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M Burdelski

Publications and source records attributed to M Burdelski.

At least 37 records · Page 2Linked to original sources
PubMed2001

Is there still a need for living-related liver transplantation in children?

OBJECTIVE: To assess and compare the value of split-liver transplantation (SLT) and living-related liver transplantation (LRT). SUMMARY BACKGROUND DATA: The concept of SLT results from the development of reduced-size transplantation. A further development of SLT, the in situ split technique, is derived from LRT, which itself marks the optimized outcome in terms of postoperative graft function and survival. The combination of SLT and LRT has abolished deaths on the waiting list, thus raising the question whether living donor liver transplantation is still necessary. METHODS: Outcomes and postoperative liver function of 43 primary LRT patients were compared with those of 49 primary SLT patients (14 ex situ, 35 in situ) with known graft weight performed between April 1996 and December 2000. Survival rates were analyzed using the Kaplan-Meier method. RESULTS: After a median follow-up of 35 months, actual patient survival rates were 82% in the SLT group and 88% in the LRT group. Actual graft survival rates were 76% and 81%, respectively. The incidence of primary nonfunction was 12% in the SLT group and 2.3% in the LRT group. Liver function parameters (prothrombin time, factor V, bilirubin clearance) and surgical complication rates did not differ significantly. In the SLT group, mean cold ischemic time was longer than in the LRT group. Serum values of alanine aminotransferase during the first postoperative week were significantly higher in the SLT group. In the LRT group, there were more grafts with signs of fatty degeneration than in the SLT group. CONCLUSIONS: The short- and long-term outcomes after LRT and SLT did not differ significantly. To avoid the risk for the donor in LRT, SLT represents the first-line therapy in pediatric liver transplantation in countries where cadaveric organs are available. LRT provides a solution for urgent cases in which a cadaveric graft cannot be found in time or if the choice of the optimal time point for transplantation is vital.

Adolescent↗
PubMed2000

Detection and monitoring of intracranial pressure dysregulation in liver failure by ultrasound.

BACKGROUND: Development of elevated intracranial pressure (ICP) in hepatic failure indicates poor prognosis. Its detection by invasive methods poses methodological problems. We applied ultrasound studies of the optic nerves to noninvasively estimated ICP status. METHODS: A total of 22 pediatric patients with hepatic failure were examined by serial B scan ultrasound and followed up clinically. Outcome was scored as survival or death due to multiorgan failure (MOF) or raised ICP. In 18 patients, transplantations were performed. RESULTS: Four patients died before transplantation was possible (raised ICP: n=3, MOF: n=1). After OLT there were 10 survivors and 8 patients died (MOF: n=3, raised ICP: n=5). In 10 patients we found optic nerve sheath diameter (ONSD) above normal limits. Eight patients died, mostly because of raised ICP (n=7). Only 2 of the 10 survivors experienced a transient ONSD increase, steadily normalized after transplantation. Preoperatively, normal ONSD was detected in four of seven patients. The outcome of these four cases was clearly superior (three survivors and one MOF) compared with abnormal pre-OLT ultrasound findings (raised ICP: n=3). CONCLUSION: Patients with poor prognosis related to raised ICP in pediatric liver failure can be identified by ultrasound measurement of ONSD without the disadvantages of invasive procedures. Although the exact intracranial pressure level cannot be deduced from single examinations, ONSD trends can reflect the evolution of ICP in hepatic encephalopathy.

Child, Preschool↗
PubMed2000

Long-term results of pre-emptive liver transplantation in primary hyperoxaluria type 1.

In primary hyperoxaluria type 1 (PH 1), deficiency or mistargeting 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 m2) 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.

Acute Kidney Injury↗
PubMed2000

Intensive care management after pediatric liver transplantation: a single-center experience.

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 occurred 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 occurred 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.

Adolescent↗
PubMed2000

Interleukin-1 receptor antagonist in ascites indicates acute graft rejection after pediatric liver transplantation.

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 nonspecific. 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 alpha-glutathione-S-transferase (alpha-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.

Acute Disease↗
PubMed1999

Hepatic thrombopoietin mRNA levels in acute and chronic liver failure of childhood.

The liver is the main production site of the hormone thrombopoietin (TPO), the major regulator of megakaryopoiesis. To investigate the role of an impaired TPO gene expression in the pathogenesis of thrombocytopenia in pediatric patients suffering from liver failure, we measured hepatic TPO mRNA in children with acute or chronic end-stage liver disease undergoing orthotopic liver transplantation. Tissue samples for RNA extraction were obtained from 12 children with compensated cirrhosis (CC), 22 children with decompensated cirrhosis (DC), and 9 children with acute liver failure (ALF). TPO mRNA was quantitated by competitive polymerase chain reaction (PCR), following reverse transcription (RT). Furthermore, in 9 children with ALF, serum TPO levels were measured by enzyme-linked immunosorbent assay before and 10 to 14 days after liver transplantation. The hepatic TPO mRNA concentration was highest in children with CC (median, 50.9 amol/micrograms RNA). This value was significantly reduced in children with DC (30.2 amol/micrograms RNA) or ALF (13.8 amol/micrograms RNA). Children with ALF (139 cells/nL) or DC (200 cells/nL) had lower platelet counts than children with CC (368 cells/nL). The serum TPO concentration increased from a median of 156 pg/mL in patients with ALF to 547 pg/mL after liver transplantation. These results show that the thrombocytopenia in children with liver failure is associated with reduced hepatic TPO mRNA levels. It remains to be investigated whether the serum TPO level and platelet counts are markers for the severity of liver damage that may serve as a prognostic indicator.

Adolescent↗
PubMed1999

Liver transplantation in children: long-term outcome and quality of life.

UNLABELLED: Liver transplantation has become a standard therapy in acute and chronic liver failure. Since 1968, 2554 paediatric patients receiving a liver transplant have been registered in the European Liver Transplant Registry (ELTR). Compared with 22,600 total transplants registered in the ELTR over the same period of time this means that about 10% of all liver transplants performed in Europe concern paediatric recipients, aged from 0 to 15 years. The indications in the paediatric population differ significantly from those of adult patients: More than 50% of patients suffer from cholestatic disorders, followed by hepatic based metabolic disorders, acute liver failure, non-cholestatic cirrhosis and liver tumours. The results of liver transplantation in paediatric patients have improved remarkably since the early 1980s. In 1997 a survival rate of 80% is almost the international standard. This improvement is due to the use of better immunosuppressive agents such as cyclosporin A and tacrolimus, followed by improvement in surgical techniques and finally by improvement in intensive care, better diagnostic tools for viral, bacterial and fungal infections and corresponding appropriate therapies. Quality of life as a measure of transplant results has not been sufficiently studied. The majority of paediatric liver transplant recipients has a good quality of life; only 10% suffer from significant morbidity. The impact of pretransplant damage to other organs such as brain, kidneys, bone and lungs and the influence of immunosuppression on somatic growth, neurological development, infection and metabolic balance are subjects of increasing concern. CONCLUSION: The results available today show convincing evidence that liver transplantation is a therapeutic option in otherwise fatal hepatic disorders. Much effort, however, has to be made in order to achieve further improvements by increasing our knowledge of the pathophysiology of both pre- and posttransplant conditions.

Adolescent↗
PubMed1999

[Mesentericoportal Rex-shunt as a treatment for extrahepatic portal vein thrombosis].

The most common cause of portal hypertension in children with healthy livers is the prehepatic block. A 7-year-old girl had presented with portal vein thrombosis after umbilical vein catheterization in the newborn period. She suffered from collateral circulation with recurrent bleeding episodes due to esophageal varices (stage III-IV) and developed hypersplenism. Ultrasound demonstrated an open branch of the left portal vein. Direct splenoportography showed an open and communicating superior mesenteric vein. Liver biopsy was normal. An autologous left jugular vein graft was used to create a bypass from the superior mesenteric vein to the umbilical portion of the left intrahepatic portal vein (mesentericoportal Rex-shunt). Postoperatively, normal intrahepatic portal vein flow was demonstrated by ultrasound. After 2 years of follow-up, the patient is asymptomatic with no signs of portal hypertension. In contrast to classic portosystemic shunt operations, this bypass restores physiological portal vein flow, thus avoiding the possible consequences of longterm portosystemic shunting and low-grade encephalopathy.

Child↗
PubMed1999

Living-donor liver transplantation in children.

INTRODUCTION: Living-related liver transplantation (LRLT) for paediatric recipients was developed 10 years ago to overcome the high mortality on the waiting list. Since then, liver transplantation programs around the world have begun to employ this method with encouraging results. This review describes the actual status of LRLT in children, aspects of donor selection, donor risks, and surgical technique, as well as an update of the results of the leading LRLT programs in the world. The donor operation has matured to the stage of being a standardised, teachable procedure with a low risk of morbidity or mortality. However, there is a percentage of potential donations that have to be declined for medical or socio-psychological reasons. LRLT provides grafts of excellent quality and short cold ischemic times. A major advantage is the fact that the optimal moment for the transplantation procedure can be chosen. Together with split-liver techniques, LRLT has a positive effect on the general situation of the paediatric waiting list for liver transplantation, with a reduction of pre-transplant mortality to nearly 0%.

Child↗
PubMed1999

High-performance liquid chromatography-coulometric electrochemical detection of ubiquinol 10, ubiquinone 10, carotenoids, and tocopherols in neonatal plasma.

A micromethod for the rapid simultaneous determination of several lipophilic antioxidants in plasma from newborn infants is presented. Because only 5 microliters of plasma is required, the procedure lends itself for repetitive use in very immature infants at risk for developing so-called "oxygen radical diseases of the premature." The method allows continuous monitoring of antioxidants in such patients and can easily be combined with monitoring other parameters of interest in this context. Reuse of blood samples taken routinely for the determination of hematocrit and bilirubin concentration is possible, reducing the blood volume required to be taken for the oxygen radical-related studies to virtually zero.

Antioxidants↗
PubMed1999

Uncommon missense and splice mutations and resulting biochemical phenotypes in German patients with X-linked chronic granulomatous disease.

Chronic granulomatous disease is an inherited disease characterized by the inability of phagocytes to generate normal amounts of superoxide, leaving patients susceptible to opportunistic, life-threatening infections. In the majority of cases, cytochrome b558 is absent in the X-chromosomal form of CGD. However, the neutrophils from six of nine X-linked CGD patients, reported here, expressed normal or decreased amounts of this cytochrome and are referred to as "variant" forms. In three of these six variant patients, a roughly proportional decrease in cytochrome b558 expression and production of H2O2 were found. In two cases this phenotype could be well explained by special splice mutations, whereas in the third case it was caused by a missense mutation, predicting Ser 193-->Phe. In the other three variant patients, cytochrome b558 expression and H2O2 production were clearly disproportionate as the generation of H2O2 was much more decreased than cytochrome expression. Missense mutations also were found in these cases. One of these mutations, predicting Leu 546-->Pro and affecting the putative nicotinamide adenine dinucleotide phosphate binding site, led to normal levels of cytochrome b558 expression and reduced H2O2 production. In the other two mutations, predicting Pro 339-->His and His 338-->Tyr, the putative flavin adenine dinucleotide binding site was affected. This could explain the corresponding uncommon phenotypes, characterized by zero or trace amounts of H2O2 production and the expression of relatively high amounts of nonfunctional or low functional cytochrome b558, respectively. The only missense mutation found that prevented the expression of any cytochrome b558 was caused by a predicted His 222-->Arg exchange in one of the three classic cases. The two other classic phenotypes were caused by splice mutations.

Adolescent↗
PubMed1998

Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis.

Class III multidrug resistance (MDR) P-glycoproteins (P-gp), mdr2 in mice and MDR3 in man, mediate the translocation of phosphatidylcholine across the canalicular membrane of the hepatocyte. Mice with a disrupted mdr2 gene completely lack biliary phospholipid excretion and develop progressive liver disease, characterized histologically by portal inflammation, proliferation of the bile duct epithelium, and fibrosis. This disease phenotype is very similar to a subtype of progressive familial intrahepatic cholestasis, hallmarked by a high serum gamma-glutamyltransferase (gamma-GT) activity. We report immunohistochemistry for MDR3 P-gp, reverse transcription-coupled PCR sequence analysis, and genomic DNA analysis of MDR3 from two progressive familial intrahepatic cholestasis patients with high serum gamma-GT. Canalicular staining for MDR3 P-gp was negative in liver tissue of both patients. Reverse transcription-coupled PCR sequencing of the first patient's sequence demonstrated a homozygous 7-bp deletion, starting at codon 132, which results in a frameshift and introduces a stop codon 29 codons downstream. The second patient is homozygous for a nonsense mutation in codon 957 (C --> T) that introduces a stop codon (TGA). Our results demonstrate that mutations in the human MDR3 gene lead to progressive familial intrahepatic cholestasis with high serum gamma-GT. The histopathological picture in these patients is very similar to that in the corresponding mdr2(-/-) mouse, in which mdr2 P-gp deficiency induces complete absence of phospholipid in bile.

ATP Binding Cassette Transporter, Subfamily B↗