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P Woo

Publications and source records attributed to P Woo.

At least 37 records · Page 2Linked to original sources
PubMed2002

Juvenile idiopathic arthritis classified by the ILAR criteria: HLA associations in UK patients.

OBJECTIVE: To determine the HLA associations with juvenile idiopathic arthritis (JIA) and its subgroups as defined by the International League of Associations for Rheumatology (ILAR) classification criteria. METHODS: Five hundred and twenty-one UK Caucasian JIA patients and 537 UK Caucasian controls were typed for HLA class II alleles. Phenotype and haplotype frequencies were compared between all JIA cases and controls and between the seven ILAR-defined JIA subgroups. RESULTS: Three haplotypes (DRB1*08-DQA1*0401-DQB1*0402; DRB1*11-DQA1*05-DQB1*03; DRB1*1301-DQA1*01-DQB1*06) were associated with increased risk and one (DRB1*04-DQA1*03-DQB1*03) with decreased risk of JIA. However, in each case the frequencies also varied between JIA subgroups. CONCLUSION: This study categorically demonstrates that there are multiple HLA class II associations with JIA. It has also, for the first time, defined these associations in the seven different ILAR subgroups in UK JIA cases. Although there are a number of common associations, each ILAR subgroup exhibits different patterns of HLA associations, suggesting that the ILAR classification system does define genetically distinct groups of patients.

Adolescent↗
PubMed2002

Immunization in rheumatic diseases of childhood: an audit of the clinical practice of British Paediatric Rheumatology Group members and a review of the evidence.

OBJECTIVES: To establish opinion and clinical practice of senior clinicians working with children with rheumatic diseases with regard to immunization and to determine whether or not this is in accordance with current recommendations. To review published guidelines on the subject and examine the evidence base supporting them. METHODS: A questionnaire was sent to all consultant members of the British Paediatric Rheumatology Group. Information on a variety of issues relating to immunization practice in children with rheumatic diseases was collected. A review of published guidelines and the medical literature on the subject was undertaken to assess current recommendations for immunization in patients on immunosuppressive agents and the evidence supporting these. RESULTS: A number of different sources of information are being used to decide whether or not to immunize patients with rheumatic diseases. Clinical practice varies between individuals. Areas of discordance include the doses of corticosteroids and disease-modifying drugs at which significant immunosuppression is felt likely to occur, the level of immunosuppression conferred by rheumatological diseases themselves and whether or not vaccination should be deferred in the presence of active disease. There was also variation in policy with regard to immunizations not part of the routine recommended schedule. CONCLUSIONS: There is variation in both opinion and clinical practice regarding immunization in children with rheumatic diseases amongst senior clinicians working in the field of paediatric rheumatology. This reflects the lack of consistency between various sets of published guidelines and their non-specificity for rheumatic diseases and their treatment, and the lack of published evidence on the safety and efficacy of different vaccines in these situations. Further research is indicated in the hope that more specific guidelines may be developed for this not uncommonly encountered area of uncertainty.

Arthritis, Juvenile↗
PubMed2001

Functional analysis of the interleukin-1-receptor-associated kinase (IRAK-1) in interleukin-1 beta-stimulated nuclear factor kappa B (NF-kappa B) pathway activation: IRAK-1 associates with the NF-kappa B essential modulator (NEMO) upon receptor stimulation.

The interleukin-1 (IL-1)-receptor-associated kinase (IRAK-1) is essential for IL-1-stimulated nuclear factor kappa B (NF-kappa B) activation. To study the role of IRAK-1 in IL-1 beta signalling, we have generated a set of IRAK-1 variants that express distinct domains of IRAK-1 either alone or in combination and have examined their effects on an NF-kappa B-responsive reporter in HeLa cells. Unlike full-length IRAK-1, the deletion mutants were unable to activate NF-kappa B in the absence of cytokine stimulation. However, an IRAK-1 variant lacking only the N-terminal domain retained the ability of the full-length protein to potentiate both IL-1 beta and tumour necrosis factor alpha (TNF alpha)-induced NF-kappa B activation. In contrast, expression of the N-terminus or the C-terminus of IRAK-1, or a fusion protein incorporating both domains, inhibited both IL-1 beta- and TNF alpha-induced effects. Expression of an IRAK-1 variant lacking only the C-terminal domain preferentially inhibited IL-1 beta versus TNF alpha-induced NF-kappa B activation. These data suggest that the C-terminal domain may link IRAK-1 to downstream signalling components common to both the IL-1 and TNF pathways. Furthermore, we have demonstrated that endogenous IRAK-1 becomes phosphorylated upon IL-1 beta treatment and can be detected along with NF-kappa B essential modulator (NEMO) and I kappa B kinase beta (IKK beta) in high-molecular-mass complexes of 600-800 kDa. Moreover, IRAK-1 could be detected in NEMO immunoprecipitates from IL-1 beta-stimulated cells. We conclude that IRAK-1 mediates IL-1 beta signal transduction through a ligand-dependent association of IRAK-1 with the IKK complex.

Binding Sites↗
PubMed2001

The developing human immune system: T-cell receptor repertoire of children and young adults shows a wide discrepancy in the frequency of persistent oligoclonal T-cell expansions.

While the T-cell receptor (TCR) repertoire of the newborn is highly diverse, a gradual alteration in diversity of the expressed TCR repertoire, in particular the oligoclonality of CD8+ T cells, occurs with increasing age. The timing of the initiation of this process is unknown. These changes are associated with an accumulation of T-cell expansions, thought to be in response to chronic antigen stimulation, frequently by persistent viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Using reverse transcription-polymerase chain reaction heteroduplex analysis we have characterized the TCR expression of CD4 and CD8 cells from healthy young children and adults in order to delineate the age range at which these oligoclonal populations appear. We demonstrate that considerable oligoclonality can occur, even in healthy young children, and also that these expanded clonotypes persist. These are shown by heteroduplex to be exclusively within the CD28- subpopulation. The presence of such oligoclonal expansions correlates closely with the percentage of CD8+ cells that have the CD28- phenotype. However, we also show that control of chronic infection with EBV or CMV may coexist with a highly diverse, polyclonal TCR repertoire well into adulthood. These studies suggest that many factors affect the overall regulation of clone size in response to chronic antigens during the development of the immune system.

Adolescent↗
PubMed2001

Physical and psychologic measures are necessary to assess overall psoriasis severity.

BACKGROUND: The assessment of psoriasis severity is complex and involves both the physical and psychologic assessment of the individual patient. OBJECTIVE: We compared the Salford Psoriasis Index and several other tools for assessing psoriasis severity for their abilities to assess both the physical and psychologic effects of psoriasis. METHODS: A total of 101 patients (44 women, 57 men) were assessed by means of the Salford Psoriasis Index (SPI), Psoriasis Area and Severity Index (PASI), Self-Administered PASI (SAPASI), Psoriasis Disability Index (PDI), Hospital Anxiety and Depression Scale (HADS), and Illness Perception Questionnaire (IPQ). RESULTS: The "signs" score of SPI (which measures the clinical extent of psoriasis), PASI, and SAPASI correlated well with each other (r = 0.69-0.99; P <.01). They also correlated significantly, but not as strongly, with scores of psoriasis-induced disability, the PDI and SPI "psychosocial disability" score (r = 0.46-0.51; P <.01), but not with general measures of psychologic distress. There was no significant correlation between the historical treatment, "intervention," score in SPI and either the physical or the psychologic score in the SPI. The PDI and "psychosocial disability" score of SPI correlated well with each other (r = 0.69; P <.01) as well as with the depression and anxiety subscale scores of HADS (r = 0.33 and r = 0.37; P <.01, respectively), the total number of symptoms suffered by the patient (r = 0.38; P <.01), and the belief that stress or worry were associated with psoriasis (r = 0.33; P <.01). CONCLUSION: Physical scores of psoriasis severity such as PASI, SAPASI, and the "signs" component of SPI give a partial indication of psychosocial disability caused by psoriasis. In many patients, however, the physical score does not reflect psychosocial disability. Patients should be assessed by a more holistic approach, which takes into account both physical and psychologic measurements, such as used in SPI, when assessing the severity of psoriasis.

Adolescent↗
PubMed2001

Divergence in the degree of clonal expansions in inflammatory T cell subpopulations mirrors HLA-associated risk alleles in genetically and clinically distinct subtypes of childhood arthritis.

Clinically distinct forms of childhood arthritis are associated with different risk alleles of polymorphic loci within the MHC, which code for the antigen-presenting class I or class II molecules. We have compared the TCR diversity of synovial T cells from children with enthesitis-related (HLA-B27(+)) arthritis and oligoarticular arthritis (with class II MHC risk allele associations) in parallel with peripheral blood T cells from each child, using a high-resolution heteroduplex TCR analysis. We demonstrate that multiple clonal T cell expansions are present and persistent within the joint in both groups, but that there is disease-specific divergence in the dominant T cell subset containing these expansions. Thus, the largest clonotypes within the inflamed joints of children with class II-associated arthritis are within the CD4(+) synovial T cell population, while the dominant clones from children with enthesitis-related arthritis (associated with a class I allele) are within the CD8(+) synovial T cell population. These data provide powerful data to support the concept that recognition of MHC-peptide complexes by T cells plays a role in the pathogenesis of juvenile arthritis.

Alleles↗
PubMed2001

Autologous stem cell transplantation for paediatric-onset polyarteritis nodosa: changes in autoimmune phenotype in the context of reduced diversity of the T- and B-cell repertoires, and evidence for reversion from the CD45RO(+) to RA(+) phenotype.

We have studied immune reconstitution in a patient with paediatric-onset polyarteritis nodosa treated with high-dose immunosuppressive agents followed by stem cell rescue. The patient developed several new autoimmune phenomena over the 18 months after immunosuppression and stem cell rescue. Flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) heteroduplex and isotype-specific RT-PCR analysis of immunoglobulin expression showed that the T- and B-cell repertoires were highly restricted in the first few months after treatment. The dominant T-cell clones seen after reconstitution were persistently expanded, were different from those which could be demonstrated before autologous stem cell transplantation, and were in the CD8(+) population. Our data also show that 12 months after treatment these expanded T-cell clones were within the CD45RA(+) population, suggesting that reversion from the CD45RO(+) to the CD45RA(+) phenotype had occurred in vivo.

Adult↗
PubMed2001

Hereditary predisposition to low interleukin-10 production in children with extended oligoarticular juvenile idiopathic arthritis.

OBJECTIVE: To determine whether children with extended oligoarticular juvenile idiopathic arthritis (JIA) produce less of the anti-inflammatory cytokine interleukin-10 (IL-10) than those with persistent oligoarticular JIA. METHODS: We measured IL-10 production in the parents of children with oligoarticular or extended oligoarticular JIA, from whole-blood cultures stimulated with lipopolysaccharide. RESULTS: IL-10 production was lower in the parents of children with extended oligoarticular JIA compared with those of children with oligoarticular JIA (P=0.034). There was an increase in the percentage of ATA-containing genotypes (i.e. genotypes ATA/ATA, ATA/ACC or ATA/GCC) in the parents of children with extended oligoarticular JIA compared with healthy controls (P<0.02) but not in the parents of children with oligoarticular JIA. CONCLUSIONS: As approximately 84% of the variation in IL-10 production is thought to be genetically regulated, these results suggest that stimulated IL-10 production would be lower in children with extended oligoarticular JIA. Because IL-10 is an anti-inflammatory cytokine, this may partly explain why this group of children has more severe disease.

Adolescent↗
PubMed2001

Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders.

AIMS: To review the precipitating events, clinical features, treatment, and outcome of macrophage activation syndrome (MAS). METHODS: Retrospective review of cases of MAS from a prospectively collected database of children with rheumatic diseases from 1980 to 2000. RESULTS: Nine patients (eight girls) were considered to have evidence of MAS. The primary diagnosis was systemic onset juvenile idiopathic arthritis in seven, enthesitis related arthritis in one, and chronic infantile neurological cutaneous articular syndrome in one. Mean age of onset was 5.7 years, and duration prior to MAS, 4.2 years. No medication was identified as a trigger. Eight had infections prior to MAS; specific infectious agents were identified in four. High grade fever, new onset hepatosplenomegaly, and lymphadenopathy were common clinical features. Platelet counts fell dramatically, from an average of 346 to 99 x 10(9)/l. Mean erythrocyte sedimentation rate (in three patients) fell from 115 to 28 mm/h. Eight had abnormal liver function during the disease course, and six had coagulopathy. Bone marrow examination supported the diagnosis with definite haemophagocytosis in four of seven. All received high dose steroids (eight intravenous, one oral), five cyclosporin, two cyclophosphamide, and one antithymocyte globulin. Two of three patients with significant renal impairment died. CONCLUSION: MAS is a rare and potentially fatal complication of childhood rheumatic disorders. Most of our patients were female, and most cases were preceded by infection. Bone marrow studies support the diagnosis. Deranged renal function may be a poor prognostic sign. Aggressive early therapy is essential.

Adolescent↗
PubMed2001

Failed medialization laryngoplasty: management by revision surgery.

OBJECTIVE: The purpose of this study was to evaluate the cause of immediate and late medialization laryngoplasty failures and to describe their management. METHODS: A retrospective analysis was performed in 20 patients who underwent revision surgery after failed medialization laryngoplasty. Analysis was based on preoperative spiral CT scan, preoperative and postoperative videostrobolaryngoscopy, and phonatory function measures. RESULTS: Three major types of failures were identified. The most common problem was arytenoid rotation with a persistent posterior glottic gap (11 of 20). Malposition or wrong size of the implants resulted in a lateralized vocal fold or false vocal fold medialization (6 of 20). Three patients had implants that were extruding. Late atrophy and bowing resulted in a glottal gap (2 of 20). One patient had fibrosis around the implant requiring removal. Spiral CT scan of the larynx located the implant precisely and showed the degree of arytenoid rotation. Patients with arytenoid rotation and posterior gap had revision medialization combined with arytenoid adduction. Revision medialization was performed in 11 patients, arytenoid adduction in 12 patients, lipoinjection in 2 patients, and 4 implants were removed. The voice was improved in 15 patients. Improved voice was correlated with improved phonation time and reduced phonatory airflow rates. CONCLUSION: Immediate and late failures of medialization laryngoplasty are due to several possible causes. Revision surgery is feasible and highly successful. To select between the surgical alternatives work up should include preoperative analysis of vocal function, videostrobolaryngoscopic analysis, and spiral CT of the larynx.

Adult↗
PubMed2001

Juvenile idiopathic polyarticular arthritis and IgA deficiency in the 22q11 deletion syndrome.

Five patients with the 22q11 deletion syndrome (velocardiofacial syndrome) developed chronic inflammatory polyarticular arthritis. These new cases add to 8 previously reported and confirm the association. The arthritis in all cases was moderate to severe, but at least partially responsive to methotrexate and/or corticosteroids, and was clinically indistinguishable from juvenile idiopathic arthritis (JIA). Analysis of the total 13 patients indicates that 2 are rheumatoid factor positive, 6 are antinuclear antibody positive, 5 have subtle T cell deficiencies, and 6 have hypergammaglobulinemia. Of particular interest is the occurrence of IgA deficiency in 4 patients, including 2 from our own series. Although IgA deficiency is seen in both JIA (2-4%) and 22q11 deletion syndrome (2-4%), the prevalence of low IgA in this series (31%) is much greater than expected. This phenomenon and the true association of inflammatory arthritis and a chromosome deletion disorder provides further evidence of important genetic factors in the pathogenesis of JIA.

Adolescent↗
PubMed2000

Clinical variability and genetic homogeneity of the camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

The camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) is an autosomal recessive condition characterized by the association of congenital or early onset camptodactyly and noninflammatory arthropathy with synovial hyperplasia. Progressive coxa vara deformity and/or noninflammatory pericardial or pleural effusions have been observed in some patients. Recently, the disease gene has been assigned to human chromosome region 1q25-q31, and truncating mutations have been identified in the megakaryocyte stimulating factor gene. Studying 12 patients from 8 unrelated families, we emphasized hip and spine involvement, particularly in the course of the disease as shown in a 58-year-old patient. Despite clinical variability, linkage studies support genetic homogeneity of the disease.

Adolescent↗
PubMed2000

Selective recruitment of polarized T cells expressing CCR5 and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis.

OBJECTIVE: To study the expression of chemokine receptors CCR5 and CXCR3 and the Th1/Th2 cytokine balance in children with oligoarticular or polyarticular juvenile idiopathic arthritis (JIA). METHODS: Using 3-color immunofluorescence, we studied the expression of CCR5 and CXCR3 on, and T cell cytokine production by, paired samples of synovial fluid (SF) and peripheral blood (PB) T cells from 20 patients with oligoarticular- or polyarticular-onset JIA. Chemokine and cytokine phenotypes were also compared within the CD45RO+,CD3+ subsets. CCR5 genotypes were confirmed by polymerase chain reaction typing and sequencing. RESULTS: In the majority of samples, the number of T cells that were CCR5+ and CXCR3+ was higher in SF than in PB, and this difference was significant. One child was homozygous for the null A32 CCR5 allele; 4 others had lower expression of CXCR3 in SF than in blood. All samples showed strongly Th1-type cytokine production by synovial T cells compared with that by PB T cells. Both features were also markedly polarized within the synovial CD45RO+ subset compared with PB CD45RO+ T cells. CONCLUSION: The high expression of CCR5 and CXCR3 and high interferon-gamma:interleukin-4 ratios suggest a type 1 phenotype of SF T cells in JIA. The difference between CD45RO+ T cells from SF and from PB suggests that specific activation events have occurred in synovial T cells. We suggest that the highly activated, Th1-type phenotype of T cells within the chronically inflamed joints of children with JIA may reflect specific recruitment events that contribute to the polarization of these cells.

Adolescent↗
PubMed2000

Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) can persist through adolescence and adulthood, resulting in significant disability. The use of low-dose oral methotrexate (MTX) for persistent polyarthritis has been shown to be effective by the USA/USSR collaborative study group. However, 2 of the most disabling subgroups of JIA, systemic and extended oligoarthritis, were underrepresented in that study. The present study was therefore conducted to investigate the efficacy of MTX in these 2 subgroups. METHODS: Patients under the age of 16 years who fulfilled the International League of Associations for Rheumatology criteria for systemic or extended oligoarticular arthritis were eligible for this multicenter, double-blind, placebo-controlled crossover trial. Forty-five patients with systemic and 43 with extended oligoarticular arthritis were enrolled. The dosage of MTX or placebo was 15 mg/m2, which could be increased to 20 mg/m2 after 2 months. Core outcome variables were considered as primary measures, giving a final score of "improved" or "not improved." Secondary measures included scores of systemic features and biochemical laboratory measures. Assessment of function was not included since there were no validated functional measures at the start of this trial in 1991. RESULTS: In the extended oligoarticular arthritis group, MTX treatment produced significant improvement in 3 of 5 core variables (erythrocyte sedimentation rate, physician's global assessment of disease activity, and parent's global assessment of disease activity). By the primary improvement criteria, there was significant overall improvement during MTX treatment. In the systemic arthritis group, only 2 of 5 core variables were significantly improved (physician's and parent's global assessment of disease activity). Systemic features were not part of the core variables, but the systemic feature score was not significantly different between MTX and placebo treatment. There was no significant overall improvement in this group during MTX treatment. However, no significant interaction between disease subgroup and treatment effect was demonstrated. When the data from both disease subgroups were combined, there was significant clinical improvement during MTX treatment (P = 0.006). CONCLUSION: MTX 15-20 mg/m2 given orally once a week was found to be an effective treatment for both extended oligoarticular and systemic JIA in this shortterm trial. Long-term efficacy needs to be addressed in future studies.

Adolescent↗
PubMed2000

Arytenoid adduction and medialization laryngoplasty.

Arytenoid adduction and medialization laryngoplasty have become the mainstay of static surgical rehabilitation of the larynx after vocal fold paralysis. The rationale for considering one versus a combination of the two procedures has not been well addressed. This article outlines the basic science of the procedures and the clinical technical modifications necessary to make the surgery easier.

Biomechanical Phenomena↗