Nutritional support in children with end-stage liver disease : a randomized crossover trial of a branched-chain amino acid supplement

Malnutrition is common in children with end-stage liver disease (ESLD) awaiting orthotopic liver transplantation (OLT), and nutritional support is assuming an important role in preoperative management. To evaluate preoperative nutritional therapy, 19 children (median age 1.25 y) with ESLD awaiting OLT were prospectively studied. Two high-energy, isoenergetic and isonitrogenous nutritional formulations delivered nasogastrically were compared: a branched-chain amino acid (BCAA)-enriched semielemental formulation and a matched standard semielemental formulation. Twelve of 19 patients completed a randomized controlled study before OLT and 10 of 19 completed a full crossover study. Improvements in weight and height occurred during the BCAA supplements, with no statistical change on the standard formulation. Significant increases in total body potassium, midupper arm circumference, and subscapular skinfold thickness occurred during the BCAA supplements, whereas no significant changes occurred during the standard formulation period. Significantly fewer albumin infusions were required during the BCAA supplement. These findings suggest that BCAA-enriched formulas have advantages over standard semielemental formulas in improving nutritional status in children with ESLD. and are deserving of wider application and study.

The nature of malnutrition in children with end-stage liver disease awaiting orthotopic liver transplantation

To evaluate malnutrition in chronic liver disease, and its relationship to nutrient deficiencies and hepatic dysfunction. 27 children with end-stage liver disease were studied. Mean protein-energy intakes were 70% of recommended daily intakes. The patients were underweight and stunted with reduced mean triceps and subscapular skinfold thicknesses and midupper arm circumference. Mean total body potassium was only 63 ± 18% of that expected for age and sex. Deficiency of essential fatty acids (32%), and low concentrations of fat-soluble vitamins (A, 92%; E, 32%), iron (32%), zinc (42%), and selenium (13%) were common. Serum ammonia concentrations were raised in all patients, and increased methionine, tyrosine, and glutamic acid, and reduced glutamine concentrations were noted. There was no correlation between the degree of malnutrition and the degree of liver synthetic function, the degree of cholestasis, or the degree of liver injury. We suggest that potentially correctable factors in addition to liver failure (eg, inadequate absorbed intake) were important determinants of malnutrition in these patients.

Malnutrition in children with chronic liver disease accepted for liver transplantation : clinical profile and effect on outcome

The nutritional profiles of 37 children (aged 0.5-14.0 years) with chronic liver disease at the time of acceptance for orthotopic liver transplantation (OLTP) have been evaluated using clinical, biochemical and body composition methods. Nutritional progress while waiting for a donor has been related to outcome, whether transplanted or not. At the time of acceptance, most children were underweight (mean standard deviation (s.d.) weight = -1.4 ± 0.2) and stunted (mean s.d. height = - 2.2 ± 0.4), had low serum albumin (27/35) and had reduced body fat and depleted body cell mass (measured by total body potassium - mean % expected for age = 58 ± 5%, n = 15). Mean ad libitum nutrient intake was 63 ± 5% of recommended daily intake (RDI). Those who died while waiting (n = 8) had significantly lower mean initial s.d. weight compared with those transplanted. The overall actuarial 1 year survival of those who were transplanted (mean waiting time = 75 days) was 81% but those who were initially well nourished (s.d. weight >-1.0) had an actuarial 1 year survival of 100%. There were no significant differences in actuarial survival in relationship to age, type of transplant (whole liver or segmental), liver biochemistry or the presence or absence of ascites. Of the total group accepted for OLTP, whether transplanted or not, the overall 1 year survival for those who were relatively well nourished was 88% and for those undernourished (initial s.d. weight <-1.0) was 38% (P<0.003). Declining nutritional status during the waiting period also adversely affected outcome. We conclude that malnutrition and/or declining nutritional status is a major factor adversely affecting survival in children awaiting OLTP. In transplant units where waiting time is greater than 40 days, earlier referral, prioritization of cases and the use of adult donor livers may reduce this risk and efforts to maintain or improve nutritional status deserve further study.

Optimal sign tests for data from ranked set samples

This paper considers the one-sample sign test for data obtained from general ranked set sampling when the number of observations for each rank are not necessarily the same, and proposes a weighted sign test because observations with different ranks are not identically distributed. The optimal weight for each observation is distribution free and only depends on its associated rank. It is shown analytically that (1) the weighted version always improves the Pitman efficiency for all distributions; and (2) the optimal design is to select the median from each ranked set.

Survival, growth and quality of life in children after orthotopic liver transplantation: A 5 year experience

The aims of this study were to investigate outcome and to evaluate areas of potential ongoing concern after orthotopic liver transplantation (OLT) in children. Actuarial survival in relation to age and degree of undernutrition at the time of OLT was evaluated in 53 children (age 0.58-14.2 years) undergoing OLT for endstage liver disease. Follow-up studies of growth and quality of life were undertaken in those with a minimum follow-up period of 12 months (n = 26). The overall 3 year actuarial survival was 70%. Survival rates did not differ between age groups (actuarial 2 year survival for ages <1, 1-5 and >5 years were 70, 70 and 69% respectively) but did differ according to nutritional status at OLT (actuarial 2 year survival for children with Z scores for weight <-1 was 57%, >-1 was 95%; P = 0.004). Significant catch-up weight gain was observed by 18 months post-transplant, while height improved less rapidly. Quality of life (assessed by Vineland Adaptive Behaviour Scales incorporating socialization, daily living skills, communication and motor skills) was good (mean composite score 91 ± 19). All school-aged children except one were attending normal school. Two children had mild to moderate intellectual handicap related to post-operative intracerebral complications. Satisfactory long-term survival can be achieved after OLT in children regardless of age but the importance of pre-operative nutrition is emphasized. Survivors have an excellent chance of a good quality of life and of satisfactory catch-up weight gain and growth.

Pre-operative nutritional support in children with end-stage liver disease accepted for liver transplantation: An approach to management

Pre-operative nutritional support was studied in 28 children with end-stage liver disease awaiting orthotopic liver transplantation. Nasogastric supplemental administration of a standard semi-elemental enteral nutritional formula was compared with a similar formula enriched with branched chain amino acids, and with a group receiving oral nutrition only. The duration of treatment in all groups was similar (mean 90 days). Energy intakes in the supplemented groups were 120-150% of recommended daily intakes (RDI), whereas ad libitum intakes in the oral group ranged 58-100% RDI. A significant improvement in mean Z-score for body weight (denoting catch-up) was noted only in those children who received nasogastric supplements enriched with branched-chain amino acids. The standard enterally-fed group maintained their body weight and Z-scores did not change significantly. In contrast, body weight Z-scores in those fed orally declined significantly. Nutritional supportive therapy of malnourished children with end-stage liver disease can minimize or improve nutritional status in children awaiting liver transplantation. The use of nutritional formulae rich in branche-chain amino acids may have nutritional advantages in children with chronic liver disease which require further study and evaluation.

The Queensland liver transplant programme: The first two years

Orthotopic liver transplantation began in Brisbane in January 1985. During the first two years of the programme an assessment committee evaluated 55 patients (38 adults, 17 children). Patients were either accepted for transplantation, rejected as unsuitable or deferred for elective reassessment. All of the 10 adults who were rejected for transplantation because they had 'too advanced' disease died within four months of assessment. Six children who were accepted for transplantation died before a suitable donor liver could be found. In the first two years, 21 orthotopic liver transplantations were performed on 18 patients (adults, 13 patients; children, five patients). Fifteen of 21 grafts were procured from within Queensland. Twelve (67%) patients are alive at three to 23 months and all have been discharged from hospital. Deaths in adults were due to sepsis (three patients), aspiration pneumonitis (one patient), rejection and hepatic artery thrombosis (one patient) and the recurrence of a hepatocellular carcinoma five months after discharge from hospital (one patient). Two patients underwent a second transplantation procedure because of chronic rejection at four months and at 11 months, respectively, after the initial operation. One patient received a second transplant for primary graft failure at four days after the operation. A scoring system which considered the presence of pre-operative patient factors, such as coma, ascites, malnutrition and previous abdominal surgery, partly predicted the operative blood loss and patient survival. In conclusion, orthotopic liver transplantation is being performed in Australia with survival rates that are comparable with those of established overseas units.

Liver transplantation in children: Experience with the development of an Australian pilot programme. The Queensland Liver Transplantation Programme

Children with end-stage liver disease now form a major sub-group of patients considered suitable for liver transplantation (ltp), and enjoy better survival statistics after transplantation than do adults. Since June 1984, a paediatric ltp programme has been developed in Brisbane with an initial working relationship and ongoing close links with two USA centres (Pittsburgh, and the UCLA Medical Center). Fourteen children with end-stage liver disease have been referred to the Queensland Liver Transplantation Programme for formal assessment. Following frank, informed discussion with their parents, 10 of these children were offered the option of ltp. During the transition stage, two infants with biliary atresia were referred to UCLA at their parents' request and, subsequently, eight children aged from 9 months to 6 years have been placed on a transplant candidacy list in Brisbane. A donor procurement team with access to a Queensland Government jet has been available to cover all mainland States except Western Australia. Six of the children have now had orthotopic ltp (two children at the UCLA Medical Center; four children at the Royal Children's Hospital, Brisbane). One UCLA patient died with a non-functioning graft, and one Brisbane patient died 5 weeks post-transplant with rejection, hepatic artery thrombosis and sepsis. The other four children are alive and well, three with normal liver function and one with unexplained intrahepatic cholestasis, during the 1-20 month follow-up to date. Three further children have died of their liver disease without a donor of an appropriate blood group and size being found, and one patient still awaits a suitable donor. The experience of these authors suggests that ltp is a major advance in the treatment of paediatric liver disease, and that the procedure can be carried out successfully in Australia with initial results comparable with leading overseas centres. The procedure requires the full array of services of a major paediatric tertiary care facility, an intensive team effort with awareness of the special needs of children, and a widespread procurement capability. A major problem for Australia is the procurement of sufficient numbers of optimal paediatric donor livers.

When using small samples to evaluate hydrocarbon reservoirs, proceed with caution

Small-angle neutron scattering (SANS) and ultra-small angle neutron scattering (USANS) with contrast matching techniques (Melnichenko and others, 2012) were used to investigate size distribution and gas accessibility in pores in an approximately 10.6 cm long Mississippian Barnett Shale butt core from the Fort Worth Basin, Texas, USA. SANS and USANS measurements record scattering from all pores, both open and closed, in the size range 10nm - ~10 μ. The techniques can also be used to determine the material that contains pores and the number of pores as a function of size. By injecting deuterated methane gas (CD4) at contrast matching pressure it is possible to distinguish which pores are accessible, or open, to fluids and which ones are not.

Association study of the dystrobrevin-binding gene with schizophrenia in Australian and Indian samples

Numerous studies have reported association between variants in the dystrobrevin binding protein 1 (dysbindin) gene (DTNBP1) and schizophrenia. However, the pattern of results is complex and to date, no specific risk marker or haplotype has been consistently identified. The number of single nucleotide polymorphisms (SNPs) tested in these studies has ranged from 5 to 20. We attempted to replicate previous findings by testing 16 SNPs in samples of 41 Australian pedigrees, 194 Australian cases and 180 controls, and 197 Indian pedigrees. No globally significant evidence for association was observed in any sample, despite power calculations indicating sufficient power to replicate several previous findings. Possible explanations for our results include sample differences in background linkage disequilibrium and/or risk allele effect size, the presence of multiple risk alleles upon different haplotypes, or the presence of a single risk allele upon multiple haplotypes. Some previous associations may also represent false positives. Examination of Caucasian HapMap phase II genotype data spanning the DTNBP1 region indicates upwards of 40 SNPs are required to satisfactorily assess all nonredundant variation within DTNBP1 and its potential regulatory regions for association with schizophrenia. More comprehensive studies in multiple samples will be required to determine whether specific DTNBP1 variants function as risk factors for schizophrenia.

Monitoring exposure to polycyclic aromatic hydrocarbons in an Australian population using pooled urine samples

Integrated exposure to polycyclic aromatic hydrocarbons (PAHs) can be assessed through monitoring of urinary mono-hydroxylated PAHs (OH-PAHs). The aim of this study was to provide the first assessment of exposure to PAHs in a large sample of the population in Queensland, Australia including exposure to infant (0-4. years). De-identified urine specimens, obtained from a pathology laboratory, were stratified by age and sex, and pooled (n. =. 24 pools of 100) and OH-PAHs were measured by gas chromatography-isotope dilution-tandem mass spectrometry. Geometric mean (GM) concentrations ranged from 30. ng/L (4-hydroxyphenanthrene) to 9221. ng/L (1-naphthol). GM of 1-hydroxypyrene, the most commonly used PAH exposure biomarker, was 142. ng/L. The concentrations of OH-PAHs found in this study are consistent with those in developed countries and lower than those in developing countries. We observed no association between sex and OH-PAH concentrations. However, we observed lower urinary concentrations of all OH-PAHs in samples from infants (0-4. years), children (5-14. years) and the elderly (>. 60. year old) compared with samples from other age groups (15-29, 30-44 and 45-59. years) which may be attributed to age-dependent behaviour-specific exposure sources.