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Biomedical subjects

M A Thomson

Publications and source records attributed to M A Thomson.

At least 19 recordsLinked to original sources
PubMed2007

Skin surveillance of a U.K. paediatric transplant population.

BACKGROUND: Solid organ transplant recipients are at increased risk of skin cancer. Melanoma is less common than nonmelanoma skin cancer (NMSC) although the relative proportion of melanoma among skin cancers has been shown to be higher in paediatric than adult recipients. Multiple melanocytic naevi and/or atypical naevi may be a risk factor for the development of melanoma. The relationship between naevus counts and phenotypic characteristics, disease-related variables and sun exposure has not been explored in paediatric transplant patients. OBJECTIVES: To determine the prevalence of premalignant and malignant skin lesions and to identify known risk factors associated with benign and atypical melanocytic naevi in a U.K. paediatric transplant population. METHODS: Paediatric (< or = 19 years) renal and liver transplant patients, who were 5 or more years post-transplantation, were reviewed over 12 months. Lifetime history of sun exposure, episodes of sunburn, sunny holidays, sunscreen use, sun bed use, demographic and transplantation details were collected using interview, questionnaire and case note review. A skin examination was performed for regional counts of malignant lesions, benign and atypical naevi. RESULTS: Ninety-eight patients (82 liver, 13 renal, three multiorgan) with a median follow up of 9 years (range 5-16) were reviewed. Neither skin cancer nor premalignant lesions for NMSC were detected in this group. Eighty-five patients had benign naevi (median 6, range 1-57). Clinical risk factors for increased counts of benign naevi included increasing age (P = 0.03), more episodes of sunburn (P = 0.003) and prolonged treatment with cyclosporin (P = 0.009). The presence of atypical naevi in six patients was significantly associated with more episodes of sunburn (P = 0.006) and more transplants (P = 0.04). Other variables including phenotype, skin type, sun exposure, holidays abroad, residence abroad and total duration of immunosuppression did not correlate with benign or atypical naevus counts. CONCLUSIONS: Skin cancer was not observed in paediatric solid organ transplant recipients who were 5-16 years post-transplantation. Both benign and atypical naevus counts were higher in children with frequent episodes of sunburn. As both naevi and sunburn are risk factors for melanoma, we should target fair-skinned transplant recipients with naevi for intensive sun avoidance education. A prospective, longitudinal follow-up study should determine the onset of skin cancer post-transplantation and the significance of benign and atypical naevus counts in this cohort.

Adolescent↗
PubMed2006

Systemic vasculitis: a cause of indeterminate intestinal inflammation.

OBJECTIVES: Indeterminate intestinal inflammation may result from a variety of inflammatory conditions in addition to ulcerative colitis and Crohn disease. The primary systemic vasculitides may present with intestinal inflammation and an indeterminate colitis. We set out to describe a series of children with primary systemic vasculitis who initially presented with clinical features suggestive of inflammatory bowel disease (IBD) to establish criteria that might help discriminate between IBD and primary systemic vasculitis. METHODS: Ten children (6 boys, median age at presentation 8.9 years, range 0.9-14.5 years) satisfied inclusion criteria. RESULTS: All had abdominal pain, weight loss, diarrhea (6 of 10 bloody) and laboratory evidence of a severe acute phase response. Extraintestinal clinical features included vasculitic rash, renal impairment, myalgia, testicular pain and polyarthritis. Endoscopy showed vascular changes or other macroscopic findings suggestive of vasculitis in 5 of 10 patients. Gut histology revealed indeterminate chronic inflammatory mucosal changes and one patient with small artery fibrinoid necrosis in the submucosal vessels. Extraintestinal biopsy was performed in 6 patients and had a higher yield for the demonstration of vasculitis than intestinal biopsy. The results of selective visceral angiography was suggestive of vasculitis in all patients, but was normal in 7 cases of treatment-unresponsive classic IBD. Treatment comprised corticosteroid and azathioprine in all patients. Cyclophosphamide was given to 7 of 10 patients. CONCLUSIONS: Extraintestinal manifestations and inflammatory responses that may be disproportionate to the degree of intestinal inflammation provide clues to the presence of an underlying primary systemic vasculitis, and these data suggest that selective visceral angiography plays a key role in the diagnosis of vasculitis in this context. It is important to identify and treat any vasculitic component because failure to do so may result in consequential morbidity or mortality.

Abdominal Pain↗
PubMed2006

Retrospective diagnosis of Kindler syndrome in a 37-year-old man.

Kindler syndrome is a rare autosomal recessive disorder characterized by acral blisters in infancy and early childhood, followed by photosensitivity, progressive poikiloderma and cutaneous atrophy. Other features include webbing of the toes and fingers, palmoplantar hyperkeratosis, gingival fragility, poor dentition, and mucosal involvement in the form of urethral, anal and oesophageal stenosis. The recent finding of KIND1 mutations in Kindler syndrome facilitates early diagnosis, prophylactic measures and more precise definition of the phenotype. In the family described here, molecular diagnosis of Kindler syndrome in an infant with acral blisters led to the belated diagnosis in a severely affected relative whose condition had remained unidentified for 37 years.

Adult↗
PubMed2005

Chronic actinic dermatitis treated with mycophenolate mofetil.

Chronic actinic dermatitis (CAD) is a persistent photodermatosis that usually affects elderly men. We report two male patients, aged 55 years (patient A) and 49 years (patient B), who presented with an eczematous eruption on sun-exposed skin. Phototesting revealed a markedly reduced 24-h minimal erythema dose (MED). Both patients had refractory disease and developed significant side-effects to conventional therapies, including topical steroids, prednisolone, psoralen with ultraviolet A, azathioprine and ciclosporin. They had each received at least 6 years of treatment prior to commencing mycophenolate mofetil (MMF). Each noted a significant improvement in symptoms within 6 weeks and subsequent clearing of the eczematous lesions. Patient A still requires continuous treatment with MMF 500 mg twice daily to prevent relapses. Patient B maintains remission by using MMF 1 g twice daily only during the spring and summer months. Both patients have tolerated the treatment well with no abnormalities in blood cell counts or liver biochemistry. Since commencing MMF, their quality of life has significantly improved. These observations suggests that MMF should be considered as an alternative treatment to conventional therapies for refractory CAD.

Chronic Disease↗
PubMed2004

Spontaneous T(H)1 cytokine production by intraepithelial but not circulating T cells in infants with or without food allergies.

BACKGROUND: It has been established that the maintenance of immunological tolerance to dietary antigen and the intestinal flora (oral tolerance) is an actively-maintained process dependent upon mucosal lymphocyte populations. Early life exposures appear critical in the development of such tolerance. However little is known about the activation status of mucosal lymphocytes in human infancy and childhood. PATIENTS AND METHODS: We have performed flow cytometric analysis for cell lineage and cytokine-production status in peripheral blood and duodenal intraepithelial lymphocytes taken during endoscopy from 20 children [median age 2.9 +/- 0.6 years (median +/- SE)] in whom investigation found no intestinal abnormalities (histologically normal controls) and 30 children (median age 1.6 +/- 0.4 years) with confirmed allergy to cow's milk and other dietary antigens. RESULTS: Regardless of clinical status, spontaneous production of cytokines was low or undetectable in peripheral blood cells. By contrast, intraepithelial CD4 and CD8 cells isolated from the small intestine were often activated, with 5% or more showing spontaneous production of T(H)1 type [interleukin-2, interferon (IFN)-gamma] cytokines in both normal controls and food-allergic children. Stimulation in vitro strongly induced cytokine production in peripheral blood but not intraepithelial lymphocytes. Immunohistochemistry showed similar density of IFN-gamma(+) intraepithelial lymphocytes in controls and allergic children. CONCLUSIONS: Duodenal intraepithelial lymphocytes in human infants show a state of increased spontaneous activation compared with peripheral blood lymphocytes, and show no significant impairment of T(H)1 responses in food allergic children.

Child↗
PubMed2004

Treatment of erosive oral lichen planus with topical tacrolimus.

BACKGROUND: Erosive oral lichen planus (LP) is a painful chronic inflammatory condition that is frequently resistant to immunosuppressive agents. Topical tacrolimus has been reported as a safe and effective treatment. OBJECTIVE: To evaluate the efficacy and safety of topical tacrolimus in the treatment of symptomatic erosive oral LP. METHODS: A retrospective review of consecutive patients with oral LP treated with topical tacrolimus between June 1999 and November 2003 was performed. Clinical improvement and adverse events were recorded by the physician. Patients were asked retrospectively to rate their symptoms immediately prior to and after tacrolimus therapy using a visual analogue scale. RESULTS: Physician-observed clinical improvement was found in 21 of 23 patients (91.3%) within 6 weeks. Six patients (26.1%) remained asymptomatic after stopping treatment and 15 patients (65.2%) required maintenance therapy to prevent subsequent flares. Patients' self-reported symptom scores were significantly better (p<0.001) with tacrolimus treatment, which supported physician-observed clinical improvement. There was no evidence of systemic absorption and only minor local side effects were noted. CONCLUSIONS: Topical tacrolimus is an effective treatment for erosive oral LP. The majority of patients require long-term therapy to maintain remission.

Administration, Topical↗
PubMed2003

High-dose azathioprine in children with inflammatory bowel disease.

BACKGROUND: Azathioprine is widely used as maintenance therapy in children with moderate to severe inflammatory bowel disease (IBD). There is no data on safety at higher doses and its impact on growth and surgical morbidity in children. METHODS: This retrospective cohort study included all children treated with azathioprine and diagnosed with IBD between 1996-2001. Outcome measures included indications for azathioprine use, adverse-effects and reasons for treatment discontinuation. Height and weight at diagnosis, treatment onset and current follow-up was recorded, and Z scores for height standardised for time. RESULTS: 107 children received azathioprine at 3 mg/kg. 61% had Crohn's disease and 83% started azathioprine within 2 years of diagnosis. Only 2/107 children had to stop azathioprine because of persistent adverse effects and 16/107 required surgery. There was a trend toward better growth in a group of children with Crohn's disease following treatment with high dose azathioprine therapy (P = 0.08). CONCLUSIONS: Azathioprine is a safe and well-tolerated maintenance therapy at 3 mg/kg for children with IBD. The prevalence of surgery and growth failure in a cohort of children with moderate to severe IBD appears less than previously reported. In children with Crohn's disease, growth velocity may be maximised by an emphasis on nutritional therapy and the use of high dose azathioprine.

Administration, Oral↗
PubMed2002

Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism.

We have reported lymphocytic colitis in children with regressive autism, with epithelial damage prominent. We now compare duodenal biopsies in 25 children with regressive autism to 11 with coeliac disease, five with cerebral palsy and mental retardation and 18 histologically normal controls. Immunohistochemistry was performed for lymphocyte and epithelial lineage and functional markers. We determined the density of intraepithelial and lamina propria lymphocyte populations, and studied mucosal immunoglobulin and complement C1q localisation. Standard histopathology showed increased enterocyte and Paneth cell numbers in the autistic children. Immunohistochemistry demonstrated increased lymphocyte infiltration in both epithelium and lamina propria with upregulated crypt cell proliferation, compared to normal and cerebral palsy controls. Intraepithelial lymphocytes and lamina propria plasma cells were lower than in coeliac disease, but lamina propria T cell populations were higher and crypt proliferation similar. Most strikingly, IgG deposition was seen on the basolateral epithelial surface in 23/25 autistic children, co-localising with complement C1q. This was not seen in the other conditions. These findings demonstrate a novel form of enteropathy in autistic children, in which increases in mucosal lymphocyte density and crypt cell proliferation occur with epithelial IgG deposition. The features are suggestive of an autoimmune lesion.

Autistic Disorder↗
PubMed2002

Upregulated eotaxin expression and T cell infiltration in the basal and papillary epithelium in cows' milk associated reflux oesophagitis.

BACKGROUND: Cows' milk sensitive reflux oesophagitis is an emerging clinical entity in children, normally indistinguishable from primary gastro-oesophageal reflux (GOR) apart from the response to dietary antigen exclusion. It is conjectural whether a tendency towards mucosal eosinophilia distinguishes this group from primary GOR. AIMS: To determine whether there may be differences in the mucosal lesion within the oesophagus in those children with reflux in association with cows' milk induced small bowel pathology, particularly in relation to the eosinophil chemokine eotaxin. METHODS: A total of 29 children underwent endoscopic assessment, including nine with cows' milk sensitive enteropathy (CMSE) and associated GOR, seven histologically normal controls, six with primary GOR, and seven disease controls. Oesophageal biopsy specimens were examined immunohistochemically for the chemokines eotaxin and MCP-2, and T cell lineage and activation markers. RESULTS: Strong upregulation of eotaxin expression, limited to basal and papillary epithelium, occurred in all CMSE patients. By contrast, weak expression was seen in a minority of controls and in 50% of primary GOR patients. Infiltration of CD3, CD4, and CD8 lymphocytes occurred in similar distribution in CMSE patients, significantly increased above controls. Significant upregulation of activation markers (CD25, HLA-DR) was also seen in the CMSE group within basal and papillary epithelium compared to controls and primary GOR. CONCLUSION: Basal and papillary epithelial eotaxin expression, with focal lymphocyte activation, was seen in infants with CMSE associated GOR. This preliminary study provides early evidence to suggest a pathogenesis distinct from primary GOR, in which specific recruitment of T cells and eosinophils may contribute to oesophageal dysmotility.

Adolescent↗
PubMed2002

Percutaneous endoscopic gastrostomy feeding in a district rehabilitation service.

OBJECTIVES: To examine gender, diagnosis, age, reasons for feeding, nutritional status, complications, outcome and duration of feeding in patients who have required a percutaneous endoscopic gastrostomy (PEG) for nutritional support at a district rehabilitation unit in the six years since the service was established. To identify potential for improvements in the management of future patients. DESIGN: Retrospective case note review of cases from 1992 to 1998. SETTING: District rehabilitation service for ages 16-64 serving the population of Fife, Scotland (population circa 350 000). SUBJECTS: All patients (n = 42) who had been fed via a PEG feeding tube in the previous six years. RESULTS: Forty-four PEG tube insertions had been conducted for 43 episodes of feeding in 42 patients. Five episodes of feeding were because of persistent vegetative state or low awareness state and 38 because of neurological swallowing impairment. Twenty-six (60%) patients were nutritionally depleted when PEG feeding was commenced. Twenty-seven (64%) patients experienced minor complications and 15 (34%) had no complications. At three months post procedure four (9.5%) patients had died and 21 (50%) had been discharged home. The mean duration of feeding on 31 October 1998 of the 20 patients (48%) who continued feeding at that date was 3.19+/-1.89 (mean +/- SD) years. CONCLUSIONS: Patients requiring PEG feeding in a district rehabilitation service have a range of diagnoses and the main indication for intervention is neurological swallowing impairment. The majority of patients were nutritionally depleted when feeding commenced and the reasons for this require further investigation.

Enteral Nutrition↗
PubMed2001

Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism.

OBJECTIVES: We have reported colitis with ileal lymphoid nodular hyperplasia (LNH) in children with regressive autism. The aims of this study were to characterize this lesion and determine whether LNH is specific for autism. METHODS: Ileo-colonoscopy was performed in 21 consecutively evaluated children with autistic spectrum disorders and bowel symptoms. Blinded comparison was made with 8 children with histologically normal ileum and colon, 10 developmentally normal children with ileal LNH, 15 with Crohn's disease, and 14 with ulcerative colitis. Immunohistochemistry was performed for cell lineage and functional markers, and histochemistry was performed for glycosaminoglycans and basement membrane thickness. RESULTS: Histology demonstrated lymphocytic colitis in the autistic children, less severe than classical inflammatory bowel disease. However, basement membrane thickness and mucosal gamma delta cell density were significantly increased above those of all other groups including patients with inflammatory bowel disease. CD8(+) density and intraepithelial lymphocyte numbers were higher than those in the Crohn's disease, LNH, and normal control groups; and CD3 and plasma cell density and crypt proliferation were higher than those in normal and LNH control groups. Epithelial, but not lamina propria, glycosaminoglycans were disrupted. However, the epithelium was HLA-DR(-), suggesting a predominantly T(H)2 response. INTERPRETATION: Immunohistochemistry confirms a distinct lymphocytic colitis in autistic spectrum disorders in which the epithelium appears particularly affected. This is consistent with increasing evidence for gut epithelial dysfunction in autism.

Adolescent↗
PubMed1999

Low-dose intravenous azathioprine may be effective in the management of acute fulminant colitis complicating inflammatory bowel disease.

BACKGROUND: The management of acute fulminant colitis unresponsive to intravenous steroids is usually surgical. However, recent evidence suggests that intravenous administration of azathioprine at very high doses may allow more rapid onset of clinical efficacy, although its use has not previously been reported in the emergency situation. AIM: To report the successful use of intravenous azathioprine in the management of acute fulminant colitis complicating both Crohn's disease and ulcerative colitis. METHOD: We initially used intravenous azathioprine because of the refusal of the family of the first patient to accept surgery following failure of conventional medical management. Importantly the azathioprine was successful at the low dose of 3 mg/kg.day, equivalent to standard oral doses. Two subsequent patients demonstrated a similar resolution. All were weaned successfully to oral azathioprine and have remained in long-term endoscopic and histological remission. CONCLUSION: These preliminary data suggest that low-dose intravenous azathioprine may be helpful adjunct therapy in selected cases of severe fulminant colitis. However, the need for close monitoring and daily surgical assessment remains paramount, and a formal trial of low-dose intravenous azathioprine is required before it may be more widely recommended.

Acute Disease↗
PubMed1998

Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.

BACKGROUND: We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. METHODS: 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. FINDINGS: Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. INTERPRETATION: We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.

Child↗
PubMed1998

Electromyographic biofeedback to improve lower extremity function after stroke: a meta-analysis.

OBJECTIVE: To examine the efficacy of electromyographic (EMG) biofeedback compared with conventional physiotherapy for improving lower extremity function in stroke patients. DATA SOURCES: A literature search covering the years 1976 to 1995 in MEDLINE, CINAHL, and EXCERPTA MEDICA. STUDY SELECTION: Studies of adults after stroke, in which the treatment group received biofeedback alone or with conventional physical therapy and the control group received conventional physical therapy. Outcomes included functional measures related to the lower extremity. The study design criterion was that all must be randomized controlled trials. DATA EXTRACTION: Study quality was assessed independently by two observers-using eight criteria. Data for analysis were extracted by two observers to ensure accuracy. DATA SYNTHESIS: For outcomes that were analyzed in more than one study, meta-analyses were done. Seventy-nine studies were identified as potentially relevant and eight studies met the selection criteria. The mean effect sizes were: for ankle dorsiflexion muscle strength, 1.17 (95% CI, .50-1.85; p = .0006); for gait quality, .48 (95% CI, -.06-1.01; p = .08); for ankle range of motion, .07 (95% CI, -.42-0.57; p = .78); for ankle angle during gait, .52 (95% CI, -.18-1.21; p = .14); for stride length, .09 (95% CI, -.56-.73; p = .80); and for gait speed, .31 (95% CI, -.16-.78; p = .20). CONCLUSIONS: The results indicate that EMG biofeedback is superior to conventional therapy alone for improving ankle dorsiflexion muscle strength.

Adult↗
PubMed1998

Implementing early warning messages on emerging health technologies.

The purpose of this study was to determine how horizon-scanning organizations can encourage the implementation of recommendations contained in their early warning messages about emerging health technologies. We reviewed the conclusions of the EUR-ASSESS Project Subgroup report on dissemination and impact, an overview of systematic reviews of interventions to promote implementation of research findings by health care professionals, and various Cochrane Effective Practice and Organisation of Care Group protocols and reviews. The evidence on the effectiveness of different implementation strategies aimed at distinct target groups is of variable quality. There is some evidence from rigorous study designs on the effectiveness of strategies designed to influence the behavior of health care professionals; the quality of the evidence relating to policy makers and the general public is more limited. Horizon-scanning organizations can improve the likelihood of their recommendations being acted upon by developing active implementation strategies based on the best available evidence, establishing links with key groups, and directing early warning messages at specific target audiences. Given the relative lack of good quality evidence, it is important that implementation strategies be rigorously evaluated to determine their effectiveness.

Diffusion of Innovation↗