bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathophysiology and assessment of neuropathic pain in Fabry disease
Authors: Schiffmann R , Scott LJC
Published: August 2010

Severe neuropathic pain and hypohidrosis are important symptoms of Fabry disease, particularly in the first three decades of life. The pain is associated with a length‐dependent small‐fibre neuropathy that also causes a selective deficiency of cold perception. Cold exposure often accentuates the pain and worsens thermal perception. The hypohidrosis leads to poor exercise and heat tolerance. The mechanisms by which α‐galactosidase A deficiency causes these physiological abnormalities are poorly understood. The stored glycolipid (globotriaosylceramide) may interfere with the function of cellular membrane proteins, such as ion channels, or may lead to cytotoxicity. The characteristic neuropathic pain can be symptomatically treated with various types of anticonvulsant drugs, such as carbamazepine. Improvement in neuropathic pain as a primary outcome measure has been useful in demonstrating that enzyme replacement therapy is effective in improving pain‐related quality of life in Fabry disease.

Conclusions: The dysfunction of the peripheral nervous system is easily assessable and more readily reversible with specific therapy than the destructive processes that occur in organs such as the kidney. In future, therefore, it is likely that neuropathic pain, quantitative sensory testing and hypohidrosis will serve as clinical outcome measures for studies of specific and effective therapies for Fabry disease.
Arterial remodelling in Fabry disease
Authors: Boutouyrie P , Laurent S , Laloux B , Lidove O , Grunfeld JP , Germain DP
Published: August 2010

Aim: The enzymatic defect in Fabry disease results in the slow systemic deposition of uncleaved glycosphingolipids in the lysosomes of vascular endothelium and smooth muscle cells, leading to ischaemic strokes, cardiomyopathy and renal failure. Whereas it is known that Fabry disease affects small blood vessels, little is known about its effects on peripheral large arteries. We therefore set out to compare parameters of arterial wall structure and function in a cohort of patients with Fabry disease and an age‐matched control group. Methods: Large artery phenotype was non‐invasively investigated in 21 hemizygous patients with Fabry disease and 24 age‐matched male controls. Common carotid and radial artery diameter, intima‐media thickness (IMT) and distensibility were determined with high‐definition echotracking systems and aplanation tonometry. Results: Patients with Fabry disease had a significant twofold increase in radial artery IMT and distensibility, independent of body surface area, age and mean blood pressure. In both groups, older age at the time of examination was significantly associated with larger radial artery IMT. The relationship between age and radial IMT was 2.3‐fold higher in patients with Fabry disease than in controls (p > 0.01). Carotid IMT was mildly but significantly increased in patients with Fabry disease (+18%), whereas distensibility was unchanged.

Conclusion: This study presents evidence of a major increase in arterial wall thickness and distensibility, measurable at the site of a medium‐sized artery, in a cohort of patients with classic Fabry disease.
Non‐viral transfer approaches for the gene therapy of mucopolysaccharidosis type II (Hunter syndrome)
Authors: Tomanin R , Friso A , Alba S , Puicher E Piller , Mennuni C , Monica N La , Hortelano G , Zacchello F , Scarpa M
Published: August 2010

Aims: Hunter syndrome is a rare X‐linked lysosomal storage disorder caused by the deficiency of the housekeeping enzyme iduronate‐2‐sulphatase (IDS). Deficiency of IDS causes accumulation of undegraded dermatan and heparan‐sulphate in various tissues and organs. Approaches have been proposed for the symptomatic therapy of the disease, including bone marrow transplantation and, very recently, enzyme replacement. To date, gene therapy strategies have considered mainly retroviral and adenoviral transduction of the correct cDNA. In this paper, two non‐viral somatic gene therapy approaches are proposed: encapsulated heterologous cells and muscle electro‐gene transfer (EGT). Methods: Hunter primary fibroblasts were co‐cultured with either cell clones over‐expressing the lacking enzyme or with the same incorporated in alginate microcapsules. For EGT, plasmid vector was injected into mouse quadriceps muscle, which was then immediately electro‐stimulated. Results: Co‐culturing Hunter primary fibroblasts with cells over‐expressing IDS resulted in a three‐ to fourfold increase in fibroblast enzyme activity with respect to control cells. Fibroblast IDS activity was also increased after co‐culture with encapsulated cells. EGT was able to transduce genes in mouse muscle, resulting in at least a tenfold increase in IDS activity 1–5 weeks after treatment.

Conclusion: Although preliminary, results from encapsulated heterologous cell clones and muscle EGT encourage further evaluations for possible application to gene therapy for Hunter syndrome.
Unexplained infant crying: an evolutionary perspective*
Authors: Hofer MA
Published: August 2010

The absence of adverse health outcomes later in development and the similarity of defining features of “colic” across cultures suggest that an evolutionary perspective may give us some insight into the nature of this puzzling condition. Evidence suggests that the larynx evolved first as a protective valve and later as a means to stabilize the upper thorax momentarily for precision upper arm movements. Recently, we found another physiological role for the larynx in regulating respiratory function to promote the recovery of young rats from severe hypothermia. In the process, bursts of calling were emitted by unconscious pups, which were nevertheless effective in eliciting maternal search and retrieval. These unexpected findings reveal how infant calling may have evolved as a communicative signal derived from more primitive physiological functions of the larynx. Repetitive calling in the normal young rat when isolated from its littermates and mother is regulated by multiple sensory cues present in the infant's social interactions, and in the paper it is described how this sensory input projects to central neuromodulatory systems known to be active in the control of anxiety behaviors in adult rats and humans.

Conclusion: This broad range of functions for infant calling in other mammals suggests several new ways to approach the further study and treatment of unexplained crying in human infants.
Plasma total homocysteine increases from day 20 to 40 in breastfed but not formula‐fed low‐birthweight infants
Authors: Fokkema MR , Woltil HA , van Beusekom CM , Schaafsma A , Dijck‐Brouwer DAJ , Muskiet FAJ
Published: August 2010

Homocysteine is an intermediate in the folate cycle and methionine metabolism. This study investigated whether formula‐fed infants have different plasma total homocysteine to their breastfed counterparts, and during what period any difference developed. Plasma total homocysteine was determined in 53 formula‐fed and 15 breastfed healthy low‐birthweight babies (≫2500 g) around days 10, 20 and 40. Total homocysteine was also measured in human milk. Mean ± SD plasma total homocysteine levels (μmol 1‐1) at days 10, 20 and 40 were 6.4 ± 2.6, 6.7 ± 2.4 and 9.1 ± 2.4 (breastfed), and 7.5 ± 3.2, 7.3 ± 2.1 and 7.4 ± 1.6 (formula‐fed). Homocysteine of breastfed babies at day 40 was higher than that of breastfed babies at day 20 (p > 0.0001), and that of formula‐fed counterparts at day 40 (p= 0.002). Homocysteine correlated negatively with formula (day 10) and breast milk (day 40) volume intakes. Median (range) homocysteine in 12 mature human milk samples was 0.30 (not detectable to 0.7) μmol 1−1.

Conclusion: Increasing plasma total homocysteine in breastfed babies to higher levels compared with formula‐fed babies may be caused by a gradually developing suboptimal B‐vitamin status in lactating women.
Impact of topical oils on the skin barrier: possible implications for neonatal health in developing countries
Authors: Darmstadt GL , Mao‐Qiang M , Chi E , Saha SK , Ziboh VA , Black RE , Santosham M , Elias PM
Published: August 2010

Topical therapy to enhance skin barrier function may be a simple, low‐cost, effective strategy to improve outcome of preterm infants with a developmentally compromised epidermal barrier, as lipid constituents of topical products may act as a mechanical barrier and augment synthesis of barrier lipids. Natural oils are applied topically as part of a traditional oil massage to neonates in many developing countries. We sought to identify inexpensive, safe, vegetable oils available in developing countries that improved epidermal barrier function. The impact of oils on mouse epidermal barrier function (rate of transepidermal water loss over time following acute barrier disruption by tape‐stripping) and ultrastructure was determined. A single application of sunflower seed oil significantly accelerated skin barrier recovery within 1 h; the effect was sustained 5 h after application. In contrast, the other vegetable oils tested (mustard, olive and soybean oils) all significantly delayed recovery of barrier function compared with control‐ or Aquaphor‐treated skin. Twice‐daily applications of mustard oil for 7 d resulted in sustained delay of barrier recovery. Moreover, adverse ultrastructural changes were seen under transmission electron microscopy in keratin intermediate filament, mitochondrial, nuclear, and nuclear envelope structure following a single application of mustard oil.

Conclusion: Our data suggest that topical application of linoleate‐enriched oil such as sunflower seed oil might enhance skin barrier function and improve outcome in neonates with compromised barrier function. Mustard oil, used routinely in newborn care throughout South Asia, has toxic effects on the epidermal barrier that warrant further investigation.
Food intake and oral sucrose in preterms prior to heel prick
Authors: Storm H , Fremming A
Published: August 2010

To investigate the soothing effect of feeding on infants in distress, the effects of 2mL 15% and 1 mL 25% sucrose given orally 2 min before heel prick in fasting preterms to reduce the pain response were assessed. The effects of milk intake by nasogastric tube were also assessed once during the last hour before heel prick, and the effects of milk intake by nasogastric tube once during the last hour before heel prick together with 1 mL 25% sucrose given orally 2 min before heel prick. The pain response was measured as changes in crying time, behavioural state, skin conductance and heart rate. Each group included 12 healthy preterm infants with a median gestational age of 32 wk and a median postnatal age of 14 d. These infants were randomly studied twice; one in connection with the intervention and once after being given sterilized water. Differences in the measured variables before and during heel prick showed that only the crying time was reduced when the infants received milk or 25% sucrose prior to heel prick (p > 0.05). If the infants received milk and 25% sucrose before heel prick, the crying time and the level of behavioural state were reduced (p > 0.05). The increase from before to during heel prick in skin conductance (number and amplitude of the waves) and heart rate correlated with the crying time (p > 0.01).

Conclusion: This study supports the hypothesis that sucrose has an antinociceptive effect and suggests that food should also be given to preterm neonates prior to procedural pain.
Epinephrine treatment of hypotension in very low birthweight infants*
Authors: Heckmann M , Trotter A , Pohlandt F , Lindner W
Published: August 2010

The aim of this study was to examine the influence of a continuous infusion of epinephrine (adrenaline) on mean arterial blood pressure (MABP), heart rate, urine output and base deficit in very low birthweight infants (VLBWI) with systemic hypotension. In VLBWI who received an infusion of epinephrine for at least 12 h the mean urine output, administered fluid volume, base deficit and administered buffer 12 h before and 12 h during the infusion were recorded. If the infusion was shorter, but given for at least 2 h, the mean heart rate and MABP 2 h before and 2 h during the infusion were recorded. Thirty‐one infants with a gestational age of 26 (23–30) wk [median (minimum‐maximum)] and birthweight 690 (390–1310) g were included in this retrospective chart review. The patients received an infusion of epinephrine at a postnatal age of 3 (1–21) d. The doses ranged between 0.05 and 2.6 μg kg‐1 per minute within the first 24 h of administration. Three of 31 infants received epinephrine on 2 different occasions. The MABP [+7 (–1 to 13) mmHg, p= 0.000001] and the heart rate [+10 (–10 to 42) bpm, p= 0.000036] increased significantly (n= 34), whereas total volume administration and urine output remained the same between the 2 periods (Wilcoxon matched pairs test). The base deficit increased significantly [–3 (–10.2 to 2.6), p= 0.0014, n= 19] without a change in the administration of buffer.

Conclusion: The infusion of epinephrine increased the MABP and the heart rate without decreasing urine output in VLBWI with hypotension not responding to a dopamine infusion up to 15 μg kg‐1 per minute. A potential adverse effect was an increase in metabolic acidosis.
Population‐based rates of severe respiratory syncytial virus infection in children with and without risk factors, and outcome in a tertiary care setting
Authors: Eriksson M , Bennet R , Rotzén‐Östlund M , von Sydow M , Wirgart B Zweygberg
Published: August 2010

The aim of this study was to make a population‐based estimate of the risk of hospitalization and complications during virologically confirmed respiratory syncytial virus (RSV) infection in relation to established risk factors, and an estimation of additional risk factors and outcome as seen in a tertiary care referral centre. During a period of 12 y, all children with virologically confirmed RSV infection were included. Recorded complications were: admission to the intensive care unit, mechanical ventilation, death and later hospitalization for wheezing. In total, 1503 cases were identified, 1354 of which originated from the population defined by the catchment area. There was a biannual seasonal variation with late small outbreaks alternating with early large ones. The hospitalization rates for infants without risk factors were 0.8 and 1.4% during the 2 epidemic types. They were 1.6–3.2% for infants born preterm (>33 gestational wk), 2.9–7.0% for children under 2 y old with chronic lung disease of prematurity and 2.8–6.4% for infants with congenital heart disease. The presence of siblings in the family more than doubled the risk of hospitalization. Later hospitalization for wheezing occurred in 8.4 and 4.9% of children without risk factors over and under the age of 2 mo, respectively (p > 0.001).

Conclusion: This study found lower population rates of hospitalization and complications than have previously been reported. The seasonal variation and the presence of siblings in the home influenced these rates by factors of 2.
Norms for grip strength in children aged 4–16 years
Authors: Häger‐Ross C , Rösblad B
Published: August 2010

The aim of this study was to provide norms for grip strength in children. A total of 530 Swedish 4–16‐y‐olds was tested with the instrument Grippit®. The instrument estimates peak grip strength over a 10 s period, and sustained grip strength averaged across the 10 s. The increase in grip strength with age was approximately parallel for boys and girls until 10 y of age, after which boys were significantly stronger than girls. Strong correlations existed between grip strength and the anthropometric measures weight, height and, in particular, hand length. Right‐handed children were significantly stronger in their dominant hand, while left‐handers did not show any strength difference between the hands. It is therefore suggested that when evaluating grip strength in left‐handed children both hands should be assumed to be about equally strong, while right‐handed children are expected to be up to 10% stronger with their right hand. Sustained grip strength was consistently about 80–85% of peak grip strength, with somewhat lower values in younger children. The present normative data for peak grip strength were slightly lower than 1980s' data from the USA and Australia, probably because of divergences in age grouping and in instruments used.

Conclusion: Norms for grip strength including estimates of variation were provided for children aged 4–16 y. These data will enable therapists and physicians to compare a patient's score with the scores of normally developed children according to age, gender, handedness and body measures.
Intravenous rifampicin in neonates with persistent staphylococcal bacteraemia
Authors: Shama A , Patole SK , Whitehall JS
Published: August 2010

Addition of intravenous rifampin is reported to be useful in prompt clearance of persistent coagulase negative staphylococcal (CONS) bacteraemia in high‐risk neonates. Four neonates (mean birthweight 823 g, mean gestation 25 wk) with persistent CONS bacteraemia for < 7–10 d (mean 11) were treated with i.v. rifampicin (10mg/kg/12 h ± 10 d) while continuing vancomycin (15mg/kg/24 h). Their age at time of infection ranged from 2 to lid. The mean (range) vancomycin peak and trough concentrations were 29 (25–35) and 6 (4–10) μg/ml, respectively. The blood isolates were Staphylococcus epidermidis, S. hominis, and S. haemolyticus. Addition of rifampicin was associated with prompt clearance of bacteraemia within 48 h (n= 3) and 5 d (n– 1). Rifampicin‐related adverse effects such as abnormal liver function tests and thrombocytopenia did not occur.

Conclusion: Addition of i.v. rifampicin to vancomycin may optimize the outcome of persistent CONS bacteraemia and the risk of bacterial resistance related to prolonged exposure to vancomycin.
Changes in serum leptin concentration after corticosteroid treatment in preterm infants
Authors: Ng PC , Lam CWK , Lee CH , Fok TF , Chan IHS , Ma KC , Wong E
Published: August 2010

The aim of this study was to investigate the effect of postnatal systemic dexamethasone on serum leptin, insulin and hormones of the hypothalamic‐pituitary‐adrenal (HPA) axis in preterm, very low birthweight (VLBW) infants. Nineteen VLBW infants who received a 3 wk dose tapering course of dexamethasone for treatment of bronchopulmonary dysplasia were prospectively enrolled. Blood for hormone assays was collected immediately before the start of the dexamethasone course (Td‐pre), 3 wk after commencement of the drug (Td‐end) and 2 wk after dexamethasone treatment had been stopped (Td‐post). In addition, 28 VLBW infants who participated in a concurrent longitudinal leptin study within the same period but did not receive corticosteroid had their serum leptin and insulin concentrations serially monitored. Blood specimens for the latter group of infants were obtained at 2 (Twk–2), 5 (Twk–5) and 7 (Twk–7) wk of postnatal age. Serum leptin and insulin at Td–end were significantly increased, whereas plasma ACTH and serum cortisol were significantly suppressed compared with the pretreatment (Td–pre) levels in the corticosteroid group (p > 0.0001 for leptin and insulin; p > 0.05 and p > 0.001 for ACTH and cortisol, respectively). In contrast, serum leptin and insulin at weeks 5 (Twk–5) and 7 (Twk–7) did not differ significantly from their respective levels at week 2 (Twk–2) in the non‐treatment group.

Conclusion: The administration of systemic corticosteroid resulted in significant increases in serum leptin and insulin, but marked suppression of hormones of the HPA axis. The effect of dexamethasone on the “adipoinsular” and HPA axes was transient and reversible. The adipoinsular axis in preterm infants is likely to be functional and active at an early stage of human development, and leptin may regulate energy balance in VLBW infants in the early postnatal period. Corticosteroids may, through the adipoinsular axis or its associated pathways, mediate in the regulation of body weight in preterm neonates.
An intestinal obstruction in an eight‐month‐old child suffering from mevalonic aciduria
Authors: Nimubona L , Laloum D , Rolland M‐O , Read M‐H , Guillois B , Duhamel JF
Published: August 2010

This report describes a case of mevalonate kinase deficiency diagnosed at 1 mo of age. Soon after delivery, symptoms were suggestive of congenital infection. An intestinal occlusion occurred towards the age of 8 mo.

Conclusion: Mevalonate kinase deficiency has variable clinical and biological signs which can lead to a delay in diagnosis. This is the first reported occurrence of bowel obstruction in this disease and the resemblance to a congenital infection in the neonatal period must be emphasized.
D‐2‐Hydroxyglutaric aciduria and subdural haemorrhage
Authors: Kwong KL , Mak T , Fong CM , Poon KH , Wong SN , So KT
Published: August 2010

D‐2‐Hydroxyglutaric aciduria (D‐2‐HG) is a rare metabolic disorder. First reported in 1980, it does not have any well‐recognized presentation or specific treatment regimen. Neuroimaging findings are heterogeneous. Subdural haemorrhage has not been a feature of any of the reported cases. This report presents a boy with bilateral subdural haematoma in whom non‐accidental injury was initially suspected and subsequent metabolic investigation led to a diagnosis of D‐2‐HG.

Conclusion: In the management of childhood subdural haemorrhages, it is very important that potentially treatable metabolic disorders are detected and that parents are not wrongly accused of injuring their children.
Long‐chain 3‐hydroxyacylCoA dehydrogenase deficiency: a new case presenting with liver dysfunction, cholestasis and fibrosis
Authors: Odievre M‐H , Sevin C , Laurent J , Laboureau J‐P , Rabier D , Brivet M , Roe C , Wanders RJA , Saudubray J‐M
Published: August 2010

A cholestatic 6‐mo‐old girl was admitted to our department because she recently presented with hypotonia and lethargy, apparently due to moderate and transient hypoglycaemia. Her urine contained 3‐hydroxy‐dicarboxylic acids of 12 to 14 carbons in length and her plasma acylcarnitine profile was consistent with long‐chain 3‐hydroxyacylCoA dehydrogenase deficiency. This diagnosis was confirmed by enzyme studies. This deficiency was due to a G1528C mutation on the paternal allele (mutation on the maternal allele as yet not identified). The patient improved dramatically with medium‐chain triglyceride supplementation.

Conclusion: Early cholestasis and hepatic fibrosis must lead to search for long‐chain 3‐hydroxyacylCoA dehydrogenase deficiency, particularly when hypoketotic hypoglycaemia is present.
Dynamics of progression markers in a non‐study population of human immunodeficiency virus‐1 vertically infected infants with different antiretroviral treatments
Authors: Resino S , Bellón JM , Gurbindo D , Ramos JT , León JA , Muñóz‐Fernández MÁ
Published: August 2010

Treatment with highly active antiretroviral therapy (HAART) has been shown to modify viral replication dynamics and lead to a significant recovery of CD4+ T‐cells. A retrospective multicentre observational study was performed in a non‐study population of 151 HIV‐1‐infected children, categorized into four groups according to therapy: untreated (NT), on monotherapy (MT) with a nucleoside inhibitor, on combination therapy (CT) with two nucleoside inhibitors, and on HAART, protease inhibitor containing regimens, to assess the “real‐life” effectiveness of these different therapies on plasma viral load (VL) and CD4+ T‐cells. VL was quantified using a standard molecular assay. CD4+ and CD8+ T‐cells subsets were determined by flow cytometry. The HAART group showed the highest relative proportion (RP) of increases in 5, 10, 15 and 20% of CD4+ T‐cells over baseline, and the earliest fall‐off of VL (0.5,1, 1.5 and 2 log10 copies ml‐1). The RP of the fall‐off of 0.5,1, 1.5 and 2 log10 VL below baseline was 3‐fold higher in HAART group than in the MT and CT groups. However, no differences were found among the groups of treated children in reaching undetectable VL.

Conclusion: A better evolution of VL and CD4+ T‐cells was evident in children on HAART, indicating a positive effect on the immune system and clinical status, inhibiting HIV‐1 replication and enabling the recovery of CD4+ T‐cell counts.
Characteristic profile of intestinal microflora in Kawasaki disease
Authors: Takeshita S , Kobayashi I , Kawamura Y , Tokutomi T , Sekine I
Published: August 2010

To investigate whether the ecology of the intestinal microflora may change in the acute phase of Kawasaki disease (KD), the distribution pattern was studied of common micro‐organisms in feces from 20 patients with KD, 20 patients with acute febrile diseases (disease control) and 20 healthy children. KD patients had a significantly lower (p > 0.001) incidence of Lactobacillus (2/20, 10%) than disease control patients (16/20, 80%) and healthy children (14/20,70%). KD patients had no significant incidences of other microbial genera, compared with both disease control and healthy children.

Conclusion: The results suggest that a lack or loss of the beneficial Lactobacillus genus in the enteric microflora may occur during the acute phase of KD.
Body composition in infants with chronic lung disease after treatment with dexamethasone
Authors: Bolt RJ , van Weissenbruch MM , Roos JC , de Waal HA Delemarre‐van , Cranendonk A , Lafeber HN
Published: August 2010

The aim of this study was to study the effect of chronic lung disease (CLD) and dexamethasone treatment on body composition in preterm infants (birthweight > 1500g). In addition, anthropo‐metric measurement of body composition were compared with dual‐energy X‐ray absorptiometry (DXA). Fourteen preterm infants with CLD and a comparison group of 18 preterm infants were studied until 3 mo corrected age. CLD infants received approximately 20 kcal kg‐1 per day extra nutritional intake during dexamethasone treatment until term. At term no differences were found between CLD and no CLD infants for percentage bone mass (1.4 ± 0.2 vs 1.4 ± 0.1%), fat mass (18.7 ± 4.5 vs 17.4 ± 3.5%), lean body mass (79.9 ± 4.6 vs 81.2 ± 3.5%) or bone mineral density (0.15 ± 0.02 vs 0.15 ± 0.01%). At 3 mo corrected age both groups were also similar for bone mass (1.6 ± 0.1 vs 1.6 ± 0.2%), fat mass (22.6 ± 5.5 vs 24.5 ± 5.7%), lean body mass (75.8 ± 5.7 vs 74.0 ± 5.8%) and bone mineral density (0.20 ± 0.02 vs 0.20 ±0.01%). All anthropometric measurements showed a high correlation with body composition. However, calculated fat mass was 56.7 ± 8.8% lower than fat mass measured with DXA.

Conclusion: Body composition at term and 3 mo corrected age in preterm infants treated with dexamethasone for CLD, who received extra caloric intake until term, did not differ from that in preterm infants without CLD.
Prevalence and associated impairments of mild mental retardation in six‐ to ten‐year old children in Pakistan: a prospective study
Authors: Bashir A , Yaqoob M , Ferngren H , Gustavson K‐H , Rydelius P‐A , Ansari T , Zaman S
Published: August 2010

The aim of this study was to find the prevalence of mild mental retardation (MMR) in 6–10‐y‐old children in a prospectively followed cohort in Pakistan from four areas with different socioeconomic conditions. Retarded children were identified by a two‐step method, comprising a household screening with the Ten Questions Screening in 649 families followed by clinical investigation and psychometric testing (WISC‐R and Griffiths) of the 132 children found by the screening. The overall prevalence of MMR among 6–10‐y‐old children was 6.2%. The distribution of MMR was uneven, with 1.2% among children from the upper‐middle class, 4.8% in the village, 6.1% in the urban slum and 10.5% in the poor periurban slum area. Additional impairments were found in 75% of the children with MMR, of which speech impairment was the most common.

Conclusion: The prevalence of MMR was found to be higher in a developing country than in developed countries. It also seemed to be related to poor socioeconomic conditions, as the prevalence in the upper‐middle class was comparable to figures from developed countries, while the prevalence in children from poor population groups was much higher.
Head‐impulse testing in Fabry disease ‐ vestibular function in male and female patients
Authors: Palla A , Widmer U , Straumann D
Published: August 2010

Aim: To study the prevalence of peripheral vestibular deficit in male and female patients with Fabry disease and to assess the effect of enzyme replacement therapy (ERT) on peripheral vestibular function using quantitative head‐impulse testing. Methods: Using dual search‐coils the vestibulo‐ocular reflex during rapid rotational head thrusts to both sides was recorded in 21 patients (13 male, 8 female) with Fabry disease prior to ERT initiation. ERT consisted of infusions of gene‐activated human α‐galactosidase A (agalsidase alfa; Replagal™) every 2 weeks at doses of 0.2mg/kg. Eight patients were tested again approximately 6 and 12 months after the initiation of ERT. Results: At baseline examination, 15 of the patients with Fabry disease (71%; 11 males, 4 females) showed reduced peripheral vestibular function. The deficit was unilateral in nine patients (3 females) and bilateral in six patients (1 female). The severity of the vestibular deficit was not significantly different between male and female patients. After 12 months of ERT, the average vestibular deficit on the weaker side tended to improve; however, the change was not significant (p= 0.10).

Conclusion: Fabry disease affects peripheral vestibular function in both male and female patients. Females seem to be affected less frequently than males, but, on average, vestibular deficits are not different between the two groups. To confirm or reject the tendency for vestibular improvement during ERT, more patients need to be tested and longer follow‐up periods are required.
Sequelae of storage in Fabry disease ‐ pathology and comparison with other lysosomal storage diseases
Authors: Elleder M
Published: August 2010

Aim: To evaluate the sequelae of the lysosomal storage of globotriaosylceramide (Gb3) in a series of patients with Fabry disease. Methods: Biopsy and post‐mortem samples from 12 patients with Fabry disease were examined microscopically, including, in some cases, immunohistochemistry and electron microscopy. Where possible, comparisons were made with other lysosomal storage disorders. Results: Storage of Gb3 in cardiocytes leads commonly to progressive hypertrophy, which is a non‐specific phenomenon also observed in other lysosomal storage disorders. Capillary endothelial storage was associated with a tendency for capillary basement membrane multiplication. In the single angiokeratoma studied, the basement membrane was rudimentary. Sinusoids in the adrenal cortex and liver displayed either a slight degree of storage or were unaffected. The glomeruli of the kidney exhibited focal hyalinization starting in the mesangial region. Proximal tubular cells were essentially free of lysosomal accumulation, including protein absorption droplets, despite the presence of proteinuria. In only one case, an autopsied Fabry heterozygote, were the proximal tubular cells loaded with protein absorption droplets. The arterial wall in large muscular arteries (coronary, renal and intrarenal) displayed arteriopathy with pronounced involvement of the smooth muscle cells in the media. Arteriopathy started with storage, followed by cell degeneration and breakdown, extracellular matrix deposition and, often, calcification (confined to the muscular layer). Smooth muscle cells occasionally exhibited shrinkage‐type necrosis, with dispersion of the stored lipid into the dense cytoplasmic mass. Intimal and mitral valve fibroblasts exhibited variable storage, which was associated with cell loss and necrosis. Intensive storage was found in Ley dig cells and in the epididymal epithelium.

Conclusion: These long‐term sequelae of Gb3 storage are mostly irreversible. Some may interfere with enzyme replacement therapy. It is important, therefore, to consider starting enzyme replacement therapy as early as possible.
Serum ferritin and transferrin receptor concentrations during the transition from adolescence to adulthood in a healthy Swedish population
Authors: Samuelson G , Lönnerdal B , Kempe B , Elverby J‐E , Bratteby L‐E
Published: August 2010

Aim:As part of a longitudinal nutrition study of adolescents, changes in serum ferritin (s‐Ft), serum transferrin receptors (s‐TfR) and the TfR/Ft ratio from 15 to 21 y of age were studied in randomly selected Swedish adolescents. Methods:Blood samples from 60 males and 66 females were drawn at 15, 17 and 21 y of age. Results:In males, median s‐Ft increased significantly from 33 (μg 1 −1 at 15 y to 96 (μg 1−1 at 21 y, and in females, after a non‐significant decrease at 17 y, from 27 at 15 y to 34 (μg 1 at 21 y. Between 15 and 17 y, s‐TfR increased significantly, in males from 5.9 to 7.7 p.g 1, and in females from 5.2 to 7.6 μg 1−1, whereas s‐TfR decreased significantly in both genders between 17 and 21 y. The log (TfR/Ft) ratio did not change in males between 15 and 17 y, but decreased significantly from 2.2 ± 0.3 to 1.8 ±0.3 by the age of 21 y. In females, the TfR/Ft ratio increased significantly between 15 and 17 y, whereas a significant decrease was found by the age of 21 y. S‐Ft <12 μg 1−1 at 15, 17 and 21 y was 3, 2 and 2% in males, and in females 18, 26 and 21%, respectively.

Conclusion:This study shows an increase in s‐Ft and a decline in s‐TfR in males, indicating increased iron stores. In females, s‐Ft did not increase significantly, whereas s‐TfR and the TfR/ Ft ratio decreased between 17 and 21 y, indicating that cellular iron needs were met.
Altered bone metabolism in children infected with human immunodeficiency virus
Authors: Zamboni G , Antoniazzi F , Bertoldo F , Lauriola S , Antozzi L , Tatò L
Published: August 2010

Aim: Data on bone homoeostasis of children infected with human immunodeficiency virus (HIV), at the time of the gain in bone mass, are very rare. To determine possible alterations in bone metabolism, 13 prepubertal vertically HIV‐infected children were studied. Methods: Viral load, CD4 count, interleukin‐6 (IL‐6), growth hormone, insulin‐like growth factor‐I (IGF‐I), IGF binding protein‐3 (IGFBP‐3), acid‐labile subunit (ALS), IGFBP‐3 proteolysis, osteocalcin in blood and N‐terminal telopeptide of type I collagen in urine were determined. Lumbar spine bone mineral density was examined by dual‐energy X‐ray absorptiometry. Results: Low osteocalcin levels were found in all patients. Low IGF‐I was found in only six children, who had low CD4 count and high IL‐6 levels, with normal levels of IGFBP‐3 and ALS, absent IGFBP‐3 proteolysis and decreased bone mineral density, irrespective of viral load or growth.

Conclusion: Low serum osteocalcin levels appear to be an initial warning sign of possible altered bone metabolism in HIV‐infected children. However, only when the immune system becomes more seriously compromised is bone loss measurable by bone densitometry.
Investigation of the mechanisms of therapy‐related hypoglycaemia in children with acute lymphoblastic leukaemia
Authors: Halonen P , Salo MK , Schmiegelow K , Mäkipernaa A
Published: August 2010

Aim: To determine the mechanisms of fasting hypoglycaemia occurring during maintenance therapy (MT) for childhood acute lymphoblastic leukaemia (ALL). Methods: Thirty‐five children and adolescents with ALL, aged 2.4–17.4 y, were fasted for up to 16 h during MT. Nineteen of the children developed hypoglycaemia after 11 to 16 h of fasting. Blood samples for determination of metabolic changes were taken on completion of fasting. Nineteen patients underwent a glucagon stimulation test after 4 to 16 h of fasting during MT. Erythrocyte concentrations of the metabolites of methotrexate (E‐MTX) and 6‐mercaptopurine (E‐TGN) were measured at the time of fasting. Fifteen out of 19 patients who became hypoglycaemic were re‐studied 3 to 4 mo after cessation of therapy. Results: In the hypoglycaemia group, plasma levels of gluconeogenic amino acids alanine and glutamine were lower (medians 117 vs 190 μmol L−1, p= 0.009, and medians 396 vs 448 μmol L−1, p= 0.031, respectively) than in the normoglycaemia group. Serum levels of free carnitine were lower (medians 20.3 vs 29.8 μmol L−1, p= 0.027), free fatty acids higher (medians 3.09 vs 1.23 mmol L −1, p < 0.001) and marked dicarboxylic aciduria was more common in the patients with hypoglycaemia (in 14/16 vs in 2/14, p < 0.001). Impaired responses to glucagon stimulation occurred in 36% (4/11) in the hypoglycaemia group and in 12.5% (1/8) in the normoglycaemia group (p= 0.243). No significant differences were detected in E‐MTX and E‐TGN between the groups. Most of the metabolic abnormalities returned to normal after cessation of chemotherapy.

Conclusions: Low levels of gluconeogenic amino acids, especially of alanine, are associated with hypoglycaemia. Reduced hepatic glycogen stores may also be involved in the aetiology.
Factors constraining adherence to referral advice for severely ill children managed by the Integrated Management of Childhood Illness approach in Imbabura Province, Ecuador
Authors: Kalter HD , Salgado R , Moulton LH , Nieto P , Contreras A , Egas ML , Black RE
Published: August 2010

Aim: Low referral completion rates in developing countries undermine the Integrated Management of Childhood Illness (IMCI) strategy for lowering child mortality. This study sought to identify factors constraining adherence to referral advice in a health system using the IMCI approach. Methods: Caregivers of 160 children urgently referred to hospital were prospectively interviewed. Caregivers who accessed and did not access hospital were compared for potential referral constraining factors, including demographics, family dynamics, the severity of their child's illness, their interaction with the health system, self‐perceived problems, and physical and financial access. Results: 67/160 (42%) referred children did not access hospital. Six factors were associated with non‐access, including two health worker actions: not being given a referral slip [adjusted odds ratio (OR)= 15.3, 95% confidence interval (95% CI) 4.4–64.6) and not being told to go to the hospital immediately (adjusted OR = 5.3, 95% CI 1.9–16.3). Receiving both of these interventions reduced the risk of not accessing hospital to 19%, from 96% for those who received neither intervention. Several indicators of illness severity, including caregivers' ranking of their children's illness severity, the presence of severe illness signs and mortality, were investigated and found not to be important explanatory factors.

Conclusion: Providing a referral slip and counseling the caregivers of severely ill children to go to the hospital immediately appear to be powerful tools for increasing successful referral outcomes.
The respiratory pump: past and present understanding
Authors: Devlieger H
Published: August 2010

The history of our understanding of the respiratory system has been long and progressive, probably starting with Galenus who did experimental spinal cord sections, and progressed through the poorly known work of Leonardo da Vinci on the structure‐function relation of chest wall components.

Conclusion: Despite numerous experiments in the past, the respiratory control system remains complex and poorly integrated because of the diversity of the afferent pathways and of the interacting respiratory centres.
β‐Glucuronidase in the diagnosis of bacterial meningitis and response to treatment
Authors: Beratis NG , Eliopoulou MI , Syrogiannopoulos GA
Published: August 2010

Aim:β‐Glucuronidase activity is increased in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. The aim of this study was to investigate the β‐glucuronidase activity in the cell‐free CSF of bacterial meningitis and its course during treatment, and compare it with other CSF parameters. Methods: The β‐glucuronidase activity, cell number, protein concentration and CSF/blood glucose ratio were measured in 43 consecutive infants and children with bacterial meningitis, and 97 control subjects. Patients had one or two follow‐up lumbar punctures. Results: The β‐glucuronidase activity was increased early in bacterial meningitis, even when the other CSF parameters were undisturbed. Before treatment, the median activity in affected children was 136umoles 4‐methylumbelliferone l‐1 h‐1 (range 44–826) and in controls 14 (7–23). In all patients who improved, the activity was lower in the follow‐up CSF samples. Six to 12 h after starting treatment, the median activity was already reduced by 59%. The other CSF parameters showed a variability during the first 24 h of treatment independently of the course of the disease. Multiple comparisons of the CSF parameters in 17 patients who had two follow‐up punctures showed that the β‐glucuronidase activity was the best prognostic index.

Conclusion: β‐Glucuronidase activity in the CSF is a reliable indicator of bacterial meningitis, which can identify the response to treatment early in the course of illness. The enzyme activity is increased early in the disease, even when the other laboratory parameters from the CSF remain normal.
Preterm delivery and calculation of survival rate below 28 weeks of gestation
Authors: Hansen B Mølholm , Greisen G
Published: August 2010

Aim: To estimate the number of still‐ and live‐births below 28 wk of gestation in a 2‐y period in Denmark, and to determine how the calculated survival rates vary using three different denominators: 1) the number of infants actively treated in the Neonatal Care Units, NNUs, 2) the number of all live‐born infants, and 3) the number of all births, including stillbirths. Methods: The number of stillbirths and live‐born infants at 20 to 27 wk of gestation was estimated over a 2‐y period in Denmark. Data on live‐born infants and survival rates were obtained from a national prospective study and the National Births Register. The number of women hospitalized owing to spontaneous abortion was obtained from The Danish National Health Register; the number of stillbirths was calculated from these data. Results: The estimated number of both still‐ and live‐births was similar in every week from 20 to 27 wk of gestation; approximately 1 per 1000 live‐births at each gestational week. At from 23 to 25 wk of gestation the overall chances of survival varied significantly depending on the denominator: actively treated infants 46% (CI 95%; 37%‐54%), all live‐born infants 34% (CI 95%; 27%–41%), all births including stillbirths 14% (CI 95%; 11%–17%).

Conclusion: The chances of survival for the intrauterine fetus below 26 wk of gestation are significantly lower than the reported survival rates from the NNUs. The low percentage of fetuses delivered before 26 wk of gestation classified as live‐born renders the reported birth‐rates sensitive to differences in the way “live‐born” is interpreted.
Mother‐to‐child transmission of HIV: developing integration of healthcare programmes with clinical, social and basic research studies Report of the International Workshop held at Chobe Marina Lodge, Kasane, Botswana, 21–25 January 2003*
Authors: Menu E , Scarlatti G , Barré‐Sinoussi F , Gray G , Bollinger B , Ioannidis JPA , Miotti P , Osborne C ,   for the Participants in the Workshop
Published: August 2010

Considerable efforts are still needed in the public health sector, as well as in clinical, social and basic research, to improve programmes for HIV‐1 MTCT (mother‐to‐child transmission) prevention and care. Advantage should be taken of the remarkable amount of expertise and resources that have accumulated over the past few years to accelerate the process of integration. Future initiatives should include integrating specialists and people with diverse backgrounds and targeting their scientific and programmatic ideas to address real‐world problems in the area of MTCT of HIV‐1.
Infant feeding practices and associated factors in the first six months of life: The Norwegian Infant Nutrition Survey
Authors: Lande B , Andersen LF , Bærug A , Trygg KU , Lund‐Larsen K , Veierød MB , Bjørneboe G‐E Aa
Published: August 2010

Aim: To describe and evaluate infant feeding practices during the first 6 mo of life in relation to recommendations, and to study infant feeding practices in relation to maternal and infant characteristics. Methods: Data from 2383 Norwegian infants aged 6 mo were collected by a self‐administered semi‐quantitative food‐frequency questionnaire measuring feeding practices at 6 mo and feeding practices retrospectively at ≤5.5 mo of age. Results: Only 1% of the infants had never been breastfed. The proportion of breastfed infants was 96% at 1 mo, 85% at 4 mo and 80% at 6 mo. The proportion of exclusively breastfed infants was 90% at 1 mo, 44% at 4 mo and 7% at 6 mo. Twenty‐one percent of the infants were introduced to solid foods before the age of 4 mo. For exclusive breastfeeding at 4 mo, breastfeeding at 6 mo and timely introduction of solid foods (not before 4 mo) significant positive trends were found for maternal age, education and degree of urbanization. Negative associations were found for maternal smoking. Furthermore, exclusive breastfeeding at 4 mo was associated with infant gender and marital status, and the odds of breastfeeding at 6 mo significantly decreased with decreasing infant birthweight. Finally, both the odds of exclusive breastfeeding at 4 mo and of breastfeeding at 6 mo increased with increasing numbers of children.

Conclusion: These results indicate that a majority of Norwegian infants are fed in accordance with infant feeding recommendations during their first 6 mo of life. However, the duration of exclusive breastfeeding is shorter than recommended. Infant feeding practices are significantly associated with maternal and infant characteristics.
Results of exercise testing at a mean age of 10 years after neonatal arterial switch operation
Authors: Hövels‐Gürich HH , Kunz D , Seghaye M‐C , Miškova M , Messmer BJ , von Bernuth G
Published: August 2010

Aim: This prospective follow‐up study investigated long‐term exercise capacity at a mean age of 10 y after neonatal arterial switch operation for transposition of the great arteries in a large group of homogeneous unselected children. Methods: 56 asymptomatic children, aged 7.9–14.3 y (10.5 ± 1.6, mean ± SD), were examined with respect to exercise tolerance, electrocardiographic (ECG) response and activity of biochemical markers for myocardial injury. The protocol included standard electrocardiography, M‐mode and two‐dimensional echocardiography at rest, a Bruce walking treadmill test to voluntary exhaustion, and determination of cardiac troponin I and T, creatine kinase and myoglobin from venous blood samples at rest and 4 h after exercise. Heart rate, blood‐pressure response to exercise stress and endurance time were compared with published results of age‐matched normal children. Results: 54 patients (96.4%) had normal exercise capacity; a reduction in 2 patients was not due to cardiac disease. Heart rate and systolic blood pressure rose significantly between rest and peak exercise and did not differ from normal controls, whereas diastolic blood pressure was lower. ECG remained normal at rest and on exercise in 54 children (96.4%). Serum values of cardiac troponin I and T, creatine kinase and myoglobin were normal at rest and after exercise in all patients.

Conclusion: The study demonstrates excellent long‐term exercise capacity after neonatal arterial switch operation. Exercise testing is a useful and non‐invasive screening method to detect patients with clinically relevant exercise‐induced myocardial ischaemia and should be routinely performed in growing patients.