Subclinical impairment of ovarian reserve in juvenile systemic lupus erythematosus after cyclophosphamide therapy

Objective To perform systematic assessment of ovarian reserve markers using a combination of tests in juvenile systemic lupus erythematosus (JSLE) patients without amenorrhoea. Methods Twenty-seven consecutive JSLE female patients and 13 healthy controls without amenorrhoea were evaluated for 6 months. Ovarian reserve was assessed during early follicular phase by serum levels of follicle stimulating hormone (FSH), luteinising hormone (LH), estradiol, inhibin A, inhibin B and anti-Mullerian hormone (AMH). Ovarian size was measured by abdominal ultrasonography. Demographic data, disease activity, damage and treatment were also analysed. Results The median of current age was similar in ISLE patients and controls (16.5 vs. 15years, p=0.31) with a significantly higher age at menarche (13 vs. 12years, p=0.03). A trend of lower median total antral follicle count was observed in JSLE compared to controls (9 vs. 14.5, p=0.062) with similar median of other ovarian reserve parameters (p>0.05). Further evaluation of patients treated with cyclophosphamide and those without this treatment revealed a higher median FSH levels (6.4 vs. 4.6 IU/L, p=0.023). Inhibin B, AMH levels and ovarian volume were also lower but did not reach statistical significance (10.8 vs. 27.6 pg/mL, p=0.175; 0.6 vs. 1.5 ng/mL, p=0.276; 3.4 vs. 5 cm(3), p=0.133; respectively). LH (2.7 vs. 2.9 IU/L, p=0.43), estradiol (50 vs. 38 pg/mL, p=0.337) and inhibin A (1.1 vs. 0 pg/mL, p=0.489) levels were comparable in both groups. Conclusions Our study suggests that ovarian reserve after cyclophosphamide treatment may be hampered in spite of the presence of menstrual cycles emphasising the relevance of gonadal protection during the use of this alkylating agent.

Tumor microenvironmental genomic alterations in juvenile nasopharyngeal angiofibroma

Background To better characterize the pathophysiology of juvenile nasopharyngeal angiofibroma (JNA), endothelial and stromal cells were evaluated by genomic imbalances in association with transcript expression levels of genes mapped on these altered regions. Methods. High-resolution comparative genomic hybridization (HR-CGH) was used in laser-captured endothelial and stromal cells from 9 JNAs. Ten genes were evaluated by quantitative real-timereverse transcription polymerase chain reaction (qRT-PCR) in 15 cases. Results. Although gains were more frequently detected in endothelial cells, 57% of chromosomal alterations were common by both components. Gene expression analyses revealed a positive correlation between endothelial and stromal components for ASPM, CDH1, CTNNB1, FGF18, and SUPT16H. A significant difference was found for FGF18 and AURKB overexpression in stromal cells and AR down-expression in endothelial cells. Conclusions. A similar pattern of gene expression and chromosomal imbalances in both exponents would suggest a common mechanism of functional regulation. AURKB, FGF18, and SUPT16H were identified as potential molecular markers in JNA. (C) 2011 Wiley Periodicals, Inc. Head Neck 34: 485-492, 2012

Organ-specific autoantibodies and autoimmune diseases in juvenile systemic lupus erythematosus and juvenile dermatomyositis patients

Objectives To our knowledge, no study assessed simultaneously a variety of organ-specific autoantibodies and the prevalence of organ-specific autoimmune diseases in juvenile systemic lupus erythematosus (ISLE) and juvenile dermatomyositis (JDM). Therefore, the purpose of this study was to evaluate organ-specific autoantibodies and autoimmune diseases in JSLE and JDM patients. Methods Forty-one JSLE and 41 JDM patients were investigated for autoantibodies associated with autoimmune hepatitis, primary biliary cirrhosis, type I diabetes mellitus (TIDM, autoimmune thyroiditis (AT), autoimmune gastritis and coeliac disease (CD). Patients with positive antibodies were investigated for the respective organ-specific autoimmune diseases. Results Mean age at diagnosis was higher in ISLE compared to JDM patients (10.3 +/- 3.4 vs. 7.3 +/- 3.1 years, p=0.0001). The frequencies of organ-specific autoantibodies were similar in JSLE and JDM patients (p>0.05). Of note, a high prevalence of TIDM and AT autoantibodies was observed in both groups (20% vs. 15%, p=0.77 and 24% vs. 15%, p=0.41; respectively). Higher frequencies of ANA (93% vs. 59%, p=0.0006), anti-dsDNA (61% vs. 2%, p<0.0001), anti-Ro, anti-Sm, anti-RNP, anti-La and IgG-aCL were observed in JSLE (p<0.05). Organ-specific autoimmune diseases were evidenced only in ISLE patients (24% vs. 0%, p=0.13). Two ISLE patients had TIDM associated with Hashimoto thyroiditis and another had subclinical thyroiditis. Another JSLE patient had CD diagnosis based on iron deficiency anaemia, anti-endomysial antibody, duodenal biopsy compatible to CD and response to a gluten-free diet. Conclusions Organ-specific diseases were observed solely in ISLE patients and required specific therapy. The presence of these antibodies recommends the evaluation of organ-specific diseases and a rigorous follow-up.

Molting dynamics and juvenile hormone titer profiles in the nymphal stages of a lower termite, Cryptotermes secundus (Kalotermitidae) - signatures of developmental plasticity

Termites are social cockroaches and this sociality is founded on a high plasticity during development. Three molting types (progressive, stationary and regressive molts) are fundamental to achieve plasticity during alate/sexual development, and they make termites a major challenge to any model on endocrine regulation in insect development. As the endocrine signatures underpinning this plasticity are barely understood, we studied the developmental dynamics and their underlying juvenile hormone OH) titers in a wood-dwelling termite. Cryptotermes secundus, which is characterized by an ancestral life style of living in dead wood and individuals being totipotent in development. The following general pattern elements could be identified during winged sexual development (i) regressive molts were accompanied by longer intermolt periods than other molting types, (ii) JH titers decreased gradually during the developmental transition from larva (immatures without wing buds), to nymph (immatures with wing buds), to winged adult, (iii) in all nymphal stages, the JH titer rose before the next molt and dropped thereafter within the first week, (iv) considerable variation in JH titers occurred in the midphase of the molting cycle of the 2nd and 3rd nymphal instar, inferring that this variation may reflect the underlying endocrine signature of each of the three molting types, (v) the 4th nymphal instar, the shortest of all, seems to be a switch point in development, as nymphs in this stage mainly developed progressively. When comparing these patterns with endocrine signatures seen in cockroaches, the developmental program of Cryprotermes can be interpreted as a co-option and repetitive use of hormonal dynamics of the post dorsal-closure phase of cockroach embryonic development. (C) 2012 Elsevier Ltd. All tights reserved.

Nonlipidized juvenile xanthogranuloma: An unusual variant with a potential diagnostic pitfall

Juvenile xanthogranuloma (JXG) is a histiocytic inflammatory disorder that can present different histologic patterns. Classic JXG consists of sheets of foamy histiocytes and numerous multinucleated Touton giant cells. Nonlipidized JXG (NJXG) is one of the unusual variants of JXG, consisting of a diffuse monomorphic infiltrate of mononuclear histiocytes, suggesting an aggressive or malignant tumor due the high mitotic index. However, NJXG behaves clinically as classic JXG. We present an unusual case of a 6-year-old boy who presented an exophytic ulcerated nodule on the lower lip diagnosed as NJXG. The boy is currently well without recurrence three years after surgical excision. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

GAUDY JUVENILE PLUMAGES OF CINEREOUS MOURNER (LANIOCERA HYPOPYRRA) AND BRAZILIAN LANIISOMA (LANIISOMA ELEGANS)

We describe the juvenile plumages of the Cinereous Mourner (Laniocera hypopyrra) and the Brazilian Laniisoma (Laniisoma elegans). Both L. hypopyrra and L. elegans possess a dramatically conspicuous plumage as juveniles in contrast to the generally cryptic plumage pattern exhibited by most juvenile birds. They are predominantly covered by cinnamon-orange feathers with black terminal spots, contrasting with the nest and the predominant colors of their environment. This colorful plumage presumably makes them more at risk from predation by visually oriented animals (e.g., raptors and primates), during one of the most vulnerable phases of their life, and strongly suggests these plumages function as a true, or false (mimicry), signal of 'unprofitability'. Previous knowledge concerning the phylogenetic relationships between these two genera, and the juvenile plumage patterns of other species placed in the Tityridae indicate this shared character in L. hypopyrra and L. elegans represents a synapomorphy within this clade, thereby providing additional evidence of their relationship. Received 13 December 2011. Accepted 1 May 2012.

Questionnaire for monitoring auditory and language development in the first year of life

Purpose: To validate a monitoring questionnaire about hearing and language development applied by community health agents in the first year of life. Methods: Seventy six community health agents, previously trained on infant hearing health, administered a questionnaire to the families of 304 children with ages from 0 to 1 year. The questionnaire contains questions regarding hearing and language development and, for all age groups, the question “Does your child hear well?” was presented. The validity of the questionnaire was assessed by analyzing false positive and false negative rates of the identified children. A double-blind study was conducted so that all children assessed by the questionnaire were submitted to hearing evaluation performed by audiologists. Results: Four children (1.32%) were diagnosed with sensorineural hearing loss (two unilateral), and 69 (22.7%) with conductive hearing loss. The monitoring questionnaire showed specificity of 96% and sensitivity of 67%, with a false-negative rate of 33% for not identifying the unilateral hearing loss, and a false-positive rate of 4%. Conclusion: The questionnaire used has shown to be feasible and relevant to actions of the community health agents of the Family Health Strategy program, with high specificity and moderate sensitivity. The use of the validated instrument should be considered to complement Newborn Hearing Screening Programs, in order to identify late onset or acquired hearing loss.

Prospective surveillance study of acute respiratory infections, influenza-like illness and seasonal influenza vaccine in a cohort of juvenile idiopathic arthritis patients

Background Acute respiratory infections (ARI) are frequent in children and complications can occur in patients with chronic diseases. We evaluated the frequency and impact of ARI and influenza-like illness (ILI) episodes on disease activity, and the immunogenicity and safety of influenza vaccine in a cohort of juvenile idiopathic arthritis (JIA) patients. Methods Surveillance of respiratory viruses was conducted in JIA patients during ARI season (March to August) in two consecutive years: 2007 (61 patients) and 2008 (63 patients). Patients with ARI or ILI had respiratory samples collected for virus detection by real time PCR. In 2008, 44 patients were immunized with influenza vaccine. JIA activity index (ACRPed30) was assessed during both surveillance periods. Influenza hemagglutination inhibition antibody titers were measured before and 30-40 days after vaccination. Results During the study period 105 ARI episodes were reported and 26.6% of them were ILI. Of 33 samples collected, 60% were positive for at least one virus. Influenza and rhinovirus were the most frequently detected, in 30% of the samples. Of the 50 JIA flares observed, 20% were temporally associated to ARI. Influenza seroprotection rates were higher than 70% (91-100%) for all strains, and seroconversion rates exceeded 40% (74-93%). In general, response to influenza vaccine was not influenced by therapy or disease activity, but patients using anti-TNF alpha drugs presented lower seroconversion to H1N1 strain. No significant differences were found in ACRPed30 after vaccination and no patient reported ILI for 6 months after vaccination. Conclusion ARI episodes are relatively frequent in JIA patients and may have a role triggering JIA flares. Trivalent split influenza vaccine seems to be immunogenic and safe in JIA patients.

Prodromal Questionnaire: translation, adaptation to Portuguese and preliminary results in ultra-high risk individuals and first episode psychosis

OBJECTIVE: The Prodromal Questionnaire (PQ) is a 92-item self-report screening tool for individuals at ultra-high risk (UHR) to develop psychosis. This study aims to present the translation to Portuguese and preliminary results in UHR and first episode (FE) psychosis in a Portuguese sample. METHODS: The PQ was translated from English to Portuguese by two bilingual researchers from the research program on early psychosis of the Instituto de Psiquiatria HCFMUSP, São Paulo, Brazil (ASAS - "Evaluation and Follow up of Adolescents and Young Adults in São Paulo") and back translated by two other researchers. The study participants (n = 11-) were evaluated through the Portuguese version of the Prodromal Questionnaire (PQ) and SIPS. RESULTS: The individuals at UHR (n = 7) presented a lower score than first episode patients (n = 4). The UHR mean scores and standard deviation on Portuguese version of the PQ were: 13.0 ± 10.0 points on positive symptoms subscale, and FE patients: 33.0 ± 10.0. CONCLUSION: The UHR and FE patients' of this study presented PQ scores similar to the ones found in the literature; what suggests that it is possible to use the PQ in Brazilian help-seeking individuals as a screening tool.

Cross-cultural adaptation of the Safety Attitudes Questionnaire - Short Form 2006 for Brazil

The objective of this study was to perform a cross-cultural adaptation of the Safety Attitudes Questionnaire - Short Form 2006 for Brazil. The instrument was applied in six hospitals in three regions of Brazil. Content, face, and construct validity was performed. Analysis of the instrument's reliability was performed by verifying the items' internal consistency through Cronbach's alpha. The sample was composed of 1301 professionals working in clinical and surgical wards of six hospitals. Confirmatory analysis showed that the model including 41 items was satisfactory. The Portuguese version presented an alpha of 0.89. The item-total correlations among the domains were moderate to strong, except for the domain Stress Recognition. We concluded that the instrument's version adapted to Portuguese and applied in our sample is valid and reliable.

Reduced occurrence of programmed cell death and gliosis in the retinas of juvenile rabbits after shortterm treatment with intravitreous bevacizumab

OBJECTIVE: Bevacizumab has been widely used as a vascular endothelial growth factor antagonist in the treatment of retinal vasoproliferative disorders in adults and, more recently, in infants with retinopathy of prematurity. Recently, it has been proposed that vascular endothelial growth factor acts as a protective factor for neurons and glial cells, particularly in developing nervous tissue. The purpose of this study was to investigate the effects of bevacizumab on the developing retinas of juvenile rabbits. METHODS: Juvenile rabbits received bevacizumab intravitreously in one eye; the other eye acted as an untreated control. Slit-lamp and fundoscopic examinations were performed both prior to and seven days after treatment. At the same time, retina samples were analyzed using immunohistochemistry to detect autophagy and apoptosis as well as proliferation and glial reactivity. Morphometric analyses were performed, and the data were analyzed using the Mann-Whitney U test. RESULTS: No clinical abnormalities were observed in either treated or untreated eyes. However, immunohistochemical analyses revealed a reduction in the occurrence of programmed cell death and increases in both proliferation and reactivity in the bevacizumab-treated group compared with the untreated group. CONCLUSIONS: Bevacizumab appears to alter programmed cell death patterns and promote gliosis in the developing retinas of rabbits; therefore, it should be used with caution in developing eyes

PReS-FINAL-2177: Safety and lack of autoantibody production following influenza H1N1 vaccination in patients with juvenile idiopathic arthritis (JIA)

Introduction Vaccination is an effective tool against several infectious agents including influenza. In 2010, the Advisory Committee on Immunization Practices (ACIP) recommended influenza A H1N1/2009 immunization for high risk groups, including juvenile idiopathic arthritis (JIA) patients and more recently the EULAR task force reinforced the importance of vaccination in immunosuppressed pediatric rheumatologic patients. We have recently shown that Influenza A H1N1/2009 vaccination generated protective antibody production with short-term safety profile among 93 JIA patients, but the possible impact of the vaccine in autoimmune response in JIA have not been studied. Therefore, we aimed to assess the production of some autoantibodies generated following influenza H1N1 vaccination in JIA patients. Objectives To assess the autoimmune response and H1N1 serology following influenza H1N1 vaccination in patients with JIA. Methods Cepa A/California/7/2009 (NYMC X-179A) anti-H1N1 was used to vaccinate JIA patients: 1 dose of immunization was given to all participants and those <9yrs of age received a second booster 3 weeks apart. Sera were analyzed before and 3 weeks following complete vaccination. Serology against H1N1 virus was performed by hemagglutination inhibition antibody assay, rheumatoid factor (RF) by latex fixation test, antinuclear antibodies (ANA) by IIF, IgM and IgG anticardiolipin (aCL) by ELISA.Results Among 98 JIA patients that were vaccinated, 58 sera were available for this study. Mean age of 58 JIA patients was 23.9 ± 9.5 yrs, 38 were females and 20 males with mean disease duration of 14.7 ± 10.1 yrs. JIA subtypes were: 33 (57%) poliarticular, 10 (17%) oligoarticular, 6 (10%) systemic and 9 (16%) other. Sixteen patients were off drugs while 42 (72%) were under different pharmacotherapy: 32 (55%) were on 1 DMARD/IS, 10 (17%) on 2 DMARDs/IS, 19 (33%) antimalarials, 29 (50%) MTX, 8(14%) sulfasalazine, 6 (10%) anti-TNFs, 4 (7%) abatacept; no patient was using prednisone >0.5 mg/kg/d. Seroprotection rates against H1N1 influenza increased from 23 to 83% and seroconversion rates were achieved in 78% JIA. Prior to vaccination, 31(53.4%) JIA patients were ANA+, 6(10.3%) RF+, and 4 (7%) IgM + IgG aCL+. After complete H1N1 vaccination, positivity for ANA remained the same whereas 1 patient became negative for IgG aCL, and another for RF, IgM and IgG aCL. One (1.7%) patient turned low titer IgG aCL+. Conclusion Vaccination of JIA patients against pandemic influenza A (H1N1) generated successful protective antibody production without the induction of autoantibody production, except for 1 patient that became positive for low titer IgG aCL, supporting its safety.