Low Height Velocity Research Articles

Approach to the Patient: Diagnosis and Treatment with Growth Hormone of Turner Syndrome and its Variants.

Turner syndrome (TS) is characterized by a partial or complete absence of the second X chromosome in female. Here, patients with Xp deletion involving SHOX haploinsufficiency caused by unbalanced X-autosome translocations were discussed and considered as TS variants. This work aimed to expand the current knowledge of TS and unbalanced X-autosome translocations and to suggest the definition, clinical characteristics, diagnosis workflow and growth hormone (GH) treatment strategy of TS and its variants. A 9.0-year-old patient of TS variant with tall target height (+2.03SD) but low height velocity (3.6cm/y) and height (-1.33SD) was evaluated as an example. Patients similar to the index patient were systematically searched in MEDLINE and EMBASE and summarized. A diagnosis workflow and scores for risk assessment of GH treatment (RiGHT scores) for TS variants were also proposed in this study. According to the diagnosis workflow, the girl's karyotype was confirmed as 46,X,der(X)t(X;7)(p11.3; p14.1), and was evaluated as low risk using RiGHT scores. After 2-year GH treatment, she had a significantly increased height (-0.94SD). Moreover, a total of 13 patients from 10 studies were summarized, characterized as short stature, growth retardation, craniofacial abnormalities, disorders of intellectual development, and psychomotor delays. Risk assessment of GH treatment using RiGHT scores were also applied in these 13 patients. The patients with Xp deletion caused by unbalanced X-autosome translocations should be considered as TS variants. The diagnosis workflow and RiGHT scores is a useful approach for clinicians in addressing complex cases of TS variants with GH treatment in clinical practice.

Evaluation of the growth response of children with growth hormone deficiency according to the peak growth hormone levels in provocation tests

BackgroundWe aimed to evaluate the relation between the peak growth hormone (GH) levels in provocation tests and response to recombinant human GH (rhGH) therapy in patients with GH deficiency (GHD). MethodsThis was a cross-sectional, single-center, and retrospective study. A total of 135 patients under the age of 16 years who were diagnosed with GHD through insulin tolerance tests and L-DOPA stimulation tests and who received rhGH therapy for at least 2 years in the Pediatric Endocrinology Clinic of Akdeniz University Hospital between 1997 and 2021 were included in the study. ResultsThe patients were divided into two groups: idiopathic GHD (group I, n = 119) and multiple pituitary hormone deficiencies or organic pathology on magnetic resonance imaging (group II, n = 16). The patients in group I were classified into three subgroups according to the peak GH values in the provocation tests (group Ia: peak GH <3 μg/L, n = 34; group Ib: peak GH between 3 and 7 μg/L, n = 71; group Ic: peak GH between 7 and 10 μg/L, n = 34). The median age was 11.5 years in group I (8.8 in group Ia, 12.1 in group Ib, 12.3 in group Ib) and 8.8 years in group II. The height standard deviation score (SDS) was −2.93 in group I (−2.85 in group Ia, −2.99 in group Ib, −2.94 in group Ic) and −3.79 in group II. The median Δheight SDS was 0.61 in group I and 1.05 in group II at the end of the first year of treatment and 0.31 in group I and 0.45 in group II at the end of the second year (p = 0.005 and p = 0.074, respectively). When the subgroups of group I were compared, height SDS, Δheight SDS, and height velocity (HV) SDS were all higher in group Ia at the end of the first year of rhGH therapy (p = 0.040, p = 0.029, and p = 0.005, respectively). The height SDS was still significantly higher in group Ia (p = 0.033) while the HV SDS and Δheight SDS were similar between the groups at the end of the second year of therapy (p = 0.164 and p = 0.522, respectively). There was a statistically significant association between the first-year HV SDS and the peak GH value in provocation tests in multiple regression analyses (p<0.001). In addition, the final model revealed that height SDS and weight SDS at the start of the treatment and the first-year HV SDS are the factors with a statistically significant effect on the second-year HV SDS (p = 0.022, p = 0.001, and p<0.001, respectively). ConclusionOur findings show that the lower the GH peak in provocation tests, the better the response to treatment. The best HV was observed in the first year of rhGH therapy, and the diagnosis should be checked in those patients who had a low first-year HV and did not have a severely low GH peak in provocation tests.

Impact of a school-based health intervention program on body composition among South African primary schoolchildren: results from the KaziAfya cluster-randomized controlled trial

BackgroundThe prevalence of overweight and obesity is increasing among African children potentially predisposing them to greater obesity and non-communicable diseases (NCDs) in adulthood. This risk may be higher among growth-impaired children who may have greater fat mass. Therefore, we examined the effects of school-based physical activity (PA) promotion and multi-micronutrient supplementation (MMNS) on body composition among South African children enrolled in a longitudinal school-based randomized controlled trial.MethodsChildren were cluster-randomized by class to one of four groups: (a) a physical activity group (PA), (b) a multi-micronutrient supplementation group (MMNS), (c) a physical activity + multi-micronutrient supplementation group (PA + MMNS), and (d) control group, and were being followed for 3 years. Linear random effects regression models with random intercepts for school classes tested the associations of each intervention arm with overall fat mass (FM), fat-free mass (FFM), truncal fat mass (TrFM), and truncal fat-free mass (TrFFM) at 9 months (T2) for boys and girls. These differences were then explored among children who differed in height velocity (HV).ResultsA total of 1304 children (614 girls, 667 boys) in twelve clusters were assessed at baseline and after 9 months follow-up (T2). At baseline, approximately 15% of children were classified as overweight or obese while approximately 38% of children were classified as mildly stunted or moderately/severely stunted. Among girls, promotion of PA was associated with reduced FM and TrFM at T2 while MMNS was associated with increased FFM. Children with reduced HV in the PA arm had reduced FM while children in the MMNS arm with lower HV had increased FFM compared to children in the control arm. Similarly, children with lower HV in the MM and PA groups had reduced TrFM compared to children in the control arm.ConclusionsOur study suggests that the promotion of school-based physical activity programs and micronutrient supplementation can reduce childhood adiposity and so reduce the risk of obesity and chronic diseases later in adulthood.Trial registrationISRCTN, ISRCTN29534081. Registered on August 9, 2018. The trial was designed, analyzed, and interpreted based on the CONSORT protocol (Additional file 1: CONSORT checklist for randomized trial)

Adaptability investigations on bottom modified blade in powder spreading process of additive manufacturing

Powder spreading in powder-bed-based fusion additive manufacturing has been regarded as one of the most fundamental steps in the fabrication of high-performance components. Modified blade geometry would promote a more desirable particle motion state during spreading that would improve the quality of the spread powder bed. In this work, the vertical blade has been modified into the intact-arc blade and the new designed half-arc blade, then packing properties of powder beds from these blades under a wide range of operation parameters have been investigated to reveal their adaptations to powder spreading. Results indicate that particle deposition behavior from powder pile to powder layer has been improved after introducing the arc-bottom part into the blade when considering all operation parameters. Particularly, the packing property from the newly designed half-arc blade shows the most significant improvement. Mechanism analysis demonstrates that the introduced half-arc-bottom part can weaken the effect of the strong force chain in front of the blade compared to the straight bottom vertical blade. Moreover, the straight-bottom part behind the arc-bottom part in the half-arc blade would maintain the compacted state of particles and gradually remove the local load rather than release it into the particle motion. Therefore, the newly designed half-arc blade has revealed the most prominent operation region compared with the other blades, especially under operation parameters of low gap height or high blade velocity, which would preferably satisfy efficient powder spreading demand in practical additive manufacturing process.

Adult height after treatment of neurosecretory dysfunction and comparison to idiopathic GHD.

Neurosecretory dysfunction (NSD) causes growth hormone deficiency (GHD). Data on adult height after recombinant human growth hormone (rhGH) treatment are lacking. We collected treatment data of all patients with NSD seen between 1990 and 2017 at our outpatient department (tertiary centre) and measured adult height. For comparison, patients with idiopathic GHD were used. Diagnoses were based on short stature (<-2 standard deviation score [SDS]), continuously low height velocity (<25th percentile), delayed bone age (by >1 SD) and low serum IGF-1 concentration (<-2 SDS). NSD was defined by normal GH challenge results, but subnormal spontaneous GH secretion. Exclusion criteria were no information on adult height, underweight and other short stature disorders. Out of 67 patients diagnosed with NSD, six were still growing, 31 had test results exceeding validated GH cut-offs and three had other disorders causing short stature. Out of the 25 eligible patients with NSD, 21 could be recruited. These patients reached an adult height of -0.85 SDS (mean); 0.34 SDS below midparental height. Height gain during treatment was 2.01 SDS. This outcome was not different to 32 patients with idiopathic GHD. Long-term results suggest the viability of the diagnosis of NSD and the efficacy of rhGH treatment.

Growth in Transgender/Gender-Diverse Youth in the First Year of Treatment With Gonadotropin-Releasing Hormone Agonists

PurposeTransgender/gender-diverse (TGD) youth are treated with gonadotropin-releasing hormone agonists (GnRHas) to halt endogenous puberty and prevent the development of secondary sex characteristics discordant with their gender identity. This treatment may have significant impact on growth and height velocity (HV). MethodsParticipants were recruited prior to GnRHa initiation from four gender specialty clinics in the U.S. Anthropometric, laboratory, and Tanner-stage data were abstracted from medical records. ResultsFifty-five TGD youth (47% designated male at birth) with a mean ± standard deviation age of 11.5 ± 1.2 years were included in the analysis. HV in the first year of GnRHa use was median (interquartile range) 5.1 (3.7–5.6) cm/year. Later Tanner stage at GnRHa initiation was associated with lower HV: 5.3 (4.4–5.6) cm/year for Tanner stage II, 4.4 (3.3–6.0) cm/year for Tanner stage III, and 1.6 (1.5–2.9) cm/year for Tanner stage IV (p = .001). When controlled for age, there was not a significant difference in mean HV between TGD youth and prepubertal youth; however, when stratified by Tanner stage individuals starting GnRHa at Tanner stage IV had an HV below that of prepubertal youth, 1.6 (1.5–2.9) versus 6.1 (4.3–6.5) cm/year, p = .006. ConclusionsOverall, TGD youth treated with GnRHa have HV similar to that of prepubertal children, but TGD youth who start GnRHa later in puberty have an HV below the prepubertal range. Ongoing follow-up of this cohort will determine the impact of GnRHa treatment on adult height.

One Year of GH Treatment for Growth Failure in Children With Anorexia Nervosa: A Randomized Placebo-Controlled Trial.

Children with anorexia nervosa (AN) are at risk of adult height deficit due to prolonged low height velocity (HV). To investigate the effects of human growth hormone (GH) injections on HV in children with AN and severe growth impairment. In this prospective, randomized, double-blind, single-center, proof-of-concept trial, children with AN and low HV (≤2 cm/year) for at least 18 months, and a bone age ≤12 years for girls and ≤14 years for boys, were randomized to receive daily subcutaneous injections of human GH (0.050 mg/kg/day) or placebo for 12 months. Change in HV after 12 months. In total, 8 patients were assigned to the GH group and 6 to the placebo group. Patients had a median (25th-75th percentile) HV of 1.0 (0.5;1.5) cm/year. The effect of GH treatment increased strongly after 6 months, with a height gain after 12 months of 9.65 (8.0;11.6) cm for the GH group vs 3.85 (1.7;7.3) cm for the placebo group, with an absolute median (2.5th-97.5th percentile) difference between the groups of 5.8 (-1.85;9.68) cm after bootstrapping. The percentage of patients with a HV > 5 cm/year during the study period was higher in the GH group than in the placebo group (100% vs 50%, P = 0.05). Adverse events occurred in similar numbers in the 2 groups, were mild or nonfatal, and did not lead to treatment being stopped. GH administration to improve HV is a potentially valid option for increasing HV in children with AN and prolonged severe growth failure.

GHD Diagnostics in Europe and the US: An Audit of National Guidelines and Practice

Introduction: Almost 20 years after the first international guidelines on the diagnosis and treatment of GHD have been published, clinical practice varies significantly. The low accuracy of endocrine tests for GHD and the burden caused by ineffective treatment of individual patients were strong motives for national endocrine societies to set up national guidelines regarding how to diagnose GHD in childhood. This audit aims to review the current state and identify common changes, which may improve the diagnostic procedure. Methods: A group of eight German pediatric endocrinologists contacted eight pediatric endocrinologists from Spain, France, Poland, the UK, the Netherlands, Denmark, Italy, and the US. Each colleague responded as a representative for the own country to a detailed questionnaire containing 22 open questions about national rules, guidelines, and practice with respect to GHD diagnostics and GH prescription. The results were presented and discussed in a workshop and then documented in this study which was reviewed by all participants. Results: National guidelines are available in 7 of 9 countries. GH is prescribed by pediatric endocrinologists in most countries. Some countries have established boards that review and monitor prescriptions. Preferred GH stimulation tests and chosen cutoffs vary substantially. Overall, a trend to lowering the GH cutoff was identified. Priming is becoming more popular and now recommended in 5 out of 9 countries; however, with different protocols. The definition of pretest-conditions that qualify the patient to undergo GH testing varies substantially in content and strictness. The most frequently used clinical sign is low height velocity, but definition varies. Height, IGF-1, and bone age are additional parameters recommended in some countries. Conclusions: GHD diagnostics varies substantially in eight European countries and in the US. It seems appropriate to undertake further efforts to harmonize endocrine diagnostics in Europe and the US based on available scientific evidence.

Pituitary deficiency and precocious puberty after childhood severe traumatic brain injury: a long-term follow-up prospective study

Objectives Childhood traumatic brain injury (TBI) is a public health issue. Our objectives were to determine the prevalence of permanent pituitary hormone deficiency and to detect the emergence of other pituitary dysfunctions or central precocious puberty several years after severe TBI. Design Follow-up at least 5 years post severe TBI of a prospective longitudinal study. Patients Overall, 66/87 children, who had endocrine evaluation 1 year post severe TBI, were included (24 with pituitary dysfunction 1 year post TBI). Main outcome measures In all children, the pituitary hormones basal levels were assessed at least 5 years post TBI. Growth hormone (GH) stimulation tests were performed 3-4 years post TBI in children with GH deficiency (GHD) 1 year post TBI and in all children with low height velocity (<-1 DS) or low IGF-1 (<-2 DS). Central precocious puberty (CPP) was confirmed by GnRH stimulation test. Results Overall, 61/66 children were followed up 7 (5-10) years post TBI (median; (range)); 17/61 children had GHD 1 year post TBI, and GHD was confirmed in 5/17 patients. For one boy, with normal pituitary function 1 year post TBI, GHD was diagnosed 6.5 years post TBI. 4/61 patients developed CPP, 5.7 (2.4-6.1) years post-TBI. Having a pituitary dysfunction 1 year post TBI was significantly associated with pituitary dysfunction or CPP more than 5 years post TBI. Conclusion Severe TBI in childhood can lead to permanent pituitary dysfunction; GHD and CPP may appear after many years. We recommend systematic hormonal assessment in children 1 year after severe TBI and a prolonged monitoring of growth and pubertal maturation. Recommendations should be elaborated for the families and treating physicians.

Pituitary deficiency and precocious puberty after childhood severe traumatic brain injury: a long-term follow-up prospective study.

Objectives Childhood traumatic brain injury (TBI) is a public health issue. Our objectives were to determine the prevalence of permanent pituitary hormone deficiency and to detect the emergence of other pituitary dysfunctions or central precocious puberty several years after severe TBI. Design Follow-up at least 5 years post severe TBI of a prospective longitudinal study. Patients Overall, 66/87 children, who had endocrine evaluation 1 year post severe TBI, were included (24 with pituitary dysfunction 1 year post TBI). Main outcome measures In all children, the pituitary hormones basal levels were assessed at least 5 years post TBI. Growth hormone (GH) stimulation tests were performed 3-4 years post TBI in children with GH deficiency (GHD) 1 year post TBI and in all children with low height velocity (<-1 DS) or low IGF-1 (<-2 DS). Central precocious puberty (CPP) was confirmed by GnRH stimulation test. Results Overall, 61/66 children were followed up 7 (5-10) years post TBI (median; (range)); 17/61 children had GHD 1 year post TBI, and GHD was confirmed in 5/17 patients. For one boy, with normal pituitary function 1 year post TBI, GHD was diagnosed 6.5 years post TBI. 4/61 patients developed CPP, 5.7 (2.4-6.1) years post-TBI. Having a pituitary dysfunction 1 year post TBI was significantly associated with pituitary dysfunction or CPP more than 5 years post TBI. Conclusion Severe TBI in childhood can lead to permanent pituitary dysfunction; GHD and CPP may appear after many years. We recommend systematic hormonal assessment in children 1 year after severe TBI and a prolonged monitoring of growth and pubertal maturation. Recommendations should be elaborated for the families and treating physicians.

Growth Hormone Deficiency in Children: From Suspecting to Diagnosing.

Isolated Growth hormone deficiency is an important and treatable cause of short stature. However, it is often difficult to diagnose the condition with certainty due to the lack of a single robust diagnostic test. Short children, other than those with the classical phenotype of immature chubby facies, truncal obesity and micropenis in boys, or those with history of cranial lesions with known association with hypopituitarism, should be evaluated for growth hormone deficiency only after excluding the other more common conditions. These children typically have height markedly below that expected for their midparental height with low height velocity and delayed bone age. Growth hormone levels should be checked by provocative testing, after ensuring that the child is euthyroid, and after priming with sex steroids if indicated. Low levels of Insulin-like growth factor 1 and Insulin-like growth factor binding protein 3 and pituitary abnormalities on neuroimaging provide important corroborative evidence to the diagnosis.

Short stature and hypoparathyroidism in a child with Kenny-Caffey syndrome type 2 due to a novel mutation in FAM111A gene

BackgroundHypoparathyroidism in children is a heterogeneous group with diverse genetic etiologies. To aid clinicians in the investigation and management of children with hypoparathyroidism, we describe the phenotype of a 6-year-old child with hypoparathyroidism and short stature diagnosed with Kenny-Caffey syndrome (KCS) Type 2 and the subsequent response to growth hormone (GH) treatment.Case presentationThe proband presented in the neonatal period with hypocalcemic seizures secondary to hypoparathyroidism. Her phenotype included small hands and feet, hypoplastic and dystrophic nails, hypoplastic mid-face and macrocrania. Postnatal growth was delayed but neurodevelopment was normal. A skeletal survey at 2 years of age was suggestive of KCS Type 2 and genetic testing revealed a novel de novo heterozygous mutation c.1622C > A (p.Ser541Tyr) in FAM111A. At 3 years and 2 months, her height was 80cms (SDS −3.86). She had normal overnight GH levels. GH therapy was commenced at a dose of 4.9 mg/m2/week for her short stature and low height velocity of 5cms/year. At the end of the first and second years of GH treatment, height velocity was 6.5cms/year and 7.2cms/year, respectively with maximal dose of 7.24 mg/m2/week.ConclusionThis case highlights the phenotype and the limited response to GH in a child with genetically proven KCS type 2. Long-term registries monitoring growth outcomes following GH therapy in patients with rare genetic conditions may help guide clinical decisions regarding the use and doses of GH in these conditions.

Longitudinal Growth in Children and Adolescents with Type 1 Diabetes.

To study longitudinal growth in children with type 1 diabetes mellitus. Anthropometry, disease duration, insulin regimens and HbA1C recorded from patients with diabetes enrolled in a specialty clinic. 160 children (75 boys; mean (SD) age 9.4 (3.3) y) were enrolled. 35% children had low (<25th centile) height velocity. Disease duration and HbA1C affected height velocity (adjusted for puberty). Children on basal-bolus had higher height velocity Z scores than those on a split mix regimen [(0.5(1.6) vs. -0.3(1.4), P<0.05)]. Children diagnosed before 5 years of age had lowest height velocity. Of the children who reached final height, 53% remained below target height. Children with type 1 diabetes mellitus have lower height velocity compared to healthy children; those diagnosed at younger age were at higher risk for growth failure.

Height, Muscle, Fat and Bone Response to Growth Hormone in Short Children with Very Low Birth Weight Born Appropriate for Gestational Age and Small for Gestational Age

Background/Aims: Growth hormone (GH) treatment is approved for short children born SGA but not for AGA. Our aim was to study the effect of GH in short VLBW SGA and AGA children. Methods: The study group comprised 44 prepubertal short children with a birth weight <1,500 g: 27 AGA (12 females) and 17 SGA (6 females). Mean values at GH start were (AGA, SGA): age 6.94, 7.14 years, height standard deviation score (SDS) -3.33, -3.33, and GH dose (mean ± SD) 54 ± 12, 51 ± 11 µg/kg/day. Arm and calf cross-sectional muscle area using peripheral quantitative computer tomography, body composition data using dual-energy X-ray absorptiometry and body impedance assessment, maximal isometric grip force and skin fold thickness, IGF-1 and IGFBP-3 were measured at the start and after 12 months of GH. Results: At GH start, both groups had similar characteristics with low height, weight, height velocity, muscle mass, bone thickness and content. The first year of GH treatment led to changes in muscle area SDS (AGA, SGA) -2.23 to -0.73 (p = 0.0010), -3.18 to -1.17 (p = 0.060) (AGA vs. SGA p = 0.61), fat area SDS -1.06 to -1.83 (p = 0.054), -0.62 to -1.75 (p = 0.12) (AGA vs. SGA p = 0.65) and height velocity SDS -0.0015 to 4.2 (p < 0.0001), -0.18 to 3.3 (p < 0.0001) (AGA vs. SGA p = 0.36). Conclusions: Growth, muscle and fat mass are similarly impaired in short prepubertal AGA and SGA VLBW children. The children born AGA show a similar or better response to GH compared to those born SGA. These results reveal the arbitrary nature of using the criterion ‘SGA' for eligibility to GH treatment in children born with a birth weight <1,500 g.

Age-based reference ranges for annual height velocity in US children.

Clinicians caring for children rely on measures of linear growth as a biomarker of development and overall health. Current reference ranges for height velocity (HV) for US children are unable to provide HV percentiles or Z-scores for early maturing and late maturing children at ages other than age at peak velocity. We present empirically acquired, age-specific reference ranges for HV from a contemporary sample of US youth. Subjects were enrolled in the Bone Mineral Density in Childhood Study, a large, multicenter, multiethnic, contemporary cohort of children (aged 5-19 y at enrollment) from the United States followed for up to 7 years. More than 4000 annual (12 ± 1 mo) HV measurements from approximately 1500 children were available. Pubertal status was determined by breast stage or testicular volume assessed by experienced health providers. Age-specific reference ranges were determined using the LMS method. Reference ranges (third to 97th percentiles) were generated for the entire cohort and for subgroups whose pubertal timing was defined as "earlier," "average," or "later." African American girls experienced earlier pubertal onset and had greater HV at younger ages and lower HV at older ages, compared to non-African American girls; differences did not persist after adjustment for pubertal timing. These differences were not observed for males. These reference ranges for annual HV can be used to assess growth relative to peers of the same age and sex, with consideration of pubertal timing. Z-scores and exact percentiles for HV can also be determined for population studies.

Traumatic Brain Injury is a Rarely Reported Cause of Growth Hormone Deficiency

We determined the frequency of traumatic brain injury (TBI)-related growth hormone deficiency (GHD) from a large registry of growth hormone-deficient subjects and compared these subjects' clinical characteristics with those of children with idiopathic growth hormone deficiency (IGHD). A surprisingly small number of subjects with TBI-induced GHD (n = 141) were registered compared with those with IGHD (n = 23,722). At onset of treatment, the subjects with TBI-induced GHD were older (P = .045), had lower height velocity (P < .001), had a greater number of other pituitary hormone deficiencies (P < .001) and, after a year of recombinant human GH treatment, demonstrated a greater change in height velocity (P = .016). We speculate that TBI-induced GHD may be a neglected phenomenon in childhood, and recommend prospective longitudinal studies to explore its natural history and frequency.

Evaluation of Insulin-like Growth Factor (IGF)-I and IGF Binding Protein-3 Generation Test in Short Stature

Differentiation between growth hormone deficiency (GHD) and idiopathic short stature (ISS) based on GH tests and basal IGF-I and IGFBP-3 levels may be difficult. The aim of this study was to evaluate the role of pharmacological GH tests, IGF-I and IGFBP-3 generation test and height velocity off-treatment in the evaluation of GHD and ISS. Thirty-three (17 M, 16 F) prepubertal short (height SDS < -2) children were divided into two groups: Group 1 (n = 19) with peak GH level <10 tg/l (GHD) and Group 2 (n = 14) GH > or =10 microg/l in two sex steroid primed pharmacological GH tests. Having excluded other diagnoses, Group 2 was regarded as having ISS. The generation test was performed concomitantly (0.1 IU/kg GH s.c. for 4 days) with IGF-I and IGFBP-3 measured on the 4th day in both groups. The patients were followed for a year for height velocity (HV). Group 1 and 2 had comparable height SDS (-2.3 +/- 0.4 and -2.3 +/- 0.3) at comparable ages (7.8 +/- 2.8 and 7.0 +/- 2.7 yr). Although the deltaIGF-I response was low (<2.0 nmol/l 115 ng/ ml]) in seven (37%) children in the GHD group, all GHD patients with low height velocity had adequate (> or =14 nmol/I [400 ng/ml]) deltaIGFBP-3 response. deltaIGFBP-3 in the generation test showed a negative correlation with HV (p = 0.021, r = -0.570) and also with basal IGFBP-3 (p <0.001, r = -0.743) in the GHD group. In the ISS group, deltaIGF-I and deltaIGFBP-3 responses were low in 31% and 7%, respectively, and the correlation between basal IGF-I, IGFBP-3 and HV and between delta values in the generation test were significantly positive, pointing to a difference in the growth response of these children. In the GHD group, based on pharmacological tests, an adequate deltaIGFBP-3 response in the generation test predicts poor height velocity at follow up and thus strengthens the diagnosis of true GHD.

Effects of nano-scale particles in chemical mechanical polishing process

Chemical mechanical polishing(CMP) is a manufacturing process used to achieve th e high levels of global and local planarity required. Currently, the slurries us ed in CMP usually contain particles at nano scale to accelerate the material rem ove ratio (MRR) and to optimize the planarity. Micro polar theory will provide a feasible candidate to describe the rheology of these fluids. It will provide so me insights into the mechanism to solve the flow equation of CMP with the micro- polar effect considered. The effects of micro polarity on load and moments are s imulated and computation results are given. The results show that micro-polarity will give rise to an increase in load capacity to a certain extent by increasin g the equivalent viscosity of the slurries, through which the material removal c an be accelerated. The size-dependent feature can be seen since it becomes more prominent with low pitch height and low pad velocity. The effects of micro-polar ity on material removal rate in CMP process were experimentally investigated by altering the polarity of the slurries, which support the theoretical analysis.

Linear growth in prepubertal children with atopic dermatitis

OBJECTIVETo define the evolution of prepubertal growth in atopic dermatitis and the factors influencing that growth pattern.METHODSHeight and height velocity over two years, weight, triceps and subscapular skin fold thickness,...

THE IMPACT OF DOSAGE ON THE EFFECT OF GROWTH HORMONE THERAPY IN CHILDREN WITH IDIOPATHIC SHORT STATURE

The growth response to growth hormone (GH) therapy in children with idiopathic short stature (ISS) is generally characterized by a rapid height velocity (HV) increment followed by a progressive decline. There are no data about the dose-response relationship in such children. We studied 24 children (19 M, 5 F) with ISS and a HV < P25, who, after two years of observation, underwent GH therapy over 3 years in three regimens: gr 1 and 2 received 3 and 4.5 IU/m2 b.s. 6 times per week, and gr 3 received 3 IU/m2 in the 1st year and 4.5 IU thereafter. The median HV SDS was -1.8 in the preinclusion year, and 0.3 in the pretreatment year (p<0.05). In the 1st year on GH the mean (SD) HV SDS rose from 0.4 (1.5) to 5.7 (2.4) on 3 IU/m2 (gr 1+3) and from 0.1 (0.7) to 7.1 (2.1) on 4.5 IU/m2. There was no statistical difference between the groups. In the 2nd and 3rd year the prepubertal children from all groups showed a similar decrease. Mean height SDS increased by 1.2 in all groups, compared to 0.3 in an untreated control group (n=40). Mean bone age (BA) in gr 1,2 and 3 increased by 3.4, 3.0 and 3.9 years (NS between groups). Predicted adult height SDS (Bayley Pinneau) increased by 1.6 (0.8) in group 2 (p=0.01), but not in groups 1 and 3 (p=0,31 and p=0.13). In conclusion: 1) short children selected on the basis of a low HV show a normal mean velocity in the next year; 2) the three dosage regimens lead to a similar initial growth acceleration followed by a similar decrease; 3) the higher dosage appears more effective in terms of predicted adult height, although attained final heights have to be awaited for definitive conclusions.