J.H. Louw Memorial Lecture. From puppy dogs to molecules: small-bowel atresia and short-gut syndrome.
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Biomedical subjects
Publications and source records attributed to D A Lloyd.
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Mental health generally and depression in particular have been repeatedly shown to vary in relation to gender, socioeconomic status, marital status, and age. These status differences may be linked to mental health because they tend to define important differences in stress exposure and in the availability of coping resources. This paper examines the capacity of the stress-process model to account for the social distribution of depression. We employ mediation analyses using data from a 1990-1991 survey of Toronto community residents. In general, we found hypothesized risk factors to vary across these statuses with depressive symptoms and disorder and the distribution of protective factors to vary inversely. Results indicate that the model as expressed in our analyses accounts for a substantial minority of observed depression differences across individuals and for a considerable portion of reliably observed variation across social statuses. Our findings with respect to major depressive disorder parallel those for depressive symptomatology. Most compelling is the nearly total explanation of the socioeconomic status association with depressive symptoms and the substantial contribution toward explaining the socioeconomic status-disorder relationship when stress process mediators are accounted for.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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OBJECTIVE: Illness is associated with the carriage of abnormal flora (aerobic Gram-bacilli except E. coli) in the oropharynx and rectum. The aim of this study was to investigate whether carriage of abnormal flora is associated with increased risk of sepsis and septicemia in surgical newborn infants. METHODS: A 2-year prospective study was carried out on 94 consecutive newborn infants requiring parenteral nutrition (PN) for gastrointestinal abnormalities. Throat and rectal swabs were taken on day 1 of PN and twice weekly. Patients were divided into two groups: abnormal flora (AF; n = 41) and normal flora (NF; n = 53). Sepsis was defined as clinical features of generalized inflammation requiring blood culture. Septicemia was the combination of sepsis and positive blood culture. RESULTS: Among the infants carrying abnormal flora Pseudomonas and Enterobacter spp. predominated. Duration of PN (AF median 30 days; NF median 9 days), incidence of sepsis (AF 29%; NF 6%), and septicemia (AF 22%; NF 2%) were significantly greater in the group of infants with abnormal flora. Surveillance cultures allow the detection of a subset of infants on PN at high risk of sepsis and septicemia. The degree of gut dysfunction related to the severity of underlying disease determines the duration of PN and the development of abnormal flora. The association between abnormal carriage and increased risk of sepsis and septicemia may be because of the intestinal endotoxin pool known to cause liver impairment and consequent suppression of systemic immunity.
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AIMS: To study the effect of prenatal glucocorticoid treatment on endothelial nitric oxide synthase (eNOS) expression in rats with congenital diaphragmatic hernia (CDH). METHODS: CDH was induced in fetal rats by the maternal administration of nitrofen on day 9.5 of gestation. Dexamethasone was administered on days 18.5 and 19.5 before delivery of the fetuses on days 20.5 and 21.5. Pulmonary eNOS protein expression was studied by western immunoblotting and immunohistochemistry. RESULTS: On day 20.5, eNOS expression was significantly reduced in CDH pups compared with normal control rats. Dexamethasone treated CDH pups had eNOS concentrations equivalent to those of normal animals. By day 21.5, however, there was no detectable difference in eNOS expression between the experimental groups. CONCLUSIONS: eNOS is deficient in near term (day 20.5) CDH rats. Dexamethasone restores eNOS expression in these animals to that seen in normal rat lungs. At term, the precise role of eNOS in the pathophysiology of CDH remains uncertain.
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