Physical activity cost in children following an acquired brain injury : a comparative study

Background: Alterations in energy expenditure during activity post head injury has not been investigated due primarily to the difficulty of measurement. Objective: The aim of this study was to compare energy expenditure during activity and body composition of children following acquired brain injury (ABI) with data from a group of normal controls. Design: Energy expenditure was measured using the Cosmed K4b2 in a group of 15 children with ABI and a group of 67 normal children during rest and when walking and running. Mean number of steps taken per 3 min run was also recorded and body composition was measured. Results: The energy expended during walking was not significantly different between both groups. A significant difference was found between the two groups in the energy expended during running and also for the number of steps taken as children with ABI took significantly less steps than the normal controls during a 3 min run. Conclusions: Children with ABI exert more energy per activity than healthy controls when controlled for velocity or distance. However, they expend less energy to walk and run when they are free to choose their own desirable, comfortable pace than normal controls. © 2003 Elsevier Ltd. All rights reserved.

Genetic, functional, and histopathological evaluation of two C-terminal BRCA1 missense variants

Background: The vast majority of BRCA1 missense sequence variants remain uncharacterised for their possible effect on protein expression and function, and therefore are unclassified in terms of their pathogenicity. BRCA1 plays diverse cellular roles and it is unlikely that any single functional assay will accurately reflect the total cellular implications of missense mutations in this gene. Objective: To elucidate the effect of two BRCA1 variants, 5236G>C (G1706A) and 5242C>A (A1708E) on BRCA1 function, and to survey the relative usefulness of several assays to direct the characterisation of other unclassified variants in BRCA genes. Methods and Results: Data from a range of bioinformatic, genetic, and histopathological analyses, and in vitro functional assays indicated that the 1708E variant was associated with the disruption of different cellular functions of BRCA1. In transient transfection experiments in T47D and 293T cells, the 1708E product was mislocalised to the cytoplasm and induced centrosome amplification in 293T cells. The 1708E variant also failed to transactivate transcription of reporter constructs in mammalian transcriptional transactivation assays. In contrast, the 1706A variant displayed a phenotype comparable to wildtype BRCA1 in these assays. Consistent with functional data, tumours from 1708E carriers showed typical BRCA1 pathology, while tumour material from 1706A carriers displayed few histopathological features associated with BRCA1 related tumours. Conclusions: A comprehensive range of genetic, bioinformatic, and functional analyses have been combined for the characterisation of BRCA1 unclassified sequence variants. Consistent with the functional analyses, the combined odds of causality calculated for the 1706A variant after multifactorial likelihood analysis (1:142) indicates a definitive classification of this variant as "benign". In contrast, functional assays of the 1708E variant indicate that it is pathogenic, possibly through subcellular mislocalisation. However, the combined odds of 262:1 in favour of causality of this variant does not meet the minimal ratio of 1000:1 for classification as pathogenic, and A1708E remains formally designated as unclassified. Our findings highlight the importance of comprehensive genetic information, together with detailed functional analysis for the definitive categorisation of unclassified sequence variants. This combination of analyses may have direct application to the characterisation of other unclassified variants in BRCA1 and BRCA2.

Measured and predicted total body water in children with myelomeningocele

Objective: Children with myelomeningocele (MMC) have an altered body composition and an atypical distribution of total body water (TBW). The aim of the present study was to determine the accuracy of current predictive equations, based on bioelectrical impedance analysis (BIA), in determining TBW when compared with measured TBW using deuterium dilution. Methods: Fourteen children with MMC were measured for whole body BIA and TBW (using deuterium dilution and the Plateau method). Total body water was predicted using equations based on the resistance and characteristic frequency from BIA measurements and heights of subjects. Results: The mean measured TBW was 15.46 ± 8.28 L and the mean predictions for TBW using equations based on the resistance and characteristic frequency from BIA measurements and heights of subjects were 18.29 ± 8.41 L, 17.72 ± 11.42 L and 12.51 ± 7.59 L, respectively. The best correlation was found using characteristic frequency. The limits of agreement between measured and predicted TBW values using Bland-Altman analysis were large. Conclusions: The present study suggests that the prediction of TBW in children with MMC can be made accurately using the equation of Cornish et al. based on BIA measurements of characteristic frequency.

Body composition and components of energy expenditure in children with end-stage liver disease

Background: Better understanding of body composition and energy metabolism in pediatric liver disease may provide a scientific basis for improved medical therapy aimed at achieving optimal nutrition, slowing progression to end-stage liver disease (ESLD), and improving the outcome of liver transplantation. Methods: Twenty-one children less than 2 years of age with ESLD awaiting liver transplantation and 15 healthy, aged-matched controls had body compartment analysis using a four compartment model (body cell mass, fat mass, extracellular water, and extracellular solids). Subjects also had measurements of resting energy expenditure (REE) and respiratory quotient (RQ) by indirect calorimetry. Nine patients and 15 control subjects also had measurements of total energy expenditure (TEE) using doubly labelled water. Results: Mean weights and heights were similar in the two groups. Compared with control subjects, children with ESLD had higher relative mean body cell mass (33 ± 2% vs 29 ± 1% of body weight, P < 0.05), but had similar fat mass, extracellular water, and extracellular solid compartments (18% vs 20%, 41% vs 38%, and 7% vs 13% of body weight respectively). Compared with control subjects, children with ESLD had 27% higher mean REE/body weight (0.285 ± 0.013 vs 0.218. ± 0.013 mJ/kg/24h, P < 0.001), 16% higher REE/unit cell mass (P < 0.05); and lower mean RQ (P < 0.05). Mean TEE of patients was 4.70 ± 0.49 mJ/24h vs 3.19 ± 0.76 in controls, (P < 0.01). Conclusions: In children, ESLD is a hypermetabolic state adversely affecting the relationship between metabolic and non-metabolic body compartments. There is increased metabolic activity within the body cell mass with excess lipid oxidation during fasting and at rest. These findings have implications for the design of appropriate nutritional therapy.

Acute liver failure in children : a regional experience

Objective: To review the outcome of acute liver failure (ALF) and the effect of liver transplantation in children in Australia. Methodology: A retrospective review was conducted of all paediatric patients referred with acute liver failure between 1985 and 2000 to the Queensland Liver Transplant Service, a paediatric liver transplant centre based at the Royal Children's Hospital, Brisbane, that is one of three paediatric transplant centres in Australia. Results: Twenty-six patients were referred with ALF. Four patients did not require transplantation and recovered with medical therapy while two were excluded because of irreversible neurological changes and died. Of the 20 patients considered for transplant, three refused for social and/or religious reasons, with 17 patients listed for transplantation. One patient recovered spontaneously and one died before receiving a transplant. There were 15 transplants of which 40% (6/15) were < 2 years old. Sixty-seven per cent (10/15) survived > 1 month after transplantation. Forty per cent (6/15) survived more than 6 months after transplant. There were only four long term survivors after transplant for ALF (27%). Overall, 27% (6/22) of patients referred with ALF survived. Of the 16 patients that died, 44% (7/16) were from neurological causes. Most of these were from cerebral oedema but two patients transplanted for valproate hepatotoxicity died from neurological disease despite good graft function. Conclusions: Irreversible neurological disease remains a major cause of death in children with ALF. We recommend better patient selection and early referral and transfer to a transplant centre before onset of irreversible neurological disease to optimize outcome of children transplanted for ALF.

Comparison of the Cosmed K4 b2 and the Deltatrac II™ metabolic cart in measuring resting energy expenditure in adults

Background and Aims: The objective of the study was to compare data obtained from the Cosmed K4 b2 and the Deltatrac II™ metabolic cart for the purpose of determining the validity of the Cosmed K4 b2 in measuring resting energy expenditure. Methods: Nine adult subjects (four male, five female) were measured. Resting energy expenditure was measured in consecutive sessions using the Cosmed K4 b2, the Deltatrac II™ metabolic cart separately and the Cosmed K4 b2 and Deltatrac II™ metabolic cart simultaneously, performed in random order. Resting energy expenditure (REE) data from both devices were then compared with values obtained from predictive equations. Results: Bland and Altman analysis revealed a mean bias for the four variables, REE, respiratory quotient (RQ), VCO2, VO2 between data obtained from Cosmed K4 b2 and Deltatrac II™ metabolic cart of 268 ± 702 kcal/day, -0.0±0.2, 26.4±118.2 and 51.6±126.5 ml/min, respectively. Corresponding limits of agreement for the same four variables were all large. Also, Bland and Altman analysis revealed a larger mean bias between predicted REE and measured REE using Cosmed K4 b2 data (-194±603 kcal/day) than using Deltatrac™ metabolic cart data (73±197 kcal/day). Conclusions: Variability between the two devices was very high and a degree of measurement error was detected. Data from the Cosmed K4 b2 provided variable results on comparison with predicted values, thus, would seem an invalid device for measuring adults. © 2002 Elsevier Science Ltd. All rights reserved.

Osteoclast formation from circulating precursors in osteoporosis

Objective: An imbalance between bone formation and bone resorption is thought to underlie the pathogenesis of reduced bone mass in osteoporosis. Bone resorption is carried out by osteoclasts, which are formed from marrow-derived cells that circulate in the monocyte fraction. Ihe aim of this study was to determine the role of osteoclast formation in the pathogenesis of bone loss in osteoporosis. Methods: The proportion of circulating osteoclast precursors and their relative sensitivity to the osteoclastogenic effects of M-CSF, 1,25(OH)2D3 and RANKL were assessed in primary osteoporosis patients and normal controls. Results: Although there was no difference in the number of circulating osteoclast precursors in osteoporosis patients and normal controls, osteoclasts formed from osteoporosis patients exhibited substantially increased resorptive activity relative to normal controls. Although no increased sensitivity to the osteoclastogenic effects of 1,25(OH)2D3 or M-CSF was noted, increased bone resorption was found in osteoporosis peripheral blood mononuclear cell (PBMC) cultures to which these factors were added. Conclusion: Our findings suggest that osteoclast functional activity rather than formation is increased in primary involutional osteoporosis and that dexamethasone acts to increase osteoclast formation.

Energy expenditure and the body cell mass in cystic fibrosis

Poor nutritional status in patients with cystic fibrosis (CF) is associated with severe lung disease, and possible causative factors include inadequate intake, malabsorption, and increased energy requirements. Body cell mass (which can be quantified by measurement of total body potassium) provides an ideal standard for measurements of energy expenditure. The aim of this study was to compare resting energy expenditure (REE) in patients with CF with both predicted values and age-matched healthy children and to determine whether REE was related to either nutritional status or pulmonary function. REE was measured by indirect calorimetry and body cell mass by scanning with total body potassium in 30 patients with CF (12 male, mean age = 13.07 ± 0.55 y) and 18 healthy children (six male, mean age = 12.56 ± 1.25 y). Nutritional status was expressed as a percentage of predicted total body potassium. Lung function was measured in the CF group by spirometry and expressed as the percentage of predicted forced expiratory volume in 1 s. Mean REE was significantly increased in the patients with CF compared with healthy children (119.3 ± 3.1% predicted versus 103.6 ± 5% predicted, P < 0.001) and, using multiple regression techniques, REE for total body potassium was significantly increased in patients with CF (P = 0.0001). There was no relation between REE and nutritional status or pulmonary disease status in the CF group. In conclusion, REE is increased in children and adolescents with CF but is not directly related to nutritional status or pulmonary disease.

Changes in body composition in adolescents with anorexia nervosa. Comparison of bioelectrical impedance analysis and total body potassium

Patients with anorexia nervosa (AN) have low body weight, depleted fat stores, and reduced muscle mass. Both total body potassium (TBK) and bioelectrical impedance analysis (BIA) have been used to measure the body composition of these patients.1–4 Whereas TBK accurately measures body cell mass, the metabolically active compartment of the body, whole body potassium counters are expensive and not readily available. The purpose of this study was to investigate the potential of multiple frequency BIA (MFBIA) to monitor changes in body compartments in patients with AN.

Growth hormone resistance and somatomedins in children with end-stage liver disease awaiting transplantation

Background: The success of orthotopic liver transplantation as treatment for end-stage liver disease has prompted investigation of strategies to maintain or improve nutrition and growth in children awaiting transplantation, because malnutrition is an adverse prognostic factor. The purpose of this study was to evaluate the effect of recombinant human growth hormone therapy on body composition and indices of liver function in patients awaiting transplant. Methods: The study was designed as a placebo- controlled, double-blind, crossover trial. Patients received 0.2 U/kg growth hormone, subcutaneously, or placebo daily for 28 days during two treatment periods, separated by a 2-week washout period. Ten patients (mean age, 3.06 ± 1.15 years; range, 0.51-11.65 years, five men), with extrahepatic biliary atresia (n = 8) or two with Alagille's syndrome (n = 2), with end-stage liver disease, completed the trial while awaiting orthotopic liver transplantation. Height, weight, total body potassium, total body fat, resting energy expenditure, respiratory quotient, hematologic and multiple biochemical profile, number of albumin infusions, insulin-like growth factor-1 and 1, growth hormone binding protein (GHBP), and insulin-like growth factor binding protein-1 (IGFBP-1) and insulin-like growth factor binding protein (IGFBP-3) were measured at the beginning and end of each treatment period. Results: Growth hormone treatment was associated with a significant decline in serum bilirubin (-34.6 ± 16.5 μmol/l vs. 18.2 ± 11.59 μmol/l; p < 0.02) but there was no significant effect on any anthropometric or body composition measurements, or on any biochemical or hematologic parameters. Conclusions: These children with end-stage liver disease displayed growth hormone resistance, particularly in relation to the somatomedin axis. Exogenous growth hormone administration may be of limited value in these patients

Colonoscopy preparation in children: Safety, efficacy, and tolerance of high- versus low-volume cleansing methods

Background: The use of large-volume electrolyte balanced solutions as preparation for colonoscopy often results in poor patient compliance and acceptance. The tolerance, safety, and efficacy of high-versus low volume colon-cleansing methods as preparation for colonoscopy in children were compared by randomized operator-blinded trial. Methods: Twenty-nine children ages 3.6-14.6 years had either high-volume nasogastric balanced polyethylene glycol electrolyte lavage (20 ml/kg/h) until the effluent was clear (n = 15), or two oral doses of sodium phosphate solution (22.5-45 ml) separated by oral fluid intake (n = 14). Results: Both preparations were equally effective. The low-volume preparation was better tolerated and caused less discomfort that the high-volume preparation, judging by serial nurse observations. The incidence of abdominal symptoms, diarrhea, sleep disturbance, and vomiting was not significantly different between the two groups. Both groups had a small reduction in mean hematocrit and serum calcium levels. The sodium phosphate preparation caused increases in mean serum sodium concentrations from 140 to 145 mmol/L and serum phosphate concentrations from 1.41 to 2.53 mmol/L. Ten hours after the commencement of the preanesthetic fast, these concentrations had returned to normal. Conclusions: There are advantages in terms of tolerance, discomfort, and case of administration with acceptable colonic cleansing with the use of the less-invasive oral sodium phosphate low-volume colon-cleansing preparation in children. Safe use requires ensuring an adequate oral fluid intake during the preparation time and avoidance of use in patients with renal insufficiency.

The treatment of recurrent abdominal pain in children : a controlled comparison of cognitive-behavioral family intervention and standard pediatric care

This study describes the results of a controlled clinical trial involving 44 7- to 14-year-old children with recurrent abdominal pain who were randomly allocated to either cognitive-behavioral family intervention (CBFI) or standard pediatric care (SPC). Both treatment conditions resulted in significant improvements on measures of pain intensity and pain behavior. However, the children receiving CBFI had a higher rate of complete elimination of pain, lower levels of relapse at 6- and 12-month follow-up, and lower levels of interference with their activities as a result of pain and parents reported a higher level of satisfaction with the treatment than children receiving SPC. After controlling for pretreatment levels of pain, children's active self-coping and mothers' caregiving strategies were significant independent predictors of pain behavior at posttreatment.

Comparative in vitro and in vivo studies of enteric-coated pancrelipase preparations for pancreatic insufficiency

We evaluated three acid-resistant pancreatic enzyme preparations by in vitro assays, and by comparing degree of steatorrhea, creatorrhea, fecal wet weight, and stool energy losses in a randomized crossover study of patients with pancreatic insufficient cystic fibrosis. Aims of the study were to assess (a) the most practicable and reliable indicator of malabsorption; (b) the variation in enzyme batch potency; (c) the decline in enzyme batch potency with prolonged shelf life; and (d) the relative bio-efficacy of the different preparations. In the in vivo study, absorption of energy, nitrogen, and fat did not differ when comparing the three preparations at roughly pharmaceu-tically equivalent doses, but when expressed per capsule of pancreatic supplement ingested, absorption reflected relative enzyme content, favoring the higher potency preparations. Although steatorrhea was reasonably controlled by these preparations, stool energy losses varied from 800 to 1,100 kJ per day, suggesting greater attention be paid to overall energy absorption rather than absorption of individual nutrients. In addition, fecal energy loss correlated more closely with fecal wet weight (r = 0.81; p < 0.05) than with steatorrhea (r = 0.40; ns), such that 1 g wet feces = 8.37 kJ (± 0.14). In vitro enzyme potency varied markedly between batches of the same brand, and also a decline of up to 20% in amylase, lipase, and trypsin activity was noted over an 8-month period for each batch. Both observations have clinical implications at times of represcription. Finally, the higher potency preparations were more effective per capsule and reduced capsule dosage is therefore attainable. © 1993 Raven Press, Ltd., New York.

Nutritional rehabilitation in cystic fibrosis: A 5 year follow-up study

Previously, we reported catch-up weight gain, growth, and improved lung function in a group of malnourished cystic fibrosis (CF) children receiving aggressive nutritional supplementation for 1 year compared with a forced expiratory volume in 1 s (FEV1)-, height-, and sex-matched comparison group receiving standard therapy. To evaluate long-term effects, the clinical progress of both groups has been studied over a 5 year period. The supplemented group (n = 10) received supplements for a median of 1.35 years to achieve nutritional rehabilitation. Compared with the nonsupplemented group (n = 14), the previously supplemented group had lower mortality (2 vs. 4, N.S.) and significantly greater weight and height z scores at 4 and 5 years. The progression of pulmonary function abnormalities as measured by FEV, and forced vital capacity (FVC) slopes was greater at 3 years in the nonsupplemented group (FEV1, p < 0.05) but no significant differences in rates of deterioration of pulmonary function were seen after 5 years in the two groups of survivors. We conclude that intensive nutritional support for 1 year has both short-and long-term effects on nutrition and growth, still evident some years after the cessation of this therapeutic modality. Supplementation for periods of longer than 1 year may produce greater gains and possibly prolong the improvement in pulmonary function observed in the earlier study. © 1992 Raven Press, Ltd., New York.

Esophageal stricture in children: Fiber-optic endoscopy and dilatation under fluoroscopic control

We made a retrospective analysis of the efficacy and complication rate of 268 esophageal dilatation procedures performed under fluoroscopic control using the fiber-optic endoscope in 45 children with esophageal stricture. Antegrade and retrograde stricture dilatation was performed under general anesthetic, mainly as an outpatient procedure. Thirty-six children had an esophageal stricture following tracheoesophageal fistula and/or esophageal atresia repair, and nine children had severe corrosive stricture of the esophagus following lye ingestion. The procedure was well tolerated and effective. © 1992 Raven Press, Ltd., New York.