Effect of erythrocyte transfusion on longitudinal bone growth of premature infants assessed by mini-knemometry.
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Anemia↗
Biomedical subjects
M Hermanussen
Publications and source records attributed to M Hermanussen.
Synthetic growth reference charts.
Distance standards of height (growth charts) tend to get out of date and must be actualized from time to time. The aim of the present meta-analysis was to investigate characteristics of the cross sectional incremental pattern of body stature, evaluating the possibility of generating distance standards of height without the need for extensive de novo measurements. In view of the differences in growth in early and late childhood, we divided the total period of child development into the period between birth and the age of 6y, and between 6 and early adulthood (15y in females, 18 y in males). With respect to birth length, we meta-analysed 50 European and US American growth studies; with respect to growth in early childhood, 14 studies were analysed; and with respect to growth in late childhood, we meta-analysed 40 male and 51 female growth studies, from 14 European countries and the USA. Variations in body stature were meta-analysed in very large data samples, including the 1992 German birth cohort with more than 500 000 measurements of newborns, 10 000 measurements of 2-y-old German children, more than 500 000 measurements of German school children, and 6 large growth surveys of Japan and Czechoslovakia, with altogether more than 24 000 000 measurements. We found a rigid pattern of cross sectional body stature increment between birth and early adulthood that could be expressed by age-specific linear regression coefficients. Body stature was found to be related between sexes. Male birth length correlated with female length (r = 0.933, p < 0.001, slope = 4.62, intercept = 0.89), stature of 6-y-old boys correlated with stature of 6-y-old girls (r = 0.96, p < 0.001, slope = 1.05, intercept= -6.75), and stature of 18-y-old boys correlated with stature of 15-y-old girls (r=0.96, p < 0.001, slope = 0.90, intercept = 2.85). The developmental pace was also strongly related in both sexes. In conclusion, age-specific linear regression coefficients can be utilized synthetically to generate distance standards for height (synthetic growth reference charts). Synthetic growth reference charts can help to actualize current growth charts without much additional effort, and they may also be used for populations for which autochthonous growth standards are not available.
Adolescent↗
Gulliver G-100 - A new device to evaluate daily growth measurement in comparison with Harpenden stadiometer.
To reduce the time to monitor success of growth hormone therapy, Gulliver G-100 (G-100), a new portable height measurement device based on ultrasound technology, was developed and compared with a conventional determination system, the Harpenden stadiometer (HS). In addition, growth of 12 children was monitored at home twice per day 3 months before and 3 months during GH therapy. Mean body height of 101 children was 144.67 cm using G-100 compared to 145.16 cm using HS. The coefficient of variability of 3 measurements from each patient was 0.29 and 0.18 using G-100 or HS, respectively. Statistic analysis of these data revealed no significant difference between G- 100 or HS. Statistical analysis of short-time growth of 12 patients revealed an increase of growth velocity for 8 patients (p < 0.01) after 3 months. Calculated growth velocity using data revealed from short-time growth analysis with G-100 and using long-term growth analysis with HS did not show any significant difference. Our data reveal that G-100 is able to produce accurate results in height measurement comparable to the HS. Using G-100, the patient can be classified as a 'responder' of GH therapy already after 3 months.
Adolescent↗
Salivary gland is capable of GH synthesis under GHRH stimulation.
Twelve female rats weighing approximately 150 g received in the submaxillary gland a pellet capable of releasing 3.5 microg GHRH/h for 60 days. Another eight sex- and weight-matched animals received placebo pellets in the same place. After two months the animals were killed, heart blood was collected and pituitary and submaxillary glands were carefully dissected. Pituitary GH content in both placebo- and GHRH-treated animals showed similar values, but plasma GH and IGF-I levels were significantly lower in the animals carrying GHRH pellets (P<0.03); these animals also had a significantly higher GH content in the submaxillary gland (19.2+/-8 ng/mg protein) compared with the placebo-treated group (1.1+/-0.3 ng/mg protein). GH mRNA was present only in the submaxillary gland of GHRH-treated rats as determined by PCR-Southern blot and by in situ hybridization methods. It is concluded that high local GHRH levels are capable of inducing transdifferentiation in submaxillary gland cells to synthesize GH.
Animals↗
Short-term growth: evidence for chaotic series of mini growth spurts in rat growth.
Five thousand and eighteen quadruplet daily measurements of lower-leg length of 62 female and 81 male rats, were performed in order to characterize short-term growth. Within a short time, growth proceeds irregularly and consists of multiple incremental bursts (mini growth spurts) with no evidence for strict periodic behavior. Mini growth spurts are S-shaped incremental patterns that can be characterized by double-exponential functions (Gompertz's functions). Gompertz's functions are S-shaped, and can be defined by three parameters that identify amplitude, inflection point (age at peak growth velocity), and slope. The latter not only refers to the rapidity of each incremental burst, but also alludes to the duration that one incremental burst needs for completion. In regard to these characteristics, mini growth spurts differ significantly between the sexes in rats. Mean amplitude of mini growth spurts was 2153 microm (SD 1034 microm) in female rats and 2958 microm (SD 1614 microm) in male rats. Peak growth velocity of mini growth spurts appeared lower in male rats than in female rats. Female rats showed mean gamma of -1.23 (SD 0.72), whereas male rats showed mean y of -0.96 (SD 0.72). Partial growth hormone deficiency led to a modification in rats that was reversed when exogenous growth hormone was administered. Mean intervals between subsequent mini growth spurts ranged between 4.2 and 4.6 days, but the large variation of these intervals (SD between 1.6 and 2.3 days) and the fact that neither spurt-spurt interval nor spurt amplitude appeared predictable, strongly suggest chaotic behavior of mini growth spurts.
Algorithms↗
The analysis of short-term growth.
The analysis of short-term growth needs repetitive measurements of body stature or of segments of the body. When body stature is measured at monthly intervals, an irregular incremental pattern becomes obvious with a number of large-scale components such as series of prepubertal and pubertal growth spurts, seasonal influences on height gain, and influences of the psychosocial and economic background. When measurement intervals decrease, incremental patterns appear even more irregular, and a number of short-scale components become apparent that are distinct from measurement error. The review summarizes the analysis of short-term growth, and presents the current findings supporting different views on how growth progresses at short term. In particular, observations are presented that suggest growth being a pulsatile, a periodic, a saltatory, and a chaotic event. Some recent animal studies and studies in human newborns are added in detail as they illustrate short-term growth on the basis of accurate 24-hour measurements of the lower leg. The latter investigations support the idea of short-term growth being characterized by chaotic series of'mini growth spurts' that occur at intervals of approximately 4-5 days, not only in human neonates, but also in rats. The amplitude of mini growth spurts ranges between 2 and some 10 mm, and growth velocity of each spurt also varies considerably so that one spurt needs between less than 1 and up to several days for completion.
Animals↗
Sexual dimorphism in growth as measured by microknemometry: different responses to GH deficiency and exogenous GH administration.
To monitor growth, a novel noninvasive leg length measurement technique, called microknemometry, which allows daily observation of tibial growth rate, was used. The rat exhibits a striking sex-related difference in postpubertal growth. Exogenous GH administration results in a sexually dimorphic response, affecting growth in normal young female rats but not in males. Here we investigated how chronic GH deficiency affects male and female rat growth patterns. The degree of growth rate recovery was investigated after exogenous GH administration to chronically deficient males and females. The deficiency was induced by neonatal monosodium glutamate (MSG) treatment. Since the neonatal gonadal environment plays an important role in the dimorphic growth pattern, neonatal androgenization of female rats with testosterone or neonatal feminization of male rats by castration was performed and the growth pattern monitored. MSG treatment decreased pituitary GH content and plasma IGF I levels in both sexes, but caused a less marked reduction of female rat tibial growth and body weight gain than in males. Additionally, only MSG-treated males showed decreased pituitary LH content, so that the dimorphic action of MSG on the gonadal axis may contribute to the observed differences in growth rate. GH administration was able to increase leg length in all MSG-treated rats but was more effective in females, despite a similar restoration of plasma IGF I levels in both sexes. Although neonatal castration of male rats resulted in a reduction of tibial growth rate and body weight, and neonatal testosterone administration to female rats caused a slight increase in body weight, a complete modification of the gender-dependent growth pattern was not achieved, indicating that appropriate steroid environment is also needed in puberty and adulthood.
Animals↗
Differential catch-up in body weight and bone growth after short-term starvation in rats.
Catch-up or compensatory growth is known as a physiological phenomenon. However, most studies of catch-up growth were based on measurements of body weight, whereas changes in longitudinal bone growth remained largely undescribed. The present study describes the dynamics of both weight and longitudinal bone growth using mikro-knemometry, during normal feeding, severe food restriction (starvation), and refeeding of 14 intact and 28 GH-deficient male rats. Starvation induced rapid weight loss (P < 0.001), and stunted leg growth (P < 0.001). Refeeding led to rapid catch-up in weight of up to 4 times above normal daily weight gain, both in intact and GH-deficient animals, whereas an equivalent compensation of lower leg growth remained undetectable. Intact and GH-deficient animals show a circaseptan spontaneous variation of growth velocity (mini growth spurts). During starvation, mini growth spurts disappear, and return to normal after refeeding with no evidence of catch-up. In GH-deficient animals, GH (1 IU/rat, administered twice daily s.c. at 10:00 hand 16:00 h) was capable of augmenting catch-up in weight and, to a lesser extent, in leg length increment.
Animal Nutritional Physiological Phenomena↗
Mikro-knemometry: an accurate technique of growth measurement in rats.
A novel, noninvasive technique for accurate measurements is presented which determines the distance between knee and heel of the rear lower leg in the conscious rat (mikro-knemometry). Each measurement consists of initially six, later four subsequent and independent estimations of this distance. During a 14-day training study, the mean standard deviation (technical error) of five (six minus the first estimation) decreased from 196 microns to 101 microns. Measurements at exact 24-h intervals revealed nonlinear increments of rat lower leg growth, with marked infradian variation once every four to six days, similar to "mini growth spurts", described in rabbit and human growth. There was also a significant circadian periodicity of leg length increment (p < 0.01), with a minimum leg increment (after midnight dip) between 2400 h and 0300 h (mean: 4.8% (SEM 2.3%) of the total 24-h increment, p < 0.01), and a maximum increment (early morning spurt) between 0600 h and 0900 h (mean: 34.9% (SEM 2.5%) of the total 24-h increment, p < 0.001). Thus, the technique of mikro-knemometry seems to be a useful tool for the investigation of longitudinal growth in laboratory rats, and may replace conventional techniques of growth measurements such as measuring body weight, nose-tail, or tail length.
Animals↗
Growth promotion by oxandrolone in a girl with short stature and early pubertal development treated with growth hormone and gonadotropin-releasing hormone-analogue. A case study.
Gonadotropin-releasing hormone (GnRH)-analogues are widely used for treating precocious puberty, and occasionally in short patients and patients with growth-hormone deficiency, in order to delay pubertal development and increase final height. Yet, many of these children only decelerate growth velocity and neither improve in final height nor even in height prediction. As GnRH-analogue treatment dramatically reduces sexual steroid levels, I hypothesized the need for steroid hormone substitution during this treatment. Growth promotion was tried in a healthy girl, with a very unsatisfying height prediction of only 144 cm, using a combination of GnRH-analogue (75 micrograms/kg/4 weeks), plus growth hormone (4 IU/m2/d), plus oxandrolone (1 mg/d). Knemometric measurements of lower leg growth velocity demonstrated that GnRH-analogue alone depresses growth. Additional GH administration only sporadically increases growth velocity, and not until the additional substitution of oxandrolone does growth velocity catch up and return to near pretreatment level. In spite of a 10.3 cm increase in body height during the 15-month period of observation, little bone age progression took place, and height prediction improved from 144 cm to over 149 cm after 9 months, and to 152 cm after 15 months of observation.
Age Determination by Skeleton↗
Acute and chronic effects of winter swimming on LH, FSH, prolactin, growth hormone, TSH, cortisol, serum glucose and insulin.
The present investigation is based on a 2.5 months selbstversuch (self-experiment) of the authors, between October 21 1992, and January 6 1993. 11 healthy students, five females and six males, age 24 to 29 years, and their teachers underwent regular winter swimming at least once a week, for 2 to 10 minutes, at the natural water temperature (6.8 degrees C (October 1992) to 2.0 degrees C (January 1993)) in the southern Baltic Sea. Blood samples were drawn before and 30 and 60 minutes after the cold bath, both at the first and the last day of the swimming season. TSH increased from 0.96 mU/l to 1.42 mU/l (p < 0.01) in the untrained, and from 0.93 mU/l to 1.43 mU/l (p < 0.01) in the cold-trained persons, and decreased thereafter (p < 0.01). Similar changes occurred in cortisol serum concentrations, though psychological stress seemed to interfere with cold stress. Cortisol increased from 99 ng/ml to 133 ng/ml in the untrained, and from 101 ng/ml to 137 ng/ml (p < 0.05) in the cold-trained persons within 30 minutes after cold water immersion, and decreased thereafter (p < 0.01). There were mild decreases in prolactin serum levels after cold stress, whereas FSH, LH and growth hormone remained unaltered. There was a mild initial elevation of serum glucose after cold stress (plus 12 mg/dl, (p < 0.01)) which disappeared after training. There were long term training effects besides the effects on glucose: Basal prolactin levels increased by almost the factor two, and insulin serum levels dropped by almost 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Hypothyroidism phenocopy in glycanosis CDG (carbohydrate-deficient glycoprotein syndrome)
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Carbohydrate Metabolism, Inborn Errors↗
A non-invasive technique for the accurate measurement of leg length in animals.
A novel, non-invasive technique for accurate measurements in animals (Kyniklometry) is presented. Kyniklometry (derived from greek ŏ kúvikloz the rabbit) determines the distance between soft tissue landmarks in conscious rabbits, in particular the rear lower leg. Each measurement consists of six subsequent and independent estimations of this distance, with a technical error of 79 microns (study I), respectively 83 microns (study II). The angle of the relaxed sitting animal's knee is approximately 45 infinity, and remains individually almost constant during subsequent measurements. The precision of the device was compared with X-ray stereophotogrammetry (technical error 30 microns). Five female New Zealand White rabbits were measured for 13 consecutive days at 24-hour-intervals both by kyniklometry and X-ray stereophotogrammetry (study I). The mean increment of 5 kyniklometric series of ten (3rd to 13th day) 24-hour-increments was 0.988 mm, the mean 24-hour-variance was 0.244 mm2. Sixty point five percent of this variance could be explained by parallel right/left leg soft tissue variation. Only 5% of the variance was explicable by the technical error. The 24-hour-correlation between kyniklometry and X-ray stereophotogrammetry was significant with r = 0.889 and p less than 0.001. Kyniklometric measurements were also performed in 5 female rabbits for 56 days at 24-hour-intervals (study II). We found spontaneous periodicity once every 8 to 14 days. There was a diurnal variation of rear lower leg increment with maxima in the early morning hours.
Animals↗
Differential effects of oestrogen treatment on the proportionality of growth in tall girls.
We studied the differential inhibitory effects of conjugated oestrogens on lower leg length and standing height increments in 17 excessively tall girls compared to a control group of 17 tall healthy untreated girls. Standing height, lower leg length and body weight were recorded at weekly or monthly intervals. Standing height velocity dropped from 150 microns/day to 122 microns/day, whereas daily weight gain increased from 17 to 48 g/day during oestrogen treatment. The oestrogen induced decrease of standing height velocity could be explained by a marked inhibition of lower leg growth velocity from 42 microns/day to 30 microns/day (native data) or 35 microns/day to 8 microns/day (data corrected for weight gain) (P less than 0.001), whereas no differences of trunk growth velocity could be detected. Thus, the findings strongly suggest that pharmacological doses of oestrogens only affect epiphyseal growth.
Adolescent↗
Predictive criteria for successful growth promotion in growth hormone therapy of short stature: a comparison between common endocrine parameters and knemometry.
Due to increased availability of growth hormone (GH) for the treatment of short stature, its use has been proposed for a number of conditions besides classic GH deficiency. We have studied growth response during a one year treatment period with 14 IU/m2/week of GH in a heterogenous group of 24 short children with various conditions associated with short stature (SDS for body height ranging between -2.2 and -4.4). Thirteen children could be classified as "responders" with growth rate increments of 2 cm/yr or more above pretreatment growth rates, and 11 children as "non-responders". The children were measured regularly both by stadiometry and knemometry at weekly intervals. GH stimulation by insulin, arginine and spontaneous overnight secretion of GH, and SM-C generation were evaluated in the children and found to be of no predictive value for the individual responsiveness to GH administration except in one boy with classic GH deficiency. However, serial measurements of the lower leg length provided useful information for individual predictions in 21 out of the 24 children as early as 10 weeks after the start of the GH treatment.
Adolescent↗
Standards for the predictive accuracy of short term body height and lower leg length measurements on half annual growth rates.
Determinations of body height and calculations of growth velocity are still the major parameters for the assessment of normal and aberrant growth. The present study was performed to investigate the minimum time interval between consecutive measurements that is necessary for a statement on significant length increment both of total body height and lower leg length. We present standards for the predictive accuracy of short term measurements for the prediction of the conventional half annual growth rate. We also provide centiles of the predictive error that occurs when the difference between two consecutive measurements is used to determine a half annual growth rate.
Adolescent↗
Analysis of differential growth of the right and the left leg.
In spite of well documented standards for length and annual growth rates of the femur and tibia, there is little information on short term longitudinal bone growth. We investigated differential growth dynamics of the lower leg in 10 children, aged 6:3 to 14:2 years, by knemometry, a novel and non-invasive technique of accurate lower leg length measurement with a technical error of 0.09 to 0.16 mm. Mini growth spurts were detectable in 7 of the children and occurred synchroneously in both legs. Approximately half of the variance of the weekly lower leg length increments could be attributed to synchrony of leg length increments, but a significant amount of residual variance remained which exceeded the technical error of the measurements. Run-analysis of the individual series of right vs. left differences of the weekly lower leg length increments provided evidence for alternating periods of overgrowth of one leg compared to the contralateral side in 5 out of the 10 children. We concluded that there is suggestive evidence of partial independence of lower leg growth in the short term.
Adolescent↗
[Measuring short-term periodicity of pediatric growth].
The study of human growth is traditionally based on investigations of body height. Differences of height which significantly surpass the technical error of the measuring device then by definition represent growth. However, this definition proved to be unsatisfying if applied to changes of body stature within very short time intervals. We have measured 73 healthy children, aged between 2.9 and 15.9 years, for periods of 180 to 306 days once or twice weekly, and 23 healthy children of similar ages for periods of 3 months, 4 to 5 times per week. The individual series of lower leg length measurements (technical error 160 microns) were analyzed by a smoothing procedure yielding mean daily lower leg growth rates. The series of almost daily measurements were additionally analyzed in order to find periodic elements. In the case of weekly measurements, marked periodic changes of mean daily lower leg growth rates were found with sharp growth spurts once every 30 to 55 days. Additional investigations of the series of almost daily lower leg length measurements showed evidence that the above periodic changes of growth rate were caused by aliasing between shorter periods overlapping each other and the exact 7-day intervals of measurements. We found a number of dominant periods particularly at 7 to 9-day intervals.
Adolescent↗