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Background: Liver transplantation is established treatment for children with end-stage liver disease and has a 5-year survival rate of 80% to 85%, even in infants under 12 months. Long-term outcome in nutritional rehabilitation and normal development is unknown. This study aimed to prospectively evaluate growth and psychoneurologic performance of children who undergo liver transplantation in infancy., Methods: Twenty-five infants (18 girls, 7 boys) who underwent liver transplantation at less than 12 months of age (median age, 9 months) were evaluated for 4 years. Growth measurements were expressed as standard deviation scores (SDSs; mean +/- SEM), and psychoneurologic performance was assessed with the unrevised Griffiths Mental Ability Scales (normal range, 80-120)., Results: Four children died during the study (4-year survival, 84%). The children were malnourished before transplantation (SDSs: weight, -1.9 +/- 0.2; midarm muscle area, -0.93 +/- 0.3; midarm fat area, -1.52 +/- 0.3; and height, -0.95 +/- 0.3). Nutritional rehabilitation for all parameters occurred within 12 to 24 months after transplantation, which was most significant for weight (-1.1 +/- 0.2, P = 0.001), midarm muscle area (0.74 +/- 0.3, P = 0.001), and midarm fat area (-0.44 +/- 0.3, P = 0.01). There was some improvement in height (-0.72 +/- 0.3, P = 0.14), which was not significant, although infants who were severely stunted before transplantation (mean height standard deviation score [SDS] -2.46) showed significant catch-up at 1 year after transplantation (mean height SDS -1.2, P = 0.003). Psychoneurologic scores were within normal limits before transplantation and were maintained for the 4-year follow-up period, although individual scores varied during this period. Improved nutritional status was associated with increased muscle bulk and subsequent improvement in motor scores from 90.6 at initial assessment to 97.3 at 4 years (P = 0.28). There was a temporary reduction in social skills and eye-hand coordination in the first year, which may have been an effect of the hospital environment or cyclosporine immunosuppression. Language abilities also regressed during the first year, possibly related to the effect of nasogastric tube feeding in delaying normal speech development., Conclusions: Liver transplantation in infancy has not only a successful outcome but is also associated with long-term catch-up growth and nutrition and maintenance of normal development.

Background: The emergence and spread of vancomycin-resistant Enterococcus faecium (VREF) has presented serious therapeutic difficulties because of the lack of reliably active antibiotics. Quinupristin/dalfopristin is a new injectable streptogramin antibiotic that is active against most strains of VREF. Experience with this agent in adults with VREF infections is well-documented; however, there are few reports of its use in children. We report on eight children with VREF infections who received quinupristin/dalfopristin under a compassionate use protocol., Methods: Quinupristin/dalfopristin was administered according to the manufacturer's recommendations. Clinical and laboratory data were recorded for each patient., Results: The infections treated comprised six cases of bacteremia and two of peritonitis. All patients had serious underlying conditions. Seven patients recovered fully. One patient died, having experienced a relapse of his infection after quinupristin/dalfopristin was discontinued. None of the patients experienced side effects or other adverse events., Conclusion: Quinupristin/dalfopristin was well-tolerated and generally effective in children with infections caused by VREF. There is increasing evidence that it may be more effective than other currently available antibiotics in some such patients.

Background: The critical shortage of size-matched donor organs for infants and small children in need of combined liver and intestinal transplantation has lead to long waiting times and a high risk of dying before transplantation. Utilizing grafts from larger donors could alleviate this problem, but using larger composite grafts in small children has been challenging and unsuccessful in the past., Methods: We conducted a pilot study for evaluating the results of transplanting into small recipients a composite graft (reduced-size liver and whole small bowel, including duodenum and pancreas head) procured from large donors. Liver size reduction was performed ex situ using the extrahilar approach, which leaves the liver hilum untouched. Straightforward implantation of the graft was performed by simple, two-step vascular anastomoses. The preservation of the donor duodenum in continuity with the combined graft avoided the need for biliary reconstruction, thus preserving maximal bowel length for gut continuity restoration in the recipient., Results: Two children, weighing 7.6 and 9.8 kg, respectively, underwent transplantation of a composite graft procured from donors weighing 35 kg. Their waiting time (68 and 97 days, respectively) was shorter compared with our previous experience with conventional techniques. Both are currently alive and well, at home and on full enteral feeds, 15 and 11 months after transplantation, respectively., Conclusion: This new technique has extended the range of possible donors for small candidates waiting for combined grafts and was successful in two patients. It should be considered for small recipients in the future.

Irreversible liver graft failure is a life-threatening complication. We reviewed the first 200 pediatric liver transplantations in Birmingham. Forty-one children developed primary graft failure, 9 of whom developed secondary graft failure. The main indications for graft failure were primary nonfunction (PRNF; 8 patients), vascular complications (VASC; 23 patients), and chronic rejection (CHRE; 19 patients). Thirty-two children underwent retransplantation (ReTx) (21 children received reduced grafts; 11 children, whole hepatic grafts). Patient survival was significantly worse for retransplant recipients compared with children receiving a single graft (63% v 76. 5% actuarial patient survival at 1 year; P <.05). Primary graft 1-year actuarial survival was 74% in first grafts compared with 47% for regrafts (P <.05), but improved with time. The graft 1-year survival rate was 55% for whole grafts and 45% for reduced and/or split grafts in the first 100 grafts compared with 83% and 66% in the second 100 grafts, respectively (P <.01). Emergency ReTx within a month of transplantation was associated with more complications and a worse outcome (1-year survival rate, 37%) compared with patients who underwent ReTx later (1-year survival rate, 72%; P <. 01). The incidence of primary graft failure decreased from 33% in the first 100 grafts to 16% in the second 100 grafts (P <.01), as did the incidence of PRNF, which decreased from 8% to 0% (P <.05). Although the rates of graft failure from VASC decreased from 15% to 8% (P =.2) and CHRE decreased from 11% to 8% (P =.6), neither reached statistical significance. The improved results overall are because of advances in surgical techniques, intensive care management, and graft preservation and refinements in immunosuppression. We conclude that ReTx for a child with primary graft failure is justified.

Small bowel transplantation is reviewed with particular reference to its role in the management of chronic intestinal failure in children. The complications of administering parenteral nutrition and the indications for considering small bowel transplantation are discussed. The unique clinical problems of small bowel transplantation include preservation/reperfusion injury, post operative dysmotility, malabsorption, abnormal permeability especially during rejection episodes, sepsis, the specific rehabilitation needs of the child and long term monitoring of graft function. International records incorporating over 300 transplants world wide: two thirds in children in 31 separate centres, show that results are variable but improving. The biggest centres have a three-year survival of 65% although a learning curve effect is evident is smaller centres. Small bowel transplantation is a complex surgical and medical enterprise, but it has been shown to be an effective means of treating chronic intestinal failure and should be considered in those patients who are experiencing life threatening complications related to the administration of parenteral nutrition.

The hepatic histology and clinical status of 37 children on long-term parenteral nutrition (PN) referred for consideration of small bowel transplantation were determined. Seventy five percent of the children had splenomegaly and plasma bilirubin level of greater than 100 mumol/L. All of 21 children who underwent liver biopsy, had increased fibrosis, but only half had established cirrhosis. Thirty-one children were considered to be in need of transplantation (combined liver and bowel transplant, 29; isolated bowel transplant, 2), but only 13 were stable enough to be placed on the transplant list. Seven out of the thirteen children waiting have died because of lack of size-matched organs, and the overall mortality rate of the 37 children was 70%. The main risk factors for death within 6 months were bilirubin level of greater than 100 mumol/L, splenomegaly, and cirrhosis (P = .01). The natural history of PN-associated liver disease is that of progressive liver failure and death 6 to 12 months after onset of cholestasis, defined as bilirubin level of greater than 100 mumol/L. The development of cirrhosis occurs after the onset of jaundice, so early referral may also permit some children to be offered isolated bowel transplantation, which has better outcome than combined liver and bowel transplantation.

The medical records of 74 neonates dependent on parenteral nutrition for at least 21 days after emergency abdominal surgery (performed between 1988 and 1992) were reviewed respectively. The role of enteral starvation, prematurity, composition and duration of parenteral nutrition, and sepsis in the evolution of parenteral nutrition-related cholestasis was evaluated by multiple regression analysis. The most important factors for cholestasis were low gestational age (median, 34 weeks), early exposure to parenteral nutrition, and sepsis. Episodes of sepsis were associated with a 30% increase in the bilirubin level. Enteral starvation and composition and the duration of parenteral nutrition solutions did not correlate significantly with the development of cholestasis. Prevention of sepsis should be the priority in minimising cholestasis in postsurgical neonates who are dependent on parenteral nutrition.

Twenty two children were evaluated for small bowel transplantation between 1989 and 1994. Eight were unfit for transplantation and died within three months; a raised plasma bilirubin concentration (> 200 mumol/l) predicted death from liver failure within six months (p = 0.0001). The 11 children who were not managed by a multidisciplinary nutritional care team were less well nourished at referral, had more complications with intravenous feeding catheters, and greater early mortality while awaiting transplantation (p < 0.05). It is recommended that children with chronic intestinal failure be referred for assessment early, before liver dysfunction is established.

The aim was to establish the prevalence of pulmonary embolism in 21 children (median age 12 months; range 5-132 months) with central venous lines in situ > 3 months (median 10 months; range 3-47). Twelve-lead electrocardiograms (ECGs) and echocardiograms were analysed in a retrospective study using ECG and echocardiographic criteria for pulmonary embolism-previously established and validated in adult patients- and standard paediatric ECG values as control data. Patients were scored as having definite (n = 7), probable (n = 5), or no pulmonary embolism (n = 9). Overall 57% of ECGs showed abnormalities compatible with pulmonary embolism. In two patients, serial ECGs obtained during an acute cardiorespiratory illness showed cumulative changes diagnostic of pulmonary embolism. Eight of 12 patients with abnormal ECGs had echocardiography; in seven of these (88%) the right ventricular end diastolic diameter was > 2SD above the mean value for age. Twelve of the patients included in this study have died; two died following an acute respiratory illness. There was postmortem evidence of pulmonary thromboembolism in both of the two children for whom necropsy information was available. The data suggest that pulmonary embolism is common in children who have central venous lines in situ for > 3 months. Serial studies are of value in some patients. Pulmonary embolism may compromise the long term survival of children with small bowel failure and preclude consideration for liver and small bowel transplantation.

Mutations of the precore region of hepatitis B virus (HBV) genome have been associated with fulminant and severe chronic hepatitis. However uncertainty remains about the clinical significance and transmissibility of these mutant strains. A point mutation assay (PMA) was developed to identify qualitatively and quantitatively mutations affecting precore amino acids 1 and 28. We have analysed serum samples from six mother-infant pairs where perinatal transmission of HBV has occurred and where the mothers were HBV carriers without detectable serum HBeAg. In three cases fulminant hepatitis developed in the infant, in two cases acute hepatitis resolved, and in one case the infant was immunised and did not become infected. We also examined serum from a healthcare worker, an anti-HBe-seropositive HBV carrier, believed to have transmitted HBV infection to a patient. The PMA results were confirmed in all cases by direct sequencing of polymerase chain reaction (PCR) products using nested and double-nested PCR with primers to the precore and X region. Precore aa28 mutant-type virus was detected in the serum of one mother at the time of delivery of three of her children, two of whom developed fulminant hepatitis. Another mother of an infant with fulminant hepatitis had no precore mutations. In one mother-infant pair a mixed viral population was found; the acute hepatitis B in the infant resolved. The HBV sequence from the healthcare worker was also of aa28 mutant type. No mutations of aa1 were detected in any of the specimens. The study supports the association of precore mutations with some cases of transmission of HBV infection from HBeAg-negative mothers to their infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To review the outcome of liver transplantation in babies aged less than 1 year., Design: Prospective evaluation of survival, clinical complications, and nutritional and developmental status before and one year after liver transplantation., Setting: The Children's Hospital and Queen Elizabeth Hospital, Birmingham., Subjects: All 25 babies who received liver transplantation from January 1989 to December 1992 were included. Median age was 9 months and median weight was 7.0 kg. Seven babies were assessed but were not given transplants because they died while on the waiting list (two) or had severe extrahepatic disease (five)., Results: 24 babies had severe decompensated liver disease and 20 were severely malnourished despite nutritional support. Six babies received a whole liver graft and 19 received a reduction hepatectomy. Postoperative complications included primary nonfunction of the transplanted liver (one baby), hepatic artery thrombosis (two), biliary obstruction (seven), acute and chronic rejection (six), and sepsis (18). Three babies required a second transplant; all survived. Three babies, two of whom presented with fulminant hepatic failure, died. The overall actuarial survival rate (4 months to 4 years) is 88%. Review at 12 months showed a dramatic improvement in growth (p < 0.001) and normal psychosocial development with good quality of life., Conclusion: The improvement in survival rates and quality of life in this group of very sick babies is related not only to the development of reduction hepatectomy but also to advances in medical and nursing expertise. Early referral for liver transplantation is justified even if babies are critically ill.

Collecting complete, timed stool samples for the estimation of faecal fat from infants wearing nappies is difficult. A gravimetric method has been adapted by applying a chloroform/methanol homophasic solvent system to extract lipids from whole soiled nappies. In a study of 22 collections in six infants, no stools were lost and the recovery of lipids was 96%, with results similar to a reference titrimetric method. In addition to total fat, individual lipids were measured using gas-liquid chromatography. The method simplifies stool collection and analysis, is aesthetically more acceptable, and leads to reduced microbial hazards. It also allows the detailed study of excreted lipid species enabling the coefficient of absorption of dietary lipids of various chain lengths to be determined individually.

The first recorded case of beta-blocker overdose complicated by rhabdomyolysis is described.