D. A. Lloyd

Strictures of ascending colon in cystic fibrosis and high-strength pancreatic enzymes

We have observed five children with cystic fibrosis, who presented over 2 months, with meconium ileus equivalent that failed to respond to medical management. At surgery, four had a stricture in the ascending colon, and all had histopathological changes of post-ischaemic ulceration repair, with mucosal and submucosal fibrosis. The only common change in the management of these children was a switch from conventional enteric-coated pancreatic enzymes to high-strength products 12-15 months before presentation.

Expression of endothelin 3 by mesenchymal cells of embryonic mouse caecum

Background Mutations in endothelin 3 (EDN3) and endothelin B receptor (EDNRB) genes cause terminal colonic aganglionosis in mice, and mutations in these genes have also been linked to the terminal aganglionosis seen in human Hirschsprung’s disease. However, details of EDN3 expression during embryogenesis are lacking, and consequently the cellular mechanism by which EDN3 regulates innervation of the terminal gut is unclear. Aims To localise the expression of EDN3 and EDNRB in the embryonic mouse gut. Methods Expression of EDN3 and EDNRB mRNA was analysed by reverse transcription polymerase chain reaction and in situ hybridisation. Results High levels of EDN3 mRNA expression were restricted to mesenchymal cells of the caecum before and after the arrival of neural crest cells. In contrast, EDNRB expression along the gut displayed a time dependent pattern similar to those of the protein tyrosine kinase ret and the neural crest cell marker PGP9.5. Conclusions Mesenchymal cells of the caecum express high levels of EDN3 mRNA during embryogenesis and hence the production of EDN3 at the caecum is likely to act on neural crest cells as a paracrine factor necessary for subsequent innervation of the terminal gut.

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)

Evidence-based surgery: interventions in a regional paediatric surgical unit

OBJECTIVES To determine the proportion of paediatric surgical interventions that are evidence-based and to identify areas where randomised controlled trials (RCTs) or further research are required. DESIGN Prospective review of paediatric general surgical inpatients. SETTING A regional paediatric surgical unit. SUBJECTS All consecutive paediatric general surgical patients admitted in November, 1995. MAIN OUTCOME MEASURES Each patient on whom a diagnosis had been made was allocated a primary diagnosis and primary intervention (n=281). On the basis of expert knowledge, Plusnet Medline, and ISI Science Citation database searches, each intervention was categorised according to the level of supporting evidence: category 1, intervention based on RCT evidence; category 2, intervention with convincing non-experimental evidence such that an RCT would be unethical and unjustified; category 3, intervention without substantial supportive evidence. RESULTS Of 281 patient interventions, 31 (11%) were based on controlled trials and 185 (66%) on convincing non-experimental evidence. Only 23% of interventions were category 3. CONCLUSIONS In common with other medical specialties, the majority of paediatric surgical interventions are based on sound evidence. However, only 11% of interventions are based on RCT data, perhaps reflecting the nature of surgical practice. Further RCTs or research is indicated in a proportion of category 3 interventions.

Assessment of protein gene product 9.5 as a marker of neural crest-derived precursor cells in the developing enteric nervous system.

Abstract The neurons and glial cells of the enteric nervous system (ENS) are derived from the neural crest. To study the developmental events involved in congenital abnormalities of the ENS, it is essential to identify all neural-crest cells (NCC) in the prenatal gut. The low-affinity neurotrophin receptor p75 is currently considered to be a gold-standard marker, but because it is a membrane protein, it is lost during procedures that permeabilise cells that are necessary to identify intracellular components and in apoptosis and cell-proliferation assays. We have therefore assessed the potential of the intracellular neuronal marker protein gene product (PGP) 9.5 as a label for neural-crest-derived precursor cells during gut development. Gut was taken from mouse embryos at 11.5 days post-coitum, at which time NCC had reached the proximal colon. Cellular p75 and PGP9.5 expression was determined by double-labelling immunofluorescence. The leading edge of neural-crest migration was defined as the 10 most distal p75-labelled cells. The neuronal marker PGP9.5 labelled NCC as they migrated along the gut at day 11.5. At the leading edge of migration, over 95% of p75-positive cells also expressed PGP9.5, and all PGP9.5-positive cells were also labelled for p75. PGP9.5 is expressed by at least 95% of neural-crest-derived precursor cells at the leading edge of migration along the gut. Thus, it can be used as a robust marker for developing NCC in the gut.

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)

Double blind randomised controlled trial of topical glyceryl trinitrate in anal fissure

AIMS To determine the effectiveness and safety of topical glyceryl trinitrate (GTN) in the management of acute anal fissure in children. METHODS Individual children were randomised to receive GTN paste or placebo for six weeks in addition to oral senna and lactulose. Patients took laxatives alone for a further 10 weeks. Each week a research nurse telephoned families to assess pain scores and give advice. Main outcome measures were validated standardised pain scores and time to painless defaecation. RESULTS Forty subjects were recruited from 46 eligible children; 31 children completed the trial (13 in the GTN group and 18 in the placebo group). No differences in the proportion of those achieving pain free defaecation with relation to time were seen between the two groups. Similarly, there were no significant differences in pain scores between the two groups over the 16 week study period. However, in both groups pain scores had decreased significantly. There were no differences in the incidence of rectal bleeding, faecal soiling, presence of visible fissure, skin tag, or faecal loading at outpatient review at the time of recruitment, or at 6 weeks and 16 weeks. No serious adverse effects were observed. CONCLUSIONS This study suggests that 0.2% GTN paste is ineffective in the treatment of acute anal fissures in childhood. However the overall fissure healing rate is high (84%) with associated reduction in pain scores, suggesting that a nurse based treatment programme can achieve a high rate of fissure healing.

Primary peritoneal drainage in necrotising enterocolitis: an 18-year experience

Primary peritoneal drainage (PPD) was initially introduced as a method for the pre-operative resuscitation of critically ill infants with complicated necrotising enterocolitis (NEC). Some have recommended it as definitive strategy for a select group of extremely low birth weight babies. The role of laparotomy in neonates who do not respond to initial PPD has also been challenged. With this background, we analysed our experience with the use of PPD in babies with NEC over an 18-year period. We retrospectively reviewed all patients with NEC who had PPD as their initial surgical management over an 18-year period. A total of 122 babies with NEC were treated surgically, of whom 42 had PPD as the initial procedure. There were 28 survivors (67%) in the PPD group, of whom 7 recovered without laparotomy. Twenty-nine infants (69%) had a good clinical response to PPD with 80% (23/29) survival, compared to a 27% survival (3/11) in those who did not respond to drainage. Six patients underwent rescue laparotomy after a poor response to PPD and three of these survived. Six of the 28 pts who underwent laparotomy had isolated intestinal perforation and their clinical characteristics were no different from those with typical NEC. PPD is a useful option in the management of complicated NEC. It is difficult to recognise with certainty those infants who will not require a subsequent laparotomy and therefore we do not support the concept of PPD solely as a definitive strategy. The response to PPD is a good prognostic indicator for ultimate survival. Despite a low salvage rate of 27% in non-responders compared to 80% in responders, there is a role for early laparotomy for those infants who do not respond to PPD.

Heparin and in-vitro experimental lung hypoplasia

Abstract Pulmonary hypoplasia (PH) is a leading contributor to the lethality of congenital diaphragmatic hernia (CDH). Studies now suggest that PH arises prior to visceral herniation. Growth factors (GF) are pivotal to this embryonic lung growth. With striking in-vitro effects on lung morphogenesis, GF are under investigation as therapies for PH. Heparin modulates the kinetics of heparan-sulphate binding ligands that drive lung development. We hypothesised that heparin may rescue PH by favourable alteration of endogenous pulmonary GF activity. Normal and hypoplastic lung primordia were microdissected on day 13.5 of gestation and cultured for up to 78 h in plain media with and without heparin. In-vitro morphological development was studied by serial measurements of terminal bud count, lung area, and lung perimeter. Nitrofen-exposed lungs cultured with heparin showed no significant improvements in terminal bud count, lung area, and lung perimeter at 30, 54, and 78 h compared to untreated hypoplastic lungs maintained in vitro. In normal lungs heparin demonstrated no sustained significant morphological effects compared to untreated control lungs. In this study, heparin did not stimulate branching morphogenesis of normal or hypoplastic lungs in our organ culture system. Known at higher concentrations to inhibit smooth-muscle proliferation, heparin may ameliorate pulmonary vascular hypermuscularisation with the prospect of benefiting CDH infants on extracorporeal membrane oxygenation. Future studies will address the impact of exogenous GF on hypoplastic lung development in organ culture.

Ultrasonography as a method of nutritional assessment.

The composition of the upper arms of five healthy individuals was measured by anthropometry (AN), ultrasonography (US), and computerized tomography (CT). Measurements of midarm fat area (MAFA) and midarm muscle area (MAMA) by CT correlated well with AN and US, but both AN and US overestimated MAMA by 22.8 +/- 17% and 10 +/- 12%, respectively, (mean +/- SD). The overestimate was largest with AN because with this method bone area cannot be excluded. To evaluate the usefulness of US measurements, 10 patients with advanced liver disease were studied. Measurement of MAFA by US, using triceps skinfold thickness as the standard, was found to be an accurate index of fat stores. MAMA measured by US correlated well with lean muscle mass, using creatinine height index as the standard. Ultrasonography is a reliable method of measuring body fat and lean muscle status.