conclude from these data that quantification of IL-1ra in ascites indicates the start of graft rejection after LTx. As long as abdominal drainage is performed, this non-invasive procedure may be of additional value in differential diagnoses and early diagnosis of rejection. [ABSTRACT FROM AUTHOR]

In primary hyperoxaluria type 1 (PH 1), deficiency or mis-targeting of hepatic alanine glyoxylate aminotransferase (AGT) results in over-production of oxalate and hyperoxaluria, leading to nephrocalcinosis and development of end-stage renal disease (ESRD) in the majority of patients. Renal transplantation (Tx) alone carries a high risk of disease recurrence as the metabolic defect is not cured. Therefore, combined liver/kidney Tx is recommended for patients with ESRD. An alternative approach is to cure PH 1 by pre-emptive isolated liver Tx (PLTx) before ESRD has occurred, but this approach has been carried out only occasionally and there are no uniformly accepted recommendations concerning the timing of this procedure. We report follow-up 3-5.7 yr after performing successful PLTx in four children (at the age of 3-9 yrs) with PH 1 prior to the occurrence of ESRD (glomerular filtration rate [GFR] range 27-98 mL/min/1.73 m2). There was no mortality or long-term morbidity associated with the Tx procedure. Plasma and urinary oxalate levels normalized rapidly within 4 weeks, and renal function did not deteriorate under immunosuppression, even in one patient with advanced chronic renal failure (GFR 27 mL/min/1.73 m⊃) who showed a stable course for more than 5.7 yrs. Although treatment must be individualized in this severe metabolic disorder, and PLTx has to be regarded as an invasive procedure, we consider that PLTx should be offered and considered early in the course of PH 1. PLTx cures the metabolic defect in PH 1 and can help to prevent, or at least delay, the progression to ESRD and systemic oxalosis. [ABSTRACT FROM AUTHOR]

Studies cases of staphylococcal septicemia in children with atopic dermatitis. Clinical manifestations; Predisposing factors; Results of diagnostic procedures; Therapeutic considerations.

Englert C, Ganschow R. Liver transplantation in a child with liver failure due to chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation from the same unrelated living donor. Abstract: We report a case of a six-yr-old boy who developed chronic GVHD of the liver, intestines, and skin following allogeneic hematopoietic SCT. The boy received an allogeneic hematopoietic stem cell transplant at the age of two yr because of early recurrence of ALL. Chimerism analysis showed complete chimerism. In the following year, he developed GVHD despite adequate immunosuppressive therapy. Liver biopsy showed liver GVHD resulting in liver cirrhosis by the age of five yr. LTx was performed with a left liver lobe from the unrelated donor from whom the stem cells had been taken. Immunosuppressive therapy consisted of low-dose steroids and low-dose cyclosporine. The postoperative course was uneventful. Graft function was excellent, and we performed protocol biopsies at seven days and three wk as well as three, six, and nine months after transplantation; none of these showed any signs of rejection or GVHD. Immunosuppressive therapy was discontinued nine months after LTx. Three yr after transplantation, the boy is in good condition with normal graft function. To our knowledge, this is the first report on LTx following allogeneic hematopoietic SCT from the same unrelated living donor. [ABSTRACT FROM AUTHOR]

The sophisticated and expensive treatment modalities of persistent pulmonary hypertension of the newborn (PPHN), such as nitric oxide, are limited in developing countries. Alternative (less expensive) treatments are being sought and bosentan, an oral dual endothelin-1 receptor antagonist, may be an option for the treatment of PPHN. We report our experience of using bosentan in a neonate with severe PPHN. Conclusion: Bosentan may be a useful adjuvant therapy in neonates with PPHN, providing significant improvement in oxygenation, and thus may be particularly useful in the treatment of PPHN in countries with limited resources. [ABSTRACT FROM AUTHOR]