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Biomedical subjects

M Hermanussen

Publications and source records attributed to M Hermanussen.

At least 55 records · Page 3Linked to original sources
PubMed1988

Knemometry, a new tool for the investigation of growth. A review.

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.

Adolescent↗
PubMed1988

Growth response after administration of pharmacological doses of growth hormone in rats.

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.

Aging↗
PubMed1987

"Negative growth" in anorexia nervosa assessed by knemometry.

Recently a novel and non-invasive technique of lower leg length measurement (knemometry) was introduced. The method estimates the distance between heel and knee in the sitting child with an accuracy of 0.09 mm(SD). Two female patients with anorexia nervosa, aged 14:4 and 13:7 years, weighing minus 27 and minus 38% of normal weight for age, were measured repeatedly with this method within periods of 72 and 129 days during hospitalization und up to 133 days thereafter. During the first 40 days of hospitalization, patient 1 was measured 30 times and showed significant shrinkage of the lower leg length of -0.040 mm/day (P less than 0.001). Over the remainder of her hospital stay her mean lower leg length increment still was much less (+0.036 mm/day) than that expected just by increase of soft tissue due to rapid weight gain (+0.126 kg/day). The second patient also showed significant shrinkage of lower leg length during a 4 month period after discharge from the hospital (-0.009 mm/day, P less than 0.01). This is the first demonstration of long term lower leg shrinkage in children. Its origin remains unclear, but this shrinkage is clearly distinct from either arbitrary changes of lower leg length due to errors of measurement or changes of body diameters due to temporary alterations of soft tissue (i.e. during periods of weight loss). We speculate that progressive atrophic changes of the epiphyseal plates still open in both patients may account for the observed long term shrinkage of lower leg length.

Adolescent↗
PubMed1987

Can the knemometer shorten the time for growth rate assessment?

A total of 105 healthy children of both sexes and various ages were measured once or twice weekly by knemometry over periods of 161-202 days on 11-50 occasions. These data were used to calculate percentiles of the predictive error that occurred if short-term lower leg length differences were used to extrapolate half-annual growth rates. From these data, and observations on day-to-day variations of the lower leg length, it was concluded that growth rates derived from single differences between two consecutive lower leg length measurements are invalid and without predictive power for mean long-term lower leg increments. However, a novel statistical approach is presented, which results in the evaluation of daily lower leg growth rates to visualize quasi-continuous growth kinetics. Examples of successful and unsuccessful growth promoting therapeutic interventions are provided to demonstrate knemometric assessment of a significant modification of short-term growth kinetics.

Adolescent↗
PubMed1986

GH deficient children receiving GH replacement do not grow during intermittent infectious illness.

Five growth hormone deficient children, aged 5.3 to 12.6 yrs, were measured regularly once or twice weekly by knemometry, a novel and noninvasive technique of accurate lower leg length measurement. The total period of observation was 40 months in the 5 children. During this time all children received replacement therapy with extractive human pituitary growth hormone 12 IU/m2/week by daily s.c. injections. 11 intermittent infectious illnesses occurred within the observation period of 40 months. During the infectious diseases a significant decrease of the mean lower leg growth velocity down to -0.012 mm/day was observed. During the following convalescent period (14 days) mean lower leg growth velocity rose up to +0.107 mm/day (p less than 0.001). Growth hormone substitution was not changed throughout the period of observation.

Bone Development↗
PubMed1986

Treatment of Silver-Russell type dwarfism with human growth hormone: effects on serum somatomedin-C levels and on longitudinal growth studied by knemometry.

Two patients, aged 5 and 12 years, with Silver-Russell type dwarfism are presented. As shown by standard tests and examination of the spontaneous nocturnal hGH secretion, there was only mild regulative hGH deficiency. HGH treatment was started with daily subcutaneous injections at age 5.5 years (height 90.3 cm, -6.1 SDS, bone age 2.75 years) and 12.6 years (height 125.7 cm, -3.7 SDS, bone age 8.75 years), respectively. Treatment was monitored by serial somatomedin-C (SM-C) determinations and by knemometry (lower leg measurement). SM-C values increased in both patients by 10.5 and 4.8 fold, respectively, and remained above the prepubertal range (greater than 2.5 U/ml) during the treatment periods of 1.5 years. Pretreatment knemometric growth rate was high (after a somatomedin generation test) in patient 1 (0.7 mm/week) and low in patient 2 (0.31 mm/week). It remained at the same level in patient 1 (0.67 mm/week) and increased markedly in patient 2 (0.46 mm/week). During a treatment interruption, in both patients, knemometric growth rates fell to 0.33 and 0.30 mm/week, respectively. After resumption of treatment, now with biosynthetic hGH, growth rates increased again in patients 1 and 2 to 0.64 and 0.48 mm/week, respectively. This lower leg growth pattern was parallelled by similar changes in total body growth velocity. Even after the relatively short treatment period of 14 to 16 months, a slight net gain in statural height could be observed, as standard deviation scores for bone age increased.

Age Determination by Skeleton↗
PubMed1985

Knemometric monitoring of early effects of human growth hormone on leg length in children with growth hormone deficiency.

The early effects of human growth hormone (hGH) were investigated by knemometry, a recently described technique of measuring lower leg length. In 14 growth hormone deficient children, the mean increase in the lower leg length was 0.47 +/- 0.10 (SE) mm within 24 h of a single intramuscular injection of 4 IU hGH. This increase occurred after about 80% of the single injections and was highly significant (p less than 0.01). 48 h after an injection, a slight but not significant reduction of the lower leg length was observed (-0.15 +/- 0.09 [SE]). These effects led to a marked zig-zag pattern of growth when hGH was given thrice weekly.

Adolescent↗
PubMed1985

Heterogeneity of Kallmann's syndrome.

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.

Adolescent↗
PubMed1985

Differentiation of male hypogonadotropic hypogonadism and constitutional delay of puberty by pulsatile administration of gonadotropin-releasing hormone.

It is not possible to differentiate reliably between male idiopathic hypothalamic hypogonadism (HH) and severe constitutional delay of puberty (CD) on the basis of a standard GnRH bolus test (GBT) or other known endocrine or clinical parameters. Therefore, we studied the response of 17 hypogonadal men, 8 with a diagnosis of HH (age, 15.5-41; bone age, 12.5-19 yr; testes, 1-4 ml) and 9 with CD (age, 14.5-20; bone age, 11-15 yr, testes, 2-10 ml) to pulsatile GnRH stimulation. Basal and peak LH and FSH levels after a single dose of GnRH greatly overlapped between the two groups. In each patient, a spontaneous nocturnal plasma profile of LH and FSH, sampled every 20 min, was followed by a pulsatile GnRH stimulation (5 micrograms iv every 90 min) via a portable minipump for 36 h. Before and after this pulsatile GnRH stimulation, a GBT (60 micrograms/m2 iv) was performed and plasma LH, FSH, testosterone, androstenedione, and dehydroepiandrosterone sulfate were measured. Pulse analysis revealed 0-5 spontaneous nocturnal LH peaks in the CD patients but only one in all of the HH patients. During the 36 h of pulsatile GnRH, mean LH and FSH levels were significantly higher (P less than 0.0001) than during the spontaneous nocturnal profile in all patients (except 1 from each group for LH). The GBT after pulsatile stimulation caused significantly higher (P less than 0.001) LH increments in CD than in HH patients, with no overlap between the two groups (range, 4.1-15.6 in CD vs. 0.8-2.4 mIU/ml in HH). Plasma testosterone rose significantly (P less than 0.01) during pulsatile GnRH from 67 to 155 ng/dl (median) in the CD men, but did not change in the HH group (21 to 22.5 ng/dl). Plasma androstenedione and dehydroepiandrosterone sulfate did not rise in either group. We conclude that, in contrast to other parameters investigated so far, the LH increment in the second GBT after 36 h of pulsatile GnRH allows clear-cut differentiation between CD and HH. These results indicate significantly lower pituitary LH reserve in patients with permanent HH after short term priming of the pituitary by pulsatile GnRH administration.

Adult↗
PubMed1985

Catch-up growth following transfer from three times weekly im to daily sc administration of hGH in GH deficient patients, monitored by knemometry.

A novel and non-invasive technique of growth measurement is introduced. By this method the length of the human lower leg is measured with an accuracy of 0.1 mm. Thus, growth velocities can be estimated within a few weeks. In the present study the immediate changes of growth velocity are demonstrated, following the transfer of growth hormone administration from three times weekly im to daily sc in 9 growth hormone deficient children, age 7.4 to 20.5 years. The first observation period (3 times weekly im administration) ranged from 32 to 72 days, the second observation period (daily sc administration) ranged from 160 to 267 days). During the study, the total weekly dosage of growth hormone remained unchanged (12 IU/m2/week). In all 9 patients growth velocity increased significantly after the transfer of application. Mean growth velocity of the lower leg rose from 0.04 mm/day up to 0.065 mm/day. Mean growth velocity of total body height rose form 4.8 cm/year up to 6.9 cm/year. In addition, differential lower leg growth rates of 3 to 4 week periods were established in all 9 patients, revealing a significant catch-up growth spurt immediately following the transfer of application. During this spurt mean lower leg growth velocity rose form 0.04 mm/day up to 0.091 mm/day. This marked increase of lower leg growth rates lasted for only a few weeks and was followed by a period of decreased growth velocity. On the long run, growth velocity shifted upward in a wave-like pattern, stabilizing on a significantly higher level than before the transfer of application.

Adolescent↗
PubMed1985

May growth be regulated by systematic, stepwise collapse of DNA? A new hypothesis for the understanding of growth kinetics.

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.

Animals↗
PubMed1984

Differential diagnosis of male central hypogonadism by short-term pulsatile LHRH administration.

UNLABELLED: In order to obtain a clinically valuable differentiation of central hypogonadism (CH), 18 male patients, including 13 with permanent gonadotropin deficiency (GD), age 14.3-41 yrs, bone age 8.5-19 yrs, and 5 with constitutional delay (CD) of puberty (age 15.3-20, bone age 12.5-15 yrs) were studied. Among the GD patients, there were 4 with anosmia (Kallmann's syndrome, KS), 6 with idiopathic hypopituitarism (HP) and 3 with isolated hypogonadotropic hypogonadism (HH). The spontaneous nocturnal plasma profile of LH and FSH was compared with that during pulsatile LHRH infusion (5 micrograms iv every 90 min) by a portable micropump (Zyklomat) for 36 hrs. The pituitary-gonadal response was evaluated by calculating the LH and FSH slopes during pulsatile LHRH and by comparing plasma testosterone (T) before and after. While spontaneous nocturnal FSH pulses were absent in all patients, between 1 and 4 significant LH pulses were seen in all CD but in none of the GD patients. In all patients, mean FSH was significantly higher during pulsatile LHRH than during sleep. During pulsatile LHRH administration, significantly increasing FSH responses were seen in all KS and HP patients, but in only 2 of the 5 CD and in none of the 3 HH patients. In all CD boys (mean testis vol, 8.6 ml), T rose markedly during pulsatile LHRH (mean, from 168 to 414 ng/dl), whereas in all GD patients (mean testis vol, 2 ml) it did not (19 vs 27 ng/dl). CONCLUSIONS: Pulsatile LHRH for 36 hrs differentiates CD and GD far more exact than was previously possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Growth tracks in pre-pubertal children.

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.

Anthropometry↗
PubMedDate not supplied

Short-term growth of premature infants treated with dexamethasone assessed by mini-knemometry.

AIM: The study aimed to measure the direct effect of dexamethasone (DEXA) on daily lower leg length per mini-knemometry of premature infants and to examine whether the administration of different doses is associated with alternations in growth. PATIENTS AND METHODS: We observed 20 premature children and had 276 complete mini-knemometrical and weight measurements (13.8 measurements per single child) for analysis. The gestational age of the infants was 26.8 +/- 1.9 weeks; the mean birth weight was 973 +/- 336 g. All infants underwent daily measurements of lower leg length performed by mini-knemometry. We divided the 41 DEXA administrations into three subgroups. Group I included a cumulative dose of 0.75 mg DEXA per kg bodyweight (BW), group II doses between 0.75 and 1.0 mg per kg BW and group III dosages above 1.0 mg per kg BW. RESULTS: We observed catch-up growth in group I within 24 h after stopping therapy. Groups II and III needed 48-72 h to achieve a normal level in short-term growth. CONCLUSION: Lower doses seemed to have an equivalent effect without long-term effect on lower leg length. In higher doses (groups II and III) the growth was suppressed for more than 24 h.

Anthropometry↗
PubMedDate not supplied

Knemometry in childhood: accuracy and standardization of a new technique of lower leg length measurement.

Recently, a new anthropometric method of accurate lower leg length measurement (knemometry) was introduced. The present study was performed to investigate rigorously its strengths and weaknesses for auxological purposes, and to promote a standardized method of use. The data are based on 6 x 2200 single estimations of the lower leg length in 90 children of both sexes with normal, tall or short stature aged between 2.4 and 17.1 years. The overall technical error of this measurement was found to be 0.16 mm, which is reduced to 0.13 mm if the first estimation within each series of six is ignored. The following sources of systematic error could be detected: intra-daily variation, dependency on physical pressure put on or removed from the leg, vigorous physical activity prior to the measuring procedure, and a slow but significant correlation between day-to-day variation of lower leg length and body weight (r = 0.299, b = 0.372 mm/kg). There was no covariation with atmospheric parameters such as outside temperature, barometric pressure and others. After elimination of a linear trend from the individual growth curves, there was a remaining day-to-day variation of SD = 0.697 mm. This represents real changes of lower leg length and cannot be explained by the technical error of measurement which contributes to less than 10% of the total variation. Some of this day-to-day variation may be explained by non-linearity of growth. Knemometry appears to be a robust and precise new tool for the investigation of short term kinetics of longitudinal growth. Proposals for a standardized use of this technique are given.

Adolescent↗
PubMedDate not supplied

Periodical changes of short term growth velocity ('mini growth spurts') in human growth.

Evidence has accumulated that predictions of annual or half-annual growth rates are of limited validity when derived from extrapolations of short term growth rates. In order to investigate whether the poor predictive qualities of short sections of individual growth curves are caused by non-linearity of human growth, we have studied 73 healthy children, aged 2.9 to 15.9 years, with standard deviation scores for body height ranging between -3.3 and +3.0. The children were measured between 18 and 106 times once or twice per week throughout periods of 180 to 306 days by knemometry, a novel and noninvasive technique of accurate lower leg length measurement. Non-linearity of growth was found in about 70% of those children who could be measured more than 35 times. 45 children provided evidence for a characteristic up-and-down pattern of lower leg growth velocity consisting of sharp growth spurts ('mini growth spurts') alternating with periods of decreased growth velocity every 30 to 55 days. This pattern seemed to appear spontaneously, though in some cases we found a marked coincidence between periods of growth arrest and intermittent infectious illness.

Adolescent↗