Outcomes following prosthetic patch repair in newborns with congenital diaphragmatic hernia.

BACKGROUND: The anatomical defect in congenital diaphragmatic hernia (CDH) can usually be closed primarily but prosthetic patch repair may be required in newborns with a deficient diaphragm. High rates of patch failure and hernia recurrence (up to 50 per cent) have been reported. This study evaluated contemporary outcomes following patch repair of CDH at a UK paediatric surgical centre. METHODS: Medical records of newborns undergoing surgery for CDH between 1 February 1990 and 1 November 2010, and attending a multidisciplinary follow-up clinic, were examined. Operative details and patch utilization are reported. RESULTS: Of 118 newborns with CDH, 37 required a patch to the diaphragmatic defect. Gore-Tex® patches were used in 35 and biological Surgisis® patches in two. Eight babies additionally required an abdominal wall patch. Seven infants had an abdominal patch alone with primary diaphragm repair. A total of 102 infants (86·4 per cent) survived after surgery. Two early recurrences were both related to the use of biological patches, leading to revisional surgery with Gore-Tex® patch reconstruction. Diaphragmatic patch use was associated with a greater requirement for intensive cardiovascular and respiratory support, although there was no significant difference in mortality between patch versus primary diaphragm repair. The mortality rate was significantly higher among infants requiring abdominal wall patching (with or without a diaphragmatic patch): 40 per cent (6 of 15) versus 9·7 per cent (10 of 103) (P = 0·006). Postoperative survival rates for infants with a diaphragmatic patch alone, abdominal wall patch alone, and both abdominal and diaphragmatic patches were 86 per cent (25 of 29), 57 per cent (4 of 7) and 63 per cent (5 of 8) respectively. CONCLUSION: Prosthetic diaphragmatic hernia repair at this centre has a good outcome and low rate of recurrence (5 per cent). The recognition of an inadequate abdominal domain prenatally may additionally prove to be a useful marker for predicting increased mortality in newborns with CDH.

Order-disorder and ionic conductivity in calcium nitride-hydride.

Recently nitrogen-hydrogen compounds have successfully been applied as co-catalysts for mild conditions ammonia synthesis. Ca2NH was shown to act as a H2 sink during reaction, with H atoms from its lattice being incorporated into the NH3(g) product. Thus the ionic transport and diffusion properties of the N-H co-catalyst are fundamentally important to understanding and developing such syntheses. Here we show hydride ion conduction in these materials. Two distinct calcium nitride-hydride Ca2NH phases, prepared via different synthetic paths are found to show dramatically different properties. One phase (ß) shows fast hydride ionic conduction properties (0.08 S/cm at 600 °C), on a par with the best binary ionic hydrides and 10 times higher than CaH2, whilst the other (α) is 100 times less conductive. An in situ combined analysis techniques reveals that the effective ß-phase conducts ions via a vacancy-mediated phenomenon in which the charge carrier concentration is dependent on the ion concentration in the secondary site and by extension the vacancy concentration in the main site.

The structure, thermal properties and phase transformations of the cubic polymorph of magnesium tetrahydroborate.

The structure of the cubic polymorph of magnesium tetrahydroborate (γ-Mg(BH(4))(2)) has been determined in space group Ia3d from a structural database of the isoelectronic compound SiO(2); this has been corroborated by DFT calculations. The structure is found to concur with that recently determined by Filinchuk et al. (Y. Filinchuk, B. Richter, T. R. Jensen, V. Dmitriev, D. Chernyshov and H. Hagemann, Angew. Chem. Int. Ed., 2011, DOI: 10.1002/anie.201100675). The phase transformations and subsequent decomposition of γ-Mg(BH(4))(2) on heating have been ascertained from variable-temperature synchrotron X-ray diffraction data combined with thermogravimetric and mass spectrometry measurements. At ~160 °C, conversion to a disordered variant of the ß-Mg(BH(4))(2) phase (denoted as ß') is observed along with a further unidentified polymorph. There is evidence of amorphous phases during decomposition but there is no direct crystallographic indication of the existence of Mg(B(12)H(12)) or other intermediate Mg-B-H compounds. MgH(2) and finally Mg are observed in the X-ray diffraction data after decomposition.

Atomic structure of thymidylate synthase: target for rational drug design.

The atomic structure of thymidylate synthase from Lactobacillus casei was determined at 3 angstrom resolution. The native enzyme is a dimer of identical subunits. The dimer interface is formed by an unusual association between five-stranded beta sheets present in each monomer. Comparison of known sequences with the Lactobacillus casei structure suggests that they all have a common core structure around which loops are inserted or deleted in different sequences. Residues from both subunits contribute to each active site. Two arginine side chains can contribute to binding phosphate on the substrate. The side chains of several conserved amino acids can account for other determinants of substrate binding.

Oesophageal atresia and tracheo-oesophageal fistula.

Oesophageal atresia-tracheo-oesophageal fistula has featured in paediatric surgery since its beginnings. The first successful primary repair was in 1941. With overall survival now exceeding 90% in dedicated centres, the emphasis has changed to reducing morbidity and achieving improvements in the quality of life. An overview of current and emerging strategies in managing patients with this condition is presented. Advances in developmental biology and molecular genetics reflecting improved understanding of the pathogenesis are highlighted.

Distribution of cells expressing myc proteins in human colorectal epithelium, polyps, and malignant tumors.

The myc gene family encodes nuclear phosphoproteins that are thought to play a role in the control of cellular proliferation and differentiation. We have undertaken an immunohistochemical study assessing the expression of myc gene family proteins in individual cells of normal colonic mucosa, colorectal polyps, and colorectal adenocarcinomas. We screened a panel of mouse monoclonal antibodies that we raised against recombinant human c-myc and N-myc proteins for recognition of myc proteins in paraffin tissue sections. Two of these antibodies, H120C69 and H8C150, were selected for indirect immunoperoxidase staining of tissue sections from 16 normal mucosas, 24 polyps, and 30 adenocarcinomas. In normal colon, about 25% of the cells in the lower one-third of the crypts of Lieberkühn stain for myc-related protein. This distribution resembles that of proliferating cells in the crypt. Benign hyperplastic polyps resemble normal mucosa in their myc staining pattern, with about 25% of the cells positive. In adenomatous polyps, the putative precursors of adenocarcinomas, from 50 to 100% of the cells stain positively for myc protein. In these cases, stained cells extend to the luminal surface, consistent with the previously reported expansion of the proliferation zone in these lesions. All adenocarcinomas examined had increased levels of myc protein relative to normal mucosa. The tumor cells exhibited markedly heterogeneous myc staining patterns, both among different tumors and, in some cases, within a single tumor. Comparison with Ki-67 monoclonal antibody staining indicates that myc protein expression in many tumors is uncoupled from cellular proliferation. Surprisingly, we observed increased numbers of myc-expressing cells and increased levels of myc protein in histologically normal colon directly adjacent to tumor, suggesting that many colorectal carcinomas secrete growth factors that activate gene expression in neighboring normal mucosa.

Vergence responses to vertical binocular disparity during lexical identification.

Humans typically make use of both eyes during reading, which necessitates precise binocular coordination in order to achieve a unified perceptual representation of written text. A number of studies have explored the magnitude and effects of naturally occurring and induced horizontal fixation disparity during reading and non-reading tasks. However, the literature concerning the processing of disparities in different dimensions, particularly in the context of reading, is considerably limited. We therefore investigated vertical vergence in response to stereoscopically presented linguistic stimuli with varying levels of vertical offset. A lexical decision task was used to explore the ability of participants to fuse binocular image disparity in the vertical direction during word identification. Additionally, a lexical frequency manipulation explored the potential interplay between visual fusion processes and linguistic processes. Results indicated that no significant motor fusional responses were made in the vertical dimension (all p-values>.11), though that did not hinder successful lexical identification. In contrast, horizontal vergence movements were consistently observed on all fixations in the absence of a horizontal disparity manipulation. These findings add to the growing understanding of binocularity and its role in written language processing, and fit neatly with previous literature regarding binocular coordination in non-reading tasks.

A comparative analysis of vertical and horizontal fixation disparity in sentence reading.

Humans have two, frontally placed eyes and during reading oculomotor and sensory processes are needed to combine the two inputs into a unified percept of the text. Generally, slight vergence errors, i.e., fixation disparities, occur but do not cause double vision since disparate retinal inputs fall into Panum's fusional area, that is, a range of disparity wherein sensory fusion of the two retinal images is achieved. In this study, we report benchmark data with respect to the mean magnitude and range of vertical compared to horizontal fixation disparities for natural reading. Our data clearly fit to an elliptical pattern of Panum's fusional area that corresponds with theoretical estimates. Furthermore, when we examined disparity-driven vergence adjustments during fixations by comparing monocular with binocular reading conditions, we found that only horizontal fixation disparities increased significantly under conditions of monocular stimulation. Also, no significant vertical fine-tuning (vergence adjustment) was observed for vergence eye movements during reading fixations. Thus, horizontal and vertical fixation disparities and vergence adjustments during reading showed quite different characteristics, and this dissociation is directly related to the functional role of vergence adjustments: vertical fusion - and vertical vergence - subserve the maintenance of a single percept and stereopsis by keeping the eyes in register and allowing for horizontal fusional processes to successfully operate over a vertically aligned input. A reliable and stable vertical alignment is, thus, a pre-requisite over which horizontal fusional responses (and depth perception) can work most efficiently - even in a task like reading.

The metabolic response to operative stress in infants.

The aim of this study was to characterize energy metabolism and substrate utilization in infants following an operation. Nineteen infants (weight 3.2 +/- 0.2 kg) who had an operation were studied. Anesthesia was standardized and operative stress score (OSS) was recorded. Five infants had a minor operation (OSS < 7), and 14 infants had a major operation (OSS > or = 7). Energy and nitrogen intake were constant during the 48-hour study period. Respiratory gas exchange was measured by indirect calorimetry preoperatively, and postoperatively for the first 12 hours continuously and at 24 hours, 48 hours, and 5 days. Urinary nitrogen excretion rate was measured for the first 48 hours following the operation. Physical activity was scored. Resting energy expenditure (REE) and nonprotein respiratory quotient (NPRQ) were calculated. REE increased postoperatively, peaking at 2 to 4 hours, and returned to baseline levels by 12 to 24 hours. Peak REE was significantly higher than baseline REE (P < .001). Substrate utilization was not altered by operation. The increase in REE was significantly greater in infants having a major operation than in infants having a minor operation (P < .05). Among infants having a major operation, the increase in REE was significantly greater in those infants more than 48 hours old, than in those infants less than 48 hours old (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose utilization in the surgical newborn infant receiving total parenteral nutrition.

Glucose is the main source of nonprotein calories in total parenteral nutrition (TPN). However, its use has been associated with various nutritional, metabolic, and respiratory complications. The aim of this study was to determine, in the stable surgical newborn infant, the characteristics of carbohydrate metabolism, in particular the maximum oxidative threshold for intravenous glucose and the thermogenic effect of glucose. Twenty-one studies were done on 11 infants (weight 2.82 +/- 0.19 kg) receiving TPN containing constant amounts of amino acids (2.5 g/kg/d) and fat (3.0 g/kg/d), and different amounts of glucose (range, 10 to 25 g/kg/d). Oxygen consumption (VO2), carbon-dioxide production (VCO2), and resting energy expenditure (REE) were measured by indirect calorimetry. Urinary nitrogen excretion rate was measured and substrate utilization calculated from the nonprotein respiratory quotient (NPRQ). There was a positive correlation between the predictor variable glucose intake and the dependent variables VO2 (r = .55; P < .05), VCO2 (r = .83; P < .0001), REE (r = .65; P < .005), NPRQ (r = .94; P < .0001), respiratory rate (r = .46; P = .06), and plasma triglycerides level (r = .67; P < .01). When glucose intake exceeded 18 g/kg/d the NPRQ was greater than 1.0, indicating glucose conversion to fat. Above this level of intake, the gradient of the correlation between the predictor variable glucose intake and the dependent variables VCO2 and REE increased. From this study we conclude that: (1) Glucose intake is the principal determinant of glucose utilization and exerts an influence on the metabolism of exogenous fat.(ABSTRACT TRUNCATED AT 250 WORDS)

A new equation to predict the resting energy expenditure of surgical infants.

It is essential that adequate calories are provided to newborns to cover their energy expenditure. This is difficult to measure and varies significantly between individuals. The aim of this study was to develop an equation to predict the basal energy requirements of stable surgical infants, using easily measurable parameters. Resting energy expenditure (REE) was measured using computerized open-circuit indirect calorimetry. One hundred twenty-two measurements were made on different days in 46 stable nonventilated infants. The measured REE was 34.41 +/- 0.46 cal/kg/min; (mean +/- SEM). Three body-size measurements correlated significantly with REE (cal/min): weight in kilograms (r = .87; P < .00001), body surface area in square meters (r = .86; P < .00001), and lean body mass in kilograms (r = .81; P < .00001). Five other independent variables correlated significantly with REE (cal/kg/min): heart rate in beats per minute (r = .60; P < .00001), postnatal age in days (r = .49; P < .00001) caloric intake in cal/kg/min (r = .44; P < .00001), gestational age in weeks (r = .43; P < .00001), and rectal temperature in degrees Celsius (r = .19; P = .04). Weight, heart rate, age, gestational age, and temperature were regarded as independent predictor variables of REE for the multiple stepwise regression analysis. Three variables entered this highly significant equation: REE (cal/min) = -74.436 + (34.661 x weight in kg) + (0.496 x heart rate in beats/min) + (0.178 x age in days) (r = .92; F = 230.07; significance, F < .00001).(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian adenocarcinoma in premenarchal girls.

Ovarian neoplasms are unusual in the paediatric age group; the majority of them are of germ cell origin. Malignant epithelial tumours of the ovary occur infrequently in adolescent girls. Ovarian carcinoma in particular is extremely rare before puberty. The authors describe 3 cases of adenocarcinoma of the ovary in premenarchal girls and highlight the unique characteristics of this tumour in this age group.

Protein metabolism kinetics in neonates: effect of intravenous carbohydrate and fat.

The aim of this study was to determine the effect of different glucose/fat ratios on protein metabolism kinetics in newborn infants receiving total parenteral nutrition (TPN). Eighteen studies were done on 14 infants receiving TPN (weight 3.15 +/- 0.22 kg [mean +/- SEM]; gestational age 37.8 +/- 0.9 weeks; postnatal age 14.0 +/- 3.7 days). There were two study groups. Group A infants (n = 9) received 10.0 g/kg/d of dextrose and 4.0 g/kg/d of fat; group B infants (n = 9) received 19.0 g/kg/d of dextrose and 0.5 g/kg/d of fat. Caloric intake (86 kcal/kg/d) and amino-acid intake (2.5 g/kg/d) were the same in the two groups. There was no difference between the groups with regard to weight, gestational age, and postnatal age. Intravenous diet was constant during the 3-day study period. Timed urinary nitrogen excretion was determined. On day 3 of the study, each infant received a priming dose of 15 mumol/kg of [13C]leucine followed by a 6-hour infusion at 6 mumol/kg/h. Plasma and breath samples were taken at hourly intervals, and CO2 production was measured by indirect calorimetry. Plateau levels of plasma [13C]-alpha Ketoisocaproic acid (KIC) enrichment and expired 13CO2 enrichment were determined by gas chromatograph mass spectrometry. Protein metabolism kinetics were calculated. Results were: nitrogen balance 0.27 +/- 0.01 g/kg/d, total protein flux 10.38 +/- 0.34 g/kg/d, total protein synthesis 9.64 +/- 0.31 g/kg/d, total protein breakdown 7.86 +/- 0.38 g/kg/d, and total protein oxidation/excretion 0.92 +/- 0.04 g/kg/d.(ABSTRACT TRUNCATED AT 250 WORDS)

Phenotypic presentation and outcome of esophageal atresia in the era of the Spitz classification.

PURPOSE: The aim of this study was to investigate contemporary patterns of presentation and outcome in newborns with esophageal atresia with or without tracheoesophageal fistula (OA) using modern prognostic criteria to appraise survival. METHODS: Over a 12-year period (1986 through 1997), 134 patients with OA were admitted to a single institution. Patient demographics, the presence of cardiac defects, other associated abnormalities (VACTERL), surgical intervention, and patient outcome were recorded. To identify and evaluate changes in the pattern of clinical presentation, frequency of associated anomalies and outcome, patients were analyzed during 4 consecutive time periods, 1986 to 1988, 1989 to 1991, 1992 to 1994, and 1995 to 1997. RESULTS: A primary repair or delayed primary repair was performed in 113 (84%) patients, with a staged procedure in 19 (14%). Two babies with trisomy 18 did not undergo surgery. Thirty-eight newborns (28%) had a major cardiac malformation (excluding patent ductus arteriosus, unless needing ligation), and 25 (19%) had recognized VACTERL associations. There was a significant increase in the proportion of infants with major cardiac defects diagnosed over the study period, 5 of 34 patients between 1986 and 1988 to 19 of 41 patients between 1995 and 1997 (chi(2) test, P <.001), but the incidence of VACTERL associations remained unchanged. Overall survival rate was 86% in those who underwent surgery. The relative risk of mortality in patients with major cardiac disease and VACTERL associations was 3.47 (95% CI; 1.51 to 7.96) and 2.54 (95% CI; 1.14 to 4.86), respectively. Birth weight was significantly higher in infants who survived (2.68 kg) compared with those who died (2.16 kg, P =.003). Thirty percent of infants with more than one system abnormality died compared with 8% of infants with 1, system abnormality (P =.004). CONCLUSIONS: This study has found a significant increase in the frequency of cardiac abnormalities encountered in a cohort of OA patients during the period under review. Cardiac disease and multiple abnormalities carried a substantial increased risk of mortality. In the era of the Spitz classification, the phenotypic presentation is important to accurately assess caseload severity and prognosis.

Transanal endorectal coloanal surgery for Hirschsprung's disease: experience in two centers.

BACKGROUND/PURPOSE: Transanal mucosal proctectomy with low coloanal anastomosis has been used widely in the treatment of rectal malignancies, ulcerative colitis, and familial polyposis. The use of this technique for Hirschsprung's disease is a relatively new concept. The aim of this study was to evaluate and compare the results of transanal endorectal coloanal anastomosis (TECA) for Hirschsprung's disease from 2 centers. METHODS: All children who underwent TECA for Hirschsprung's disease at Alder Hey Children's Hospital, Liverpool, England from January 1995 to December 1998 (n = 41) and the Children's Hospital, Helsinki, Finland from June 1988 to December 1998 (n = 95) were evaluated. Patient demographics, age at diagnosis, initial management, length of aganglionic segment, and age at operation were documented. Postoperative complications and functional outcome were analyzed. RESULTS: Patient demographics were similar in the 2 centers. Age at diagnosis was less than 1 month in 71% of children at Liverpool, compared with 53% at Helsinki. Sixteen (39%) patients in Liverpool and 75 (79%) patients in Helsinki underwent primary TECA without colostomy. Postoperative enterocolitis occurred in 14 of 136 patients (10%). An ischemic stricture of the colon was documented in 4 children in the Liverpool series, 2 of whom had TECA as a salvage procedure after a previously failed Duhamel pull-through operation. Frequency of bowel movements, seen in the immediate postoperative period in most patients gradually improved with time from a median of 5 (range, 2 to 12) bowel movements a day at 3 months after TECA to 2 (range, 1 to 6) bowel movements a day at 2 years' follow-up. Assessment of continence was possible in 51 of 136 patients (37%) over the age of 4 years. Thirty-nine children had normal bowel function giving an overall success rate of 76%. CONCLUSIONS: Transanal endorectal coloanal anastomosis is a good technique for treatment of Hirschsprung's disease with few operation-related complications. Based on the data emerging from these 2 centers the functional outcome is highly satisfactory and comparable with other established procedures.

The effect of major operations on heart rate, respiratory rate, physical activity, temperature and respiratory gas exchange in infants.

Perioperative changes in heart rate (HR), respiratory rate (RR), physical activity, body temperature, oxygen consumption (VO2), carbon dioxide production (VCO2) and resting energy expenditure (REE) were studied in fourteen infants (weight 3.1 +/- 0.2 kg) who had a major operation. VO2 and VCO2 were measured by indirect calorimetry preoperatively, and postoperatively for the first 12 hours continuously and at 24 hours, 48 hours and 5 days. HR, RR and physical activity were recorded on a minute to minute basis, and rectal temperature was recorded hourly. REE was calculated. HR, RR, VO2, VCO2 and REE increased postoperatively, peaking at 2-4 hours, and returned to baseline levels by 12-24 hours. In all of these variables, peak levels were significantly higher than Baseline levels (p < 0.001 for all variables). Physical activity and rectal temperature did not vary significantly throughout the study. This study demonstrates that newborn infants exhibit a short-lived postoperative increase in HR, RR, VO2, VCO2 and REE, which is not related to any alteration in physical activity or body temperature.

Umbilical pyloromyotomy--an alternative to laparoscopy?

AIMS: To evaluate the utility of umbilical pyloromyotomy for infantile hypertrophic pyloric stenosis (IHPS) compared to published series promoting laparoscopy. METHODS: Eighty-six babies with IHPS had pyloromyotomy using an umbilical skin fold incision. Operating times, post-operative hospital stay and cosmetic appearance of the umbilical wound were studied. Data extracted from recent series promoting laparoscopy were identified using a MEDLINE search strategy and used for comparative analysis. RESULTS: Mean operating time for umbilical pyloromyotomy was 30 min (range 15-50 min). All patients went home at an average period of 58 h (range 48-72 h) following surgery. The umbilical scar was barely visible in the post-operative period. Laparoscopic pyloromyotomy operating times ranging from 18-41 min (mean overall 30 min) are recorded in the literature. Post-operative stay following laparoscopy has been variable (23-91 h), where reported. In contrast with umbilical pyloromyotomy, "pox" marks observed following port insertions for laparoscopy can give an unsightly scar. CONCLUSIONS: This study has found that umbilical pyloromyotomy can be performed with minimal morbidity and equivalent operating times to laparoscopy. The shorter hospital stay reported in some series promoting laparoscopy must be balanced against local practice influencing hospital stay, the financial implications of offering a laparoscopic service, the skills needed for laparoscopy, and the short learning curve required by paediatric surgical trainees to become proficient at umbilical pyloromyotomy. The cosmesis of the umbilical incision is excellent. These findings suggest that umbilical pyloromyotomy is a reliable alternative to laparoscopy.

A multidisciplinary combinatorial approach for tuning promising hydrogen storage materials towards automotive applications.

HyStorM is a multidisciplinary hydrogen-storage project aiming to synthesise and tune materials hydrogen storage properties for automotive applications. Firstly, unique high-throughput combinatorial thin-film technologies are used to screen materials' hydrogen storage properties. Then promising thin-film candidate compositions are synthesised and examined in the bulk. In this paper, we report on our results within the ternary compositions Mg-Ti-B and Ca-Ti-B. Primary screening of the Mg-Ti-B ternary identified a high capacity hotspot corresponding to Mg0.36Ti0.06B0.58, with 10.6 wt% H2 capacity. Partial reversibility has been observed for this material in the thin-film. Bulk Ti-doped Mg(BH4)2 composites show rehydrogenation to MgH2 under the conditions used. The synthesised thin-film Ca-Ti-B ternary showed only low hydrogen storage capacities. In the bulk, Ti-doping experiments on Ca(BH4)2 demonstrated reversible storage capacities up to 5.9 wt% H2. Further characterisation experiments are required to decipher the role of the Ti-dopant in these systems in both films and in the bulk.