Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases.

Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders: earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10(-5)): three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA.

The association of maternal polyunsaturated fatty acids during pregnancy with social competence and problem behaviours at 7 years of age: The MEFAB cohort.

BACKGROUND: The prenatal exposure to maternal n-6 and n-3 polyunsaturated fatty acids (PUFAs) might influence the development of social competence and internalizing and externalizing behaviours of the child, because of the numerous functions of PUFAs within the nervous system. METHODS: To analyse the association of selected maternal PUFAs (i.e., AA, EPA, DHA, total n-6, total n-3, and the n-6:n-3 ratio) measured during gestation with childhood social competence and problem behaviours, we examined 311 mother-child pairs from the Maastricht Essential Fatty Acid Birth (MEFAB) cohort. For each woman, PUFA-specific changes in relative concentrations were calculated by identifying the best-fitting curve of PUFA concentration by linear splines of gestational age. The associations of changes in maternal PUFAs in early and late pregnancy with childhood social competence, total problems, internalizing and externalizing behaviours, measured with the Child Behaviour Checklist 4/18 at age 7, were investigated with linear regression analyses adjusted for maternal and children's socio-demographic characteristics. RESULTS: In late gestation (i.e., from gestational week 30), an increase in AA was associated with higher social competence, while a decrease in total n-6 was associated with lower externalizing behaviours. No other significant associations were found. DISCUSSION: In this prospective study, increasing maternal AA and decreasing total n-6 were associated with improved social competence and externalizing behaviours, respectively, in 7-year old children. Nonetheless, the clinical significance of the identified associations is modest and further investigations are warranted to clarify the relationship between maternal AA and total n-6 during pregnancy and childhood social and behavioural development.

Wrist Arthroscopy in Juvenile Idiopathic Arthritis: A Review of Current Literature and Future Implications.

Introduction Juvenile Idiopathic Arthritis (JIA) is the most common rheumatological condition in children and frequently affects the wrist. The roles for wrist arthroscopy and arthroscopic synovectomy (AS) in JIA are unclear. Our aim was to find the current evidence supporting its use. Methods Systematic literature review of relevant publications from 1990 to present in the Cochrane Library, Clinical Knowledge Summaries, DynaMed, PEMSoft, NICE Guidance, MEDLINE, EMBASE, and PubMed. Results We found no publications detailing the use of arthroscopy or AS specifically in patients with JIA involving the wrist. There is evidence that AS reduces pain, improves function, and induces remission in patients with rheumatoid arthritis resistant to medical management. Discussion and Conclusion Although there is paucity in evidence for the use of AS in the wrists of patients with JIA, studies suggest it to be safe and effective, and could be applied to patients with refractive JIA. It is possible that early identification of patients suffering from JIA with extensive joint destruction and little symptoms could benefit from AS, delaying joint destruction and preserving function.

Unconventional remedies used for patients with juvenile arthritis.

While attending arthritis youth camps, 53 patients with juvenile arthritis from Australia (31 patients), New Zealand (4 patients), and Canada (18 patients) completed individual questionnaires concerning their treatment. Between 1 and 8 unconventional remedies (mean 2.6) had been used by 37 (70%) of the patients. The most commonly used unconventional remedies were copper bracelets (68%), diet (43%), and patent medicines (38%). The potential dangers of unconventional remedy use in children are illustrated by three case reports. Professionals caring for patients with juvenile arthritis should be aware that most of them will probably use unconventional remedies at some time.

The micro-organisms of tsetse flies.

Micro-organisms from tsetse fly mycetomes were maintained in culture, where they were more pleomorphic than in the mycetomes, but were in some cases very similar to those observed in ovaries by other authors. Agglutination tests on the cultured forms indicated in affinity to Rickettsia. They were sensitive to antibiotics introduced by feeding flies on hosts treated with Ampicillin; this reduced the longevity and fecundity of the tsetse flies and appeared to disturb normal digestion of bloodmeals.

The impact of predation on the viburnum whitefly, (Aleurotrachelus jelinekii).

In association with a detailed study of the population dynamics of the viburnum whitefly, Aleurotrachelus jelinekii, observations were made on the predators including spiders and five species of insect, notably the mirid Campyloneura virgula and the neuropteran Conwentzia psociformis. Although the species richness of the predator guild was positively correlated with prey population density, at the individual level there was little evidence over twelve years of a density dependent relationship. In these populations natural enemies do not seem to play an important role in the dynamics.

Trophic diversity, niche breadth and generation times of exopterygote insects in a secondary succession.

Various ecological characteristics have been determined for the exopterygote insect fauna of three sites in a secondary succession, with successional ages zero-two years (ruderal and early successional - Young Field), seven to eight years (mid successional - Old Field) and around 60 years (late successional - Woodland). The taxonomic diversity of the group as a whole (Table 1) and the trophic diversity (major types of feeding habits) (Table 2) increased with successional age. A comparison of the numbers of individuals and species of insect with the abundance and species of plant of each of the main life forms (annuals, biennials, perennials, trees, grasses (and rushes), ferns and lower plants) showed that at the start of secondary succession there was a good correlation between the number of species of insect and number of species of plant. In the second year and later the correlation is between plant abundance and insect abundance (the number of individuals) (Table 3). The sap-feeding insects may be divided into three specialised guilds: phloem feeders, xylem feeders and mesophyll feeders. The proportion of species in each guild was similar in all four successional stages (Table 4). Niche breadth (determined from host plant records) in the sap feeding herbivores was inversely related to the successional age of their habitat (Table 6). Herbivore species colonising the stages early in succession had, on average, shorter generation times than those of later stages (Table 7).

The relationship between palatability to invertebrates and the successional status of a plant.

The palatability of common plants from three stages of secondary sere have been assessed by a bioassay method. Foliage was exposed to five taxonomically very different herbivores (Agriolimax, Schistocera, Spodoptera, Myzus and Trialeurodes). Palatability was measured by foliage consumption or, for sap suckers, by survival and reporduction. The results of these experiments supported the predictions of Feeny's 'Apparency theory', but indicated considerable variations in palatability within plant communities and between herbivores.

Leaf palatability, life expectancy and herbivore damage.

Observations on leaves from plants with a wide range of life-forms, ruderals to trees, indicate that palatability to insect herbivores is strongly correlated with the life-expectancy of the leaves. The amount of damage suffered in the field is however inversely correlated with palatability; although the rate of damage is less on unpalatable leaves, their longer life means that they accumulate damage over a longer period. It is only with extremely well-defended evergreen leaves, that the total damage is less than that experienced by less palatable (but short-lived) leaves. These observations are related to the current theories on relative palatability (the apparency theory and the resource availability theory), within the framework of the habitat templet.

Use of quantitative ultrasound to assess bone status in children with juvenile idiopathic arthritis: a pilot study.

Periarticular osteoporosis around inflammed joints and generalized osteoporosis have been shown to be markers of disease activity and severity in children with juvenile idiopathic arthritis (JIA). Bone mineral density (BMD) in adults can be assessed precisely by dual X-ray absorptiometry (DXA), but this technique has not been used widely in children. Quantitative ultrasound (QUS) may provide an alternative method for assessment of bone status. The aim of this pilot study was to compare QUS to DXA in assessing generalized osteoporosis in a cohort of patients JIA. Twenty-two Caucasian children (15 females, 7 males) with JIA of duration 19-142 months (mean 71 mo) and age 7-17 yr were recruited. Total body and lumbar spine BMD and bone mineral content (BMC) were measured by DXA using standard procedures on a Lunar DPX-L scanner. QUS was performed using Myriad SoundScan 2000. Speed of sound (SOS) was measured at the right midtibia. The DXA results were compared to QUS using linear regression analysis. Spine and total body BMD measured by DXA correlated significantly with tibia SOS (spine: r = 0.57, p < 0.007; total body: r = 0.68, p < 0.001). Spine BMC was similarly related to SOS as BMD (r = 0.58, p < 0.007). Individual patient weight and height were strong predictors of BMD, but only moderate predictors of SOS. The mean spine BMD was lower in the JIA patients compared to the normal ranges (mean Z-score of -1.19). BMD Z-scores were negatively associated with disease duration. Patients taking steroids were associated with lower Z-scores. In conclusion, SOS shows a significant correlation with BMD as measured by DXA, albeit with wide 95% confidence intervals in this small pilot study. QUS was also well tolerated and was technically easy to perform in these children. With the added advantage that it is free from radiation risk, further assessment of this potentially valuable tool for measuring bone status in children is warranted.

Immunohistochemical and cytokine analysis of eyes from rats with adjuvant arthritis.

Adjuvant induced arthritis in the rat is an animal model of juvenile chronic arthritis (JCA). An anterior uveitis may also develop in this model which closely resembles that seen in association with JCA in the human. Female Lewis rats (150-225 g) were injected intradermally with either Freund's complete adjuvant (FCA, n=5) or Freund's incomplete adjuvant (FIA, n=5). Eyes were examined by slit-lamp biomicroscopy every two days, and the animals sacrificed 21 days post-immunisation. Aqueous humour and serum interleukin-6 (IL-6) levels were determined using the B(9) bioassay, and serial tissue sections of the globes were stained with a variety of monoclonal antibodies. In the FCA group, arthritis was detected in two rats, but no rats from either group developed clinical uveitis. Immunohistochemical analysis revealed greater numbers of macrophages and MHC class II+ve cells in the irises and ciliary bodies of FCA treated rats than were seen in the FIA group. No other cellular infiltrate was detected. Serum IL-6 levels were greater in the FCA group (range 6-122 U/ml, median 42) than the FIA group (range 2-27, median 3) (p=0.018), the highest values seen in the two rats which developed arthritis (100, 122 U/ml). In the aqueous of both groups, IL-6 levels were <5 U/ml, and albumin levels were not significantly different (FCA median=2.0 mg/ml, FIA median=1.8). The authors″ results suggest that in the adjuvant induced arthritis model, infiltration with macrophages and MHC class II+ve cells occurs in the absence of clinical uveitis.

Intrauterine environment and cognitive development in young twins.

Intrauterine factors important for cognitive development, such as birth weight, chorionicity and umbilical cord characteristics were investigated. A total of 663 twin pairs completed the Wechsler Intelligence Scale for Children-Revised and scores were available for Performance, Verbal and Total Intelligence Quotient (IQ). The intrauterine factors examined were birth weight, placental weight and morphology, cord knots, cord length and cord insertion. IQ scores for the varying levels of the intrauterine markers adjusting for gender and gestational age were calculated. The heritability of IQ and the association between IQ and intrauterine environment were examined. Twins with lower birth weight and cord knots had lower IQ scores. The aetiology of IQ is largely distinct from that of birth weight and cord knots, and non-shared environment may influence the observed relationships.

The impact of a coordinated transitional care programme on adolescents with juvenile idiopathic arthritis.

OBJECTIVE: There is an extensive evidence base for the need of transitional care, but a paucity of robust outcome data. The aim of the study was to determine whether the quality of life of adolescents with juvenile idiopathic arthritis (JIA) could be improved by a co-ordinated, evidence-based programme of transitional care. METHODS: Adolescents with JIA aged 11, 14 and 17 yrs and their parents were recruited from 10 rheumatology centres in the UK. Data were collected at baseline, 6 and 12 months including core outcome variables. The primary outcome measure was health-related quality of life (HRQL): Juvenile Arthritis Quality of Life Questionnaire (JAQQ). Secondary outcome measures included: knowledge, satisfaction, independent health behaviours and pre-vocational experience. RESULTS: Of the 359 families invited to participate, 308 (86%) adolescents and 303 (84%) parents accepted. A fifth of them had persistent oligoarthritis. Median disease duration was 5.7 (0-16) yrs. Compared with baseline values, significant improvements in JAQQ scores were reported for adolescent and parent ratings at 6 and 12 months and for most secondary outcome measures with no significant deteriorations between 6 and 12 months. Continuous improvement was observed for both adolescent and parent knowledge with significantly greater improvement in the younger age groups at 12 months (P = 0.002). CONCLUSIONS: This study represents the first objective evaluation of an evidence-based transitional care programme and demonstrates that such care can potentially improve adolescents' HRQL.

Young people's satisfaction of transitional care in adolescent rheumatology in the UK.

BACKGROUND: To examine the quality of transitional health care from the perspectives of young people with juvenile idiopathic arthritis (JIA) and their parents. METHODS: Adolescents with JIA and their parents were recruited from 10 major UK rheumatology centres. Satisfaction with health-care delivery was measured prior to, and 12 months after, the implementation of a structured and co-ordinated programme of transitional care using self-completed questionnaires designed for this study. RESULTS: Of 359 families invited to participate, 308 (86%) adolescents with JIA and 303 (84%) parents/guardians accepted. A fifth of adolescents had persistent oligoarthritis. Median age was 14.2 (11-18) years with median disease duration of 5.7 (0-16) years. Young people and their parents rated provider characteristics more important than aspects of the physical environment or process issues. Staff honesty and knowledge were rated as the most essential aspects of best practice. Prior to implementing the programme of transitional care, parents rated service delivery for all items significantly worse than best practice. Overall satisfaction improved 12 months after entering the programme. However, while parent satisfaction improved for 70.4% of items, significant improvements were only observed for three (13.6%) items rated by adolescents. CONCLUSION: The perceived quality of health care for young people with JIA and their parents was significantly lower than what they would like. Satisfaction with many aspects of care during transition from paediatric to adult services can be improved through the implementation of a structured, co-ordinated programme of transitional care.