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Biomedical subjects

M S Murphy

Publications and source records attributed to M S Murphy.

At least 19 recordsLinked to original sources
PubMed2006

Immunosuppression in infants with short bowel syndrome undergoing isolated liver transplantation.

BACKGROUND: Little data exist on immunosuppressive drug absorption in children with short bowel syndrome and intestinal failure associated liver disease (SBS-IFALD). AIM: To evaluate the absorption of immunosuppressive medications in children with SBS-IFALD undergoing isolated liver transplantation (iLTx). METHODS: A retrospective review was performed in children with SBS-IFALD undergoing LTx and comparison made with weight, age-matched children undergoing iLTX (extra-hepatic biliary atresia (EHBA) and normal intestinal length and function). RESULTS: Seven children with SBS-IFALD undergoing iLTx (median residual bowel length, 60 cm, range 40-80) were compared with 15 children undergoing LTx for EHBA. SBS-IFALD children had significantly lower trough tacrolimus levels at three months (5.8 vs. 7.9 ng/mL, p<0.05) and six months (5.0 vs. 8.0 ng/mL, p<0.05), but equivalent levels at 12 months after iLTx. The median calculated dose-normalized concentrations indicated that systemic availability of tacrolimus was comparable in two groups at 3, 6, 12 months (33.1 vs. 23.3; 42.4 vs. 36; 51 vs. 52.9) despite the differences in enteral function. The incidence of acute rejection was 1/7 (SBS-IFALD) and 10/15 (EHBA) group (p = 0.06). CONCLUSION: Children with SBS-IFALD demonstrated adequate absorption of oral tacrolimus without significant acute rejection rate after iLTx suggesting that modification of immunosuppression is not necessary.

Female↗
PubMed2005

Treatment of active Crohn's disease in children using partial enteral nutrition with liquid formula: a randomised controlled trial.

BACKGROUND AND AIMS: Total enteral nutrition (TEN) with a liquid formula can suppress gut inflammation and induce remission in active Crohn's disease. The mechanism is obscure. Studies have suggested that long term nutritional supplementation with a liquid formula (partial enteral nutrition (PEN)) may also suppress inflammation and prevent relapse. The aim of this study was to compare PEN with conventional TEN in active Crohn's disease. PATIENTS AND METHODS: Fifty children with a paediatric Crohn's disease activity index (PCDAI)>20 were randomly assigned to receive 50% (PEN) or 100% (TEN) of their energy requirement as elemental formula for six weeks. The PEN group was encouraged to eat an unrestricted diet while those receiving TEN were not allowed to eat. The primary outcome was achievement of remission (PCDAI<10). Secondary analyses of changes in erythrocyte sedimentation rate (ESR), C reactive protein, albumin, and platelets were performed to look for evidence of anti-inflammatory effects. RESULTS: Remission rate with PEN was lower than with TEN (15% v 42%; p=0.035). Although PCDAI fell in both groups (p=0.001 for both), the reduction was greater with TEN (p=0.005). Moreover, the fall in PCDAI with PEN was due to symptomatic and nutritional benefits. With both treatments there were significant improvements in relation to abdominal pain, "sense of wellbeing", and nutritional status. However, only TEN led to a reduction in diarrhoea (p=0.02), an increase in haemoglobin and albumin, and a fall in platelets and ESR. CONCLUSIONS: TEN suppresses inflammation in active Crohn's disease but PEN does not. This suggests that long term nutritional supplementation, although beneficial to some patients, is unlikely to suppress inflammation and so prevent disease relapse.

Adolescent↗
PubMed2004

Performance of blood tests in diagnosis of inflammatory bowel disease in a specialist clinic.

AIMS: To determine the reliability of a panel of blood tests in screening for ulcerative colitis and Crohn's disease. METHODS: The subjects were 153 children referred to a paediatric gastroenterology department with possible inflammatory bowel disease (IBD). Of these, 103 were found to have IBD (Crohn's disease 60, ulcerative colitis 37, indeterminate colitis 6). The 50 without IBD formed the controls. Blood tests evaluated included haemoglobin, platelet count, ESR, CRP, and albumin. Receiver operating characteristic curves were used where possible to determine optimal threshold values. Binary logistic regression analysis was used to investigate the five screening tests in combination, and a stepwise method was used to find the best test combination. RESULTS: The optimal screening strategy used a combination of haemoglobin and platelet count and "1 of 2 abnormal" as the criterion for positivity. This was associated with a sensitivity of 90.8% (95% CI 83.3 to 95.7%), a specificity of 80.0% (95% CI 65.7 to 89.8%), and positive and negative predictive values of 94.4% and 75.9% respectively. CONCLUSIONS: Haemoglobin and platelet count provide a useful screening test combination for patients with suspected IBD. These tests are not completely reliable however. If clinical suspicion is high further investigations are required.

Adolescent↗
PubMed2002

Use of the lactose H2 breath test to monitor mucosal healing in coeliac disease.

UNLABELLED: Confirmation of the diagnosis of coeliac disease requires unequivocal evidence of recovery on a gluten-free diet. The lactose H2 breath test is a non-invasive technique for detecting lactose malabsorption, and this may occur in untreated coeliac disease. The utility of this test was investigated in objectively confirming a response to gluten exclusion. The study included 44 children from 0.9 to 14.75 y of age (median 3.2) with coeliac disease. Five children were asymptomatic, being identified through coeliac antibody screening. Breath tests were performed prior to dietary treatment. If positive, they were repeated at 4-wk intervals following gluten exclusion. Overall, 21/44 (48%) children had positive breath tests at presentation. In 18/21 children on a gluten-free diet, this became negative after 4 wk (86%) and in all the children by 8 wk. In two children with positive tests at 4 wk, problems with dietary adherence were identified. A positive test before treatment was not associated with significant differences in individual symptoms, height, weight and body mass index standard deviation scores, serum haemoglobin or albumin. However, no positive results were found in the asymptomatic patients (p = 0.05). Lactose malabsorption was associated with earlier age of presentation (p = 0.008). CONCLUSION: The lactose H2 breath test objectively confirms a response to gluten exclusion. In selected cases it can help confirm a diagnosis of coeliac disease. However, the test tends to be less informative in asymptomatic patients, and in older children.

Adolescent↗
PubMed2001

Upper gastrointestinal mucosal disease in pediatric Crohn disease and ulcerative colitis: a blinded, controlled study.

BACKGROUND: Upper gastrointestinal endoscopic biopsies often show histologic abnormalities in Crohn disease. Consequently, it has been proposed that routine endoscopy could help to distinguish Crohn disease from ulcerative colitis. Surprisingly, however, recent case reports and an uncontrolled study suggested that similar abnormalities may occur in ulcerative colitis. Therefore, a blinded, controlled study was performed. METHODS: Esophageal, gastric antral, and duodenal biopsies from children with Crohn disease (n = 28) and ulcerative colitis (n = 14) were compared with those from controls undergoing endoscopy for suspected reflux esophagitis (n = 22). Two pathologists, unaware of patient identity and diagnosis, agreed on a consensus report. Severity of inflammation was scored semiquantitatively. Helicobacter pylori colonization was an exclusion criterion. RESULTS: Inflammation was reported as follows: esophagitis: controls 91%; Crohn disease: 72%; ulcerative colitis: 50%; gastritis: controls: 27%; Crohn disease: 92% (P < 0.001); ulcerative colitis: 69%; duodenitis: controls: 9%; Crohn disease: 33%; ulcerative colitis: 23%. In Crohn disease, granulomas were noted in 40% of patients (P = 0.001). Duodenal cryptitis was noted in 26% of patients with Crohn disease but not ulcerative colitis. In one patient with ulcerative colitis, neutrophilic infiltration of gastric glands was seen. Abnormalities seen in Crohn disease and ulcerative colitis included gastroduodenal ulceration (Crohn disease, 7%; ulcerative colitis, 8%), villus atrophy (Crohn disease, 11%; ulcerative colitis, 15%), and increased intraepithelial lymphocytes (Crohn disease, 15%; ulcerative colitis, 31% [P < 0.05]). None of these abnormalities was noted in the controls. CONCLUSION: Although the presence of granulomas can support a diagnosis of Crohn disease, severe inflammation and other abnormalities occur in the proximal gastrointestinal tract in Crohn disease and ulcerative colitis.

Adolescent↗
PubMed2001

Helicobacter pylori.

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Helicobacter Infections↗
PubMed2001

99mTc-HMPAO leucocyte scintigraphy fails to detect Crohn's disease in the proximal gastrointestinal tract.

OBJECTIVE: To investigate the use of (99m)Tc-HMPAO (hexamethyl propylene amine oxime) leucocyte scintigraphy as a non-invasive screening test for inflammatory bowel disease. PATIENTS: 10 children with suspected Crohn's disease, in whom routine investigation using barium contrast radiology, upper gastrointestinal endoscopy, colonoscopy, and mucosal biopsies had identified severe gastroduodenal and/or jejunal involvement. DESIGN: (99m)Tc-HMPAO leucocyte scintigraphic studies performed in each of these cases were assessed by a radiologist who was blinded to the disease distribution. RESULTS: In nine cases there was no scintigraphic evidence of inflammation in the proximal gastrointestinal tract. The 10th child had both gastroduodenal and jejunal involvement, but scintigraphy only revealed faint jejunal positivity. CONCLUSIONS: (99m)Tc-HMPAO leucocyte scintigraphy should not be depended upon as a screening test for Crohn's disease. False negative results are likely in cases with Crohn's disease confined to the proximal gastrointestinal tract.

Barium Sulfate↗
PubMed2001

Current diagnosis, management and morbidity in paediatric inflammatory bowel disease.

UNLABELLED: In the 1970s several reports highlighted the long delay in diagnosis often experienced by children with Crohn's disease. In recent years this disorder has attracted much publicity, and many believe that the incidence has increased substantially. The aim of this investigation was to determine whether heightened awareness had shortened the interval to diagnosis, improved clinical management and reduced morbidity. A retrospective study was therefore carried out on 112 children with inflammatory bowel disease (64 Crohn's disease, 41 ulcerative colitis, 7 indeterminate colitis) referred to a paediatric gastroenterology department in the UK between 1994 and 1998. In Crohn's disease the median interval to diagnosis was 47 wk (maximum 7 y). In those without diarrhoea this was longer (66 vs 28 wk; p = 0.005). In ulcerative colitis the median interval was 20 wk (maximum 3 y). Even in severe colitis the median interval was 5.5 wk (range 3-9 wk) and 4 required urgent colectomy soon after referral. Many with unrecognized Crohn's disease had undergone inappropriate treatments, such as growth hormone or psychiatric therapy. Nineteen (17%) had undergone endoscopic investigations in adult units prior to referral. Malnutrition was equally common in Crohn's disease and ulcerative colitis (11%). Short stature was present in 19% with Crohn's disease, and 5% with ulcerative colitis, and was severe in 8% with Crohn's disease. There was a significant correlation between symptom duration and the degree of growth impairment present (r(s) = -0.4; p = 0.004). CONCLUSION: This study suggests that late diagnosis and inappropriate investigation and management are still significant problems.

Adolescent↗
PubMed2000

Perilunate injuries. Repair by dual dorsal and volar approaches.

Controversy persists regarding optimal management of perilunate injuries. Traditionally, closed treatment, with or without percutaneous pin fixation, was advocated for these highly unstable carpal disruptions, but the inconsistent and often disappointing outcome of closed reduction, coupled with the recognition that functional recovery closely parallels the accuracy of restoring carpal alignment, have led to increasing enthusiasm for open treatment. The favorable outcome reported in this article supports both the contention that the acute perilunate injury affords the opportune time for operative preservation of carpal stability and the efficacy of the combined dorsal and volar approaches as the optimal means of surgical repair. This clinical experience also corroborates experimental evidence that perilunate injuries are apt to cause a predictable spectrum of osseous and soft tissue lesions--lesions usually suitable for early, precise repair. For the skilled athlete, prompt recognition and precision treatment of all components of injury are the critical factors to attain a functional outcome commensurate with a successful return to competition.

Athletic Injuries↗
PubMed1998

Growth factors and the gastrointestinal tract.

This paper reviews areas of interest in gut mucosal growth factor physiology. Several epidermal growth factor (EGF)-like peptides (EGF, transforming growth factor [TGF]-alpha, heparin-binding EGF-like peptide, amphiregulin, and betacellulin) have been identified in the gut, EGF is produced by the salivary glands and is present in milk. It may act on the mucosa from the lumen as a surveillance peptide promoting mucosal repair. A stem-cell-derived "ulcer-associated cell lineage" develops adjacent to ulcers and produces EGF, which may play a role in ulcer healing. TGF-alpha is expressed by villus enterocytes and may have an important role in mucosal healing. The Trefoil peptides (pS2, spasmolytic polypeptide, intestinal trefoil factor) are protease resistant molecules secreted by mucin cells throughout the gut, with a role in mucosal healing. The TGF-beta family inhibit cell proliferation, and promote cell differentiation. TGF-beta has a gradient of expression along the crypt villus axis, with maximum production at the villus tip. It is suspected that it may prevent cell proliferation and support differentiation of villus enterocytes. Hepatocyte growth factor is a multifunctional growth factor expressed in many tissues, including the gastrointestinal tract. It has a role in organogenesis. Intestinal adaptation is highly dependent on enteral nutrition, and it is likely that growth factors are involved in adaptation. Little is known, however, about interactions between nutrients and growth factors. Milk contains a range of potentially important growth factors. Their biological significance is uncertain, and this is an area of active research.

Animals↗
PubMed1997

Inflammatory cloacogenic polyp: an unrecognized cause of hematochezia and tenesmus in childhood.

The rectal "inflammatory cloacogenic polyp" is a recognized pathologic entity in adulthood. We report three cases in children aged between 8 and 12 years. This disorder should be included in the differential diagnosis in patients with hematochezia and tenesmus. These polyps are usually located at the anorectal junction and so may be overlooked at colonoscopy unless an endoscopic retroflexion maneuver is performed.

Anus Diseases↗