Invasive aspergillosis: a severe infection in juvenile systemic lupus erythematosus patients

Infections are an important cause of morbidity and mortality in juvenile systemic lupus erythematosus (JSLE). Among them, invasive aspergillosis (IA), which is usually related to immunosuppressed patients, has been rarely reported in JSLE. From 1983 to 2011, 5604 patients were followed at our institution and 283 (5%) met the American College of Rheumatology (ACR) classification criteria for SLE. Six (2.1%) of our JSLE patients had IA. One of them was previously reported and five will be described herein. Four of them were female. The median age at JSLE diagnosis was 12 years (8-16) and the median interval between diagnosis of JSLE and IA was 6 months (1-38). All had pulmonary involvement and three of them had systemic involvement. The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was 19 (7-22). Diagnosis of IA was performed by isolation of Aspergillus spp., two in bronchoalveolar lavage culture and by way of autopsy in the others. All of them were treated with corticosteroids and/or immunosuppressive drugs at IA diagnosis (azathioprine and/or intravenous cyclophosphamide). They all required treatment in the pediatric intensive care unit with mechanical ventilation and antifungal therapy (fluconazole, amphotericin B, itraconazole and/or voriconazole); nonetheless, none of them survived. In conclusion, this was the first report that evaluated the prevalence of IA in a large population of JSLE patients from a tertiary pediatric hospital, and clearly showed the severity of the outcome, especially in patients with active disease and treated with immunosuppressive agents. This study reinforces the importance of early diagnosis and treatment with certain antifungals, especially in critically ill patients. Lupus (2012) 21, 1011-1016.

Alveolar hemorrhage: distinct features of juvenile and adult onset systemic lupus erythematosus

We compared outcomes of alveolar hemorrhage (AH) in juvenile (JSLE) and adult onset SLE (ASLE). From 263 JSLE and 1522 ASLE, the AH occurred in 13 (4.9%) and 15 (1.0%) patients, respectively (p < .001). Both groups had comparable disease duration (2.6 +/- 3.0 vs. 5.6 +/- 7.0 years, p = .151) and median SLEDAI scores [17.5 (2 to 32) vs. 17.5 (3 to 28), p = 1.000]. At AH onset, a higher frequency of JSLE were already on a high prednisone dose ( > 0.5 mg/kg/day) compared to ASLE (54% vs. 15%, p = .042). The mean drop of hemoglobin was significantly lower in JSLE (2.9 +/- 0.9 vs. 5.5 +/- 2.9 g/dL, p = .006). Although treatments with methylprednisolone, plasmapheresis, intravenous immunoglobulin and cyclophosphamide were similar in both groups (p > .050), regarding outcomes, there was a trend in high frequency of mechanical ventilation use (85% vs. 47%, p = .055) and also significant mortality (69% vs. 13%, p = .006) in JSLE compared to ASLE. The sepsis frequency was comparable in both groups (50% vs. 27%, p = .433). We have identified that AH in JSLE has a worse outcome most likely related to respiratory failure. The AH onset in JSLE already treated with high-dose steroids raises the concern of inadequate response to this treatment and reinforces the recommendation of early aggressive alternative therapies in this group of patients. Lupus (2012) 21, 872-877.

Reduced occurrence of programmed cell death and gliosis in the retinas of juvenile rabbits after short-term 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.

Exercise training in juvenile dermatomyositis

Objective. To investigate the effects of a supervised exercise training program on health parameters, physical capacity, and health-related quality of life in patients with mild and chronic juvenile dermatomyositis (DM). Methods. This was a prospective longitudinal study following 10 children with mild and chronic juvenile DM (disease duration >1 year). The exercise program consisted of twice-a-week aerobic and resistance training. At baseline and after the 12-week intervention, we assessed muscle strength and function, aerobic conditioning, body composition, juvenile DM scores, and health-related quality of life. Results. Child self-report and parent proxy-report Pediatric Quality of Life Inventory scores were improved after the intervention (-40.3%; P = 0.001 and -48.2%; P = 0.049, respectively). Importantly, after exercise, the Disease Activity Score was reduced (-26.9%; P = 0.026) and the Childhood Muscle Assessment Scale was improved (+2.5%; P = 0.009), whereas the Manual Muscle Test presented a trend toward statistical significance (+2.2%; P = 0.081). The peak oxygen consumption and time-to-exhaustion were increased by 13.3% (P = 0.001) and 18.2% (P = 0.003), respectively, whereas resting heart rate was decreased by 14.7% (P = 0.006), indicating important cardiovascular adaptations to the exercise program. Upper and lower extremity muscle strength and muscle function were also significantly improved after the exercise training (P < 0.05). Both the whole-body and the lumbar spine bone mineral apparent density were significantly increased after training (1.44%; P = 0.044 and 2.85%; P = 0.008, respectively). Conclusion. We showed for the first time that a 12-week supervised exercise program is safe and can improve muscle strength and function, aerobic conditioning, bone mass, disease activity, and health-related quality of life in patients with active and nonactive mild and chronic juvenile DM with near normal physical function and quality of life.

GENETIC VARIABILITY FOR JUVENILE CHARACTERS OF Cedrela fissilis VELL. PROGENIES: A SUBSIDY FOR DEFINITION OF SEED COLLECTION ZONE

The objective of this study was to evaluate the genetic differences among three matrix groups of Cedrela fissilis based on quantitative juvenile variables on a progeny test to define seed collecting zones and use of seeds of this species in the study region as well as to evaluate genetic variability of the sampled material. A progeny test was established in a nursery with seeds from 48 seed trees collected in the municipalities of Rio Negrinho, Mafra and Sao Bento do Sul, state of Santa Catarina, and in the municipalities of Lapa, Rio Negro, Campo do Tenente and Antonio Olinto, state of Parana. Of the collected seed trees, 33 sampled trees were distributed in three sites and 15 trees were dispersed in the studied region. It was used a complete random block design, with 8 replicates and 20 plants per plot. Evaluated data included: emergency rate; seedling base diameter and height (61, 102 and 145 days after the seeds were sowed); seedling survival; number of leaves per seedling; aerial section dry mass and root dry mass; and the foliar area of the third fully expanded leaf measured from the apical meristem. The Maximum Restricted Likelihood Method (REML) was used, using the software SELEGEN for analysis. It was found that the juvenile characters are strongly genetically controlled and they can be used to estimate genetic variability of population samples of Cedrela fissilis. The three groups of trees spatially limited did not significantly differ among each other, allowing to conclude that the three areas are part of the same tree seed transfer zone.

Juvenile angiofibroma: major and minor complications of preoperative embolization

Introduction: Juvenile angiofibromas (JA) are highly vascular, benign tumours for which surgery is the treatment of choice. In most services, embolisation is performed prior to resection. Nevertheless, there are few data on the complications of preoperative embolisation for JA. Aim: To describe major and minor complications of preoperative embolisation in a 32-year experience of patients undergoing surgical resection of JA at a tertiary hospital. Methods: Retrospective chart review study of 170 patients who underwent surgical resection of JA at a tertiary hospital between September 1976 and July 2008. Results: All patients were male. Age ranged from 9 to 26 years. Ninety-one patients had no complications after embolisation. Overall, 105 complication events occurred of which four major and 101 minor. Conclusion: In our series, preoperative embolisation for JA produced no irreversible complications and no aesthetic or functional sequelae. The vast majority of complications were transient and amenable to clinical management.

Disseminated histoplasmosis in a juvenile lupus erythematosus patient

Introduction: Histoplasmosis is an infection caused by dimorphic fungus, Histoplasma capsulatum, and it has not been reported in juvenile systemic lupus erythematosus (JSLE) patients, particularly progressive disseminated histoplasmosis (PDH) subtype. Case report: We reported herein a 14-year old girl who was diagnosed with JSLE. Six months later, she had abdominal distension and received prednisone, hydroxychloroquine and azathioprine. Computer tomography evidenced hepatosplenomegaly and multiple mesenteric, mediastinal and retroperitoneal enlarged lymph nodes, forming large conglomerates at the mesentery, suggestive of lymphoproliferative disorder. After 10 days, she had acute surgical abdominal, and underwent a laparotomy and intestinal perforation and conglomerates of lymph nodes were observed. The jejunum biopsy showed perforated acute enteritis with hemorrhage and necrosis, and Grocott staining identified Histoplasma sp. and the culture showed a heavy growth of Histoplasma capsulatum. At that moment liposomal amphotericin B (1.0 mg/Kg/day) was introduced. Despite this treatment she died due to septic shock eight days later. Diffuse Histoplasma capsulatum was evidenced at autopsy. Conclusion: We reported a severe opportunistic infection in JSLE patient with adenopathy and multiple intestinal perforations. This study reinforces the importance of early diagnosis and antifungal therapy, especially in patients with these uncommon clinical manifestations.

Influenza A H1N1/2009 vaccine in juvenile dermatomyositis: reduced immunogenicity in patients under immunosuppressive therapy

Objectives The aim of the present paper is to assess the influence of demographic, muscle enzymes, JDM scores and treatment on non-adjuvanted influenza A H1N1/2009 vaccine immunogenicity in juvenile dermatomyositis (JDM) patients. Methods Thirty JDM patients and 81 healthy age-matched controls were vaccinated. All participants were evaluated pre- and 21 days post-vaccination and serology for anti-HI NI was performed by haemagglutination inhibition assay. Muscle enzymes, JDM scores and treatment were evaluated before and after vaccination. Adverse events were reported. Results After immunisation seroconversion rates were significantly lower in JDM patients compared to age-matched controls (86.7 vs. 97.5%, p=0.044), whereas seropmtection (p=0.121), geometric mean titres (GMT) (p=0.992) and factor increase (FI) in GMT (p=0.827) were similar in both groups. Clinical and labomtorial evaluations revealed that JDM scores and muscle enzymes remained stable throughout the study (p>0.05). A higher frequency of chronic course was observed in non-seroconverted compared to seroconverted (100% vs. 27%, p=0.012). Regarding treatment, a lower rate of seroconversion was observed in patients under prednisone>20mg/day (50% vs. 4%, p=0.039), and in those treated with a combination of prednisone, methotrexate and cyclosporine (50% vs. 4%, p=0.039). Local and systemic vaccine adverse events were mild and similar in patients and controls (p>0.05). Conclusion This study identified that chronic course and immunosuppressive therapy are the major factors hampering seroconversion was JDM, suggesting that a specific protocol may be required for this subgroup of patients. In spite of that, a single dose of non-adjuvanted influenza A/H1N1 2009 vaccine was generally seroprotective in this disease with no evident deleterious effect in disease itself (ClinicalTrials.gov, no. NCT01151644).

Kawasaki disease and juvenile systemic lupus erythematosus

Kawasaki disease (KD) is a common vasculitis in childhood. To the authors' knowledge, only one case of juvenile systemic lupus erythematosus (JSLE)-like onset mimicking KD and another case of KD and JSLE association have previously been described. However, the prevalence of this association of the two diseases was not reported. Therefore, over 27 consecutive years, 5419 patients were followed at the Pediatric Rheumatology Unit and 271 (5%) of them met the ACR classification criteria for JSLE. Two (0.7%) of them were female. These also had KD according to European League against Rheumatism / Paediatric Rheumatology European Society (EULAR/PReS) consensus criteria and are described in this report. One case was a 13-year-old who presented all six KD criteria. Echocardiogram showed pericardial effusion, dilatation and tortuosity of right and left coronary, and her symptoms promptly improved after treatment with intravenous immunoglobulin (IVIG). Lupus diagnosis was established a few days later. Another case was a 4-year-old who had also met all six KD criteria, with improvement after IVIG, and lupus diagnosis was made 1 year later. In conclusion, the frequency of the association between these two autoimmune diseases was rare. The occurrence of a second autoimmune systemic disease in a patient with a history of KD should also be considered. Furthermore, the initial presentation of lupus may mimic KD. Lupus (2012) 21, 89-92.

Assessment of the sublethal toxicity of organochlorine pesticide endosulfan in juvenile common carp (Cyprinus carpio)

This study is aimed at evaluating the sublethal effects of endosulfan (EDS) in juvenile common carp (Cyprinus carpio). For this purpose, fish were exposed for 15 days to the technical EDS (95% pure) diluted in dimethyl sulfoxide (DMSO) 0.1% of the total volume in water solution in a semi-static system at sublethal concentration (1 mu g/L). Subsequently, the liver somatic index (LSI) and factor condition (K) were determined. The total cytocrome P450 (CYP), CYP1A isoform, and the ethoxyresorufin-O-deethylase (EROD) activity were determined from the hepatic microsomal fraction as well as the activity of the oxidative stress enzyme system such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GP(X)), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH). Among the parameters assessed, EDS at the sublethal concentration in subchronic exposure caused significant changes in liver somatic indices as well as induction of the phase I biotransformation system and oxidative stress in juvenile common carp (Cyprinus carpio). Thus, it is seen that the use of biochemical biomarkers of environmental contamination in this study proved to be an extremely important tool for detecting the adverse effects of xenobiotics in the aquatic environment, even at low concentration.

Juvenile myoclonic epilepsy: The impact of clinical variables and psychiatric disorders on executive profile assessed with a comprehensive neuropsychological battery

Executive dysfunction is reported in juvenile myoclonic epilepsy (JME). However, batteries employed in previous studies included no more than three tests of executive function. In this study, we aimed to assess executive and attentional functions in JME using a comprehensive battery of eight tests (encompassing fifteen subtests). We also evaluated neuropsychological profiles using a clinical criterion of severity and correlated these findings with epilepsy clinical variables and the presence of psychiatric disorders. We prospectively evaluated 42 patients with JME and a matched control group with Digit Span tests (forward and backward), Stroop Color-Word Test, Trail Making Test, Wisconsin Card-Sorting Test, Matching Familiar Figures Test and Word Fluency Test. We estimated IQ with the Matrix Reasoning and Vocabulary subtests of the Wechsler Abbreviated Intelligence Scale. The patients with JME showed specific deficits in working memory, inhibitory control, concept formation, goal maintenance, mental flexibility, and verbal fluency. We observed attentional deficits in processes such as alertness and attention span and those requiring sustained and divided attention. We found that 83.33% of the patients had moderate or severe executive dysfunction. In addition, attentional and executive impairment was correlated with higher frequency of seizures and the presence of psychiatric disorders. Furthermore, executive dysfunction correlated with a longer duration of epilepsy. Our findings indicate the need for comprehensive neuropsychological batteries in patients with JME, in order to provide a more extensive evaluation of attentional and executive functions and to show that some relevant deficits have been overlooked. (C) 2012 Elsevier Inc. All rights reserved.

Assessment of trophic transfer of benzo(a)pyrene genotoxicity from the post-larval pink shrimp F. brasiliensis to the juvenile Florida pompano T. carolinus

In the present study, the polycyclic aromatic hydrocarbon (PAH) genotoxicity was investigated in a one-step predator-prey relationship with the trophic-related marine species. Florida pompanos were fed for 5 and 10 days with pink shrimp post larvae previously exposed to benzo(a)pyrene (BaP) concentrations. Parent BaP body burden was measured in samples of Farfantepenaeus brasiliensis. BaP metabolites were determined in bile samples of Trachinotus carolinus and DNA damage was assessed through the comet and erythrocyte nuclear abnormalities (ENAs) assays in fish erythrocytes. BaP body burden increased significantly with the PAH concentration in pink shrimp PLs as well as the fish bile BaP metabolites. Both, comet and ENAs assays indicated significant increase on erythrocyte DNA damage of Florida pompanos fed with BaP-exposed pink shrimp on both feeding periods. The trophic route of BaP genotoxicity is discussed as well as the PAH biotransformation as the inducing mechanism for the DNA damages observed.

Growth, body composition and hematology of juvenile pacu (Piaractus mesopotamicus) fed increasing levels of ractopamine

The effects of four levels of dietary ractopamine (RAC) on growth, body composition and hematology of pacu, Piaractus mesopotamicus juveniles (103.6+/-3.3g) were studied. Fish were housed into 12 circular tanks of 1 m(3) - 15 fish per tank - and fed for 60 days with practical diets supplemented with 0; 10; 20 or 40mg RAC per kg of diet, in a totally randomized design trial (n=3). Fish fed diets containing up to 40mg RAC/kg diet for 60 days did not have improved growth or body composition parameters. There were no significant differences in hematocrit, hemoglobin and mean corpuscular hemoglobin. Plasma glucose and triglycerides were significantly smaller in fish fed with RAC; however no significant differences between RAC levels were detected. The inclusion of up to 40mg RAC/kg of diet did not improve growth and body composition, but influenced some hematological and biochemical parameters of juvenile pacu.

Glucocorticoid: Major Factor for Reduced Immunogenicity of 2009 Influenza A (H1N1) Vaccine in Patients with Juvenile Autoimmune Rheumatic Disease

Objective. To assess the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with juvenile autoimmune rheumatic disease (ARD) and healthy controls, because data are limited to the adult rheumatologic population. Method's. A total of 237 patients with juvenile ARD [juvenile systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), juvenile scleroderma, and vasculitis] and 91 healthy controls were vaccinated. Serology for anti-H1N1 was performed by hemagglutination inhibition assay. Seroprotection rate, seroconversion rate, and factor-increase in geometric mean titer (GMT) were calculated. Adverse events were evaluated. Results. Age was comparable in patients and controls (14.8 +/- 3.0 vs 14.6 +/- 3.7 years, respectively; p = 0.47). Three weeks after immunization, seroprotection rate (81.4% vs 95.6%; p = 0.0007), seroconversion rate (74.3 vs 95.6%; p < 0.0001), and the factor-increase in GMT (12.9 vs 20.3; p = 0.012) were significantly lower in patients with juvenile ARD versus controls. Subgroup analysis revealed reduced seroconversion rates in JSLE (p < 0.0001), JIA (p = 0.008), JDM (p = 0.025), and vasculitis (p = 0.017). Seroprotection (p < 0.0001) and GMT (p < 0.0001) were decreased only in JSLE. Glucocorticoid use and lymphopenia were associated with lower seroconversion rates (60.4 vs 82.9%; p = 0.0001; and 55.6 vs 77.2%; p = 0.012). Multivariate logistic regression including diseases, lymphopenia, glucocorticoid, and immunosuppressants demonstrated that only glucocorticoid use (p = 0.012) remained significant. Conclusion. This is the largest study to demonstrate a reduced but adequate immune response to H1N1 vaccine in patients with juvenile ARD. It identified current glucocorticoid use as the major factor for decreased antibody production. The short-term safety results support its routine recommendation for patients with juvenile ARD. ClinicalTrials.gov; NCT01151644. (First Release Nov 15 2011; J Rheumatol 2012;39:167-73; doi:10.3899/jrheum.110721)

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.