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BACKGROUND: Thiopurine drugs are effective treatment options in inflammatory bowel disease and other conditions but discontinued in some patients due to toxicity. METHODS: We investigated thiopurine-induced toxicity in a pediatric inflammatory bowel disease cohort by utilizing exome sequencing data across a panel of 46 genes, including TPMT and NUDT15. RESULTS: The cohort included 487 patients with a median age of 13.1 years. Of the 396 patients exposed to thiopurines, myelosuppression was observed in 11%, gastroenterological intolerance in 11%, hepatotoxicity in 4.5%, pancreatitis in 1.8%, and "other" adverse effects in 2.8%. TPMT (thiopurine S-methyltransferase) enzyme activity was normal in 87.4%, intermediate 12.3%, and deficient in 0.2%; 26% of patients with intermediate activity developed toxicity to thiopurines. Routinely genotyped TPMT alleles associated with defective enzyme activity were identified in 28 (7%) patients: TPMT*3A in 4.5%, *3B in 1%, and *3C in 1.5%. Of these, only 6 (21%) patients developed toxic responses. Three rare TPMT alleles (*3D, *39, and *40) not assessed on routine genotyping were identified in 3 patients, who all developed toxic responses. The missense variant p.R139C (NUDT15*3 allele) was identified in 4 patients (azathioprine 1.6 mg/kg/d), but only 1 developed toxicity. One patient with an in-frame deletion variant p.G13del in NUDT15 developed myelosuppression at low doses. Per-gene deleteriousness score GenePy identified a significant association for toxicity in the AOX1 and DHFR genes. CONCLUSIONS: A significant association for toxicity was observed in the AOX1 and DHFR genes in individuals negative for the TPMT and NUDT15 variants. Patients harboring the NUDT15*3 allele, which is associated with myelosuppression, did not show an increased risk of toxicity.
This study reports thiopurine-induced toxicity in pediatric patients with inflammatory bowel disease. The findings are presented in the context of genetic variations, focusing on genes implicated in thiopurine drug metabolism, thereby contributing to the missing pharmacogenomic association in patients developing toxicity.
ABSTRACT
BACKGROUND: Oral manifestations of paediatric Crohn's disease (CD) are reported in up to 60% of cases. Lip biopsy can be used to histologically diagnose oral CD. We evaluated the utility of lip biopsy in children under initial investigation for potential CD. METHODS: A 10-year retrospective review of electronic patient records at a single tertiary paediatric surgery centre was performed. All patients aged ≤16 years who underwent lip biopsy were included. Clinical features, histology, and diagnostic details were extracted. RESULTS: Forty-two children underwent lip biopsy. Median age at biopsy was 13.3 years (11.0-14.9). Final diagnosis was CD in 21/42 (50%) children, indeterminant colitis in 3/42 (7%), orofacial granulomatosis (OFG) in 3/42 (7%), coeliac disease in 1/42 (2%), and eosinophilic oesophagitis in 1/42 (2%). Thirteen children (31%) received no formal diagnosis. The most common symptoms reported were oral ulceration (33/42, 79%), lip swelling (21/42, 50%), and abdominal pain (19/42, 45%). Lip biopsy histology was normal in 11/42 (26%). In 24/42 (57%), non-granulomatous inflammation was seen. In 7/42 (17%) lip biopsy identified granulomatous inflammation: three (7%) had endoscopic biopsies concordant for CD, three (7%) had negative endoscopic biopsies but were diagnosed with CD, and one was diagnosed with OFG (2%). Sensitivity was 29% and specificity was 95%. CONCLUSION: Lip biopsy has low sensitivity but high specificity for diagnosing CD. Lip biopsy diagnosed CD in 7% when endoscopic biopsies were negative, enabling treatment. LB is a useful diagnostic test for CD in children presenting with oral symptoms. LEVEL OF EVIDENCE: III.
Subject(s)
Crohn Disease , Granulomatosis, Orofacial , Lip , Child , Humans , Adolescent , Retrospective Studies , Granulomatosis, Orofacial/diagnosis , Granulomatosis, Orofacial/drug therapy , Biopsy , InflammationABSTRACT
OBJECTIVES: Patients with paediatric inflammatory bowel disease (IBD) constitute one of the largest cohorts requiring transition from paediatric to adult services. Standardised transition care improves short and long-term patient outcomes. This study aimed to detail the current state of transition services for IBD in the United Kingdom (UK). METHODS: We performed a nationwide study to ascertain current practice, facilities and resources for children and young people with IBD. Specialist paediatric IBD centres were invited to contribute data on: timing of transition/transfer of care; transition resources available including clinics, staff and patient information; planning for future improvement. RESULTS: Twenty of 21 (95%) of invited centres responded. Over 90% of centres began the transition process below 16âyears of age and all had completed transfer to adult care at 18âyears of age. The proportion of patients in the transition process at individual centres varied from 10% to 50%.Joint clinics were held in every centre, with a mean of 12.9 clinics per year. Adult and paediatric gastroenterologists attended at all sites. Availability of additional team members was patchy across the UK, with dietetic, psychological and surgical attendance available in <50% centres. A structured transition tool was used in 75% of centres. Sexual health, contraception and pregnancy were discussed by <60% of teams. CONCLUSIONS: This study provides real-world clinical data on UK-wide transition services. These data can be used to develop a national strategy to complement current transition guidelines, focused on standardising services whilst allowing for local implementation.
Subject(s)
Colitis , Inflammatory Bowel Diseases , Transitional Care , Adolescent , Adult , Child , Female , Humans , Inflammatory Bowel Diseases/therapy , Pregnancy , United KingdomABSTRACT
The precise role of periostin, an extra-cellular matrix protein, in inflammatory bowel disease (IBD) is unclear. Here, we investigated periostin in paediatric IBD including its relationship with disease activity, clinical outcomes, genomic variation and expression in the colonic tissue. Plasma periostin was analysed using ELISA in 144 paediatric patients and 38 controls. Plasma levels were assessed against validated disease activity indices in IBD and clinical outcomes. An immuno-fluorescence for periostin and detailed isoform-expression analysis in the colonic tissue was performed in 23 individuals. We integrated a whole-gene based burden metric 'GenePy' to assess the impact of variation in POSTN and 23 other genes functionally connected to periostin. We found that plasma periostin levels were significantly increased during remission compared to active Crohn's disease. The immuno-fluorescence analysis demonstrated enhanced peri-cryptal ring patterns in patients compared to controls, present throughout inflamed, as well as macroscopically non-inflamed colonic tissue. Interestingly, the pattern of isoforms remained unchanged during bowel inflammation compared to healthy controls. In addition to its role during the inflammatory processes in IBD, periostin may have an additional prominent role in mucosal repair. Additional studies will be necessary to understand its role in the pathogenesis, repair and fibrosis in IBD.
Subject(s)
Cell Adhesion Molecules/genetics , Colitis, Ulcerative/genetics , Colon/metabolism , Crohn Disease/genetics , Gene Regulatory Networks , Intestinal Mucosa/metabolism , Adolescent , Adult , Case-Control Studies , Cell Adhesion Molecules/blood , Child , Child, Preschool , Colitis, Ulcerative/blood , Colitis, Ulcerative/pathology , Colon/pathology , Crohn Disease/blood , Crohn Disease/pathology , Female , Gene Expression Regulation , Humans , Intestinal Mucosa/pathology , Male , Prospective Studies , Protein Isoforms/blood , Protein Isoforms/geneticsABSTRACT
OBJECTIVES: The current classification of inflammatory bowel disease (IBD) is based on clinical phenotypes, which is blind to the molecular basis of the disease. The aim of this study was to stratify a treatment-naïve paediatric IBD cohort through specific innate immunity pathway profiling and application of unsupervised machine learning (UML). METHODS: In order to test the molecular integrity of biological pathways implicated in IBD, innate immune responses were assessed at diagnosis in 22 paediatric patients and 10 age-matched controls. Peripheral blood mononuclear cells (PBMCs) were selectively stimulated for assessing the functionality of upstream activation receptors including NOD2, toll-like receptor (TLR) 1-2 and TLR4, and the downstream cytokine responses (IL-10, IL-1ß, IL-6, and TNF-α) using multiplex assays. Cytokine data generated were subjected to hierarchical clustering to assess for patient stratification. RESULTS: Combined immune responses in patients across 12 effector responses were significantly reduced compared with controls (Pâ=â0.003) and driven primarily by "hypofunctional" TLR responses (P values 0.045, 0.010, and 0.018 for TLR4-mediated IL-10, IL-1ß, and TNF-α, respectively; 0.018 and 0.015 for TLR1-2 -mediated IL-10 and IL-1ß). Hierarchical clustering generated 3 distinct clusters of patients and a fourth group of "unclustered" individuals. No relationship was observed between the observed immune clusters and the clinical disease phenotype. CONCLUSIONS: Although a clinically useful outcome was not observed through hierarchical clustering, our study provides a rationale for using an UML approach to stratify patients. The study also highlights the predominance of hypo-inflammatory innate immune responses as a key mechanism in the pathogenesis of IBD.
Subject(s)
Inflammatory Bowel Diseases , Leukocytes, Mononuclear , Cells, Cultured , Child , Cytokines , Humans , Inflammatory Bowel Diseases/diagnosis , Unsupervised Machine LearningABSTRACT
OBJECTIVES: Caring for a child on home parenteral nutrition (HPN) is stressful, and its emotional impact not fully appreciated. This study explored the emotional wellbeing and coping styles of parents and children on HPN. METHODS: Questionnaire data were collected for parents of children (0-18 years) on HPN. Children 8 years and older completed the revised children's anxiety and depression scale. Parents completed the Hospital Anxiety and Depression Scale, Paediatric Inventory for Parents (PIP) and brief COPE. RESULTS: A total of 14 children were included, 20 parents (13 females) and 4 children completed the survey. Parents had mean PIP difficulty and frequency score of 117.9 and 124, respectively, higher compared to parents of children with other chronic illness. PIP scores were significantly higher where children were also enterally tube fed (Pâ<â0.05). Thirty-five per cent parents scored above clinical threshold on anxiety subscale of Hospital Anxiety and Depression Scale and 30% in borderline range. On depression subscale 15% scored above clinical threshold range and 15% in borderline range. Mean anxiety and depression scores in parents of children with short bowel syndrome (11.8, 7.8) were significantly higher than those with neuromuscular disease (5.8, 1.6) Pâ<â0.05. Coping styles differed according to health condition and whether child was enterally fed. CONCLUSIONS: There is a significant emotional impact of caring for a child on HPN, assessment and treatment of anxiety, depression, and stress should be a routine part of care. Individual needs of the child and parent need to be taken into account in providing the most appropriate psychological support.
Subject(s)
Parenteral Nutrition, Home , Parents , Adaptation, Psychological , Anxiety , Child , Depression , Female , Humans , Surveys and QuestionnairesSubject(s)
Parenteral Nutrition, Total , Parenteral Nutrition , Energy Intake , Humans , Infant , Weight GainABSTRACT
PURPOSE OF REVIEW: The development of nutritional screening tools has done much to raise the profile of nutrition and encourage healthcare practitioners to consider how to identify children at nutritional risk. However, the next challenge is to ensure nutritional screening accurately identifies those who have immediate and ongoing risk and therefore the potential to impact on it. RECENT FINDINGS: In this article, we review recent evidence which suggests that the large-scale use of these tools outside of a research setting is not always helpful. Most are highly sensitive but not particularly specific and therefore cases may be 'overdiagnosed' but also missed. It may therefore be time for nutritional screening to evolve into a process which is able to better consider the cause of risk and requirements for nutrition support with referral criteria, defined goals and outcome measures and exit criteria using a 'measure, plot, think, act' approach embedded into physician rounds. Key challenges relate to improving compliance around nutritional screening within the hospital setting and comparison of nutrition risk between centres, as well as an understanding of the barriers which prevent nutritional screening and assessment from occurring. SUMMARY: It remains to be elucidated as to whether returning to a process which embeds nutritional assessment within the medical review rather than relying on a 'nutrition score' from a screening tool is a more effective way in which to identifying those patients that are malnourished or at risk of malnutrition during their hospital stay.
Subject(s)
Child Nutrition Disorders/diagnosis , Malnutrition/diagnosis , Mass Screening/methods , Nutrition Assessment , Nutritional Status , Child , Hospitals , Humans , Pediatrics/methods , Risk AssessmentABSTRACT
The aim of our study was to assess the utility of next generation sequencing (NGS) for predicting toxicity and clinical response to thiopurine drugs in paediatric patients with inflammatory bowel disease. Exome data for 100 patients were assessed against biochemically measured TPMT enzyme activity, clinical response and adverse effects. The TPMT gene and a panel of 15 other genes implicated in thiopurine toxicity were analysed using a gene based statistical test (SKAT-O test). Nine patients out of 100 (Crohn's disease- 67, ulcerative colitis- 23 and IBDU-10) had known TPMT mutations associated with deficient enzyme activity. A novel and a highly pathogenic TPMT variant not detectable through standard genotyping, was identified through NGS in an individual intolerant to thiopurines. Of the 14 patients intolerant to thiopurines, NGS identified deleterious TPMT variants in 5 individuals whereas the biochemical test identified 8 individuals as intolerant (sensitivity 35.7% and 57.14%; specificity 93.75% and 50% respectively). SKAT-O test identified a significant association between MOCOS gene and TPMT activity (p = 0.0015), not previously reported. Although NGS has the ability to detect rare or novel variants not otherwise identified through standard genotyping, it demonstrates no clear advantage over the biochemical test in predicting toxicity in our modest cohort.
Subject(s)
Azathioprine/adverse effects , Colitis, Ulcerative , Crohn Disease , Exome , Mercaptopurine/adverse effects , Methyltransferases , Mutation , Sulfurtransferases , Adolescent , Azathioprine/administration & dosage , Child , Child, Preschool , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/enzymology , Crohn Disease/drug therapy , Crohn Disease/enzymology , Crohn Disease/genetics , Female , Genome-Wide Association Study , High-Throughput Nucleotide Sequencing , Humans , Infant , Male , Mercaptopurine/administration & dosage , Methyltransferases/genetics , Methyltransferases/metabolism , Sulfurtransferases/genetics , Sulfurtransferases/metabolismABSTRACT
BACKGROUND: Over the last 2 decades, there has been an ever-expanding catalog of genetic variants implicated in inflammatory bowel disease (IBD) through genome-wide association studies and next generation sequencing. In this article, we highlight the remarkable developments in understanding the genetic and immunological basis of IBD. The main objective of the study was to perform a systematic review of published literature detailing functional/immunological studies in patients known to harbor genetic variations in the implicated genes. METHODS: A panel of 71 candidate genes implicated in IBD was prioritized using 5 network connectivity in silico methods. An electronic search using MEDLINE and EMBASE from 1996 to February 2014 for each of the selected genes was conducted. Only studies describing genotyped IBD cohorts with concurrent in vivo functional studies were included. RESULTS: Between the reviewers, a total of 35,142 potentially eligible publications were identified. Only 8 genes had publications meeting the inclusion criteria. A total of 67 studies were identified across the selected genes. The NOD2 gene had the most number with 41 studies followed by IL-10 with 11 eligible studies. A meta-analysis was not practical given the heterogeneity of the study design and the number of implicated genes with diverse immunological and physiological functions. CONCLUSIONS: There is a clear lack of functional studies in humans to assess the in vivo impact of the various genetic variants implicated. A collaborative approach merging genomics and functional studies will help to unravel the obscure mechanisms involved in IBD.
Subject(s)
Biomarkers/analysis , Genome-Wide Association Study , Genomics/methods , High-Throughput Nucleotide Sequencing , Inflammatory Bowel Diseases/genetics , Inflammatory Bowel Diseases/immunology , Genetic Predisposition to Disease , Genotype , Humans , Meta-Analysis as Topic , PrognosisABSTRACT
OBJECTIVE: There are no specific data available regarding paediatric endoscopy provision in the UK and anecdotal experiences suggest that such provision varies widely between the units. The aim of our study was to identify the current provision of paediatric endoscopy services in the UK, the number of endoscopies performed in each unit, the number of operators performing these endoscopies and whether endoscopies were performed under sedation or general anaesthesia. METHODS AND RESULTS: An email questionnaire was sent to all 31 units in the UK performing paediatric endoscopies and responses were received from 25 centres (81%). The median number of total endoscopies (upper and lower) per unit each year was 332 (range 64-2040). The median number of gastrosopy per consultant in each centre was 101 (range 20-288) and median number of colonoscopies performed per consultant per year was 49 (range 10-215). 18 of the 25 centres performed all endoscopies under general anaesthesia with 7 centres using sedation as well as general anaesthesia. Percutaneous endoscopic gastrostomy insertion (PEG) was performed in 24 out of 25 centres with the service undertaken by paediatric surgeons in 11 centres. 11 centres provided formal out of hours endoscopy services. CONCLUSION: There is wide variation in paediatric endoscopy provision and the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) endoscopy working group is collaborating with the Joint Advisory Group (JAG) to provide specific standards for paediatric endoscopy services in the UK.
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BACKGROUND AND AIMS: Exclusive enteral nutrition is used as primary therapy in Crohn's disease. Nutrition support is frequently required in children with both Crohn's disease and Ulcerative Colitis when acutely unwell and during periods of recovery. There is considerable controversy about nutritional needs during phases of active and inactive disease. It is, for example, often assumed that in acute illness a child requires increased nutritional support however the precise relationship between illness severity and energy expenditure is uncertain. This study explores the relationship between disease activity and resting energy expenditure (REE) in children with inflammatory bowel disease. METHODS: Patients were recruited from the regional paediatric gastroenterology unit at Southampton University Hospitals NHS Trust. Disease activity was assessed using standard scoring systems (Paediatric Crohn's Disease Activity Index; Simple Colitis Activity Index) and biochemical markers of inflammation (C-Reactive Protein, CRP). Fat free mass was estimated from skinfold thickness and Bioelectrical Impedance Analysis. Resting energy expenditure was measured by indirect calorimetry. A logarithmic correction and a linear regression model were used for analysis of REE corrected for body size. RESULTS: 55 children were studied; 37 (67%) with Crohn's disease and 18 (33%) with Ulcerative Colitis. Median PCDAI was 10 (range 0-60), 22 (59%) had PCDAI > or =10 (active disease). Median SCAI was 1.5 (range 0-12). Within disease groups there were strong correlations between REE/KgFFM(0.52) and disease activity; PCDAI (r -0.386, p 0.018) in Crohn's disease and SCAI (r -0.456, p 0.057) in Ulcerative Colitis. In the cohort as a whole there was no increase in REE/KgFFM(0.52) with increasing CRP (r 0.129, p 0.361). Using the regression model each mg/l increase in CRP was associated with a reduction in REE of nearly 1.5 kCal/day. CONCLUSIONS: We were unable to demonstrate a significant relationship between REE and disease activity in children with inflammatory bowel disease.
Subject(s)
Basal Metabolism/physiology , Inflammatory Bowel Diseases/metabolism , Adipose Tissue , Adolescent , Body Mass Index , C-Reactive Protein/analysis , Calorimetry, Indirect , Child , Electric Impedance , Energy Metabolism/physiology , Female , Humans , Male , Motor Activity , Severity of Illness Index , Skinfold Thickness , Statistics as Topic , Surveys and QuestionnairesABSTRACT
BACKGROUND & AIMS: Dendritic cells (DCs) play a crucial role in immune responses by controlling the extent and type of T-cell response to antigen. Celiac disease is a condition in which T-cell immunity to gluten plays an important pathogenic role, yet information on DCs is scant. We examined mucosal DCs in celiac disease in terms of phenotype, activation/maturation state, cytokine production, and function. METHODS: Mucosal DCs from 48 celiacs and 30 controls were investigated by flow cytometry. In situ distribution of DCs was analyzed by confocal microscopy. Interferon (IFN)-alfa, interleukin (IL)-4, IL-5, IL-12p35, IL-12p40, IL-18, IL-23p19, IL-27, and transforming growth factor-beta transcripts were measured by real-time reverse-transcription polymerase chain reaction in sorted DCs. DC expression of IL-6, IL-12p40, and IL-10 was assessed by intracellular cytokine staining. The effect of IFN-alfa and IL-18 blockade on the gluten-induced IFN-gamma response in celiac biopsy specimens grown ex vivo also was investigated. RESULTS: Mucosal DCs were increased in untreated, but not treated, celiacs. The majority of them were plasmacytoid with higher levels of maturation (CD83) and activation (CD80/CD86) markers. Higher transcripts of Th1 relevant cytokines, such as IFN-alfa, IL-18, and IL-23p19, were produced by celiac DCs, but because IL-12p40 was undetectable, a role for IL-23 is unlikely. Intracellular cytokine staining of celiac DCs showed higher IL-6, but lower IL-10 expression, and confirmed the lack of IL-12p40. Blocking IFN-alfa inhibited IFN-gamma transcripts in ex vivo organ culture of celiac biopsy specimens challenged with gluten. CONCLUSIONS: These data suggest that IFN-alfa-producing DCs contribute to the Th1 response in celiac disease.
Subject(s)
Celiac Disease/metabolism , Dendritic Cells/metabolism , Glutens/immunology , Immunity, Cellular , Immunity, Mucosal , Interferon-alpha/metabolism , Intestinal Mucosa/metabolism , Th1 Cells/metabolism , Antibodies , Antigens, CD/analysis , Case-Control Studies , Celiac Disease/diet therapy , Celiac Disease/genetics , Celiac Disease/immunology , Cell Differentiation , Cell Separation , Cells, Cultured , Cyclooxygenase 2/analysis , Dendritic Cells/immunology , Diet, Protein-Restricted , Flow Cytometry , Gliadin/immunology , Humans , Interferon-alpha/genetics , Interferon-alpha/immunology , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interleukins/genetics , Interleukins/metabolism , Intestinal Mucosa/enzymology , Intestinal Mucosa/immunology , Microscopy, Confocal , Peptide Fragments/immunology , Phenotype , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Th1 Cells/immunology , Tissue Culture Techniques , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolismABSTRACT
Twenty-five percent of inflammatory bowel disease (IBD) diagnoses present in childhood, with Crohn's disease (CD) being the most common type. Many children have poor nutrition status at presentation of the disease, which may worsen during the clinical course, with a significant number of children having impaired linear growth. The cause of this poor nutrition status is complex, and contributing factors include inadequate intake, malabsorption, altered energy demands, and losses through stool, particularly in colitis. The principal aim of medical management is to induce disease remission, with minimal side effects, thereby enabling normal growth and development. This must include active consideration of the nutrition needs of such children and how they may be best met. However, our understanding of the manner in which the disease process affects the energy demands of children with CD or how poor nutrition, in turn, may affect the disease course is limited. This may constrain the efficacy and effectiveness of standard therapeutic approaches to care. This review explores the many factors of relevance in the delivery of nutrition support to children with inflammatory bowel disease, and explores the role of exclusive enteral nutrition as a corticosteroid-sparing strategy to induce remission in children with active Crohn's disease.
Subject(s)
Child Development/physiology , Child Nutritional Physiological Phenomena , Crohn Disease/physiopathology , Crohn Disease/therapy , Growth/physiology , Nutritional Support , Child , Child, Preschool , Humans , Infant , Nutritional Requirements , Nutritional StatusABSTRACT
In 1997, three lines of inbred Peromyscus leucopus--GS109A, GS16A1, and GS16B--were acquired by the Peromyscus Genetic Stock Center. Since then, records have been kept on tumors detected by visible inspection of live animals. The inbred lines GS109A and GS16A1 presented tumors with frequencies substantially higher than that of the other inbred line or of random-bred P. leucopus stock. The average age of detection was 456 +/- 75 days (n = 24) for GS109A and 568 +/- 168 days (n = 12) for GS16A1 respectively. Surprisingly, the majority of the tumors (23 of 24 for GS109A and 8 of 12 for GS16A1) appeared to be Harderian gland lesions. During the same time period only a single tumor, a fibrosarcoma, was noted in the other inbred strain (GS16B), and one Harderian gland tumor was detected in the random bred stock. On the basis of the number of animals born to each group, tumor frequencies were approximately 22.7%, 8.3%, 0.67%, and 0.07%, for GS109A, GS16A1, GS16B, and randombred P. leucopus stock, respectively. The periocular tumors appeared to be highly malignant, with elevated mitotic indices, marked anaplasia, and metastases to regional lymph nodes and lungs. The tumors were readily transplantable to other animals of the same line. Among various other species, malignant Harderian gland tumors are relatively rare.
Subject(s)
Adenocarcinoma/veterinary , Eye Neoplasms/veterinary , Harderian Gland/pathology , Peromyscus , Rodent Diseases/pathology , Adenocarcinoma/epidemiology , Adenocarcinoma/pathology , Animals , Eye Neoplasms/epidemiology , Eye Neoplasms/pathology , Prevalence , Rodent Diseases/epidemiology , Rodentia , Species Specificity , Staining and LabelingABSTRACT
Crohn's disease in childhood is a chronic relapsing and remitting condition that can significantly impact normal growth and development. This influences choice of both initial and ongoing management. The goal of therapy is to induce and maintain remission with minimal side effects. Enteral nutrition is effective in active disease and will induce disease remission in most cases avoiding corticosteroid use. The high frequency of relapse means additional immunosuppressive therapies are usually required but nutrition remains a key priority as part of the subsequent management strategy.
Subject(s)
Crohn Disease/therapy , Enteral Nutrition , Growth/physiology , Immunosuppressive Agents/therapeutic use , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Child , Crohn Disease/physiopathology , Humans , Immunosuppressive Agents/adverse effects , Inflammation/prevention & control , Intestines/pathology , Remission Induction , Treatment OutcomeABSTRACT
Dr Beattie describes the different types of gastrooesophageal reflux and the investigations that may be needed. Management in infants and children is discussed, from simple measures through to more complex medications and, in a minority of cases, surgery. Mild reflux occurs in 50% of all babies and most cases are managed by health visitors and general practitioners. Simple strategies, including feeding advice and reassurance about the natural history, are usually sufficient. Feed thickeners or an anti-reflux milk help in selected cases. There is a need, however, for careful clinical assessment of cases and consideration of the differential diagnosis. It is important that resistant or difficult cases are assessed by a paediatrician with an interest in reflux.