Dietary protein restriction and selective preference for a protein-containing diet in the golden hamster (Mesocricetus auratus)

The corrected midparental height method was introduced by Tanner in 1970 (Tanner method) and is commonly used to estimate target height in children to evaluate the effectiveness of growth-promoting therapies. It has not been established if the equation used to compute target height should be the same for children with short, normal, or tall parents. In this study, we examined the predicted target height values by parental heights in a large population-based study (n = 2402). A simple linear function of midparental height (x) was proposed to estimate target height (y): y = 45.99 + 0.78x (boys), y = 37.85+0.75x (girls), with a 95% predicted interval of about +/-10 cm. The prediction model was similar for boys and girls in SD scores (SDS), and was not affected by assortative mating or difference in parental heights. The model may underestimate the potential stature by about 2 cm for children with midparental height below -2 SDS, or 163 cm. In comparison, the Tanner method may lead to a 6-cm error in underestimating target height for these children. The function would be a better choice than the Tanner method for estimating target height in the clinical evaluation of growth promotion treatments because it is common that short children also have short parents. Children with very short parents will usually be much taller than their parents in adult stature, and we believe that a different function should be developed. The results support the proposed nondominant, non-sex-linked, polygenic inheritance in stature. The estimated heritability values were 0.75-0.78 in cm or 0.55-0.60 in SDS.     

Growth impairment in very low birthweight children at 12 years: correlation with perinatal and outcome variables

AIM: To compare the growth of very low birthweight (VLBW) children in early adolescence with that of their normal birthweight peers; to examine the role of factors contributing to growth-parental height, perinatal variables, bone maturity and sexual maturation; to examine the correlation between head growth and cognitive and educational outcome. METHODS: Standing and sitting heights, weight, occipito-frontal circumference (OFC), skinfold thicknesses and pubertal staging were assessed in 137 VLBW children and 160 controls at 11-13.5 years of age. Ninety six (70%) of the VLBW children had their bone age assessed using the TW2 method. Reported parental heights were obtained by questionnaire. All children had standardised tests of cognitive and educational ability. Perinatal data had been collected prospectively as part of a longitudinal study. RESULTS: VLBW children had lower heights, weight, and OFC. Skinfold thicknesses were no different. The children's short stature was not accounted for by difference in parental height, degree of pubertal development, or by retarded bone age. Indeed, the TW2 RUS score was significantly advanced in the VLBW children. Using the bone ages to predict final adult height, 17% have a predicted height below the third centile and 33% below the tenth. Weight was appropriate for height, but there was a residual deficiency in OFC measurements after taking height into account. In the VLBW group smaller head size was associated with lower IQ and mathematics and reading scores. CONCLUSIONS: Growth problems persist in VLBW children and final heights may be even more abnormal than present heights suggest. VLBW children have smaller OFCs than expected from their short stature alone and this may be associated with poorer educational and cognitive outcomes.     

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)     

Growth screening and urban deprivation

OBJECTIVES: To assess the effect of urban deprivation on childhood growth in a modern British society by analysing data from a regional growth survey, the Tayside growth study. SETTING: The Tayside Region in Scotland, which has three districts with distinct socioeconomic status: Dundee (D, urban city), Angus (A, rural), and Perth (P, rural and county town). SUBJECTS AND METHODS: Height and weight of 23,046 children (> 90% of the regional childhood population) were measured as part of a child health surveillance programme, by community health care workers at 3, 5, 7, 9, 11, and 14 years. Height standard deviation score (calculated against Tanner) and body mass index (BMI-weight (kg)/height (m)2) were calculated for each child by a central computer program; mean height standard deviation score and BMI standard deviation score were calculated for each measuring centre (school, health clinic). A deprivation score for each centre was calculated from the prevalence of single parent families; families with more than three children; unemployment rate; the number of social class V individuals; the percentage of council houses. RESULTS: Mean height standard deviation score for Tayside was 0.11. An intraregional difference was demonstrated: mean height standard deviation score (SD) D = 0.04 (1.0); A = 0.14 (1.1); P = 0.21 (1.1); P < 0.002. There was a positive association between short stature and increasing social deprivation seen throughout Tayside (P < 0.05), with a strong association in Dundee primary school children (r = 0.6; P < 0.001). Analysis by district showed that the association was significant only above the age of 8 (P < 0.004). There was no relation between BMI and social deprivation. CONCLUSIONS: In an industrialised developed society, urban deprivation appears to influence height mostly in late childhood, and this association should be taken into consideration in the clinical management of short stature. Height seems to be a better physical indicator of urban deprivation, and hence an index of childhood health, than BMI.     

Operation theatres after the year 2000. A colleague assists via satellite]

OBJECTIVE: To evaluate the stature of Russian children with cleft lip and palate (CLP). DESIGN: One hundred twelve Russian children predominantly with repaired unilateral CLP 4 through 10 years of age underwent studies including height measurement, physical examinations, and record review. Children with health concerns that could affect growth were excluded. U.S. growth data from the National Center for Health Statistics (NCHS) and Russian parental heights were used in the absence of Russian growth norms. RESULTS: Based on U.S. norms, the distribution curve for heights for the Russian children was largely confined to the +1 to -1 standard deviation (SD) range. Sixty-two percent of the Russian children had heights below the 50th percentile for American female and male children of the same age. The proportion of children found outside the +1 to -1 SD range approximated the proportion expected statistically for the general population, with 14.4% < -1 SD (16th percentile) and 12% > +1 SD (84th percentile). A total of 3.6% of the children ranked below the third percentile, which is close to the expected 3%. Russian parents' (n = 209) mean heights were 0.5 SD below NCHS's 50th percentile values for adults. CONCLUSION: These results indicate that there is no increased risk of true short stature in 4- to 10-year-old Russian children with repaired CLP.     

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.     

Human in vivo somatic mutation measured at two loci: individuals with stably elevated background erythrocyte glycophorin A (gpa) variant frequencies exhibit normal T-lymphocyte hprt mutant frequencies

The P3 event-related potential (ERP) component was recorded from 7- to 18-year-old children of alcoholics (COAs, n = 50) and age- and sex-matched control children (n = 50) using a visual oddball paradigm, involving nontarget (76%), target (12%), and novel (12%) stimuli. Topographic maps of P3 and associated scalp current density were obtained to supplement a topographic profile analysis. COAs manifested a smaller amplitude P3 to target stimuli over the centroparietal, parietal, and occipital scalp locations than controls. Also, COAs exhibited a smaller amplitude P3 to novel stimuli over the occipital scalp than controls. There were no significant differences between COAs and controls in the P3 scalp topography, indicating that differences in intracranial source strength rather than in source configuration were responsible for the between-group amplitude differences. Also, no significant group differences were observed in the P3 peak latency or in behavioral performance. These results support the notion that the visual P3 may provide a vulnerability marker of alcoholism.     

Stature in Ecuadorians heterozygous for growth hormone receptor gene E180 splice mutation does not differ from that of homozygous normal relatives

Heterozygosity for certain mutations of the GH receptor (GHR) gene has been proposed as the cause of partial resistance to GH, and there has been a recent demonstration of a dominant-negative effect of such a mutation in a mother and child. To examine the effect of heterozygosity in a large genetically homogeneous population with GHR deficiency, in which a substantial number of heterozygous (carrier) subjects and homozygous normal individuals can be compared, we studied a population in Ecuador in which 70 individuals with GHR deficiency were homozygous for the E180 splice mutation. We found that 58 heterozygous relatives of probands were not significantly shorter than 37 homozygous normal relatives [SD score (SDS) for height -1.85 +/- 1.04 (SD) vs. -1.55 +/- 0.96, P > 0.10]. When only those families with both homozygous normals and carriers were compared, the 33 heterozygous and 29 normal relatives did not differ significantly in height SDS (-1.98 +/- 1.07 vs. -1.77 +/- 0.91, P > 0.3). If heterozygosity for the E180 splice mutation were to influence stature, heights of heterozygous parents of probands would be expected to correlate with those of probands and of carriers who are their offspring and not with heights of their homozygous normal children. Parental height SDS did not correlate with height SDS of affected offspring (r = 0.24). For unaffected siblings as a group or analyzed separately as normals or carriers, there was a strong correlation between parental and offspring SDS for height (P < 0.01 for all comparisons). Thus, the effect of homozygosity for the GHR mutation was so profound as to abolish parental influence on height, and there was no difference in the influence of parental stature between carrier and noncarrier offspring. These findings demonstrate no meaningful effect on stature of heterozygosity for the E180 splice mutation of the GHR, which is a functional null mutation and, in the homozygous state, results in profound short stature from severe insulin-like growth factor-I deficiency.     

Increased urinary adrenomedullin excretion in children with urinary-tract infection

BACKGROUND: Adrenomedullin (AM), a smooth-muscle relaxant peptide, is stimulated by cytokines and bacterial endotoxins. We hypothesized that urinary-tract infections may be associated with elevated urinary AM excretion. METHODS: AM in urine was quantified in eleven children with urinary-tract infection and 11 age- and sex-matched controls by radioimmunoassay. RT-PCR was used to demonstrate local AM mRNA expression in the urinary tract. RESULTS: In healthy controls but not in diseased children there was a significant correlation between AM and creatinine in urine (r = 0.91, P < 0.001). AM levels in children with urinary-tract infection were significantly higher than in controls (0.6 +/- 0.41 vs 0.15 +/- 0.14 ng/micromol creatinine; P < 0.001; (means +/- SD)). There was a significant correlation between white cell count and AM in urine (r = 0.78, P < 0.001). AM mRNA was expressed in renal tissue, renal pelvis, ureter, bladder, and urethra. CONCLUSION: The smooth-muscle relaxant peptide adrenomedullin that is synthesized in tissue of the human urinary tract is elevated in urine of patients with urinary-tract infections. A possible consequence might be the interference with the ureteral anti-reflux mechanisms.     

Bone alkaline phosphatase and collagen markers as early predictors of height velocity response to growth-promoting treatments in short normal children

OBJECTIVE: A number of long-term research studies are in progress to evaluate the effects of treatment with GH on growth and final height in children with short stature but no demonstrable abnormality of GH secretion. Such treatment is invasive, expensive and carries some risk to the child. An early indication of growth response would allow restriction of treatment to those children most likely to benefit, but anthropometric measurements are relatively subjective, insensitive and imprecise. The aim of this study was to evaluate bone alkaline phosphatase, procollagen Type I C-terminal propeptide, procollagen Type III N-terminal propeptide and the cross-linked carboxy-terminal telopeptide of Type I collagen as early biochemical predictors of height velocity response to growth-promoting treatments in short normal children. DESIGN: A prospective intervention study, partially placebo controlled on a double blind basis. PATIENTS: Fifty healthy children with familial short stature or constitutional delay in growth and puberty (8 girls, 42 boys, ages 5.5-16.5 years and all either prepubertal (45) or in very early puberty (5 boys) at the start of treatment) were treated with placebo (6), GH alone (32), GH plus oxandrolone (8) or GH plus testosterone (4). MEASUREMENTS: Bone alkaline phosphatase and the collagen markers were measured at the start of treatment and 3 months later. Height velocity was calculated at the start of treatment and again after one year. RESULTS: Pre-treatment biochemical marker concentrations did not predict height velocity response after one year. Increments in all markers after 3 months were significantly correlated with height velocity increments after one year of treatment, the highest correlations being observed for bone alkaline phosphatase (r = 0.67, P < 0.0001) and procollagen Type III N-terminal propeptide (r = 0.57, P < 0.0001). Highly significant correlations (P < 0.0001) were also observed between bone alkaline phosphatase and procollagen Type I C-terminal propeptide (r = 0.55) and between procollagen Type III N-terminal propeptide and the cross-linked carboxy-terminal telopeptide of Type I collagen (r = 0.62). Multiple linear regression with stepwise selection of variables identified bone alkaline phosphatase and procollagen Type III N-terminal propeptide as the only two independent variables that contributed significantly to the prediction of height velocity response after one year (analysis of variance, P < 0.0001). Together they predicted 59% of the variability in height velocity response after a year. CONCLUSIONS: The best early predictors of height velocity response were bone alkaline phosphatase (a protein found in hypertrophic chondrocytes in the epiphyseal growth plate, in calcifying matrix vesicles and in mature osteoblasts) and procollagen Type III N-terminal propeptide, a marker of interstitial fibril biosynthesis in soft tissues. Using these markers, GH treatment could be targeted to those children most likely to benefit in the medium term.     

Overnight growth hormone concentrations are usually normal in pubertal children with idiopathic short stature--a Clinical Research Center study

To estimate the incidence of low growth hormone (GH) concentration in children and adolescents with idiopathic short stature, overnight GH levels were measured in 167 subjects. The results were compared with data from 132 normal children of similar pubertal stage, bone age, or body mass index. The majority of short children had normal overnight GH concentrations in a distribution not significantly different from that observed in normal children. However, in 6% of children grouped by pubertal stage and in 13% of children grouped by bone age, overnight GH levels were below the 95% confidence limits of normal. The overnight GH levels were above normal in 6%. The observed frequencies of both low and high GH levels were significantly greater than expected (P < 0.001). However, when body mass index was included in the analysis, only 5% of the children had low GH measures, and only 4% had high GH measures (both not significant). This frequency of low overnight GH levels in short children is considerably less than that reported by others. Thus, these data do not support the hypothesis that a deficiency of spontaneous GH secretion is a common cause of short stature. We conclude that standard GH stimulation tests, despite their limitations, remain the best definitive test of GH secretion. Subsequent overnight GH studies may be useful, however, in selected clinical settings such as previous cranial irradiation or other central nervous system disorder.     

Short- and long-term (final height) data in children with normal variant short stature treated with growth hormone

Seventeen children with normal variant short stature and a predicted height below -2 SDS were treated with growth hormone (GH) six times a week for a period of 5 years. Patients were randomly selected to receive three different doses of GH, group 1 (n = 6) 3 IU/m2 per day, group 2 (n = 6) 4.5 IU/m2 per day and group 3 (n=5) 3 IU/m2 per day in the 1st year and 4.5 IU/m2 per day thereafter. There was a significant increase in height after 1 and 2 years for all patients and for all subgroups. However, this increase was not dependent on GH dose. The decrease in height velocity during the 2nd year was not prevented by the increase of GH dose in group 3. The change of predicted height after 2 years was +0.75 SDS (according to Tanner Whitehouse). Fourteen children have been treated for 4 years and 8 children for 5 years without a further change in height prediction. Nine patients have reached final height which was 2.4 cm (+0.41 SDS) above pretreatment height prediction. Final height was nearly identical to predicted height after 1 year of therapy. CONCLUSION: An increment in height prediction was observed during the first 2 years of GH treatment and maintained thereafter. However, there was only a minor increase in final height over predicted height which does not justify the general use of GH in children with normal variant short stature.     

Climatic influences on human body size and proportions: ecological adaptations and secular trends

This study reevaluates the long-standing observation that human morphology varies with climate. Data on body mass, the body mass index [BMI; mass (kg)/stature (m)2], the surface area/body mass ratio, and relative sitting height (RSH; sitting height/stature) were obtained for 223 male samples and 195 female samples derived from studies published since D.F. Roberts' landmark paper "Body weight, race, and climate" in 1953 (Am. J. Phys. Anthropol. 11:533-558). Current analyses indicate that body mass varies inversely with mean annual temperature in males (r=-0.27, P < 0.001) and females (r=-0.28, P < 0.001), as does the BMI (males: r=-0.22, P=0.001; females: r=-0.30, P < 0.001). The surface area/body mass ratio is positively correlated with temperature in both sexes (males: r=0.29, P < 0.001; females: r=0.34, P < 0.001), whereas the relationship between RSH and temperature is negative (males: r=-0.37, P < 0.001; females: r=-0.46, P < 0.001). These results are consistent with previous work showing that humans follow the ecological rules of Bergmann and Allen. However, the slope of the best-fit regressions between measures of body mass (i.e., mass, BMI, and surface area/mass) and temperature are more modest than those presented by Roberts. These differences appear to be attributable to secular trends in mass, particularly among tropical populations. Body mass and the BMI have increased over the last 40 years, whereas the surface area/body mass ratio has decreased. These findings indicate that, although climatic factors continue to be significant correlates of world-wide variation in human body size and morphology, differential changes in nutrition among tropical, developing world populations have moderated their influence.     

Free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and IGFBP-3 and their relationships to the presence of diabetic retinopathy and glomerular hyperfiltration in insulin-dependent diabetes mellitus

The existing literature on serum insulin-like growth factor I (IGF-I) levels in insulin-dependent diabetes mellitus (IDDM) is conflicting. Free IGF-I may have greater physiological and clinical relevance than total IGF-I. Recently, a validated method has been developed to measure free IGF-I levels in the circulation. Serum free and total IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured in 56 insulin-treated IDDM patients and 52 healthy sex- and age-matched controls. Diabetic retinopathy was established by direct fundoscopy. In 54 IDDM patients, the glomerular filtration rate (GFR) and effective renal plasma flow were calculated from the clearance rate of [125I]iothalamate and [131I]iodohippurate sodium. Fasting free IGF-I, total IGF-I, and IGFBP-3 levels were significantly lower in IDDM patients than in age- and sex-matched healthy controls (free IGF-I, P < 0.005; total IGF-I, P < 0.001; IGFBP-3, P = 0.001), whereas IGFBP-1 levels were higher (P < 0.001). In IDDM subjects, decreases in free IGF-I, total IGF-I, and IGFBP-3 levels with age were observed (free IGF-I, r = -0.27 and P = 0.05; total IGF-I, r = -0.52 and P < 0.001; IGFBP-3, r = -0.37 and P = 0.005). Free IGF-I was inversely related to fasting glucose in IDDM subjects (r = -0.35; P = 0.01), whereas the relationship between total IGF-I and fasting glucose did not reach significance (r = -0.27; P = 0.06). Age-adjusted free IGF-I levels were significantly higher (P < 0.05) in IDDM subjects with retinopathy than in subjects without retinopathy after adjustment for age. Total IGF-I and IGFBP-3 levels were positively related to GFR (total IGF-I, r = 0.35 and P < 0.05; IGFBP-3, r = 0.28 and P < 0.05). Both of these differences lost significance after adjustment for age. Free IGF-I, total IGF-I, and IGFBP-3 levels were lower and IGFBP-1 levels were higher in insulin-treated IDDM subjects compared to those in age- and sex-matched controls. Free IGF-I, total IGF-I, and IGFBP-3 levels decreased significantly with age in IDDM subjects. Age-adjusted free IGF-I levels in subjects with diabetic retinopathy were higher than those in subjects without diabetic retinopathy. Total IGF-I and IGFBP-3 levels were positively related to GFR in IDDM subjects, but these relations were lost after adjustment for age. Measurement of serum free IGF-I levels in IDDM subjects did not have clear advantages compared to that of total IGF-I, IGFBP-1, and IGFBP-3 levels. Serum IGF-I and IGFBPs reflect their tissue concentrations to a various degree. Consequently, extrapolations concerning the pathogenetic role of the IGF/IGFBP system in the development of diabetic complications at the tissue level remain speculative.     

Combined effect of short stature and socioeconomic status on body mass index and weight gain during reproductive age in Brazilian women

Short stature, a marker for undernutrition early in life, has been associated with obesity in Brazilian women, but not in men. We tested the hypothesis that weight gain during the reproductive years could explain this gender difference. A national two-stage household survey of mothers with one or more children under five years of age was conducted in Brazil in 1996. The subjects were women aged 20 to 45 years (N = 2297), with last delivery seven months or more prior to the interview. The regions of the country were divided into rural, North/Northeast (urban underdeveloped) and South/Southeast/Midwest (urban developed). The dependent variables were current body mass index (BMI) measured, BMI prior to childbearing (reported), and BMI change. Socioeconomic variables included mother's years of education and family purchasing power score. A secondary analysis was restricted to primiparous women. The prevalence of current overweight and overweight prior to childbearing (BMI > or = 25 kg/m2) was higher among shorter women (<1.50 m) compared to normal stature women only in the urban developed region (P < 0.05). After adjustment for socioeconomic variables, age, parity, BMI prior to childbearing, and age at first birth, current BMI was 2.39 units higher (P = 0.008) for short stature women living in the urban developed area compared with short stature women living in the urban underdeveloped area. For both multiparous and primiparous women, BMI gain compared to the value prior to childbearing was significantly higher among short stature women living in the urban developed region (P <= 0.04). These results provide clear evidence that short stature was associated with a higher BMI and with an increased risk of weight gain/retention with pregnancy in the developed areas of Brazil, but not in the underdeveloped ones.     

Growth changes in children and adolescents with short-term diabetes

OBJECTIVE: Height and weight changes during the first 3 years of diabetes were prospectively followed in 152 diabetic children and adolescents. RESEARCH DESIGN AND METHODS: The study sample consisted of 152 Caucasian diabetic patients (84 boys; 68 girls) followed from diabetes onset in the Paediatric Diabetes Unit and 80 Caucasian normal subjects (49 boys; 31 girls) assessed in the Outpatient General Paediatric Clinic of the same hospital for routine examination and not affected by problems that might influence growth. Diabetic patients and control subjects were consecutively enrolled in the study between 1989 and 1992; diabetic patients with positive markers for celiac disease (positive antiendomysial antibodies) and thyroid disease (positive antimicrosomial antibodies) or any other chronic disease were not considered in the study. Mean age of diabetic patients (8.9 +/- 4.1 years) and control subjects (8.5 +/- 4.2 years) at recruitment in the study was similar. RESULTS: At onset of diabetes, the mean height expressed as the height standard deviation score (HSDS) was significantly greater than the expected values (P < 0.0001) and was independent of sex and pubertal stage. During the first 3 years of diabetes, HSDS decreased significantly (F = 6.9; P < 0.001). Meanwhile, growth velocity as standard deviation score (SDS) decreased significantly between the 1st and 2nd year (-0.12 +/- 2.1; -0.76 +/- 2.6, respectively; P < 0.05), but it was similar between the 2nd and 3rd year of diabetes. Weight expressed as SDS increased significantly during the first 2 years of diabetes but not thereafter. Height changes during the study period were independent from pubertal stage and sex. Metabolic control and insulin requirement, in our series, were not clearly related to height and weight changes. CONCLUSIONS: Diabetic patients at onset of diabetes are taller than age- and sex-matched nondiabetic subjects. During the first years of the disease, linear growth decreases independently of metabolic control and weight changes.     

Reduced speed of sound in tibial bone of haemodialysed patients: association with serum PTH level

BACKGROUND: In end-stage renal disease, average bone mineral density has been reported to be normal or only modestly reduced, more so in the cortical bone. The purpose of the present study was to explore the potential use of quantitative ultrasound, a method reflecting both quantitative and qualitative properties of bone, in assessing bone status in patients on maintenance haemodialysis. METHODS: We studied 71 patients (age 17-81 years, time on dialysis 0-18 years). The speed of sound waves (tSOS; m/s) propagating along the cortical bone has been determined at the tibial shaft. tSOS results were expressed as Z scores, i.e. units of standard deviations from age- and sex-matched normal mean values, and correlated with relevant clinical and biochemical variables. RESULTS: SOS Z score averaged -2. 0 (range -6.8 to 0.6; P<0.001) and was negative in 93% of the patients. Significant inverse correlations were found between SOS Z score and both time on dialysis (r=-0.52; P<0.0001) and serum PTH (r=-0.39; P=0.0002). Markedly reduced SOS Z score, below -2, was found in 80% of the patients whose PTH levels exceeded 34 pmol/l (five times the upper normal limit), compared with 43% of the patients whose PTH levels were below 34 pmol/l(P=0.04). Compared to patients without bone pain (n=51), subjects with bone pain (n=20) had somewhat lower SOS Z scores -2.5+/-2.0 versus -1.8+/-1.4; P=0. 08), but this could be accounted for by longer time on dialysis. CONCLUSIONS: tSOS is substantially reduced in the majority of haemodialysed patients and is related to time on dialysis and serum PTH level. The clinical value of this novel method needs further exploration.     

Body habitus as a predictor of burn risk in children: do fat boys still get burned?

Previous research at this institute has demonstrated that heavy-for-age boys are more burn prone than their normal sized counterparts. As this study is now 26 years old, we reexamined the anthropomorphic indices of 372 children admitted to one burn center between January 1991 and July 1997 to determine if this trend was still evident. Male children were over-represented in the < or =5th and >95th percentiles for both height (p < 0.001, p < 0.05) and weight (p < 0.01, p < 0.001). Female children were over-represented in the < or =5th and > 95th percentiles for height (p < 0.01, p < 0.05). Twenty-eight percent of boys at or below the 5th percentile for weight were burned as a result of known or suspected intentional injury, compared to 5.9% of the entire pediatric burn population. (p < 0.0004). 'Fat boys' continue to be over-represented in the pediatric burn population. Additionally, in the more recent time period, boys at or below the 5th percentile for height or weight and girls= < 5th percentile or >95th percentile for height are also over-represented. The increased frequency of burn injury in small-for-age children may reflect an increased risk of burn injury secondary to neglect or nonaccidental trauma.     

Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate

Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s-PIIINP changed significantly with age and pubertal development stages. For s-PIIINP, a peak was seen at 12 yr for girls and 13 yr for boys; no peak could be discerned for s-PICP. The prepubertal (Tanner stage 1) s-PICP value (mean +/- SD) for girls was 374 +/- 132 micrograms/L, the midpubertal value (stage 3) was 442 +/- 135 micrograms/L, and the postpubertal value (stage 5) was 203 +/- 103 micrograms/L. The mean s-PIIINP levels for girls were 9.1 +/- 2.4, 15.0 +/- 4.3, and 6.8 +/- 3.1 micrograms/L, respectively. For boys, levels were 362 +/- 119, 544 +/- 138, and 359 +/- 256 micrograms/L for s-PICP and 8.5 +/- 2.2, 14.5 +/- 5.0, and 8.6 +/- 3.8 micrograms/L for s-PIIINP (P < 0.001 for both propeptides in both boys and girls). There was, however, a large variation in normal values for both propeptides within the age groups and pubertal stages. There was a significant correlation of s-PICP and s-PIIINP levels to height velocity in girls (r = 0.35; P < 0.001 and r = 0.33; P < 0.001, respectively), while in boys, only s-PIIINP showed significant correlation to height velocity (r = 0.40; P < 0.001). In untreated girls with CPP, serum levels of s-PIIINP were elevated [PIIINP SD score (SDS), 2.13]. Levels of s-PICP were normal (PICP SDS, 0.39). Levels of both propeptides decreased within 2 months after initiation of therapy and remained below initial values (P < 0.01). The decrease in s-PIIINP after 2 months of therapy showed a significant correlation with the fall in height velocity SDS for chronological age after 6 months of therapy (r = 0.64; P < 0.01). We conclude that s-PIIINP and, to a lesser degree, s-PICP reflect growth in normal children, but due to the large variation, both propeptides seem unsuitable as markers for screening of growth disorders in children.     

Pretreatment with somatostatin analog SMS 201-995 potentiates growth hormone (GH) responsiveness to GH-releasing factor in short children

Previous studies in children have shown inconsistent, poorly reproducible GH responses to exogenous GH-releasing factor (GRF), with wide individual variability. In the present study, we tested the hypothesis that prior administration of the long-acting somatostatin analog, SMS 201-995 (SMS), will enhance GH responsiveness to a subsequent GRF challenge. Two study protocols were employed in 37 children with short stature [M = 31, F = 6, ages 11.8 +/- 1.6 yr (mean +/- SEM), height -2.25 +/- 0.55 SDS (SD scores)]. In both studies, each subject served as his/her own control. In the first study, which was designed to determine optimal SMS dose and regimen, SMS, in doses ranging from 0.8-2.2 micrograms/kg sc, was randomly administered or omitted at 0800 h after an overnight fast, and a GRF bolus (50 micrograms, iv) was given 4 h later. In the second study, we employed a protocol identical to study 1 except for the use of standard doses of SMS (1 microgram/kg, sc) and GRF (1 microgram/kg, iv) and an additional 1-h delay of the GRF injection. Plasma GH levels were measured every 20 min from 0800 h until 2 h after the GRF injection in both studies. In study 1 (n = 12; M = 10, F = 2), SMS significantly suppressed spontaneous GH secretion (expressed as the mean +/- SEM GH AUC during the 4-h SMS-GRF interval, AUC 1:2.2 +/- 0.4 vs. 6.2 +/- 0.9 micrograms/L.h; P < 0.001), GH responsiveness to GRF (GH AUC during the 2 h after the GRF injection, AUC 2: 41.5 +/- 7.8 vs. 85.0 +/- 13.5 micrograms/L.h; P < 0.001), and the GH peak response (17.4 +/- 3.1 vs. 36.0 +/- 6.2 micrograms/L; P < 0.001), compared to control tests. In contrast, in study 2 (n = 25; M = 21, F = 4), whereas spontaneous GH secretion was still suppressed during the 5-h SMS-GRF interval (AUC 1:3.8 +/- 0.4 vs. 7.4 +/- 1.1 micrograms/L.h; P < 0.001), both the GH peak response (56.7 +/- 5.5 vs. 30.5 +/- 3.0 micrograms/L; P < 0.0001) and the GH AUC (AUC 2: 103.7 +/- 10.3 vs. 77.5 +/- 6.8 micrograms/L.h; P < 0.05) after GRF administration were significantly augmented by pretreatment with SMS, compared to control tests. Taken together, these results indicate that a priming SMS dose of 1 microgram/kg has a significant permissive effect on GH responsiveness to exogenous GRF administered 5 h later.(ABSTRACT TRUNCATED AT 400 WORDS)