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E V O'Loughlin

Publications and source records attributed to E V O'Loughlin.

At least 19 recordsLinked to original sources
PubMed2005

NMR measurements of the diffusional permeability of water in cultured colonic epithelial cancer cells.

The water residence time and diffusional water permeability in colonic epithelial T84 cancer cells was measured using (1)H NMR spectroscopy; the values estimated were 35.2+/-2.8 ms and (7.4+/-0.6)x10(-3)cms(-1), respectively. Water permeability was inhibited to approximately 10% of its original value by the mercurial diuretic, p-chloromercuribenzenesulfonate (PCMBS; 1mM), and fully restored by dithiothreitol (DTT; 1mM). The permeability was also inhibited reversibly to approximately 55%, by extracellular glibenclamide (1mM), an inhibitor of some ATP-binding cassette (ABC) transporters, including the cystic fibrosis transmembrane conductance regulator (CFTR). Addition of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IMBX; 0.1-1mM) and the adenylate cyclase activator, forskolin (0.1-1mM) did not alter water permeability. It is concluded that in T84 cells water diffuses through the membrane lipid bilayer and via channels that are inhibited by PCMBS, including the channels that are known to be inhibited by glibenclamide.

4-Chloromercuribenzenesulfonate↗
PubMed2005

Anterior abdominal wall defects and biliary obstruction.

Three infants with anterior abdominal wall defects (gastroschisis and exomphalos) who presented with obstructive jaundice secondary to biliary obstruction, are described. All three infants had abnormal biliary systems, with mechanical distortion of the biliary tree. Biliary obstruction secondary to structural biliary anomalies should be considered in patients with abdominal wall defects and cholestasis, as prolonged unrelieved biliary obstruction may lead to biliary cirrhosis and portal hypertension.

Cholangiography↗
PubMed2004

Aquaporin expression is downregulated in a murine model of colitis and in patients with ulcerative colitis, Crohn's disease and infectious colitis.

Colitis is associated with alterations in electrolyte and water transport. These changes give rise to some of the symptoms experienced by patients with colitis. Alterations in fluid flux may also contribute to increased susceptibility to mucosal injury. Recently, endogenous water channel proteins (aquaporins; AQPs), have been identified in colonic tissue. The expression of AQP4, AQP7 and AQP8 was examined, via reverse transcription/polymerase chain reaction, Western blotting and immunohistochemistry, in a murine model of colitis and in patients with inflammatory bowel disease or infectious colitis. Colitis was induced in C57BL/6 mice by the addition of 2.5% dextran sodium sulphate (DSS) to their drinking water. AQP expression in these mice was assessed following 12 h to 7 days of DSS exposure and during the recovery phase from 1 to 15 days following cessation of DSS exposure. Colonic water transport was measured after 1 and 3 days of DSS and following 7 days of recovery. The expression of AQP4 and AQP8 mRNA was significantly decreased after 12-24 h of DSS exposure and remained depressed throughout the treatment period. Expression of AQP7 was more variable. Protein expression followed a similar pattern to that observed for AQP mRNA. Significant alteration in colonic fluid secretion was correlated with reduced expression of AQP isoforms. Significantly, patients with active ulcerative colonic, Crohn's colitis or infectious colitis had similar dramatic reductions in AQP expression that appeared to be correlated with disease activity. Thus, colonic injury in both mouse and man is associated with a downregulation in AQP expression.

Animals↗
PubMed2004

Non-surgical interventions for eosinophilic oesophagitis.

BACKGROUND: Patients with eosinophilic oesophagitis (EO) present with difficulty swallowing, vomiting, regurgitation, chest and/or abdominal pain. People with EO frequently fail to respond to treatment with gastric acid suppressants or anti-reflux surgery. OBJECTIVES: To evaluate the benefits and harms of medical interventions for eosinophilic oesophagitis. SEARCH STRATEGY: We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group trials register (The Cochrane Library Issue 1, 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to February 2004) and EMBASE (1980 to February 2004). SELECTION CRITERIA: Randomised controlled trials were included if they compared a medical or dietary intervention for eosinophilic oesophagitis with a placebo or one medical intervention with another medical intervention. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened the title of abstracts. MAIN RESULTS: No completed RCTs were found in the published literature. We found one abstract reporting preliminary data from an RCT (not completed) comparing oral prednisolone with topical (swallowed metered dose) fluticasone in children. In this study (50 children enrolled to date) healing rates of oesophagitis and symptom resolution with fluticasone were similar to those with prednisolone. For another ongoing RCT, comparing the efficacy of swallowed fluticasone with placebo for eosinophilic oesophagitis in males and females aged 3 to 21 years no results are available. REVIEWERS' CONCLUSIONS: The lack of completed RCT's makes it impossible to compare the relative benefits and harms of the wide range of medical interventions currently used for treating EO. Published case series suggest that an elemental diet, oral steroids and topical steroids all offer some benefits. However, lack of a comparison group in these studies makes it impossible to evaluate the effect of these interventions.

Androstadienes↗
PubMed2001

Effect of Shiga toxin and Shiga-like toxins on eukaryotic cells.

Shigella dysenteriae and Shiga-toxin-producing Escherichia coli (STEC) elaborate the AB holotoxins, Shiga or Shiga-like toxins (Stx). Stx play a major role in the pathogenesis of haemorrhagic colitis and haemolytic uremic syndrome. This review provides an overview of the mechanisms of action of Stx and a model of the pathogenesis of Stx-induced disease.

Colitis↗
PubMed2001

The changing pattern of diagnosis of infantile cholestasis.

OBJECTIVE: Cholestatic liver disease in infancy is caused by a wide range of conditions. This study reviews the pattern of diagnosis of infants with cholestasis presenting to a tertiary referral paediatric hospital in Sydney, Australia, during a 12-year period (1985-96). METHODOLOGY: Infants aged less than 6 months with cholestasis were identified retrospectively from hospital records and data retrieved from the medical records. RESULTS: There were 205 infants identified as having cholestatic liver disease. The aetiology of the cholestasis was idiopathic in 25%, metabolic/genetic in 23%, and due to obstruction in 20%, parenteral nutrition in 20%, infection in 9% and bile duct hypoplasia in 3%. CONCLUSIONS: This study highlights the changing patterns of diagnosis of cholestatic liver disease in infants at a tertiary paediatric facility, demonstrating that up to 50% of cases are now due to genetic/metabolic diseases or parenteral nutrition, and a high proportion are due to idiopathic disease.

Age of Onset↗
PubMed2001

Nationwide study of haemolytic uraemic syndrome: clinical, microbiological, and epidemiological features.

AIMS: To establish the incidence and aetiology of haemolytic uraemic syndrome (HUS) in Australia and compare clinical and microbial characteristics of sporadic and outbreak cases. METHODS: National active surveillance through the Australian Paediatric Surveillance Unit with monthly case notification from paediatricians, July 1994 to June 1998. Children under 15 years presenting with microangiopathic haemolytic anaemia, thrombocytopenia, and acute renal impairment were identified. RESULTS: Ninety eight cases were identified (incidence 0.64 per 10(5) children <15 years/annum and 1.35 per 10(5) children <5 years/annum). Eighty four were associated with diarrhoea (64 sporadic, 20 constituting an outbreak) and 14 were atypical. Shiga toxin producing Escherichia coli (STEC) O111:H- was the most common isolate in sporadic HUS and caused the outbreak. However O111:H- isolates from outbreak and sporadic cases differed in phage type and subtyping by DNA electrophoresis. STEC isolates from sporadic cases included O26:H-, O113:H21, O130:H11, OR:H9, O157:H-, ONT:H7, and ONT:H-. STEC O157:H7 was not isolated from any case. Only O111:H- isolates produced both Shiga toxins 1 and 2 and possessed genes encoding E coli attaching and effacing gene (intimin) and enterohemolysin. Outbreak cases had worse gastrointestinal and renal disease at presentation and more extrarenal complications. CONCLUSIONS: Linking national surveillance with a specialised laboratory service allowed estimation of HUS incidence and provided information on its aetiology. In contrast to North America, Japan, and the British Isles, STEC O157:H7 is rare in Australia; however, non-O157:H7 STEC cause severe disease including outbreaks. Disease severity in outbreak cases may relate to yet unidentified virulence factors of the O111:H- strain isolated.

Adolescent↗
PubMed2001

Interleukin 2 modulates ion secretion and cell proliferation in cultured human small intestinal enterocytes.

AIMS: To determine if interleukin 2 (IL-2) alters epithelial transport and barrier function in cultured human small intestinal enterocytes. METHODS: Confluent monolayers of small intestinal cells derived from duodenal biopsies were treated with IL-2 0.2-50 U/ml for 24 hours prior to study. Transport measurements were performed under short circuited conditions in Ussing chambers, with and without the secretagogues forskolin and 3-isobutyl-1-methyl xanthine (IBMX). Serosal to mucosal flux of 3[H] mannitol (permeability) and 3[H] thymidine uptake (proliferation) were measured. IL-2 receptor and cystic fibrosis transmembrane conductance regulator (CFTR) mRNA were identified using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: IL-2 did not alter baseline electrical parameters but caused a significant increase in cAMP dependent chloride secretion. The effect was mediated by the IL-2 receptor and paralleled a rapid increase in tyrosine phosphorylation, janus kinase 1, and signal transducers and activators of transcription (STATs) 1, 3, and 5. IL-2 significantly increased proliferation but at a lower dose than observed for enhanced secretion but did not alter permeability. IL-2 receptor beta and gammac chains and CFTR mRNA were identified by RT-PCR. CONCLUSIONS: IL-2 treatment enhances cAMP stimulated chloride secretion and cellular proliferation in a human small intestinal cell line expressing a functional IL-2 receptor.

Analysis of Variance↗
PubMed2000

Esophageal dysmotility in brothers with an FG-like syndrome.

We present 4 brothers with developmental delay, minor anomalies, and symptoms due to gastrointestinal dysmotility. There was some resemblance with FG syndrome, although none of the brothers had sufficient findings to make this diagnosis. The index case presented with at age 1 month with screaming episodes, mild gastro-esophageal reflux (GER), and severe constipation. Esophageal manometry studies were consistent with the diagnosis of "nutcracker esophagus." Symptomatic and manometric improvement followed treatment with oral calcium channel blockers. Two older and less severely affected brothers had similar manometric findings but did not require treatment. A fourth brother with symptoms in infancy now has normal esophageal manometry findings. These boys in all likelihood have an X-linked syndrome with manifestations of FG syndrome, in which treatment with calcium channel blockers, produces clinical and manometric improvement. The FG syndrome is an X-linked syndrome of multiple congenital anomalies/mental retardation with facultative manifestations of gastrointestinal dysmotility, including gastro-esophageal reflux, severe feeding difficulties, and constipation. Esophageal dysmotility, in particular "nutcracker esophagus," should be suspected in infants with the FG syndrome and screaming attacks.

Abnormalities, Multiple↗
PubMed2000

Do eicosanoids cause colonic dysfunction in experimental E coli O157:H7 (EHEC) infection?

BACKGROUND: The pathophysiology of enterohaemorrhagic Escherichia coli (EHEC) infection remains unclear. Eicosanoids have been implicated as pathophysiological mediators in other colitides. AIMS: To determine if prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) contribute to mucosal inflammation and dysfunction in EHEC colitis. METHODS: Ten day old rabbits were infected with EHEC. For five days after infection, mucosal synthesis of PGE(2) and LTB(4) was measured in distal colonic tissue from control and infected animals and (51)Cr-EDTA permeability was assessed in vivo. Myeloperoxidase activity was measured and histological inflammation and damage were assessed at five days in control and infected animals and after treatment of infected animals with the LTB(4) synthesis inhibitor MK-886. In separate experiments, ion transport was measured in Ussing chambers, before and after in vitro addition of the cyclooxygenase inhibitor indomethacin. RESULTS: LTB(4) synthesis was increased from day 2 after infection onwards and PGE(2) synthesis was increased on day 3. Mucosal permeability did not increase until day 5 after infection. MK-886 inhibited colonic LTB(4) production but did not reduce diarrhoea, inflammation, or mucosal damage. Electrolyte transport was not significantly altered on day 3 after infection. However, both Cl secretion and reduced Na absorption found on day 5 were partially reversed by indomethacin. CONCLUSIONS: Tissue synthesis of PGE(2) and LTB(4) did not correlate temporally with EHEC induced inflammation or changes in mucosal permeability and ion transport. Cyclooxygenase inhibition partially reversed ion transport abnormalities but lipoxygenase inhibition did not affect mucosal inflammation or histological damage. We conclude that the contribution of eicosanoids to mucosal injury and dysfunction is more complex than previously suggested.

Animals↗
PubMed1999

Accidental paracetamol overdosing and fulminant hepatic failure in children.

OBJECTIVE: To delineate clinical characteristics useful for identifying children with liver failure due to accidental paracetamol overdose. DESIGN: Retrospective review of medical records of all patients admitted from 1985 to 1998 with fulminant hepatic failure. SETTING: Royal Alexandra Hospital for Children, a tertiary referral centre for paediatric liver transplantation. MAIN OUTCOME MEASURES: Contribution of paracetamol to liver failure; other risk factors for liver failure; comparison of clinical features of paracetamol group and others. RESULTS: 18 patients were identified. Eight were considered to have accidental paracetamol hepatotoxicity. In a further three, other risk factors were present but paracetamol was considered a major contributor to liver failure. The seven remaining patients had other risk factors for liver failure. Patients with paracetamol-induced liver failure usually had an acute prodromal illness with prolonged fasting and, at presentation, had encephalopathy, coagulopathy, very high transaminase levels, but disproportionately low total bilirubin levels. Five patients had hypoglycaemia. End-stage liver failure occurred in 4/11 of the paracetamol group compared with 7/7 of the others. CONCLUSION: Accidental paracetamol overdose is associated with fulminant hepatic failure in infants and children. Patients present with high transaminase levels and liver synthetic failure out of proportion to the level of serum bilirubin. Prompt identification of such patients is important as many recover with supportive therapy.

Acetaminophen↗
PubMed1999

Elevated plasma levels of F2 alpha isoprostane in cystic fibrosis.

Cystic fibrosis (CF) is associated with chronic lung infection, inflammation, and elevated indices of oxidative stress. Recently, isoprostanes were shown to be a reliable in vivo marker of oxidant injury with 8-iso-PGF2 alpha, shown to cause airflow obstruction and plasma exudation in guinea pig lung. The present study was designed to examine the relationship between 8-iso-PGF2 alpha levels, plasma antioxidants, and clinical status in CF. We hypothesized that plasma 8-iso-PGF2 alpha levels would be higher in subjects with CF compared to healthy controls. Plasma 8-iso-PGF2 alpha levels were prospectively measured in 22 subjects with CF and nine healthy controls using an 8-isoprostane enzyme immunoassay kit along with plasma vitamins A, E, and beta-carotene. Plasma 8-iso-PGF2 alpha levels were shown to be significantly elevated in the CF subjects compared to controls (319.6 +/- 52.6 vs. 145.0 +/- 21.0 pg/mL, P = 0.005). Plasma levels of antioxidants were significantly lower for the CF subjects compared to the controls (vitamin A, P < 0.003; vitamin E, P < 0.001; and beta-carotene, P < 0.01). This study confirms significantly elevated lipid peroxidation in CF using 8-iso-PGF2 alpha levels.

Adolescent↗
PubMed1999

Cisapride in the control of symptoms in infants with gastroesophageal reflux: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of cisapride in the treatment of uncomplicated gastroesophageal reflux in children younger than 36 months of age. STUDY DESIGN: A total of 95 patients satisfied the entry criteria and were randomly assigned to double-blind treatment with either cisapride (n = 50), 0.2 mg/kg 4 times daily, or placebo (n = 45) for 2 weeks. At the end of the 2-week treatment period, symptom diary and parental evaluation with repeat 24-hour pH study were performed. RESULTS: Sixty-eight patients completed the trial (38 in the cisapride group and 30 in the placebo group). There were no significant differences in the symptoms of crying, vomiting, or gagging; the overall symptom intensity score; or parental global evaluations. There was a significant difference (P <.03) in the percent time pH <4, the number of reflux episodes lasting more than 5 minutes, and the duration of the longest episode. No significant difference was demonstrated for the number of episodes with pH <4 or the reflux score. CONCLUSIONS: Cisapride was no better than placebo for relief of symptoms in children with uncomplicated gastroesophageal reflux. A beneficial effect was demonstrated in the cisapride group in relation to the measured parameters for esophageal acid exposure time.

Administration, Oral↗
PubMed1999

Normal growth in cystic fibrosis associated with a specialised centre.

OBJECTIVE: To assess the impact of lifetime continuous care within the John Hunter Hospital cystic fibrosis (CF) clinics on growth and lung function. DESIGN: A cross sectional survey of variables affecting nutritional status in CF was undertaken for 1993 and 1997. Data were retrieved from medical records and grouped into 5 year age bands. MAIN OUTCOME MEASURES: Change in height z-score, weight centile, and forced expiratory volume in one second (FEV(1)) between patient cohorts receiving specialised care for different lengths of time. RESULTS: Improved mean height z-score (-0.880 v -0.047) and weight centile (28.3% v 48.1%) for the 10-15 year age group in 1997, who had received continuous lifetime care within the clinic, compared with the same age group in 1993, for whom continuous medical care started at an older age. There was no corresponding improvement in FEV(1), as an indicator of lung function, in this group (81.6% predicted v 89.5% predicted). CONCLUSIONS: This study suggests that lifetime continuous care within a specialised CF centre is associated with improved growth but not improved lung function.

Adolescent↗
PubMed1998

Discrepancies between males and females with cystic fibrosis in dietary intake and pancreatic enzyme use.

BACKGROUND: Length of survival of females with cystic fibrosis is worse than it is in males. Results of current research have shown an important correlation among dietary intake, nutritional status, lung function, and survival. The purpose of this study was to explore gender differences in dietary intake and pancreatic enzyme replacement therapy in males and females with cystic fibrosis. METHODS: The study was a cross-sectional measurement of clinical characteristics, energy, and fat intakes in males and females attending the cystic fibrosis outpatients clinics of the John Hunter Hospital, Newcastle, Australia. Twenty-nine subjects, (17 females and 12 males), completed 4-day weighed food records to measure total energy intake and the contribution of macronutrients and to document use of pancreatic enzyme replacement therapy. Energy intake was assessed as the percentage of the recommended energy intake for age and sex. RESULTS: Females with cystic fibrosis had significantly lower energy and fat intakes than males, whereas the females used significantly more pancreatic enzyme replacement therapy. There were no significant differences in clinical characteristics between groups. CONCLUSION: The results support the possibility that gender differences in the energy and fat intakes of older patients may contribute to differential median survival time of males and females with cystic fibrosis.

Adolescent↗
PubMed1997

Management of childhood gastroenteritis in the community.

OBJECTIVE: To examine general practitioners' (GPs') management of childhood gastroenteritis and their perceptions about barriers to optimal management in the community. DESIGN: Cross-sectional postal survey in which GPs' self-reported practices were assessed by a paediatric gastroenterologist for compliance with published guidelines. SETTING: Hunter region of NSW, mid 1994. PARTICIPANTS: All 422 urban and rural GPs practising in the Hunter region were sent questionnaires; 289 (243 urban and 46 rural) GPs responded. RESULTS: Nearly all GPs (97%) recommended clear fluids in the management of childhood gastroenteritis, with 195 (67%) recommending oral electrolyte solution. Management practices were assessed as: optimal, 170 GPs (59%); acceptable, 33 GPs (11%); inappropriate or potentially dangerous, 38 GPs (13%); and too vague to classify, 48 GPs (17%). Multiple logistic regression analysis showed that better management strategies were associated with being younger and practising in rural areas. GPs perceived the main barriers to effective management of gastroenteritis were: inadequate parenting skills, 131 GPs (45%); lack of parental understanding about the illness, 118 GPs (41%); other social problems, 67 GPs (23%); parental anxiety, 57 GPs (20%); and conflicting advice given by others, 42 GPs (15%). Only 33 GPs (11%) identified the taste and 16 (6%) the cost of oral electrolyte solution as major barriers. CONCLUSIONS: Most GPs reported management of gastroenteritis was acceptable, although not necessarily optimal. GPs need to ensure that parents fully understand the nature of their child's illness and their recommendations for management at home.

Child↗
PubMed1997

Neurofibromatosis of the small intestine mesentery in a child with neurofibromatosis type 1.

The authors present a case of mesenteric neurofibromatosis in a child, which is a rare complication of neurofibromatosis type 1 (NF1). This case is presented to illustrate the clinical features and the radiological appearance of mesenteric neurofibromatosis, which, in the appropriate clinical setting of NF1, are diagnostic. The authors also discuss the long-term complications of this condition, which includes the potential risk of malignant degeneration.

Child↗