bluuebunny/crossref_metadata_2025 huggingface dataset:
Pro- and Anti-Nociceptive Effects of Corticotropin-Releasing Factor (CRF) in Central Amygdala Neurons Are Mediated Through Different Receptors
Authors: Ji Guangchen , Neugebauer Volker
Published: January 2008

Corticotropin-releasing factor (CRF) is not only a stress hormone but also acts as a neuromodulator outside the hypothalamic-pituitary-adrenocortical axis, playing an important role in anxiety, depression, and pain modulation. The underlying mechanisms remain to be determined. A major site of extra-hypothalamic expression of CRF and its receptors is the amygdala, a key player in affect-related disorders such as anxiety. The latero-capsular division of the central nucleus of the amygdala (CeLC) is also important for pain modulation and pain affect. This study analyzed the effects of CRF on nociceptive processing in CeLC neurons and the contribution of CRF1 and CRF2 receptors and protein kinases A and C. Extracellular single-unit recordings were made from CeLC neurons in anesthetized adult rats. All neurons responded more strongly to noxious than innocuous mechanical stimulation of the knee. Evoked responses and background activity were measured before and during administration of CRF into the CeLC by microdialysis. CRF was administered alone or together with receptor antagonists or protein kinase inhibitors. CRF (0.01–1 μM; concentrations in microdialysis probe; 15 min) facilitated the evoked responses more strongly than background activity; a higher concentration (10 μM) had inhibitory effects. Facilitation by CRF (0.1 μM) was reversed by a selective CRF1 receptor antagonist ( NBI27914 , 10 μM) but not a CRF2 receptor antagonist (astressin-2B, 100 μM) and by a protein kinase A (PKA) inhibitor (KT5720, 100 μM) but not a protein kinase C inhibitor (GF109203X, 100 μM). Inhibitory effects of CRF (10 μM) were reversed by astressin-2B. These data suggest that CRF has dual effects on amygdala neurons: CRF1 receptor-mediated PKA-dependent facilitation and CRF2 receptor-mediated inhibition.
Identification of DEIN, a Novel Gene with High Expression Levels in Stage IVS Neuroblastoma
Authors: Voth Harald , Oberthuer André , Simon Thorsten , Kahlert Yvonne , Berthold Frank , Fischer Matthias
Published: January 2008

Neuroblastoma at stage IVS, defined by dissemination to specific tissues and age <1 year at diagnosis, regularly follows spontaneous regression without cytotoxic treatment. To uncover the molecular characteristics of this subtype, Serial Analysis of Gene Expression (SAGE) profiles from stage IVS and fatal stage IV tumors were compared. A SAGE tag (GCAACTTAAC) was detected that was overrepresented in stage IVS disease and that had no reliable match in current National Center for Biotechnology Information databases of SAGE profiles, thus pointing to a novel gene. The corresponding gene, which maps to chromosome 4q33-34, was identified using a modified 3′- and 5′-rapid amplification of cDNA ends PCR and was designated as DEIN (differentially expressed in neuroblastoma). The gene comprises five transcript variants and its sequence overlaps with expressed sequences of the yet uncharacterized UniGene cluster Hs.61435. DEIN exhibits nucleotide sequence conservation over a broad range of species with an overall homology of 65% between human and mouse. As none of the predicted amino acid sequences is homologous to known proteins, it remains to be determined whether DEIN represents a coding or noncoding RNA. Northern blot analysis and semiquantitative reverse transcription-PCR showed high DEIN expression in neuroblastoma, whereas expression was absent or weak in most normal adult tissues. Analysis of 121 primary neuroblastomas by real-time reverse transcription-PCR revealed a strong association with age at diagnosis <1 year and particularly with stage IVS disease (both P < 0.001). The characteristic expression pattern of DEIN suggests a specific role of this gene in the unique biology of stage IVS tumors and may help to molecularly define this special subtype of neuroblastoma. (Mol Cancer Res 2007;5(12):1276–84)
CtIP Silencing as a Novel Mechanism of Tamoxifen Resistance in Breast Cancer
Authors: Wu Minhao , Soler David Ramos , Abba Martin C. , Nunez Maria I. , Baer Richard , Hatzis Christos , Llombart-Cussac Antonio , Llombart-Bosch Antonio , Aldaz C. Marcelo
Published: January 2008

Acquired resistance to the antiestrogen tamoxifen constitutes a major clinical challenge in breast cancer therapy. However, the mechanisms involved are still poorly understood. Using serial analysis of gene expression, we identified CtIP, a BRCA1- and CtBP-interacting protein, as one of the most significantly down-regulated transcripts in estrogen receptor α–positive (ER+) MCF-7 tamoxifen-resistant breast cancer cells. We further confirmed the association of CtIP down-regulation with tamoxifen resistance in an additional ER+ breast cancer line (T47D), strengthening the relevance of the phenomenon observed. In additional studies, we found CtIP protein expression in a majority of ER+ breast cancer cell lines that we tested, but no or very little CtIP expression in ER-negative lines. Furthermore, CtIP protein expression status correlates with clinical response to neoadjuvant endocrine therapy, and patients with progressive disease express significantly lower CtIP protein in their primary breast carcinomas than those who respond. Meta-analysis of seven publicly available gene expression microarray data sets showed that CtIP expression is significantly associated with ER, disease-free survival, and breast cancer metastasis status. Importantly, we found that silencing endogenous CtIP in tamoxifen-sensitive breast cancer cells confers tamoxifen resistance. On the other hand, reexpression of CtIP in tamoxifen-resistant breast cancer cells restores sensitivity to the inhibitory growth effects of tamoxifen. Together, our findings indicate that CtIP silencing might be a novel mechanism for the development of tamoxifen resistance in breast cancer, suggesting that CtIP is likely associated with ER function, and that CtIP gene and protein expression may be useful biomarkers for breast cancer prognosis and clinical management. (Mol Cancer Res 2007;5(12):1285–95)
Interference of Macrophage Migration Inhibitory Factor Expression in a Mouse Melanoma Inhibits Tumor Establishment by Up-Regulating Thrombospondin-1
Authors: Culp W. David , Tsagozis Panagiotis , Burgio Michael , Russell Paul , Pisa Pavel , Garland Donita
Published: January 2008

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with proinflammatory, proangiogenic, and protumorigenic properties. The molecular mechanisms underlying the role of MIF in tumorigenesis and angiogenesis are not well understood. To address these roles, an interfering MIF (iMIF) RNA was stably introduced into the B16-F10 mouse melanoma cell line, reducing MIF mRNA expression 1.6-fold and MIF protein expression 2.8-fold relative to control cells. When iMIF cells were subcutaneously injected into C57BL/6 mice, tumor establishment was significantly delayed and there was a marked absence of intratumoral vasculature in iMIF tumors relative to controls. A comparative gene expression analysis of iMIF and control melanoma cell lines revealed that thrombospondin-1 (TSP-1) mRNA expression was up-regulated 88-fold in the iMIF cells by real-time PCR. A 2-fold increase in TSP-1 protein levels was observed in iMIF cell culture supernatants. These results strongly suggest that the delayed tumor establishment and reduced vasculature in iMIF melanomas are linked to the up-regulation of the antiangiogenic TSP-1. They further define a novel function of MIF as a regulator of TSP-1 in a mouse melanoma model. (Mol Cancer Res 2007;5(12):1225–31)
Teacher Unions and the Politics of Fear in Labor Relations
Authors: Cooper Bruce S. , Sureau John
Published: January 2008

Union-management relationships have been filled with fear since the rise of capitalism; public education is no different. Workers fear exploitation by owners (profits depend on it) and capitalist/management has always worried that the working classes will organize and either take over the firm or strike and bring production to a screeching halt. In public education, teachers turned to collective bargaining in the 37 states that allow it to give them greater voice and power over their wages, benefits, and working conditions using collective actions through the American Federation of Teachers (AFL-CIO) and National Education Association, not unlike worker unionism in the private sector. Fear still resides beneath the surface but, since the 1990s, strikes are less common and teachers are well organized and earning better salaries and benefits than ever before. Whenever policies change, as under No Child Left Behind (NCLB) or charter school laws, teacher unions take the lead and are now even opening charter schools to guarantee that these teachers remain union members.
BAFF enhances chemotaxis of primary human B cells: a particular synergy between BAFF and CXCL13 on memory B cells
Authors: Badr Gamal , Borhis Gwenoline , Lefevre Eric A. , Chaoul Nada , Deshayes Frederique , Dessirier Valérie , Lapree Genevieve , Tsapis Andreas , Richard Yolande
Published: January 2008

B-cell–activating factor of the TNF family, (BAFF), and a proliferation-inducing ligand (APRIL) regulate B-lymphocyte survival and activation. We report that BAFF, but not APRIL, increased the chemotactic response of primary human B cells to CCL21, CXCL12, and CXCL13. The BAFF-induced increase in B-cell chemotaxis was totally abolished by blockade of BAFF-R and was strongly dependent on the activation of PI3K/AKT, NF-κB, and p38MAPK pathways. BAFF had similar effects on the chemotaxis of naive and memory B cells in response to CCL21 but increased more strongly that of memory B cells to CXCL13 than that of naive B cells. Our findings indicate a previously unreported role for the BAFF/BAFF-R pair in mature B-cell chemotaxis. The synergy between CXCL13 and BAFF produced by stromal cells and follicular dendritic cells may have important implications for B-cell homeostasis, the development of normal B-cell areas, and for the formation of germinal center–like follicles that may be observed in various autoimmune diseases.
Use of Medication for the Management of Behavior Problems Among Adults With Intellectual Disabilities: A Clinicians' Consensus Survey
Authors: Unwin Gemma Louise , Deb Shoumitro
Published: January 2008

Current prescribing preferences among relevant experts regarding the use of psychotropic medication for the management of behavior problems in adults with intellectual disabilities in the absence of a diagnosed psychiatric illness was defined. We used a questionnaire design to synthesize the preferences of a large group, namely, clinical psychiatrists, thereby establishing a consensus. A total of 108 completed questionnaires were analyzed. A very strong preference for the use of nonmedication-based interventions was established. Of the medication options presented, atypical antipsychotics were most favored, with Risperidone the most preferred option from within this group. Citalopram was the most preferred antidepressant and Carbamazepine, the most preferred mood stabilizer/antiepileptic.
Moving Theory into Practice: Digital Imaging Tutorial, Cornell University Library/Department of Preservation & Conservation, 2000
Authors: Meyer Lars
Published: January 2008

This online web site of digital conversion fundamentals serves a number of purposes. According to the Preface page, it “offers base-level information on the use of digital imaging to convert and make accessible cultural heritage materials. It also introduces some concepts advocated by Cornell University Library, in particular the value of benchmarking requirements before undertaking a digital initiative.” Although the tutorial can stand alone, it complements Anne R. Kenney and Oya Rieger's
DLGS97/SAP97 Is Developmentally Upregulated and Is Required for Complex Adult Behaviors and Synapse Morphology and Function
Authors: Mendoza-Topaz Carolina , Urra Francisco , Barría Romina , Albornoz Valeria , Ugalde Diego , Thomas Ulrich , Gundelfinger Eckart D. , Delgado Ricardo , Kukuljan Manuel , Sanxaridis Parthena D. , Tsunoda Susan , Ceriani M. Fernanda , Budnik Vivian , Sierralta Jimena
Published: January 2008

The synaptic membrane-associated guanylate kinase (MAGUK) scaffolding protein family is thought to play key roles in synapse assembly and synaptic plasticity. Evidence supporting these rolesin vivois scarce, as a consequence of gene redundancy in mammals. The genome ofDrosophilacontains only one MAGUK gene,discs large(dlg), from which two major proteins originate: DLGA [PSD95 (postsynaptic density 95)-like] and DLGS97 [SAP97 (synapse-associated protein)-like]. These differ only by the inclusion in DLGS97 of an L27 domain, important for the formation of supramolecular assemblies. Knowndlgmutations affect both forms and are lethal at larval stages attributable to tumoral overgrowth of epithelia. We generated independent null mutations for each,dlgAanddlgS97. These allowed unveiling of a shift in expression during the development of the nervous system: predominant expression of DLGA in the embryo, balanced expression of both during larval stages, and almost exclusive DLGS97 expression in the adult brain. Loss of embryonic DLGS97 does not alter the development of the nervous system. At larval stages, DLGA and DLGS97 fulfill both unique and partially redundant functions in the neuromuscular junction. Contrary todlganddlgAmutants,dlgS97mutants are viable to adulthood, but they exhibit marked alterations in complex behaviors such as phototaxis, circadian activity, and courtship, whereas simpler behaviors like locomotion and odor and light perception are spared. We propose that the increased repertoire of associations of a synaptic scaffold protein given by an additional domain of protein–protein interaction underlies its ability to integrate molecular networks required for complex functions in adult synapses.
HEALTH RISK BEHAVIORS OF STUDENTS IN AN ANATOLIAN UNIVERSITY
Authors: Bulbul Selda Fatma Hizel , Sanli Cihat , Fidan Serdar , Agar Ayca , Ceyhun Gulsen
Published: January 2008

INTRODUCTION: Adolescence is a period of rapid personal development in which health risk behaviors that contribute to the leading causes of social problems, morbidity, and mortality among youth and adults are often established.

OBJECTIVE: The purpose of this cross-sectional study was to investigate the health risk behaviors of Anatolian university students.

METHODS: Differences according to gender and socioeconomic status in risk behaviors regarding use of tobacco, alcohol, and illegal substances; sexual activity; and physical activity were analyzed. Students from Kirikkale University (1060) were enrolled. The students' privacy was protected by allowing for anonymous and voluntary participation.

RESULTS: Mean age of the 684 male (64.5%) and 376 female (35.5%) students was 20.3 years (minimum: 17; maximum: 30 years). of all the students, 876 (82.9%) had some kind of information about sexuality; however, this number dropped to 546 students (51.5%) within the context of adequacy. Also, 25.3% of all the students had had some kind of sexual intercourse, and only 53.9% used protection during intercourse. Tobacco usage was 35.1% among those in the group, and 8.7% of the male and 3.6% of the female students were using illegal substances. Thirty percent of all the students reported having weight problems. The majority of students had witnessed violence (eg, 32.7% from parents, 77.2% from their friends, and 76.2% at school).

CONCLUSIONS: Risk-taking behaviors are considerably common among Turkish university students, and family characteristics have significant effects.
FOCAL AREAS OF HIGH-SIGNAL INTENSITY ON BRAIN T2-WEIGHTED MAGNETIC RESONANCE IMAGING SCANS ARE SIGNIFICANT FOR THE DIAGNOSIS OF NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYPE 1
Authors: Petrak Borivoj , Lisy Jiri , Kraus Josef , Kyncl Martin , Zatrapa Tomas
Published: January 2008

INTRODUCTION: Neurofibromatosis von Recklinghausen type 1 (NF1) is characterized by the following National Institutes of Health (NIH) diagnostic criteria: café au lait spots, freckling, neurofibromas, Lisch nodules, optic glioma, distinct osseous lesions, and first-degree relative with NF1. Focal areas of high-signal intensity (FASI) in white matter and deep gray matter are typical brain MRI findings in children with NF1.

OBJECTIVE: This study evaluated the frequency of FASI and the possibility of using FASI as a diagnostic criterion.

METHODS: In a group of 160 children, the diagnosis of NF1 was confirmed in keeping with the NIH criteria. All children had MRI examination of the brain. The MRI findings of FASI in the children with NF1 were compared both with the brain MRI findings of the control group of 160 children with different diagnoses and with frequencies of the NIH diagnostic criteria.

RESULTS: In 137 (86%) patients with NF1, ≥1 FASI were found. The difference between frequency of FASI in the NF1 group and in the control group (14 [9%]) is highly significant. The frequencies of the diagnostic criteria were as follows: café au lait spots: 157 (98%); freckling: 123 (77%); neurofibromas: 112 (70%); NF1 relatives: 89 (56%); Lisch nodules: 71 (44%); optic glioma: 45 (28%); and osseous lesions: 15 (9%; only partial examination of the group).

CONCLUSIONS: The findings of FASI in T2-weighted images of the brain MRI are significantly frequent in children with NF1. Frequency of FASI is comparable with frequency of NIH diagnostic criteria. FASI could be proposed as an additional or new criterion for the NF1, mainly in childhood.
IDIOPATHIC PULMONARY HEMOSIDEROSIS IN CHILDREN: A ROMANIAN EXPERIENCE
Authors: Bulucea Catalina , Sorin Dinescu
Published: January 2008

INTRODUCTION: Idiopathic pulmonary hemosiderosis (IPH) is a rare disease with unknown cause and variable outcome. It is characterized by recurrent episodes of severe hypochromic anemia, alveolar bleeding, and typical radiologic findings.

OBJECTIVE: The objective of this study was to develop an early diagnosis of IPH with real therapeutic benefits.

METHODS: We conducted a multicenter, retrospective, and prospective study using patients who were admitted to 3 Romanian pediatric clinics between 1984 and 2006. Secondary causes of pulmonary hemosiderosis were excluded.

RESULTS: Fifteen patients received a diagnosis of IPH during a 22-year period (1984–2006). The symptoms started at a mean age of 6.8 years (range: 9 months to 13 years), with a mean delay of 2.4 years before diagnosis. From the beginning, all patients had anemia, and only 6 children presented with pulmonary symptoms as well. The classical triad (anemia, hemoptysis, and pulmonary infiltrates) was found from early in the disease in only 4 patients. The majority of patients' disease was diagnosed by bronchoalveolar lavage, and 3 were diagnosed at necropsy. Eight patients died in a period of 1 to 3 years from the diagnosis. The clinical course was variable: treatment with corticosteroids alone was not effective because 12 patients continued to have recurrent bleeding. Three patients who received immunosuppressive agents had a better outcome.

CONCLUSIONS: IPH is a severe condition with variable prognosis and has a better outcome when diagnosis is made at an early age. We believe that it is necessary to include in the screening of any severe, recurrent, hypochromic anemia a well-interpreted chest radiograph and to look for hemosiderin-laden phages in bronchoalveolar lavage.
CORRELATION BETWEEN ALLERGIC RHINITIS, ASTHMA, AND ATOPIC DERMATITIS IN CHILDREN
Authors: Šofranac Milica
Published: January 2008

INTRODUCTION: Allergic rhinitis, asthma, and atopic dermatitis are atopic diseases with the same pathogenic base with regard to the allergic reaction and the type of oversensitivity (facilitated by immunoglobulin E antibodies) with the release of numerous mediators causing allergic inflammation. The incidence of these diseases is increasing constantly. One precedes the others, or they often appear combined.

OBJECTIVE: The goal of this research was to establish the correlation between allergic rhinitis, asthma, and atopic dermatitis in children treated at our health center.

METHODS: In preparation for the research, 3638 medical charts of children aged 3 to 18 years were studied.

RESULTS: Processed were the cases of 142 children with allergic rhinitis (105 boys [73.9%] and 37 girls [26.1%]) who were diagnosed to have allergic rhinitis, asthma, or atopic dermatitis over the previous 4 years. The diagnosis was made on the basis of anamnesis, clinical record, skin-prick test, and consultation with the otolaryngologist. Of all the patients, 25 (17.6%) boys and 18 (12.6%) girls had atopic dermatitis, and 105 (73.9%) boys and 36 (25.3%) girls had asthma. The total number of children with atopic dermatitis was 43 (30.3%), and there were 141 (99.3%) with asthma.

CONCLUSIONS: In 30.3% of the cases, the children with allergic rhinitis also had atopic dermatitis; in 99.3% of the cases, the children with allergic rhinitis also had asthma. The degree of correlation between allergic rhinitis and asthma was higher than that between allergic rhinitis and atopic dermatitis. The boys suffered more often from allergic rhinitis, and its correlation with asthma was greater than that in girls, with whom it was combined with atopic dermatitis to a larger degree.
ASSESSMENT OF DIFFERENCES BETWEEN THE NEW WORLD HEALTH ORGANIZATION CHILD-GROWTH STANDARDS AND THE CENTERS FOR DISEASE CONTROL AND PREVENTION 2000 GROWTH CHARTS IN LATIN AMERICAN CHILDREN: WHICH REFERENCE SHOULD WE USE?
Authors: Ponce-Rivera L. N. Mariana , Blanco-Montero Andrιs , Reyes-Vazquez Horacio , Lopez-Enriquez Claudia , Fuentes-Lugo Daniel
Published: January 2008

INTRODUCTION: Evaluation of growth patterns significantly depends on the reference used. Last year the World Health Organization (WHO) released new standards for assessing child growth during the first 5 years of life.

OBJECTIVE: Our goal was to assess differences between the 2000 Centers for Disease Control and Prevention (CDC) growth charts and 2006 WHO growth standards.

METHODS: A longitudinal study was conducted on a sample of 300 healthy children (167 boys and 133 girls) from a pediatric outpatient clinic in Mexico City. Weight-for-age z score, length/height-for-age z score, and weight-for-length/height z score were obtained yearly from birth to age 5 and compared by using the 2000 CDC growth charts and 2006 WHO growth standards.

RESULTS: Significant statistical differences were found at all ages in both genders. Main differences were found in early-infancy weight-for-age z scores. The prevalence of girls who were undernourished at birth was 3 times higher with the CDC reference than with that of the WHO (13.53% vs 4.50%, respectively), but the opposite was found for boys (2.99% vs 9.58%, respectively). During the first 4 years of life, a higher prevalence of length/height-for-age z scores less than −2.0 was found in both boys (10.77%) and girls (4.51%) when using WHO standards as opposed to the CDC charts. Furthermore, at the age of 5 years, obesity was significantly higher in girls according to WHO standards than in boys according to the CDC charts, although the CDC reference failed to detect a fast rate of weight gain in early infancy.

CONCLUSIONS: The new WHO standards are a better tool than the CDC charts for monitoring growth and detecting early overweight in Latin American children. Therefore, using this new international reference in daily clinical practice in our countries should be emphatically encouraged.
COMPARISON OF THE 2 BRONCHIAL PROVOCATION TESTS OF DIFFERENT DOSAGE CONCENTRATION GRADIENTS FOR INFANTS
Authors: Huang Ying
Published: January 2008

INTRODUCTION: Bronchial provocation tests (BPTs) assist in diagnosing and evaluating the curative effect of asthma.

OBJECTIVE: The objective of this study was to compare the sensitivity, reliability, and safety between 2 tidal breathing methods in BPT.

METHODS: Sixty-five infants, including those with asthma and chronic cough, were divided into groups A and B at random. BPT by the improvement of tidal breathing method was performed in group A (35 infants), and the traditional tidal breathing method was performed in group B (30 infants). In 10 normal infants (control subjects), the traditional tidal breathing method was used. In addition, we observed arterial oxygen saturation, respiratory system resistance, %T-PF, percent of tidal volume of peak tidal expiratory flow, and lung symptoms and monitored the vital sign and adverse effects of the test.

RESULTS: Results of the BPTs for all children with asthma were positive. The positive rates for children with chronic cough were 69.57% and 60.00% in groups A and B, respectively; the results of BPTs in control subjects were completely negative. There was no significant difference in positive rate, and both methods had a similar degree of airway hyperresponsiveness; however, in group A, the effect was of shorter duration and the test was more efficient. During the BPT, 6 infants in group A and 9 in group B had cough, but none exhibited an acute asthma episode.

CONCLUSIONS: The improved tidal breathing method, used as a BPT, outweighs the traditional method in sensitivity, specificity, efficiency of detection, dosage of medicine, and safety.
THE CHILDREN IN DISASTERS PROJECT: ADDRESSING THE SPECIAL NEEDS OF CHILDREN IN MAN-MADE AND NATURAL DISASTERS
Authors: Olness Karen , Mandalakas Anna , Pairojkul Srivieng , Holsinger Eva , Bothe Denise , Herran Marisa
Published: January 2008

INTRODUCTION: Natural and man-made disasters have increased dramatically over the past 15 years. Children are the most vulnerable population in disasters and suffer acute and long-term physical and psychological damage. In 2005, there were 17 million children displaced from their homes as a result of humanitarian emergencies.

OBJECTIVE: The Children in Disasters Project of the Rainbow Center for Global Child Health aims to reduce the traumatic acute and long-term effects of disasters for children by providing training to health professionals and relief workers, both in the United States and around the world, on how to recognize and respond to the special needs of children in disasters.

RESULTS: Since 1996 the project has provided intensive, interactive, 5-day training programs entitled “Management of Complex Humanitarian Emergencies: Focus on Children and Families.” These were the first programs to emphasize that children need special attention in disasters. This course has been replicated with colleagues in 9 countries and has trained 980 people to help care for disaster-affected children. Course evaluations have been excellent, and trainees have done well in disaster work.

CONCLUSIONS: Because of ongoing humanitarian emergencies, there is a need to continue training relief workers about the special needs of children.
STUDY ON THE DAMAGE OF CULTURED HIPPOCAMPAL NEURONS INDUCED BY SEIZURE-LIKE DISCHARGE AND THE EFFECT OF BRAIN-DERIVED NEUROTROPHIC FACTOR ON THE INJURED NEURONS
Authors: Jiang Li , Zhang Ming , Li Tingsong
Published: January 2008

OBJECTIVE: The objective of this study was to observe the damage of cultured hippocampal neurons induced by seizure-like discharge and study the effects of brain-derived neurotrophic factor (BDNF) on such injury.

METHODS: Primary cultured hippocampal neurons were randomly divided into 3 groups: (1) control group: cultured neurons were exposed to regular extracellular solution for 3 hours, then returned to regular medium; (2) seizure-like discharge group: cultured neurons were exposed to magnesium-free extracellular solution for 3 hours, then maintained for 24 hours in regular medium; and (3) BDNF-treated group: cultured neurons were precultured with regular medium added to BDNF (200 ng/mL) for 24 hours and exposed to magnesium-free extracellular solution for 3 hours, then maintained for 24 hours in regular medium that contained BDNF. The morphologic changes of neurons dyed by acridine orange/ethidium bromide were observed. Mitochondria membrane potential (MEP) by JC-1 dye was assessed with laser scanning confocal microscope. Lactic acid dehydrogenase (LDH) in supernatant was detected by autobiochemical analyzer. BDNF was detected by immunocytochemistry and assessed by optical density.

RESULTS: There were some apoptotic and necrotic neurons in the seizure-like discharge group. Compared with the control group, MEP was significantly decreased and LDH level and BDNF expression were significantly increased in the seizure-like discharge group. Compared with the seizure-like discharge group, MEP was significantly increased and LDH level was significantly decreased in BDNF-treated group, but there was no significant difference on BDNF expression between them.

CONCLUSIONS: Seizure-like discharge could induce injury to hippocampal neurons and could upregulate BDNF expression in hippocampal neurons. BDNF could relieve the damage of neurons induced by seizure-like discharge, so BDNF has protective effects on hippocampal neurons.
SEROLOGICAL STUDY ON IMMUNITY TO MEASLES AND MUMPS IN NORTHERN GREEK CHILDREN
Authors: Haidopoulou Katerina , Fylaktou Asimina , Goutaki Myrofora , Papadimitriou Aikaterini , Kalamitsou Serafeia , Varlamis George
Published: January 2008

INTRODUCTION: Routine immunization against measles and mumps has substantially reduced the number of these infections annually. However, outbreaks have been reported recently, even in highly vaccinated populations.

OBJECTIVE: Our goal was to determine the levels of serum antibodies against measles and mumps in a population of children who were vaccinated against measles-mumps-rubella (MMR).

METHODS: The study population consisted of 260 healthy children (aged 15 months to 14.5 years) who were separated into 2 groups according to the number of MMR vaccine doses previously administered: groups A (1 dose) and B (2 doses). Immunoglobulin G (IgG) and IgM antibody levels for measles and mumps were determined in blood serum by the enzyme-linked immunosorbent assay (Genzyme Virotech, Rüsselsheim, Germany) semiquantitive method.

RESULTS: Groups A and B consisted of 53 children aged 15 months to 8 years and 207 children aged 5 to 14.5 years old, respectively. A majority (93.08%) of the children were protected against measles. Group A and B protection rates were similar (92.27% and 96.23%, respectively). Although most of the children were protected against mumps, the total protection rate was significantly less (81.92%) (P < .01). The protection rate against mumps in group A was significantly lower than that in group B (67.92% vs 85.51%; P < .03).

CONCLUSIONS: Our results indicate high protection rates against measles conferred even by a single dose of the MMR vaccine. A respected percentage of the children were found to be susceptible to mumps even after completion of a 2-dose immunization schedule. Primary vaccine failure may be implicated as a cause of recent mumps outbreaks, but additional studies are needed.
RHEUMATIC FEVER IN THE NEW MILLENNIUM
Authors: Kotby Alyaa
Published: January 2008

INTRODUCTION: During the past 2 decades the presentation of rheumatic fever (RF) has changed markedly from that of an acute florid illness to a more subtle subacute form that is frequently missed.

OBJECTIVE: With this work we attempted to describe the changing face of RF with its different patterns and time of presentation, particularly subclinical carditis.

METHODS: This work included 1732 patients with RF followed up in the pediatric department and pediatric cardiology clinic at Pediatric Hospital, Ain Shams University. Every patient was subjected to a thorough clinical examination, measurement of erythrocyte sedimentation rate and antistreptolysin O titer and C-reactive protein levels, a chest radiograph, electrocardiography, and echocardiography Doppler. Echocardiography was performed at the time of admission and repeated after 2, 4, and 6 weeks and 1 year after the attack. Diagnosis of RF was based on the revised Jones criteria.

RESULTS: Age at the first attack was <5 years for 10% of the patients, 5 to 10 years for 51%, 11 to 15 for 36%, and >15 for 3%; the male/female ratio was 1:1.34. Major clinical RF manifestations were carditis (60%), polyarthritis (56%), chorea (15%), erythema marginatum (0.12%), and subcutaneous nodules (0.12%). Seventy-two percent had carditis, after we combined clinical and echocardiographic criteria of cardiac affection 6 weeks after the attack. Pure arthritis was present in 41% of the patients, arthritis and carditis in 29%, and arthritis and subclinical carditis in 30%. One year after the initial attack the number of patients with echocardiographic features of valve affection remained the same. Pure chorea was present in 55% of the patients, chorea and carditis in 30%, and chorea and subclinical carditis in 25%. One year after the initial attack, 70% of the patients with chorea had echocardiographic features of valve affection. Chronicity of chorea is common with multiple relapses.

CONCLUSIONS: RF is not uncommon in children <5 years of age. Subclinical carditis should be anticipated and looked for at the right time in susceptible patients, particularly those with rheumatic arthritis and chorea. Multicenter studies should be carried out for the addition of the echocardiographic features of carditis to Jones' minor criteria for the diagnosis of RF. Diagnosis of carditis requires a high index of suspicion in at least 1 of 3 cases.
CONGENITAL MALFORMATIONS ASSOCIATED WITH PESTICIDES IN ENCARNACIÓN, PARAGUAY
Authors: Benítez Leite Stela , Acosta Marta , Luisa Macchi María
Published: January 2008

INTRODUCTION: Exposure to pesticides is a known risk to human health. The association between parental exposure and congenital malformations is described.

OBJECTIVE: We sought to study the association between exposure to pesticides and congenital malformations in newborns who were born at the Regional Hospital of Encarnación in Itapúa, Paraguay.

METHODS: This was a prospective case and control study from March 2006 to February 2007. A case was defined as a newborn who was born with congenital malformations, and a control case was defined as a newborn of the same gender who was born immediately after and was found to be healthy. The exposure to pesticides was considered along with other risk factors that are known to cause congenital malformations.

RESULTS: The cases (52) and controls (87) were analyzed. The average number of births per month was 216. The risk factors that were significantly associated were living near fumigated fields (odds ratio [OR]: 2.46 [95% confidence interval (CI): 1.09–5.57]; P < .02), having pesticides in the house (OR: 15, 35 [95% CI: 1.96–701.63]; P < .003), direct or accidental contact with pesticides (OR: 3.19 [95% CI: 0.97–11.4]; P < .04), and history of family malformations (OR: 6.81 [95% CI: 1.94–30.56]; P < .001). The other risk factors known to cause malformations did not have statistical significance.

CONCLUSIONS: The results show an association between the exposure to pesticides and congenital malformation in newborns who were born at the Regional Hospital of Encarnación. Future studies are required to confirm these findings.
ROTASCORE STUDY: EPIDEMIOLOGICAL OBSERVATIONAL STUDY OF ACUTE GASTROENTERITIS WITH OR WITHOUT ROTAVIRUS IN GREEK CHILDREN YOUNGER THAN 5 YEARS
Authors: Papaevangelou Vassiliki , Kavaliotis Ioannis , Kokori Heleni , Mantagou Lito , Trimis Georgios , Papadopoulou Vithleem , Niotakis Georgios , Nikolakopoulou Nikoleta , Konstantopoulos Andreas
Published: January 2008

INTRODUCTION: Pediatric rotavirus gastroenteritis (PRG) is the most frequent cause of severe acute gastroenteritis (AGE) in children up to 5 years of age worldwide.

OBJECTIVE: We sought to determine the proportion of PRG and compare its clinical burden to that of AGE caused by other pathogens.

METHODS: The study was conducted in 4 hospital emergency units (HEUs) and 50 private pediatric clinics between January and May 2006. Children up to 5 years of age were included. A rapid stool immunochromatographic test for rotavirus antigen detection was performed. Symptom-severity scores were calculated by using the Clark scale.

RESULTS: Seven hundred and six children participated in the study (median age: 20 months; 385 boys [54.5%]); 273 patients (38.6%) visited HEUs, and 433 (61.4%) visited private clinics. The proportion of PRG was 29% (95% confidence interval [CI]: 25.9%–32.6%) in the total study group, 18.3% (95% CI: 14.9%–22.3%) in private clinics, 45.7% (95% CI: 40.0%–51.7%) in HEUs, and 49.1% in hospitalized patients (95% CI: 42.3%–55.7%). Most children with PRG (71.7%) were between 6 months and 3 years old. Behavioral changes and signs of dehydration, weight loss, fever at ≥38°C, diarrhea, and vomiting were more prevalent with PRG (P < .01). In children with PRG, a higher incidence of moderate or severe gastroenteritis (P = .013 and .021, respectively), hospitalization (P = .011), and need for a clinical reevaluation (P = .012) was observed, as was longer hospitalization (5.14 ± 3.18 vs 3.69 ± 2.25 days; P = .039).

CONCLUSIONS: PRG was responsible for nearly half the patients with AGE who visited HEUs or required hospitalization. Vaccination against rotavirus would help prevent this frequent and often severe disease.
ROLES OF SCAP (STEROL REGULATORY ELEMENT–BINDING PROTEIN CLEAVAGE-ACTIVATING PROTEIN) IN THE MECHANISM FOR MESANGIAL FOAM-CELL FORMATION UNDER INFLAMMATORY STRESS
Authors: Li Qiu , Ruan Xiong Zhong
Published: January 2008

INTRODUCTION: Our previous studies have demonstrated that lipid abnormalities play a significant role in glomerulosclerosis. Inflammatory cytokines promote lipid accumulation in human mesangial cells (HMCLs) by disrupting low-density lipoprotein receptor (LDLr) feedback regulation. The sterol regulatory element–binding protein (SREBP) cleavage-activating protein (SCAP) carries SREBP from endoplasmic reticulum (ER) to Golgi, where it is known to cleave SREBP, thereby enhancing LDLr gene expression and cholesterol uptake when cells need cholesterol.

OBJECTIVE: We aimed to investigate whether inflammatory mediators interfere with SCAP translocation and its biological consequence.

METHODS: HMCLs were used in all experiments. Total cellular RNA was isolated from these cells for detecting LDLr, SREBP-2, and SCAP messenger RNA levels with real-time quantitative polymerase chain reaction. LDLr protein expression was measured by Western blot. Translocation of the SCAP-SREBP complex from the ER to Golgi was investigated by confocal microscopy.

RESULTS: In the absence of exposure to interleukin 1β, a high concentration of LDL retained SCAP in the ER, a low LDLr promoter activity, messenger RNA synthesis, and protein expression were found, respectively. However, exposure to interleukin 1β caused overexpression of SCAP and enhanced its translocation from the ER to Golgi. This disrupted normal feedback regulation and resulted in inappropriately increased LDL uptake with transformation of HMCLs into foam cells. Overexpression of SCAP in HMCLs resulted in an increased translocation of SCAP from the ER to Golgi, and high concentrations of LDL were unable to suppress SREBP-2 and LDLr gene expression.

CONCLUSIONS: These data suggest that inflammatory mediators promote abnormal translocation of SCAP from the ER to Golgi and play an important role in lipid accumulation in HMCLs.
IMMUNOGENICITY AND SAFETY OF CONCOMITANT ADMINISTRATION OF MEASLES-MUMPS-RUBELLA VACCINE AND VARICELLA VACCINE BY THE INTRAMUSCULAR OR SUBCUTANEOUS ROUTE
Authors: Gillet Yves , Habermehl Pirmin , Fiquet Anne , Thomas Stephane , Eymin Cecile , Bertrand Isabelle , Ledesma Emilio
Published: January 2008

INTRODUCTION: In Europe, recommended administration route for vaccines and physicians' preferences vary.

OBJECTIVE: The aim of this study was to compare the immunogenicity and safety profile (injection-site and systemic adverse events) of a measles-mumps-rubella vaccine (M-M-RvaxPRO) and a varicella vaccine (Varivax) when given by intramuscular or subcutaneous route.

METHODS: A total of 752 healthy children who were 12 to 18 months of age were randomly assigned to receive concomitantly at 2 separate injection sites 1 dose of both vaccines by the same route, either intramuscular or subcutaneous.

RESULTS: Six weeks after vaccination, response rates in patients who were initially seronegative were similar for all antigens (intramuscular noninferior to subcutaneous), and geometric mean titers were comparable irrespective of the administration route (Table 1). Similar numbers and types of systemic adverse events were observed in both groups, excepted for varicella/varicella-like rashes, which were less frequent in the intramuscular group. Injection-site reactions were also less frequent for both vaccines in the intramuscular group compared with the subcutaneous group (15.8% and 25.8% of patients for M-M-RvaxPRO and 20.9% and 34.3% for Varivax, respectively), but the safety pattern was comparable between groups.

CONCLUSIONS: These results support both intramuscular and subcutaneous administration routes for M-M-RvaxPRO and Varivax.

TABLE 1.Response Rates and Geometric Mean Titers of the Measles-Mumps-Rubella and Varicella Vaccines When Given by Different RoutesPer-Protocol AnalysisIntramuscularSubcutaneous n Relative Risk, %GMTs n Relative Risk, %GMTsMeasles, ≥255 mIU/mL34994.32396.436396.12560.6Mumps, ≥10 ELISA Ab U/mL34997.786.436398.189.8Rubella, ≥10 IU/mL32198.197.231898.194.4Varicella    ≥5 gpELISA U/mL33688.49.834585.59.2    ≥1.25 gpELISA U/mL33698.59.834599.49.2
IMMUNE FINDINGS IN CHILDREN WITH IDIOPATHIC NEPHROTIC SYNDROME: COULD THEY PREDICT THE RESPONSE TO STEROID THERAPY?
Authors: Printza Nikoleta , Papachristou Fotios , Tzimouli Vassiliki , Taparkou Anna , Kanakoudi-Tsakalidou Floredia
Published: January 2008

INTRODUCTION: Nephrotic syndrome (NS) is thought to be associated with primary immune disturbances.

OBJECTIVE: The aim of our study was to investigate prospectively the immune disturbances in steroid-sensitive (SS) and steroid-resistant (SR) NS and identify whether these immune disturbances may predict the response to steroid therapy.

METHODS: Thirty children with SS NS and 7 children with SR NS (aged 2 to 14 years) were studied. To evaluate the possible relationship between immune disturbances and response to treatment, patients were evaluated during different disease stages. Data were compared with those obtained from 25 age-matched controls. The following parameters were assessed: basic B- and T-cell populations, percentages of CD23+, CD3+/CD69+/interferon γ+ (IFN-γ+) cells, and CD3+/CD69+/interleukin 4+ (IL-4+) T cells, and serum levels of IL-13 and IL-18.

RESULTS: In patients with SS NS percentages of CD23+ and CD19+ B cells, CD3+/CD69+/IL-4+ T cells and serum levels of IL-13, IL-18 were significantly higher in the active stage compared with the remission stage on steroids, remission off steroids, and controls (P < .05). On the contrary, percentages of CD3+/CD69+/IFN-γ+ T cells were significantly decreased (P < .05). In patients with SR NS, percentages of CD23+B cells, CD3+/CD69+/IL-4+ T cells, and serum levels of IL-13 and IL-18 presented no significant difference between active stage and partial remission. Percentages of CD19+ B cells and CD3+/CD69+/IFN-γ+ T cells were elevated in active stage compared with remission stage of patients with SR NS and in controls (P < .05).

CONCLUSIONS: These findings suggest that when a type-2 immune response is found in the active stage of NS, one could predict a good response to steroid therapy.
RENAL INVOLVEMENT IN CHILDREN WITH GLYCOGEN-STORAGE DISEASE
Authors: Safouh Hesham , Elsayyed Rokayya , Mansour Samah , Taha Gamal , Elshabrawy Mortada , Elkaraksy Hanaa
Published: January 2008

INTRODUCTION: Long-term complications of glycogen-storage diseases (GSDs) include delayed puberty, hepatic adenomata, and renal disease.

OBJECTIVE: In this study, our aim was to detect renal involvement in children with GSD and to determine the most accurate laboratory test to be the gold standard for early detection of this renal dysfunction.

METHODS: Twenty-seven children known to have GSD were included in this study. Fifteen healthy age- and gender-matched children were also included as controls. Routine urine analysis and measurement of urinary β2-microglobulin and microalbumin levels were performed for all patients and controls. Renal-function tests, measurement of serum electrolyte, alkaline phosphatase, urinary calcium, blood, and urine pH levels, creation of a urinary and plasma aminogram, calculation of the glomerular filtration rate, bone radiography to detect rachitic manifestations, and abdominal ultrasound to measure renal size were performed for all patients.

RESULTS: Twenty-one patients had ≥1 renal abnormality. The most common was increased urinary β2-microglobulin level (15 of 21) followed by an abnormal glomerular filtration rate, whether low or high (8 of 21), and microalbuminuria (6 of 21). Sonographically, there was nephrocalcinosis in 1 case and renal stone in another. The area under the receiver operating characteristic curve for β2-microglobulin was 0.86 (P = .01) and 0.7 for the urinary microalbumin/creatinine ratio (P = .15). The best cutoff level for predicting renal abnormality for urinary β2-microglobulin was 0.22 mg/L with 70% sensitivity and 100% specificity, and the best cutoff value for the urinary microalbumin/creatinine ratio was 4.5 with 86% sensitivity and 50% specificity.

CONCLUSIONS: Renal abnormalities are common in patients with GSD. Urinary B2-microglobulin level can be considered the gold standard for early detection of renal dysfunction in these patients.
MANAGEMENT OF CHILDREN WITH OTITIS MEDIA: A SURVEY OF AUSTRALIAN ABORIGINAL MEDICAL SERVICES
Authors: Gunasekera Hasantha , Morris Peter , Daniels John , Couzos Sophie , Craig Jonathan
Published: January 2008

INTRODUCTION: Otitis media remains one of the most common reasons for childhood primary health care presentations. Indigenous children are at the highest risk, but there are scarce data on how they are managed.

OBJECTIVE: We sought to determine how Australian primary health care medical practitioners diagnose and manage otitis media in Indigenous and non-Indigenous children.

METHODS: We contacted all of Australia's Aboriginal Medical Services by using the national government's register to identify their medical practitioners. We mailed a pilot 5-page clinical vignette questionnaire instrument to these primary health care practitioners (N = 257). Responses for Indigenous children were compared with those for non-Indigenous children.

RESULTS: Questionnaires were returned from 40.9% of medical practitioners (105 of 257) and 64.8% (57 of 88) of the nation's Aboriginal Medical Services. When examining children, practitioners used otoscopy (99.0% often/always) but not pneumatic otoscopy (67.0% never) or tympanometry (55.8% never). When practitioners diagnosed acute otitis media, they were more likely to use antibiotics (104 of 113 [92.0%]) when the child was Indigenous versus non-Indigenous (53 of 112 [47.3%]) (odds ratio: 12.9 [95% confidence interval: 5.9–27.9]). Amoxicillin was the most common antibiotic used (309 of 356 [86.8%]). The major factors that determined the practitioners' otitis media antibiotic use were Indigenous status (65.7%), wet perforations (63.7%), bulging tympanic membranes (58.3%), and fever (56.3%). The major factors for choosing no antibiotics were dry perforations (35.3%) and a well child (24.8%). Most practitioners were aware of the national guidelines (97.1%) but not the guidelines for Indigenous children (47.0%).

CONCLUSIONS: Aboriginal Medical Service practitioners rely on otoscopy alone to diagnose otitis media and are more likely to use antibiotics for Indigenous children despite not knowing the guidelines.