bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical manifestations of Fabry disease in children: Data from the Fabry Outcome Survey
Authors: Ramaswami Uma , Whybra Catharina , Parini Rosella , Pintos‐Morell Guillem , Mehta Atul , Sunder‐Plassmann Gere , Widmer Urs , Beck Michael ,   ON BEHALF OF THE FOS EUROPEAN INVESTIGATORS
Published: August 2010

Background: Fabry disease is a rare X‐linked disorder caused by deficient activity of the enzyme α‐galactosidase A. This produces progressive lysosomal accumulation of globotriaosylceramide throughout the body, leading to organ failure and premature death. Aim: Here, we present the clinical manifestations of Fabry disease in children enrolled in FOS—the Fabry Outcome Survey—a European database of the natural history of Fabry disease and the effects of enzyme replacement therapy with agalsidase alfa (Replagal™). Methods: Currently, there are 545 patients in FOS, from 11 European countries. We analysed the baseline demographic and clinical characteristics of 82 of these patients (40 boys, 42 girls) who were below 18 y of age. The median age at evaluation (defined as the median age at entry into FOS) was 12.5 and 13.2 y for boys and girls, respectively. Results: The most frequent early clinical manifestations of Fabry disease were neurological (acroparaesthesiae, altered temperature sensitivity) and gastrointestinal symptoms (altered bowel habits and abdominal pain), which were documented in about 80% and 60% of patients, respectively, at the time of evaluation and subsequent entry into FOS. Tinnitus, vertigo, fatigue and angiokeratoma were present in over 40% of patients. Symptoms were noted in early childhood and occurred with similar frequency in boys and girls, although the onset of symptoms was 2–5 y later in girls than in boys. There was an approximately 3‐y delay from onset of symptoms to diagnosis, and patients were frequently misdiagnosed.

Conclusion: Although the life‐threatening complications of Fabry disease, such as stroke and renal and heart failure, are not seen in children, the present analysis shows that other symptoms are common and may have an impact on quality of life.
8‐hydroxy‐2‐desoxyguanosine serum concentrations as a marker of DNA damage in patients with classical galactosaemia
Authors: Schulpis Kleopatra H. , Papassotiriou Ioannis , Tsakiris Stylianos
Published: August 2010

Background:Classical galactosaemia is caused by a deficiency of galactose‐1‐phosphate uridyl transferase, resulting in high galactose (Gal), galactose‐1‐phosphate (Gal‐1‐P) and galactitol blood levels. Galactose/lactose restriction intake is the only treatment. 8‐hydroxy‐2‐desoxyguanosine (8‐OHdG) is a marker of oxidized DNA damage.Aim:Since galactosaemia outcome is closely related to restriction of Gal intake, we aimed to evaluate correlations between Gal‐1‐P, total antioxidant status (TAS) and 8‐OHdG blood levels in galactosaemic patients on poor or strict diet.Methods:Venous blood samples were obtained from galactosaemic patients (n = 11) on poor diet (group A) and after 30 d on strict diet (group B). Twenty‐eight healthy children were the controls. Gal‐1‐P and TAS were evaluated in their blood spectrophotometrically and 8‐OHdG with an immunoassay.Results:TAS was significantly decreased (905±112 µmol/l) in patients on a “loose diet” (group A) as compared to those when restored to their diet (group B) (1340±112 µmol/l,p<0.001) and controls (1558±115 µmol/l,p<0.001). As expected, Gal‐1‐P levels were remarkably increased in group A. 8‐OHdG level was twofold higher (0.25±0.03 ng&ml) in group A than that of group B (0.11±0.04 ng/ml) and threefold higher than that of the controls (0.08±0.02 ng/ml). TAS and Gal‐1‐P inversely correlated to 8‐OHdG (r= − 0.802,p<0.001), whereas Gal‐1‐P positively correlated to 8‐OHdG (r=0.820,p<0.001) in all the groups.

Conclusion:a) Low TAS and high Gal‐1‐P levels are implicated with high 8‐OHdG blood levels in galactosaemic patients; b) 8‐OHdG may be a sensitive biomarker of DNA damage in patients with classical galactosaemia.
Oral ranitidine and duration of gastric pH >4.0 in infants with persisting reflux symptoms
Authors: Salvatore Silvia , Hauser Bruno , Salvatoni Alessandro , Vandenplas Yvan
Published: August 2010

Background:Ranitidine is a drug commonly used in pathological gastro‐oesophageal reflux (GOR) in infants. Non‐responsiveness has been reported. Data regarding the effect of ranitidine on oesophageal acid exposure and reduction of gastric acid secretion are limited in this age group.Objective:To evaluate oesophageal acid exposure, reduction of gastric acid secretion and histology of oesophageal biopsies in infants who clinically do not respond to oral ranitidine.Patients and design:103 infants (mean age 3.3±1.8 mo) with persisting symptoms of reflux despite administration of ranitidine, prescribed previously by a referring physician, at a mean (SD) dose of 9.4 (±3.3) mg/kg/d for at least 2 wk (mean 30 d), were submitted to a 24‐h pH study and oesophageal biopsy (90/103 patients).Results:Histological oesophagitis was present in 21/90 (23%). The oesophageal reflux index (RI) was >5% and >10% in 21/103 (20%) and 6/103 (6%) infants, respectively. Gastric pH was >4.0 during <50%, >50%, >75% and >90% of the duration of pH monitoring in 33/103 (32%), 70/103 (68%), 22/103 (21%) and 7/103 (7%), respectively. By simple regression analysis, the dosage of ranitidine correlated with the oesophageal RI (r=0.21;p=0.05), but not with the duration of time gastric pH was >4.0 (r=0.09;p=0.39). Histological oesophagitis did not correlate with ranitidine dosage, duration of treatment, duration gastric pH was >4.0 and oesophageal reflux index.

Conclusion:Some infants presenting with symptoms assumed to be GOR and acid related fail to respond to acid suppression with ranitidine, either because they need better acid suppression or because the symptoms are not acid related.
Absence of hypoglycemia in response to varying doses of recombinant human insulin‐like growth factor‐I (rhIGF‐I) in children and adolescents with low serum concentrations of IGF‐I
Authors: Guevara‐Aguirre Jaime , Guevara‐Aguirre Marco , Rosenbloom Arlan L.
Published: August 2010

Aim: To determine whether recombinant human insulin‐like growth factor‐I (rhIGF‐I) administration to children with low IGF‐I and relatively low insulin‐like growth factor binding protein‐3 (IGFBP3) serum concentrations would result in hypoglycemia. Methods: Eighteen children age 11–19 y with serum levels of IGF‐I < − 2 SDS and IGFBP3 < 0 SDS were randomly assigned to receive rhIGF‐I at 80 µg/kg body weight daily (n=6), 40 µg/kg twice daily (n=6), or 80 µg/kg twice daily (n=6). After a 10‐d dose escalation and 15 d of treatment at the specified dosage, a 25‐h pharmacokinetic/pharmacodynamic profile was obtained, which included 22 blood glucose measurements. Regular meals and snacks were provided. Results: No signs or symptoms of hypoglycemia were noted throughout the study. There were no differences in mean blood glucose concentrations among the three dosage groups. The lowest glucose value recorded, 3.44 mmol/l, was 15 min after a morning injection of 80 µg/kg IGF‐I, and promptly rose. Although subjects were selected on the basis of low concentrations of IGF‐I to represent proposed candidates for rhIGF‐I therapy, the mean and range of SDS for height were not different from those of previously studied normal Ecuadorian controls.

Conclusion: In normal individuals with low serum concentrations of IGF‐I and relatively low concentrations of IGFBP3, the administration of therapeutic doses of rhIGF‐I, while maintaining reasonable food intake, does not result in hypoglycemia.
Very‐low‐birthweight and term small‐for‐gestational‐age adolescents: Attention revisited
Authors: Kulseng Siri , Jennekens‐Schinkel Aag , Naess Per , Romundstad Pål , Indredavik Marit , Vik Torstein , Brubakk Ann‐Mari
Published: August 2010

Aim: To assess whether adolescents with very low birthweight (VLBW) and peers born small for gestational age (SGA) at term are at a disadvantage when attending to or executing tasks. Methods: Cohorts of 54 VLBW (≤1500 g), 60 SGA and 83 controls were tested with the Knox Cube Test, Conners’ Continuous Performance Test (CPT II), Stroop Colour‐Word Test, Trail Making Test (TMT) A & B, and Wisconsin Card Sorting Test (WCST). IQ was estimated using the subtests vocabulary and picture arrangement of WISC III. Results: VLBW adolescents scored worse than controls on Knox Cube Test, Stroop Colour‐Word Test, TMT A & B and WCST, whereas term SGA adolescents only made more non‐perseverative errors in WCST and more errors in the interference condition of the Stroop Colour‐Word Test. Thirty‐two (38.6%) adolescents in the control group had poor performance (< 2 SD) on at least one of the tests compared with 40 (74.1%) VLBW (p<0.01) and 32 (53.3%) SGA adolescents (not significant).

Conclusion: VLBW adolescents are at risk of disadvantage in aspects of attention and/or executive functions. The adverse effects of being born SGA at term appear to be few in these domains of cognitive function.
Anakinra therapy for CINCA syndrome with a novel mutation in exon 4 of the CIAS1 gene
Authors: Matsubayashi Tadashi , Sugiura Hiroshi , Arai Takashi , Oh‐Ishi Tsutomu , Inamo Yasuji
Published: August 2010

We report on a patient with chronic infantile neurological cutaneous and articular (CINCA) syndrome. Sequence analysis revealed a novel missense mutation in exon 4 of the CIAS1 gene. The patient was unresponsive to several treatments including prednisolone, immunosuppressants (azathioprine and cyclosporin), disease‐modifying antirheumatic drugs (DMARDs: penicillamine, salazopyrin and methotrexate) and the tumour necrosis factor‐alpha (TNF‐α)‐blocker infliximab. At 32 mo of age, administration of the recombinant human interleukin‐1 receptor antagonist anakinra commenced, which caused an immediate and marked improvement in the clinical symptoms and laboratory test results. Continuous inhibition of the inflammation required a dose of 1.0 mg/kg every 12 h.

Conclusion: Following the diagnosis of CINCA syndrome, anakinra treatment should be commenced as the first line of therapy.
The prevalence of ADHD in children with enuresis: Comparison between a tertiary and non‐tertiary care sample
Authors: Baeyens Dieter , Roeyers Herbert , D'Haese Leen , Pieters Femke , Hoebeke Piet , Vande Walle Johan
Published: August 2010

Objective: The main aim of the current study was to determine reliable comorbidity rates of ADHD for enuretic children admitted either to non‐tertiary care or to a specialized paediatric clinic, i.e. tertiary care, since previous research has failed to incorporate a possible setting effect in this comorbidity; and to use a multi‐method multi‐informant assessment of ADHD. Material and methods: Eighty children, aged between 6 and 12 y, admitted to non‐tertiary care with enuresis and 120 children referred to tertiary care were screened for the presence of ADHD using a multi‐method (diagnostic interview, questionnaires) multi‐informant (parents, teachers) assessment. Results: Enuretic children from the tertiary care sample have a 3.4 times increased chance of having comorbid ADHD when compared to children with enuresis admitted to non‐tertiary care, corresponding to a prevalence rate of 28% and 10%, respectively. Overall, the tertiary care sample was older, showed more daytime incontinence and revealed an increasing prevalence of ADHD with older age when compared with the non‐tertiary care group.

Conclusion: The prevalence rate of ADHD is increased in an enuretic population compared to community samples (3–5%). Moreover, enuretic children admitted to tertiary care show significantly higher comorbidity than non‐tertiary care patients. The ADHD prevalence in the former group increases with older age, suggesting therapy resistance and a negative prognosis for enuresis in the case of comorbidity.
Disappearance of middle ear effusion in acute otitis media monitored daily with tympanometry
Authors: Renko Marjo , Kontiokari Tero , Jounio‐Ervasti Katariina , Rantala Heikki , Uhari Matti
Published: August 2010

Background: Disappearance of middle ear effusion is one of the most important outcomes in the treatment of acute otitis media (AOM). Aim: To evaluate the duration of effusion in AOM treated by antimicrobials and to find factors influencing it. Methods: Parents of 90 children with AOM monitored daily the disappearance of effusion with tympanometry. The children were randomly allocated to be treated with either oral amoxicillin or cefuroxime‐axetil for 10 d. Daily monitoring lasted for 14 d or until the tympanogram was normal (curve A or C) in both ears. Pneumatic otoscopy was carried out every 2 wk. Results: Normal tympanograms were obtained after a median time of 7.5 d (range 1–58 d) among 75 successfully monitored patients. In two‐thirds (69%) of them, effusion resolved in 14 d. The median duration of effusion did not differ significantly between the two treatment groups (8 vs 7 days, p=0.7). The children who had unilateral AOM cured more rapidly than those with bilateral AOM (5 vs 19 d, p<0.001). In logistic regression analysis adjusted for age, bilaterality explained treatment failure at 2 wk with an odds ratio of 28.1 (95% CI 4.6–169.5, p<0.001).

Conclusion: The choice of antimicrobials did not influence the duration of middle ear effusion, which was much shorter than had been thought previously. Children with unilateral AOM were cured much more quickly than those with bilateral AOM.
Delays in the diagnosis of anorectal malformations are common and significantly increase serious early complications
Authors: Lindley Richard M , Shawis Rang N , Roberts Julian P
Published: August 2010

Aim: To clarify the extent of delayed diagnosis of anorectal malformations and the consequences of delaying this diagnosis. Methods: We performed a retrospective case review of all neonatal admissions with an anorectal malformation to a tertiary paediatric surgery unit. A delayed diagnosis was considered to be one made 24 h or more after birth. Results: 75 patients were included in the study group: 31 (42%) had a delay in the diagnosis; 44 (58%) had no delay in the diagnosis. The time of diagnosis where a delay had occurred ranged from 2–16 (median 2) d. A delay in diagnosis could not be accounted for by differences in age, sex, birthweight, gestational age, the severity or visibility of the lesion, the need for neonatal special or intensive care, or the presence of other anomalies. There were significantly more complications (including one death) amongst the group of children who had a delay in the diagnosis of an anorectal malformation. There was no significant difference in long‐term functional outcome.

Conclusion: Delays in the diagnosis of anorectal malformations are much more common than previously thought. A delay in diagnosis significantly increases the risk of serious early complications and death.
Childhood drug‐resistant tuberculosis in the Western Cape Province of South Africa
Authors: Simon Schaaf H. , Marais Ben J. , Hesseling Anneke C. , Gie Robert P. , Beyers Nulda , Donald Peter R.
Published: August 2010

Aim: Continued surveillance of drug resistance amongst children presenting with culture‐confirmed tuberculosis to a tertiary care hospital and to community clinics. Methods: Drug susceptibility testing for isoniazid and rifampicin was prospectively done on all children presenting with culture‐confirmed tuberculosis from three study populations: children diagnosed at Tygerberg Children's Hospital in the Western Cape Province, South Africa, between March 2003 and February 2005 (recent survey, hospital‐based group), and August 1994 and April 1998 (previous hospital‐based survey), and a community‐based group from five clinics during the recent survey. Results: Isoniazid resistance increased significantly from 6.9% (21/306 children) in the previous survey to 12.8% (40/313 children) in the recent survey (odds ratio (OR) 1.99, 95% confidence interval (CI) 1.11–3.59). Resistance to isoniazid and rifampicin (multidrug resistance) did not increase significantly between the surveys (7/306 in previous survey vs 17/313 in recent survey; OR 2.45, 95% CI 0.94–6.62). All resistance (isoniazid and/or rifampicin) was 18/127 (14.2%) in the community‐based group compared to 23/192 (12.0%) in the hospital‐based group (OR 0.82, 95% CI 0.41–1.68).  Conclusion: The prevalence of drug‐resistant tuberculosis in this setting is increasing, reflecting ongoing transmission of drug‐resistant Mycobacterium tuberculosis.
Resistance to implementing Kangaroo Mother Care in developing countries, and proposed solutions
Authors: Charpak Nathalie , Gabriel Ruiz‐Peláez Juan
Published: August 2010

Background: Randomized clinical trials have shown that Kangaroo Mother Care (KMC) can decrease morbidity and mortality due to low birthweight. Between 1994 and 2004, 44 teams in 25 developing countries were trained in KMC in Bogotá, Colombia; however, not all the teams were successful in initiating their own programmes and, of those that started, not all replicated the validated model. Aim: To identify factors involved in unsuccessful KMC implementation and find solutions. Methods: A study was conducted in which 17 open‐ended questionnaires were sent by e‐mail to the coordinators of functioning KMC programmes in 15 countries, and 15 site visits were made to institutes that reported problems in starting programmes. The information was classified according to the perceived obstacle and the KMC model component involved. Results: The early‐discharge component (including ambulatory follow‐up) was that found most difficult to implement. Resistance from health professionals, mothers and families was often related to local cultural practices.

Conclusion: Active surveillance for and appropriate identification of obstacles usually indicated the appropriate solution. Some of the obstacles were common to many second‐generation KMC programmes, making this information valuable for the implementation of programmes.
Growth from birth to age 19 for children in Sweden born in 1981: Descriptive values
Authors: Werner Bo , Bodin Lennart
Published: August 2010

Aim: To describe Swedish children's growth (i.e. height, weight and body mass index) from birth to age 19 y. Methods: Every infant born on the 15th of any month in 1981 and living in Sweden as of 31 December 1989 was sampled. Longitudinal data were collected from childhood and school health records, and analysis by piecewise linear regression gave statistical descriptions of height, weight and body mass index for every age group. Results: The data include measurements of 3107 of 3158 sampled children; 1.6% of individuals are missing, so non‐response bias is minimal. Thus, statistical descriptions and comparisons with similar data sets can be based on data with unusually high national representativeness. Selected subgroups (i.e. individuals born outside Sweden, suffering from chronic disease causing major growth impairment, or with birthweight <2500 g) deviate in growth pattern, and exclusion of these subgroups increases means and decreases SD for height but only slightly influences summary statistics for weight and body mass index. Conclusion: This study represents, without selection bias, the current growth situation among children and adolescents in Sweden, enabling both epidemiological comparisons over time and comparisons with other national surveys.
Long‐term relationships between symptoms of Attention Deficit Hyperactivity Disorder and self‐esteem in a prospective longitudinal study of twins
Authors: Edbom Tobias , Lichtenstein Paul , Granlund Mats , Larsson Jan‐Olov
Published: August 2010

Aim: To study the long‐term relationship between symptoms of Attention Deficit Hyperactivity Disorder and the developing self‐esteem in a population‐based sample of twins. Methods: The cohort is all twin pair families born in Sweden between May 1985 and December 1986 (n = 1.480). Wave 1 took place in 1994 when the twins were 8 years old and wave 2 in 1999 when the children were 13 years old. In wave 1 and 2 the parents completed questionnaires regarding ADHD‐symptoms about their children. In wave 2 the twins completed a questionnaire about self‐esteem and Youth Self Report (YSR). ADHD‐symptoms and self‐esteem were analyzed in the total study group. Results: There was a long‐term relationship between high scores of parental‐reported ADHD‐symptoms at 8 and 13 years of age and low scores in measures of self‐reported self‐esteem at 13 years of age. In the cotwin control method controlling for YSR internalizing problem, paired comparisons within the twin pairs revealed that a high score of ADHD‐symptoms at age 8 was related to significantly lower scores at age 13 in the self‐esteem.

Conclusions: The long‐term relationships between ADHD‐symptoms and a low self‐esteem in a population‐based sample were confirmed by the co‐twin analyses.
Health complaints in children with attention‐deficit/hyperactivity disorder
Authors: Holmberg Kirsten , Hjern Anders
Published: August 2010

Aim: To assess recurrent subjective health complaints in Swedish schoolchildren with attention‐deficit/hyperactivity disorder (ADHD). Methods: Cohort study of 577 fourth‐graders (10‐y‐olds) in one municipality in Stockholm County. All children were screened for attention and behaviour problems through interviews with their parents and teachers. Children with high scores underwent further clinical and cognitive assessments. Information about health complaints was collected from the children themselves in a classroom questionnaire. The 516 children for whom there was information from all three data sources were included in the final study population. Hypotheses were tested in multivariate analyses with adjustment for sex and parental education. Results: Recurrent abdominal pain (RAP), sleeping problems and tiredness were associated with ADHD (stratified relative risks: 2.2 [1.4–3.4], 1.7 [1.1–2.7] and 2.7 [1.7–4.1], respectively), while there was no association with headache.

Conclusion: This study indicates that treatment strategies for children with ADHD need to include an effective evaluation and treatment of RAP, tiredness and sleeping disturbances. Evaluation of ADHD should be considered in children with recurrent health complaints.
Fatal infant nasal seawater spray instillation
Authors: Novak Milivoj , Cvitkovic Miran , Galic Slobodan , Saric Dalibor , Cadez Josip , Dorcic Dorotea
Published: August 2010

The use of seawater nasal spray is considered safe and sold as a non‐prescription medicine. However, it is well known that nasal manipulations can provoke vagal reaction leading to acute life‐threatening events. A case of fatal seawater nasal spray application in an infant is presented.

Conclusion: We do not consider the use of seawater nasal spray to be absolutely safe, especially among infants with disordered autonomic function.
Secular change in adult stature has come to a halt in northern Europe and Italy
Authors: Larnkjær Anni , Attrup Schrøder Stine , Maria Schmidt Ida , Hørby Jørgensen Marianne , Fleischer Michaelsen Kim
Published: August 2010

Aim: To investigate whether the increase in adult stature in European countries is continuing.Methods: The secular trend in growth after 1990 for various European countries was assessed by national conscript data. Results: In Scandinavia and the Netherlands, the height has reached a plateau at 179–181 cm, and in Italy a plateau at 174 cm. In Belgium, Portugal and Spain, height continued to increase.

Conclusion: Only in the northern European countries and Italy height has ceased to increase.
General vaccination of children against influenza?
Authors: Trollfors Birger
Published: August 2010

Due to the high incidence of influenza in children, general vaccination has been discussed. There are, however, reasons to believe that general vaccination of children will not solve the influenza problem because influenza vaccines induce type‐specific immunity of short duration.

Conclusion: Vaccination of several cohorts of children will be a tremendous commitment, probably with little hope of success in decreasing the morbidity and spread of influenza.
Urological complications and copper replacement therapy in childhood Menkes syndrome
Authors: Zaffanello Marco , Maffeis Claudio , Fanos Vassilios , Franchini Massimo , Zamboni Giorgio
Published: August 2010

Background: Urological complications are frequent in Menkes syndrome, a very rare X‐linked recessive disorder of copper (Cu) metabolism. Aim: To evaluate the role of Cu therapy in preventing the progression of urological complications. Subjects and methods: We retrospectively enrolled 57 patients with Menkes syndrome (55 published case reports and two of our own unpublished cases) and investigated the reported urological complications, distinguishing the patients with or without Cu replacement therapy and evaluating the efficacy of this therapy in the prevention of urological complications. Results: The most frequent urological complication was bladder diverticulum (38.6% of the total patients); obstruction bladder outflow and rupture of the kidney were less frequent (both 1.8% of the total). The number of congenital urological complications increased progressively by age category; in fact, 77.8% of patients did not report urological complications at the age of 0.4±0.2 y, and 28.6% of them displayed ≥ two congenital urological complications at the age of 9.3±2.6 y. The percentage of urological complications found in younger patients not on Cu therapy did not differ from that of older patients treated with Cu therapy. A comparison between patients of the same age interval, who were or were not treated with Cu, showed that treated children had fewer urological complications than untreated children.

Conclusion: Our investigation suggests that Cu therapy in patients with Menkes syndrome does not prevent the progression of urological complications; however, it might delay their worsening.
Pleural effusions in the neonate
Authors: Rocha Gustavo , Fernandes Paula , Rocha Paula , Quintas Conceição , Martins Teresa , Proença Elisa
Published: August 2010

Introduction: Pleural effusions are rare in the neonate and may be associated to several clinical conditions. Only a few series of pleural effusions in the fetus and newborn are described in the literature.

Aim: This study was undertaken to determine more accurately the causes and prognostic significance of pleural effusions in a population of high‐risk neonates.

Materials and methods: A retrospective chart review of 62 neonates admitted to the neonatal intensive care unit of six medical centers in the north of Portugal, between 1997 and 2004, that presented the diagnosis of pleural effusion.

Results: 33M/29F newborns; preterms 47 (76%); GA 33 (25–40) wk; BW 1830 (660–4270) g; C‐section 39 (63%). Pleural effusions were congenital in 20 (32%) newborns and acquired in 42 (68%). Congenital pleural effusions occurred as fetal hydrops in 11 (18%) patients and as chylothorax in 9 (15%). In four cases of hydrops, the cause was a congenital chylothorax. Congenital chylothorax (n=13) was the most common (65%) congenital pleural effusion in this study. The incidence of congenital chylothorax was 1:8.600 deliveries and male:female ratio was 2:1. Mortality occurred in five newborns due to pulmonary hypoplasia. Traumatic (iatrogenic) were the most frequent (n=31) acquired pleural effusions. These included 8 (13%) cases of hemothorax and 8 (13%) cases of total parenteral nutrition leakage. Pleural effusions after intra‐thoracic surgery were mainly (79%) chylothoraces. There were 11 (26%) non‐iatrogenic acquired pleural effusions. No mortality was associated with acquired pleural effusions.

Conclusions: Congenital pleural effusions usually occur as hydrops or congenital chylothorax. Traumatic (iatrogenic) are the most frequent acquired pleural effusions in a tertiary NICU. Pleural effusions after intra‐thoracic surgery are mainly chylothoraces. Non‐iatrogenic acquired pleural effusions are associated to several clinical conditions, and mortality is usually associated to the underlying condition.
Decreasing ratio of plasma N‐terminal pro‐B‐type natriuretic peptide and B‐type natriuretic peptide according to age
Authors: Koch Andreas M.E. , Rauh Manfred , Zink Stefan , Singer Helmut
Published: August 2010

Background: B‐type natriuretic peptide (BNP) and the N‐terminal fragment of proBNP (NT‐proBNP) seem to be useful diagnostic tools also in children with cardiac disease. Recent data suggest that plasma levels of both peptides show different patterns from infancy to adolescence. Aim: To investigate the relationship of BNP and NT‐proBNP in children and adolescents according to age. Subjects and methods: In 46 individuals without cardiac disease (22 males, 24 females, aged 0.4–17.5 years) and 30 patients with congenital heart disease (17 males, 13 females, aged 0.2–18.4 years), plasma levels of BNP and NT‐proBNP were measured in the same sample (triage BNP assay, Biosite® and Elecsys NT‐proBNP assay, Roche Diagnostics®). Results: The range of BNP plasma levels was 5–32 pg/ml in individuals without heart disease and 5–1300 pg/ml in the patient group, the range of NT‐proBNP was 10–298 pg/ml and 30–18966 pg/ml, respectively. In both groups, the ratio NT‐proBNP/BNP decreased with increasing age (P<0.001). Conclusion: Although proBNP is cleaved into the two fragments NT‐proBNP and BNP, there is a decreasing ratio of NT‐proBNP/BNP with increasing age caused probably by age‐dependent differences in the metabolic clearance of both peptides. This has to be considered in comparison studies on BNP and NT‐proBNP regarding their benefit to paediatric cardiology.
Case‐control study of breast milk calcium in mothers of children with and without nutritional rickets
Authors: Thacher Tom D. , Pettifor John M. , Fischer Philip R. , Okolo Selina N. , Prentice Ann
Published: August 2010

Aim: Despite similarly low calcium intakes and normal vitamin D status, only some Nigerian children develop nutritional rickets. We hypothesized that mothers with children who had developed rickets might have lower breast‐milk calcium concentration than mothers with normal children and compared the breast‐milk calcium concentration of mothers who had had children with rickets with those who had not (controls). Methods: We collected breast milk from 35 Nigerian mothers who had previously had children with nutritional rickets. For each case mother, we collected breast milk from three matched control mothers at the same stage of lactation (±4 weeks) who had had no children with rickets. Data were collected about parity, stage of lactation, and the infant's intake. The mother's bone density was measured. Results: The mean breast milk calcium concentration of mothers of children with rickets (4.30±1.24 mmol/L) was less than that of control mothers (4.65±1.03 mmol/L; P=0.034 in multivariate regression controlling for duration of lactation and resumption of menses). Forearm bone mineral content was significantly related to breast milk calcium concentration (r = 0.20) after adjusting for height, weight, and bone area (P=0.028). Conclusion: : Reduced breast‐milk calcium concentration may contribute to a reduced calcium intake in infancy and predispose children to nutritional rickets.
Non‐alcoholic fatty liver disease in obese children evaluated by magnetic resonance imaging
Authors: Radetti Giorgio , Kleon Wolfgang , Stuefer Joseph , Pittschieler Klaus
Published: August 2010

Aim: To investigate the prevalence of non‐alcoholic fatty liver disease (NAFLD) in a group of obese children (BMI> 97th %) and to establish correlations between the severity of hepatic fatty infiltration, auxological findings and parameters of insulin resistance. Methods: 44 obese children, aged 6–16 years, with a BMI above the 97th centile were selected for analysis. Hepatic fat content was assessed by phase contrast MRI. Demographic data included weight, height, body mass index, body fat mass and waist circumference. Blood tests included fasting blood glucose, fasting insulin and lipid profile. Insulin sensitivity was evaluated with QUICKI. Results: Elevated hepatic fat fraction (FF) was identified in 14 subjects (31.8%; 0.07 SEM). Children with fatty liver (FF > 9%) had higher ALT (P<0.0001), AST (P=0.002) and triglycerides (P=0.008) values compared to the children without NAFLD. All the children showed a decreased insulin sensitivity (P<0.0001), but no difference was found between children with or without NAFLD. The degree of liver fatty infiltration was positively correlated with ALT (P<0.0001), AST (P<0.002) and γGT (P<0.0001), with height (P<0.006) and BMI (P<0.05) but not with estimates of body fat mass or fat distribution.

Conclusion: Obese children are frequently affected by NAFLD, which cannot be predicted by clinical and/or anthropometrical findings. There is however a strict correlation between the degree of liver fatty infiltration and elevation of liver enzymes.
Ultrasonographic evaluation of fatty meal stimulated gallbladder contraction in the diagnosis of biliary dyskinesia in children
Authors: Çay Ali , İmamoğlu Mustafa , Sarihan Haluk , Ahmetoğlu Ali
Published: August 2010

Aim: Biliary dyskinesia (BD) is characterized by symptoms of biliary disease, no evidence of gallstones on ultrasonography (USG), and diminished gallbladder ejection fraction. The diagnosis is based on findings of abnormal gallbladder ejection fraction diagnosed by hepatobiliary scintigraphy before and after stimulation of gallbladder contraction with cholecystokinin (CCK). We used an easier diagnostic technique defined as ultrasonographic evaluation of fatty meal stimulated gallbladder contraction, employing USG with the diagnosis of biliary dyskinesia in children. The study was conducted by USG to investigate the volume and contractility of the gallbladder (GB) in fasting conditions and 45 min after a standardized fatty meal (SFM) in normal children and in a group of BD patients, and to compare the diagnostic value of this test with scintigraphy and to evaluate its use as a new method in the diagnostic algorithm of BD. Methods: We assessed the volume changes and contractility of the GB in response to SFM by USG in 14 patients with BD diagnosed by cholecystokinin stimulated hepatobiliary scintigraphy (CCKs‐HBS); and compared them with 14 control patients matched for age and gender before cholecystectomy. After an overnight fasting, GB volume was measured by USG then the GB volume was again measured after the SFM ingestion. Using USG, length, width and height of GB were measured, and volume of the GB was calculated using the ‘Dodds’ formula. These volume measurements were used to calculate the percentage of gallbladder emptying (ejection fraction). Fasting, after SFM and EF values comparisons between groups were done with student's t‐test. Results: No statistically significant difference of fasting GB volumes were demonstrated between BD and control groups (14.1±6.7 cm3 and 13.4±4.0 cm3 respectively). GB volumes of the BD group after SFM were significantly greater than in healthy controls (13.1±1.8 cm3 and 3.4±0.9 cm3 respectively, P<0.0005). The calculated percentage of gallbladder contraction (ejection fraction) was found to be lower in BD patients than in healthy controls (7.1%±1.8% and 73.8%±6.4%, respectively, P<0.0005). Conclusion: Ultrasonographic evaluation of fatty meal stimulated gallbladder contraction provides relatively reliable and reproducible results. Thus it can be used for scanning in patients with biliary symptoms as a prior modality to CCK‐HBS since it is a relatively easier, safer and available method with which to make a definitive diagnosis of BD. The patients with symptoms of biliary disease and no evidence of gallstones on USG should be evaluated by the method proposed in this study before the routine laboratory and radiologic tests.
Reliability of motor development data in the WHO Multicentre Growth Reference Study
Authors:   WHO MULTICENTRE GROWTH REFERENCE STUDY GROUP, de Onis Mercedes
Published: August 2010

Aim:To describe the methods used to standardize the assessment of motor milestones in the WHO Multicentre Growth Reference Study (MGRS) and to present estimates of the reliability of the assessments.

Methods:As part of the MGRS, longitudinal data were collected on the acquisition of six motor milestones by children aged 4 to 24 mo in Ghana, India, Norway, Oman and the USA. To ensure standardized data collection, the sites conducted regular standardization sessions during which fieldworkers took turns to examine and score about 10 children for the six milestones. Assessments of the children were videotaped, and later the other fieldworkers in the same site watched the videotaped sessions and independently rated performances. The assessments were also viewed and rated by the study coordinator. The coordinator's ratings were considered the reference (true) scores. In addition, one cross‐site standardization exercise took place using videotapes of 288 motor assessments. The degree of concordance between fieldworkers and the coordinator was analysed using the Kappa coefficient and the percentage of agreement.

Results:Overall, high percentages of agreement (81–100%) between fieldworkers and the coordinator and “substantial” (0.61–0.80) to “almost perfect” (>0.80) Kappa coefficients were obtained for all fieldworkers, milestones and sites. Homogeneity tests confirm that the Kappas are homogeneous across sites, across milestones, and across fieldworkers. Concordance was slightly higher in the cross‐site session than in the site standardization sessions. There were no systematic differences in assessing children by direct examination or through videotapes.

Conclusion:These results show that the criteria used to define performance of the milestones were similar and applied with equally high levels of reliability among fieldworkers within a site, among milestones within a site, and among sites across milestones.
WHO Child Growth Standards based on length/height, weight and age
Authors:   WHO MULTICENTRE GROWTH REFERENCE STUDY GROUP, de Onis Mercedes
Published: August 2010

Aim:To describe the methods used to construct the WHO Child Growth Standards based on length/height, weight and age, and to present resulting growth charts.Methods:The WHO Child Growth Standards were derived from an international sample of healthy breastfed infants and young children raised in environments that do not constrain growth. Rigorous methods of data collection and standardized procedures across study sites yielded very high‐quality data. The generation of the standards followed methodical, state‐of‐the‐art statistical methodologies. The Box‐Cox power exponential (BCPE) method, with curve smoothing by cubic splines, was used to construct the curves. The BCPE accommodates various kinds of distributions, from normal to skewed or kurtotic, as necessary. A set of diagnostic tools was used to detect possible biases in estimated percentiles or z‐score curves.Results:There was wide variability in the degrees of freedom required for the cubic splines to achieve the best model. Except for length/height‐for‐age, which followed a normal distribution, all other standards needed to model skewness but not kurtosis. Length‐for‐age and height‐for‐age standards were constructed by fitting a unique model that reflected the 0.7‐cm average difference between these two measurements. The concordance between smoothed percentile curves and empirical percentiles was excellent and free of bias. Percentiles and z‐score curves for boys and girls aged 0–60 mo were generated for weight‐for‐age, length/height‐for‐age, weight‐for‐length/height (45 to 110 cm and 65 to 120 cm, respectively) and body mass index‐for‐age.

Conclusion:The WHO Child Growth Standards depict normal growth under optimal environmental conditions and can be used to assess children everywhere, regardless of ethnicity, socio‐economic status and type of feeding.
Lysosomal dysfunction, cellular pathology and clinical symptoms: basic principles
Authors: Reuser Arnold J. J. , Drost Maarten R.
Published: August 2010

Between 40 and 50 lysosomal storage disorders are known at present. Fine details of the pathogenic process involved are in general not known. This overview highlights the basic principles of lysosomal pathogenesis and the clinical consequences of defective genes involved in lysosomal functions. The subject is discussed in the context of the possibility of prevention and reversal of cellular and organ damage by enzyme replacement therapy. Also presented is a mechanical model for the muscle pathology observed in Pompe disease. Direct mechanical effects of the non‐contractile inclusions – glycogen‐loaded lysosomes – seem to be a key factor in the loss of force during both early and late stages of the disease.

Conclusion: Each lysosomal storage disorder and each patient with a given lysosomal disorder has unique molecular, pathological and clinical features. But, the order of pathological events is largely the same. Mutations in a gene cause lysosomal dysfunction which, in turn, results in cellular pathology affecting organ structure and function. Clinical symptoms are the ultimate manifestation. The reversibility of symptoms with enzyme replacement therapy will vary according to the disease, as well as the nature and stage of organ pathology.
FABRY DISEASE – CLINICAL MANIFESTATIONS AND GENETICS
Authors: Karetova D. , Bultas J. , Linhart A. , Lubanda J.C. , Magage S. , Uklikova P. , Palecek T. , Ledvinova J. , Poupetova H. , Dobrovolny R. , Hrebicek M. , Elleder M.
Published: August 2010

Background: The severity of organ impairment in heterozygous females with Fabry disease may be as serious as in males. It has been repeatedly shown that the incidence of affected organs increases with age and comes one decade later than in males. Besides age, the process of X inactivation also has an important influence. The ratio between inactivated normal and defective chromosomes could influence the level of the key enzyme: α‐galactosidase A. We have tried to prove this hypothesis.

Methods and Results: Analysis of this relationship was carried out in a cohort of 54 heterozygous females (average age, 41.2 years) from 16 families. Diagnosis of Fabry disease was based on the identification of a chromosomal defect. We used the Mainz Severity Score Index to evaluate the extent of disease. To clarify the relationship between levels of α‐galactosidase A in leukocytes, age and organ impairment, we conducted multivariant analysis. The correlation coefficients were highly significant for age (r = 0.5765, p < 0.0001) and for α‐galactosidase A activity (r = − 0.4856, p < 0.05). For better demonstration of the relationship, the cohort of women was divided into tertiles according to age and α‐galactosidase A activity in leukocytes (Figure 1).

Correlation between the Mainz Severity Score Index (MSSI), age and α‐galactosidase A activity in leukocytes (nmol/h/mg) in females with Fabry disease

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Conclusion: From the presented graph and correlation analysis it is clear that, in addition to age, the level of α‐galactosidase A in leukocytes is also an important predictor of the degree of organ involvement in heterozygous females with Fabry disease.
Clearing of globotriaosylceramide from endothelial vessels of ocular conjunctiva in patients with Fabry disease treated with agalsidase alfa
Authors: Rozenfeld P. , Ebner R. , Croxatto O. , Fossati C.
Published: August 2010

Introduction: Fabry disease is an X‐linked inborn metabolic error caused by a deficiency of lysosomal α‐galactosidase A. Globotriaosylceramide (Gb3) accumulates in lysosomes of various cells. At the moment, enzyme replacement therapy (ERT) is the only available specific treatment for patients with Fabry disease. Enzyme infusions reduce the Gb3 content of plasma, urine sediment and tissue. In a previous study, we reported the development of a method to specifically detect Gb3 deposits by immunofluorescence in conjunctival biopsies.

Aim: The aim of this work is to evaluate the clearance of Gb3 in cells from the conjunctiva in patients with Fabry disease treated with agalsidase alfa.

Methods: Conjunctival biopsies were obtained from three hemizygous and two heterozygous patients, before and after 6 months of treatment with agalsidase alfa. The specimens were processed for direct immunofluorescence using an anti‐Gb3 monoclonal antibody and light microscopy using a mouse polyclonal antiserum specific for α‐galactosidase A.

Results: Positive immunofluorescence was not observed in cells from the blood vessels of patients with Fabry disease after 6 months of treatment, as compared with the specimens before the treatment, which were positive. We detected Gb3 in stromal/macrophage cells that were distal from the blood vessels where the enzyme was circulating. Specific staining for α‐galactosidase A revealed the presence of this protein in the tissue of patients after ERT, but not before.

Conclusion: Agalsidase alfa eliminated Gb3 deposits from the cells of blood vessel walls in patients with Fabry disease after 6 months of treatment. The deposits in stromal cells were not removed, probably because the enzyme must diffuse into the tissue to reach these cells and/or because of the short length of therapy. This method may be useful to evaluate the effectiveness of ERT.
UNTERSUCHUNGEN ÜBER S. ABORTUS BOVIS, S. SCHLEISSHEIM SOWIE ZWEI NEUE SALMONELLA‐TYPEN S. ABONY UND S. TEL‐AVIV.
Authors: Kauffmann F.
Published: August 2010

1. Es wird ein neuer serologischer Salmonella‐Typus S. abony beschrieben, dessen Antigenformel I. IV. V. b ? e, n, x lautet, und der nahe serologische Beziehungen zu S. abortus bovis I. IV.XXVII. b ? e, n, x und S. schleissheim IV. XXVII. b, z12 ‐ hat.

2. Es wird als Erreger einer Seuche unter Küken ein neuer Salmonella‐Typus S. tel‐aviv beschrieben, dessen Antigen‐formel XXVIII. y ? e, n lautet.
ÜBER DAS SOG. MYOBLASTENMYOM MIT BESCHREIBUNG 7 NEUER FÄLLE.
Authors: Ringertz Nils
Published: August 2010

Die Abrikossoffschen sog. Myoblastenmyome wurden vom Verf. an Hand eines eigenen Materials von 7 bisher unveröffentlichten Fällen studiert, und ferner wurde das Primärmaterial bei 4 von Frenckner früher beschriebenen Fällen untersucht. Aus dem Schrifttum wurden weitere 66 Fälle zusammengestellt, welche nach Verf.s Ansicht sicher Gebilde von dieser Art sind. Dieses Gesamtmaterial von 77 Fällen wurde mit Bezug auf Geschlechts‐ und Altersverteilung (Abb. 1), makroskopische Anatomie sowie biologische Eigenschaften bearbeitet.

Verf. will nachdrücklich betonen, dass die sarkomatösen Tumoren, welche in der Literatur under der Bezeichnung malignes Myoblastenmyom, Myoblastom etc. beschrieben worden sind, nichts mit den charakteristischen Abrikossoff‐schen Geschwülsten zu tun haben. Die letzteren haben stets gutartigen Charakter.

Verf. bestreitet, dass irgendein Übergang zwischen quergestreiften Muskelzellen und den granulierten Zellen des Myoblastenmyoms vorkommt oder dass die granulierten Zellen eine Streifung aufweisen können. Bilder, welche in diesem Sinne gedeutet worden sind, treten in Zungen‐ und Lippentumoren dieser Art auf, sind aber Trugbilder, welche dort zustandekommen, wo granulierte Zellen Muskelfaserbündel interstitiell infiltrieren. Zwei vom Verf. untersuchte Fälle deuten darauf hin, dass die Zungentumoren submukös entstehen und die Zungenmuskulatur sekundär infiltrieren, nicht umgekehrt, wie früher geltend gemacht worden war. Auf Grund des soeben angeführten und der Tatsache, dass ungefähr die Hälfte sämtlicher bekannter Myoblastenmyome an Stellen sassen, wo keine quergestreifte Muskulatur vorhanden ist, steht Verf. auf dem Standpunkt, dass die Annahme, diese Gebilde hätten irgendeinen genetischen Zusammenhang mit der Muskulatur, völlig unbegründet ist. Es wird auch darauf hingewiesen, dass die Angabe Abrikossoffs, die granulierten Zellen des Myoblastenmyoms seien embryonalen Myoblasten ähnlich, nicht richtig ist.

Nach Verf.s Ansicht sind also diese Gebilde nicht myogen, sondern die granulierten zellen, aus welchen sie sich zusammensetzen, entstehen im Bindegewebe und können bei gewissen Lokalisationen die Muskulatur infiltrieren. Ob die Gebilde den Charakter wirklicher Neoplasmen haben, ist zweifelhaft; als Hypothese könnte in Betracht kommen, dass sie durch eine örtliche Störung des Proteinstoffwechsels entstehende Speicherungstumoren sind.