High-dose growth hormone treatment of short children born small for gestational age

The effect of GH administration was evaluated over 2 yr in 50 short, prepubertal, non-GH deficient children born small for gestational age, who had been randomly allocated to a group receiving no treatment or daily sc GH treatment at a dose of 0.2 or 0.3 IU/kg. At the start of the study, mean age was 5.2 yr, bone age was 4.0 yr, height SDS was -3.5, height velocity SDS was -0.8, weight SDS was -2.7, and body mass index SDS was -1.9. Catch-up growth was observed in none of the untreated and all of the treated children. The response to GH treatment included a near doubling of growth velocity and of weight gain and a mean height increment of more than 2 SDS. GH treatment was associated with a distinct acceleration of bone maturation. The differences between the growth responses evoked by the two GH doses were minor. The prepubertal GH-induced catch-up growth was associated with elevated serum concentrations of insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and osteocalcin, whereas insulin-like growth factor-II levels remained unaltered. GH treatment was well tolerated. In conclusion, high-dose GH administration over 2 yr is emerging as a potential therapy to increase the short stature that results from insufficient catch-up growth in young children born small for gestational age. The long-term impact of this approach remains to be delineated.     

Spontaneous 24-hour growth hormone profiles in prepubertal small for gestational age children

To evaluate spontaneous GH secretion in terms of both secretory rate and pulsatile pattern in prepubertal children born small for gestational age (SGA) and still short (below -2 SD scores) at or after 2 yr of age, 24-h GH profiles were investigated in 106 such patients (75 boys and 31 girls; mean age, 7.3 +/- 0.3 yr), 14 of whom (10 boys and 4 girls) had Silver-Russell syndrome. The 24-h secretion of GH was compared with that in 2 reference populations of prepubertal children born at an appropriate size for gestational age (AGA): 179 short healthy children (143 boys and 36 girls; mean age, 10.2 +/- 0.2 yr) and 73 children of normal stature (54 boys and 19 girls; mean age, 10.4 +/- 0.3 yr). Plasma GH concentrations from the 24-h profiles were transformed to GH secretion rates by means of a deconvolution technique. For the SGA children, the mean GH secretion rate was 0.3 U/24 h, with a positive correlation with age, whereas for the reference groups it was higher, 0.5 U/24 h for the short children (P < 0.05) and 0.7 U/24 h for the children of normal stature (P < 0.001). Interestingly, the GH secretion rate correlated positively with weight for height, expressed as the SD score, in girls born SGA (r = 0.40; P < 0.05), whereas an inverse correlation was found for the short AGA girls (r = -0.44; P < 0.05). The mean baseline GH level in the SGA children correlated negatively with age (r = -0.53; P < 0.01), with the highest values found for children younger than 6 yr of age. On the average, 8 GH peaks/24-h period were found in all groups of children, and using Fourier time-series analyses, a similar rhythmicity was found in all groups. In the SGA group, the children younger than 6 yr of age had more GH peaks with lower amplitudes than the older children. It is concluded that children born SGA and still short at or after 2 yr of age spontaneously secrete less GH than healthy children of short stature born AGA. Both of these subgroups of prepubertal short children, however, secrete less GH than children of normal height. This finding might in part explain the growth failure in SGA children. Moreover, in the youngest SGA children (2-6 yr of age) there was another pattern of GH secretion, with a high basal GH level, a low peak amplitude, and a high peak frequency.(ABSTRACT TRUNCATED AT 400 WORDS)     

Human growth hormone treatment of short-stature children born small for gestational age: effect on muscle and adipose tissue mass during a 3-year treatment period and after 1 year's withdrawal

In addition to its growth promoting effect, GH has profound metabolic effects that have not always been evaluated in longitudinal studies. We have recently shown that the effect of GH on body composition can be evaluated by magnetic resonance imaging measurement of adipose and muscle tissue cross-sectional (cs) areas in the thigh. The aim of this study was to evaluate the long-term effects of human GH (hGH) (0.2 IU/kg day) on muscle and adipose tissue mass during a 3-yr treatment period and after 1 year's withdrawal in short SGA (small for gestational age) children. Measurement of muscle and fat tissue mass by magnetic resonance imaging of the thighs was used to study the metabolic effect of hGH in 14 prepubertal short children born SGA. Results were compared with those of a control group of 7 normal children followed longitudinally. An increase of muscle tissue cs area was observed during the 3 yr of hGH treatment, an increase which was significantly different during the first 2 yr of treatment from that seen in controls (+31.2+/-2.6% and +18.1+/-1.8% during the 1st and 2nd year, respectively, vs. +9.1+/-2.6% change during 1 yr in controls). After a significant decrease in adipose tissue cs area during the first year of therapy (-16.4+/-3.4% vs. baseline values), an increase in adipose tissue cs area occurred during the second and third years. At the end of the third year, the muscle tissue cs area change was significantly greater in SGA-treated children, as compared with controls (+71.6+/-4.6% vs. 22.1+/-4.6%; P < 0.001), whereas the adipose tissue cs area change was similar in the two groups (+12.6+/-9.5% vs. +19.9+/-4.2%). After hGH withdrawal, the effects were opposite after 3 months, as compared with those observed after the first 3 months of hGH administration, whereas no additional significant change was seen after 1 yr off treatment, indicating the maintenance of muscle and adipose tissue mass. In conclusion, hGH administered to SGA children is effective in improving growth velocity and has long-term effects on muscle and adipose tissue mass. These effects may lead to speculation about the sensitivity of these tissues to GH. The physiological consequences of such effects must be evaluated.     

Postnatal growth and psychomotor development in small for gestational age Brazilian infants.

Early psychomotor development (PD), as measured by the Gesell Developmental Schedules, of 29 infants that were small for gestational age (SGA) was more dependent on postnatal growth than the PD of 51 infants whose birth weight was appropriate for gestational age. The significant association of postnatal growth with PD in SGA Ss at 4, 8, and 12 mo of age was not explained by birth weight or SES. Findings support the hypothesis that the factors that determine postnatal growth in SGA infants also affect neurointegrative development. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Growth of infants and young children born small or large for gestational age: findings from the Third National Health and Nutrition Examination Survey

An allele-specific polymerase chain reaction (ASPCR) assay for prenatal genotyping of the Kidd antigen system in order to identify pregnancies at risk for haemolytic disease of the newborn (HDN) was developed. Oligonucleotide primers were designed for ASPCR of JKA and JKB. A validation study was performed using DNA isolated from 54 serotyped whole blood samples and 8 amniocentesis samples. A concordance rate of 100 per cent was observed between serotyping and ASPCR detection of the JKA and JKB alleles. Experiments were conducted to quantify the maternal contamination that could be tolerated in Kidd ASPCR assays. The sensitivity of this assay ranged from 0.2 per cent when detecting the presence of JKB and JKA background, to 2 per cent for detecting the presence of JKA in a JKB background. This sensitive assay is particularly useful for rapid genotyping of fetal amniotic cells to identify pregnancies at risk for HDN due to incompatibilities within the Kidd blood group system.     

Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children

We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an i.v. bolus injection of growth hormone releasing hormone 1-29, 1 microgram/kg, significantly enhanced the growth hormone response to the neuropeptide, confirming the results of previous studies which used the i.v. route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.     

Glucose disappearance rate, insulin response and growth hormone response in the small for gestational age and premature infant of very low birth weight

The pulmonary resorption of air pollutants constitute a significant factor for the whole body burden of men, as can be shown for lead, SO2 and CO. Particle size as well as water and lipid solubility of the noxious agents are important variables for the extent of the interaction with the pulmonary surface. Main objects for the inhalative pollutants are the bronchioli terminales and the respiratory epithel. The electronmicroscopic investigations point out a specific irritability of these structures as far as lead, oxydants and fibers are concerned. Comparatively low concentrations of the agents produce, in chronic exposure, changes in the caliber of the small airways and widening of the ductus alveolares and the alveoli. In addition to the reduction of the inner lungsurface one observes a thickening of the diffusion barrier in loco through some harmful substances. A number of pollutants influence a primary cytotoxic effect on alveolar macrophages. Thereby the bacterial infection resistance of the lung is reduced; moreover the phagozytes play an important part for the detoxification of carcinogenic carbohydrates. Hence the lung functions as a resorptionorgan, as a protectionorgan and as an object of damage for various air pollutants.     

First-trimester growth restriction and fetal aneuploidy: the effect of type of aneuploidy and gestational age

Changes in the proportions of the various lipid components in spermatozoa were investigated throughout the reproductive period (24-72 wk of age) of male chickens. Sperm motility and in vivo fertility were also measured, and correlation coefficients with the lipid values were determined. The proportion of total phospholipid (PL) increased to reach a maximum value at 39 wk and decreased significantly thereafter. The relative content of free cholesterol and triacylglycerols showed no change in spermatozoa during aging or in relation to fertility values; free fatty acids and cholesterol esters increased continuously with age. Of the various PL classes, phosphatidylserine and phosphatidylcholine displayed a pattern of changes with age positively and negatively, respectively, in relation to the changes of fertility. The proportion of phosphatidylethanolamine had significantly decreased by the end of the reproductive period. The proportions of C16:0, C18:0, and C18:1n-9 within the PL of the spermatozoa increased with age, and those of C20:4n-6, C22:4n-6, and C22:6n-3 decreased. Positive correlations were found between fertility and total PLs, phosphatidylserine, and PL-bound C20:4n-6 and C22:4n-6; a negative correlation was found between fertility and phosphatidylcholine. Motility was positively correlated with the level of PL and negatively with that of free cholesterol; it was also positively correlated with the levels of C22:4n-6 and C22:6n-3 and negatively with those of C16:0, C18:0, and C18:1n-9. The results suggest that the lipid and fatty acid compositions of spermatozoa may be important predictors of fertility.     

Illegal parking in handicapped zones: Demographic observations and review of the literature.

Found that the overall rate of illegal parking in a parking space reserved for handicapped persons by a total of 266 drivers was 62.0%. 67.7% of Ss were White, and 85.7% were estimated to be above the age of 25 yrs. Although there were more violations recorded for Whites and older drivers, the percentage of young and Black drivers who were violators was higher than that for Whites and older drivers. Violators tended to remain in the spaces for shorter durations than did legal parkers. Availability of equally convenient, illegal parking alternatives (e.g., fire lanes) appeared to reduce violations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased proportion of circulating non-22-kilodalton growth hormone isoforms in short children: a possible mechanism for growth failure

Current knowledge about the interaction between GH and its receptor suggests that the molecular heterogeneity of circulating GH may have important implications for growth. The aim of this study was to investigate the proportion of circulating non-22-kDa GH isoforms in prepubertal children with short stature (height less than -2 SD score) of different etiologies. We have also evaluated the relationships among the ratio of non-22-kDa GH isoforms, auxology, and spontaneous GH secretion. The study groups consisted of 17 girls with Turner's syndrome (TS), aged 3-13 yr, 25 children born small for gestational age (SGA) without postnatal catch-up growth, aged 3-13 yr; and 24 children with idiopathic short stature (ISS), aged 4-15 yr. The results were compared with those from 23 prepubertal healthy children of normal stature (height +/- 2 SD score), aged 4-13 yr. Serum non-22-kDa GH levels, expressed as a percentage of the total GH concentration, were determined by the 22-kDa GH exclusion assay, which is based on immunomagnetic extraction of monomeric and dimeric 22-kDa GH from serum and quantitation of non-22-kDa GH using a polyclonal antibody-based GH assay. All samples were selected from spontaneous GH peaks in 24-h GH profiles. The median proportion of non-22-kDa GH isoforms was increased in children born SGA (9.8%; P = 0.05) and girls with TS (9.9%; P = 0.01), but not in the group of children with ISS (8.9%), compared with that in normal children (8.1%). Individually, increased proportions of non-22-kDa GH isoforms, with values more than 2 SD above the mean for the normal group, were observed in 5 girls with TS, 5 children born SGA, and 4 children with ISS. In children born SGA, the proportion of non-22-kDa GH isoforms was directly correlated with different estimates of spontaneous GH secretion [mean 24-h GH concentration (r = 0.41; P = 0.04), area under the curve over baseline (r = 0.41; P = 0.04), and GH peak area (r = 0.61; P = 0.003)], whereas it was inversely correlated with height SD score (r = -0.42; P = 0.04). In conclusion, an increased proportion of circulating non-22-kDa GH isoforms was observed at spontaneous GH peaks in some non-GH-deficient short children. Our results suggest that the ratio of non-22-kDa GH isoforms in the circulation may have important implications for normal and abnormal growth.     

Faecal chymotrypsin in small for gestational age infants: effects of nucleotides and breast feeding

The effect of diet on pancreatic exocrine function, measured by faecal chymotrypsin activity (FCA), was studied longitudinally in three groups of small for gestational age (SGA) infants in the first six months of life. The three groups comprised breastfed infants (group B), those randomly allocated to receive a standard infant formula (group S), or the same formula supplemented with nucleotides (group N). The three groups did not differ in their birthweight or gestational age. Nucleotide supplementation of infant formula improves catchup growth in SGA infants but whether this is due to effects on the gastrointestinal mucosa or the exocrine pancreas is not known. There were no differences in FCA at study entry but by one month group B had significantly lower values than the other groups, and this was maintained at 2, 4, and 6 months. Groups N and S did not differ significantly at any time point. Nucleotide supplementation of infant formula does not influence pancreatic exocrine function and its effect on growth is unlikely, therefore, to be mediated through the pancreas. This study shows that breast feeding is associated with lower FCA which may be related to the lower protein content of human milk. Reliable interpretation of FCA in young infants requires information about their diet.     

Morbidity during the first year of life in small for gestational age infants

OBJECTIVE: To study the effect of early postnatal dexamethasone (days 1-3) on the incidence and severity of chronic lung disease in preterm infants with respiratory distress syndrome. METHODS: A multicentre, randomised, placebo controlled, blinded study was carried out in 18 neonatal intensive care units in Israel. The primary outcome measure was survival to discharge without requirement for supplemental oxygen therapy beyond 28 days of life. The secondary outcome measures were requirement for mechanical ventilation at 3 and 7 days, duration of ventilation or oxygen therapy, need for subsequent steroids for established chronic lung disease and incidence of major morbidities. RESULTS: The study consisted of 248 infants (dexamethasone n = 132; placebo n = 116). No differences were found in the outcome variables except for a reduction in requirement for mechanical ventilation at age 3 days in treated infants (dexamethasone 44%, placebo 67%; P = 0.001). Gastrointestinal haemorrhage, hypertension, and hyperglycaemia were more common in treated infants, but no life threatening complications, such as gastrointestinal perforation, were encountered. CONCLUSIONS: These data do no support the routine use of early postnatal steroids, but may justify further study in a selected, high risk group of infants.     

Precocious maturation of auditory evoked potentials in prematures: influence of gestational age and sex]

This study was undertaken to determine the effect of 5-fluorouracil on gastrointestinal carcinogenesis. Sixty rats were divided into three groups of 20 rats each. All rats were exposed to N-methyl-N'-nitro-N-nitrosoguanidine for the first 20 weeks. Group 1 rats received intraperitoneal injections of 5-fluorouracil for the first 20 weeks and were then observed for the second 20 weeks. Group 2 rats also received 5-fluorouracil injections, but for the second 20 weeks. Group 3 rats received no 5-fluorouracil treatment. Four of 20 rats in group 1 developed an invasive adenocarcinoma. In group 3, invasive squamous cell carcinoma and adenocarcinoma developed in one rat each. None of the group 2 rats had malignant lesions. These results suggested that 5-fluorouracil is not effective in suppressing the initial stage of gastrointestinal carcinogenesis with a coexisting carcinogen. Rather, the therapeutic effect is exerted in later stages of tumor progression.     

Overnight urinary growth hormone in normally growing prepubertal children: effect of urine volume. The one-year growth study

Wear of the polyethylene tibial components is a potential cause of failure in total knee arthroplasty. In addition to pitting, burnishing, and scratching, subtle striations on the bearing portion of the tibial surface have been observed in components retrieved relatively early after implantation. The striated pattern most typically occurred in areas centrally located within the articulating surface. The striations were anteroposterior directed and were identified as local cold flow at the surface. There was a strong correlation between the medial and lateral striated areas, suggesting that these patterns are related to cyclic rolling of the knee. The general characteristics and alignment of the striations could be attributed to the compressive and tractive forces occurring during femoral rollback. For the clinician, these results suggest that kinematics, as well as contact stress, should be considered when evaluating wear of polyethylene components.     

The future of dental amalgam: a review of the literature. Part 2: Mercury exposure in dental practice

This is the second article in a series of seven on the future of dental amalgam. It describes the means of exposure to mercury which can occur in dental surgeries from the storage of mercury, preparation and placement of dental amalgam restorations, polishing dental amalgam restorations, the removal of amalgam fillings and the storage of waste amalgam. It also reports on the monitoring of dental practices and studies on the mercury air levels in dental surgeries and blood and urine levels in dentists and their staff. Also, studies which compare these levels with the health and neurobehaviour of dentists and their staff are included. In addition, it discusses post-mortem studies of the mercury levels in body organs in dentists and controls. It then recommends methods for the safe handling of mercury and dental amalgam. Finally, it discusses the issues surrounding the release of mercury into the environment from dental practices and industry.     

Behavioral treatments for nocturnal enuresis in children: A review of the recent literature.

Reviews recent literature on the use of behavioral treatments for functional nocturnal enuresis in children. The treatment procedures are divided into 3 categories: (a) those that used the standard urine alarm or bell-and-pad, (b) those that employed retention control training, and (c) those that modified existing stimulus or consequent events but that did not use the urine alarm or retention control training as the primary mode of treatment. The results are presented and evaluated under each of the 3 categories. (3 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Diagnosis and treatment of encopresis: A review of the literature.

Describes diagnostic indicators that distinguish psychological from physiological encopresis. A behavioral definition of psychogenic encopresis is presented, and 4 treatment approaches to this problem are examined: (a) psychoanalytic, (b) medical, (c) behavioral, and (d) a combination of medical and behavioral. Evidence suggests that approaches (c) and (d) yield the most effective and efficient results. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An early rise in urine N-telopeptide predicts the growth response of normal prepubertal short children to growth hormone therapy

The effects of growth hormone (GH) therapy on biochemical markers of bone turnover were investigated in 11 short prepubertal children without GH deficiency by measuring serum osteocalcin, a marker for bone formation, and urinary concentrations of pyridinium cross-linked amino acids of collagen (PCL), and the peptide-bound pyridinoline residue N-telopeptide (NT), which are specific markers for bone resorption. GH treatment for three months increased bone turnover in this group of children: urinary PCL concentrations increased from 69 +/- 6.2 to 114 +/- 9.3 nmol/mmol Cr (p < 0.01), and urinary NT levels increased from 512 +/- 65 to 766 +/- 74 pmol BCE/mumol Cr (p = 0.058). Serum osteocalcin concentrations increased from 13.64 +/- 2.57 ng/ml to 26.45 +/- 1.39 ng/ml (p < 0.01). The increment in 12-hour urinary concentrations of PCL was highly correlated with the increment in 12-hour urinary NT levels (r = 0.92, p < 0.01). Stepwise multiple regression analysis revealed that the urinary concentrations of NT after 3 months of GH therapy were the best predictor of growth after 12 months of treatment (r = 0.78, F = 7.9, p = 0.037).     

Pubertal growth, sexual maturation, and final height in children with IDDM. Effects of age at onset and metabolic control

The effects of free ampicillin, microencapsulated ampicillin anhydrate (MEAA) and antibiotic-free microspheres on the cell-mediated immune response in Balb/c mice were measured by lymphoproliferation assay, delayed-type hypersensitivity (DTH) and cytokine production. Injection into mice for seven consecutive days with equivalent subcutaneous doses of ampicillin, MEAA or placebo microspheres did not produce any consistent change in lymphocyte proliferation nor did it affect DTH responses or interleukin-2 production. Although the production of interleukin-4 in mice treated with ampicillin or MEAA increased compared with the control mice, this increase was not statistically significant. These results indicate that ampicillin and MEAA have similar effects on cell-mediated immunity in mice.