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WHO documents characterize stunting as, “…impaired growth and development that children experience from poor nutrition, repeated infection, and inadequate psychosocial stimulation.” The equation of stunting with malnutrition is common. This contrasts with historic and modern observations indicating that growth in height is largely independent of the extent and nature of the diet. We measured 1716 Indonesian children, aged 6.0–13.2 years, from urban Kupang/West-Timor and rural Soe/West-Timor, urban Ubud/Bali, and rural Marbau/North Sumatra. We clinically assessed signs of malnutrition and skin infections. There was no relevant correlation between nutritional status (indicated by skinfold thickness) and height SDS (hSDS). In total 53% of boys, and 46% girls in rural Soe were stunted, with no meaningful association between mean of triceps and subscapular skinfolds (xSF) and height. Skinfold thickness was close to German values. Shortest and tallest children did not differ relevantly in skinfold thickness. The same applied for the association between hSDS and mid-upper-arm circumference (MUAC) using linear mixed effects models with both fixed and random effects. In total 35.6% boys and 29.2% girls in urban Ubud were overweight; 21.4% boys and 12.4% girls obese, but with mean hSDS = −0.3, still short. Relevant associations between hSDS and xSF and MUAC were only found among the overweight urban children confirming that growth is accelerated in overweight and obese children. There were no visible clinical signs of malnutrition or chronic infection in the stunted children. The present data seriously question the concept of stunting as prima facie evidence of malnutrition and chronic infection.

Kallmann's syndrome is a rare condition defined as a combination of hypogonadotropic hypogonadism and anosmia. The present study shows two genealogical tables. In the first family six male members in four generations had Kallmann's syndrome. All carrier females seemed to have normal fertility and normal olfactory function. X-linked recessive or - less probable - dominant sex linked inheritance was considered to be most probable. Renal malformation was discovered in one and was excluded in two affected members. In the second family only one affected female was discovered. She had a monozygotic twin sister with normal pubertal development, but also total anosmia. Four individuals with anosmia alone were found in this family, but no further cases of hypogonadism. The possibility of an acquired hypothalamic insufficiency on the basis of hereditary anosmia is discussed.

Aim: To discuss a hypothesis regarding the impact and possible side effects of glutamate in paediatric parenteral nutrition. Results: Published evidence suggests that the arcuate nucleus, which is a potent site of leptin action, is severely damaged by elevated glutamate levels. Early administration of glutamate (GLU) to the neonatal rat disrupts the hypothalamic signalling cascade of leptin action. Conclusion: We are concerned that GLU-containing parenteral nutrition may not only increase the risk of hypothalamic damage in neurosurgical patients with an impaired blood–brain barrier, and in patients with periventricular leukomalacia, but may also permanently damage the arcuate nucleus neurones in the very immature infant. This may result in later impairment of feeding regulation, obesity, hyperleptinaemia, and other symptoms that characterize the “thrifty phenotype” and the dysmetabolic syndrome. We strongly suggest reconsidering the recommended daily allowances of amino acids, particularly the use of GLU, in current paediatric parenteral nutrition.

The regulation of appetite relies on complex hypothalamic neurocircuitry of which the arcuate nucleus, and the hormone leptin play important roles. Arcuate nucleus neurones are essential for the regulation of eating behaviour, but they can be intoxicated by elevated serum levels of the amino acid glutamate (GLU). Neurotoxic effects of GLU are mediated by the N-methyl-D-aspartate receptor (NMDA-R). But the neurotoxic effects of GLU can be prevented. Concurrent administration of dizocilpine maleate (MK-801), a selective and highly potent non-competitive NMDA-R antagonist, antagonises GLU-gated Ca2+ ion channels and completely prevents the adverse effects of GLU. Also the non-competitive NMDA-R antagonist memantine displays neuroprotective properties. In view of a previously published hypothesis that human obesity results from chronic over-consumption of GLU, we performed a therapeutic trial in five obese, but otherwise healthy women. Memantine treatment markedly decreased appetite within few hours and complete suppressed the binge-eating disorder within 24 h. Body weight decreased markedly within a few days. The findings strongly support the hypothesis that elevated levels of nutritional GLU play an important role in the pathomechanism of human obesity. We suggest to treat human obesity by protecting the hypothalamic signalling cascade of leptin action with low to moderate affinity, non-competitive NMDA-R antagonists that selectively block the GLU-gated Ca2+ ion channels.

Substantial differences exist between traditionally cooked and chemically designed ready-to-serve products and raise questions about the general principles and requirements of current food law.Differences in amino acid patterns were analyzed in four examples of chicken preparations (boiled chicken meat, traditionally prepared broth from whole chicken, and two commercial chicken broths), and four examples of vegetable broth (traditionally prepared, two commercial products one of which was claimed a BIO-product, and the classic German bouillon cube).Chicken meat contained 284 mg of free amino acids in 100 ml of the boiled meat homogenate, with physiological peaks of glutamate (14.5 mg/100 ml), glutamine (8.5 mg/100 ml), anserine (88 mg/100 ml) and carnosine (55 mg/100 ml). The patterns significantly differ in industrially designed chicken soups with elevated peaks of glutamate, and missing anserine or carnosine. Similar results were obtained in vegetable broths. In the classic German bouillon cube, glutamate accounts for 96% of all free amino acids.The amino acid composition of modern ready-to-serve chicken soups and vegetable broths are far from being similar to any natural composition. We need to question current legal definitions of food, and consider its impact on eating habits, appetite regulation and obesity.

Aim National European growth references differ. We aimed to convert (harmonize) currently used charts into a single unified interchangeable LMS format for each European nation. Methods Nine currently used national European growth references from Belgium (2009), France (1979), Poland (2001), Sweden (2002), Switzerland (1989), the UK (1990), Italy (2006) and Germany (1979 and 1997) were harmonized and compared with the international WHO child growth standards and WHO growth reference data for 5–19 years. Results European growth charts can be harmonized. The approach appears useful as height, and body mass index (BMI) is inappropriately represented by WHO references. European height references exhibit warping when plotted against the WHO reference. The French appears too short, the other Europeans too tall. Also, the BMI is not appropriately represented by the WHO references. Conclusions Harmonizing references is a novel, convenient and cost-effective approach for converting historic and/or incomplete local or national growth reference charts into a unified interchangeable LMS format. Harmonizing facilitates producing growth references ‘on demand’, for limited regional purposes, for ethnically, socio-economically or politically defined minorities, but also for matching geographically different groups of children and adolescents for international growth and registry studies.

Overweight and obesity have developed into major illnesses in most Western societies and significantly contribute to the financial burden of modern public health systems. Almost daily, new therapeutic proposals are published in the lay press, and also the scientific literature has increased dramatically in recent years. E.g., when searching MEDLINE (1966 - May 2008 (1)), the key word "obesity" meanwhile appears in more than 108,000 articles. Primary focus however, is put upon aspects of treatment, neglecting the role of taste and appetite regulation. Combining keywords like "obesity + treatment" results in over 50.000 citations, "obesity + diet" in over 23.000, "obesity + energy + expenditure" in over 13.000 citations (even "obesity + gastric + bypass" still evoke 2.600 citations), whereas "obesity + appetite + regulation" result in some 3.000, "obesity + NPY" - neuropeptid Y being one of the major chemical stimulators of appetite - evoke some 500 and "obesity + Arc + nucleus" - the arcuate nucleus being the anatomical centre of appetite regulation - no more than 370 scientific publications. The apparent scarcity of literature about taste and appetite regulation and the amazing lack of interest in neuronal information processing in overweight and obesity, has prompted the authors to brainstorm new aspects of the world-wide derailment of weight control.

Preventing and treating obesity has become a major public health concern. Obesity results from the imbalance of energy intake and energy expenditure. Energy intake has increased, energy expenditure has decreased in recent years. In addition, the proportion of macronutrient intake has changed with a substantial decline in the percentage of energy from nutritional fat, and an increase in energy from sweetened beverages. We focus on the interaction between body mass index and the recent population wide increase in protein consumption. 7182 three-day weighing and nutritional protocols and anthropometric data of the DONALD (Dortmund Nutritional and Anthropometrical Longitudinally Designed) Study from 1028 healthy children and adolescents, aged 2 to 18 years (51.3% girls, 48.7% boys), measured between 1985 and March 2006, were obtained and re-analyzed. Mean daily energy intake (r=0.060, p0.1), and the absolute daily intake of fat (r=0.031, p0.1), and carbohydrate (r=0.050, p0.1) were independent from BMI standard deviation scores (BMI-SDS). However, a significant interaction between BMI-SDS and the mean absolute daily intake of all protein (r=0.143, p0.0001), and animal protein (r=0.151, p0.0001) was found. When expressing macronutrient intake as percentage of daily energy intake, the fat and carbohydrate correlations remained insignificant with r= -0.040, and r= -0.037, respectively, whereas the correlation between BMI-SDS and all protein (r=0.203, p0.0001), and animal protein (r=0.163, p0.0001) further increased. The correlation depended on age and reached maxima in the group of 10-12 year old boys (r=0.31, p0.0001), and girls (r=0.36, p0.0001). Protein intake explained up to 13% of the BMI variance in young adolescents. We strongly suggest reconsidering the recommended daily allowances of nutritional protein, to abstain from the popular very high protein diets, and particularly from adding the flavouring agent monosodium glutamate.

Summary Growth charts represent body stature, body weight, and body mass index (BMI) from birth to maturity. Due to secular changes in these parameters, growth charts tend to become outdated, and must be revised from time to time. Recently, we developed alternative strategies that facilitate developing and renewing growth charts, and suggested synthetic standards for body stature. The increasing prevalence of obesity has made it necessary to develop similar techniques also for monitoring body weight and BMI. Two-hundred-and-forty historic and modern growth studies (108 studies of male growth, 132 studies of female growth) were selected from 22 European, 6 American, 3 African, and 6 Asian nations, published between 1831 and 2001. The studies contained annual information on weight and stature, either between birth and 6 years, or between 6 years and maturity, or information on the whole age range between birth and maturity. Since historic studies up to the mid-20th century usually ignore the fact that body weight (in contrast to body stature) is not normally distributed, a group of 92 more recent studies (45 male, 47 female), published between 1943 and 2001, presenting centiles for weight, was chosen for additional analysis. Furthermore, the skewness of body weight distributions, was investigated in original raw data of body weight obtained from five well reputed longitudinal growth studies, performed at Jena, Germany, Lublin, Poland, Paris, France, Prague, Czech Republic, and Zurich, Switzerland. Average body stature and average weight differ markedly between different populations. But within the same population, both parameters are closely interrelated. In males, birth length and weight correlated with r = 0.503, stature and weight correlated with r = 0.873 at the age of 2 years; with r = 0.882 at the age of 6 years; with r = 0.935 at the age of 14 years, and with r = 0.891 at the age of 18 years. Similar results were obtained in females. At birth, length and weight correlated with r = 0.619. Stature and weight correlated with r = 0.863 at the age of 2; with r = 0.912 at the age of 6; with r = 0.935 at the age of 12; and with r = 0.918 at the age of 15 years. Tables of linear regression coefficients for relative stature and weight at all ages enable the reversal of the process of the meta-analysis and allow the generation of synthetic growth references for stature and weight. Synthetic reference charts help in the revision of current growth charts without much additional effort, and may be used for populations for which autochthonous growth standards are not available.

Summary Many disorders of child development can only be treated successfully when they are detected early. Thus, child development should be checked periodically. Usually, a few parameters are sufficient to check whether or not a child is developing normally in terms of growth. By making such checks publicly available on the website: willi-will-wachsen.de the authors hope to provide a tool which helps the automatisation of simple check procedures and thereby detect with less effort more children with growth disorders.

The present investigation characterizes common growth tracks in pre-pubertal children. Growth tracks denominate areas of probability within which subsequent measurements of the body height (or body height SDS) of a healthy individual will predominantly be found. Growth tracks are defined over several years and they are insensitive to the timing of measurements. The concept of growth tracks was developed to improve separating aberrant patterns from normal growth. Longitudinal data on height were obtained from six large national growth studies, performed at Berkeley, USA, Jena, Germany, Lublin, Poland, Paris, France, Prague, Czech Republic and Zurich, Switzerland with a total of 515 healthy boys and 532 healthy girls. Four hundred and two series of annual height measurements were available in pre-pubertal boys (aged 3-11 years), 416 series in pre-pubertal girls (aged 3-10). Body height was converted into height SDS. Thereafter, average personal height SDS was determined, and subtracted from height SDS, resulting in individual series of residual height SDS. These were sorted by cluster analysis and distributed into groups (clusters) according to similarity or dissimilarity (squared difference). We identified similar clusters, and named them 'growth tracks'. We found five pre-pubertal male growth tracks, each containing between 4 and 37% of the boys. Twenty boys could not be assigned to either one of the five tracks. Very similar results were obtained in girls, with five pre-pubertal growth tracks also, each containing between 3 and 50%. Twenty-three individuals grew irregularly and could not be assigned. Growth tracks are narrow, with an average width between 12.1 and 14.8% of the SD of body height. Most children exhibited almost horizontal height SDS patterns. Others showed linearly declining, rising, or intersection -shaped patterns. None of the patterns were predominantly found in particularly short or tall children. Preliminary data support the practical advantages of the concept of growth tracks.

The growth and development of a child is a mirror of his living conditions and health. For decades pediatricians have been trying to achieve an earlier identification of children with growth disorders. The measures of prevention in Germany have not been successful so far. Diagnosis for example of GH-deficiency to ensure optimal substitution with growth hormone is usually not early enough. A screening system using an auxological data bank for growth disorders has been set up by us recently. Since 1998 we have collected height and weight measurements in relation to age and sex from patients cared for by a large number of pediatricians in the region of Leipzig, Germany. By september 1999, 30,182 children of different ages have been screened. The system identifies children with short stature below the 3. centile and tall stature above the 97. centile of the German Synthetic Normcurve (Hermanussen/Burmeister 1999). In 6.81% of the children a growth disorder was identified (3.03% above 97. and 3.78% below 3. centile). In 54 cases (0.18%) we found a pathological reason for short or tall stature. A sensitive screening system has been set up for the early detection of growth disorders and obesity in childhood. We generate a data pool for multiple questions in research of human growth. We will generate yearly reports for the development of new strategies in preventive medicine.

OBJECTIVE: To investigate the shape of the natural distribution of body weight in conscripts. DESIGN: Investigation of weight and weight distributions in German, Austrian and Norwegian conscripts. SUBJECTS: A total of 10 706 651 West German conscripts (30 birth cohorts born between 1938 and 1971, except for the cohorts born 1941–1944), 507 095 Austrian conscripts (10 birth cohorts born between 1966 and 1975), and 27 311 Norwegian conscripts (1997 conscription). RESULTS: In Germans, average body weight increased by 100 g/y up to birth cohort 1965, thereafter by 400 g/y, and by 200 g/y in Austrians. Body weight is not normally distributed, but skewed to the right. Also power transformation was inadequate to sufficiently describe the shape of this distribution. The right tail of weight distributions declines exponentially, beyond a cut-off of +0.5 standard deviations. There is a strong relation between average weight and the prevalence of obesity, except for those cohorts that suffered from severe starvation (1945–1948) during early and mid-childhood. These cohorts appeared to be more resistant against obesity. CONCLUSION: Obesity appears to be a characteristic feature of a population as a whole, and does not seem to be a separate problem of only the obese people. It may be questioned whether (in terms of public health) the optimal solution for treating obesity is treating the obese people, or whether one should consider measures to reduce average weight in a population instead, as this might reduce the number obese people and the severity of the illness.

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, p0.001, slope = 4.62, intercept = 0.89), stature of 6-y-old boys correlated with stature of 6-y-old girls (r = 0.96, p0.001, slope = 1.05, intercept= -6.75), and stature of 18-y-old boys correlated with stature of 15-y-old girls (r=0.96, p0.001, 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.

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

Lower leg length measurements in 19 healthy preterm infants were obtained by knemometry to assess short term growth. Eight infants received fortified human milk and 11 infants commercially available preterm formulas. Two independent observers measured lower leg length in each infant daily during the study period, weight was measured daily with a neonatal scale. While weight gain showed linearity in all infants, lower leg length growth showed mini growth spurts of 5 +/- 1.7 days, growth periods of 20 +/- 11 days or both types of short term growth. The overall weight gain was 35 +/- 5.6 g/day in infants fed human milk and 33 +/- 7 g/day in infants fed preterm formula. The overall lower leg length growth velocity was 0.51 +/- 0.04 mm/day versus 0.54 +/- 0.09 mm/day, respectively. Both groups had comparable weight and length increments. No correlation existed between the type of nonlinear lower leg length growth (mini growth spurts versus growth periods) and the feedings received by the infants.

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 (p0.01) in the untrained, and from 0.93 mU/l to 1.43 mU/l (p0.01) in the cold-trained persons, and decreased thereafter (p0.01). 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 (p0.05) in the cold-trained persons within 30 minutes after cold water immersion, and decreased thereafter (p0.01). 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, (p0.01)) 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)

Using digital dividers (analogue-digital transformer, Brandt-Hermanussen device), it has become possible to measure distances between human teeth with a technical error of 0.04 mm. The technique implies a small preparation (trough) into the respective teeth. The ball-shaped metal probes of the instrument fit into these troughs and enable the determination of this distance directly in the patient. It does not require the use of casts. The present method was compared with two conventional and popular techniques of tooth arch determination, using the natural retentions of the deepest points of the central fossa of the respective teeth without the preparation of an artificial trough (manual caliper rule with nonius, digital caliper rule). The technical error of these techniques ranged between 0.46 mm and 0.52 mm. In order to investigate whether the preparation of an artificial trough could be avoided, the digital measuring dividers were modified and equipped with sharp probes for the determination of the natural distance between the deepest points of the central fossa, in analogy to the conventional techniques. Under these circumstances however, the technical error increased up to 0.27 mm (observer 1), and 0.21 mm (observer 2). It is concluded that dental marking is necessary for accurate dental measurement.

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.

Since ancient times, men tried to slow down the process of aging. This was done mainly by dietary means, and since the work of McCay and coworkers, it is general knowledge that caloric restriction is the most reliable technique in prolonging life of laboratory animals. To date, the importance of DNA-methylation, its influence on the three-dimensional structure of the genomic DNA, and the importance of growth factors on the process of aging are well known. Many of these factors modify the velocity of both transcription and cell growth and promote transformation of aging cells. First studies with growth hormone have been performed to investigate its influence on the process of aging.

Cross-sectional and longitudinal studies of human growth have revealed almost every detail of the typical human growth pattern. Yet, the description of this pattern is still limited to the traditional vocabulary of "growth rates", i.e. height or length differences divided by certain time intervals such as months or years. Almost no information is yet available on finer details of this pattern. This review concerns the existing experimental and clinical data collected by a novel and non-invasive technique of accurate lower leg length measurement named "knemometry" that has been used for the study of short-term growth. This technique estimates the distance between heel and knee of the sitting child with an accuracy (technical error) of 0.09-0.16 mm. Several authors have presented evidence that lower leg growth is non-linear. There is not only a marked day-to-day variation of the lower leg length which far exceeds the error of the measurement itself, but there is also a characteristic up-and-down pattern of lower leg growth consisting of sharp growth spurts ("mini-growth-spurts") alternating with periods of decreased growth velocity every 30-55 days in 45 out of 73 healthy children. This pattern can be visualized by the calculation of "mean daily lower leg growth velocities", an approach that gives information on the kinetic properties of the growth process. In spite of much initial criticism, knemometry has opened a fascinating new dimension of the physiology of human growth and provided finer details of growth than hitherto obtainable by conventional techniques of growth measurement.

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.

Cultured human and animal cells are predestined to undergo irreversible functional decrement that mimic age change in the whole organism. The underlying mechanism of this process, however, has not yet been discovered. A new hypothesis is introduced: The secondary structure of DNA is not stabile per se. It needs additional material surrounding it such as histones and non-histone proteins ("external stabilization"). In case of dissociations between the DNA and its additional stabilizer, well-defined localized break-downs of the chromatin structure will take place, which may happen predominantly during DNA replication. During subsequent cell divisions the number of break-downs will increase. Thus, higher molecular density will be reached which modifies not only the regulation of gene expression but also reduces the velocity of further cell division. A final state of density will be reached, where further replication is no longer possible.

Increased levels of endogenous growth hormone (GH) during childhood and adolescence result in a significant elevation of final height both in humans and in laboratory animals. We investigated the growth promoting effects of the administration of pharmacological doses of human GH (25 to 100 IU/kg/day) in 7 rats with severe intrauterine growth retardation (IUGR) due to artificially induced embryofetal alcohol syndrome (EFAS). Such doses of GH led to a marked growth spurt during the time of administration (14 days) exceeding the expected daily length and weight gain significantly, compared to placebo-treated EFAS litter and healthy controls (P less than 0.01, resp. P less than 0.05). This growth increment persisted in all treated animals throughout the total period of observation (250 days). Three out of the seven animals even showed incremental growth curves of both length and weight that stayed continuously within the +/- 2 standard deviation range of normally growing animals. Thus, it is shown for the first time that also exogenous GH administered temporarily at doses beyond the physiological level results in a significant elevation of final body size.

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.

Mevalonate aciduria is an inherited disorder of cholesterol synthesis. Mevalonate kinase activity in lysates of fibroblasts from a patient was

It is now possible to study short-term growth by knemometry, a non-invasive technique measuring the exact distance between heel and knee in sitting children. During the measurement the lower leg length (LLL) is determined by repeatedly moving the child's knee under the measuring board. Each single measurement consists of six independent estimations, the SD of which is