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Biomedical subjects

D A Lloyd

Publications and source records attributed to D A Lloyd.

At least 19 recordsLinked to original sources
PubMed1999

Pulmonary neuroendocrine cells in nitrofen-induced diaphragmatic hernia and the effect of prenatal glucocorticoids.

The high mortality associated with congenital diaphragmatic hernia (CDH) is due to pulmonary hypoplasia and hypertension, structural and functional abnormalities which can to some extent be ameliorated by prenatal administration of glucocorticoids. In the hypoplastic, hypertensive lungs of neonatal rats in which CDH has been induced by nitrofen, those pulmonary neuroendocrine cells (PNCs) containing calcitonin gene-related peptide (CGRP) increase in number, and it has been suggested that this might be due to inhibition of secretion of the peptide, the consequent decrease in its vasodilatory effects contributing to the hypertension. Whether this increase affects the entire population of PNCs, however, and how these cells are affected by administration of prenatal glucocorticoids, is unknown. As revealed by immunolabelling for protein gene product (PGP) 9.5, a general marker of NCs and expressed per cm2 tissue section, the total PNC population in rats with nitrofen-induced CDH was significantly greater than in controls receiving only olive oil (672 vs 375/cm2, P = 0.03) and was further increased (824 per cm2) in animals treated prenatally with dexamethasone (n = 8 in all groups). The increase in the total PNC population in rats with CDH is similar in magnitude to that described for the CGRP-containing subpopulation. Since the major role of the products of PNCs is now thought to be the regulation of development of pulmonary tissues and their response to injury, it is probable that the expansion of their population in the abnormal lungs associated with CDH is an adaptive response to pulmonary maldevelopment, a response possibly augmented by exogenous corticosteroids.

Animals↗
PubMed1999

Cardiovascular malformations in experimental congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Newborns with congenital diaphragmatic hernia (CDH) frequently have associated anomalies that have a major impact on survival rate independent of pulmonary hypoplasia and pulmonary hypertension. Cardiovascular malformations (CVM) represent a major group of lethal extrapulmonary abnormalities that often assume greatest prognostic significance in most CDH studies. Animal models resembling human CDH may aid knowledge of the basic embryology that leads to the coexpression of CDH and CVM. This study, therefore, analyzed the incidence and spectrum of CVM in fetal rats with CDH. METHODS: Left-sided CDH (LCDH) was induced in fetal rats by the maternal administration of 100 mg of nitrofen by gavage on day 9.5 gestation (term, day 22). Control animals received olive oil (OO) and were used for comparative analysis. Fetal rats were harvested by cesarean section on day 21.5 or day 22, histologically processed and examined for CVM. RESULTS: A significant number of CVM were observed in 15 of 60 (25%) LCDH rats compared with 4 of 60 (6.7%) nitrofen non-CDH rats (P = .01). The spectrum of abnormalities in CDH included ventricular septal (VSD) defects (n = 6), vascular rings (n = 4), anomalous subclavian arteries (n = 3), atrioventricular septal defects (n = 1) and Fallot's tetralogy (n = 1). A VSD (n = 1), double-outlet right ventricle VSD (n = 1) and Fallot's tetralogy (n = 2) were noted in nitrofen non-CDH rats. Control (OO) fetal rats (n = 60) displayed no malformations. CONCLUSIONS: These results confirm a significant incidence and spectrum of CVM in a teratogenic CDH model similar to that seen in humans with CDH. The findings of this study reinforce the validity of the nitrofen model as a research tool to uncover the genetic and molecular mechanisms responsible for the genesis of CDH and allied malformations.

Animals↗
PubMed1999

Ontogeny of interstitial cells of Cajal in the human intestine.

BACKGROUND/PURPOSE: Interstitial cells of Cajal (ICC) recently have been identified as intestinal pacemaker cells. Abnormalities in ICC are increasingly recognized in a number of neonatal disorders such as infantile hypertrophic pyloric stenosis, Hirschsprung's disease, and transient intestinal pseudo-obstruction. The aim of this study was to determine the fetal and postnatal differentiation and development of ICC in the human gastrointestinal tract to aid interpretation of pathological specimens. METHODS: Specimens of human gastrointestinal tract from (1) fetuses (9 to 17 weeks' gestation; n = 12), (2) premature and full-term neonates with non-gut motility-related disorders, (age 26 to 59 weeks' gestation; n = 13), and (3) children (age 4 months to 13 years; n = 7) were immunohistochemically stained with antibodies to c-kit(a marker for ICC) and protein gene product 9.5 (PGP9.5, a marker for neural tissue). RESULTS: (1) C-kit-positive ICC were present throughout the gut in all specimens including those from the earliest gestational ages. C-kit and PGP9.5 immunoreactivities were present in different cell populations. (2) The distribution of ICC varied with gestational age and with region of the gut. (3) Maturation of ICC networks continues postnatally in a region-specific manner. CONCLUSIONS: ICC are present from an early stage in human gut development. Interpretation of apparent abnormalities in ICC distribution as being of pathological significance should be tempered by the knowledge that ICC networks continue to develop postnatally and that ICC development varies throughout the gut.

Child↗
PubMed1999

Intravenous glutamine or short-chain fatty acids reduce central venous catheter infection in a model of total parenteral nutrition.

BACKGROUND/PURPOSE: In children receiving total parenteral nutrition (TPN) translocated enteric organisms are a possible cause of central venous catheter infection. The aim of this study was to determine the relationship between gut mucosal atrophy, bacterial translocation, and catheter sepsis in rats receiving TPN alone or supplemented with intravenous short chain fatty acids (SCFA) or glutamine. METHODS: Mature Wistar rats were studied. Groups 2 to 5 had a central venous catheter inserted. Group 1 (n = 12) had enteral feeds only, group 2 (n = 14) had enteral feeds and intravenous saline, group 3 (n = 15) had TPN only, group 4 (n = 13) had TPN with SCFA, and group 5 (n = 15) had TPN with glutamine. At 1 week, blood, tissue, and catheter specimens were obtained for culture and mucosal morphometry. RESULTS: Villus height and crypt depth were reduced significantly in group 3 compared with group 1 (P < .05). Glutamine and SCFA significantly ameliorated the mucosal atrophy. Significant bacterial translocation and catheter infection occurred in group 3. Reduced translocation with SCFA was not significant, but catheter infection was (P < .05). Glutamine significantly reduced translocation and catheter infection. CONCLUSIONS: There is an association between bacterial translocation and central venous catheter infection. The risk of catheter infection is reduced by supplementing TPN with SCFA or glutamine.

Animals↗
PubMed1999

Long-term outcome and colonic motility after the Duhamel procedure for Hirschsprung's disease.

BACKGROUND/PURPOSE: The aim of this study was to investigate long-term functional outcome and colonic motility in children who had undergone the Duhamel-type operation for Hirschsprung's disease (HSCR). METHODS: All patients (n = 91) who underwent the Duhamel or Lester Martin Modified Duhamel operation for HSCR from 1980 to 1991 were included in the study. Twenty-two healthy age-matched children were used as controls. Functional outcome was assessed by questionnaire (response rate 100%). Total and segmental colonic transit time (CTT) was determined using the saturation method (80% participation rate). RESULTS: Outcome scores were significantly worse in the study group for patients with rectosigmoid (RS, P < .001), long segment (LS, P < .001), and total colonic (TC) aganglionosis (P < .05), when compared with controls. The CTT was significantly prolonged in the RS group (P = .01) compared with LS, TC, and control groups; this was caused by prolonged "rectosigmoid" transit in the RS group compared with controls (P = .012). There was a positive linear correlation (P = .0002) between age and outcome score in patients with RS disease unrelated to CTT. Nine patients required a late long-term enterostomy. A satisfactory outcome (defined as outcome score > or = 10th percentile of the control group, and absence of stoma or requirement for major revisional surgery) was seen in only 42% of patients overall and in 79% of patients over 14 years of age. CONCLUSIONS: The Duhamel procedure, in common with other pull-through procedures, is associated with significant long-term morbidity, the aetiology of which is poorly understood.

Adolescent↗
PubMed1999

Oral contrast with computed tomography in the evaluation of blunt abdominal trauma in children.

BACKGROUND: The use of oral contrast in evaluating children by computed tomography (CT) following blunt trauma is controversial. The aim of this study was to evaluate retrospectively the use of oral contrast with abdominal CT in children with suspected abdominal injury. METHODS: The medical records of 101 children who underwent CT for abdominal trauma between 1993 and 1997 were reviewed for data pertaining to the mechanism of injury, clinical findings and management. Scans were reviewed by a paediatric radiologist and criteria of intestinal injury on CT described by Cox and Kuhn were used: (1) extraluminal air or contrast material, (2) focal area of thickening of bowel wall and mesentery, and (3) free intraperitoneal fluid in the absence of solid organ injury. RESULTS: CT was performed within a median time of 2.4 (range 1-48) h after the injury. On 37 (62 per cent) of 60 scans in children who had oral contrast, the duodenum was not opacified after a mean delay of 30 min. Intestinal injury was suspected on CT in four children. In two children with CT evidence of intestinal injury (with/without oral contrast) rupture of the duodenojejunal flexure (n = 1) or ileal perforation (n = 1) was found at laparotomy. Two children had a false-positive scan, leading to negative laparotomy; one scan with oral contrast incorrectly suggested a duodenal leak and in another child CT without oral contrast showed thickening of bowel wall with free intraperitoneal fluid but no specific intestinal injury was identified at laparotomy. One patient had two negative CT scans (with and without oral contrast) and underwent laparotomy for clinical suspicion of bowel injury; rupture of the splenic flexure of the colon was found at laparotomy. CONCLUSION: CT is not reliable for diagnosing intestinal injuries and this is not improved by use of oral contrast. Omission of oral contrast was not associated with delay in the diagnosis of intestinal injury. Since intestinal injuries are uncommon in children, a prospective multicentre study would determine more precisely the role of the routine use of oral contrast.

Abdominal Injuries↗
PubMed1999

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.

Animals↗
PubMed1998

The value of early postoperative oesophagography following repair of oesophageal atresia.

The aim of the study was to examine the relationship between anastomotic leaks and the development of symptomatic anastomotic strictures after primary repair of oesophageal atresia (OA) with or without tracheo-oesophageal fistula (TOF) and the prognostic value of the anastomotic appearance on postoperative oesophagography. The records and X-ray films of 49 patients with OA with or without TOF admitted between January 1990 and June 1995 were reviewed retrospectively. Of these, 37 had a primary repair (34 immediate and 3 delayed) and a postoperative contrast swallow was done between day 5 and day 30 (median day 7). Radiological leaks were documented. In addition, the maximum transverse diameters of the upper pouch and anastomotic region and the length of the anastomotic narrow segment were measured; the ratio of upper-pouch diameter to that of the anastomosis was calculated (anastomotic index, AI). The need for dilatation of symptomatic anastomotic strictures and for repeat dilatation as a separate episode were documented. Of the 37 patients, 4 developed an anastomotic leak (11%), 3 radiological and 1 clinical. A symptomatic stricture occurred in 55% of patients. There was no correlation between a leak and later development of a symptomatic stricture, although the small number of patients with leaks precluded definite conclusions. No radiological leak progressed to a clinical leak. There was no correlation between the AI or the length of the anastomotic narrow segment and the need for dilatation, the need for repeat dilatation, or the number of dilatations. In this study, the presence of a leak, the AI, and the length of the narrow segment on early postoperative contrast swallow did not correlate with the later development of a symptomatic stricture. A radiological leak was of no clinical significance. Since major leaks are apparent clinically, an early routine contrast study did not influence management and is not necessary.

Esophageal Atresia↗
PubMed1998

Congenital diaphragmatic hernia--does the side of the defect influence the incidence of associated malformations?

BACKGROUND/PURPOSE: Patients with congenital diaphragmatic hernia (CDH) frequently have associated anomalies. Experiments in the nitrofen CDH model have shown differential embryonic cell death patterns in rodents suggesting unique mechanisms in the formation of right-sided (RCDH) or left-sided (LCDH) diaphragmatic hernia. These findings provide insight into the pathogenesis of CDH and may aid our understanding on the spectrum of associated anomalies commonly observed in humans. This study therefore set out to test the hypothesis that the side of the diaphragmatic defect in humans is related to the incidence and severity of coexistent organ malformations. METHODS: The medical and autopsy records of 301 CDH patients presenting to two institutions over a 23-year period were examined to analyze these factors. RESULTS: One hundred patients (33%) were found to have one or more associated anomalies. The incidence of multiple-RCDH (10%) versus LCDH (7.3%) and cardiac anomalies-RCDH (10%) versus LCDH (8.5%) was similar in both groups of patients. However, the hypoplastic heart syndrome was a unique feature in 5 of 22 patients (23%) with LCDH who had cardiac abnormalities. This cardiac anomaly may be related developmentally to LCDH. CONCLUSION: The cellular mechanisms underlying the genesis of this spectrum of abnormalities in humans and the nitrofen CDH model warrant further study to elucidate factors governing embryonic cell fate and phenotype expression.

Abnormalities, Multiple↗
PubMed1998

Effect of prenatal glucocorticoids on pulmonary vascular muscularisation in nitrofen-induced congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Pulmonary hypertension (PH) contributes significantly to the mortality of congenital diaphragmatic hernia (CDH). Pulmonary vascular changes in CDH include a reduced vascular bed with increased arterial medial wall thickness and peripheral extension of muscle into intraacinar vessels. Antenatal steroids improve biochemical immaturity, lung compliance, and morphology in experimental CDH animals. The aim of this study was to examine the effects of prenatal glucocorticoid therapy on pulmonary artery muscularisation in CDH rats. METHODS: CDH was induced in fetal rats by the maternal administration of 100 mg of nitrofen by gavage on day 9.5 of gestation (term, day 22). Control animals received olive oil (OO). Dexamethasone (Dex, 0.25 mg/kg) or normal saline (NS) was given by intraperitoneal injection on days 18.5 and 19.5, and fetuses were delivered by caesarean section on day 21.5. Lung sections from five fetuses in each of four experimental groups were studied by a blinded investigator- OO-NS controls, CDH-NS, CDH-Dex, and non-CDH-NS. The external diameter (ED), medial wall thickness (MT), percent of medial wall thickness, and wall structure were evaluated from preacinar arteries accompanying conducting airways, and the intraacinar arterioles associated with the respiratory bronchi and saccules. RESULTS: In the preacinar arteries, CDH-NS animals had a significantly increased MT percentage compared with OO-NS controls (21.2+/-8.8 v 17.8+/-10.3, P = .0001). CDH-Dex rats had a lower MT percentage than CDH-NS rats (15.5+/-6.7 v 21.2+/-8.8, P = .0001). In the intraacinar region, CDH-Dex fetuses had a reduced percentage of muscularised intraacinar blood vessels compared with CDH-NS and OO-NS controls (10% v 24% and 28%, respectively, P = .01). Dexamethasone-treated CDH pups also displayed a significantly lower MT percentage of the intraacinar arteries compared with CDH-NS and OO-NS animals (15.7+/-13 v 23.4+/-9 and 25.4+/-12, P = .003). CONCLUSIONS: Medial hypertrophy is present in the preacinar but not the intraacinar blood vessels of CDH rats before birth. Dexamethasone inhibits medial hypertrophy and reduces the number of muscularised intraacinar vessels. Antenatal glucocorticoids may reduce the risk of PH developing in human newborns with antenatally diagnosed CDH.

Animals↗
PubMed1998

Delayed maturation of the interstitial cells of Cajal: a new diagnosis for transient neonatal pseudoobstruction. Report of two cases.

The case histories of two neonates presenting with intestinal pseudoobstruction are presented. One boy infant was premature and the girl infant was full term. Both patients needed a defunctioning ileostomy, and biopsy findings of the intestine in both patients showed a lack of interstitial cells of Cajal (ICC). At the time of closure of the ileostomies to restore intestinal continuity, repeat biopsy results showed a normal pattern of distribution of ICC. Delay in the development of ICC in the gastrointestinal tract may be a cause of intestinal pseudoobstruction in the newborn.

Colon↗
PubMed1998

Abnormal colonic interstitial cells of Cajal in children with anorectal malformations.

BACKGROUND/PURPOSE: Constipation is a frequent functional problem in children after operation for all types of anorectal malformations. Although this has been assumed to be caused by hypomotility of the rectosigmoid colon, recent studies have demonstrated generalized colonic hypomotility in children with high or intermediate anomalies. The cause of this disorder is unknown. The aim of this study was to determine whether the observed colonic hypomotility seen in patients with anorectal malformations was caused by defects in distribution or density of interstitial cells of Cajal (ICC), recently identified as 'intestinal pacemaker cells'. METHODS: Colostomy specimens from 12 patients with high anorectal anomalies (ARM group; age 0 to 14 months) were compared with colostomy specimens from five control patients with nonmotility-related gastrointestinal pathology (age, 1 to 4 months). Specimens were immunohistochemically labelled with antibodies to PGP9.5, a marker for neural tissue, and antibodies to c-kit, a recently characterized marker for interstitial cells of Cajal (ICC). RESULTS: Ganglion cells were present in all histological specimens. Abnormalities in distribution and density of c-kit-positive ICC were present in 7 of 12 ARM patients. In two ARM patients, ICC were completely absent, and in five patients, ICC density was markedly reduced in circular muscle and at the submucosal border of circular muscle. Only five ARM patients had a distribution of ICC similar to that of control patients. CONCLUSION: Defects in the population of intestinal pacemaker cells may underlie the colonic hypomotility seen in high anorectal malformations and hence may contribute to refractory constipation.

Anus, Imperforate↗
PubMed1998

Antenatal glucocorticoid therapy suppresses angiotensin-converting enzyme activity in rats with nitrofen-induced congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Neonates with congenital diaphragmatic hernia (CDH) have a high morbidity and mortality rate caused by pulmonary hypoplasia associated with pulmonary hypertension (PH). In experimental CDH, antenatal glucocorticoid therapy improves surfactant biochemical immaturity, enhances lung compliance, and induces morphological maturation in CDH rats. The effects of steroid therapy on preventing or treating PH in this condition have not been studied. Angiotensin converting enzyme (ACE), which is produced by the vascular endothelium, is implicated in the pathogenesis of pulmonary hypertension. The aim of this study was to evaluate the effect of antenatal glucocorticoid therapy on ACE activity and expression in CDH rat lungs. METHODS: CDH was induced in fetal rats by the maternal administration of 100 mg nitrofen on day 9.5 of gestation (term, day 22). Dexamethasone (Dex) (0.25 mg/kg) was given by intraperitoneal injection on days 18.5 and 19.5 before delivery of the fetuses by cesarean section on day 21.5. Control animals received olive oil (OO) by gavage and normal saline (NS) as vehicle injection. ACE activity was measured spectrophotometrically in the lungs of rats from four treatment groups: CDH-NS, non-CDH-NS, CDH-Dex, and OO-NS controls. Total lung ACE activity (mU per lung) was significantly lower in CDH-NS (P = .002) and CDH-Dex (P = .004) rats compared with non-CDH-NS and OO-NS controls (9.1 +/- 1.0 and 10.7 +/- 1.3 v 16.2 +/- 1.6 and 15.4 +/- 1.7). When specific ACE activity (mU/mg protein) was derived by expressing ACE activity per milligram of lung protein, CDH-NS animals showed elevated specific ACE activity (P = .05) compared with OO-NS controls (6.31 +/- 1.1 v 4.4 +/- 0.4). CDH-Dex animals had a significantly lower specific ACE activity (P = .01) compared with CDH-NS and Non-CDH-NS rats (4.0 +/- 0.4 v 6.31 +/- 1.1 and 5.83 +/- 0.54). The specific ACE activity levels of CDH-Dex rats were equivalent to those seen in the lungs of OO-NS controls (P = .24). CONCLUSION: Antenatal steroid therapy, by suppressing pulmonary ACE activity, may reduce the risk of pulmonary hypertension developing in human newborns with antenatally diagnosed CDH.

Animals↗
PubMed1998

Energy requirements of surgical newborn infants receiving parenteral nutrition.

The energy requirement for mature newborn infants receiving total parenteral nutrition is approximately 100 kcal.kg-1.d-1. There is no necessity to increase the caloric intake after an uncomplicated operation. Energy requirements are affected by the maturity of the infant, the degree of operative stress, opioid medication, and the presence or absence of sepsis. In general, glucose intake should not exceed the resting energy expenditure. Glucose administration exceeding 18 g.kg-1.d-1 is associated with lipogenesis and reduced oxygenation of exogenous lipid. Resting energy expenditure varies widely between infants, and energy intake, based on clinical and biochemical monitoring, should be adjusted for individual patients.

Energy Intake↗
PubMed1998

Functional results following the antegrade continence enema procedure.

BACKGROUND: Forty children who underwent the antegrade continence enema (ACE) procedure for faecal soiling were studied to determine factors predictive of outcome. METHODS: There were four patient groups: (1) ambulant with spinal dysraphism (n = 13), (2) wheelchair bound with spinal dysraphism (n = 14), (3) ambulant with miscellaneous disorders (n = 11) and (4) wheelchair bound with miscellaneous disorders (n = 2). Effectiveness of the procedure was assessed using technical evaluation and quality-of-life improvement (QOLI) scores (0-5). Objective assessment included colonic transit time (CTT) and anorectal manometry. Median follow-up was 21 (range 5-37) months. RESULTS: Some 28 of 40 children achieved continence. The procedure was reversed in four of 40 children. Of the other 36 children with a functioning ACE stoma, all reported improvement in quality of life (mean QOLI score 3.5). There were no significant differences in technical evaluation score, QOLI score, CTT, manometry findings or continence between ambulant groups and the wheelchair-bound group with miscellaneous disorders. QOLI score, anorectal squeeze pressure and continence were significantly poorer in those who were wheelchair bound with spinal dysraphism. Absent squeeze pressure was associated with poor outcome. CONCLUSION: Wheelchair-bound children with spinal neuropathy have a poorer outcome following the ACE procedure. Although ACE is an effective method of promoting faecal continence, it is essential to determine the aetiology of incontinence and sphincter function before operation.

Adolescent↗
PubMed1998

Abscess after appendicectomy in children: the role of conservative management.

BACKGROUND: Intra-abdominal abscess remains a significant cause of morbidity following appendicectomy. In children, little emphasis has been placed on the non-invasive management of this complication using antibiotic therapy alone. This study reviews the experience of a paediatric surgical department in managing abscess arising after appendicectomy. METHODS: Hospital records of all children undergoing appendicectomy between January 1992 and January 1997 were reviewed retrospectively. RESULTS: Some 1024 children underwent appendicectomy over a 5-year period. Twenty three patients (2.2 per cent) developed abscesses after appendicectomy. Non-operative management with intravenous or oral antibiotics alone was successful in 21 patients, with complete clinical and radiological resolution of the abscess. Drainage of the septic collection was performed in only two patients: by laparotomy (n=1) and by the transrectal route (n=1). CONCLUSION: Antibiotic therapy alone is an efficacious and safe first-line treatment modality in children who develop this complication. Drainage of an abscess developing after appendicectomy is rarely necessary in children.

Abdominal Abscess↗