bluuebunny/crossref_metadata_2025 huggingface dataset:
PLACENTAL ADENOVIRAL GENOME: POLYMERASE CHAIN REACTION DETECTION AND PLACENTAL HISTOLOGY IN PRETERM AND TERM INFANTS
Authors: Tsekoura Eufrosini , Konstantinidou A. , Tsakris A. , Antsaklis A. , Kafetzis D.
Published: January 2008

INTRODUCTION: Intrauterine infection is an important cause of spontaneous preterm birth. However, evidence-based etiology for the causative role of viral infection is still lacking. Intervillous trophoblasts express adenovirus receptor. Infection of trophoblast cells in vitro by adenovirus early in pregnancy has shown increased apoptosis. Adenovirus early in pregnancy may cause placental dysfunction. Mature syncytiotrophoblasts do not express adenovirus receptor.

OBJECTIVE: The aim of this study was to test the hypothesis that detection of adenovirus in placental tissue is associated with preterm birth and correlates with placental histopathological findings that are suggestive of infection.

METHODS: Placentas were prospectively collected from consecutive deliveries. Detection of the adenovirus genome was tested by polymerase chain reaction assay. Placental histology and immunohistochemistry studies with monoclonal antibody CD45 were evaluated for signs of placental inflammation in the samples that tested positive for adenovirus.

RESULTS: Between January 2005 and December 2006, 193 placenta samples (71 from preterm deliveries and 122 from term deliveries) were collected in Alexandra's Maternity Hospital in Athens, Greece. The adenoviral genome was isolated in 54 (28%) of 193 placentas. The frequency of adenovirus detection in preterm placentas compared with those from term placentas was significantly increased (29 of 71[41%] vs 25 of 122 [20%]; P = .002; odds ratio [OR]: 2.6 [95% confidence interval (CI): 1.4–5.1]). Stratification by gestational age (GA) revealed a stronger association between preterm delivery and adenovirus detection as GA decreased below 33 weeks (GA ≤ 29 weeks, OR: 2.8 [95% CI: 1.1–7.0]; and GA 30–33 weeks, OR: 2.7 [95% CI: 1.1–6.5]). In the subgroup of deliveries at 34 to 36 weeks' GA, the association was no longer significant (OR: 2.6 [95% CI: 0.9–7.0]). Adenoviral genome detection followed the seasonal variation of adenovirus respiratory infections (beginning of March to end of June). Chorioamnionitis was present more frequently in the adenovirus-positive preterm placentas compared with term placentas (P = .006). The presence of villitis (P = .03) and chorioamnionitis (P = .02) was significantly increased in the adenovirus-positive preterm placentas compared with preterm adenovirus-negative placentas.

CONCLUSIONS: Our results indicate that there is an association between placental adenoviral genome detection and spontaneous early premature birth. Adenovirus may cause preterm birth through placental inflammation (chorioamnionitis and villitis).
DOES INTRAFAMILIAL SPREAD PLAY A ROLE FOR HELICOBACTER PYLORI INFECTION IN CHILDREN?
Authors: Roma Eleftheria , Panayiotou Joanna , Pachoula Joanna , Kafritsa Yota , Constantinidou Cathrin , Mentis Andreas , Syriopoulou Vasiliki
Published: January 2008

INTRODUCTION: Acquisition of Helicobacter pylori (Hp) infection in children occurs mainly in those under 5 years of age.

OBJECTIVE: Our aim was to investigate intrafamilial spread of Hp infection.

METHODS: One hundred symptomatic children without previous eradication treatment were investigated by gastroscopy and the 13C-urea breath test (UBT). All family members of each index patient were investigated by using the UBT. Infected members were estimated according to UBT results, and for those members who were UBT-negative and had recently received eradication therapy after confirmation of infection by endoscopy, the previous positivity was taken into account.

RESULTS: Ηp infection was identified in 44 (44%) of 100 symptomatic index children. There was no statistical difference between Ηp+ and Ηp− index children concerning demographic factors except age, which was higher in Ηp+ index children (P = .009). In all Ηp+ index children (100%) and in 71.4% of Ηp− children, at least 1 more family member was infected (P < .001); in all cases (100%) at least 1 parent in the group of Ηp+ index children, compared with 69.6% in Ηp− index children (P < .001), was infected. The rate of infected siblings of the Ηp+ index children was 43.2%, and that in the Ηp− group was 3.6% (P < .001). There were more infected mothers in the Ηp+ index children group (83.7% vs 50% in the Ηp− group; P = .001) and more infected fathers (76.7% vs 56.4%, respectively; P = .035).

CONCLUSIONS: The identification of at least 1 more infected member in each family of Hp+ index patients, including a parent in all cases, strongly indicates family as the main source of infection for children and confirms the hypothesis of intrafamilial spread of Hp.
MONOCYTES EXPRESSING TISSUE FACTOR AS A DIAGNOSTIC MARKER FOR NEONATAL SEPSIS
Authors: Youssry Ilham , Edris Amira , Tawfik Naglaa , Rizk Samia , Abou-Elew Heba , Mokhtar Doha , El Messery Lobna
Published: January 2008

INTRODUCTION: For neonatal sepsis, several clinical and laboratory parameters have been proposed for its diagnosis but with variable sensitivity and specificity. The bacterial products in sepsis, including endotoxin, induce the production of proinflammatory cytokines that evoke the expression of tissue factor (TF) on monocytes and endothelial cells.

OBJECTIVE: Our goal was to estimate the percentage of monocytes that express TF (TF%) by flow cytometry in patients with neonatal sepsis and to delineate its significance in diagnosing neonatal sepsis.

METHODS: Twenty-seven neonates with neonatal sepsis and positive blood-culture results were recruited and evaluated clinically for their risk factors. Laboratory investigations including obtaining complete blood count and C-reactive protein level and estimation of the monocytes' TF expression by flow cytometry were performed. Twenty-four normal newborns were included as controls for the laboratory data.

RESULTS: The monocytes that expressed TF% of the studied patients was significantly higher than that of the controls (P = .0001). The level of TF% was significantly influenced positively by premature rupture of membranes, multiplicity, white blood cell (WBC) count, staff/segment ratio, and C-reactive protein level and negatively by gestational age, body weight, and platelet count. The sensitivity and overall accuracy of the TF% were higher than those of the staff/segment ratio and the WBC count for diagnosing neonatal sepsis. The areas under the receiver operating characteristic curve of TF%, staff/segment ratio, and WBC count were 0.84, 0.79, and 0.60, respectively.

CONCLUSIONS: The monocytes expressing TF% is a promising diagnostic and prognostic marker of infection in neonatal sepsis with high sensitivity and overall accuracy. Adding the estimation of monocytes expressing TF% to the sepsis screen may improve the diagnosis of neonatal sepsis.
DOUBLE-BLIND TRIAL OF FORMULA IN DISTRESSED AND REGURGITATING INFANTS
Authors: Vandenplas Yvan , Devreker T. , Hauser B.
Published: January 2008

INTRODUCTION: Many parents seek medical help because of frequent regurgitation and inconsolable crying of their formula-fed infant.

OBJECTIVE: We aimed to assess the effectiveness of special formulas in distressed and regurgitating infants.

METHODS: We included 12 consecutive infants in a prospective, randomized, single-blinded (parents), cross-over trial (6 infants were started on G1 [80/20 casein/whey, tapioca starch, and locust bean] for 2 weeks and then switched for 2 weeks to G3 [partial whey hydrolysate, tapioca starch, and locust bean]; for the other 6 infants, the order of the formulas was opposite). Infants were exclusively formula fed, were crying for >3 hours/day for at least 3 weeks, and regurgitated several times after each feeding. Before inclusion, all of them had been given ≥3 different commercialized AR formulae, formulae for digestive comfort, and at least 1 extensive hydrolysate without success. All infants had been treated without success with a prokinetic agent (domperidone/cisapride) and an acid-blocking drug (H2-receptor agonist/proton-pump inhibitor).

RESULTS: Gastric emptying time, as evaluated with a 13C acetate breath test, was 117.1 ± 18.3 minutes with Novalac-AR (80/20 casein/whey and corn starch), 104.5 ± 15.5 minutes with G1, and 79.2 ± 14.0 minutes with G3 (P < .001 [Friedman test]). The mean number of regurgitations per day was 5.1 ± 1.2 with G1 and 1.8 ± 1.2 with G3 (P = .002). Quality of life, as assessed by the parents in a diary, was 4.20 ± 1.79 with G1 and 2.10 + 0.74 with G3 (P = .005). The mean duration of crying per day was 84.5 ± 50.1 minutes with G1 and 26.7 ± 18.1 minutes with G3 (P = .003).

CONCLUSIONS: The cross-over design protected for bias. G3 scored better than G1 for all parameters evaluated and decreased regurgitation and infant distress significantly.
PREVALENCE OF SEXUAL ABUSE AMONG ADOLESCENT MEDICAL AND NURSING STUDENTS IN A COLLEGE IN PUNJAB, INDIA
Authors: Sobti Praveen , Biswas Gautam
Published: January 2008

OBJECTIVE: We sought to determine the prevalence of sexual abuse among adolescent medical and nursing students who were attending a college in Punjab, India.

METHODS: Five hundred thirty-two subjects (150 male medical students, 220 female medical students, and 162 female nursing students) between 17 and 26 years old filled out a detailed questionnaire, in absolute privacy, to gather demographic and sexual abuse information.

RESULTS: of the participating students, 28.2% were male and 71.8% were female. The overall prevalence rate of any form of sexual abuse was 32.1% (171 subjects). A severe form of sexual abuse (intercourse) was reported by 30 subjects (10 among males and 20 among females). The most common type of abuse reported was in the form of showing pornographic material among male students (41 subjects [23%]) and touching of breasts (58 subjects [33.9%]) among females. The minimum age of victims at the time of the first incident was >16 years in 83 subjects (48.5%). The abuser was a friend in 32.1% (29 in males and 27 in females) of the cases. The perpetrators of sexual abuse were males for 132 subjects of both genders. In 56% (96 subjects), the time of abuse was between 2 and 10 pm. Forty-one subjects (23%) currently experience abuse memories in the form of unwanted scenes flashing in dreams, difficulty in maintaining relationships, feeling of guilt, fear, or nausea when touched, and disturbing sexual thoughts, alone or in combination.

CONCLUSIONS: These results provide baseline information on the prevalence and type of sexual abuse among adolescents. Abuse involved both genders, but the perpetrators were male. For nearly one fourth of the students the incident seems to have left a long-term psychological impact on the victim.
PEDIATRICIANS' AWARENESS OF AND ATTITUDES ABOUT OTITIS MEDIA: RESULTS OF A MULTINATIONAL SURVEY
Authors: Arguedas Adriano , Lefebvre Cedric , Vercruysse Severine , Dean Carol , Maudrich Julie
Published: January 2008

INTRODUCTION: Otitis media (OM) is a common problem in primary care and constitutes a significant health burden in <5-year-olds. Middle-ear effusion after acute OM is also a common problem that causes hearing loss in a substantial proportion of children and is a frequent reason why primary care providers refer children to specialists. However, there are limited non-US data on pediatricians' awareness and attitudes toward OM disease burden, complications, and causative pathogens.

OBJECTIVE: A multinational survey was undertaken to validate and measure primary care physicians' attitudes and behaviors toward OM.

METHODS: Two thousand pediatricians from 10 countries (4 European, 3 Asian, 2 Latin American, and 1 Middle Eastern) were interviewed. Questions focused on the number of children younger than 5 who were treated for OM in the previous year, perceptions about complications and sequelae, awareness of OM pathogens, and concerns about current disease-management practice.

RESULTS: Reported estimates of OM in <5-year-olds was 349 (range: 125–1000) cases per year per practice (ie, pediatricians treated at least 1 patient with OM per day). Eighty-two percent of the pediatricians reported that they treat OM with first-line antibiotics; they were generally satisfied but viewed antibiotic resistance as a serious issue. Nineteen percent of children were referred to an ear, nose, and throat specialist because of treatment failure, recurrent/chronic OM, or hearing problems or for surgery. Pediatricians associated OM with 2 main pathogens: Streptococcus pneumoniae (77%) and Haemophilus influenzae (73%). Association of nontypeable H influenzae was significantly lower (40%).

CONCLUSIONS: OM is frequently treated by pediatricians in daily practice. A majority of them seem to use antibiotics as first-line treatment. The most common reasons for specialist referrals include treatment failures, recurrent/chronic OM, hearing problems, and surgery. Hearing loss and antibiotic resistance are of concern. Nontypeable H influenzae is less well known as an otopathogen.
RESEARCH OF MANNOSE-BINDING LECTIN AND INTERLEUKINS 10, 12, AND 18 IN CHILDREN WITH HENOCH-SCHÖNLEIN PURPURA
Authors: Li Qiu , She Ping-li , Chen Jia , Zhang Wei
Published: January 2008

INTRODUCTION: Henoch-Schönlein Purpura (HSP) is a common vasculitis in children, and the unbalance of T-helper 1/T-helper 2 plays an important part in its pathogenesis. Mannose-binding lectin (MBL) is an important component of innate immunity and related with a lot of diseases with immunologic derangement. However, we do not know the relationship between MBL and HSP.

OBJECTIVE: We aimed to explore the serum level and gene polymorphisms of MBL and the levels of interleukin 10 (IL-10), IL-12, and IL-18 in supernatant of peripheral blood mononuclear cells of children with HSP and HSP nephritis (HSPN) and of healthy children.

METHODS: The concentrations of MBL and IL-10, IL-12, and IL-18 were measured by enzyme-linked immunosorbent assay: MBL gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction with sequence-specific primers.

RESULTS: The serum MBL levels in the 23 children with HSP were not significantly different from 27 children with HSPN (P = .95) or 18 normal children. The levels of IL-18 in the supernatant of peripheral blood mononuclear cells in the 3 groups were not significantly different from each other (P = .47, .15, and .14). The levels of IL-10 in children with HSP and HSPN were not different from each other (P = .70), but both were significantly different from those in the normal children (P = .04 and .01). The levels of IL-12 in children with HSP were different from those in the children with HSPN (P = .04). The MBL promoter genotype and the frequency of alleles were not different between the children with HSP and HSPN or between those 2 groups compared with the normal group.

CONCLUSIONS: IL-12 probably plays an important role in the renal involvement in HSP. The position of MBL in the pathogenesis of HSP and HSPN remains to be confirmed.
CHILDREN WITH PERSISTENT WHEEZING ASSOCIATED WITH HUMAN BOCAVIRUS INFECTION IN CHINA
Authors: Enmei Liu , Yu Deng , Xiaodong Zhao , Yuan Ding , Qubei Li , Zhengxiu Luo , Lijia Wang , Xiqiang Yang
Published: January 2008

INTRODUCTION: Human bocavirus (HBoV) is a newly identified human parvovirus that was originally isolated from children with lower respiratory tract disease. The impact of HBoV on childhood persistent wheezing has not been identified.

OBJECTIVE: Our aim was to study the impact of HBoV on childhood persistent wheezing.

METHODS: In this study, a total of 40 tracheal aspirates were obtained by bronchofibroscope from children with persistent wheezing who had been wheezing for at least >4 weeks. HBoV was detected by polymerase chain reaction. A rapid immunofluorescence method was used for diagnosis of respiratory syncytial virus, adenovirus, influenza A and B, and parainfluenza 1, 2, and 3.

RESULTS: In 40 children with persistent wheezing, 13 (32.5%) had DNA sequences that were HBoV-positive. Age of the patients with HBoV-positive infection ranged from 1 month to 2 years. The results of polymerase chain reaction products sequencing proved that these 13 samples were exactly identical to the sequence of HBoV published in GenBank (accession Nos. DQ988934 and DQ457413). Two children with HBoV infection were found to have coinfection with respiratory syncytial virus.

CONCLUSIONS: This study confirmed that HBoV is a common pathogen for children with lower respiratory infection and might particularly be attributed to persistent wheezing. However, more studies should be performed to study the mechanism of HBoV on chronic airway inflammation.
LYMPHOCYTES IN PERIPHERAL BLOOD AND THYROID TISSUE IN CHILDREN WITH GRAVES' DISEASE
Authors: Ben-Skowronek Iwona , Szewczyk Leszek , Sierocinska-Sawa Jadwiga , Korobowicz Elzbieta
Published: January 2008

OBJECTIVE: Our goal was to analyze interactions of lymphocytes in peripheral blood and thyroid tissue in children with Graves' disease (GD).

METHODS: The prospective study concerned 15 children affected with GD and 15 healthy children. The levels of autoantibodies against thyrotropin receptor, thyroid peroxidase, and thyroglobulin were assayed. Monoclonal antibodies (Ortho Diagnostic Systems, Raritan, NJ) were used to define peripheral blood lymphocyte subsets and analyzed by using a flow cytometer. After thyroidectomy, thyroid specimens were stained with hematoxylin/eosin. T cells were detected by CD3+, CD4+, and CD8+ antibodies and the antigen-presenting dendritic cells with CD1a+ and CD35+ antibodies (DakoCytomation, Glostrup, Denmark).

RESULTS: Before treatment, all children with GD had increased thyroid autoantibody levels, an increased percentage of CD4+ helper cells, and decreased levels of CD8+ suppressor/cytotoxic T cells, which resulted in an elevated CD4/CD8 ratio. The percentage of CD19+Cd5+ B cells was increased, although the total population of CD19+ B cells did not differ from that of the control group. The number of lymphocytes in the thyroid was decreased in 10 patients after long-term thiamazole treatment. In 5 patients with short-term therapy (<6 months after relapse of GD), the lymphocytes had formed lymphatic follicles: antigen-presenting dendritic cells CD1a+CD35+ in the germinal center and T-helper CD4+, T-suppressor CD8+, and B cells CD79+ on the edges.

CONCLUSIONS: The primary defect of immunoregulation in GD consists of an increase of T-helper lymphocytes with a simultaneous decrease in the number of T-cytotoxic/suppressor cells. Thiamazole therapy probably leads to reduction of the lymphocyte amount in the thyroid.
MILK-SPECIFIC IMMUNOGLOBULIN E/TOTAL IMMUNOGLOBULIN E RATIO AS A PREDICTOR OF POSITIVE ORAL FOOD CHALLENGES IN CHILDREN WITH ALLERGY TO COW'S MILK
Authors: Konstantinou George , Kalobatsou Alexandra , Koutli Maria , Xepapadaki Paraskevi , Douladiris Nikolaos , Saxoni-Papageorgiou Photini , Manoussakis Emmanuel , Papadopoulos Nikolaos G.
Published: January 2008

INTRODUCTION: Skin-prick test wheal size and serum-specific immunoglobulin E (IgE) levels are able to predict, to an extent, the presence of allergy to certain foods. Nevertheless, the predictive value of these markers is not enough to substitute for oral food challenges, which suggests the need for improvement.

OBJECTIVE: The goal was to determine the prognostic value of specific IgE/total IgE (tIgE) ratio in patients with allergy to cow's milk by using receiver operating characteristic (ROC) analysis.

METHODS: Thirty-four open challenges were performed in children with a mean age of 18.4 months (range: 10.3–69.2 months) who had a previously diagnosed IgE-mediated allergy to cow's milk to reintroduce milk into their diet. Specific IgE levels, assessed by ImmunoCAP fluorescence enzyme immunoassay (Pharmacia Corp, Bridgewater, NJ), were obtained, and skin-prick tests were performed just before the challenge. The specific IgE (f2)/tIgE ratio was evaluated as a potential predictor of a positive challenge and compared with f2 alone by using ROC analysis.

RESULTS: Of 34 challenges, 6 (17.6%) results were positive. Prechallenge milk-specific IgE levels and the f2/tIgE ratio were significant predictors (Pf2 = .007; Pratio = .008) of a positive challenge outcome. After ROC analysis, f2 provided a discrimination (between positive and negative provocations) of 0.8601 (ROC area under the curve); however, the f2/tIgE ratio provided a significantly greater discrimination of 0.9464. Values of the f2/tIgE ratio that are >0.1121 provide a 100% diagnostic accuracy (probability of a positive provocation result).

CONCLUSIONS: The f2/tIgE ratio may be a novel, promising predictor of positive oral food-challenge results and should be evaluated prospectively in a larger sample.
CLINICAL COURSE AND OUTCOME IN CHILDREN WITH RARE CONNECTIVE TISSUE DISEASES: A RETROSPECTIVE REVIEW OF A 17-YEAR EXPERIENCE
Authors: Dracou-Kakava Christina , Karakontinou Katerina , Galetselli Marianthi , Avgeri Maria , Drakonaki Sophia
Published: January 2008

INTRODUCTION: Juvenile dermatomyositis/juvenile polymyositis (JDM/JPM), juvenile systemic scleroderma (JSCL-SYST), and juvenile mixed connective tissue disease (JMCTD) are rare in childhood.

OBJECTIVE: The objective of this study was to evaluate the prognosis of the rare connective tissue diseases (RCTDs) in children,

METHODS: We reviewed the medical charts of children with a diagnosis of RCTD since 1989 and a minimum follow-up of 5 years.

RESULTS: Twenty-four (16 female, 8 male) children with JDM/JPM, JSCL-SYST, and JMCTD were studied. The age at disease onset ranged from 4 to 13 years. The follow-up duration was 5 to 12 years. Sixteen children had JDM, and 2 had JPM. Four had JSCL-SYST, and 2 had JMCTD. Until now, 13 children have reached clinical remission, lasting >3 years after stopping drug therapy. Twelve children had JDM/JPM, and 1 had JMCTD. Persistent disease activity was noted in 11 children: 4 with JSCL-SYST, 6 with JDM/JPM, and 1 with JMCTD. Severe pulmonary disease developed in 3 children: 2 with JSCL-SYST and 1 with JMCTD. None of the children with JDM had pulmonary disease. Pulmonary hypertension (PH) was found in 2 children with JMCTD or JSCL-SYST. The child with JSCL-SYST and PH died. Persistent scleroderma pattern by wide-field capillaroscopy was noted in 4 children who had JDM and had had skin ulcerations and have developed subcutaneous calcifications. One of them has also had marked muscle atrophy and severe contractures.

CONCLUSIONS: Persistent activity and/or severe pulmonary involvement may be present during the clinical course of RCTD. The presence of PH indicates very poor prognosis in JSCL-SYST/JMCTD cases. Capillaroscopy may identify children who have JDM and are candidates for aggressive therapy.
IMPAIRED DIURNAL BLOOD PRESSURE AND HEART RATE VARIATION AND THEIR RELATIONSHIP WITH LEFT-VENTRICULAR FUNCTION IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS
Authors: Karavanaki Kyriaki , Kazianis George , Tsouvalas Emmanouil , Konstantopoulos Ilias , Karayianni Christina
Published: January 2008

INTRODUCTION: Diabetic cardiomyopathy is a well-defined complication of diabetes that occurs in the absence of ischemic heart disease or hypertension and has been associated with autonomic dysfunction.

OBJECTIVE: Our aim was to evaluate diurnal blood pressure (BP) fluctuations and autonomic function and their possible association with left-ventricular function in adolescents with type 1 diabetes mellitus.

METHODS: In 48 normotensive, normoalbuminuric diabetic adolescents, with a mean (±SD) age of 17.3 (±4.1) years and diabetes duration of 8.5 (±3.3) years, 24-hour ambulatory BP and heart rate (HR) monitoring was performed. Left-ventricular end-diastolic and end-systolic diameters were estimated by echocardiography, and left-ventricular mass index (LVMI) was calculated.

RESULTS: The patients were divided into 2 groups according to the absence of decrease (nondippers) or the decrease (dippers) of nocturnal diastolic BP. The nondippers presented, in comparison with the dippers, reduced mean HR during 24 hours (79.6 vs 84.0 beats/minute; P = .05) and also during daytime (81.3 vs 86.0 beats/minute; P = .05). The nondippers also presented greater end-systolic diameter (28.7 vs 25.9 mm; P = .001) and left-ventricular end-diastolic diameter (47.8 vs 45.1 mm; P = .040) and greater LVMI (90.2 vs 78.3 g/m2; P = .044) compared with the dippers. During stepwise multiple regression, the most important factors affecting LVMI were mean HR (day) (b = −0.40; P = .001), high-frequency variable of heart rate variability (b = 0.38; P = .016), and hemoglobin A1c: (b = 0.67; P = .001).

CONCLUSIONS: A group of normotensive diabetic adolescents with abnormal nocturnal BP reduction and impaired heart rate variation also had impaired left-ventricular function. Our findings suggest that an altered diurnal BP profile, as a result of autonomic dysfunction, may contribute to the development of left-ventricular hypertrophy in patients with type 1 diabetes mellitus.
PREVALENCE OF TUBERCULOSIS AMONG CHILDREN WHO HAD TYPE 1 DIABETES AND WERE ADMITTED TO ELMINIA UNIVERSITY HOSPITAL
Authors: Abdelmoez Basma , Abd-El-Nasser A. , Baheeg Mohamed G. , Sedky Ali A.
Published: January 2008

INTRODUCTION: Tuberculosis has been a cause of significant morbidity and mortality for humans throughout history. There are 20 million cases of tuberculosis worldwide with 8 million new cases each year. Three million deaths annually are directly attributable to tuberculosis. Previous clinic-based studies in developed countries demonstrated an association between tuberculosis and diabetes but did not determine whether this is attributable an increase in recently transmitted or reactivated infection of tuberculosis.

OBJECTIVE: The objective of this study was to identify the epidemiologic relationship between tuberculosis and diabetes in children by using MycoDot, a simple, rapid, and reliable test.

METHODS: This study was a cross-sectional study of 2 groups. The first group was 110 children who had type 1 diabetes, were aged 5 to 10 years, and had a regular follow-up in the pediatric diabetes outpatient clinic in Elminia University Hospital. The second group consisted of 110 children (as a control group without diabetes) who were age and gender matched from the pediatric outpatient clinic in Elminia University Hospital. The children were subjected to tuberculin skin test and Ziehl Neelsen staining on sputum. The children with diabetes only were subjected to chest radiograph. The children's sera were subjected to MycoDot test.

RESULTS: Among the 110 children with diabetes, 6 (5.5%) were determined to have positive tuberculosis results using the MycoDot technique. Only 1 (0.9%) control patient was determined to have a positive tuberculosis result using the same test. Among the children with diabetes (110), 4 (3.8%) were found to have positive tuberculosis results by tuberculin skin test, whereas 2 (1.8%) were found to have positive tuberculosis results by Ziehl Neelsen staining on sputum.

CONCLUSIONS: Many studies have explored the association between diabetes and tuberculosis. In developed countries, studies dating to the first half of the 20th century demonstrated considerable increase in the frequency of tuberculosis among patients with diabetes, although the proportion with comorbidity ranged widely from 1.0% to 9.3%. Other studies have shown a higher frequency of diabetes among individuals with tuberculosis. In our results, 5.5% of children with diabetes had tuberculosis by MycoDot test, which is a simple and reliable test, whereas only 1 (0.9%) positive result was found in the group without diabetes by the same test. The former indicates that risk for tuberculosis increases among children with diabetes, which indicates that regular screening for the presence of active tuberculosis among children with diabetes should be conducted.
ADIPONECTIN AND PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR γ EXPRESSION IN SUBCUTANEOUS AND OMENTAL ADIPOSE TISSUE IN CHILDREN
Authors: Li Xiaonan , Lindquist Susanne , Angsten Gertrud , Myrnas Torbjorn , Yi Jun , Chen Ronghua , Hans Stenlund , Olsson Tommy , Hernell Olle
Published: January 2008

INTRODUCTION: Adiponectin is an adipocyte-specific protein with insulin-sensitizing properties. Peroxisome proliferator-activated receptor γ (PPARγ) may be involved in its gene transcription.

OBJECTIVE: The aim of this study was to compare the expression levels of the genes that encode adiponectin and PPARγ in subcutaneous and omental adipose tissue in children in relation to age and anthropometric variables.

METHODS: Paired biopsies (from subcutaneous and omental adipose tissue) were obtained from 53 children (age: 0.2–14.0 years; BMI: 12.5–25.8 kg/m2). Messenger RNA (mRNA) levels of adiponectin and PPARγ were measured by using reverse-transcription and quantitative real-time polymerase chain reaction.

RESULTS: Adiponectin mRNA levels in adipose tissue were positively associated with PPARγ mRNA levels in children (subcutaneous adipose: r = 0.73, P < .001; omental adipose: r = 0.78, P < .001). In overweight children, the median adiponectin mRNA level was lower in omental adipose tissue (odds ratio: 0.51 [95% confidence interval: 0.1–2.17]) compared with subcutaneous adipose tissue (odds ratio: 1.29 [95% confidence interval: 0.16–5.08]) (P = .032) but not in normal-weight children (P = .54), and the difference remained significant after adjustment for age (P = .045).

CONCLUSIONS: The close association between adiponectin and PPARγ expression supports the hypothesis that PPARγ is involved in adiponectin gene regulation. The fact that adiponectin expression was decreased in omental adipose tissue relative to subcutaneous adipose tissue in overweight children suggests that a risk of insulin resistance may be present in childhood, which allows such resistance to develop after a relatively short duration of overweight.
IDENTIFICATION OF 7 NOVEL TRANSFORMING GROWTH FACTOR β RECEPTOR 2 MUTATIONS IN CHINESE PATIENTS WITH MARFAN SYNDROME
Authors: Chung Brian Hon-Yin , Li Susanna , Lam Stephen Tak-Sum , Yang Wanling , Lun Kin-Shing , Lau Yu-Lung
Published: January 2008

INTRODUCTION: Marfan syndrome (MFS) (Online Mendelian Inheritance in Man [OMIM] No. 154700) is an autosomal-dominant connective tissue disorder that affects multiple systems including the cardiovascular, ocular, and musculoskeletal systems. Fibrillin 1 (FBN1) (OMIM No. 134797) mutations are causative in >90% of the cases, and recent studies have shown that transforming growth factor β receptor 2 (TGFBR2) (OMIM No. 190182) mutations could be identified in ∼10% of non-FBN1 probands (Mátyás G, Arnold E, Carrel T, et al. Hum Mutat. 2006;27:760–769).

OBJECTIVE: Our objective was to examine the mutation spectrum of TGFBR2 in non-FBN1 Chinese patients with MFS and related phenotypes.

METHODS: All Chinese probands who were referred for evaluation of MFS and tested negative for FBN1 mutations were included. Mutational screening was performed by denaturing high-pressure liquid chromatography (Kosaki K, Udaka T, Okuyama T. Mol Genet Metab. 2005;86:117–123). Amplicons with an abnormal elution pattern were selected for direct sequencing.

RESULTS: Seven novel mutations were identified in 7 of 41 probands. All of them had prominent cardioskeletal phenotypes without ocular or dural involvement, which confirmed previous findings (Disabella E, Grasso M, Marziliano N, et al: Eur J Hum Genet. 2006;14;34–38). Six mutations were missense (R190H, D247V, T325P, G357R, I510N, and T530I), and 1 was frameshift (P501fsX17). Except for R190H, all were found in the functionally important kinase domain. Bioinformatic analyses showed that (1) all mutations occurred in conserved positions by cross-species comparison between 6 orthologs, and (2) R190H, T325P, T530I, and G357R were also found in conserved positions among 3 paralogs (TGFBR1 and activin receptors AVR2A and AVR2B) in the TGFBR superfamily. None of the 7 were found in 50 unaffected individuals (100 normal alleles). With the TGFBR2 mutations, 4 additional probands would fulfill the diagnostic criteria of MFS.

CONCLUSIONS: TGFBR2 mutation was identified in 17% of our non-FBN1 probands. It should be considered in the evaluation for MFS after FBN1 screening, especially if there are compatible clinical features.
N-TERMINAL PRO–BRAIN NATRIURETIC PEPTIDE AND PATENT DUCTUS ARTERIOSUS IN PRETERM INFANTS
Authors: Nuntnarumit Pracha , Thanomsingh Pichaya , Khositseth Anant
Published: January 2008

INTRODUCTION: N-terminal pro–brain natriuretic peptide (NT-proBNP) in adults has been reported to be a diagnostic marker of ventricular enlargement and volume overload. However, clinical studies using NT-proBNP in premature infants have been very limited.

OBJECTIVE: We sought to determine whether plasma NT-proBNP in premature infants can identify hemodynamically significant patent ductus arteriosus (hsPDA) and determine the correlation between serial plasma NT-proBNP level and echocardiographic assessment of PDA.

METHODS: Thirty-nine preterm infants underwent clinical and echocardiographic examinations for PDA on days-of-life 2, 4, and 7 and simultaneous blood sampling to measure plasma NT-proBNP concentrations. When ≥2 clinical features of PDA were detected along with left-to-right ductal shunting demonstrated by echocardiogram, hsPDA was diagnosed and the patient treated with indomethacin or ibuprofen.

RESULTS: On day 2, the mean NT-proBNP concentration in the hsPDA group (n = 12) was significantly higher than that in the non-hsPDA group (n = 23) (3160.3 ± 3104.9 vs 618.1 ± 490.7 pmol/L; P ≤ .05). Eight infants (72%) in the hsPDA group became asymptomatic after an initial course of indomethacin or ibuprofen, and their NT-proBNP levels concomitantly declined. NT-proBNP concentrations were significantly correlated with the magnitudes of the ductal shunt, such as left-atrium/aorta ratio and left-atrium volume index (r = 0.753 and 0.596, respectively). The cutoff of NT-proBNP concentration at 1204 pmol/L on day 2 gave the best predictive values for hsPDA with 100% sensitivity, 91% specificity, 86.7% positive predictive value, 100% negative predictive value, and a likelihood ratio of 11.5.

CONCLUSIONS: The plasma NT-proBNP level on day-of-life 2 is a sensitive marker for predicting hsPDA in preterm infants. Successful closure of PDA corresponds with a decline in plasma levels of NT-proBNP.
EFFECT OF BODY WEIGHT ON BONE AGE AND HORMONAL PARAMETERS IN CHILDREN WITH PREMATURE ADRENARCHE
Authors: Papathanasiou Asteroula , Lekka Garyfallia , Evangelopoulou Catherine , Petrou Vasilios , Petros Papachilleos , Nikolopoulos Panagiotis , Paraskaki Irini , Hadjiathanasiou Charalambos
Published: January 2008

OBJECTIVE: Our goal was to investigate the effect of body weight on bone age (BA) and hormonal features in children with benign premature adrenarche.

METHODS: We studied 221 children (175 girls, 46 boys) with premature adrenarche (pubic and/or axillary hair at <8 years of age in girls and <9 years of age in boys) and mean chronological age (CA) at presentation of 7.0 years (girls) and 7.8 years (boys). Anthropometric features and laboratory data (dehydroepiandrosterone sulfate [DHEA-S], 17-hydroxyprogesterone, Δ4-androstenedione [Δ4-A], testosterone, estradiol, insulin-like growth factor I [IGF-I], cholesterol, triglycerides, high- and low-density lipoprotein cholesterol, and BA) were recorded. The population was divided into 3 groups according to BMI: (1) normal weight, (2) overweight (BMI: 85th–95th percentile), and (3) obese (BMI: >95th percentile). Children with late-onset congenital adrenal hyperplasia were excluded from study.

RESULTS: Mean CA of adrenarche was 6.3 years (girls) and 7.1 years (boys). The percentages of overweight and obese children was significantly higher than those reported in the general population of children in Greece. Obese children had significantly more advanced BA compared with overweight and normal-weight children. Higher levels of DHEA-S and Δ4-A were observed in overweight and obese girls compared with normal-weight girls, whereas higher levels of DHEA-S, testosterone, and IFG-I were observed in overweight and obese boys (Table 1). No statistically significant difference was observed between the 3 groups in the levels of 17-hydroxyprogesterone, estradiol, cholesterol, triglycerides, or high- and low-density lipoprotein cholesterol.

CONCLUSIONS: A higher frequency of obesity and advanced BA was observed in children with benign premature adrenarche, with a strong correlation between BA and degree of obesity. Furthermore, obese children were characterized by higher levels of adrenal androgens compared with normal-weight children.

TABLE 1.Levels of Adrenal Androgens in Normal-Weight and Obese ChildrenNormal Weight Mean (Range)Overweight Mean (Range)Obese Mean (Range) P                 a Girls    Testosterone, ng/mL0.11 (0.06–0.20)0.14 (0.10–0.21)0.16 (0.09–0.24).112    DHEAS, μg/mL0.71 (0.41–1.10)0.85 (0.61–1.15)0.88 (0.57–1.21)b.081    Δ 4-A, ng/mL0.4 (0.2–0.8)b0.6 (0.4–1.1)b0.6 (0.4–0.8)b<.05b    IGF-1, ng/mL199 (140–318)236 (180–283)200 (190–266).681Boys    Testosterone, ng/mL0.08 (0.04–0.15)b0.17 (0.06–0.26)b0.28 (0.09–0.39)b<.05b    DHEAS, μg/mL0.51 (0.21–0.92)1.10 (0.82–1.24)b1.12 (0.20–2.12).056    Δ 4-A, ng/mL0.4 (0.2–0.7)0.5 (0.3–0.6)0.6 (0.4–1.0).524    IGF-1, ng/mL200 (89–257)b170 (116–207)b288 (267–369)b<.05baKruskal-Wallis test.bResults were significant.
PREDICTIVE VALUE OF AMPLITUDE-INTEGRATED ELECTROENCEPHALOGRAPHY ON OUTCOME IN NEONATAL EXTRACORPOREAL MEMBRANE OXYGENATION
Authors: Pappas Athina , Shankaran Seetha , Stockmann Paul
Published: January 2008

INTRODUCTION: The early and accurate assessment of cerebral function in neonates who undergo extracorporeal membrane oxygenation (ECMO) may identify high-risk infants who are amenable to neuroprotective strategies or, at least, in need of more detailed neuroimaging and neurodevelopmental follow-up.

OBJECTIVE: The specific aims of this study were to assess the clinical utility and long-term predictive value of amplitude-integrated electroencephalography (aEEG) in neonatal ECMO.

METHODS: Thirty-four infants who required ECMO for respiratory failure were enrolled in the study prospectively. Serial aEEGs were recorded before, during, and after ECMO and classified by 2 independent interpreters on the basis of background pattern and amplitude criteria. Surviving infants were followed up to 18 to 22 months and assessed with a structured neurologic examination and formal developmental testing by using the Bayley Scales of Infant Development II. The primary outcome was death or neurodevelopmental impairment (defined as moderate-to-severe cerebral palsy and/or a Mental Developmental Index or Psychomotor Development Index score of <70).

RESULTS: Preliminary data analysis on the first 20 patients was performed. Thirteen patients survived, 3 died while on ECMO, and 4 died before discharge. All surviving infants were evaluated at follow-up. A severely abnormal aEEG predicted death or moderate-to-severe neurodevelopmental impairment with a sensitivity of 0.85 (95% confidence interval [CI]: 0.70–0.95), a specificity of 0.57 (95% CI: 0.3–0.76), a positive predictive value of 0.79 (95% CI: 0.65–0.88), and a negative predictive value of 0.67 (95% CI: 0.35–0.88).

CONCLUSIONS: aEEG is a useful neuromonitoring tool during neonatal ECMO.
RECURRENT MAJOR INFECTIONS IN JUVENILE-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS: A CLOSE LINK WITH LONG-TERM DISEASE DAMAGE
Authors: Lee Pamela Pui-Wah , Lee Tsz-Leung , Ho Marco Hok-Kung , Wong Wilfred Hing-Sang , Lau Yu-Lung
Published: January 2008

INTRODUCTION: Infection is a significant cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). We postulated that patients with recurrent infections are more likely to have poorer disease outcome.

OBJECTIVE: The objectives of this study were to describe the pattern of infections and disease damage that occurred in a cohort of patients with juvenile-onset SLE and to determine whether cumulative disease damage was associated with recurrent infections in these patients.

METHODS: We retrospectively reviewed (1988–2004) the clinical characteristics, infective complications, and disease damage as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index Score (SDI) in 47 patients with juvenile-onset SLE. Potential risk factors for disease damage were evaluated by univariate analysis and logistic regression. The correlation between number of major infections and disease damage was determined.

RESULTS: Thirty-two (68.1%) patients had lupus nephropathy, and 16 (34.0%) patients had neuropsychiatric lupus. Sixty-one episodes of major infections, defined as infections that required more than 1 week of antimicrobial agents, occurred in 27 (57.4%) patients, and 18 (31.4%) patients had recurrent major infections (≥2 episodes). Organ damage (SDI ≥ 1) was documented in 21 (44.7%) patients. By logistic regression, occurrence of major infections was the only significant risk factor for disease damage. There was a positive correlation between SDI score and the number of recurrent major infections.

CONCLUSIONS: Infections and disease damage are common comorbidities in juvenile-onset SLE. Recurrent infections could predict poorer disease outcome and associated organ damage in SLE.
SEVERE LUNG HYPOPLASIA IS OBSERVED IN DHCR24-KNOCKOUT MICE: A MOUSE MODEL OF DESMOSTEROLOSIS
Authors: Mirza Rusella , Hayasaka Sizu , Kaji Takehide , Murata Yoshiharu , Seo Hisao
Published: January 2008

INTRODUCTION: The DHCR24 gene encodes an enzyme that converts desmosterol to cholesterol in the last step of cholesterol synthesis. Desmosterolosis is an autosomal-recessive disorder that is caused by mutation in the DHCR24 gene, resulting multiple developmental anomalies.

OBJECTIVE: The objective of this study was to understand the pathophysiology of desmosterolosis.

METHODS: DHCR24-knockout mice were used in this study. All homozygous mice (−/−) died soon after birth. DHCR24−/− mice demonstrated features of lethal restrictive dermopathy, associated with impaired skin barrier function as a result of hyperproliferation of undifferentiated keratinocytes throughout the epidermis. One other possible cause for neonatal death in DHCR24−/− mice is respiratory failure, as evidenced by severe cyanosis immediately after birth. We therefore studied the lung development of these mice. Lungs from the newborn alive pups were subjected to weight measurement and histologic and Western blot analyses.

RESULTS: DHCR24−/− mice were identified by their phenotype and genotyping. Lung-to-body weight ratio was decreased in DHCR24−/−. The space between lung surface and the thoracic wall was significantly increased as a result of less expansion of the lung. The majority of the lung portion consisted of collapsed alveoli and decreased saccular space in DHCR24−/− mice. No differentiation defect in alveolar type I cell was detected by Western blot and immunohistochemistry with anti-T1 α antibody, a type I cell–specific marker. Immunohistochemistry with anti–caveolin 1 demonstrated no change in vascular development.

CONCLUSIONS: A distinct saccular hypoplasia in DHCR24−/− mice suggests that there is an important role of DHCR24 in lung development. Additional experiments with surfactant compositions are needed to explore the underlying respiratory pathology.
IMMUNE STATUS AND IMMUNE RECOVERY IN CHILDREN WITH LYMPHOMA AT THE END OF THERAPY (CHEMOTHERAPY AND/OR RADIOTHERAPY) AND IN FOLLOW-UP EVALUATIONS
Authors: Kosmidis Sofia , Pourtsidis Apostolos , Bouhoutsou Despina , Baka Margarita , Varvoutsi Maria , Doganis Dimitrios , Kallergi Constantina , Douladiris Nikolaos , Synodinou Maria , Saxoni-Papageorgiou Fotini , Kosmidis Helen
Published: January 2008

OBJECTIVE: We aimed to evaluate the immune status and immune recovery after completion of chemotherapy and/or radiotherapy in children with lymphoma.

METHODS: We prospectively evaluated humoral and cellular immunity in 22 children with lymphoma (11 with Hodgkin's disease [HD] and 11 with non-Hodgkin's lymphoma [NHL]) at the completion of therapy and every 6 months thereafter.

RESULTS: Immunoglobulin (Ig) levels were normal before the onset of therapy in all but 1 child. At the end of therapy, Ig levels decreased: IgM in 18, IgG in 12, and IgA in 7 children. In addition, 17 of 22 had decreased CD19 levels. In HD after radiotherapy, IgG and CD19 levels increased significantly (P = .013 and .004, respectively). IgM levels remained abnormally low in 16 of 22 children up to 18 months after therapy completion. At the end of therapy, helper T lymphocyte (CD4) levels were low in 20 of 22 children, and suppressor (CD8) levels were elevated in 13 of 22 children. (For those with HD before radiotherapy, the CD8 level was high in 10 of 11 children, and the CD4 level was low in 6 of 11 children.) The suppressor CD8 level remained elevated in 12 of 20 children, and helper CD4 level remained abnormally low in 18 of 20 children for a period of 6 to 18 months after therapy. Some immunized children became nonimmune to polio (15 of 22), mumps (6 of 22), rubella (5 of 22), and measles (1 of 22).

CONCLUSIONS: In children with lymphoma, IgM levels remained low for long periods. Helper T lymphocyte levels were low and suppressor levels were high at the end of therapy. Suppressor cells normalized faster, whereas helper cell levels remained abnormally low for a long period. Most children became nonimmune to polio, whereas the majority had antibodies to measles, mumps, and rubella. Despite depressed immunity, serious infections were not documented.
SURVEILLANCE OF INFLUENZA IN CHILDREN YOUNGER THAN 5 YEARS IN A TERTIARY CARE HOSPITAL IN BANGKOK, THAILAND
Authors: Suntarattiwong Piyarat , Thongtip Parada , Sian-nork Chortip , Thawatsupha Pranee , Kitphati Rungruang , Chotpitayasunondh Tawee
Published: January 2008

INTRODUCTION: Influenza is a common febrile illness with a significant impact on the pediatric population. Few data regarding influenza in young children have come from tropical resource-limited countries.

OBJECTIVE: We aimed to study epidemiological data, clinical manifestations, influenza rapid tests, and oseltamivir treatment in children with influenza.

METHODS: We conducted influenza surveillance at Queen Sirikit National Institute of Child Health, a tertiary care children's hospital in Bangkok, Thailand. From July 5, 2004, to July 3, 2005, 2 groups of patients aged 0 to 5 years were enrolled: (1) patients diagnosed with lower respiratory tract infections (ie, viral croup, bronchitis, bronchiolitis, and pneumonia) and (2) patients diagnosed with influenza-like illness on the basis of World Health Organization criteria. Subjects must have had symptoms for <5 days. We collected nasal swabs to perform influenza A antigen tests by rapid-test kit and nasopharyngeal swab to perform viral cultures. Clinical signs and symptoms were recorded. Oseltamivir (Tamiflu) was given to the patients with positive rapid-test results, and parents agreed to receive an antiviral agent. Other treatment was provided by attending physicians as the routine standard of care.

RESULTS: We enrolled 495 patients, 49 (9.9%) of which had influenza virus. The virus was isolated year-round with 2 peaks. Fever and myalgia were symptoms with a statistically significant difference between patients with and without influenza infection. The rapid test for influenza A showed 51% sensitivity and 98% specificity compared with viral culture. Eighteen (37%) of 49 patients received oseltamivir treatment. The oseltamivir-treated patients had, on average, 1.12, 0.41, and 0.55 days' shorter oxygen duration, hospital stay, and time to improvement, respectively, but there was no statistically significant difference.

CONCLUSIONS: Influenza in young children in Thailand can be found in 10% of patients with lower respiratory tract and influenza-like illness. Two peaks occurred during July to October and January to April. Rapid-test kits have moderate sensitivity but high specificity. Benefit from oseltamivir treatment was observed but not statistically significant.