Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome is linked to dysregulated monocyte IL-1β production.

BACKGROUND: The exact pathogenesis of the pediatric disorder periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome is unknown. OBJECTIVES: We hypothesized that PFAPA might be due to dysregulated monocyte IL-1β production linked to genetic variants in proinflammatory genes. METHODS: Fifteen patients with PFAPA syndrome were studied during and outside a febrile episode. Hematologic profile, inflammatory markers, and cytokine levels were measured in the blood. The capacity of LPS-stimulated PBMCs and monocytes to secrete IL-1β was assessed by using ELISA, and active IL-1β secretion was visualized by means of Western blotting. Real-time quantitative PCR was performed to assess cytokine gene expression. DNA was screened for variants of the MEFV, TNFRSF1A, MVK, and NLRP3 genes in a total of 57 patients with PFAPA syndrome. RESULTS: During a febrile attack, patients with PFAPA syndrome revealed significantly increased neutrophil counts, erythrocyte sedimentation rates, and C-reactive protein, serum amyloid A, myeloid-related protein 8/14, and S100A12 levels compared with those seen outside attacks. Stimulated PBMCs secreted significantly more IL-1β during an attack (during a febrile episode, 575 ± 88 pg/mL; outside a febrile episode, 235 ± 56 pg/mL; P < .001), and this was in the mature active p17 form. IL-1β secretion was inhibited by ZYVAD, a caspase inhibitor. Similar results were found for stimulated monocytes (during a febrile episode, 743 ± 183 pg/mL; outside a febrile episode, 227 ± 92 pg/mL; P < .05). Genotyping identified variants in 15 of 57 patients, with 12 NLRP3 variants, 1 TNFRSF1A variant, 4 MEFV variants, and 1 MVK variant. CONCLUSION: Our data strongly suggest that IL-1β monocyte production is dysregulated in patients with PFAPA syndrome. Approximately 20% of them were found to have NLRP3 variants, suggesting that inflammasome-related genes might be involved in this autoinflammatory syndrome.

Use of Existing Meningococcal Group C Vaccine - Students in Higher Education (PDF 20KB)

This document is also available in the Publications Section of the DHSS website at:www.dhssni.gov.uk åÊ åÊ

Report of the National Joint Steering Group on the Working Hours of Non Consultant Hospital Doctors

The introduction of a maximum 48 hour working week for Non Consultant Hospital Doctors by 2010 will have significant implications for both Doctors in training and service delivery in our hospitals. This report focuses on how this reduction in working hours can be achieved and the many directly related issues that need to be addressed Download the Report here

Protecting Our Future - Report of the Working Group on Elder Abuse

The Working Group on Elder Abuse is pleased to present this Report. It provides a foundation for the development of policy and procedures to respond to actual or alleged cases of elder abuse.  Aim of policy and proceduresThe aim of the policy and procedures presented here is to create a context in which older people and those concerned about the abuse of older people can disclose their concerns and receive an appropriate response. The basis of the policy (and the procedures flowing from it) is the recognition of the right of older people to live independent lives with dignity. Download document here

Oral Susceptibility to Yellow Fever Virus of Aedes aegypti from Brazil

The oral susceptibility to yellow fever virus was evaluated in 23 Aedes aegypti samples from Brazil. Six Ae. aegypti samples from Africa, America and Asia were also tested for comparison. Mosquito samples from Asia showed the highest infection rates. Infection rates for the Brazilian Ae. aegypti reached 48.6%, but were under 13% in 60% of sample tested. We concluded that although the low infection rates estimated for some Brazilian mosquito samples may not favor the establishment of urban cycle of yellow fever in some parts of the country, the founding of Ae. aegypti of noteworthy susceptibility to the virus in cities located in endemic and transition areas of sylvatic yellow fever, do pose a threat of the re-emergence of the urban transmission of the disease in Brazil.

Second Report of the Working Group on Child and Adolescent Psychiatric Services

Second Report of the Working Group on Child and Adolescent Psychiatric Services The Minister for Health and Children established a Working Group on Child and Adolescent Psychiatry in June 2000 with the following terms of reference:·  To examine the current state of child and adolescent psychiatric services in the country; ·  To carry out a needs analysis of the population aged 0-18 years for such services and to identify shortcomings in meeting such needs; ·  To make recommendations on how child and adolescent psychiatric services should be developed in the short, medium and long term to meet identified needs. Click here to download PDF 58kb

Treatment of severe infectious purpura in children with human plasma from donors immunized with Escherichia coli J5: a prospective double-blind study. J5 study Group.

To evaluate the efficacy of anti-J5 serum in the treatment of severe infectious purpura, 73 children were randomized to receive either anti-J5 (40) or control (33) plasma. Age, blood pressure, and biologic risk factors were similar in both groups. At admission, however, tumor necrosis factor serum concentrations were 974 +/- 173 pg/ml compared with 473 +/- 85 pg/ml (P = .023) and interleukin-6 serum concentrations were 129 +/- 45 compared with 19 +/- 5 ng/ml (P = .005) in the control and treated groups, respectively. The duration of shock and the occurrence of complications were similar in both groups. The mortality rate was 36% in the control group and 25% in the treated group (P = .317; odds ratio, 0.76; 95% confidence interval, 0.46-1.26). This trend disappeared after correction for unbalances in risk factors at randomization using a logistic regression model. These results suggest that anti-j5 plasma did not affect the course or mortality of severe infectious purpura in children.

Second Report of the Working Group on Child and Adolescent Psychiatric Services

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The National Primary Care Steering Group - Progress Report

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Report of the Expert Group on Midwifery and Children's Nursing Education

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Pharmacy Review Group Report

Pharmacy Review Group Report (PDF, 420KB) Indecon Assessment of the 1996 Pharmacy Regulations (PDF, 430KB) Indecon Review of Proposed Regulatory Models for the Pharmacy Sector (PDF, 400KB)  

National Blood Strategy Implementation Group Report

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Classification of human astrocytic gliomas on the basis of gene expression: a correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes.

The development of targeted treatment strategies adapted to individual patients requires identification of the different tumor classes according to their biology and prognosis. We focus here on the molecular aspects underlying these differences, in terms of sets of genes that control pathogenesis of the different subtypes of astrocytic glioma. By performing cDNA-array analysis of 53 patient biopsies, comprising low-grade astrocytoma, secondary glioblastoma (respective recurrent high-grade tumors), and newly diagnosed primary glioblastoma, we demonstrate that human gliomas can be differentiated according to their gene expression. We found that low-grade astrocytoma have the most specific and similar expression profiles, whereas primary glioblastoma exhibit much larger variation between tumors. Secondary glioblastoma display features of both other groups. We identified several sets of genes with relatively highly correlated expression within groups that: (a). can be associated with specific biological functions; and (b). effectively differentiate tumor class. One prominent gene cluster discriminating primary versus nonprimary glioblastoma comprises mostly genes involved in angiogenesis, including VEGF fms-related tyrosine kinase 1 but also IGFBP2, that has not yet been directly linked to angiogenesis. In situ hybridization demonstrating coexpression of IGFBP2 and VEGF in pseudopalisading cells surrounding tumor necrosis provided further evidence for a possible involvement of IGFBP2 in angiogenesis. The separating groups of genes were found by the unsupervised coupled two-way clustering method, and their classification power was validated by a supervised construction of a nearly perfect glioma classifier.

Report of the Maternity and Infant Care Scheme Review Group

The Irish service was last reviewed in 1980.  Much of the valuable recommendations made at that time have been given effect.  The present Review Group examined that report and, to the extend that recommendations then made have not been acted upon, incorporated them in this report. The views and rights of mothers were of course paramount in the consideration of the members of the Group and issues of choice, privacy, consent and information were considered and appropriate recommendations made. Download the Report here