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Biomedical subjects

M Hermanussen

Publications and source records attributed to M Hermanussen.

At least 19 recordsLinked to original sources
PubMed2006

Sex-specific differences in birth weight due to maternal smoking during pregnancy.

INTRODUCTION: We investigated the sex-specific risk of maternal smoking during pregnancy on the birth weight and the proportion of small-for-gestational-age (SGA) newborns in 888,632 (49.9%) of 1,815,318 singleton births (ca. 80% of all singleton births in Germany from 1995 to 1997) in whom data on maternal cigarette consumption were available. RESULTS AND DISCUSSION: Newborns below the 10th percentile for weight and duration of pregnancy were classified SGA. Maternal smoking during pregnancy lowers the mean birth weight and increases the risk of SGA newborns. The negative effect depends on the daily number of cigarettes consumed, and is greater in girls than in boys. In non-smokers, 9.8% of the newborns were SGA, with a sex-ratio of females:males=1, but this percentage increased with increasing number of cigarettes consumed (p<0.001), as did the sex-ratio, i.e. the negative effect of smoking on growth was greater in girls than in boys. In mild smokers (1-5 cigarettes/day), the risk of giving birth to an SGA girl was 1.7275-fold (95% CI: 1.7266-1.7284) above normal, but was 1.7143-fold (95% CI: 1.7137-1.7150) in boys. More than 21 cigarettes/day increased the risk of SGA 3.15-fold for a boy, but 3.51-fold for a girl (p<0.001). CONCLUSION: In conclusion, particularly in heavy smokers, the negative effect of maternal smoking during pregnancy on the mean birth weight and risk of SGA is significantly greater in newborn girls than in newborn boys.

Birth Weight↗
PubMed2006

Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite.

BACKGROUND: World-wide obesity has risen to alarming levels. We present experimental support for a new and very challenging hypothesis linking obesity, voracity, and growth hormone (GH) deficiency, to the consumption of elevated amounts of the amino-acid glutamate (GLU). Supraphysiological doses of GLU are toxic for neuronal cells. METHODS: Human data were obtained from 807,592 German conscripts born between 1974 and 1978, and from 1,432,368 women of the German birth statistics (deutsche Perinatalerhebung) 1995-1997. The effects of orally administered monosodium glutamate (MSG) were investigated in 30 pregnant Wistar rats and their offspring. Pregnant animals either received no extra MSG, or 2.5 g MSG, or 5 g MSG per day, up to the end of the weaning period. In all, 2.5 g, respectively 5 g, MSG accounted for some 10%, respectively 20%, of dry weight of the average daily food ration. After weaning, MSG feeding was continued in the offspring. FINDINGS: Morbid obesity associates with short stature. Average stature of conscripts progressively declines when body mass index increases above 38 kg/m2. Also morbidly obese young women are shorter than average though to a lesser extent than conscripts. Oral administration of MSG to pregnant rats affects birth weight of the offspring. Maternal feeding with 5 g MSG per day results in severe birth weight reduction (P<0.01). Weight increments remain subnormal when MSG feeding to the mothers is maintained during weaning (P < 0.01). GH serum levels are affected in animals that received MSG during prenatal life via maternal feeding. Animals that are kept on high MSG diet (5 g MSG per day) continue to show serum GH levels that are as low or even lower than those of MSG injected animals (P < 0.05), both at day 30 and at day 90 of life. Animals that were kept on medium MSG diet (2.5 g MSG per day) showed low serum GH levels at day 30 of life (P < 0.01), but seemed to partially recover before day 90. Almost identical results were observed in IGF-1 serum levels. Oral MSG resulted in dose dependent voracity. The animals fed 5 g MSG per day increased water uptake by threefold (P < 0.01), and food uptake by almost two-fold (P < 0.01). The influence of MSG is in general more marked in males than in females. INTERPRETATION: GLU is a widely used nutritional substance that potentially exhibits significant neuronal toxicity. Voracity, and impaired GH secretion are the two major characteristics of parenterally administered GLU-induced neuronal damage. GLU maintains its toxicity in animals even when administered orally. Males appear to be more sensitive than females. The present study for the first time demonstrates, that a widely used nutritional monosubstance--the flavouring agent MSG--at concentrations that only slightly surpass those found in everyday human food, exhibits significant potential for damaging the hypothalamic regulation of appetite, and thereby determines the propensity of world-wide obesity. We suggest to reconsider the recommended daily allowances of amino acids and nutritional protein, and to abstain from the popular protein-rich diets, and particularly from adding the flavouring agents MSG.

Adult↗
PubMed2005

A new anti-obesity drug treatment: first clinical evidence that, antagonising glutamate-gated Ca2+ ion channels with memantine normalises binge-eating disorders.

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.

Adult↗
PubMed2005

How much glutamate is toxic in paediatric parenteral nutrition?

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.

Animals↗
PubMed2005

Morbid obesity is associated with short stature.

Body height and body mass index (BMI) were obtained from 807,592 German conscripts born between 1974 and 1978, aged 19-20 years. The conscripts had either completed Gymnasium (secondary school, more than 10 years, A-level), Realschule (secondary school, 10 years, O-level), or Hauptschule (elementary school, 9 years). Maternal data on body height and weight at the beginning of pregnancy from 1,432,368 women were obtained from the German birth statistics (deutsche Perinatalerhebung) 1995-1997. Morbid obesity is associated with short stature. Regardless of school education, average stature of conscripts progressively declines by up to 10 cm when the BMI increases above 38 kg/m2. In addition, morbidly obese young women are shorter than average, though the impact of overweight on adult stature appears to be less pronounced than in males.

Adult↗
PubMed2003

Automatic analysis of longitudinal growth data on the Website willi-will-wachsen.de.

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 automatization of simple check procedures and thereby detect with less effort more children with growth disorders.

Adolescent↗
PubMed2003

Synthetic standards for body weight.

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 Zürich, 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.

Adolescent↗
PubMed2003

Does high glutamate intake cause obesity?

World-wide obesity has risen to alarming levels. The average weight of German conscripts now increases by almost 400 g/year. Similar data were obtained in Austria, Norway and the UK. The rising prevalence of obesity coincides with a rising popularity of protein-rich diets. On average, Germans consume meat at 100 kg/year. Children eat some threefold more protein than recommended; infants of 6 to 12 months receive daily up to 5 g/kg body weight of protein. We hypothesise that it is not the protein, but the amino acid glutamate that determines the propensity of obesity. Chronic hyperglutamataemia may intoxicate arcuate nucleus (AN) neurons, thereby disrupting the hypothalamic signalling cascade of leptin action, causing hyperphagia, obesity and hyperleptinaemia. Hyperleptinaemia also exerts sympathetic effects including blood pressure elevation that are mediated via mechanisms different from the hypothalamic system, and other symptoms of the 'metabolic syndrome'. This may happen even before birth when in small-for-gestational-age foetuses with impaired umbilical plasma flow, foetal hyperglutamataemia induces AN damage followed by later impairment of feeding regulation, hyperleptinaemia and symptoms that characterise the 'thrifty phenotype'. We suggest abandoning the flavouring agent monosodium glutamate and reconsidering the recommended daily allowances of protein and amino acids, particularly during pregnancy.

Diet↗
PubMed2002

Short-term growth response to GH treatment and considerations upon the limits of short-term growth predictions.

OBJECTIVES: To investigate the impact of short-term growth measurements on predicting the individual growth response to GH treatment, and to elucidate the possible reasons for the limited accuracy of current growth prediction models for GH-treated children. METHODS: Short-term growth measurements by knemometry and stadiometer in 99 short, GH-treated children (27 girls, 72 boys), aged 10.3 +/- 2.3 years, from the Children's University Hospital, Leipzig, Germany. RESULTS: GH treatment significantly accelerated the mean height velocity (HV) from 4.3 +/- 1.0 to 8.1 +/- 1.8 cm/year during the first year of treatment, the average height standard deviation score (SDS) shifted by +0.52 SD. The variation in HV also increased, from S(2) = 1.0 before to S(2) = 3.4 cm(2)/year(2) during treatment. Lower leg length (LLL) velocity accelerated from 1.6 +/- 0.7 before treatment to 3.4 +/- 1.0 cm/year during the first 8 weeks of treatment. Four coefficients of correlation appeared clinically meaningful: (1) LLL velocity vs. body HV during the first year of GH treatment (r = 0.87), indicating that GH acts simultaneously on leg and rump growth; (2) early (first 8 weeks) LLL velocity vs. 1-year body HV during treatment, with r = 0.61 (R(2) = 0.38), indicating that 38% of the variation in HV during the first year of treatment is already predictable by an initial 8-week period of knemometry; (3) early (first 8 weeks) LLL velocity vs. 1-year LLL velocity during treatment, with r = 0.63 (R(2) = 0.39), and (4) early (first 8 weeks) LLL velocity vs. later LLL velocity, up to the end of the first year, with r = 0.53 (R(2) = 0.28) indicating that the early response on lower leg growth persists for at least 1 year of GH treatment. CONCLUSIONS: (1) Thirty-eight percent of the variation in HV during the first year of GH treatment is predictable by an initial 8-week period of knemometry. This parallels early changes in biochemical markers of bone turnover after GH treatment. (2) There is evidence for a baseline variability in HV both in healthy children and in children with growth disorders that make growth prediction difficult.

Anthropometry↗
PubMed2001

Canalisation in human growth: a widely accepted concept reconsidered.

According to the concept of canalisation, infants and children stay within one or two growth channels, and therefore, any crossing of height centiles always warrants further evaluation. In view of evidence against this concept we re-investigated the variability of individual growth in the First Zürich Longitudinal Growth Study. The investigation is based on height measurements of 232 children (112 females, 120 males) measured at annual intervals during childhood and half-yearly during adolescence. Height data were transformed into height standard deviation scores (SDS) and canalisation defined by the width of an individual's growth channel, i.e., by the differences between maximum and minimum height SDS, in the individual series of measurements. Many subjects of the First Zürich Longitudinal Growth Study crossed numerous centiles with patterns that often seemed to show characteristic features. For approximately two thirds of the subjects, the SDS channel during the whole growth process covers more than one SDS. In childhood, between the age of two and age of minimal height velocity, only about one fourth of the subjects have an SDS channel below 0.5, indicating acceptable canalisation. During childhood, growth in boys appeared slightly more canalised than in girls (P = 0.02). Conclusion. The present investigation does not support the concept of strict canalisation of individual growth. We suggest to consider crossing of centiles a normal event in child development, though in a clinical setting crossing centiles should still be taken seriously, at least at first until a medical cause for this has been excluded.

Adolescent↗
PubMed2001

Body weight and the shape of the natural distribution of weight, in very large samples of German, Austrian and Norwegian conscripts.

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.

Austria↗
PubMed2001

Growth tracks in early childhood.

AIM: Child growth is modulated by numerous factors and, particularly in infancy and early childhood, often tends to follow apparently irregular patterns, with many centiles crossed before the later growth channels are reached. The aim of this study was to visualize the diversity of individual growth. DESIGN: The study investigated 333 girls and 329 boys without chronic illnesses from four paediatric practices in Kiel, Germany. The children were measured on natural, i.e., on various occasions, when they were presented to their doctors for preventive care examinations and for minor illnesses, at the age of 0.25 (range +/- 0.08) y, 0.5 (range +/- 0.16) y, 0.75 (range +/- 0.16) y, 1.0 (range +/- 0.25) y, and at the ages of 1.5, 2, 3, 4 and 5 (range +/- 0.25) y. Each individual growth curve was converted into a series of height SDS (standard deviation scores) using one of the most reputable longitudinal German growth studies as background reference. Height SDS was then converted into residual height SDS (differences between height SDS of each measurement and average personal height SDS of the respective child). Cluster analysis was used to identify groups of children (clusters) with similarities in residual height SDS patterns (growth tracks). The clusters contained a minimum of at least 10 children. Single children or small sets of individuals below the minimum number were rejected from further analysis. RESULTS: In males, 10 growth tracks were identified, each consisting of 11 to 52 boys. Growth in 111 boys was so heterogeneous that they could not be assigned to growth tracks. In females, 11 growth tracks were identified, each consisting of 12 to 48 girls; 112 girls could not be assigned. Approximately 7% of boys and 15% of girls showed evidence of a mild intermittent growth spurt at the end of infancy. Some growth tracks were almost horizontal, or showed declining residual height SDS up to the age of 3 and 4 y, with no evidence of growth spurts during early childhood. Others showed sharply declining growth in early infancy, or irregular patterns. Similar results were obtained when using cross-sectional standards as background reference. CONCLUSION: Cluster analysis provides evidence that the substantial diversity in infant and early child growth, is limited to a small number of narrow but characteristic tracks of yet unknown biological significance.

Algorithms↗
PubMed2000

Recombinant human growth hormone enhances tibial growth in peripubertal female rats but not in males.

OBJECTIVE: A novel non-invasive technique termed microknemometry, which allows daily leg length measurement, was used to investigate the growth promoting effect of growth hormone (GH) on peripubertal rats. We compared the effect of different patterns of recombinant human (rh) GH administration to peripubertal male rats with the effect produced by two daily administrations of the same amount of rhGH to peripubertal female rats or adult male rats. Another group of peripubertal male rats was also submitted to a 3-day period of starvation, in order to study catch-up growth during refeeding and to determine whether this process could be stimulated by exogenous GH administration. RESULTS: GH treatment was unable to stimulate tibial growth or weight gain in peripubertal males, whereas a clear growth promoting effect was observed in female rats and also in adult male rats. Starvation caused a dramatic body weight loss, and a reduction in tibial growth rate. Peripubertal male rats gained body weight faster than unstarved animals during refeeding, although recovery was not complete after nine days. Tibial growth, however, was resumed at the same speed as in normally fed males. This means that no catch-up effect was observed after refeeding in animals either with or without GH treatment. CONCLUSIONS: During peripuberty, normal male rats grow at a maximal speed that cannot be further increased by exogenous GH treatment, whereas age-matched female rats or older males grow at a slower rate than peripubertal males. Thus, exogenous rhGH administration is capable of enhancing growth velocity.

Aging↗
PubMed2000

[Model program for the early detection and optimal treatment of disorders of growth and physical development using a medical competence netwok].

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.

Body Composition↗