Luciano Molinari

Low insulin, IGF-I and IGFBP-3 levels in children with Prader-Labhart-Willi syndrome

Abstract It is well established that insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and insulin are low in growth hormone deficiency, but due to their dependence on nutrition, they are elevated in healthy obese children. As the presence of growth hormone deficiency in Prader-Labhart-Willi syndrome (PWS) is still controversial, we studied insulin, IGF-I and IGFBP-3 levels in 19 children with PWS (age range 0.5–14.6 years). Serum concentrations of insulin (SDS: −0.7±0.9, P=0.01) and IGF-I (SDS: −0.7±0.8,P=0.002) were low, but IGFBP-3 (SDS: −0.3±1.2, P=0.2) was normal compared to normal weight age-matched children. Since children with PWS are typically obese, insulin, IGF-I and IGFBP-3 levels should be compared to normal obese children who present increased levels of these hormones. In comparison to data of healthy obese children reported in the literature, not only IGF-I, but also IGFBP-3 levels are low and fasting insulin levels even very low, suggesting a growth hormone deficiency.

Low-energy epicardial pacing in children: the benefit of autocapture

BACKGROUNDnPermanent cardiac pacing in children results commonly in augmented energy consumption because of the high pacing rates and the ample stimulation safety margin applied in children. Cardiovascular anatomy and limited venous access sometimes preclude the otherwise preferred endocardial approach. In this multicenter patient series, we studied the feasibility, safety, and energy saving obtained by a combination of steroid-eluting epicardial leads with autocapture devices capable of ongoing adjustment of the stimulation output to the prevailing threshold.nnnMETHODSnAutocapture devices (Pacesetter Microny SR+/- and Regency SR+/-; Pacesetter, Solna, Sweden) and steroid-eluting epicardial pacing leads (Medtronic CapSure Epi 10366; Medtronic, Inc, Minneapolis, MN) were implanted in 14 children. Thresholds, telemetry data, evoked response, and polarization signals were obtained at discharge and follow-up, and battery service life was calculated.nnnRESULTSnDuring a median follow-up of 6.5 months, autocapture pacing was applied in 12 of 14 children. The automatically adjusted pulse amplitude of autocapture devices demonstrated low-energy pacing with no significant changes between discharge and 6 months follow-up (1.1 +/- 0.3 versus 0.9 +/- 0.3 V). Autocapture-programmed pacemakers had calculated life spans of 7.8 +/- 1.4 years (Microny) and 21.0 +/- 1.6 years (Regency). No adverse effects were noted.nnnCONCLUSIONSnAutocapture-controlled pacing with bipolar epicardial pacing leads is feasible and safe in children. Autocapture programming results in substantial energy savings and extends battery life markedly.

Serum and CSF levels of neuron-specific enolase (NSE) in cardiac surgery with cardiopulmonary bypass: a marker of brain injury?

We investigated whether neuron-specific enolase (NSE) in serum or cerebrospinal fluid (CSF) reflects subtle or manifest brain injury in children undergoing cardiac surgery using cardiopulmonary bypass (CPB). NSE was measured in serum (s-NSE) before, and up to, 102 h after surgery in 27 children undergoing cardiac surgery with CPB. In 11 children, CSF-NSE was also measured 48 or 66 h post-surgery. As erythrocytes contain NSE, hemoglobin concentration in the samples was determined spectrophotometrically at 550 nm (cut-off limit: absorbance 0.4 = 560 mg/l) in 14 children and in a further 13 children by spectroscopic multicomponent analysis (cut-off limit 5 micromol/l = 80 mg/l). One hundred and one of 214 post-operative serum samples (47%) had to be discarded because of hemolysis (18% spectrophotometrically at 550 nm and 88% with spectroscopic multicomponent analysis). On the first and second post-operative day, the median s-NSE values were significantly higher when compared with samples taken after 54 h or longer (P = 0.008 and P = 0.002). All CSF-NSE levels were within the normal range and below the s-NSE measured in the same patient. Although in our study elevated s-NSE seems to indicate brain injury in CPB-surgery, the low concentration of NSE in the post-operative CSF of 11 children puts the neuronal origin of s-NSE in question. NSE from other non-neuronal tissues probably contributes to the elevated s-NSE. Additionally, normal post-operative CSF-NSE values in two children with post-operative neurological sequelae might question the predictive value of CSF-NSE with regard to brain injury.

The analysis of the EEG.

The quantitative analysis of the electroencephalogram (EEG) relies heavily on methods of time series analysis. A quantitative approach seems indispensable for research (be it clinical or basic neurophysical research), but it can also be a useful information for purely clinical purposes. Apart from the ongoing spontaneous EEG, evoked potentials (EPs) also play an important role. They can be elicited by simple sensory stimuli or more complex stimuli. Their analysis requires methods which are different from those for the spontaneous EEG. Those methods operate usually in the time domain and offer many challenging problems to statisticians. Methods for analysing the spontaneous EEG usually work in the frequency domain in terms of spectra and coherences. Biomedical engineers who take care of the equipment are usually also trained in time series analysis. Thus, they have contributed much more to methodological progress for analysing EEGs and EPs, compared with statisticians. However, the availability of a sample of subjects, and the associated problems in modelling followed by an inferential analysis could make a larger influence from the statistical side quite profitable. This paper tries to give an overview of a fascinating area. In doing so we treat more extensively problems with some statistical appeal. This leads inevitably to some overlap with our own work.

Short stature a common feature in duchenne muscular dystrophy

In a retrospective growth evaluation, which included parental height, birth length and a longitudinal analysis of growth and bone maturation, it has been shown that short stature is a common finding in Duchenne muscular dystrophy already in an early or even preclinical stage. Normal length and weight at birth, slow subsequent growth with a curve crossing the centiles in the 1st years of life, and normal bone maturation are characteristic of this type of short stature.

Maximal mouth opening capacity: percentiles for healthy children 4–17 years of age

BackgroundA reduced mouth opening capacity may be one of the first clinical signs of pathological changes in the masticatory system. The aim of this retrospective cross-sectional study was to create age related percentiles for unassisted maximal mouth opening capacity (MOC) of healthy children.MethodsAll recordings of MOC as measured at the yearly dental examinations of school children in the city of Zurich, Switzerland, between August 2009 and August 2010 were extracted from the database. The program LMSchartMaker Pro Version 2.43, Huiqi Pan and Tim Cole, Medical Research Council, 1997–2010 was used to calculate age and sex related reference centiles.ResultsRecords from 22′060 dental examinations were found during the study period. In 1286 (5.8%) the maximal interincisal measurement was missing. Another 55 examinations were excluded because of missing data for sex (7), age at examination (11) or because the value was deemed to be pathologically low (37). Thus, a total of 20′719 measurements (10′060 girls, 10′659 boys) were included in the analysis. The median age (range) was 9.9xa0years (3.3-18.3) for girls and 10.0xa0years (2.8-18.7) for boys. The mean MOC (range) was 45xa0mm (25–69) for girls and 45xa0mm (25–70) for boys. Age related percentiles were created for girls and boys separately, showing the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentile from 3 through 18xa0years of age.ConclusionsIn these 20′719 unselected school children MOC increased with age but showed a wide range within children of the same age.

Dural ectasia in children with marfan syndrome : A prospective, multicenter, patient-control study

The clinical diagnosis of Marfan syndrome in childhood is difficult, because symptoms may not have developed to their full expression until adulthood. The Ghent nosology for the diagnosis of Marfan syndrome classifies dural ectasia as a major diagnostic criterion. More than two thirds of adult patients with Marfan syndrome show dural ectasia, while the frequency in childhood is unknown. This prospective multicenter observational patient‐control study was performed to identify pathologic changes of the lumbosacral spine in young patients with Marfan syndrome. Design: Prospective clinical trial, multicentric, cross‐sectional. Setting: MRI of the lumbosacral spine. Patients: Twenty patients with proven Marfan syndrome, 20 patients suspicious for Marfan syndrome and 38 healthy controls. Outcome measures: Vertebral body diameter (VBD) from L1 to S1, dural sac diameter (DSD) from L1 to S1, dural sac ratio (DSR), qualitative assessment of the lumbosacral spine. Results: DSD and VBD in different age groups were higher in patients with proven or suspected Marfan syndrome than in healthy controls (DSD: L1, 6–8 years, Pu2009<u20090.05). VBD related to body height showed a similar growth related increase in patients with proven or suspected Marfan syndrome and controls. DSD related to body height was elevated in patients with proven or suspected Marfan syndrome at different levels of the lumbar spine. DSD at levels L1, L5, and S1, and DSR at levels L5 and S1 of patients with proven Marfan syndrome were significantly higher (Pu2009<u20090.05) than in controls. Conclusion: Even during childhood pathologic changes inside the lumbosacral spine of patients with Marfan syndrome can be observed. Dural ectasia, which occurs at different levels of the lumbar spine, can be detected at levels L5 and S1 in up to 40% of patients with Marfan syndrome.

Canalisation in human growth: a widely accepted concept reconsidered

Abstract According to the concept of canalisation, infants and children stay within one or two growth channels, and therefore, any crossing of height centiles always warrants further evaluation. In view of evidence against this concept we re-investigated the variability of individual growth in the First Zürich Longitudinal Growth Study. The investigation is based on height measurements of 232 children (112 females, 120 males) measured at annual intervals during childhood and half-yearly during adolescence. Height data were transformed into height standard deviation scores (SDS) and canalisation defined by the width of an individuals growth channel, i.e., by the differences between maximum and minimum height SDS, in the individual series of measurements. Many subjects of the First Zürich Longitudinal Growth Study crossed numerous centiles with patterns that often seemed to show characteristic features. For approximately two thirds of the subjects, the SDS channel during the whole growth process covers more than one SDS. In childhood, between the age of two and age of minimal height velocity, only about one fourth of the subjects have an SDS channel below 0.5, indicating acceptable canalisation. During childhood, growth in boys appeared slightly more canalised than in girls (P=0.02).nConclusion The present investigation does not support the concept of strict canalisation of individual growth. We suggest to consider crossing of centiles a normal event in child development, though in a clinical setting crossing centiles should still be taken seriously, at least at first until a medical cause for this has been excluded.

Phenotypic heterogeneity of growth and psychometric intelligence in Prader-Willi syndrome: Variable expression of a contiguous gene syndrome or parent–child resemblance?

Phenotypic variability in children with Prader-Willi syndrome (PWS) was investigated with respect to variable expression of the contiguous gene syndrome and trait variance. In a prospective study, parent/child resemblance of anthropometric and psychometric measures was analyzed in 22 children with PWS (11 females and 11 males; 18 deletions, 4 uniparental disomy (UPD)) and in a control group (88 females and 88 males). The average child-midparent Z-score difference for height in females was -1.9 and in males -0.9, head circumference -1.7 and -1.0, and body mass index (BMI) 2.3 and 2.7, respectively. Intellectual performance of females and males was, on average, -2.7 and -2.6 below maternal performance. Range and standard deviation were moderately increased for height and head circumference, doubled for BMI, and unchanged for IQ. Parent/child correlations for anthropometric and psychometric measurements in the study group did not significantly differ from those of the control group. Exceptions were higher correlations between mothers and daughters for height (P < 0.05) and BMI (P < 0.01), and lower correlations for head circumference between midparent values and daughters (P < 0.05) than in the control group. In conclusion, parent-child resemblance in growth and intellectual development among children with PWS was found to be comparable to that noted in the normal population, indicating a strong determination by trait variance. Children with PWS differed significantly with respect to a lower trait level and-with the exception of IQ-a larger variability. The latter may indicate a variable expression of the contiguous gene syndrome.

Longitudinal monthly body measurements from 1 to 12 months of age: a study by practitioners for practitioners

Abstract A longitudinal growth study with monthly measurements during the 1st year of life was conducted by nine paediatricians working in private practice in Zurich. Of 92 children, none was lost to the study and only 32 of 1104 planned visits were missed; the quality of the measurements was comparable to that of a specialised university clinic. Compared to the Zurich Longitudinal Growth Studies, children of this study were considerably heavier and taller. In 92% of the subjects, growth velocity was at least once outside the reference range (3rd–97th percentile). For weight increments, the corresponding proportion was 87%.nConclusions The data indicate that current standards for the 1st year of life for the Zurich area might no longer be appropriate and need to be updated. The currently used velocity percentiles based on 3-monthly measurements are not suitable to assess individual height and weight increments calculated from monthly measurements.