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Biomedical subjects

Kevin J Murray

Publications and source records attributed to Kevin J Murray.

11 recordsLinked to original sources
PubMed2006

Hypermobility disorders in children and adolescents.

It is well recognized that many if not most children and adolescents attending paediatric rheumatology clinics will have a non-inflammatory origin for their complaints or disorder. Mechanical causes are frequently identified, and hypermobility or ligamentous laxity of joints is increasingly recognized as an aetiological factor in the presentation. Such conditions include 'growing pains', recurrent lower-limb arthralgia, anterior knee pain syndromes, and back pain. Studies of significant cohorts of such patients have now been published supporting the link of ligamentous laxity to particular symptom complexes. However, much disagreement remains as to the validity of hypermobility as an aetiogical factor. What seems clear is that not all hypermobile individuals will be symptomatic or indeed possibly have any risk for specific musculoskeletal disorders in later life. Screening tools such as the Beighton score are likely to be inadequate in many paediatric populations. Along with increasing recognition of these disorders in childhood and adolescence has been the development of a multidisciplinary management approach, which usually involves predominantly allied health professionals such as podiatrists, physiotherapists and occupational therapists. The challenge remains to interpret symptoms correctly as being related to the hypermobility and to predict why such children become symptomatic. The answer is likely to involve physiological and psychosocial factors. In addition, early identification and modification of risk factors may have major implications for subsequent prevalence of many adult medical disorders such as low back pain, chronic pain syndromes and degenerative osteoarthritis.

Adolescent↗
PubMed2005

Quantitative assessments of the effects of a single exercise session on muscles in juvenile dermatomyositis.

OBJECTIVE: To investigate the short-term effects of exercise on muscle inflammation in children with juvenile dermatomyositis (juvenile DM). Magnetic resonance imaging (MRI), muscle strength, and blood parameters were used as outcome measures. METHODS: Children with active juvenile DM, inactive juvenile DM, and healthy children were assessed for muscle strength (using myometry) and function, and MRI T2-weighted relaxation time measurement; blood was obtained from patients with juvenile DM. A standardized physiotherapy-led exercise program was completed, and the MRI was performed immediately afterwards. All children were reassessed with myometry and MRI at 30 minutes and 60 minutes, and repeat blood tests were performed at 60 minutes for the patients with juvenile DM. RESULTS: Ten children with active juvenile DM, 10 with inactive juvenile DM, and 20 healthy controls completed the study. Muscle inflammation assessed by MRI, myometry, and blood parameters did not change significantly in response to exercise either immediately after or up to 60 minutes after the exercise program in any group. CONCLUSION: In the short term, a single bout of exercise does not change the degree of inflammation within the muscles of children with active or inactive juvenile DM or in healthy children. The data suggest that, at least in this time period, there is no evidence that exercise increases the inflammation within the muscles. We propose therefore that a moderate exercise program is safe for children with juvenile DM.

Child↗
PubMed2004

A randomized trial of parenteral methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate.

OBJECTIVE: To compare the safety and efficacy of parenteral methotrexate (MTX) at an intermediate dosage (15 mg/m(2)/week) versus a higher dosage (30 mg/m(2)/week) in patients with polyarticular-course juvenile idiopathic arthritis (JIA) who failed to improve while receiving standard dosages of MTX (8-12.5 mg/m(2)/week). METHODS: In the screening phase, 595 patients who were newly started on a standard dose of MTX were followed up for 6 months. Subsequently, the nonresponders, defined according to the American College of Rheumatology (ACR) pediatric 30% improvement criteria (pediatric 30), were randomized to receive an intermediate dose or higher dose of parenteral MTX for an additional 6 months. Improvement in the screening and randomization phase was defined by the ACR pediatric 30 response, as well as by the 50% and 70% response levels (ACR pediatric 50 and ACR pediatric 70, respectively). RESULTS: In the screening phase, after receiving standard doses of MTX, 430 patients (72%) improved according to the ACR pediatric 30, while 360 (61%) met the ACR pediatric 50 and 225 (38%) met the ACR pediatric 70; among these patients, 69 (12%) also met the definition of complete disease control. Of the 133 nonresponders, 80 were randomized to receive an intermediate dose or higher dose of MTX. In the randomization phase, the ACR pediatric 30 response rate was 25 of 40 children (62.5%) in the intermediate-dose group versus 23 of 40 children (57.5%) in the higher-dose group. An ACR pediatric 50 response rate was attained by 23 patients (57.5%) receiving an intermediate dose versus 22 (55%) in the higher-dose group. An ACR pediatric 70 response rate was seen in 18 children (45%) receiving an intermediate dose versus 19 (47.5%) receiving a higher dose. Five children (12.5%) in the intermediate-dose group versus 4 (10%) receiving the higher dose of MTX also met the definition of complete disease control. None of the intergroup differences in response rate were significant. There were no significant differences in the frequency of adverse events or laboratory abnormalities between the 2 randomized groups. CONCLUSION: This study shows that the plateau of efficacy of MTX in JIA is reached with parenteral administration of 15 mg/m(2)/week and that a further increase in dosage is not associated with any additional therapeutic benefit. MTX should be administered for up to 9-12 months to appreciate its full therapeutic effect.

Antirheumatic Agents↗
PubMed2004

Analysis of 1p, 19q, 9p, and 10q as prognostic markers for high-grade astrocytomas using fluorescence in situ hybridization on tissue microarrays from Radiation Therapy Oncology Group trials.

Survival periods vary considerably for patients with high-grade astrocytomas, and reliable prognostic markers are not currently available. We therefore investigated whether genetic losses from chromosomes 1p, 19q, 9p, or 10q were associated with survival in 89 high-grade astrocytomas using tissue microarrays (TMAs) derived from Radiation Therapy Oncology Group clinical trials. Cases included 15 anaplastic astrocytomas (AAs) and 74 glioblastomas (GBMs) selected on the basis of survival times significantly shorter or longer than the expected median. Genetic analysis was performed by TMA-fluorescence in situ hybridization (FISH) on array sections using 8 DNA probes, including those directed at 1p32, 19q13.4, 9p21 (p16/CDKN2A), and 10q (PTEN and DMBT1). Genetic status for each locus was correlated with patient survival group, and data were analyzed by using Fisher's exact test of association (adjusted P = 0.025). Losses of chromosome 1p, either alone or in combination with 19q, were encountered in only 2 cases, both AAs. This contrasts with oligodendrogliomas, in which combined 1p and 19q losses are frequent and predictive of prolonged survival. Solitary 19q loss was noted in 3/15 AAs and in 7/70 GBMs and was more frequent in the long-term survival group (P = 0.041, AA and GBM combined). Chromosome 9p loss was seen in 5/8 AAs and 39/57 GBMs, whereas chromosome 10q loss was detected in 4/15 AAs and 48/68 GBMs. The 9p and 10q deletions were slightly more frequent in short-term survivors, though none of the comparisons achieved statistical significance. Long-term and short-term survival groups of high-grade astrocytomas appear to have dissimilar frequencies of 19q, 9p, and 10q deletions. TMA-FISH is a rapid and efficient way of evaluating genetic alterations in such tumors.

Adult↗
PubMed2004

Oral health of children with juvenile idiopathic arthritis.

OBJECTIVE: s. To estimate dental disease indices and temporomandibular joint (TMJ) dysfunction in children with juvenile idiopathic arthritis (JIA). METHODS: Indices were recorded for dental caries, bacterial dental plaque, gingival inflammation, and TMJ dysfunction in children with JIA and matched controls. RESULTS: There was no significant difference in dental caries experience or the mean plaque score between children with JIA and controls. The mean gingivitis score for the permanent teeth only was significantly greater in the JIA children compared with the controls (p = 0.02). There was a significantly greater proportion of children with JIA with signs of both left and right TMJ dysfunction (p = 0.05, p = 0.02) and symptoms (p = 0.0001, p = 0.0001) compared with controls. CONCLUSION: The low caries rate was attributed to the fact that children with JIA had received preventive dental care from an early age combined with sugar free medication.

Arthritis, Juvenile↗
PubMed2003

Preliminary core sets of measures for disease activity and damage assessment in juvenile systemic lupus erythematosus and juvenile dermatomyositis.

OBJECTIVE: To identify preliminary core sets of outcome variables for disease activity and damage assessment in juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). METHODS: Two questionnaire surveys were mailed to 267 physicians from 46 different countries asking each member to select and rank the response variables used when assessing clinical response in patients with JSLE or JDM. Next, 40 paediatric rheumatologists from 34 countries met and, using the nominal group technique, selected the domains to be included in the disease activity and damage core sets for JSLE and JDM. RESULTS: A total of 41 response variables for JSLE and 37 response variables for JDM were selected and ranked through the questionnaire surveys. In the consensus conference, domains selected for both JSLE and JDM activity or damage core sets included the physician and parent/patient subjective assessments and a global score tool. Domains specific for JSLE activity were the immunological tests and the kidney function parameters. Concerning JDM, functional ability and muscle strength assessments were indicated for both activity and damage core sets, whereas serum muscle enzymes were included only in the activity core set. A specific paediatric domain called 'growth and development' was introduced in the disease damage core set for both diseases and the evaluation of health-related quality of life was advised in order to capture the influence of the disease on the patient lifestyle. CONCLUSIONS: We developed preliminary core sets of measures for disease activity and damage assessment in JSLE and JDM. The prospective validation of the core sets is in progress.

Child↗
PubMed2002

Scleroderma in children and adolescents.

The scleroderma disorders remain challenging conditions in pediatric rheumatology to understand pathologically and indeed for which to provide care. It is clear that much progress is being made in the clinical approach to understanding this group of group of disorders. It seems likely that the different lesions of LS may represent unique immunopathogenic mechanisms or perhaps reflect unique genetic or other characteristics of the patients themselves. To take advantage of the revolution in therapies now occurring in rheumatology it is critical that controlled clinical trials are developed with appropriate agreed upon outcome measures for both localized and systemic disease.

Adolescent↗
PubMed2002

Advanced therapy for juvenile arthritis.

The management of juvenile idiopathic arthritis (JIA) has undergone dramatic changes in the last decade with undoubtedly great benefit for many patients. In particular, more effective use of available drugs and the application of newly discovered drugs have been responsible for much of this improvement. Methotrexate is the gold standard for management of moderate to severe polyarthritis. Other disease-modifying antirheumatic drugs (DMARDs) such as sulphasalazine and cyclosporine are finding a specific role for resistant disease where they may be used in combination with methotrexate, for example. The introduction of anti-TNF agents, such as etanercept, is likely to herald a major shift to the use of biological agents in those intolerant to, or unresponsive to, standard DMARD therapy. DMARDs provide major steroid spring effect in many children with severe JIA with the hope that osteoporosis and growth failure will be reduced. More judicious use of corticosteroids and techniques such as intravenous 'pulse therapy' rather than long-term high-dose use of oral corticosteroids are also major changes. Intra-articular corticosteroids are commonly used in children with oligoarticular JIA and as a useful adjunct to DMARD therapy in children with other forms of JIA. Autologous stem cell transplantation is an exciting new development currently restricted to use in patients with very severe, resistant disease. Modifications of technique, experience and increased safety may make this a more widely applicable technique, in particular for patients with a poor prognosis, such as those with systemic JIA. Although the focus of this chapter is on drug therapy, multidisciplinary team management for children with chronic arthritis focusing on the physical, nutritional, intellectual and psychosocial wellbeing of the child will continue to be important.

Antirheumatic Agents↗