Rate of tuberculosis infection in children and adolescents with household contact with adults with active pulmonary tuberculosis as assessed by tuberculin skin test and interferon-gamma release assays.

Tuberculosis (TB) infection was evaluated in Brazilian immunocompetent children and adolescents exposed and unexposed (control group) to adults with active pulmonary TB. Both groups were analysed by clinical and radiological assessment, TST, QFT-IT and T-SPOT.TB. The three tests were repeated after 8 weeks in the TB-exposed group if results were initially negative. Individuals with latent tuberculosis infection (LTBI) were treated and tests were repeated after treatment. Fifty-nine TB-exposed and 42 controls were evaluated. Rate of infection was 69·5% and 9·5% for the exposed and control groups, respectively. The exposed group infection rate was 61% assessed by TST, 57·6% by T-SPOT.TB, and 59·3%, by QFT-IT. No active TB was diagnosed. Agreement between the three tests was 83·1% and 92·8% in the exposed and control groups, respectively. In the exposed group, T-SPOT.TB added four TB diagnoses [16%, 95% confidence interval (CI) 1·6-30·4] and QFT-IT added three TB diagnoses (12%, 95% CI 0-24·7) in 25 individuals with negative tuberculin skin test (TST). Risk factors associated to TB infection were contact with an adult with active TB [0-60 days: odds ratio (OR) 6·9; >60 days: OR 27·0] and sleeping in the same room as an adult with active TB (OR 5·2). In Brazilian immunocompetent children and adolescents, TST had a similar performance to interferon-gamma release assays and detected a high rate of LTBI.

Whole-body magnetic resonance imaging in the assessment of muscular involvement in juvenile dermatomyositis/polymyositis patients.

OBJECTIVES: Our aim was to demonstrate the benefit of whole-body magnetic resonance imaging (WBMRI) as a diagnostic modality in the detection of muscle activity in juvenile dermatomyositis (JDM)/polymyositis (JPM) patients and to correlate these findings with clinical evaluation, laboratory examinations, nailfold capillaroscopy (NFC), and muscle biopsy. METHOD: Thirty-four patients aged 5.5 to 18.9 years with a diagnosis of JDM/JPM were prospectively evaluated using clinical examination, muscle enzyme determination, the Childhood Myositis Assessment Scale (CMAS), Disease Activity Score (DAS), Manual Muscle Testing (MMT), NFC, and WBMRI. An open muscle biopsy was performed if muscle disease activity was detected on WBMRI. RESULTS: Disease activity was detected in WBMRI in four (11.7%) patients and confirmed by muscle biopsy. All four patients had elevation of at least one muscle enzyme and NFC showed scleroderma patterns in these patients. CONCLUSIONS: WBMRI allows us to evaluate the extent and symmetry of muscle disease and inflammatory activity. NFC is an important additional examination to assess disease activity.

Cerebral abnormalities in adults with ataxia-telangiectasia.

Ataxia-telangiectasia, an autosomal recessive disorder caused by defect of the ataxia-telangiectasia mutated gene, is characterized by progressive neurologic impairment with cerebellar atrophy, ocular and cutaneous telangiectasia, immunodeficiency, heightened sensitivity to ionizing radiation and susceptibility to developing lymphoreticular malignancy. Supratentorial brain abnormalities have been reported only rarely. In this study, brain MRI was performed in 10 adults with ataxia-telangiectasia having stable neurologic impairment. Intracerebral telangiectasia with multiple punctate hemosiderin deposits were identified in 60% of subjects. These lesions were apparently asymptomatic. They are similar in appearance to radiation-induced telangiectasia and to cryptogenic vascular malformations. Also noted, in the 2 oldest subjects, was extensive white matter T2 hyperintensity, and in 1 of these a space-occupying fluid collection consistent with transudative capillary leak and edema as evidenced by reduced levels of metabolites on MR spectroscopic imaging. Asymptomatic supratentorial vascular abnormalities appear to be common in adults with ataxia-telangiectasia.

Longitudinal relationship of early life immunomodulatory T cell phenotype and function to development of allergic sensitization in an urban cohort.

BACKGROUND: Immunomodulatory T cells are thought to influence development of allergy and asthma, but early life longitudinal data on their phenotype and function are lacking. OBJECTIVES: As part of the Urban Environment and Childhood Asthma (URECA) study, we investigated the development of immunomodulatory T cell phenotype and function, and characterized their relation to allergic disease progression from birth through to 2 years of age. METHODS: Immunomodulatory T cell phenotype and function in cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) at 1 and 2 years of age were characterized by analysing CD25(bright) and FoxP3(+) expression, proliferative responses and cytokine production. The relation of immunomodulatory T cell characteristics to allergic sensitization and disease at 1- and 2-years of age was investigated. RESULTS: The proportion of CD4(+)CD25(bright) and CD4(+)CD25(+)FoxP3(+)T cells (n = 114, 83, 82 at birth, 1- and 2-years respectively) increased significantly, whereas there were no significant changes in the suppressive function of CD25(+)T cells (n = 78, 71, 81 at birth, 1- and 2-years respectively). Birth immunomodulatory T cell characteristics were not related to subsequent allergic sensitization or disease. However, increases in the numbers of CD4(+)CD25(bright) cells and their ability to suppress lymphoproliferative responses at 1 year of age were associated with reduced allergic sensitization at 1 (P = 0.03) and 2 (P = 0.02) years of age. Production of the anti-inflammatory cytokine IL-10 by CD25(+)T cells appeared to mediate this protective suppressive function. In contrast, by 2 years of age, we observed the emergence of a positive association of CD4(+)CD25(+) FoxP3(+) T cell numbers with allergic sensitization (P = 0.05) and eczema (P = 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: These findings suggest that the relationship between immunomodulatory T cell subsets, allergic sensitization and eczema is developmentally regulated. In the first year of life, CD4(+)CD25(+) IL-10 producing T cells are associated with a reduced incidence of allergic sensitization. Once allergic sensitization or eczema is established, CD4(+)CD25(+)FoxP3(+)T-reg cells expand to potentially counteract the allergic inflammatory response. Understanding the relationship between development of immunoregulatory T cells and early onset atopy could lead to new preventive strategies for allergic diseases.

The use of joint-specific and whole-body MRI in osteonecrosis: a study in patients with juvenile systemic lupus erythematosus.

OBJECTIVE: This study aimed to estimate the prevalence of osteonecrosis (ON) in juvenile systemic lupus erythematosus (SLE) patients using joint-specific and whole-body MRI; to explore risk factors that are associated with the development of ON; and to evaluate prospectively patients 1 year after initial imaging. METHOD: Within a 2 year period, we studied 40 juvenile SLE patients (aged 8-18 years) with a history of steroid use of more than 3 months duration. Risk factors including disease activity, corticosteroid use, vasculitis, Raynaud's phenomenon and lipid profile were evaluated. All patients underwent MRI of the hips, knees and ankles using joint-specific MRI. Whole-body STIR (short tau inversion recovery) MRI was performed in all patients with ON lesions. RESULTS: Osteonecrosis was identified in 7 patients (17.5 %) upon joint-specific MRI. Whole-body STIR MRI detected ON in 6 of these 7 patients. There was no significant difference between the ON and non-ON groups in the risk factors studied. One patient had pre-existing symptomatic ON. At 1 year follow-up, the ON lesions had resolved in one patient, remained stable in four and decreased in size in two. No asymptomatic patients with ON developed clinical manifestations. CONCLUSION: Whole-body STIR MRI may be useful in detecting ON lesions in juvenile SLE patients but larger studies are needed to define its role.

The role of orexigenic and anorexigenic factors in an interdisciplinary weight loss therapy for obese adolescents with symptoms of eating disorders.

AIM: The aim of this study was to evaluate the role of orexigenic and anorexigenic factors in an interdisciplinary weight loss therapy for obese adolescents with symptoms of eating disorders. METHODS: Thirty-seven post-pubertal, obese adolescents (14 to 19 years old) with symptoms of eating disorders were submitted to long-term interdisciplinary therapy (1 year). Bulimic and binge eating symptoms were measured using the Bulimic Investigatory Test, Edinburgh, and the Binge Eating Scale respectively. Neuropeptide Y, melanin-concentrating hormone, total ghrelin, alpha-melanocyte stimulating hormone and leptin were measured using radioimmunoassay. RESULTS: After long-term interdisciplinary therapy, the adolescents showed significantly improved body composition, visceral and subcutaneous fat and reduced symptoms of bulimia and binge eating. Intriguingly, orexigenic peptides were up-regulated after short-term therapy and down-regulated at the end of therapy, whereas the anorexigenic pathway was improved with therapy. Furthermore, after long-term therapy, a negative correlation was observed between leptin concentration and melanin-concentrating hormone. DISCUSSION: We suggest that long-term therapy promotes an intrinsic association between weight loss, improvement of eating disorder symptoms and a decrease in orexigenic factors. Together, these results represent a more effective course by which patients can normalise behaviours related to eating disorders as well the actions of hormones involved in energy balance, and thus advance obesity control. CONCLUSION: Long-term interdisciplinary therapy was effective to improve anorexigenic and orexigenic factors that influence energy balance and avoid the development of eating disorders in obese adolescents. However, the associations between eating disorders and neuroendocrine factors need to be confirmed in future studies.

Ultrasound evaluations of internal jugular vein punction techniques in children: the easiest method to reach the target area.

The objective of this study is to determine the best way to access and the position in which the patients must remain in order to obtain the best transversal section of the right internal jugular vein (RIJV) section during the catheterization by ultrasound, allowing a safer and precise access. The three possible ways to access the RIJV, anterior, lateral and posterior, from 57 healthy children, were examined by ultrasound in one similar sequence of positions: horizontal dorsal decubitus with the head centered in neutral position with and without the use of a pillow; horizontal dorsal decubitus with contralateral rotation of the head with and without the use of a pillow; horizontal dorsal decubitus with the head centered in neutral position and the patient in the Trendelenburg position without the use of a pillow. The relation between the different positions and punction regions in RIJV were established using analysis of variance. As a result, the lateral punction with the patient in the Trendelemburg position offered a largest area of the RIJV transversal section in comparison to all the other options (P<0.0001). In conclusion, this study demonstrated that the safer and precise way for the RIJV catheterization in pediatric patients is obtained in Trendelenburg position with lateral access and without a pillow.

Relationship between nonalcoholic fatty liver disease prevalence and visceral fat in obese adolescents.

BACKGROUND: Visceral adiposity is the major risk factor for paediatric nonalcoholic fatty liver disease. AIMS: Determine the prevalence of nonalcoholic fatty liver disease according to the visceral fat quartile. SUBJECTS: 181 obese adolescents including 113 girls (16.58+/-1.56 years) and 68 boys (16.87+/-1.62 years) were evaluated. METHODS: The inclusion criteria were obesity and post-pubertal stage of Tanner. Visceral fat of obese adolescents was distributed in quartiles after ultrasound nonalcoholic fatty liver disease diagnosis. RESULTS: Nonalcoholic fatty liver disease prevalence was 45.30%. It was observed that 62.07% and 76.47% of girls and boys with nonalcoholic fatty liver disease were found in the 4th quartile. In a multivariate logistic analysis it was observed that only visceral fat remained statistically significant, every 1cm increase in visceral fat was associated with a 1.97 fold (95% CI 1.06-3.66) in boys and 2.08 fold (95% CI 1.38-3.13) in girls increased risk to develop nonalcoholic fatty liver disease. Indeed it was verified a positive correlation between visceral fat, body mass index, insulin levels, homeostasis model assessment insulin resistance index and steatosis degree. CONCLUSIONS: Our findings suggested that the expansion of visceral fat was a determinant factor to increase nonalcoholic fatty liver disease prevalence and the visceral fat measured by ultrasound might be a good predictor to identify risk for nonalcoholic fatty liver disease in obese adolescents. It was confirmed by a stronger correlation between visceral fat and body mass index.

Proton MR spectroscopic imaging in ataxia-telangiectasia.

OBJECT: Ataxia-telangiectasia (A-T) is a recessively inherited neurodegenerative disorder with prominent progressive ataxia and cerebellar degeneration, as well as manifest abnormalities of tone, posture, and movement suggesting extrapyramidal dysfunction. In this study, we tested the hypothesis that regional metabolite levels, as measured by proton magnetic resonance spectroscopic imaging, would be abnormal in patients with A-T in the posterior fossa and basal ganglia, reflecting the underlying neurodegenerative processes in these regions. METHODS: Spectroscopic images of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) were obtained in 8 patients with A-T and 8 age-matched controls. Normalized metabolite levels were compared between A-T patients and control subjects in various regions of interest, including the cerebellum, brainstem, and basal ganglia. RESULTS: A-T patients were distinguished from controls by the profound loss of all metabolites in the cerebellar vermis (NAA, p < 0.01; Cr and Cho, p < 0.05) and a trend for decreased metabolites within the cerebellar hemispheres. No abnormalities were detected in the basal ganglia. CONCLUSIONS: Proton MR spectroscopic features in A-T closely correlate with the morphologic neuroimaging findings of posterior fossa atrophy. Although symptoms suggesting extrapyramidal dysfunction are part of the A-T phenotype, these are not associated with altered metabolite levels in the basal ganglia.

How to improve IVF-ICSI outcome by sperm selection.

In previous studies, a new IVF method of intracytoplasmic morphologically selected sperm injection (IMSI) was introduced, based on motile sperm organellar morphology examination (MSOME). It was concluded that microinjection of morphologically selected sperm cells with strictly normal nucleus, defined by MSOME, improves IVF-ICSI outcome. The aim of the present study was to confirm this conclusion in new, enlarged study groups. Comparison between 80 couples, who underwent an IVF-IMSI trial, with matched couples, who underwent a standard IVF-ICSI procedure, confirmed that pregnancy rate following IVF-IMSI was significantly higher, and abortion rate significantly lower than in the routine IVF-ICSI (60.0 versus 25.0%, and 14 versus 40% respectively, P

Survival probability in ataxia telangiectasia.

Ataxia telangiectasia is a rare, multiorgan neurodegenerative disorder with enhanced vulnerability to cancer and infection. Median survival in two large cohorts of patients with this disease, one prospective and one retrospective, is 25 and 19 years, with a wide range. Life expectancy does not correlate well with severity of neurological impairment.

Use of interferon alpha in intratumoral chemotherapy for cystic craniopharyngioma.

OBJECTIVES: This study analyzed the intratumoral activity of interferon alpha (IFN-alpha) in the treatment of cystic craniopharyngiomas. PATIENTS AND METHODS: From January 2000 to January 2004, nine patients presenting with cystic craniopharyngiomas were treated with intratumoral injection of IFN-alpha at the Pediatric Oncology Institute of the Federal University of São Paulo-Escola Paulista de Medicina. Age ranged from 1 year and 10 months to 18 years (mean 10 years). All intratumoral catheters were inserted by a subfrontal approach. Doses varied from 36 to 108 MU. RESULTS: There was complete disappearance of the lesion in seven cases. In two cases, partial reduction of tumor size was observed at follow-up. Follow-up varied from 1 year to 3 years and 6 months (mean 1 year 8 months). CONCLUSIONS: IFN-alpha proved to be an effective drug in the control of cystic craniopharyngiomas. Additional studies should be carried out to determine the optimal dose of IFN-alpha in the treatment of cystic craniopharyngioma. In addition, other drugs possessing high efficacy and low neurotoxicity should be analyzed.

Helicobacter cinaedi bacteremia presenting as macules in an afebrile patient with X-linked agammaglobulinemia.

We describe a 54-year-old man with X-linked agammaglobulinemia (XLA) and Helicobacter cinaedi bacteremia, who presented with tender, hyper-pigmented skin macules without increased local warmth or fever. We propose that this presentation may be a characteristic early sign of bacteremia caused by H. cinaedi and related organisms in otherwise healthy immunocompromised patients. This case demonstrates the importance of a high index of suspicion for H. cinaedi bacteremia in immunocompromised patients with unexplained skin lesions.

Use of single photon emission computed tomography and magnetic resonance to evaluate central nervous system involvement in patients with juvenile systemic lupus erythematosus.

The objective of the present study was to identify the single photon emission computed tomography (SPECT) and magnetic resonance (MR) findings in juvenile systemic lupus erythematosus (JSLE) patients with CNS involvement and to try to correlate them with neurological clinical history data and neurological clinical examination. Nineteen patients with JSLE (16 girls and 3 boys, mean age at onset 9.2 years) were submitted to neurological examination, electroencephalography, cerebrospinal fluid analysis, SPECT and MR. All the evaluations were made separately within a period of 15 days. SPECT and MR findings were analyzed independently by two radiologists. Electroencephalography and cerebrospinal fluid analysis revealed no relevant alterations. Ten of 19 patients (53%) presented neurological abnormalities including present or past neurological clinical history (8/19, 42%), abnormal neurological clinical examination (5/19, 26%), and abnormal SPECT or MR (8/19, 42% and 3/19, 16%, respectively). The most common changes in SPECT were cerebral hypoperfusion and heterogeneous distribution of blood flow. The most common abnormalities in MR were leukomalacia and diffuse alterations of white matter. There was a correlation between SPECT and MR (P<0.05). We conclude that SPECT and MR are complementary and useful exams in the evaluation of neurological involvement of lupus.

Use of single photon emission computed tomography and magnetic resonance to evaluate central nervous system involvement in patients with juvenile systemic lupus erythematosus

The objective of the present study was to identify the single photon emission computed tomography (SPECT) and magnetic resonance (MR) findings in juvenile systemic lupus erythematosus (JSLE) patients with CNS involvement and to try to correlate them with neurological clinical history data and neurological clinical examination. Nineteen patients with JSLE (16 girls and 3 boys, mean age at onset 9.2 years) were submitted to neurological examination, electroencephalography, cerebrospinal fluid analysis, SPECT and MR. All the evaluations were made separately within a period of 15 days. SPECT and MR findings were analyzed independently by two radiologists. Electroencephalography and cerebrospinal fluid analysis revealed no relevant alterations. Ten of 19 patients (53 percent) presented neurological abnormalities including present or past neurological clinical history (8/19, 42 percent), abnormal neurological clinical examination (5/19, 26 percent), and abnormal SPECT or MR (8/19, 42 percent and 3/19, 16 percent, respectively). The most common changes in SPECT were cerebral hypoperfusion and heterogeneous distribution of blood flow. The most common abnormalities in MR were leukomalacia and diffuse alterations of white matter. There was a correlation between SPECT and MR (P<0.05). We conclude that SPECT and MR are complementary and useful exams in the evaluation of neurological involvement of lupus

Skin test reactivity and cellular immune responses to Mycobacterium avium sensitin in AIDS patients at risk for disseminated M. avium infection.

Skin tests and lymphocyte proliferation assays (LPA) were performed with Mycobacterium avium sensitin on patients with AIDS. Among 139 subjects, 13% had positive skin test results and 32% had positive LPA results. The LPA may be a more sensitive indicator of prior M. avium infection in this population.

Successful treatment of enterovirus infection with the use of pleconaril in 2 infants with severe combined immunodeficiency.

Two patients with severe combined immunodeficiency and enterovirus infections were successfully treated with pleconaril. There were no adverse affects.

Fatal warm autoimmune hemolytic anemia resulting from IgM autoagglutinins in an infant with severe combined immunodeficiency.

Autoimmune diseases are rare in patients with severe combined immunodeficiency (SCID). The authors describe an 11-month-old infant girl with SCID with fatal warm autoimmune hemolytic anemia (AIHA) resulting from IgM autoagglutinins. Serologic evaluation revealed IgM autoantibodies that caused in vitro hemagglutination at 37 degrees C. The patient had clinical evidence of ongoing hemolysis and agglutination despite aggressive treatment. She had three strokes and died 6 weeks after unsuccessful bone marrow transplantation. Autoimmune disease is an unexpected complication of SCID. The presence of warm reactive IgM autoagglutinins in AIHA confers a dismal prognosis.

JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome.

X-linked autoimmunity-allergic disregulation syndrome (XLAAD) is an X-linked recessive immunological disorder characterized by multisystem autoimmunity, particularly early-onset type 1 diabetes mellitus, associated with manifestations of severe atopy including eczema, food allergy, and eosinophilic inflammation. Consistent with the allergic phenotype, analysis of two kindreds with XLAAD revealed marked skewing of patient T lymphocytes toward the Th2 phenotype. Using a positional-candidate approach, we have identified in both kindreds mutations in JM2, a gene on Xp11.23 that encodes a fork head domain-containing protein. One point mutation at a splice junction site results in transcripts that encode a truncated protein lacking the fork head homology domain. The other mutation involves an in-frame, 3-bp deletion that is predicted to impair the function of a leucine zipper dimerization domain. Our results point to a critical role for JM2 in self tolerance and Th cell differentiation.

Safety and immunogenicity of heptavalent pneumococcal vaccine conjugated to CRM(197) among infants with sickle cell disease. Pneumococcal Conjugate Vaccine Study Group.

OBJECTIVES: To determine the immunogenicity and safety of heptavalent pneumococcal polysaccharide vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to CRM(197) (7-valent conjugate pneumococcal vaccine [7VPnC]) among infants with sickle cell disease (SCD) and a comparison group of infants without SCD (non-SCD). DESIGN: Two cohorts of infants were enrolled and received open-label doses of 7VPnC vaccine; infants enrolled before 2 months of age received 7VPnC vaccine at 2, 4, and 6 months of age followed by 23-valent pneumococcal polysaccharide vaccine (PS-23) at 24 months of age for those infants with SCD (schedule A), and infants enrolled between 2 and 12 months of age received 7VPnC at 12 months of age followed by PS-23 at 24 months of age for infants with SCD (schedule B). Safety data were collected for 3 days after each dose of vaccine. Antibody concentrations were measured to each of the 7VPnC serotypes by enzyme-linked immunosorbent assay before each vaccine dose and 1 month after the last 7VPnC dose and the PS-23 vaccine dose. RESULTS: Forty-five infants (34 SCD and 11 non-SCD) were vaccinated according to schedule A and 16 infants (13 SCD and 3 non-SCD) according to schedule B. The 7VPnC vaccine was highly immunogenic for all serotypes among infants with and without SCD who received 3 doses of vaccine according to schedule A: depending on serotype, 89% to 100% achieved antibody concentrations above.15 microg/mL and 56% to 100% achieved antibody concentrations above 1.0 microg/mL. Among infants immunized according to schedule B, a single dose of 7VPnC vaccine resulted in antibody concentrations above.15 microg/mL in 53% to 92% by serotype and above 1.0 microg/mL in 31% to 71% by serotype. A single dose of PS-23 resulted in dramatic increases in the antibody concentrations to all serotypes regardless of 1- or 3-dose priming. There was no difference in the reactogenicity of the 7VPnC vaccine between those with and without SCD. There were no serious reactions to the 7VPnC or PS-23 vaccines, even among those with high antibody concentrations before immunization. CONCLUSIONS: Infants with SCD respond to 7VPnC vaccine with antibody concentrations that are at least as high as infants without SCD. Infants immunized with 7VPnC vaccine at 2, 4, and 6 months of age developed antibody concentrations in the same range as those achieved among infants without SCD enrolled in a large trial that demonstrated vaccine efficacy against invasive disease. Significant rises were seen in antibody concentrations to all 7VPnC serotypes after the PS-23 booster in children receiving schedule A or B.