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Biomedical subjects

J M Fell

Publications and source records attributed to J M Fell.

At least 19 recordsLinked to original sources
PubMed2006

Inflammatory bowel disease.

Twenty five per cent of inflammatory bowel disease presents in childhood. Growth and nutrition are key issues in the management with the aim of treatment being to induce and then maintain disease remission with minimal side effects. Only 25% of Crohn's disease presents with the classic triad of abdominal pain, weight loss, and diarrhoea. Most children with ulcerative colitis have blood in the stool at presentation. Inflammatory markers are usually although not invariably raised at presentation (particularly in Crohn's disease). Full investigation includes upper gastrointestinal endoscopy and ileocolonoscopy. Treatment requires multidisciplinary input as part of a clinical network led by a paediatrician with special expertise in the management of the condition.

Adolescent↗
PubMed2004

Improvement in quality of life of children with acute Crohn's disease does not parallel mucosal healing after treatment with exclusive enteral nutrition.

BACKGROUND: Crohn's disease is a chronic debilitating disorder affecting a child's physical and emotional well-being. Recent emphasis on 'quality of life' (QOL) has led to re-evaluation of available medical treatments. AIM: To assess prospectively change in QOL, clinical disease activity and intestinal mucosal inflammation in active paediatric Crohn's disease after treatment with exclusive enteral nutrition. In addition, we evaluated whether change in QOL could predict changes in paediatric Crohn's disease activity index (PCDAI) and mucosal inflammation (endoscopic and histologic). METHODS: The IMPACT II questionnaire was used prospectively and longitudinally in 26 consecutively recruited children [16 males (67%), median 14 years, s.d. = 1.7 years] with active Crohn's disease (PCDAI > 20). They were treated with a new polymeric enteral feed (ACD004, Nestle) for a period of 8 weeks. All had PCDAI, QOL and endoscopic assessment at the time of diagnosis and after 8 weeks of treatment. RESULTS: Twenty-three of 26 children achieved a clinical remission at 8 weeks, with improvement in the QOL scores (P < 0.05). The change in QOL score after treatment was predictive of achieving a clinical remission, but not of histological improvement. CONCLUSIONS: Although children may find dietary restrictions difficult, this study confirms a clear improvement in QOL after treatment with exclusive enteral nutrition. However, improvement in QOL scores is not reflected by improvement in mucosal inflammation. Whilst improving QOL remains a core principal in patient management, the long-term consequences of ongoing mucosal inflammation must be better understood before relying only on short-term QOL measures to dictate treatment choices.

Acute Disease↗
PubMed2001

Portal vein thrombosis and pancreatic failure.

We report a case of a child with portal vein thrombosis presenting with protein losing enteropathy. He later developed exocrine and endocrine pancreatic failure. This association has not been reported before.

Abdomen↗
PubMed2001

Effect of enteral nutrition on antioxidant enzyme systems and inflammation in paediatric Crohn's disease.

UNLABELLED: Crohn's disease is characterized by chronic inflammation of the gastrointestinal mucosa, which can be successfully treated with enteral nutrition. In this study, the activities of the antioxidant metalloenzymes copper/zinc-superoxide dismutase (Cu/Zn-SOD) and selenium-glutathione peroxidase (Se-GPx) were determined in erythrocyte lysates from children with Crohn's disease. Both enzymes exhibited significantly lower activities relative to healthy control subjects: 1.55 +/- 0.33 vs 2.13 +/- 0.75 SOD U mg(-1) protein (p < 0.025) for Cu/Zn-SOD, and 61.9 +/- 17.7 vs 93.6 +/- 28.7 mU mg(-1) protein (p < 0.01) for Se-GPx. Treatment of patients with a specific polymeric diet, CT3211, for a period of 8 wk did not significantly alter the activities of the enzymes. In contrast, clinically, enteral nutritional therapy induced a remission in 13/14 children, and a significant fall in both median serum C-reactive protein and mean serum tumour necrosis factor-alpha levels. CONCLUSION: The results imply that the anti-inflammatory action of enteral nutrition in Crohn's disease is caused by a mechanism other than restitution of these antioxidant enzymes.

Adolescent↗
PubMed2000

Mucosal healing and a fall in mucosal pro-inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn's disease.

BACKGROUND: Although enteral nutrition is a recognized form of treatment for intestinal Crohn's disease, there are persisting problems with feed palatability and only limited data as to its mode of action. AIM: To assess the effects of a specific oral polymeric diet (CT3211; Nestle, Vevey, Switzerland), which is rich in transforming growth factor beta2, on the mucosal inflammatory process. METHODS: Twenty-nine consecutive children with active intestinal Crohn's disease were treated with CT3211 as the sole source of nutrition for 8 weeks. Patients were assessed clinically, and endoscopically, whilst cytokine mRNA was measured in mucosal biopsies before and after treatment by quantitative reverse transcriptase polymerase chain reaction. RESULTS: After 8 weeks 79% of children were in complete clinical remission. Macroscopic and histological healing in the terminal ileum and colon was associated with a decline in ileal and colonic interleukin-1beta mRNA (pre-treatment to post-treatment ratio 0.008 and 0.06: P < 0.001, P = 0.006). In the ileum there was also a fall in interferon gamma mRNA (ratio 0.15, P < 0.001) with a rise in transforming growth factor beta1 mRNA (ratio 10, P = 0.04), whilst in the colon interleukin-8 mRNA fell with treatment (ratio 0.06, P < 0.05). CONCLUSIONS: The clinical response to oral polymeric diet CT3211 is associated with mucosal healing and a down regulation of mucosal pro-inflammatory cytokine mRNA in both the terminal ileum and colon. In the ileum there was also an increase in transforming growth factor beta1 mRNA.

Adolescent↗
PubMed2000

Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children.

AIM: To establish a reference range in the paediatric population for the new glomerular filtration rate (GFR) marker, cystatin C, and to compare it with that of creatinine. METHODS: Cystatin C and creatinine were measured by particle enhanced nephelometric immunoassay (PENIA) and fixed interval Jaff¿e methods, respectively, in 291 children aged 1 day to 17 years, including 30 premature infants with gestational ages ranging from 24 to 36 weeks. RESULTS: In the premature infants, concentrations of both cystatin C and creatinine were significantly raised compared with term infants, with cystatin C concentrations being between 1.10 and 2.06 mg/litre and creatinine between 32 and 135 micromol/litre. In premature infants, there was no significant relation between gestational age and cystatin C or creatinine concentration. Creatinine concentrations fell to a nadir at 4 months of age, rising gradually to adult values by about 15-17 years of age, in contrast to cystatin C, which fell to a mean concentration of 0.80 mg/litre by the 1st year of life, and remained constant throughout adulthood up to the age of 50 years. Neither analyte showed any influence of sex. CONCLUSION: The measurement of cystatin C, rather than creatinine, is more practical for monitoring GFR changes in the paediatric population.

Adolescent↗
PubMed1999

Remission induced by a new specific oral polymeric diet in children with Crohn's disease.

We have been able to show that CT3211 is an effective oral treatment in children with active Crohn's disease. It was well tolerated, and there were minimal side effects. At the mucosal site of disease there was macroscopic and histological improvement, together with evidence of downregulation of the pro-inflammatory cytokines IL-1 beta, IL-8, and IFN-gamma.

Adolescent↗
PubMed1998

A p55 TNF receptor immunoadhesin prevents T cell-mediated intestinal injury by inhibiting matrix metalloproteinase production.

Anti-TNF-alpha Ab therapy has been shown to be of benefit in the treatment of active Crohn's disease, but the tissue-injuring processes in the gut mediated by TNF-alpha that might be inhibited by neutralizing Ab are unknown. In this work, we have used a p55 TNF receptor-human IgG fusion protein (TNFR-IgG) to prevent the severe mucosal injury that ensues when lamina propria T cells in explant cultures of human fetal small intestine are directly activated with the lectin PWM. Following T cell activation and associated with mucosal injury, there is a marked elevation of soluble TNF-alpha in organ culture supernatants and a large increase in TNF-alpha mRNA transcripts. The addition of TNFR-IgG at the onset of cultures greatly reduced PWM-induced tissue injury, without inhibiting the increase in TNF-alpha and IFN-gamma transcripts seen following T cell activation. Mucosal injury in this model is mediated by endogenously-produced matrix metalloproteinases (MMPs). When TNFR-IgG was added to PWM-stimulated explants, there was a reduction in MMPs in the explant culture supernatants, especially stromelysin-1. Recombinant TNF-alpha and IL-1beta added directly to mucosal mesenchymal cell lines also caused an increase in MMP production, but only the former was inhibited by the TNFR-IgG. These results suggest that one of the ways in which TNF-alpha causes tissue injury in the gut is by stimulating mucosal mesenchymal cell to secrete matrix-degrading metalloproteinases. Neutralization of this activity should help maintain tissue integrity.

Antigens, CD↗
PubMed1997

Measurement of albumin and low molecular weight proteins in the urine of newborn infants using a cotton wool ball collection method.

OBJECTIVE: The aim of this study was to investigate the inter-relationship between urinary excretion of alpha-1-microglobulin (A1M), retinol-binding protein (RBP) and albumin in term and premature neonates, with urine collected into cotton wool balls and extracted by a novel method. SUBJECTS AND METHODS: Sixty-four infants were studied on the first day of life; 26 had been born at term (37-42 weeks gestation) and 38 prematurely (24-28 weeks n = 16, 29-36 weeks n = 22). Urine collected into cotton wool balls was analysed following a new detergent extraction method, which resulted in a recovery rate of 94-107% for albumin. A1M, RBP and creatinine. RESULTS: Urinary protein excretion, expressed as a ratio to urinary creatinine, decreased significantly with increasing gestational age (24-28 weeks, 29-36 weeks, 37-42 weeks: albumin:creatinine ratio mg/mmol mean 96.9, 31.7, 19.3; A1M:creatinine ratio mg/mmol mean 99.3, 37.0, 7.8; RBP:creatinine ratio mg/mmol mean 16.2, 3.8, and < 0.01, below the limit of detection, respectively). When results were corrected for birthweight, this gestation-associated effect was still present for A1M and RBP, but not for albumin. In premature infants there was a significant positive correlation between A1M:creatinine ratio and RBP:creatinine ratio (r = 0.85), and also between albumin and both A1M and RBP (r = 0.82 and 0.77). CONCLUSION: Increased excretion of A1M, RBP and albumin at earlier gestational ages is probably due to proximal tubular immaturity, although tubular damage and also glomerular dysfunction cannot be excluded as possible explanations.

Albuminuria↗
PubMed1996

Manganese toxicity in children receiving long-term parenteral nutrition.

BACKGROUND: In patients receiving long-term parenteral nutrition (PN), cholestatic disease and nervous system disorders have been associated with high blood concentrations of manganese. In such patients, the normal homoeostatic mechanisms of the liver and gut are bypassed and the requirement for this trace element is not known; nor has it been certain whether hypermanganesaemia causes the cholestasis or vice versa. We explored the direction of effect by serial tests of liver function after withdrawal of manganese supplements from children receiving long-term PN. We also examined the relation between blood manganese concentrations and brain lesions, as indicated by clinical examination and magnetic resonance imaging (MRI). METHODS: From a combined group of 57 children receiving PN we identified 11 with the combination of hypermanganesaemia and cholestasis; one also had a movement disorder. Manganese supplements were reduced in the first three and withdrawn in the remainder. MRI was done in two of these children. We also looked at manganese concentrations and MRI scans in six children who had received PN for more than 2 years without developing liver disease. FINDINGS: In the hypermanganesaemia/cholestasis group, four of the 11 patients died. In the seven survivors baseline whole-blood manganese was 615-1840 nmol/L, and after 4 months it had declined by a median of 643 nmol/L (p < 0.01). Over the same interval total bilirubin declined by a median of 70 mumol/L (p < 0.05). Two of these children had movement disorders, one of whom survived to have an MRI scan; this showed, with T1 weighted images, bilateral symmetrically increased signal intensity in the globus pallidus and subthalamic nuclei. Such changes were also seen in five other children--one from the hypermanganesaemia/cholestasis group and four of six in the long-term PN group without liver disease (in all of whom blood manganese was above normal). INTERPRETATION: The cholestasis complicating PN is multifactorial, but these results add to the evidence that manganese contributes. In view of the additional hazard of basal ganglia damage from high manganese levels in children receiving long-term PN, we recommend a low dose regimen of not more than 0.018 mumol/kg per 24 h together with regular examination of the nervous system.

Bilirubin↗
PubMed1996

MRI in children receiving total parenteral nutrition.

Cranial MRI was obtained in 13 of a group of 57 children receiving long-term parenteral nutrition, who were being investigated for hypermanganasaemia. Increased signal intensity on T1-weighted images has been reported in adult patients on long-term parenteral nutrition and with encephalopathy following chronic manganese exposure in are welding. It has been postulated that these changes are due to deposition of the paramagnetic trace element manganese. In excess manganese is hepato- and neurotoxic and we present the correlation of whole blood manganese levels with imaging findings. The age range of our patients was 6 months to 10 years, and the duration of therapy 3 months to 10 years. In 7 children we found characteristic increased signal intensity on T1-weighted images, with no abnormality on T2-weighted images. All patients had elevated whole blood manganese levels, suggesting that the basis for this abnormality is indeed deposition of manganese within the tissues.

Brain↗
PubMed1996

The distribution of dividing T cells throughout the intestinal wall in inflammatory bowel disease (IBD).

T cell hypersensitivity has been implicated in the tissue damage in Crohn's disease (CD). All studies to date have examined mucosal T cells, although much of the tissue damage occurs in the submucosa and muscle layers. The aim of this work was to study T cell proliferation throughout the intestinal wall in children with IBD. Surgical resection material from 19 children with CD (10 ileal, 10 colonic), seven with ulcerative colitis (UC), and 12 normal controls was studied. The distribution of dividing T cells was investigated by double-immunohistochemistry using Ki67 to identify proliferating cells, and CD3 to identify T cells. In ileal and colonic lamina propria virtually no Ki67+, CD3+ cells were seen in control, UC or CD tissue. In contrast, there were significantly more Ki67+, CD3+ cells within the lymphoid follicles of ileal and colonic CD than in the follicles in UC and controls. Increased numbers of Ki67+, CD3+ cells were present in the submucosa, muscle layers (M) and serosa in Crohn's ileitis and colitis compared with the lamina propria (LP), although only in the muscle of the colon was the difference statistically significant (LP, 0.4% (0-1%); M, 1.6% (0-5.2%); P = 0.03). Pooling data from ileal and colonic CD, however, did show significantly increased Ki67+, CD3+ cells in both serosa and muscle layers compared with the LP. Dividing T cells have been identified in the deeper layers of the gut wall in CD. These may contribute to the fibrosis and muscle hyperplasia characteristic of the condition.

Adolescent↗
PubMed1996

Neonatal and infantile upper gastrointestinal endoscopy using a new small diameter fibreoptic gastroscope.

Using a new prototype (Olympus XPGIF 5.2/ N30) gastroscope, upper gastrointestinal endoscopy was safely performed under sedation on 99 infants (weights 0.9 to 10.1 kg). No complications occurred. Macroscopic and microscopic abnormalities were found in 60%, including abnormal duodenal biopsies in 47% of cases with protracted diarrhoea. Duodenal biopsy material was, however, of suboptimal standard for histologic assessment in 25% of the cases. In 52% of those under 3.5 kg diagnoses were made that would not have otherwise been possible and, in 75% of those in the Intensive Care Unit, abnormalities were found. The use of this new endoscope represents a significant advance in clinical practice.

Biopsy↗
PubMed1996

Infantile chronic idiopathic intestinal pseudo-obstruction: the role of small intestinal manometry as a diagnostic tool and prognostic indicator.

BACKGROUND: Chronic idiopathic intestinal pseudo-obstruction (CIIP) presenting in infancy is a rare but serious condition of heterogeneous aetiology often with an uncertain outcome. AIM: To assess whether intestinal manometry in the first two years of life can help define a neuropathic or myopathic aetiology or clinical outcome, or both, in cases of infantile CIIP. SUBJECTS AND METHODS: 14 consecutive children who presented in the first year of life with CIIP were studied histologically and by small intestinal manometry. RESULTS: Five had a myopathic disorder, four were neuropathic, and five unclassified following histological investigation of full thickness intestinal biopsy specimens. Analysis of fasting phase III activity showed four patterns: (1) (n = 4) no detectable motor activity, (2) (n = 5) low amplitude phase III activity, (3) (n = 3) poorly formed phase III complexes of short duration, (4) (n = 2) well formed cyclical phase III activity with abnormal propagation. The seven children with low amplitude phase III: motility index (MI) < 10 KPa/min, all had a poor outcome (death or dependence on parenteral nutrition) after 1-10 years follow up, compared with two of seven of those with a MI > 10 KPa/min. Of the five with myopathic histology, four had a MI < 10 KPa/min. CONCLUSION: These results show that small intestinal manometry is useful not only as an aid in diagnosing the aetiology of CIIP presenting in infancy, but also in predicting outcome.

Chronic Disease↗
PubMed1992

Congenital sodium diarrhea with a partial defect in jejunal brush border membrane sodium transport, normal rectal transport, and resolving diarrhea.

Defective jejunal sodium/proton exchange causes severe, congenital secretory diarrhea. We report a boy who presented typically in utero, but in whom diarrhea resolved during the first year of life. Pregnancy was complicated by polyhydramnios, and an ultrasound at 31 weeks showed a distended fetal small intestine. The abdomen was grossly distended at birth, and profuse secretory diarrhea began immediately. He subsequently thrived on breast milk and electrolyte supplements. Studies of jejunal brush border sodium/proton exchange at 6 months showed a partial defect. Nonequilibrium rectal dialysis showed rectal sodium and potassium transport to be intact. Diarrhea lessened after 9 months, and the patient subsequently required occasional laxatives. These observations suggest that there is a spectrum of congenital abnormality in this exchanger, and that in children with incomplete defects normal colonic sodium salvage can subsequently mask net small intestinal secretion.

Biological Transport↗