A new DLK1 defect in a family with idiopathic central precocious puberty: elucidation of the male phenotype.

PURPOSE: We aimed to investigate a cohort of female and male patients with idiopathic central precocious puberty (CPP), negative for Makorin Ring Finger Protein 3 (MKRN3) defect, by molecular screening for Delta-like 1 homolog (DLK1) defects. DLK1 is an imprinted gene, whose mutations have been described as a rare cause of CPP in girls and adult women with precocious menarche, obesity and metabolic derangement. METHODS: We enrolled 14 girls with familial CPP and 13 boys with familial or sporadic CPP from multiple academic hospital centers. Gene sequencing of DLK1 gene was performed. Circulating levels of DLK1 were measured and clinical and biochemical characteristics were described in those with DLK1 defects. RESULTS: A novel heterozygous mutation in DLK1, c.288_289insC (p.Cys97Leufs*16), was identified in a male proband, his sister and their father. Age at onset of puberty was in line with previous reports in the girl and 8 years in the boy. The father with untreated CPP showed short stature. No metabolic derangement was present in the father except hypercholesterolemia. Undetectable Dlk1 serum levels indicated the complete lack of protein production in the three affected patients. CONCLUSION: A DLK1 defect has been identified for the first time in a boy, underscoring the importance of genetic testing in males with idiopathic or sporadic CPP. The short stature reported by his untreated father suggests the need for timely diagnosis and treatment of subjects with DLK1 defects.

Preterm infants with severe extrauterine growth retardation (EUGR) are at high risk of growth impairment during childhood.

UNLABELLED: Extrauterine growth retardation (EUGR) seriously affects premature newborns and is related to the impairment of growth during childhood. There are very limited data available concerning the growth outcome of EUGR children. Our aim was to assess the growth outcome in a cohort of children born before 34 weeks of gestation with severe EUGR. This was a retrospective multicenter study, performed in outpatient endocrinology clinic. A total of 103 premature children with weight and/or length below -2 standard deviation score (SDS) of "intrauterine" growth expectation at the time of discharge from hospital (within 42 weeks of postmenstrual age) were included in the study. The study participants underwent a thorough anthropometric assessment at a mean age of 3.9 years ± 1.7 SD. Of the EUGR children, 12.6 % showed a height below -2 SDS and 7.7 % even below -2.5 SDS. Growth impairment was more common in males than in females (17 vs. 8 %). The prevalence of subnormal weight (below -2 SDS) was 13.6 %, being higher in males than in females (17 vs. 10 %). BMI values below -2 SDS were found in 18.4 % of our study population (22.7 % in males and 12 % in females). The 19.6 % of EUGR children did not catch up in head circumference during early childhood. Length at term was the major predictor of height in childhood (P < 0.001). CONCLUSION: A significant proportion of children born prematurely with severe EUGR show growth retardation in childhood thus suggesting the need for a close clinical follow-up to determine their growth potential and implement effective intervention strategies.

Responses to GHRH plus arginine test are more concordant with IGF-I circulating levels than responses to arginine and clonidine provocative tests.

BACKGROUND/OBJECTIVE: Although pharmacological GH stimulation tests are still considered the gold standard for GH deficiency (GHD) diagnosis, they are burdened by poor specificity. The majority of children diagnosed as having GHD show normal GH responses when re-tested at the end of growth, thus questioning the initial diagnosis. We evaluated the concordance between IGF-I levels and GH responses to provocative tests. METHODS: We analyzed 105 GHRH plus arginine tests, 79 arginine tests, and 124 clonidine tests performed in 192 short children. IGF-I levels ≤-2SD score (SDS) were considered suggestive for high likelihood of GHD. The percentage of positive and negative results for each test was determined and compared with IGF-I levels, clinical follow-up and response to therapy. RESULTS: In children with IGF-I>-2SDS the arginine test showed a concordance rate of 6.9%, the clonidine test of 28.6%, and GHRH plus arginine test of 70%. In children with IGF-I≤-2SDS the concordance was 96.1%, 85.7%, and 46.4%, respectively. The overall concordance was 66.7% for GHRH plus arginine, 42.7% for clonidine, and 27.8% for arginine tests. CONCLUSION: Our results suggest that GHRH plus arginine test provides the best concordance with the assessment of IGF-I levels thus suggesting that the combination of the two procedures may significantly reduce the need of a second provocative test.

Retinol-binding protein 4 in neonates born small for gestational age.

BACKGROUND: Retinol-binding protein 4 (RBP4) is an adipocyte-derived 'signal' that may contribute to the pathogenesis of insulin resistance and Type 2 diabetes. The relationship of RBP4 with insulin resistance and metabolic risk in human beings has been the subject of several studies. Subjects born small for gestational age (SGA) are at risk of insulin resistance and Type 2 diabetes. Though RBP4 could represent an early marker of insulin resistance, to date, none have determined RBP4 in SGA children. AIM: Our aim was to measure RBP4 concentrations in cord blood of SGA newborns compared with those in children born with a birth weight appropriate for gestational age (AGA) and to determine whether serum RBP4 levels at birth correlate with insulin sensitivity markers. SUBJECTS AND METHODS: Sixty-four newborns, 17 born SGA (mean gestational age: 36.4+/-2.1 weeks), and 47 born AGA (mean gestational age: 37.0+/-3.6 weeks) were studied. The main outcome measures included anthropometry, lipid profile, insulin, homeostasis model assessment, quantitative insulin-sensitivity check index, adiponectin, and RBP4. RESULTS: RBP4 concentrations were significantly reduced in SGA newborns (p<0.002). No relationship was found between RBP4 and insulin sensitivity parameters. Stepwise regression analysis revealed that birth weight was the major predictor of RBP4 serum concentrations (p<0.001). CONCLUSION: RBP4 is reduced in SGA newborns, birth weight representing the major determinant of RBP4 concentrations, and is not related to insulin sensitivity. No significant difference in adiponectin levels and insulin sensitivity markers was found between SGA and AGA neonates.

Assessment of sub-division of plantar pressure measurement in children.

Methods for the measurement of plantar pressure are poorly defined particularly when describing sub-sections of the plantar surface of the foot in the presence of deformity. The aim of this study was to assess foot pressure measurement in healthy children, using an automatic technique of sub-area definition that has the potential for objective evaluation of treatment of foot deformity. Twelve healthy children were examined on three occasions. Plantar pressure data were collected and time synchronised with force plate and stereophotogrammetric data. The footprint was divided into five sub-sections by using the position of the markers on the foot at mid-stance projected onto the pressure footprint. Repeatability for peak pressure and peak force was assessed. Automatic sub-area definition based on marker placement was found to be reliable in healthy children. A comparison of results revealed that peak vertical force was a more consistent measure than peak pressure for each of the five sub-areas. This suggests that force may be a more appropriate measurement for outcome studies.

Does the thickening of Achilles tendon and plantar fascia contribute to the alteration of diabetic foot loading?

BACKGROUND: The diabetic foot often undergoes abnormal plantar pressures, changing in walking strategy, ulcerative processes. The present study focuses on the effects that diabetes-induced alterations of Achilles tendon, plantar fascia and first metatarso-phalangeal joint-both anatomical and functional-may have on foot loading. METHODS: Sixty-one diabetic patients, with or without neuropathy, and 21 healthy volunteers were recruited. Thickness of Achilles tendon and plantar fascia was measured by ultrasound. Flexion-extension of the first metatarso-phalangeal joint was measured passively. Main biomechanic parameters of foot-floor interaction during gait were acquired and related to the above measurements. FINDINGS: Plantar fascia and Achilles tendon were significantly (P<0.05) thicker in diabetics than in controls; mean values (SD) for controls, diabetics without and with neuropathy were 2.0 mm (0.5), 2.9 mm (1.2) and 3.0 mm (0.8) for plantar fascia, respectively, and 4.0 mm (0.5), 4.6 mm (1.0) and 4.9 mm (1.7) for Achilles tendon, respectively. Flexion-extension of the first metatarso-phalangeal joint was significantly (P<0.05) smaller in diabetics than in controls; mean values (SD) for controls, diabetics without and with neuropathy were 100.0 degrees (10.0), 54.0 degrees (29.4) and 54.9 degrees (17.2), respectively. The increase in the vertical force under the metatarsals was strongly related (R=0.83, explained variance=70.1%) to the changes in the three above parameters. INTERPRETATION: Thickening of plantar fascia and Achilles tendon in diabetics, more evident in the presence of neuropathy, concurs to develop a rigid foot, which poorly absorbs shock during landing (performs the physiological impact force absorption during landing). More generally, an overall alteration of the foot-ankle complex motion likely occurs throughout the whole gait cycle, which partly explains the abnormal loading under the forefoot.

Alteration of spatial-temporal parameters of gait in Chronic Fatigue Syndrome patients.

Chronic Fatigue Syndrome (CFS) has been widely studied and a lot of information is available in the literature regarding the immunological, virological, neuroendocrinal and psychiatric aspects of the disease, but its aetiology is still poorly understood. Great attention has also been paid to the alteration of the muscular function caused by CFS. The aim of the present work was to study CFS patients' gait in order to find out objective measures which can better characterize the pathology. Spatial and temporal parameters of gait were collected from a group of 12 CFS informed volunteers by using the typical instrumentation of movement analysis, and raw data were statistically elaborated. Comparisons with reference data from a population of healthy subjects revealed significant abnormalities in the symmetry indices of the bilateral parameters and in the linear relationships among parameters, and between these parameters and the physical characteristics of the patients. Interestingly, the abnormalities were present as from the beginning of the gait, which indicates that they are unlikely to be caused by the rapid increasing fatigue. This strengthens the hypothesis of a direct involvement of the central nervous system (CNS) in the onset of the disease.

Spatial-temporal parameters of gait: reference data and a statistical method for normality assessment.

Spatial and temporal parameters of gait are of recognised clinical relevance in the assessment of motor pathologies, because they normally occur in established combinations which can be altered by pathologies. The data collected from 596 healthy subjects have been used to establish relationships among these parameters and a procedure to estimate deviation from normality based on the comparison between measured values and values estimated by exploiting these relationships. The applied multiple linear regression method (MLRM) was preliminarily validated by comparing its outputs with those of corresponding equations found in the literature, and by applying it to a control group of 12 healthy subjects.

New instrumental set for the assessment of the hand functionality.

Hand motor deficits have been widely investigated, and several devices have been proposed for the selective and accurate study of specific hand motor tasks. Most studies have focused on the four, long fingers. The thumb function, although extremely important for the performance of most daily activities involving the hand, has scarcely been documented. A set of general-purpose, instrumental measuring devices has been designed and constructed at the authors' laboratory to measure and monitor the force each finger exerts separately, under isometric conditions, during pressing tasks. More generally, it is meant for the functional evaluation of the normal hand in different postures, but it also provides reliable measurements of the injured or deformed hand. The instrumental set is suitable for both biomechanical research and clinical applications. Effectively integrated with a visual feedback tool, it could be exploited in delivering and monitoring custom-designed rehabilitation programmes. The characteristics of the force transducers (range 0-100 N) were: inter-axis crosstalk < 4%; non-linearity < +/- 0.4% f.s.; hysteresis < 0.3% f.s.; overall accuracy +/- 1% f.s. The overall measurement system resolution was better than 0.1 N, and the keys response to the mechanical shock (acquired at 10 kHz) showed a resonance frequency of about 1 kHz. It was observed that the thumb contributed more than 30% of the overall pressing force.

Integrated pressure-force-kinematics measuring system for the characterisation of plantar foot loading during locomotion.

Plantar pressure, ground reaction force and body-segment kinematics measurements are largely used in gait analysis to characterise normal and abnormal function of the human foot. The combination of all these data together provides a more exhaustive, detailed and accurate view of foot loading during activities than traditional measurement systems alone do. A prototype system is presented that integrates a pressure platform, a force platform and a 3D anatomical tracking system to acquire combined information about foot function and loading. A stereophotogrammetric system and an anatomically based protocol for foot segment kinematics is included in a previously devised piezo-dynamometric system that combines pressure and force measurements. Experimental validation tests are carried out to check for both spatial and time synchronisation. Misalignment of the three systems is found to be within 6.0, 5.0 and 1.5 mm for the stereophotogrammetric system, force platform and pressure platform, respectively. The combination of position and pressure data allows for a more accurate selection of plantar foot subareas on the footprint. Measurements are also taken on five healthy volunteers during level walking to verify the feasibility of the overall experimental protocol. Four main subareas are defined and identified, and the relevant vertical and shear force data are computed. The integrated system is effective when there is a need for loading measurements in specific plantar foot subareas. This is attractive both in clinical assessment and in biomechanics research.

Measurement device for ankle joint kinematic and dynamic characterisation.

The paper describes a measurement device for obtaining the kinematic characterisation and isometric loading of ankle joints under different working conditions. Non-invasive, in vivo experiments can be conducted with this experimental apparatus, the potential of which could be usefully exploited in basic biomedical research, prosthesis design, clinical applications, sports medicine and rehabilitation. The device determines the 3D movement of the foot with respect to the shank and evaluates the torques and moments around the three articular axes in relation to any desired angular position of the ankle complex. When integrated with superficial electromyographic techniques and electrical stimulation, it allows the assessment of the functionality of the lower leg in both mechanical and myo-electrical terms. The paper reports the main mechanical and electronic features of the device (high linearity; maximum moment ranges +/- 300 Nm for flexion-extension, +/- 35 Nm for both pronation-supination and internal-external rotation; angular ranges: +/- 100 degrees of dorsi-plantar flexion, +/- 50 degrees of internal-external rotation and prono-supination; linear ranges: +/- 25 mm along each axis). Results from a healthy volunteer, under voluntary or stimulated conditions, helped in testing its operatability, reliability, robustness, repeatability and effectiveness. Preliminary simplified protocols have been also applied to 20 healthy volunteers, and the main results were 80.8 +/- 11.9 degrees of internalexternal rotation, 46.2 +/- 9.1 degrees of prono-supination and 74.6 +/- 13.1 degrees of flexion-extension. Torques and moments were normalised with respect to a body mass index of 30. The maximum plantar flexion moment (57.5 + 21.3 Nm) was measured with the foot at 150 of dorsal flexion; the maximum dorsal flexion moment (50.2 + 20.3 Nm) was measured with the foot at 150 of plantar flexion.

Pattern of abnormal tangential forces in the diabetic neuropathic foot.

OBJECTIVES: The role of tangential stress in neuropathic foot ulceration is yet unknown. The aim of this study was to investigate the tangential forces developed during gait by the whole foot and by selected subareas of it, namely the heel, the metatarsals and the hallux. METHODS: 61 diabetic patients have been evaluated: 27 without neuropathy, 19 with neuropathy and 15 with previous neuropathic ulcer. The patients were compared with 21 healthy volunteers. A piezo-dynamometric platform was used to measure the three components of the ground reaction force under the total foot and the selected subareas. RESULTS: A significant reduction was observed for the forward peak and the backward peak of the anteroposterior ground reaction force component measured under the whole foot. Patients with previous neuropathic ulcer showed a significant increase of the mediolateral stress under the metatarsals. CONCLUSIONS: Tangential stress is altered in diabetic neuropathic patients; the increased mediolateral component suggests that tangential stress could have a role in the high risk of recurrence observed in patients with previous ulceration. RELEVANCE: To assess the effectiveness of a non-invasive methodology for the estimation and the monitoring of significant alterations of the tangential stress with the increase of neuropathy.

A device for the measurement of malleoli diastasis.

Assessment of the degree of laxity of the distal tibio-fibular joint ligaments is of great importance in the treatment of some ankle pathologies resulting from traumas and when evaluating the effectiveness of re-constructive operations. This can be done by measuring the variation in the intermalleolar distance while loading and flexing the joint in a known way. So far, only X-ray techniques have been applied for this purpose, but they are invasive and do not allow for analysis under dynamic conditions. We have developed a wearable strain gauge device to be positioned directly over the malleoli for measurement of the intermalleolar distance variation. It has been tested on healthy and injured subjects, in both static and dynamic conditions. Data obtained in the static tests are in agreement with those found in literature. Dynamic analysis allowed for correlation of malleoli diastasis (MD) with the different phases of gait and different injured states.

Serum insulin-like growth factor-I (IGF-I) reference ranges for chemiluminescence assay in childhood and adolescence. Data from a population of in- and out-patients.

BACKGROUND: Insulin-like growth factor I (IGF-I) measurement is widely used for the diagnosis of disorders of GH secretion and sensitivity, and for monitoring of both GH and IGF-I replacement therapies. However, the lack of appropriate reference values obtained from large and representative samples undermines its practical utility. OBJECTIVE: To establish IGF-I reference values for a commonly used enzyme-labeled chemiluminescent immunometric assay in a large population of children aged 0 to 18 years. DESIGN: Cross-sectional analysis of serum IGF-I levels from samples collected in the two major Italian Children's Hospitals. SUBJECTS AND METHODS: IGF-I was measured using a solid-phase, enzyme-labeled chemiluminescent immunometric assay in 24403 children (50.6% girls) aged 0 to 18 years. Quantile regression coupled to multivariable fractional polynomials was used to produce age- and sex-specific reference values. MAIN OUTCOME MEASURE: Age- and sex-specific IGF-I reference values. RESULTS AND CONCLUSION: Reference values for immunometric assay of IGF-I were produced in a large sample of children and adolescents. Prediction equations were provided to automatize their calculations.

Abnormal foot function in diabetic patients: the altered onset of Windlass mechanism.

AIM: The aim of this study was to examine foot function in the presence of diabetes-induced alterations of the anatomical and biomechanical unit formed by the Achilles tendon, plantar fascia and metatarso-phalangeal joints. More specifically, we focused on the Windlass mechanism, the physiological mechanism which entails stiffening of the foot during propulsion. METHODS: Sixty-one diabetic patients, with or without neuropathy, and 21 healthy volunteers were recruited. The thickness of Achilles tendon and plantar fascia was measured by ultrasound. The main biomechanical parameters of foot-floor interaction during gait were acquired by means of dedicated platforms. The range of motion of the 1st metatarso-phalangeal joint was measured passively. RESULTS: The plantar fascia (PF) and Achilles tendon (AT) were significantly thickened in diabetic patients [control subjects: PF 2.0+/-0.5 mm, AT 4.0+/-0.5 mm; diabetic patients without neuropathy: PF 2.9+/-1.2 mm (P=0.002), AT 4.6+/-1.0 mm (P=0.016); diabetic patients with neuropathy: PF 3.0+/-0.8 mm (P<0.0001), AT 4.9+/-1.7 mm (P=0.026)]. Joint mobility was significantly reduced [control subjects: 100.0+/-10.0 degrees; diabetic patients without neuropathy: 54.0+/-29.4 degrees (P<0.0001); diabetic patients with neuropathy: 54.9+/-17.2 degrees (P<0.0001)]. Loading times and force integrals under the heel and the metatarsals increased [metatarsal loading time (% stance phase): control subjects 88.2+/-4.1%; diabetic patients without neuropathy 90.1+/-4.7% (P=0.146); diabetic patients with neuropathy 91.7+/-6.6% (P=0.048)]. CONCLUSIONS: Increased thickness of Achilles tendon and plantar fascia, more evident in the presence of neuropathy, may contribute to an overall increase of tensile force and to the occurrence of an early Windlass mechanism, maintained throughout the whole gait cycle. This might play a significant role in the overall alteration of the biomechanics of the foot-ankle complex.

Piezo-dynamometric platform for a more complete analysis of foot-to-floor interaction.

A compound instrument was constructed by superimposing a dedicated pressure platform on a commercial force platform. This instrument simultaneously estimates the ground reaction force resultants (vertical and shear forces, free moment and location of the center of pressure), pressure distribution throughout the foot-floor contact area, the trajectory of the center of pressure superimposed on the contact area (footprint). On the basis of the readings provided by the force plate we calibrated pressure sensors more accurately. We could therefore accurately estimate the vertical local components of the ground reaction. This information and the measured shear force resultants were essential for computing the shear forces acting on elementary areas corresponding to the active surface of each pressure sensor. This, in turn, allowed us to estimate the vertical and shear force resultants and free moment for subareas of the foot. This is a feature peculiar to this compound instrument, and for its effective exploitation we have implemented a few methods for the reliable identification of the subareas of interest. Two application instances are hereby reported.

High current-density anodic electro-dissolution in flow-injection systems for the determination of aluminium, copper and zinc in non-ferroalloys by flame atomic absorption spectrometry.

An automatic procedure with a high current-density anodic electrodissolution unit (HDAE) is proposed for the determination of aluminium, copper and zinc in non-ferroalloys by flame atomic absorption spectrometry, based on the direct solid analysis. It consists of solenoid valve-based commutation in a flow-injection system for on-line sample electro-dissolution and calibration with one multi-element standard, an electrolytic cell equipped with two electrodes (a silver needle acts as cathode, and sample as anode), and an intelligent unit. The latter is assembled in a PC-compatible microcomputer for instrument control, and for data acquisition and processing. General management of the process is achieved by use of software written in Pascal. Electrolyte compositions, flow rates, commutation times, applied current and electrolysis time were investigated. A 0.5 mol l(-1) HN03 solution was elected as electrolyte and 300 A/cm(2) as the continuous current pulse.The performance of the proposed system was evaluated by analysing aluminium in Al-alloy samples, and copper/zinc in brass and bronze samples, respectively. The system handles about 50 samples per hour. Results are precise (R.S.D. < 2%) and in agreement with those obtained by ICP-AES and spectrophotometry at a 95% confidence level.

Desenvolvimento de um centro de cuidados de enfermagem / Development of a center of nursing care

Um estabelecimento que constitua uma inovação e um meio de ampliação dos cenários de prática da universidade torna-se importante por configurar uma atividade acadêmica muito importante: a extensão. O trabalho possui como objetivo um relato de experiência da presente definição do Centro de Cuidados de Enfermagem (CCENF), espaço em que a enfermagem pode atuar junto à comunidade, proporcionando melhorias das condições de saúde e existência dela. Desta forma o método é a descrição do desenvolvimento das atividades previstas para a implantação e desenvolvimento do CCENF e o seu andamento (1ª publicação). O resultado é a exposição das atividades já executadas e daquelas pendentes, cuja abordagem contribuirá para a efetivação do trabalho de implantação. É possível, assim, realizar o embasamento deste ambiente de autonomia para a atuação da enfermagem, proporcionando imensa satisfação aos profissionais em fazê-lo e apresentá-lo.