Steven Leach - Academia.edu (original) (raw)

Papers by Steven Leach

Research paper thumbnail of Role of capsule endoscopy and fecal biomarkers in small-bowel Crohn's disease to assess remission and predict relapse

Gastrointestinal Endoscopy

Capsule endoscopy (CE) is the most sensitive test to diagnose small-bowel Crohn&a... more Capsule endoscopy (CE) is the most sensitive test to diagnose small-bowel Crohn's disease (CD). Conventional parameters poorly assess CD remission, and although fecal biomarkers assess colonic activity, their role in assessing remission is uncertain. We report CE findings in small-bowel CD patients in clinical remission compared with fecal biomarkers and standard clinical tools to determine mucosal remission and predict relapses. Forty-three adult small-bowel CD patients in clinical remission (Crohn's Disease Activity Index [CDAI] <150) were prospectively enrolled at 4 academic centers and followed clinically for 12 months. Baseline CE studies were scored using the Capsule Endoscopy Scoring Index (CESI or Lewis score). Baseline and endpoint fecal biomarkers were assayed. CE findings were normal in 17 patients (40%), mild inflammation in 19 (44%), and moderate to severe inflammation in 7 (16%). Of the 26 patients (60%) with mucosal inflammation on CE, 85% had elevated baseline fecal calprotectin and 77% elevated lactoferrin level. Calprotectin and lactoferrin were normal in all patients without inflammation and elevated in all with moderate to severe inflammation. CESI correlated significantly with calprotectin, lactoferrin, and S100A12 levels but not either CDAI or C-reactive protein. During follow-up, 14% of patients exhibited a clinical flare; all had mucosal inflammation at CE and 83% had elevated baseline calprotectin and lactoferrin levels. In small-bowel CD patients in clinical remission, many had ongoing mucosal inflammation assessed by CE and fecal biomarkers. Only some developed a clinical flare during medium-term follow-up. These findings suggest CE and fecal biomarkers are useful in monitoring small-bowel CD progress.

Research paper thumbnail of Novel Biomarkers and the Future Potential of Biomarkers in Inflammatory Bowel Disease

Mediators of inflammation, 2017

There is increasing importance placed upon noninvasive assessment of gut inflammation. These tool... more There is increasing importance placed upon noninvasive assessment of gut inflammation. These tools are likely to be the key in differentiating intestinal inflammatory disease from functional disorders and in monitoring the response to intervention in individuals with known inflammatory conditions. Although various noninvasive markers are currently available, they have limitations and do not provide ideal utility. This review focuses on emerging markers of gut inflammation, highlighting the potential of specific markers.

Research paper thumbnail of Faecal Biomarkers in Inflammatory Bowel Disease

Journal of Gastroenterology and Hepatology, 2016

Over the last two decades, knowledge on fecal biomarkers has substantially increased. Nowadays, t... more Over the last two decades, knowledge on fecal biomarkers has substantially increased. Nowadays, these non-invasive markers of inflammation have significant clinical utility in the management of inflammatory bowel disease. Their use informs the decision to perform endoscopy before diagnosis is made right through to influencing therapeutic choices and the need for interval endoscopic assessment. In this review, the roles of two S100 proteins, calprotectin, and S100A12 are described along with that of lactoferrin, in the context of inflammatory bowel disease.

Research paper thumbnail of Vitamin D Deficiency in Children with Inflammatory Bowel Disease

Digestive Diseases and Sciences, Jan 11, 2011

Osteopenia and osteoporosis are commonly seen in inflammatory bowel disease (IBD). Vitamin D defi... more Osteopenia and osteoporosis are commonly seen in inflammatory bowel disease (IBD). Vitamin D deficiency potentially contributes to diminished bone acquisition in childhood.

Research paper thumbnail of S100 calgranulin proteins S100A8, S100A9 and S100A12 are expressed in the inflamed gastric mucosa of Helicobacter pylori-infected children

Canadian journal of gastroenterology = Journal canadien de gastroenterologie

ST Leach, HM Mitchell, CL Geczy, PM Sherman, AS Day. S100 calgranulin proteins S100A8, S100A9 and... more ST Leach, HM Mitchell, CL Geczy, PM Sherman, AS Day. S100 calgranulin proteins S100A8, S100A9 and S100A12 are expressed in the inflamed gastric mucosa of Helicobacter pyloriinfected children. Can J Gastroenterol 2008;22 :461-464.

Research paper thumbnail of P-006: The effect of exclusive enteral nutrition on the microbiota of newly diagnosed pediatric Crohn’s disease patients

Journal of Crohn's and Colitis, 2014

Research paper thumbnail of Effect of Exclusive Enteral Nutrition on Bone Metabolism in Children With Crohn's Disease

Journal of Pediatric Gastroenterology and Nutrition

An abstract is unavailable. This article is available as HTML full text and PDF.

Research paper thumbnail of Fecal Human β-Defensin 2 in Children with Cystic Fibrosis: Is There a Diminished Intestinal Innate Immune Response?

Digestive diseases and sciences, Jan 14, 2015

Defects in bacterial host defenses in the cystic fibrosis (CF) airways have been extensively inve... more Defects in bacterial host defenses in the cystic fibrosis (CF) airways have been extensively investigated, but the role of the intestinal innate immune system in CF is unknown. Human β-defensin 2 (HBD-2) is an antimicrobial protein produced by epithelial surfaces and upregulated by inflammation. Its expression in the CF intestine is unknown. To determine whether HBD-2 was present in the feces of patients with CF, and to compare fecal HBD-2 levels between CF and healthy controls (HC). To compare fecal HBD-2 levels in inflamed and noninflamed states, as measured by fecal calprotectin, as a secondary aim. Feces from children with CF and HC were collected for analysis. Thirty-three CF patients and 33 HC were recruited. All CF patients had detectable fecal HBD-2. There was no difference between fecal HBD-2 in CF and HC (median (IQR) 49.1 (19.7-77.2) versus 43.4 (26.5-71.9) ng/g; P = 0.7). Fecal calprotectin was significantly higher in the CF cohort than in HC (median (IQR) 61.3 (43.8-143...

Research paper thumbnail of Multiple Opportunistic Pathogens, but Not Pre-existing Inflammation, May Be Associated with Necrotizing Enterocolitis

Digestive Diseases and Sciences, 2015

Necrotizing enterocolitis (NEC) leads to significant morbidity and mortality in the neonatal inte... more Necrotizing enterocolitis (NEC) leads to significant morbidity and mortality in the neonatal intensive care unit. Although current evidence would suggest that bacteria contribute to the pathogenesis of NEC, no single bacterium has yet been identified. The aims of this study were to investigate fecal S100A12 concentrations and the intestinal bacterial community in premature infants (24-32 weeks) and investigate any associations between the microbiota and the development of NEC. Meconium and feces were collected from premature newborn infants (between 24 and 32 weeks gestation) over the first 4 weeks of life. Fecal S100A12 concentrations were assayed by immunoassay, and samples were subject to 16S rDNA analysis using next-generation sequencing techniques. Fecal samples were collected from four infants that developed NEC and 18 control infants. Prior to developing NEC, fecal S100A12 concentrations were not elevated; however, following NEC diagnosis, concentrations were highly elevated. The fecal bacterial communities of infants with NEC did not differ significantly from control infants. However, potentially pathogenic bacteria were detected in significantly more infants with NEC than in controls (p = 0.0007). At birth, fecal S100A12 concentrations were not elevated in premature infants subsequently developing NEC in this cohort. Following NEC diagnosis, S100A12 concentrations were highly elevated, suggesting that this potentially could act as a marker of disease progression. Higher detection rates of potentially pathogenic bacteria in NEC infants suggest that a range of potentially pathogenic bacteria may collectively contribute to NEC pathogenesis.

Research paper thumbnail of Mo1231 Attenuation of Intestinal Inflammation by Co-Supplementation of Glutamine and Arginine

Research paper thumbnail of Mo1232 Development of an Enhanced Nutritional Therapy for the Treatment of Crohn's Disease

Research paper thumbnail of Ablation of Dicer leads to widespread perturbation of signaling pathways

Biochemical and biophysical research communications, Jan 30, 2015

Dicer is an essential ribonuclease involved in the biogenesis of miRNAs. Previous studies have re... more Dicer is an essential ribonuclease involved in the biogenesis of miRNAs. Previous studies have reported downregulation of Dicer in multiple cancers including hepatocellular carcinoma. To identify signaling pathways that are altered upon Dicer depletion, we carried out quantitative phosphotyrosine profiling of liver tissue from Dicer knockout mice. We employed antibody-based enrichment of phosphotyrosine containing peptides coupled with SILAC spike-in approach for quantitation. High resolution mass spectrometry-based analysis identified 349 phosphotyrosine peptides corresponding to 306 unique phosphosites of which 75 were hyperphosphorylated and 78 were hypophosphorylated. Several receptor tyrosine kinases including MET, PDGF receptor alpha, Insulin-like growth factor 1 and Insulin receptor as well as non-receptor tyrosine kinases such as Src family kinases were found to be hyperphosphorylated upon depletion of Dicer. In addition, signaling molecules such as IRS-2 and STAT3 were hype...

Research paper thumbnail of P-119: Tacrolimus use in paediatric inflammatory bowel disease

Journal of Crohn's and Colitis, 2014

Research paper thumbnail of Su1367 Faecal Human Beta-Defensin 2 Levels in Children With Cystic Fibrosis

Research paper thumbnail of Single High Dose Oral Vitamin D3 Therapy (Stoss)- A Solution to Vitamin D Deficiency in Children with Inflammatory Bowel Disease?

Journal of pediatric gastroenterology and nutrition, Jan 15, 2015

Vitamin D deficiency is common in children with inflammatory bowel disease. The aim of this study... more Vitamin D deficiency is common in children with inflammatory bowel disease. The aim of this study was to determine the safety and efficacy of stoss therapy on vitamin D levels over a period of 6 months in children with inflammatory bowel disease and vitamin D deficiency (<50nmol/L). A retrospective chart review was undertaken, focusing upon children managed in the IBD clinic at Sydney Children's Hospital between 2006 and 2010. Those with a 25-hydroxyvitamin D level below 50nmol/L and who received stoss therapy were included in this study. Seventy six children received stoss therapy. There was a significant and sustained increase in 25-hydroxyvitamin D levels at all time points compared to baseline (40.8+/-7.5nmol/L), 1 month (145.6+/-51.8nmol/L), 3 months (87.1+/-28.4nmol/L) and 6 months 69.2+/-31.3nmol/L). There were no significant changes in serum calcium, phosphate or parathyroid hormone at any time points. Stoss therapy safely and effectively achieved and maintained a lev...

Research paper thumbnail of p21(Waf1/Cip1) inhibition of cyclin E/Cdk2 activity prevents endoreduplication after mitotic spindle disruption

Molecular and cellular biology, 1999

During a normal cell cycle, entry into S phase is dependent on completion of mitosis and subseque... more During a normal cell cycle, entry into S phase is dependent on completion of mitosis and subsequent activation of cyclin-dependent kinases (Cdks) in G1. These events are monitored by checkpoint pathways. Recent studies and data presented herein show that after treatment with microtubule inhibitors (MTIs), cells deficient in the Cdk inhibitor p21(Waf1/Cip1) enter S phase with a >/=4N DNA content, a process known as endoreduplication, which results in polyploidy. To determine how p21 prevents MTI-induced endoreduplication, the G1/S and G2/M checkpoint pathways were examined in two isogenic cell systems: HCT116 p21(+/+) and p21(-/-) cells and H1299 cells containing an inducible p21 expression vector (HIp21). Both HCT116 p21(-/-) cells and noninduced HIp21 cells endoreduplicated after MTI treatment. Analysis of G1-phase Cdk activities demonstrated that the induction of p21 inhibited endoreduplication through direct cyclin E/Cdk2 regulation. The kinetics of p21 inhibition of cyclin E/...

Research paper thumbnail of Fate mapping of ptf1a-expressing cells during pancreatic organogenesis and regeneration in zebrafish

Developmental dynamics : an official publication of the American Association of Anatomists, Jan 12, 2015

Pancreas development in zebrafish shares many features with mammals, including the participation ... more Pancreas development in zebrafish shares many features with mammals, including the participation of epithelial progenitor cells expressing pancreas transcription factor 1a (ptf1a). However, to date it has remained unclear whether, as in mammals, ptf1a-expressing zebrafish pancreatic progenitors are able to contribute to multiple exocrine and endocrine lineages. To delineate the lineage potential of ptf1a-expressing cells, we generated ptf1a:creER(T2) transgenic fish and performed genetic-inducible lineage tracing in developmental, regenerating, and ptf1a-deficient zebrafish pancreas. In addition to their contribution to the acinar cell lineage, ptf1a-expressing cells give rise to both pancreatic Notch-responsive-cells (PNCs) as well as small numbers of endocrine cells during pancreatic development. In fish with ptf1a haploinsufficiency, a higher proportion of ptf1a lineage-labeled cells are traced into the PNC and endocrine compartments. Further reduction of ptf1a gene dosage conver...

Research paper thumbnail of English

Research paper thumbnail of P-081: The major pathway by which polymeric formula reduces intestinal inflammation in Crohn’s disease patients a microarray-based analysis

Journal of Crohn's and Colitis, 2014

Introduction: Enteral nutrition (EN) and anti-TNF therapy (TNF) represent alternative approaches ... more Introduction: Enteral nutrition (EN) and anti-TNF therapy (TNF) represent alternative approaches to treat Crohn's disease (CD) with varying potential to impact quality of life (QOL). Aim: To contrast QOL for patients receiving partial EN (PEN), exclusive EN (EEN), and TNF therapies with ad lib diet for CD. Methods: Children with active CD, initiating treatment with PEN, EEN and TNF were prospectively followed over 8 weeks. All EN delivered by NG tube. PCDAI, and IMPACT for diseasespecific QOL were evaluated. Results: Patients on TNF had longer disease duration (n = 52; 1.3±1.7 years) than the PEN (n = 16; 0.3±0.7) or EEN (n = 22; 0.1±0.2) (p < 0.001) groups. Baseline PCDAI was higher among EEN patients (38.8±11.0) than those on PEN (38.1±18.6, ns) or TNF (30.2±12.0, p = 0.02), but there were no differences in disease activity after 8 weeks (ns) between the three groups. There were no baseline differences by mean age, or height z-scores (ns). There were no differences in mean IMPACT total scores at baseline between PEN (64.8±14.9), EEN (64.2±14.9) or TNF (64.0±14.9) groups, or at follow-up (77.1±15.1, 75.2±13.1, 75.5±14.9, respectively) (ns). There were also no differences in IMPACT domain scores, including social and emotional functioning across groups (ns). Patients in each group significantly improved in QOL scores over time. Conclusion: All groups showed improved QOL over the study period. EN patients did not show impaired social or emotional functioning compared to TNF group.

Research paper thumbnail of P011 FAECAL OSTEOPROTEGRIN IN PAEDIATRIC CROHN DISEASE

Journal of Crohn's and Colitis Supplements, 2009

Poster Communications 5 autoquestionnaires assessing depressed mood and were investigated during ... more Poster Communications 5 autoquestionnaires assessing depressed mood and were investigated during a psychiatric interview. They were also evaluated at D7 (7 days after), D15, D21 and D42. Circulating concentrations of TNFa and other cytokines were measured before beginning the treatment on day 0 (D0) and on D15 and D42. Analyses are currently in process.

Research paper thumbnail of Role of capsule endoscopy and fecal biomarkers in small-bowel Crohn's disease to assess remission and predict relapse

Gastrointestinal Endoscopy

Capsule endoscopy (CE) is the most sensitive test to diagnose small-bowel Crohn&amp;amp;amp;a... more Capsule endoscopy (CE) is the most sensitive test to diagnose small-bowel Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (CD). Conventional parameters poorly assess CD remission, and although fecal biomarkers assess colonic activity, their role in assessing remission is uncertain. We report CE findings in small-bowel CD patients in clinical remission compared with fecal biomarkers and standard clinical tools to determine mucosal remission and predict relapses. Forty-three adult small-bowel CD patients in clinical remission (Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Disease Activity Index [CDAI] &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;150) were prospectively enrolled at 4 academic centers and followed clinically for 12 months. Baseline CE studies were scored using the Capsule Endoscopy Scoring Index (CESI or Lewis score). Baseline and endpoint fecal biomarkers were assayed. CE findings were normal in 17 patients (40%), mild inflammation in 19 (44%), and moderate to severe inflammation in 7 (16%). Of the 26 patients (60%) with mucosal inflammation on CE, 85% had elevated baseline fecal calprotectin and 77% elevated lactoferrin level. Calprotectin and lactoferrin were normal in all patients without inflammation and elevated in all with moderate to severe inflammation. CESI correlated significantly with calprotectin, lactoferrin, and S100A12 levels but not either CDAI or C-reactive protein. During follow-up, 14% of patients exhibited a clinical flare; all had mucosal inflammation at CE and 83% had elevated baseline calprotectin and lactoferrin levels. In small-bowel CD patients in clinical remission, many had ongoing mucosal inflammation assessed by CE and fecal biomarkers. Only some developed a clinical flare during medium-term follow-up. These findings suggest CE and fecal biomarkers are useful in monitoring small-bowel CD progress.

Research paper thumbnail of Novel Biomarkers and the Future Potential of Biomarkers in Inflammatory Bowel Disease

Mediators of inflammation, 2017

There is increasing importance placed upon noninvasive assessment of gut inflammation. These tool... more There is increasing importance placed upon noninvasive assessment of gut inflammation. These tools are likely to be the key in differentiating intestinal inflammatory disease from functional disorders and in monitoring the response to intervention in individuals with known inflammatory conditions. Although various noninvasive markers are currently available, they have limitations and do not provide ideal utility. This review focuses on emerging markers of gut inflammation, highlighting the potential of specific markers.

Research paper thumbnail of Faecal Biomarkers in Inflammatory Bowel Disease

Journal of Gastroenterology and Hepatology, 2016

Over the last two decades, knowledge on fecal biomarkers has substantially increased. Nowadays, t... more Over the last two decades, knowledge on fecal biomarkers has substantially increased. Nowadays, these non-invasive markers of inflammation have significant clinical utility in the management of inflammatory bowel disease. Their use informs the decision to perform endoscopy before diagnosis is made right through to influencing therapeutic choices and the need for interval endoscopic assessment. In this review, the roles of two S100 proteins, calprotectin, and S100A12 are described along with that of lactoferrin, in the context of inflammatory bowel disease.

Research paper thumbnail of Vitamin D Deficiency in Children with Inflammatory Bowel Disease

Digestive Diseases and Sciences, Jan 11, 2011

Osteopenia and osteoporosis are commonly seen in inflammatory bowel disease (IBD). Vitamin D defi... more Osteopenia and osteoporosis are commonly seen in inflammatory bowel disease (IBD). Vitamin D deficiency potentially contributes to diminished bone acquisition in childhood.

Research paper thumbnail of S100 calgranulin proteins S100A8, S100A9 and S100A12 are expressed in the inflamed gastric mucosa of Helicobacter pylori-infected children

Canadian journal of gastroenterology = Journal canadien de gastroenterologie

ST Leach, HM Mitchell, CL Geczy, PM Sherman, AS Day. S100 calgranulin proteins S100A8, S100A9 and... more ST Leach, HM Mitchell, CL Geczy, PM Sherman, AS Day. S100 calgranulin proteins S100A8, S100A9 and S100A12 are expressed in the inflamed gastric mucosa of Helicobacter pyloriinfected children. Can J Gastroenterol 2008;22 :461-464.

Research paper thumbnail of P-006: The effect of exclusive enteral nutrition on the microbiota of newly diagnosed pediatric Crohn’s disease patients

Journal of Crohn's and Colitis, 2014

Research paper thumbnail of Effect of Exclusive Enteral Nutrition on Bone Metabolism in Children With Crohn's Disease

Journal of Pediatric Gastroenterology and Nutrition

An abstract is unavailable. This article is available as HTML full text and PDF.

Research paper thumbnail of Fecal Human β-Defensin 2 in Children with Cystic Fibrosis: Is There a Diminished Intestinal Innate Immune Response?

Digestive diseases and sciences, Jan 14, 2015

Defects in bacterial host defenses in the cystic fibrosis (CF) airways have been extensively inve... more Defects in bacterial host defenses in the cystic fibrosis (CF) airways have been extensively investigated, but the role of the intestinal innate immune system in CF is unknown. Human β-defensin 2 (HBD-2) is an antimicrobial protein produced by epithelial surfaces and upregulated by inflammation. Its expression in the CF intestine is unknown. To determine whether HBD-2 was present in the feces of patients with CF, and to compare fecal HBD-2 levels between CF and healthy controls (HC). To compare fecal HBD-2 levels in inflamed and noninflamed states, as measured by fecal calprotectin, as a secondary aim. Feces from children with CF and HC were collected for analysis. Thirty-three CF patients and 33 HC were recruited. All CF patients had detectable fecal HBD-2. There was no difference between fecal HBD-2 in CF and HC (median (IQR) 49.1 (19.7-77.2) versus 43.4 (26.5-71.9) ng/g; P = 0.7). Fecal calprotectin was significantly higher in the CF cohort than in HC (median (IQR) 61.3 (43.8-143...

Research paper thumbnail of Multiple Opportunistic Pathogens, but Not Pre-existing Inflammation, May Be Associated with Necrotizing Enterocolitis

Digestive Diseases and Sciences, 2015

Necrotizing enterocolitis (NEC) leads to significant morbidity and mortality in the neonatal inte... more Necrotizing enterocolitis (NEC) leads to significant morbidity and mortality in the neonatal intensive care unit. Although current evidence would suggest that bacteria contribute to the pathogenesis of NEC, no single bacterium has yet been identified. The aims of this study were to investigate fecal S100A12 concentrations and the intestinal bacterial community in premature infants (24-32 weeks) and investigate any associations between the microbiota and the development of NEC. Meconium and feces were collected from premature newborn infants (between 24 and 32 weeks gestation) over the first 4 weeks of life. Fecal S100A12 concentrations were assayed by immunoassay, and samples were subject to 16S rDNA analysis using next-generation sequencing techniques. Fecal samples were collected from four infants that developed NEC and 18 control infants. Prior to developing NEC, fecal S100A12 concentrations were not elevated; however, following NEC diagnosis, concentrations were highly elevated. The fecal bacterial communities of infants with NEC did not differ significantly from control infants. However, potentially pathogenic bacteria were detected in significantly more infants with NEC than in controls (p = 0.0007). At birth, fecal S100A12 concentrations were not elevated in premature infants subsequently developing NEC in this cohort. Following NEC diagnosis, S100A12 concentrations were highly elevated, suggesting that this potentially could act as a marker of disease progression. Higher detection rates of potentially pathogenic bacteria in NEC infants suggest that a range of potentially pathogenic bacteria may collectively contribute to NEC pathogenesis.

Research paper thumbnail of Mo1231 Attenuation of Intestinal Inflammation by Co-Supplementation of Glutamine and Arginine

Research paper thumbnail of Mo1232 Development of an Enhanced Nutritional Therapy for the Treatment of Crohn's Disease

Research paper thumbnail of Ablation of Dicer leads to widespread perturbation of signaling pathways

Biochemical and biophysical research communications, Jan 30, 2015

Dicer is an essential ribonuclease involved in the biogenesis of miRNAs. Previous studies have re... more Dicer is an essential ribonuclease involved in the biogenesis of miRNAs. Previous studies have reported downregulation of Dicer in multiple cancers including hepatocellular carcinoma. To identify signaling pathways that are altered upon Dicer depletion, we carried out quantitative phosphotyrosine profiling of liver tissue from Dicer knockout mice. We employed antibody-based enrichment of phosphotyrosine containing peptides coupled with SILAC spike-in approach for quantitation. High resolution mass spectrometry-based analysis identified 349 phosphotyrosine peptides corresponding to 306 unique phosphosites of which 75 were hyperphosphorylated and 78 were hypophosphorylated. Several receptor tyrosine kinases including MET, PDGF receptor alpha, Insulin-like growth factor 1 and Insulin receptor as well as non-receptor tyrosine kinases such as Src family kinases were found to be hyperphosphorylated upon depletion of Dicer. In addition, signaling molecules such as IRS-2 and STAT3 were hype...

Research paper thumbnail of P-119: Tacrolimus use in paediatric inflammatory bowel disease

Journal of Crohn's and Colitis, 2014

Research paper thumbnail of Su1367 Faecal Human Beta-Defensin 2 Levels in Children With Cystic Fibrosis

Research paper thumbnail of Single High Dose Oral Vitamin D3 Therapy (Stoss)- A Solution to Vitamin D Deficiency in Children with Inflammatory Bowel Disease?

Journal of pediatric gastroenterology and nutrition, Jan 15, 2015

Vitamin D deficiency is common in children with inflammatory bowel disease. The aim of this study... more Vitamin D deficiency is common in children with inflammatory bowel disease. The aim of this study was to determine the safety and efficacy of stoss therapy on vitamin D levels over a period of 6 months in children with inflammatory bowel disease and vitamin D deficiency (<50nmol/L). A retrospective chart review was undertaken, focusing upon children managed in the IBD clinic at Sydney Children's Hospital between 2006 and 2010. Those with a 25-hydroxyvitamin D level below 50nmol/L and who received stoss therapy were included in this study. Seventy six children received stoss therapy. There was a significant and sustained increase in 25-hydroxyvitamin D levels at all time points compared to baseline (40.8+/-7.5nmol/L), 1 month (145.6+/-51.8nmol/L), 3 months (87.1+/-28.4nmol/L) and 6 months 69.2+/-31.3nmol/L). There were no significant changes in serum calcium, phosphate or parathyroid hormone at any time points. Stoss therapy safely and effectively achieved and maintained a lev...

Research paper thumbnail of p21(Waf1/Cip1) inhibition of cyclin E/Cdk2 activity prevents endoreduplication after mitotic spindle disruption

Molecular and cellular biology, 1999

During a normal cell cycle, entry into S phase is dependent on completion of mitosis and subseque... more During a normal cell cycle, entry into S phase is dependent on completion of mitosis and subsequent activation of cyclin-dependent kinases (Cdks) in G1. These events are monitored by checkpoint pathways. Recent studies and data presented herein show that after treatment with microtubule inhibitors (MTIs), cells deficient in the Cdk inhibitor p21(Waf1/Cip1) enter S phase with a >/=4N DNA content, a process known as endoreduplication, which results in polyploidy. To determine how p21 prevents MTI-induced endoreduplication, the G1/S and G2/M checkpoint pathways were examined in two isogenic cell systems: HCT116 p21(+/+) and p21(-/-) cells and H1299 cells containing an inducible p21 expression vector (HIp21). Both HCT116 p21(-/-) cells and noninduced HIp21 cells endoreduplicated after MTI treatment. Analysis of G1-phase Cdk activities demonstrated that the induction of p21 inhibited endoreduplication through direct cyclin E/Cdk2 regulation. The kinetics of p21 inhibition of cyclin E/...

Research paper thumbnail of Fate mapping of ptf1a-expressing cells during pancreatic organogenesis and regeneration in zebrafish

Developmental dynamics : an official publication of the American Association of Anatomists, Jan 12, 2015

Pancreas development in zebrafish shares many features with mammals, including the participation ... more Pancreas development in zebrafish shares many features with mammals, including the participation of epithelial progenitor cells expressing pancreas transcription factor 1a (ptf1a). However, to date it has remained unclear whether, as in mammals, ptf1a-expressing zebrafish pancreatic progenitors are able to contribute to multiple exocrine and endocrine lineages. To delineate the lineage potential of ptf1a-expressing cells, we generated ptf1a:creER(T2) transgenic fish and performed genetic-inducible lineage tracing in developmental, regenerating, and ptf1a-deficient zebrafish pancreas. In addition to their contribution to the acinar cell lineage, ptf1a-expressing cells give rise to both pancreatic Notch-responsive-cells (PNCs) as well as small numbers of endocrine cells during pancreatic development. In fish with ptf1a haploinsufficiency, a higher proportion of ptf1a lineage-labeled cells are traced into the PNC and endocrine compartments. Further reduction of ptf1a gene dosage conver...

Research paper thumbnail of English

Research paper thumbnail of P-081: The major pathway by which polymeric formula reduces intestinal inflammation in Crohn’s disease patients a microarray-based analysis

Journal of Crohn's and Colitis, 2014

Introduction: Enteral nutrition (EN) and anti-TNF therapy (TNF) represent alternative approaches ... more Introduction: Enteral nutrition (EN) and anti-TNF therapy (TNF) represent alternative approaches to treat Crohn's disease (CD) with varying potential to impact quality of life (QOL). Aim: To contrast QOL for patients receiving partial EN (PEN), exclusive EN (EEN), and TNF therapies with ad lib diet for CD. Methods: Children with active CD, initiating treatment with PEN, EEN and TNF were prospectively followed over 8 weeks. All EN delivered by NG tube. PCDAI, and IMPACT for diseasespecific QOL were evaluated. Results: Patients on TNF had longer disease duration (n = 52; 1.3±1.7 years) than the PEN (n = 16; 0.3±0.7) or EEN (n = 22; 0.1±0.2) (p < 0.001) groups. Baseline PCDAI was higher among EEN patients (38.8±11.0) than those on PEN (38.1±18.6, ns) or TNF (30.2±12.0, p = 0.02), but there were no differences in disease activity after 8 weeks (ns) between the three groups. There were no baseline differences by mean age, or height z-scores (ns). There were no differences in mean IMPACT total scores at baseline between PEN (64.8±14.9), EEN (64.2±14.9) or TNF (64.0±14.9) groups, or at follow-up (77.1±15.1, 75.2±13.1, 75.5±14.9, respectively) (ns). There were also no differences in IMPACT domain scores, including social and emotional functioning across groups (ns). Patients in each group significantly improved in QOL scores over time. Conclusion: All groups showed improved QOL over the study period. EN patients did not show impaired social or emotional functioning compared to TNF group.

Research paper thumbnail of P011 FAECAL OSTEOPROTEGRIN IN PAEDIATRIC CROHN DISEASE

Journal of Crohn's and Colitis Supplements, 2009

Poster Communications 5 autoquestionnaires assessing depressed mood and were investigated during ... more Poster Communications 5 autoquestionnaires assessing depressed mood and were investigated during a psychiatric interview. They were also evaluated at D7 (7 days after), D15, D21 and D42. Circulating concentrations of TNFa and other cytokines were measured before beginning the treatment on day 0 (D0) and on D15 and D42. Analyses are currently in process.