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Biomedical subjects

P N Malleson

Publications and source records attributed to P N Malleson.

At least 19 recordsLinked to original sources
PubMed2005

Cytokine genotypes correlate with pain and radiologically defined joint damage in patients with juvenile rheumatoid arthritis.

OBJECTIVES: Single nucleotide polymorphisms (SNPs) in cytokine genes have been associated with risk of a number of autoimmune diseases. Moreover, some SNPs are associated with variations in rates of in vitro gene expression, and it is therefore possible that these functional polymorphisms may differentially affect inflammatory processes and disease outcome. This project's objective was to determine whether cytokine genotypes correlate with disease outcomes in patients with juvenile rheumatoid arthritis (JRA). METHODS: Genotypes of SNPs of pro-inflammatory cytokines, tumour necrosis factor-alpha -308G -->A, interleukin-6 (IL-6) -174G -->C and interferon-gamma +874G -->A, and anti-inflammatory, immunosuppressive cytokines, interleukin-10 -1082G -->A, -819C -->T and -592A -->C and transforming growth factor-beta1 (TGF-beta1) codon 10T -->C and codon 25G -->C, were determined for patients with JRA who previously participated in a long-term outcome study. Cytokine genotypes and clinical variables showing significant correlations with clinical outcomes at the alpha = 0.100 level in univariate analyses were entered in multivariate tests. RESULTS: In multivariate tests, the IL-6 genotype -174G/G was positively correlated with pain [regression coefficient B = 0.899, 95% confidence intervals (CI) 0.185, 1.612, P = 0.014]. The homozygous TGF-beta1 codon 25G/G genotype showed a protective effect against joint space narrowing on radiographs taken within 2 yr of disease onset, but confidence intervals were wide [odds ratio (OR) 0.176, 95% CI 0.037, 0.837 P = 0.029]. CONCLUSIONS: The correlation of IL-6 genotype with pain and the possible association of the TGF-beta1 codon 25 genotype with short-term radiographic damage (G/C with greater risk and G/G with decreased risk) suggests that both these polymorphisms may be useful early prognostic indicators. Further studies of the relation between cytokine genotypes and outcomes in patients with all forms of juvenile idiopathic arthritis (JIA) are warranted.

Adolescent↗
PubMed2003

Chronic pain in adolescents: evaluation of a programme of interdisciplinary cognitive behaviour therapy.

AIM: To determine the effectiveness of an interdisciplinary cognitive behavioural treatment for adolescents with chronic pain. METHODS: Fifty seven adolescents (mean age 14.28 years) with chronic pain and 57 accompanying adults underwent an interdisciplinary three week residential programme of group cognitive behavioural therapy. Mean chronicity of pain was 4.02 years; 75% were absent from full time education (mean absence 17 months). RESULTS: Post-treatment adolescents reported significant improvements for self report of disability (mean difference 3.37 (95% CI 0.65 to 6.09)), physical function (mean difference timed walk of 2.61 seconds (1.02 to 4.2) and sit to stand of 3.22 per minute (0.79 to 5.65)). At three months post-treatment adolescents maintained physical improvements and reduced anxiety (mean difference 1.7 (0.72 to 2.67)), disability (mean difference 4.3 (1.44 to 7.17)), and somatic awareness (mean difference 4.43 (1.53 to 7.33)). Following treatment adults reported significant improvement in their report of adolescent disability (mean difference 4.43 (2.17 to 6.7)), adult anxiety (mean difference 1.73 (0.54 to 2.92)), depression (mean difference 1.16 (0.34 to 1.98)), and parental stress (mean difference 10.81 (2.91 to 18.78)). At three months significant improvements were maintained. At three months 64% improved school attendance; 40% had returned to full time education. CONCLUSIONS: Interdisciplinary cognitive behavioural pain management (with family involvement) is a promising approach to the management of pain, pain related distress, and disability.

Absenteeism↗
PubMed2001

Echocardiography and pulmonary function testing in childhood onset systemic lupus erythematosus.

The aim of this paper was to investigate the frequency of echocardiography (ECHO) and pulmonary function test (PFT) abnormalities in childhood onset systemic lupus erythematosus (SLE), and to determine the relationship of these abnormalities to disease activity. The charts of 50 patients with childhood onset SLE attending a pediatric rheumatology clinic were reviewed for ECHO and PFT studies. The frequency and description of ECHO and PFT abnormalities were documented. Possible associations of PFT and ECHO abnormalities with clinical cardiopulmonary disease, radiographic findings, and measures of lupus disease activity were evaluated. Forty patients (80%) had at least one ECHO study. Twenty-seven (68%) had an abnormal initial study. Nine of 14 patients with an initial abnormal ECHO had normal findings on repeated study. Three abnormalities were considered moderately severe. Thirty-three patients (66%) had at least one PFT performed. Sixteen (48%) were abnormal initially. Four of these 'abnormal' studies were repeated and the abnormalities persisted. Nine patients (27%) were considered to have a severe abnormality. Thirty-one children (62%) had both studies performed. An initial abnormal ECHO and abnormal PFT was found in 10 (32%) of these children. No relationship between ECHO or PFT abnormality and any measure of disease activity (physician's global assessment, anti DNA, C3 or ESR) could be found. Occult cardiac and pulmonary disease as demonstrated by ECHO or PFT occurs frequently in childhood onset SLE. If we wish to understand the natural history of these abnormal heart and lung findings, it will be necessary to do serial testing with ECHO and PFTs in this population.

Adolescent↗
PubMed2001

Lipodystrophy in patients with juvenile dermatomyositis--evaluation of clinical and metabolic abnormalities.

OBJECTIVE: Lipodystrophy and associated metabolic abnormalities are being increasingly recognized as complications of juvenile dermatomyositis (JDM). We investigated the prevalence of lipodystrophy and the extent of metabolic abnormalities related to lipoatrophic diabetes mellitus in patients with JDM. METHODS: Twenty patients with JDM were evaluated for evidence of lipodystrophy and associated lipoatrophic diabetes mellitus. All patients underwent clinical assessment, laboratory investigations, and metabolic studies (oral glucose tolerance test, lipid studies, insulin antibodies). RESULTS: We found clinical evidence of lipodystrophy and lipoatrophic diabetes mellitus in 4 of 20 patients with JDM and metabolic abnormalities known to be associated with lipodystrophy in another 8 patients. The 20 patients with JDM were categorized as follows: Group 1 (Patients 1-4) consisted of patients with lipodystrophy and either diabetes mellitus (2 patients) or impaired glucose tolerance (2 patients); Group 2 (Patients 5-12): no lipodystrophy but abnormal glucose and/or lipid studies; Group 3 (Patients 13-20): no lipodystrophy and no abnormalities of glucose and lipid studies. CONCLUSION: We found 25% of patients with JDM have lipodystrophy, and 50% present with hypertriglyceridemia and insulin resistance. Screening for metabolic abnormalities in JDM should be included in routine followup because of the effect of lipodystrophy on longterm prognosis.

Adolescent↗
PubMed2000

Comparison of criteria for the classification of childhood arthritis.

OBJECTIVE: To evaluate the applicability of the ILAR criteria for classification of childhood arthritis in an outpatient pediatric rheumatology clinic population, and to determine the proportion of children who met standard classification criteria, but failed to meet ILAR criteria for specific arthritides, and therefore became unclassifiable. METHODS: We reviewed the charts of 70 consecutive patients who had arthritis for at least 6 months, and attended the clinic between September and November 1997. Sixty-nine patients were categorized according to one of the traditional classifications [ACR for juvenile rheumatoid arthritis (JRA), European Spondylarthropathy Study Group (ESSG) for spondyloarthropathy, Vancouver Criteria for juvenile psoriatic arthritis (JPsA)], and the ILAR classification system. RESULTS: Sixty-one patients (88.4%) were classifiable by the ILAR system; 8 others failed to fulfill ILAR criteria for any specific category, and were assigned to the "other arthritis" category. Of the 29 patients with oligoarticular onset JRA, 6 were unclassified, 5 because of exclusions, and one because he fulfilled criteria for 2 categories. Presence of a family history of psoriasis accounted for most of the exclusions in the oligoarthritis and enthesitis related arthritis categories. All patients with polyarticular onset or systemic onset JRA were classified in the corresponding category in the ILAR system. One 9-year-old patient with spondyloarthropathy was reclassified as "other arthritis" because of exclusions. All 6 children with definite JPsA met ILAR criteria for PsA. Of 4 patients with probable JPsA, only 2 met ILAR criteria for PsA, a third was classified as rheumatoid factor negative polyarthritis, and the fourth was classified as "other arthritis" because of exclusions. CONCLUSION: The ILAR classification criteria applied to a group of children with chronic arthritis classified by traditional criteria results in reassignment of 11.6% of the patients, predominantly in the oligoarticular group. It will be important to determine the role of the presence of a family history of psoriasis in classifying these patients.

Ambulatory Care Facilities↗
PubMed1999

Knee magnetic resonance imaging in childhood chronic monarthritis.

OBJECTIVE: To describe the usefulness of magnetic resonance imaging (MRI) of the knee in the evaluation of chronic monarthritis of uncertain cause in childhood. METHODS: We retrospectively reviewed 21 children referred to our clinic with a putative diagnosis of chronic inflammatory monarthritis of the knee who had MRI performed between May 1993 and June 1997. The median age was 13 years (range 2-17) and 11 were girls. RESULTS: The clinical diagnosis prior to MRI assessment was inflammatory arthritis in 16 patients, and a primary noninflammatory cause in 5. MRI was done in the patients with presumptive inflammatory arthritis when there were atypical symptoms, signs, or radiographs (n = 14), or when they failed to respond to therapy (n = 2). In the patients with a presumptive noninflammatory diagnosis, MRI was performed to clarify the diagnosis. Twelve children (57%) had MRI evidence of a noninflammatory diagnosis. In 4 children (19%) the MRI study indicated the presence of arthritis, and in 5 children (24%) the MRI studies were normal. The noninflammatory diagnoses included: lipoma arborescens (n = 1), vascular malformation [intraarticular (n = 1), extraarticular (n = 1)], synovial chondromatosis (n = 2), partial anterior cruciate ligament tear (n = 2), traumatic bone contusion (n = 2), possible meniscal tear (n = 1), osteochondritis dissecans (n = 1), and a soft tissue mass of uncertain significance in the suprapatellar pouch (n = 1). CONCLUSION: Inflammatory arthritis is usually diagnosed by clinical assessment alone. Uncommonly, when a single joint is involved, and atypical features are identified by a pediatric rheumatologist, other causes of chronic pain and swelling need to be excluded. In this selected patient population, MRI is a useful tool either to confirm the presence of inflammatory arthritis or to investigate a wide range of pathology that can mimic knee joint arthritis.

Adolescent↗
PubMed1997

Intestinal pseudo-obstruction as an initial presentation of systemic sclerosis in two children.

Two children are reported in whom intestinal pseudo-obstruction was the initial manifestation of systemic sclerosis. Gastrointestinal symptoms and skin changes resolved or improved in both children following treatment with prednisone and penicillamine (case 1) or methotrexate (case 2), although radiological changes of the gastrointestinal tract persisted at 3 and 2 yr of follow-up, respectively.

Adolescent↗
PubMed1997

Anti-RNP antibody in a child with undifferentiated carcinoma and no evidence of mixed connective tissue disease.

We describe a young girl who presented with musculoskeletal symptoms and who was found to have high titres of antinuclear antibody with anti-RNP antibody. She was initially suspected of having mixed connective tissue disease, but ultimately was found to have metastatic undifferentiated carcinoma with an unknown primary site. This is a very uncommon malignancy of childhood and an association with anti-RNP antibody has, to our knowledge, not been described. The clinical significance of this finding is discussed.

Antibodies, Antinuclear↗
PubMed1997

Clinical and therapeutic aspects of juvenile-onset spondyloarthropathies.

Relatively little is written about the juvenile spondyloarthropathies. The literature of the past year has included data on the frequency of juvenile spondyloarthropathies, which indicate that these are almost certainly a more common form of childhood arthropathy than formerly believed. Although clinical differences exist between juvenile spondyloarthropathies and juvenile rheumatoid arthritis, there is only limited information about differences in the pathophysiology of these diseases. One study suggests some differences in the expression of tumor necrosis factor and its receptors. Evidence also presented this year suggests that juvenile psoriatic arthritis is probably a separate condition from the spondyloarthropathies. It is hoped that better understanding of the epidemiology and pathophysiology of the juvenile spondyloarthropathies will lead to better treatment strategies.

Age of Onset↗
PubMed1997

Usefulness of antinuclear antibody testing to screen for rheumatic diseases.

OBJECTIVE: To assess the usefulness of the indirect immunofluorescence antinuclear antibody test (FANA) using human laryngeal epithelial carcinoma cells as nuclear substrate, to screen for childhood rheumatic diseases. STUDY DESIGN: A review of all FANA tests performed on children at British Columbia's Children's Hospital between 7 March 1991 and 31 July 1995. RESULTS: FANA tests were positive at titres of 1:20 or greater in 41% of all subjects tested, and in 65% of all subjects in whom the diagnosis was obtained. FANA positivity occurred in 67% of those with a rheumatic disease, compared with 64% of those with a non-rheumatic disease (p = 0.4). More girls had high titre FANA positivity than boys independent of whether or not they had a rheumatic disease (p = 0.05). At a screening serum dilution of 1:40 a positive test has a sensitivity of only 0.63, and a positive predictive value of only 0.33 for any rheumatic disease. For systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), or overlap syndrome at a screening dilution of 1:40 the test has a very high sensitivity of 0.98, but a very low positive predictive value of only 0.10, the test having slightly better characteristics for boys than girls. CONCLUSION: Although a negative FANA test makes a diagnosis of SLE or MCTD extremely unlikely, a positive test even at moderately high titres of 1:160 or higher is found so frequently in children without a rheumatic disease that a positive result has little or no diagnostic value. It is suggested that a screening serum dilution of 1:160 or 1:320 would increase the usefulness of the test, by decreasing false positive tests, without significantly increasing false negative tests for SLE or MCTD, and would have the potential for considerable cost savings.

Antibodies, Antinuclear↗
PubMed1997

Rheumatoid factor positive, oligoarticular onset juvenile rheumatoid arthritis.

We describe 2 children with oligoarticular onset juvenile rheumatoid arthritis (JRA) with early erosive disease. Both patients were rheumatoid factor (RF) positive, but neither had HLA-DR4. These findings suggest RF is associated with early erosive disease, independent of HLA-DR4. RF positive oligoarticular onset JRA should probably be recognized as a separate subgroup of JRA.

Adolescent↗
PubMed1996

Seasonal onset of systemic-onset juvenile rheumatoid arthritis.

OBJECTIVE: This study was undertaken to investigate the recent finding of a seasonal difference in the onset of systemic-onset juvenile rheumatoid arthritis (SoJRA). We hypothesized that a seasonal onset pattern might implicate on infectious agent as a cause of SoJRA. METHODS: The date of onset was collected from the records of all patients with SoJRA from 1980 to 1992 at presentation to pediatric rheumatology clinics across Canada. The onset pattern of SoJRA was then compared with incidence data on viral infections obtained for the same period. RESULTS: Across Canada the onset of SoJRA was constant across the seasons. However, in the Prairie region there was a statistically significant seasonal pattern, with peaks in autumn and early spring. We could find no evidence that viral incidence correlated with disease incidence either throughout Canada or in the Prairie region. CONCLUSIONS: If a seasonal infectious agent causes SoJRA, then it is likely only one of several causes and may act only in certain regions. Future studies should be carried out in those areas where SoJRA does have a seasonal onset pattern.

Adolescent↗